Download PDF

Clinical Trial Results:
A Randomised Placebo Controlled Trial of the effectiveness of Early MEtformin in Addition to Usual Care in the Reduction of Gestational Diabetes Mellitus Effects (EMERGE)

Summary
EudraCT number	2016-001644-19
Trial protocol	IE
Global end of trial date	13 Apr 2023

Results information
Results version number	v1(current)
This version publication date	28 Apr 2024
First version publication date	28 Apr 2024
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

NUIG-2016-01

ISRCTN number

US NCT number

WHO universal trial number (UTN)

Sponsor organisation name

HRB Clinical Research Facility Galway

Sponsor organisation address

University Road, Galway, Ireland,

Public contact

Fidelma Dunne , HRB Clinical Research Facility Galway, fidelma.dunne@nuigalway.ie

Scientific contact

Fidelma Dunne, HRB Clinical Research Facility Galway, fidelma.dunne@nuigalway.ie

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

10 Apr 2024

Is this the analysis of the primary completion data?

Yes

Primary completion date

13 Apr 2023

Global end of trial reached?

Yes

Global end of trial date

13 Apr 2023

Was the trial ended prematurely?

Main objective of the trial

The primary objective is to determine if metformin (a) reduces the requirement for insulin or (b) reduces fasting glucose at gestational weeks 32 and 38.

Protection of trial subjects

The EMERGE trial was initially approved by Galway University Hospital Clinical Research Ethics Committee on 16th Dec 2016. The trial was transitioned to the National Research Ethics Committee (NREC-CT), following a substantial amendment to the protocol, in July 2021. This study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with good clinical practices (GCPs) and the applicable laws and regulations.

Background therapy

Evidence for comparator

Actual start date of recruitment

06 Jun 2017

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Ireland: 535

Worldwide total number of subjects

535

EEA total number of subjects

535

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

535

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

The population for the trial was pregnant women between the ages of 18-50 years, with a diagnosis of gestational diabetes mellitus (GDM) up to 28 weeks gestation. Women were diagnosed with GDM using a 75g oral glucose tolerance test (OGTT).

Screening details

2308 pregnancies were identified with gestational diabetes mellitus. 173 were excluded from participation- 1773 were outside the study window; 400 patients declined participation; 200 had partner that disagreed study participation; 50 already on study drug; 20 excluded per exclusion criteria; 5 had twin pregnancy; 2 known congenital anomalies.

Period 1 title

Baseline

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Data analyst, Carer, Assessor

Blinding implementation details

Patients, investigators, and all other personnel involved in the conduct of the study were blinded to individual treatment assignments for the duration of the study/during the active treatment phase of the study. Unblinding did not occur until the reporting database was validated and locked for final statistical analysis.

Are arms mutually exclusive

Yes

Metformin group

Arm description

Women randomised to the Metformin Group received metformin 500mg OD, with the dose titrated upwards every 2 days over 10 days increasing to a maximum of 2500mg Metformin daily (5 tablets) or maximum tolerated dose, in addition to usual care (exercise and MNT), and taken until delivery.

Arm type

Experimental

Investigational medicinal product name

Metformin

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

500mg OD by mouth, with the dose titrated upwards every 2 days over 10 days increasing to a maximum of 2500mg Metformin daily (5 tablets) or maximum tolerated dose.

Placebo

Arm description

Subjects randomised to the Placebo Group received 1 placebo tablet OD, with the dose titrated upwards every 2 days over 10 days increasing to a maximum of five placebo tablets daily, in addition to usual care (exercise and MNT), and taken until delivery.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

1 placebo tablet OD, with the dose titrated upwards every 2 days over 10 days increasing to a maximum of five placebo tablets daily.

Number of subjects in period 1	Metformin group	Placebo
Started	268	267
Completed	268	267

Period 2 title

Randomized and treated

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Data analyst, Carer, Assessor

Are arms mutually exclusive

Yes

Metformin

Arm description

Arm type

Experimental

Investigational medicinal product name

Metformin

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

500mg OD by mouth, with the dose titrated upwards every 2 days over 10 days increasing to a maximum of 2500mg Metformin daily (5 tablets) or maximum tolerated dose.

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Placebo

Arm description

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

1 placebo tablet OD, with the dose titrated upwards every 2 days over 10 days increasing to a maximum of five placebo tablets daily.

Number of subjects in period 2	Metformin	Placebo
Started	268	267
Completed	263	265
Not completed	5	2
Consent withdrawn by subject	4	1
Other	1	1

Period 3 title

Study completion

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Data analyst, Carer, Assessor

Are arms mutually exclusive

Yes

Metformin

Arm description

Arm type

Experimental

Investigational medicinal product name

oMetformin

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

500mg OD by mouth, with the dose titrated upwards every 2 days over 10 days increasing to a maximum of 2500mg Metformin daily (5 tablets) or maximum tolerated dose.

Placebo

Arm description

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

1 placebo tablet OD, with the dose titrated upwards every 2 days over 10 days increasing to a maximum of five placebo tablets daily.

Number of subjects in period 3	Metformin	Placebo
Started	263	265
Completed	211	220
Not completed	52	45
Adverse event, serious fatal	1	-
Consent withdrawn by subject	3	4
Physician decision	-	1
Other	30	22
Lost to follow-up	18	18

Baseline characteristics

Top of page

Reporting group title

Metformin group

Reporting group description

Reporting group title

Placebo

Reporting group description

Reporting group values	Metformin group	Placebo	Total
Number of subjects	268	267	535
Age categorical
Age in years at baseline
Units: Subjects
Adults (18-64 years)	268	267	535
Age continuous
Age (years)
Units: years
arithmetic mean (standard deviation)	34.3 ± 4.9	34.3 ± 4.7	-
Gender categorical
Gender
Units: Subjects
Female	268	267	535
Male	0	0	0
Race/Ethnic Group
Units: Subjects
African	6	6	12
Asian, other	17	29	46
Irish	175	171	346
Irish Traveller	11	2	13
Other	14	21	35
White, other	44	38	82
Black, other	1	0	1
Not recorded	0	0	0
Educational Level
Level of education completed
Units: Subjects
Primary only	25	12	37
Secondary only	78	78	156
Tertiary education	165	176	341
Not recorded		1	1
Employment status
Units: Subjects
Unemployed	19	27	46
Other	249	239	488
Not recorded		1	1
Have a medical card
Units: Subjects
Yes	63	63	126
No	205	203	408
Not recorded		1	1
Have Private Health Insurance
Units: Subjects
Yes	126	116	242
No	142	150	292
Not recorded		1	1
Smoking Status
Units: Subjects
Current	17	17	34
Former	124	100	224
Never	127	150	277
Not recorded	0	0	0
Nulliparous
Units: Subjects
Yes	84	84	168
No	184	183	367
Not recorded	0	0	0
History of Macrosomia
Prior delivery of infant with birthweight >4000g
Units: Subjects
Yes	57	44	101
No	211	223	434
Not recorded	0	0	0
History of Miscarriage
Units: Subjects
Yes	106	93	199
No	162	174	336
NA	0	0	0
Not recorded	0	0	0
History of Congenital Deformities
Prior pregnancy with delivery of infant with congenital deformities.
Units: Subjects
Yes	13	13	26
No	255	254	509
NA	0	0	0
Not recorded	0	0	0
History of Gestational Diabetes
Units: Subjects
Yes	64	64	128
No	120	119	239
NA	84	84	168
Not recorded	0	0	0
History of Pre-eclampsia
Units: Subjects
Yes	24	23	47
No	160	160	320
NA	84	84	168
Not recorded	0	0	0
History of Postpartum Haemorrhage
Units: Subjects
Yes	28	20	48
No	156	163	319
NA	84	84	168
Not recorded	0	0	0
History of Polyhydramnios
Units: Subjects
Yes	10	7	17
No	258	260	518
Not recorded	0	0	0
History of Antepartum Haemorrhage
Units: Subjects
Yes	20	15	35
No	164	168	332
NA	84	84	168
Not recorded	0	0	0
History of Stillbirth
Units: Subjects
Yes	2	2	4
No	182	181	363
NA	84	84	168
Not recorded	0	0	0
Body Mass Index
BMI kg/m2
Units: kg/m2
arithmetic mean (standard deviation)	30.4 ± 6.4	30.7 ± 5.7	-
Systolic blood pressure
Units: mmHg
arithmetic mean (standard deviation)	114.9 ± 9.5	114.4 ± 9.2	-
Diastolic blood pressure
Units: mmHg
arithmetic mean (standard deviation)	68.9 ± 8.0	68.7 ± 8.8	-
HbA1c
Units: mmol/mol
arithmetic mean (standard deviation)	33.0 ± 3.4	32.9 ± 3.5	-
Fasting serum glucose
Overnight fasting serum glucose
Units: mmol/l
arithmetic mean (standard deviation)	5.2 ± 0.5	5.2 ± 0.5	-
1 hour glucose tolerance test result
Units: mmol/l
arithmetic mean (standard deviation)	9.4 ± 1.9	9.7 ± 1.9	-
2 hours glucose tolerance test value
Units: mmol/l
arithmetic mean (standard deviation)	7.1 ± 1.6	7.1 ± 1.6	-

Subject analysis set title

Intention to treat

Subject analysis set type

Intention-to-treat

Subject analysis set description

The intention to treat (ITT) analysis set will include all randomised subjects.

