• Change of haemoglobin (Hb) intervals used for stratification of randomisation from 9.0 10.4 g/dL (mild) and 7.0-8.9 g/dL (moderate) to 9.0 10.4 g/dL (mild) and 6.5-8.9 g/dL (moderate). • Addition of strata as a factor in the logistic regression model used to analyse the primary endpoint and in the Mixed Model for Repeated Measures (MMRM) used to analyse the majority of the secondary efficacy endpoints. • Change of the definition of the safety analysis set from ‘all randomised subjects who received at least one dose of the trial drugs’ to ‘all subjects who received at least one dose of the trial drugs’. • Specification that adverse event (AE) results were to be presented for the safety analysis set and that listings were also to be prepared for non-treatment emergent serious AEs (in non-exposed subjects and for the safety analysis set).

• Addition to the introduction section of results from previous trials on the efficacy and safety of other IV iron solutions used during pregnancy as well as a discussion of the risk that the investigational product can cross placenta, and how that would influence the foetus, based on a request from the Danish Medicines Agency. • Change of exclusion criterion 7 from ‘Decompensated liver cirrhosis or active hepatitis (defined as aspartate aminotransferase (ASAT) or alanine aminotransferase (ALAT) >3 times upper limit of normal for a pregnant woman at a given gestational age)’ to ‘Decompensated liver cirrhosis or active hepatitis (defined as ALAT >3 times upper limit of normal for a pregnant woman at a given gestational age)’ and removal of ASAT from the laboratory safety assessments, since it was no longer clinical practice at the clinical site to measure ASAT. • Change of timepoint for collection of demography from the baseline to the screening visit, so it was possible to describe the population that failed screening. • Removal of compliance assessment by pill count at weeks 3 and 12. • Change of collected information on concomitant medication from generic name to brand name, and addition of route and frequency. • Specification that if vital signs were measured more than once in a given time interval, the lowest measurement of diastolic blood pressure for the period (including the simultaneously measured systolic blood pressure and heart rate) should be noted in the electronic case report form. • Addition of a definition of treatment emergent AEs and non-treatment emergent AEs, and specification that in non-treated subjects only serious AEs should be reported and that in treated subjects all AEs should be reported from the subject signed the informed consent form.

• Change of inclusion criterion 3 from ‘Hb <10.5 g/dL (6.5 mmol/L) and ferritin <30 μg/L after 4 weeks of standard treatment in a clinical setting’ to ‘Hb ≤10.5 g/dL (6.5 mmol/L) and ferritin <30 μg/L after 4 weeks of standard treatment in a clinical setting’ in order to avoid rounding errors. The Hb cut off used to determine if intravenous (IV) iron isomaltoside was allowed at weeks 6 and/or 12 was changed accordingly. • Change of exclusion criterion 7 from ‘Decompensated liver cirrhosis or active hepatitis (defined as ALAT >3 times upper limit of normal for a pregnant woman at a given gestational age)’ to ‘ALAT > 3 times upper limit of normal for a pregnant woman at a given gestational age (e.g. decompensated liver cirrhosis or active hepatitis)’ since subjects with increased ALAT levels > 3 times upper limit of normal should not be enrolled even though they were not diagnosed with decompensated liver cirrhosis or active hepatitis. • Deletion of exclusion criterion 16 (‘Inability to read and understand the Danish language’) in order to increase the number of potential subjects. • Rewording of Hb intervals used for