Subject analysis sets values	Intention to treat
Number of subjects	535
Age categorical
Age in years at baseline
Units: Subjects
Adults (18-64 years)	268
Age continuous
Age (years)
Units: years
arithmetic mean (standard deviation)	34.3 ± 4.8
Gender categorical
Gender
Units: Subjects
Female	535
Male	0
Race/Ethnic Group
Units: Subjects
African	12
Asian, other	46
Irish	346
Irish Traveller	13
Other	35
White, other	82
Black, other	1
Not recorded	0
Educational Level
Level of education completed
Units: Subjects
Primary only	37
Secondary only	156
Tertiary education	341
Not recorded	1
Employment status
Units: Subjects
Unemployed	46
Other	488
Not recorded	1
Have a medical card
Units: Subjects
Yes	126
No	408
Not recorded	1
Have Private Health Insurance
Units: Subjects
Yes	242
No	292
Not recorded	1
Smoking Status
Units: Subjects
Current	34
Former	224
Never	277
Not recorded	0
Nulliparous
Units: Subjects
Yes	168
No	367
Not recorded	0
History of Macrosomia
Prior delivery of infant with birthweight >4000g
Units: Subjects
Yes	101
No	434
Not recorded	0
History of Miscarriage
Units: Subjects
Yes	199
No	336
NA	0
Not recorded	0
History of Congenital Deformities
Prior pregnancy with delivery of infant with congenital deformities.
Units: Subjects
Yes	26
No	509
NA	0
Not recorded	0
History of Gestational Diabetes
Units: Subjects
Yes	128
No	239
NA	168
Not recorded	0
History of Pre-eclampsia
Units: Subjects
Yes	47
No	320
NA	168
Not recorded	0
History of Postpartum Haemorrhage
Units: Subjects
Yes	48
No	319
NA	168
Not recorded	0
History of Polyhydramnios
Units: Subjects
Yes	17
No	434
Not recorded	0
History of Antepartum Haemorrhage
Units: Subjects
Yes	35
No	332
NA	168
Not recorded	0
History of Stillbirth
Units: Subjects
Yes	4
No	363
NA	168
Not recorded	0
Body Mass Index
BMI kg/m2
Units: kg/m2
arithmetic mean (standard deviation)	30.5 ± 6.1
Systolic blood pressure
Units: mmHg
arithmetic mean (standard deviation)	114.6 ± 9.4
Diastolic blood pressure
Units: mmHg
arithmetic mean (standard deviation)	68.8 ± 8.4
HbA1c
Units: mmol/mol
arithmetic mean (standard deviation)	32.9 ± 3.5
Fasting serum glucose
Overnight fasting serum glucose
Units: mmol/l
arithmetic mean (standard deviation)	5.2 ± 0.5
1 hour glucose tolerance test result
Units: mmol/l
arithmetic mean (standard deviation)	9.5 ± 1.9
2 hours glucose tolerance test value
Units: mmol/l
arithmetic mean (standard deviation)	7.1 ± 1.6

End points

Top of page

Reporting group title

Metformin group

Reporting group description

Reporting group title

Placebo

Reporting group description

Reporting group title

Metformin

Reporting group description

Reporting group title

Placebo

Reporting group description

Reporting group title

Metformin

Reporting group description

Reporting group title

Placebo

Reporting group description

Subject analysis set title

Intention to treat

Subject analysis set type

Intention-to-treat

Subject analysis set description

The intention to treat (ITT) analysis set will include all randomised subjects.

Primary: Insulin Initiated Yes/No

Top of page

End point title

Insulin Initiated Yes/No

End point description

End point type

Primary

End point timeframe

Initiation of insulin treatment at any time prior to delivery.

End point values	Metformin	Placebo	Intention to treat
Number of subjects analysed	268	267	535
Units: subjects
Yes	101	134	235
No	167	133	300
Not recorded	0	0	0

Biinary logistic regression

Comparison groups

Metformin v Placebo

Number of subjects included in analysis

535

Analysis specification

Pre-specified

Analysis type

other ^[1]

P-value

= 0.005

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

0.61

Confidence interval

level

95%

sides

2-sided

lower limit

0.43

upper limit

0.86

Notes
[1] - Two-sided

Primary: Composite outcome

Top of page

End point title

Composite outcome

End point description

Initiation of insulin OR fasting glucose at 32 weeks' gestation >=5.1mmol/l OR fasting glucose at 38 weeks' gestation >=5.1mmol/l

End point type

Primary

End point timeframe

Any time prior to delivery.

End point values	Metformin	Placebo	Intention to treat
Number of subjects analysed	268	267	535
Units: subjects
Yes	150	167	317
No	118	100	218
Not recorded	0	0	0

Binary Logistic Regression

Comparison groups

Metformin v Placebo

Number of subjects included in analysis

535

Analysis specification

Pre-specified

Analysis type

other ^[2]

P-value

= 0.1

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

0.74

Confidence interval

level

95%

sides

2-sided

lower limit

0.52

upper limit

1.06

Notes
[2] - Two-sided

Primary: Fasting hyperglycaemia

Top of page

End point title

Fasting hyperglycaemia

End point description

End point type

Primary

End point timeframe

Overall trial

End point values	Metformin	Placebo	Intention to treat
Number of subjects analysed	268	267	535
Units: Subjects
Yes	94	106	200
No	174	161	335
Not recorded	0	0	0

Binary Logistic Regression

Comparison groups

Metformin v Placebo

Number of subjects included in analysis

535

Analysis specification

Pre-specified

Analysis type

other ^[3]

P-value

= 0.005

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

0.78

Confidence interval

level

95%

sides

2-sided

lower limit

0.55

upper limit

1.12

Notes
[3] - Two-sided

Secondary: Pre-eclampsia

Top of page

End point title

Pre-eclampsia

End point description

Subject diagnosed with pre-eclampsia.

End point type

Secondary

End point timeframe

Any time during pregnancy

End point values	Metformin	Placebo	Intention to treat
Number of subjects analysed	268	267	535
Units: subjects
Yes	9	5	14
No	259	261	520
Not recorded	0	0	0

Logistic Regression

Comparison groups

Metformin v Placebo

Number of subjects included in analysis

535

Analysis specification

Pre-specified

Analysis type

other ^[4]

P-value

= 0.282

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.84

Confidence interval

level

95%

sides

2-sided

lower limit

0.63

upper limit

6.04

Notes
[4] - Two-sided

Secondary: Pregnancy-induced hypertension

Top of page

End point title

Pregnancy-induced hypertension

End point description

Diagnosed with. Pregnancy-induced hypertension at any time during pregnancy

End point type

Secondary

End point timeframe

Any time during pregnancy

End point values	Metformin	Placebo	Intention to treat
Number of subjects analysed	268	267	535
Units: subjects
Yes	17	19	36
No	251	248	499
Not recorded	0	0	0

Logistic Regression

Comparison groups

Metformin v Placebo

Number of subjects included in analysis

535

Analysis specification

Pre-specified

Analysis type

other ^[5]

P-value

= 0.739

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

0.89

Confidence interval

level

95%

sides

2-sided

lower limit

0.45

upper limit

1.76

Notes
[5] - Two-sided

Secondary: Labour type

Top of page

End point title

Labour type

End point description

Whether labour spontaneous or induced or delivery by elective Caesarian Section

End point type

Secondary

End point timeframe

Labour

End point values	Metformin	Placebo	Intention to treat
Number of subjects analysed	268	267	535
Units: subjects
Induced	73	87	160
Elective Caesarian Section	116	101	217
Spontaneous	70	74	114

Multinomial Logistic Regression

Statistical analysis description

Caesarean delivery

Comparison groups

Metformin v Placebo

Number of subjects included in analysis

535

Analysis specification

Pre-specified

Analysis type

other ^[6]

P-value

= 0.367

Method

Multinomial Logistic Regression

Parameter type

Odds ratio (OR)

Point estimate

1.21

Confidence interval

level

95%

sides

2-sided

lower limit

0.8

upper limit

1.85

Notes
[6] - Two-sided

Multinomial Logistic Regression

Statistical analysis description

Induced delivery

Comparison groups

Metformin v Placebo

Number of subjects included in analysis

535

Analysis specification

Pre-specified

Analysis type

other ^[7]

P-value

= 0.603

Method

Multinomial Logistic Regression

Parameter type

Odds ratio (OR)

Point estimate

0.89

Confidence interval

level

95%

sides

2-sided

lower limit

0.56

upper limit

1.39

Notes
[7] - Two-sided

Secondary: Weight Gain during pregnancy

Top of page

End point title

Weight Gain during pregnancy

End point description

End point type

Secondary

End point timeframe

Difference between weight at baseline and weight prior to delivery

End point values	Metformin	Placebo	Intention to treat
Number of subjects analysed	268	267	535
Units: kg
arithmetic mean (standard deviation)	0.9 ± 3.3	2 ± 3.5	1.4 ± 3.5

Linear Regression

Comparison groups

Metformin v Placebo v Intention to treat

Number of subjects included in analysis

1070

Analysis specification

Pre-specified

Analysis type

other ^[8]

P-value

= 0.005

Method

Regression, Linear

Parameter type

Mean difference (final values)

Point estimate

-1.08

Confidence interval

level

95%

sides

2-sided

lower limit

-1.84

upper limit

-0.32

Notes
[8] - Two-sided

Secondary: Postpartum impaired fasting glucose

Top of page

End point title

Postpartum impaired fasting glucose

End point description

Impaired fasting glucose was diagnosed if fasting glucose level was 5.6-6.9 mm/L .

End point type

Secondary

End point timeframe

12 weeks postpartum

End point values	Metformin	Placebo	Intention to treat
Number of subjects analysed	268	267	535
Units: subjects
Yes	51	52	103
No	217	215	432
Not recorded	0	0	0

Binary Logistic Regression

Comparison groups

Metformin v Placebo

Number of subjects included in analysis

535

Analysis specification

Pre-specified

Analysis type

other ^[9]

P-value

= 0.99

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.65

upper limit

1.55

Notes
[9] - Two-sided

Secondary: Postpartum impaired glucose tolerance by 2hr OGTT

Top of page

End point title

Postpartum impaired glucose tolerance by 2hr OGTT

End point description

Impaired glucose tolerance was diagnosed when 2hr OGTT result was 7.8-11 mmol/L.

End point type

Secondary

End point timeframe

12 weeks postpartum

End point values	Metformin	Placebo	Intention to treat
Number of subjects analysed	268	267	535
Units: subjects
Yes	15	16	31
No	253	251	504
Not recorded	0	0	0

Binary Logistic Regression

Comparison groups

Metformin v Placebo

Number of subjects included in analysis

535

Analysis specification

Pre-specified

Analysis type

other ^[10]

P-value

= 0.911

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

0.96

Confidence interval

level

95%

sides

2-sided

lower limit

0.46

upper limit

Notes
[10] - Two-sided

Secondary: Postpartum metabolic syndrome

Top of page

End point title

Postpartum metabolic syndrome

End point description

Metabolic Syndrome was diagnosed if the participant had three or more of the following: (a) abdominal obesity with waist circumference >88cm (b) hypertriglyceridaemia >1.69mmol/l (c) low HDL < 1.29mmol/l (d) high blood pressure >130/85 mmHg (e) fasting glucose >6.1mmol/l.

End point type

Secondary

End point timeframe

12 weeks postpartum

End point values	Metformin	Placebo	Intention to treat
Number of subjects analysed	268	267	535
Units: subjects
Yes	20	25	45
No	248	242	490
Not recorded	0	0	0

Binary Logistic Regression

Comparison groups

Metformin v Placebo

Number of subjects included in analysis

535

Analysis specification

Pre-specified

Analysis type

other ^[11]

P-value

= 0.519

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

0.82

Confidence interval

level

95%

sides

2-sided

lower limit

0.44

upper limit

1.51

Notes
[11] - Two-sided

Secondary: Birth weight

Top of page

End point title

Birth weight

End point description

Infant birth weight

End point type

Secondary

End point timeframe

Birth

End point values	Metformin	Placebo	Intention to treat
Number of subjects analysed	268	267	535
Units: g
arithmetic mean (standard deviation)	3393.5 ± 527.2	3504.8 ± 509.7	3449.2 ± 521.0

Linear Regression

Comparison groups

Metformin v Placebo v Intention to treat

Number of subjects included in analysis

1070

Analysis specification

Pre-specified

Analysis type

other ^[12]

P-value

= 0.014

Method

Regression, Linear

Parameter type

Mean difference (final values)

Point estimate

-111.37

Confidence interval

level

95%

sides

2-sided

lower limit

-200.28

upper limit

-22.46

Notes
[12] - Two-sided

Secondary: Large for gestational age

Top of page

End point title

Large for gestational age

End point description

End point type

Secondary

End point timeframe

At birth

End point values	Metformin	Placebo	Intention to treat
Number of subjects analysed	268	267	535
Units: neonates
Yes	17	39	56
No	251	228	479
Not recorded	0	0	0

Binary Logistic Regression

Comparison groups

Metformin v Placebo

Number of subjects included in analysis

535

Analysis specification

Pre-specified

Analysis type

other ^[13]

P-value

= 0.002

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

0.4

Confidence interval

level

95%

sides

2-sided

lower limit

0.21

upper limit

0.71

Notes
[13] - Two-sided

Secondary: Small for gestational age

Top of page

End point title

Small for gestational age

End point description

End point type

Secondary

End point timeframe

At birth

End point values	Metformin	Placebo	Intention to treat
Number of subjects analysed	268	267	535
Units: neonates
Yes	15	7	22
No	253	260	513
Not recorded	0	0	0

Binary Logistic Regression

Comparison groups

Metformin v Placebo

Number of subjects included in analysis

535

Analysis specification

Pre-specified

Analysis type

other ^[14]

P-value

= 0.089

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.21

Confidence interval

level

95%

sides

2-sided

lower limit

0.92

upper limit

5.88

Notes
[14] - Two-sided

Secondary: Antepartum hemorrhage

Top of page

End point title

Antepartum hemorrhage

End point description

Diagnosed with antepartum hemorrhage any time during pregnancy

End point type

Secondary

End point timeframe

Any time during pregnancy

End point values	Metformin	Placebo	Intention to treat
Number of subjects analysed	268	267	535
Units: subjects
Yes	15	27	42
No	253	240	493
Not recorded	0	0	0

Binary Logistic Regression

Comparison groups

Metformin v Placebo

Number of subjects included in analysis

535

Analysis specification

Pre-specified

Analysis type

other ^[15]

P-value

= 0.058

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

0.53

Confidence interval

level

95%

sides

2-sided

lower limit

0.27

upper limit

1.01

Notes
[15] - Two-sided

Secondary: Infant crown-heel lenght

Top of page

End point title

Infant crown-heel lenght

End point description

End point type

Secondary

End point timeframe

at birth

End point values	Metformin	Placebo	Intention to treat
Number of subjects analysed	268	267	535
Units: cm
arithmetic mean (standard deviation)	51 ± 3.2	51.7 ± 3.2	51.3 ± 3.2

Linear Regression

Comparison groups

Metformin v Placebo v Intention to treat

Number of subjects included in analysis

1070

Analysis specification

Pre-specified

Analysis type

other ^[16]

P-value

= 0.62

Method

Regression, Linear

Parameter type

Mean difference (final values)

Point estimate

0.05

Confidence interval

level

95%

sides

2-sided

lower limit

-0.34

upper limit

0.25

Notes
[16] - two-sided

Secondary: Need for neonatal ICU

Top of page

End point title

Need for neonatal ICU

End point description

End point type

Secondary

End point timeframe

early neonatal period

End point values	Metformin	Placebo	Intention to treat
Number of subjects analysed	268	267	535
Units: neonates
yes	41	33	74
no	227	234	461
not recorded	0	0	0

Binary Logistic Regression

Comparison groups

Metformin v Placebo v Intention to treat

Number of subjects included in analysis

1070

Analysis specification

Pre-specified

Analysis type

other ^[17]

P-value

= 0.308

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.29

Confidence interval

level

95%

sides

2-sided

lower limit

0.79

upper limit

2.13

Notes
[17] - two-sided

Secondary: Respiratory distress syndrome

Top of page

End point title

Respiratory distress syndrome

End point description

End point type

Secondary

End point timeframe

early neonatal period

End point values	Metformin	Placebo	Intention to treat
Number of subjects analysed	268	267	535
Units: neonates
yes	24	18	42
no	244	249	493
not recorded	0	0	0

Binary Logistic Regression

Comparison groups

Metformin v Placebo

Number of subjects included in analysis

535

Analysis specification

Pre-specified

Analysis type

other ^[18]

P-value

= 0.33

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.37

Confidence interval

level

95%

sides

2-sided

lower limit

0.73

upper limit

2.63

Notes
[18] - two-sided

Secondary: Jaundice

Top of page

End point title

Jaundice

End point description

End point type

Secondary

End point timeframe

early neonatal period

End point values	Metformin	Placebo	Intention to treat
Number of subjects analysed	268	267	535
Units: neonates
yes	128	132	260
no	140	135	275
not recorded	0	0	0

Binary Logistic Regression

Comparison groups

Metformin v Placebo

Number of subjects included in analysis

535

Analysis specification

Pre-specified

Analysis type

other ^[19]

P-value

= 0.76

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

0.95

Confidence interval

level

95%

sides

2-sided

lower limit

0.67

upper limit

1.33

Notes
[19] - two-sided

Secondary: Major cogenital anomalies

Top of page

End point title

Major cogenital anomalies

End point description

End point type

Secondary

End point timeframe

early neonatal period

End point values	Metformin	Placebo	Intention to treat
Number of subjects analysed	268	267	535
Units: neonates
yes	10	7	17
no	258	260	518
not recorded	0	0	0

Binary Logistic Regression

Comparison groups

Metformin v Placebo

Number of subjects included in analysis

535

Analysis specification

Pre-specified

Analysis type

other ^[20]

P-value

= 0.457

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.45

Confidence interval

level

95%

sides

2-sided

lower limit

0.55

upper limit

4.05

Notes
[20] - two-sided

Secondary: APGAR score

Top of page

End point title

APGAR score

End point description

End point type

Secondary

End point timeframe

5 minutes postpartum

End point values	Metformin	Placebo	Intention to treat
Number of subjects analysed	268	267	535
Units: number
median (inter-quartile range (Q1-Q3))	9 (9 to 9)	9 (9 to 9)	9 (9 to 9)

Linear Regression

Comparison groups

Metformin v Placebo

Number of subjects included in analysis

535

Analysis specification

Pre-specified

Analysis type

other ^[21]

P-value

= 0.664

Method

Regression, Linear

Parameter type

Median difference (final values)

Point estimate

0.02

Confidence interval

level

95%

sides

2-sided

lower limit

-0.07

upper limit

0.11

Notes
[21] - two-sided

Secondary: Neonatal hypoglycaemia

Top of page

End point title

Neonatal hypoglycaemia

End point description

End point type

Secondary

End point timeframe

early neonatal period

End point values	Metformin	Placebo	Intention to treat
Number of subjects analysed	268	267	535
Units: neonates
yes	34	25	59
no	234	242	476
not recorded	0	0	0

Binary Logistic Regression

Comparison groups

Metformin v Placebo

Number of subjects included in analysis

535

Analysis specification

Pre-specified

Analysis type

other ^[22]

P-value

= 0.21

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.42

Confidence interval

level

95%

sides

2-sided

lower limit

0.82

upper limit

2.48

Notes
[22] - two-sided

Secondary: Infant morbidities

Top of page

End point title

Infant morbidities

End point description

End point type

Secondary

End point timeframe

early neonatal period

End point values	Metformin	Placebo	Intention to treat
Number of subjects analysed	268	267	535
Units: neonates
yes	144	147	291
no	124	120	244
not recorded	0	0	0

Binary Logistic Regression

Comparison groups

Metformin v Placebo

Number of subjects included in analysis

535

Analysis specification

Post-hoc

Analysis type

other ^[23]

P-value

= 0.83

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

0.96

Confidence interval

level

95%

sides

2-sided

lower limit

0.68

upper limit

1.36

Notes
[23] - two-sided

Secondary: DTSQ satisfaction scale

Top of page

End point title

DTSQ satisfaction scale

End point description

End point type

Secondary

End point timeframe

Week 12 visit

End point values	Metformin	Placebo	Intention to treat
Number of subjects analysed	268	267	535
Units: score
median (inter-quartile range (Q1-Q3))	34 (31 to 36)	33 (29 to 36)	34 (30 to 36)

Linear Regression

Comparison groups

Metformin v Placebo

Number of subjects included in analysis

535

Analysis specification

Pre-specified

Analysis type

other ^[24]

P-value

= 0.288

Method

Regression, Linear

Parameter type

Median difference (final values)

Point estimate

0.47

Confidence interval

level

95%

sides

2-sided

lower limit

-0.4

upper limit

1.35

Notes
[24] - Two-sided

Secondary: DTSQ burden scale

Top of page

End point title

DTSQ burden scale

End point description

End point type

Secondary

End point timeframe

Week 12 visit

End point values	Metformin	Placebo	Intention to treat
Number of subjects analysed	268	267	535
Units: score
median (inter-quartile range (Q1-Q3))	2 (1 to 3)	2 (1 to 4)	2 (1 to 4)

Linear Regression

Comparison groups

Metformin v Placebo

Number of subjects included in analysis

535

Analysis specification

Pre-specified

Analysis type

other ^[25]

P-value

= 0.003

Method

Regression, Linear

Parameter type

Median difference (final values)

Point estimate

-0.68

Confidence interval

level

95%

sides

2-sided

lower limit

-1.13

upper limit

-0.24

Notes
[25] - Two-sided

Secondary: Gestational age at birth

Top of page

End point title

Gestational age at birth

End point description

End point type

Secondary

End point timeframe

At birth

End point values	Metformin	Placebo	Intention to treat
Number of subjects analysed	268	267	535
Units: weeks
median (inter-quartile range (Q1-Q3))	39.4 (38.6 to 40.0)	39.3 (38.7 to 40.0)	39.3 (38.7 to 40.0)

Linear Regression

Comparison groups

Metformin v Placebo

Number of subjects included in analysis

535

Analysis specification

Pre-specified

Analysis type

other ^[26]

P-value

= 0.662

Method

Regression, Linear

Parameter type

Median difference (final values)

Point estimate

-0.06

Confidence interval

level

95%

sides

2-sided

lower limit

-0.39

upper limit

0.19

Notes
[26] - Two-sided

Secondary: Maternal BMI

Top of page

End point title

Maternal BMI

End point description

End point type

Secondary

End point timeframe

12 weeks post partum

End point values	Metformin	Placebo	Intention to treat
Number of subjects analysed	268	267	535
Units: kg/m^2
median (inter-quartile range (Q1-Q3))	28.2 (25.2 to 32.1)	29.7 (26.6 to 34.5)	29.1 (25.8 to 33.2)

Linear Regression

Comparison groups

Metformin v Placebo

Number of subjects included in analysis

535

Analysis specification

Pre-specified

Analysis type

other ^[27]

P-value

= 0.018

Method

Regression, Linear

Parameter type

Median difference (final values)

Point estimate

-1.22

Confidence interval

level

95%

sides

2-sided

lower limit

-2.22

upper limit

-0.21

Notes
[27] - Two-sided

Secondary: Maternal waist circumference

Top of page

End point title

Maternal waist circumference

End point description

End point type

Secondary

End point timeframe

12 weeks postpartum

End point values	Metformin	Placebo	Intention to treat
Number of subjects analysed	268	267	535
Units: cm
arithmetic mean (standard deviation)	93 ± 13	95.2 ± 12.2	94.0 ± 12.6

Linear Regression

Comparison groups

Metformin v Placebo

Number of subjects included in analysis

535

Analysis specification

Pre-specified

Analysis type

P-value

= 0.061

Method

Regression, Linear

Parameter type

Mean difference (final values)

Point estimate

-2.2

Confidence interval

level

95%

sides

2-sided

lower limit

-4.51

upper limit

0.1

Secondary: Infant head circumference

Top of page

End point title

Infant head circumference

End point description

End point type

Secondary

End point timeframe

at birth

End point values	Metformin	Placebo	Intention to treat
Number of subjects analysed	268	267	535
Units: cm
arithmetic mean (standard deviation)	34.7 ± 1.6	34.7 ± 1.8	34.7 ± 1.7

Linear Regression

Comparison groups

Placebo v Metformin

Number of subjects included in analysis

535

Analysis specification

Pre-specified

Analysis type

other ^[28]

P-value

= 0.762

Method

Regression, Linear

Parameter type

Mean difference (final values)

Point estimate

-0.05

Confidence interval

level

95%

sides

2-sided

lower limit

-0.34

upper limit

0.25

Notes
[28] - Two-sided

Adverse events

Top of page

Timeframe for reporting adverse events

Maternal events during pregnancy and up to 12 weeks postpartum; Neonatal events intrapartum and early neonatal period.

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

26.1

Reporting group title

Metformin

Reporting group description

Reporting group title

Placebo

Reporting group description

Serious adverse events	Metformin	Placebo
Total subjects affected by serious adverse events
subjects affected / exposed	159 / 262 (60.69%)	172 / 263 (65.40%)
number of deaths (all causes)	2	1
number of deaths resulting from adverse events	2	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Haemangioma
Additional description: Haemangioma
subjects affected / exposed	3 / 262 (1.15%)	5 / 263 (1.90%)
occurrences causally related to treatment / all	0 / 4	0 / 6
deaths causally related to treatment / all	0 / 0	0 / 0
Haemangioma to right neck
Additional description: Haemangioma to right neck
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Haemangiomas
Additional description: Haemangiomas
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hemangiomas
Additional description: Hemangiomas
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Naevus
Additional description: Naevus
subjects affected / exposed	0 / 262 (0.00%)	2 / 263 (0.76%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Nevus simplex
Additional description: Nevus simplex
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Vascular disorders
Exacerbation of essential hypertension
Additional description: Exacerbation of essential hypertension
subjects affected / exposed	2 / 262 (0.76%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Subgaleal haematoma
Additional description: Subgaleal haematoma
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Superficial thrombophlebitis
Additional description: Superficial thrombophlebitis
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Surgical and medical procedures
Monitoring post vaccine
Additional description: Monitoring post vaccine
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Presumed early onset sepsis from gbs infection
Additional description: Presumed early onset sepsis from gbs infection
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Prophylactic antibiotic administration
Additional description: Prophylactic antibiotic administration
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Suspected sepsis
Additional description: Suspected sepsis
subjects affected / exposed	1 / 262 (0.38%)	2 / 263 (0.76%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Pregnancy, puerperium and perinatal conditions
Absent end diastolic flow umbilical artery
Additional description: Absent end diastolic flow umbilical artery
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Abdominal tightenings
Additional description: Abdominal tightenings
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Birth weight less than 2500g
Additional description: Birth weight less than 2500g
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Breastfeeding jaundice
Additional description: Breastfeeding jaundice
subjects affected / exposed	1 / 262 (0.38%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cholestatic jaundice
Additional description: Cholestatic jaundice
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cephalohaematoma
Additional description: Cephalohaematoma
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Contractions
Additional description: Contractions
subjects affected / exposed	0 / 262 (0.00%)	2 / 263 (0.76%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Excessive weight loss after birth
Additional description: Excessive weight loss after birth
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Fetal growth restriction
Additional description: Fetal growth restriction
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Growth restriction
Additional description: Growth restriction
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hellp syndrome
Additional description: Hellp syndrome
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Jaundice
Additional description: Jaundice
subjects affected / exposed	3 / 262 (1.15%)	3 / 263 (1.14%)
occurrences causally related to treatment / all	0 / 3	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Irritable uterus
Additional description: Irritable uterus
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Intrauterine growth restriction (iugr)
Additional description: Intrauterine growth restriction (iugr)
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Intra-uterine death at 34 weeks gestation
Additional description: Intra-uterine death at 34 weeks gestation
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Intermittent absent end diastolic flow
Additional description: Intermittent absent end diastolic flow
subjects affected / exposed	1 / 262 (0.38%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Increased head circumference measurement
Additional description: Increased head circumference measurement
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hypertensive disorder in pregnancy
Additional description: Hypertensive disorder in pregnancy
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Low birthweight due to prematurity
Additional description: Low birthweight due to prematurity
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Low birth weight
Additional description: Low birth weight
subjects affected / exposed	2 / 262 (0.76%)	2 / 263 (0.76%)
occurrences causally related to treatment / all	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Neonatal jaundice
Additional description: Neonatal jaundice
subjects affected / exposed	2 / 262 (0.76%)	2 / 263 (0.76%)
occurrences causally related to treatment / all	0 / 3	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Nicu admission for low birth weight
Additional description: Nicu admission for low birth weight
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Oligohydamnios
Additional description: Oligohydamnios
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Oligohydramnios
Additional description: Oligohydramnios
subjects affected / exposed	3 / 262 (1.15%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pathological (dct positive) jaundice
Additional description: Pathological (dct positive) jaundice
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Persistant jaundice
Additional description: Persistant jaundice
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Placental abruption
Additional description: Placental abruption
subjects affected / exposed	1 / 262 (0.38%)	4 / 263 (1.52%)
occurrences causally related to treatment / all	0 / 1	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Polyhydramnios
Additional description: Polyhydramnios
subjects affected / exposed	0 / 262 (0.00%)	2 / 263 (0.76%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Possible intrauterine growth restriction
Additional description: Possible intrauterine growth restriction
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Possible pet
Additional description: Possible pet
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Possible placental abruption
Additional description: Possible placental abruption
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pre-eclampsia
Additional description: Pre-eclampsia
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pre-term labour
Additional description: Pre-term labour
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Prematurity
Additional description: Prematurity
subjects affected / exposed	4 / 262 (1.53%)	4 / 263 (1.52%)
occurrences causally related to treatment / all	0 / 4	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Pressure with decreased foetal movement
Additional description: Pressure with decreased foetal movement
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Post-partum haemorrhage
Additional description: Post-partum haemorrhage
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Query pre-term labour
Additional description: Query pre-term labour
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Reduced feeding/ weight loss >10% of birth weight
Additional description: Reduced feeding/ weight loss >10% of birth weight
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Reduced fetal movement
Additional description: Reduced fetal movement
subjects affected / exposed	8 / 262 (3.05%)	8 / 263 (3.04%)
occurrences causally related to treatment / all	0 / 8	0 / 8
deaths causally related to treatment / all	0 / 0	0 / 0
Reduced fetal movements
Additional description: Reduced fetal movements
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Reduced foetal movement
Additional description: Reduced foetal movement
subjects affected / exposed	8 / 262 (3.05%)	7 / 263 (2.66%)
occurrences causally related to treatment / all	0 / 10	0 / 7
deaths causally related to treatment / all	0 / 0	0 / 0
Retained placenta
Additional description: Retained placenta
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Retained placental tissue
Additional description: Retained placental tissue
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Secondary post partum haemorrhage
Additional description: Secondary post partum haemorrhage
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Small for gestational age
Additional description: Small for gestational age
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Suspected pre-term labour
Additional description: Suspected pre-term labour
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Threatened pre-term labour
Additional description: Threatened pre-term labour
subjects affected / exposed	2 / 262 (0.76%)	2 / 263 (0.76%)
occurrences causally related to treatment / all	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Threatened preterm labour
Additional description: Threatened preterm labour
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Umbilical cord prolapse
Additional description: Umbilical cord prolapse
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Unstable fetal lie in utero
Additional description: Unstable fetal lie in utero
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Unstable lie
Additional description: Unstable lie
subjects affected / exposed	1 / 262 (0.38%)	2 / 263 (0.76%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Weight loss
Additional description: Weight loss
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Weight loss >10% of birth weight
Additional description: Weight loss >10% of birth weight
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Weight loss greater than 10%
Additional description: Weight loss greater than 10%
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Weight loss of more than 10% since birth
Additional description: Weight loss of more than 10% since birth
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Weight loss > 10% of birth weight
Additional description: Weight loss > 10% of birth weight
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
General disorders and administration site conditions
Chest pain due to anemia
Additional description: Chest pain due to anemia
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Chest pain
Additional description: Chest pain
subjects affected / exposed	2 / 262 (0.76%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Feeling weak
Additional description: Feeling weak
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Left calf swelling
Additional description: Left calf swelling
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pain and pressure upper chest
Additional description: Pain and pressure upper chest
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pain post c-section and tubal ligation
Additional description: Pain post c-section and tubal ligation
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pain under breast bone bilaterally
Additional description: Pain under breast bone bilaterally
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pyrexia
Additional description: Pyrexia
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Swollen lower left limb
Additional description: Swollen lower left limb
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Swollen right leg
Additional description: Swollen right leg
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Immune system disorders
Post vaccine reaction
Additional description: Post vaccine reaction
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Reproductive system and breast disorders
Patient thought her waters broke
Additional description: Patient thought her waters broke
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Vaginal bleed
Additional description: Vaginal bleed
subjects affected / exposed	1 / 262 (0.38%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Vaginal discharge
Additional description: Vaginal discharge
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Vaginal spotting
Additional description: Vaginal spotting
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Dyspnoea
Additional description: Dyspnoea
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Cyanosis
Additional description: Cyanosis
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Massive pulmonary embolism
Additional description: Massive pulmonary embolism
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Low oxygen saturation levels
Additional description: Low oxygen saturation levels
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumothorax
Additional description: Pneumothorax
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pulmonary emboli
Additional description: Pulmonary emboli
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory arrest
Additional description: Respiratory arrest
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory distress
Additional description: Respiratory distress
subjects affected / exposed	7 / 262 (2.67%)	10 / 263 (3.80%)
occurrences causally related to treatment / all	0 / 7	0 / 10
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory distress syndrome
Additional description: Respiratory distress syndrome
subjects affected / exposed	3 / 262 (1.15%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Transient tachypnea of the newborn
Additional description: Transient tachypnea of the newborn
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Tachypnoea
Additional description: Tachypnoea
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Transient tachypnoea of newborn
Additional description: Transient tachypnoea of newborn
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Transient tachypnoea of the newborn
Additional description: Transient tachypnoea of the newborn
subjects affected / exposed	6 / 262 (2.29%)	2 / 263 (0.76%)
occurrences causally related to treatment / all	0 / 6	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Psychiatric disorders
Irritability
Additional description: Irritability
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Investigations
Borderline elevated blood pressure
Additional description: Borderline elevated blood pressure
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Deranged liver function tests
Additional description: Deranged liver function tests
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Elevated blood pressure
Additional description: Elevated blood pressure
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Heart murmur
Additional description: Heart murmur
subjects affected / exposed	2 / 262 (0.76%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Raised blood pressure
Additional description: Raised blood pressure
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Systolic murmur
Additional description: Systolic murmur
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Weight loss
Additional description: Weight loss
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Injury, poisoning and procedural complications
Ankle fracture
Additional description: Ankle fracture
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Close contact with group a streptococus
Additional description: Close contact with group a streptococus
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Contact in person with ringworm
Additional description: Contact in person with ringworm
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Fall
Additional description: Fall
subjects affected / exposed	2 / 262 (0.76%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hip subluxation
Additional description: Hip subluxation
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Haematoma over caesarean section scar
Additional description: Haematoma over caesarean section scar
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Head injury
Additional description: Head injury
subjects affected / exposed	1 / 262 (0.38%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Headache
Additional description: Headache
subjects affected / exposed	1 / 262 (0.38%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Patient fell at home
Additional description: Patient fell at home
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Reaction to 2 month vaccine
Additional description: Reaction to 2 month vaccine
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Skull fracture
Additional description: Skull fracture
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Spinal headache
Additional description: Spinal headache
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Superficial burn to right hand
Additional description: Superficial burn to right hand
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Suspected hip subluxation
Additional description: Suspected hip subluxation
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Tick bite
Additional description: Tick bite
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Trauma to right abdomen post fall
Additional description: Trauma to right abdomen post fall
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Congenital, familial and genetic disorders
?Tongue tie
Additional description: ?Tongue tie
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Aortic arch hypoplasia
Additional description: Aortic arch hypoplasia
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Atrial septal defect
Additional description: Atrial septal defect
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Atrial septal defect (asd)
Additional description: Atrial septal defect (asd)
subjects affected / exposed	1 / 262 (0.38%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Bifid uvula
Additional description: Bifid uvula
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Bilateral cryptorchidism
Additional description: Bilateral cryptorchidism
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Bilateral hydroceles
Additional description: Bilateral hydroceles
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Bilateral webbed feet
Additional description: Bilateral webbed feet
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Birthmark
Additional description: Birthmark
subjects affected / exposed	8 / 262 (3.05%)	8 / 263 (3.04%)
occurrences causally related to treatment / all	0 / 8	0 / 8
deaths causally related to treatment / all	0 / 0	0 / 0
Birthmark on nape of neck
Additional description: Birthmark on nape of neck
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Birthmarks
Additional description: Birthmarks
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cleft lip
Additional description: Cleft lip
subjects affected / exposed	1 / 262 (0.38%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cleft gum
Additional description: Cleft gum
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Chordee
Additional description: Chordee
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Congenital dermal melanocytosis
Additional description: Congenital dermal melanocytosis
subjects affected / exposed	6 / 262 (2.29%)	2 / 263 (0.76%)
occurrences causally related to treatment / all	0 / 6	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Congenital heart defect
Additional description: Congenital heart defect
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Congenital heart defects (chd)
Additional description: Congenital heart defects (chd)
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Congenital melanocytic naevus
Additional description: Congenital melanocytic naevus
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Congenital pneumonia
Additional description: Congenital pneumonia
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Dermal melanocytosis
Additional description: Dermal melanocytosis
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Cryptorchidism
Additional description: Cryptorchidism
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Epispadias
Additional description: Epispadias
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Left sided torticollis
Additional description: Left sided torticollis
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hydrocele
Additional description: Hydrocele
subjects affected / exposed	1 / 262 (0.38%)	3 / 263 (1.14%)
occurrences causally related to treatment / all	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Laryngomalacia
Additional description: Laryngomalacia
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hypospadias
Additional description: Hypospadias
subjects affected / exposed	2 / 262 (0.76%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Mongolion blue spot
Additional description: Mongolion blue spot
subjects affected / exposed	0 / 262 (0.00%)	2 / 263 (0.76%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Mongolian blue spots
Additional description: Mongolian blue spots
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Mongolian blue spot birthmark
Additional description: Mongolian blue spot birthmark
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Mongolian blue spot
Additional description: Mongolian blue spot
subjects affected / exposed	2 / 262 (0.76%)	7 / 263 (2.66%)
occurrences causally related to treatment / all	0 / 2	0 / 7
deaths causally related to treatment / all	0 / 0	0 / 0
Lip tie
Additional description: Lip tie
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Multiple congenital dermal melanocytosis
Additional description: Multiple congenital dermal melanocytosis
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Naevus simplex
Additional description: Naevus simplex
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Nevus flammeus simplex
Additional description: Nevus flammeus simplex
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Nevus simplex
Additional description: Nevus simplex
subjects affected / exposed	0 / 262 (0.00%)	2 / 263 (0.76%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Patent foramen ovale
Additional description: Patent foramen ovale
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Persistent pulmonary hypertension of the newborn
Additional description: Persistent pulmonary hypertension of the newborn
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Polydactyly
Additional description: Polydactyly
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Possible foetal hydronephrosis
Additional description: Possible foetal hydronephrosis
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Possible hydrocele
Additional description: Possible hydrocele
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Possible hypospadias
Additional description: Possible hypospadias
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pectus carinatum
Additional description: Pectus carinatum
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Preauricular skin tag
Additional description: Preauricular skin tag
subjects affected / exposed	1 / 262 (0.38%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pyloric stenosis
Additional description: Pyloric stenosis
subjects affected / exposed	2 / 262 (0.76%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Suspected laryngomalacia
Additional description: Suspected laryngomalacia
subjects affected / exposed	1 / 262 (0.38%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Salmon patch right eyelid and nasal bridge
Additional description: Salmon patch right eyelid and nasal bridge
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Skin tag
Additional description: Skin tag
subjects affected / exposed	1 / 262 (0.38%)	2 / 263 (0.76%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Stork mark
Additional description: Stork mark
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Suspected ventricular septal defect
Additional description: Suspected ventricular septal defect
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Talipes
Additional description: Talipes
subjects affected / exposed	1 / 262 (0.38%)	2 / 263 (0.76%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Talipes varus
Additional description: Talipes varus
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Tongue tie
Additional description: Tongue tie
subjects affected / exposed	20 / 262 (7.63%)	35 / 263 (13.31%)
occurrences causally related to treatment / all	0 / 20	0 / 35
deaths causally related to treatment / all	0 / 0	0 / 0
Trisomy 13
Additional description: Trisomy 13
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Unilateral cryptorchidism
Additional description: Unilateral cryptorchidism
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Undescended right testicle
Additional description: Undescended right testicle
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Trisomy 21
Additional description: Trisomy 21
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Ventricular septal defect
Additional description: Ventricular septal defect
subjects affected / exposed	2 / 262 (0.76%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiac disorders
Bradycardia
Additional description: Bradycardia
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Fetal bradycardia
Additional description: Fetal bradycardia
subjects affected / exposed	0 / 262 (0.00%)	2 / 263 (0.76%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Fetal bradycardia in labour
Additional description: Fetal bradycardia in labour
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Foetal bradycardia
Additional description: Foetal bradycardia
subjects affected / exposed	2 / 262 (0.76%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Maternal tachycardia
Additional description: Maternal tachycardia
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Persistent maternal tachycardia
Additional description: Persistent maternal tachycardia
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Tachycardia
Additional description: Tachycardia
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Nervous system disorders
Focal migraine
Additional description: Focal migraine
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Grade 4 intraventricular haemorrhage
Additional description: Grade 4 intraventricular haemorrhage
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Headache
Additional description: Headache
subjects affected / exposed	2 / 262 (0.76%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Migraine headache
Additional description: Migraine headache
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Migraine aura
Additional description: Migraine aura
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Occipital headache
Additional description: Occipital headache
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Possible bell's palsy
Additional description: Possible bell's palsy
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Possible evolving pet (pre-eclamptic toxaemia)
Additional description: Possible evolving pet (pre-eclamptic toxaemia)
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Posterior reversible encephalopathy syndrome
Additional description: Posterior reversible encephalopathy syndrome
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Posterior reversible encephalopathy syndrome (pres
Additional description: Posterior reversible encephalopathy syndrome (pres
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pre-syncope
Additional description: Pre-syncope
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Seventh nerve palsy
Additional description: Seventh nerve palsy
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Severe frontal headache
Additional description: Severe frontal headache
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Syncope
Additional description: Syncope
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Blood and lymphatic system disorders
Anaemia
Additional description: Anaemia
subjects affected / exposed	1 / 262 (0.38%)	2 / 263 (0.76%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Echogenic mass on ultrasound
Additional description: Echogenic mass on ultrasound
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Eye disorders
Eye twitching/jerking episode
Additional description: Eye twitching/jerking episode
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pale optic disc
Additional description: Pale optic disc
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Ptosis
Additional description: Ptosis
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal disorders
Abdominal pain
Additional description: Abdominal pain
subjects affected / exposed	4 / 262 (1.53%)	3 / 263 (1.14%)
occurrences causally related to treatment / all	0 / 5	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Abdominal cramps
Additional description: Abdominal cramps
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Admitted with abdominal pain and contractions 1:10
Additional description: Admitted with abdominal pain and contractions 1:10
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Admitted with abdominal pain
Additional description: Admitted with abdominal pain
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Diarrhoea
Additional description: Diarrhoea
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Colic
Additional description: Colic
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Gastro-intestinal upset
Additional description: Gastro-intestinal upset
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Gastro-oesophageal reflux
Additional description: Gastro-oesophageal reflux
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal upset
Additional description: Gastrointestinal upset
subjects affected / exposed	5 / 262 (1.91%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	1 / 5	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Left lower abdominal pain.
Additional description: Left lower abdominal pain.
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Left sided abdominal pain
Additional description: Left sided abdominal pain
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Lower abdominal pain
Additional description: Lower abdominal pain
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Left-sided abdominal pain
Additional description: Left-sided abdominal pain
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Nipple confusion
Additional description: Nipple confusion
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Projectile vomiting
Additional description: Projectile vomiting
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Small anal fissure
Additional description: Small anal fissure
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Right sided inguinal hernia
Additional description: Right sided inguinal hernia
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Upper abdominal pain
Additional description: Upper abdominal pain
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Viral gastritis
Additional description: Viral gastritis
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Vomiting
Additional description: Vomiting
subjects affected / exposed	2 / 262 (0.76%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 3	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hepatobiliary disorders
Cholestasis
Additional description: Cholestasis
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Cholecystitis
Additional description: Cholecystitis
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Transient neonatal hepatitis
Additional description: Transient neonatal hepatitis
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Caesearen section scar tenderness
Additional description: Caesearen section scar tenderness
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Casarean section scar tenderness
Additional description: Casarean section scar tenderness
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Generalised rash on all limbs and torso
Additional description: Generalised rash on all limbs and torso
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pruritic rash
Additional description: Pruritic rash
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pruritus
Additional description: Pruritus
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Uriticaria to chin
Additional description: Uriticaria to chin
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Renal and urinary disorders
Chronic kidney disease 3a
Additional description: Chronic kidney disease 3a
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Elevated protein creatinine level (pcr)
Additional description: Elevated protein creatinine level (pcr)
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Ketonuria
Additional description: Ketonuria
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Moderate right hydronephrosis
Additional description: Moderate right hydronephrosis
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Meatal stenosis
Additional description: Meatal stenosis
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Raised protein creatinine ratio (pcr)
Additional description: Raised protein creatinine ratio (pcr)
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Urinary incontinence
Additional description: Urinary incontinence
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Urinary retention
Additional description: Urinary retention
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Back pain
Additional description: Back pain
subjects affected / exposed	1 / 262 (0.38%)	3 / 263 (1.14%)
occurrences causally related to treatment / all	0 / 1	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Lower limb cramps
Additional description: Lower limb cramps
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Right leg calf pain
Additional description: Right leg calf pain
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Right hip pain
Additional description: Right hip pain
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Right leg musle cramps
Additional description: Right leg musle cramps
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Upper back pain
Additional description: Upper back pain
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Infections and infestations
Acute bronchiolitis
Additional description: Acute bronchiolitis
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Adenovirus
Additional description: Adenovirus
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Broncholitis
Additional description: Broncholitis
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Bronchiolitis
Additional description: Bronchiolitis
subjects affected / exposed	4 / 262 (1.53%)	4 / 263 (1.52%)
occurrences causally related to treatment / all	0 / 4	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Breast abcess
Additional description: Breast abcess
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Chronic sinusitis
Additional description: Chronic sinusitis
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
E coli urinary tract infection
Additional description: E coli urinary tract infection
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Covid-19
Additional description: Covid-19
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Covid 19
Additional description: Covid 19
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Endometritis
Additional description: Endometritis
subjects affected / exposed	1 / 262 (0.38%)	2 / 263 (0.76%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Enteroviral meningitis
Additional description: Enteroviral meningitis
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Genito -urinary tract infection
Additional description: Genito -urinary tract infection
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Group b streptococcus urinary tract infection
Additional description: Group b streptococcus urinary tract infection
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastroenteritis
Additional description: Gastroenteritis
subjects affected / exposed	2 / 262 (0.76%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Infected axillary abscess
Additional description: Infected axillary abscess
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Oral thrush
Additional description: Oral thrush
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Possible urinary tract infection
Additional description: Possible urinary tract infection
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Possible pyelonephritis
Additional description: Possible pyelonephritis
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory synctial virus (rsv)
Additional description: Respiratory synctial virus (rsv)
subjects affected / exposed	1 / 262 (0.38%)	2 / 263 (0.76%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory syncytial virus
Additional description: Respiratory syncytial virus
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory tract infection
Additional description: Respiratory tract infection
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Right frontal sinusitis
Additional description: Right frontal sinusitis
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Sepsis
Additional description: Sepsis
subjects affected / exposed	1 / 262 (0.38%)	2 / 263 (0.76%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Sepsis secondary to endometritis group a streptoco
Additional description: Sepsis secondary to endometritis group a streptoco
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Suspected sepsis
Additional description: Suspected sepsis
subjects affected / exposed	0 / 262 (0.00%)	2 / 263 (0.76%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Umbilical flare
Additional description: Umbilical flare
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Viral meningitis
Additional description: Viral meningitis
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Upper respiratory tract infection
Additional description: Upper respiratory tract infection
subjects affected / exposed	1 / 262 (0.38%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Urinary tract infection
Additional description: Urinary tract infection
subjects affected / exposed	6 / 262 (2.29%)	3 / 263 (1.14%)
occurrences causally related to treatment / all	0 / 6	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Urosepsis
Additional description: Urosepsis
subjects affected / exposed	1 / 262 (0.38%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Vaginal infection
Additional description: Vaginal infection
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Viral illness
Additional description: Viral illness
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Viral infection
Additional description: Viral infection
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Viral respiratory tract infection
Additional description: Viral respiratory tract infection
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Wound infection
Additional description: Wound infection
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Metabolism and nutrition disorders
Dehydration
Additional description: Dehydration
subjects affected / exposed	1 / 262 (0.38%)	4 / 263 (1.52%)
occurrences causally related to treatment / all	0 / 1	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Failure to thrive
Additional description: Failure to thrive
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hypoglycaemia
Additional description: Hypoglycaemia
subjects affected / exposed	3 / 262 (1.15%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 3	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Neonatal hypoglycaemia
Additional description: Neonatal hypoglycaemia
subjects affected / exposed	2 / 262 (0.76%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Neonatal hypoglycemia
Additional description: Neonatal hypoglycemia
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Poor feeding
Additional description: Poor feeding
subjects affected / exposed	1 / 262 (0.38%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Poor feeding and lethargy
Additional description: Poor feeding and lethargy
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Presumed early onset sepsis
Additional description: Presumed early onset sepsis
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Reduced feeding
Additional description: Reduced feeding
subjects affected / exposed	1 / 262 (0.38%)	0 / 263 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Symptomatic hypoglycaemia
Additional description: Symptomatic hypoglycaemia
subjects affected / exposed	0 / 262 (0.00%)	1 / 263 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 0%

Non-serious adverse events	Metformin	Placebo
Total subjects affected by non serious adverse events
subjects affected / exposed	247 / 262 (94.27%)	258 / 263 (98.10%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Fibroids
Additional description: Fibroids
subjects affected / exposed	0 / 262 (0.00%)	3 / 263 (1.14%)
occurrences all number	0	3
Vascular disorders
Facial suffusion
Additional description: Facial suffusion
subjects affected / exposed	0 / 262 (0.00%)	3 / 263 (1.14%)
occurrences all number	0	3
Hypotension
Additional description: Hypotension
subjects affected / exposed	13 / 262 (4.96%)	4 / 263 (1.52%)
occurrences all number	13	4
Maternal hypotension
Additional description: Maternal hypotension
subjects affected / exposed	2 / 262 (0.76%)	4 / 263 (1.52%)
occurrences all number	2	4
Pregnancy, puerperium and perinatal conditions
Cephalohaematoma
Additional description: Cephalohaematoma
subjects affected / exposed	0 / 262 (0.00%)	3 / 263 (1.14%)
occurrences all number	0	3
Decreased foetal movement
Additional description: Decreased foetal movement
subjects affected / exposed	0 / 262 (0.00%)	3 / 263 (1.14%)
occurrences all number	0	3
Jaundice
Additional description: Jaundice
subjects affected / exposed	17 / 262 (6.49%)	14 / 263 (5.32%)
occurrences all number	17	14
Neonatal jaundice
Additional description: Neonatal jaundice
subjects affected / exposed	19 / 262 (7.25%)	21 / 263 (7.98%)
occurrences all number	21	22
Oligohydramnios
Additional description: Oligohydramnios
subjects affected / exposed	3 / 262 (1.15%)	4 / 263 (1.52%)
occurrences all number	3	4
Post-partum haemorrhage
Additional description: Post-partum haemorrhage
subjects affected / exposed	4 / 262 (1.53%)	0 / 263 (0.00%)
occurrences all number	4	0
Reduced fetal movements
Additional description: Reduced fetal movements
subjects affected / exposed	3 / 262 (1.15%)	1 / 263 (0.38%)
occurrences all number	3	1
Reduced fetal movement
Additional description: Reduced fetal movement
subjects affected / exposed	34 / 262 (12.98%)	38 / 263 (14.45%)
occurrences all number	38	41
Reduced foetal movement
Additional description: Reduced foetal movement
subjects affected / exposed	22 / 262 (8.40%)	26 / 263 (9.89%)
occurrences all number	25	29
General disorders and administration site conditions
Oedema
Additional description: Oedema
subjects affected / exposed	1 / 262 (0.38%)	3 / 263 (1.14%)
occurrences all number	1	3
Pedal oedema
Additional description: Pedal oedema
subjects affected / exposed	2 / 262 (0.76%)	5 / 263 (1.90%)
occurrences all number	2	5
Peripheral oedema
Additional description: Peripheral oedema
subjects affected / exposed	17 / 262 (6.49%)	26 / 263 (9.89%)
occurrences all number	18	26
Pyrexia
Additional description: Pyrexia
subjects affected / exposed	2 / 262 (0.76%)	4 / 263 (1.52%)
occurrences all number	2	4
Reproductive system and breast disorders
Breast lump
Additional description: Breast lump
subjects affected / exposed	3 / 262 (1.15%)	1 / 263 (0.38%)
occurrences all number	3	1
Cervical ectropion
Additional description: Cervical ectropion
subjects affected / exposed	7 / 262 (2.67%)	3 / 263 (1.14%)
occurrences all number	7	3
Vaginal discharge
Additional description: Vaginal discharge
subjects affected / exposed	10 / 262 (3.82%)	8 / 263 (3.04%)
occurrences all number	10	8
Respiratory, thoracic and mediastinal disorders
Cough
Additional description: Cough
subjects affected / exposed	9 / 262 (3.44%)	10 / 263 (3.80%)
occurrences all number	10	10
Low oxygen saturation level
Additional description: Low oxygen saturation level
subjects affected / exposed	3 / 262 (1.15%)	2 / 263 (0.76%)
occurrences all number	3	2
Nasal congestion
Additional description: Nasal congestion
subjects affected / exposed	1 / 262 (0.38%)	7 / 263 (2.66%)
occurrences all number	1	7
Respiratory distress
Additional description: Respiratory distress
subjects affected / exposed	18 / 262 (6.87%)	18 / 263 (6.84%)
occurrences all number	18	18
Sore throat
Additional description: Sore throat
subjects affected / exposed	3 / 262 (1.15%)	6 / 263 (2.28%)
occurrences all number	3	7
Psychiatric disorders
Low mood
Additional description: Low mood
subjects affected / exposed	3 / 262 (1.15%)	1 / 263 (0.38%)
occurrences all number	3	1
Postnatal depression
Additional description: Postnatal depression
subjects affected / exposed	7 / 262 (2.67%)	3 / 263 (1.14%)
occurrences all number	7	3
Investigations
Elevated blood pressure
Additional description: Elevated blood pressure
subjects affected / exposed	4 / 262 (1.53%)	3 / 263 (1.14%)
occurrences all number	4	3
Leucocytes in urine
Additional description: Leucocytes in urine
subjects affected / exposed	13 / 262 (4.96%)	10 / 263 (3.80%)
occurrences all number	14	11
Systolic murmur
Additional description: Systolic murmur
subjects affected / exposed	4 / 262 (1.53%)	3 / 263 (1.14%)
occurrences all number	4	3
Urinary leucocytes
Additional description: Urinary leucocytes
subjects affected / exposed	7 / 262 (2.67%)	10 / 263 (3.80%)
occurrences all number	7	10
Injury, poisoning and procedural complications
Mechanical fall
Additional description: Mechanical fall
subjects affected / exposed	2 / 262 (0.76%)	3 / 263 (1.14%)
occurrences all number	2	3
Congenital, familial and genetic disorders
Closed sacral dimple
Additional description: Closed sacral dimple
subjects affected / exposed	0 / 262 (0.00%)	3 / 263 (1.14%)
occurrences all number	0	3
Click hip
Additional description: Click hip
subjects affected / exposed	5 / 262 (1.91%)	3 / 263 (1.14%)
occurrences all number	5	3
Positional talipes
Additional description: Positional talipes
subjects affected / exposed	5 / 262 (1.91%)	7 / 263 (2.66%)
occurrences all number	5	7
Sacral dimple
Additional description: Sacral dimple
subjects affected / exposed	6 / 262 (2.29%)	7 / 263 (2.66%)
occurrences all number	6	7
Cardiac disorders
Bradycardia
Additional description: Bradycardia
subjects affected / exposed	2 / 262 (0.76%)	4 / 263 (1.52%)
occurrences all number	2	4
Fetal tachycardia
Additional description: Fetal tachycardia
subjects affected / exposed	1 / 262 (0.38%)	3 / 263 (1.14%)
occurrences all number	1	4
Foetal tachycardia
Additional description: Foetal tachycardia
subjects affected / exposed	1 / 262 (0.38%)	3 / 263 (1.14%)
occurrences all number	1	3
Maternal tachycardia
Additional description: Maternal tachycardia
subjects affected / exposed	6 / 262 (2.29%)	10 / 263 (3.80%)
occurrences all number	6	11
Neonatal tachycardia
Additional description: Neonatal tachycardia
subjects affected / exposed	2 / 262 (0.76%)	3 / 263 (1.14%)
occurrences all number	2	3
Palpitations
Additional description: Palpitations
subjects affected / exposed	0 / 262 (0.00%)	3 / 263 (1.14%)
occurrences all number	0	3
Tachycardia
Additional description: Tachycardia
subjects affected / exposed	4 / 262 (1.53%)	3 / 263 (1.14%)
occurrences all number	4	3
Nervous system disorders
Dizzy spells
Additional description: Dizzy spells
subjects affected / exposed	0 / 262 (0.00%)	5 / 263 (1.90%)
occurrences all number	0	6
Dizziness
Additional description: Dizziness
subjects affected / exposed	5 / 262 (1.91%)	3 / 263 (1.14%)
occurrences all number	5	3
Headache
Additional description: Headache
subjects affected / exposed	26 / 262 (9.92%)	32 / 263 (12.17%)
occurrences all number	30	38
Headaches
Additional description: Headaches
subjects affected / exposed	5 / 262 (1.91%)	5 / 263 (1.90%)
occurrences all number	5	5
Migraine
Additional description: Migraine
subjects affected / exposed	5 / 262 (1.91%)	1 / 263 (0.38%)
occurrences all number	6	2
Pre-syncope
Additional description: Pre-syncope
subjects affected / exposed	2 / 262 (0.76%)	4 / 263 (1.52%)
occurrences all number	2	5
Presyncope
Additional description: Presyncope
subjects affected / exposed	0 / 262 (0.00%)	3 / 263 (1.14%)
occurrences all number	0	3
Sciatica
Additional description: Sciatica
subjects affected / exposed	1 / 262 (0.38%)	3 / 263 (1.14%)
occurrences all number	1	3
Syncope
Additional description: Syncope
subjects affected / exposed	2 / 262 (0.76%)	4 / 263 (1.52%)
occurrences all number	2	4
Blood and lymphatic system disorders
Anaemia
Additional description: Anaemia
subjects affected / exposed	42 / 262 (16.03%)	55 / 263 (20.91%)
occurrences all number	43	55
Postnatal anaemia
Additional description: Postnatal anaemia
subjects affected / exposed	10 / 262 (3.82%)	18 / 263 (6.84%)
occurrences all number	10	18
Pregnancy anaemia
Additional description: Pregnancy anaemia
subjects affected / exposed	6 / 262 (2.29%)	4 / 263 (1.52%)
occurrences all number	6	4
Thrombocytopenia
Additional description: Thrombocytopenia
subjects affected / exposed	1 / 262 (0.38%)	4 / 263 (1.52%)
occurrences all number	1	4
Worsening of pregnancy anaemia
Additional description: Worsening of pregnancy anaemia
subjects affected / exposed	3 / 262 (1.15%)	1 / 263 (0.38%)
occurrences all number	3	1
Eye disorders
Left sticky eye
Additional description: Left sticky eye
subjects affected / exposed	1 / 262 (0.38%)	3 / 263 (1.14%)
occurrences all number	1	3
Sticky eye
Additional description: Sticky eye
subjects affected / exposed	6 / 262 (2.29%)	6 / 263 (2.28%)
occurrences all number	6	6
Visual disturbance
Additional description: Visual disturbance
subjects affected / exposed	5 / 262 (1.91%)	0 / 263 (0.00%)
occurrences all number	5	0
Gastrointestinal disorders
Abdominal cramps
Additional description: Abdominal cramps
subjects affected / exposed	8 / 262 (3.05%)	3 / 263 (1.14%)
occurrences all number	8	3
Adhesions
Additional description: Adhesions
subjects affected / exposed	8 / 262 (3.05%)	7 / 263 (2.66%)
occurrences all number	8	7
Abdominal pain
Additional description: Abdominal pain
subjects affected / exposed	12 / 262 (4.58%)	17 / 263 (6.46%)
occurrences all number	12	17
Gastric reflux
Additional description: Gastric reflux
subjects affected / exposed	16 / 262 (6.11%)	16 / 263 (6.08%)
occurrences all number	16	16
Diarrhoea
Additional description: Diarrhoea
subjects affected / exposed	12 / 262 (4.58%)	11 / 263 (4.18%)
occurrences all number	13	14
Gastric upset
Additional description: Gastric upset
subjects affected / exposed	5 / 262 (1.91%)	6 / 263 (2.28%)
occurrences all number	5	6
Colic
Additional description: Colic
subjects affected / exposed	12 / 262 (4.58%)	9 / 263 (3.42%)
occurrences all number	13	9
Constipation
Additional description: Constipation
subjects affected / exposed	12 / 262 (4.58%)	12 / 263 (4.56%)
occurrences all number	12	13
Gastrointestinal upset
Additional description: Gastrointestinal upset
subjects affected / exposed	63 / 262 (24.05%)	14 / 263 (5.32%)
occurrences all number	66	14
Gi upset
Additional description: Gi upset
subjects affected / exposed	4 / 262 (1.53%)	1 / 263 (0.38%)
occurrences all number	4	1
Haemorrhoids
Additional description: Haemorrhoids
subjects affected / exposed	4 / 262 (1.53%)	3 / 263 (1.14%)
occurrences all number	4	3
Lower abdominal pain
Additional description: Lower abdominal pain
subjects affected / exposed	4 / 262 (1.53%)	3 / 263 (1.14%)
occurrences all number	4	3
Nausea
Additional description: Nausea
subjects affected / exposed	6 / 262 (2.29%)	6 / 263 (2.28%)
occurrences all number	6	7
Umbilical hernia
Additional description: Umbilical hernia
subjects affected / exposed	4 / 262 (1.53%)	1 / 263 (0.38%)
occurrences all number	4	1
Toothache
Additional description: Toothache
subjects affected / exposed	2 / 262 (0.76%)	6 / 263 (2.28%)
occurrences all number	2	6
Reflux
Additional description: Reflux
subjects affected / exposed	5 / 262 (1.91%)	3 / 263 (1.14%)
occurrences all number	5	3
Silent reflux
Additional description: Silent reflux
subjects affected / exposed	3 / 262 (1.15%)	1 / 263 (0.38%)
occurrences all number	3	1
Vomiting
Additional description: Vomiting
subjects affected / exposed	7 / 262 (2.67%)	6 / 263 (2.28%)
occurrences all number	7	6
Skin and subcutaneous tissue disorders
Abdominal rash
Additional description: Abdominal rash
subjects affected / exposed	2 / 262 (0.76%)	3 / 263 (1.14%)
occurrences all number	2	3
Eczema
Additional description: Eczema
subjects affected / exposed	2 / 262 (0.76%)	3 / 263 (1.14%)
occurrences all number	2	3
Erythema
Additional description: Erythema
subjects affected / exposed	3 / 262 (1.15%)	0 / 263 (0.00%)
occurrences all number	3	0
Erythema toxicum
Additional description: Erythema toxicum
subjects affected / exposed	8 / 262 (3.05%)	8 / 263 (3.04%)
occurrences all number	8	8
Itch
Additional description: Itch
subjects affected / exposed	6 / 262 (2.29%)	8 / 263 (3.04%)
occurrences all number	6	8
Rash
Additional description: Rash
subjects affected / exposed	3 / 262 (1.15%)	5 / 263 (1.90%)
occurrences all number	3	5
Scar tenderness
Additional description: Scar tenderness
subjects affected / exposed	3 / 262 (1.15%)	3 / 263 (1.14%)
occurrences all number	3	3
Renal and urinary disorders
Dysuria
Additional description: Dysuria
subjects affected / exposed	1 / 262 (0.38%)	3 / 263 (1.14%)
occurrences all number	1	3
Haematuria
Additional description: Haematuria
subjects affected / exposed	12 / 262 (4.58%)	8 / 263 (3.04%)
occurrences all number	12	9
Ketonuria
Additional description: Ketonuria
subjects affected / exposed	28 / 262 (10.69%)	29 / 263 (11.03%)
occurrences all number	33	36
Proteinuria
Additional description: Proteinuria
subjects affected / exposed	46 / 262 (17.56%)	40 / 263 (15.21%)
occurrences all number	56	54
Urinary incontinence
Additional description: Urinary incontinence
subjects affected / exposed	2 / 262 (0.76%)	3 / 263 (1.14%)
occurrences all number	2	3
Musculoskeletal and connective tissue disorders
Back pain
Additional description: Back pain
subjects affected / exposed	6 / 262 (2.29%)	5 / 263 (1.90%)
occurrences all number	6	5
Lower back pain
Additional description: Lower back pain
subjects affected / exposed	4 / 262 (1.53%)	3 / 263 (1.14%)
occurrences all number	4	3
Symphysis pubis dysfunction
Additional description: Symphysis pubis dysfunction
subjects affected / exposed	3 / 262 (1.15%)	0 / 263 (0.00%)
occurrences all number	3	0
Infections and infestations
Cellulitis
Additional description: Cellulitis
subjects affected / exposed	0 / 262 (0.00%)	3 / 263 (1.14%)
occurrences all number	0	3
Candidiasis
Additional description: Candidiasis
subjects affected / exposed	5 / 262 (1.91%)	3 / 263 (1.14%)
occurrences all number	5	3
Bronchiolitis
Additional description: Bronchiolitis
subjects affected / exposed	1 / 262 (0.38%)	7 / 263 (2.66%)
occurrences all number	1	8
Ear infection
Additional description: Ear infection
subjects affected / exposed	3 / 262 (1.15%)	1 / 263 (0.38%)
occurrences all number	3	1
Covid-19
Additional description: Covid-19
subjects affected / exposed	17 / 262 (6.49%)	15 / 263 (5.70%)
occurrences all number	23	19
Conjunctivitis
Additional description: Conjunctivitis
subjects affected / exposed	2 / 262 (0.76%)	6 / 263 (2.28%)
occurrences all number	2	6
Chest infection
Additional description: Chest infection
subjects affected / exposed	3 / 262 (1.15%)	3 / 263 (1.14%)
occurrences all number	3	3
Gastroenteritis
Additional description: Gastroenteritis
subjects affected / exposed	3 / 262 (1.15%)	4 / 263 (1.52%)
occurrences all number	3	4
Head cold
Additional description: Head cold
subjects affected / exposed	10 / 262 (3.82%)	8 / 263 (3.04%)
occurrences all number	10	9
Headcold
Additional description: Headcold
subjects affected / exposed	3 / 262 (1.15%)	4 / 263 (1.52%)
occurrences all number	3	4
Maternal pyrexia
Additional description: Maternal pyrexia
subjects affected / exposed	0 / 262 (0.00%)	10 / 263 (3.80%)
occurrences all number	0	10
Oral candida
Additional description: Oral candida
subjects affected / exposed	5 / 262 (1.91%)	1 / 263 (0.38%)
occurrences all number	6	1
Oral candidiasis
Additional description: Oral candidiasis
subjects affected / exposed	2 / 262 (0.76%)	7 / 263 (2.66%)
occurrences all number	2	8
Oral thrush
Additional description: Oral thrush
subjects affected / exposed	3 / 262 (1.15%)	1 / 263 (0.38%)
occurrences all number	3	1
Pyrexia
Additional description: Pyrexia
subjects affected / exposed	3 / 262 (1.15%)	3 / 263 (1.14%)
occurrences all number	3	3
Upper respiratory tract infection
Additional description: Upper respiratory tract infection
subjects affected / exposed	1 / 262 (0.38%)	3 / 263 (1.14%)
occurrences all number	2	3
Throat infection
Additional description: Throat infection
subjects affected / exposed	0 / 262 (0.00%)	3 / 263 (1.14%)
occurrences all number	0	4
Respiratory tract infection
Additional description: Respiratory tract infection
subjects affected / exposed	14 / 262 (5.34%)	17 / 263 (6.46%)
occurrences all number	16	19
Sinusitis
Additional description: Sinusitis
subjects affected / exposed	4 / 262 (1.53%)	4 / 263 (1.52%)
occurrences all number	4	4
Vaginal candidiasis
Additional description: Vaginal candidiasis
subjects affected / exposed	10 / 262 (3.82%)	10 / 263 (3.80%)
occurrences all number	10	10
Urinary tract infection
Additional description: Urinary tract infection
subjects affected / exposed	32 / 262 (12.21%)	40 / 263 (15.21%)
occurrences all number	39	48
Viral respiratory tract infection
Additional description: Viral respiratory tract infection
subjects affected / exposed	0 / 262 (0.00%)	3 / 263 (1.14%)
occurrences all number	0	3
Vomiting bug
Additional description: Vomiting bug
subjects affected / exposed	2 / 262 (0.76%)	4 / 263 (1.52%)
occurrences all number	2	4
Metabolism and nutrition disorders
Hyperuricaemia
Additional description: Hyperuricaemia
subjects affected / exposed	3 / 262 (1.15%)	0 / 263 (0.00%)
occurrences all number	3	0
Impaired fasting glucose
Additional description: Impaired fasting glucose
subjects affected / exposed	1 / 262 (0.38%)	5 / 263 (1.90%)
occurrences all number	1	5
Neonatal hypoglycaemia
Additional description: Neonatal hypoglycaemia
subjects affected / exposed	10 / 262 (3.82%)	4 / 263 (1.52%)
occurrences all number	10	4

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

05 Dec 2017

Update to inclusion criteria – removal of lower limit of gestational age (24 weeks gestation) to enter the trial as the previous wording excluded women who were diagnosed with GDM prior to 24 weeks gestation; Update to exclusion criteria of women with a fasting glucose of >7 mmol/l or a 2hr value of >11.1mmol/l to a fasting glucose of ≥ 7 or a 2hr value of ≥ 11.1, as fasting glucose values of 7mmol/l and 11.1mmol/l were not represented in previous wording of inclusion/exclusion criteria; Update to exclusion criteria to correct the typographical error in the laboratory test for moderate to severe liver dysfunction from alkaline phosphatase greater than 3 times the upper limit of normal to aspartate aminotransferase (AST) greater than 3 times the upper limit of normal; Update to Exclusion criteria of known fetal anomaly and known small for gestational age as determined by the early or mid-trimester scan amended to remove ‘as determined by the early of mid- trimester scan’ as some patients may be diagnosed with GDM before the early or mid- trimester scan and this may impede recruitment of these patients; Clarification of ‘current’ gestational hypertension as an exclusion criterion; Addition of a biobanking section to clarify that maternal biobank samples would be taken at randomisation and week 12 post randomisation and a cord blood sample would be collected at delivery; Clarification on exemptions from AE reporting as the previous protocol wording was non-specific and open to interpretation in relation to maternal events.

24 May 2019

Exclusion criterion ‘known fetal anomaly’ was updated to ‘Major congenital malformations or an abnormality deemed unsuitable for metformin by the site PI or attending consultant’ as the description of “known foetal anomaly” was vague;Addition of text describing exclusion criterion ‘Small for gestational age (SGA) refers to foetal growth less than the 10th percentile (RCOG, 2014)’ to add ‘or if foetal growth is deemed unsatisfactory by the treating obstetrician’;Update to the 4-week post-partum visit window from (+/- 5 days) to (+/- 7 days) to accommodate weekend days;Reference from two to three trial sites updated;Clarification of definition for neonatal hypoglycaemia;Removal of reference to herbal and vitamin supplements as concomitant medications;Removal of bio-banking section from the main EMERGE protocol;Collection of physical measurements and vital signs aligned to the primary outcome visits at 32 and 38 weeks gestation;Option of a telephone visit for those pre- natal visits that did not require an in person physical measurement, laboratory assessment or drug dispensation;Height and weight measurements of baby removed from the 12 week post-partum visit;Medical history list for documentation of conditions was rationalised as some were already included in exclusion criteria/previously recorded outcomes;clarification on the options around withdrawal of consent and withdrawal from study treatment;Update to prior and concomitant therapy list of medications required to be recorded;Clarification and additional information added for valid SAE criteria, evaluation and reporting timelines to ensure clarity for site on responsibilities and requirements;Addition of list of exemptions to safety reporting for events considered common in pregnancy/postpartum period and those which must be captured as outcomes;Estimate of annual diagnosis figures of GDM updated to include relevant delivery figures from additional study sites referenced in this protocol update.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials

Clinical Trial Results: A Randomised Placebo Controlled Trial of the effectiveness of Early MEtformin in Addition to Usual Care in the Reduction of Gestational Diabetes Mellitus Effects (EMERGE)

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Insulin Initiated Yes/No

Primary: Insulin Initiated Yes/No

Primary: Composite outcome

Primary: Composite outcome

Primary: Fasting hyperglycaemia

Primary: Fasting hyperglycaemia

Secondary: Pre-eclampsia

Secondary: Pre-eclampsia

Secondary: Pregnancy-induced hypertension

Secondary: Pregnancy-induced hypertension

Secondary: Labour type

Secondary: Labour type

Secondary: Weight Gain during pregnancy

Secondary: Weight Gain during pregnancy

Secondary: Postpartum impaired fasting glucose

Secondary: Postpartum impaired fasting glucose

Secondary: Postpartum impaired glucose tolerance by 2hr OGTT

Secondary: Postpartum impaired glucose tolerance by 2hr OGTT

Secondary: Postpartum metabolic syndrome

Secondary: Postpartum metabolic syndrome

Secondary: Birth weight

Secondary: Birth weight

Secondary: Large for gestational age

Secondary: Large for gestational age

Secondary: Small for gestational age

Secondary: Small for gestational age

Secondary: Antepartum hemorrhage

Secondary: Antepartum hemorrhage

Secondary: Infant crown-heel lenght

Secondary: Infant crown-heel lenght

Secondary: Need for neonatal ICU

Secondary: Need for neonatal ICU

Secondary: Respiratory distress syndrome

Secondary: Respiratory distress syndrome

Secondary: Jaundice

Secondary: Jaundice

Secondary: Major cogenital anomalies

Secondary: Major cogenital anomalies

Secondary: APGAR score

Secondary: APGAR score

Secondary: Neonatal hypoglycaemia

Secondary: Neonatal hypoglycaemia

Secondary: Infant morbidities

Secondary: Infant morbidities

Secondary: DTSQ satisfaction scale

Secondary: DTSQ satisfaction scale

Secondary: DTSQ burden scale

Secondary: DTSQ burden scale

Secondary: Gestational age at birth

Secondary: Gestational age at birth

Secondary: Maternal BMI

Secondary: Maternal BMI

Secondary: Maternal waist circumference

Secondary: Maternal waist circumference

Secondary: Infant head circumference

Secondary: Infant head circumference

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Randomised Placebo Controlled Trial of the effectiveness of Early MEtformin in Addition to Usual Care in the Reduction of Gestational Diabetes Mellitus Effects (EMERGE)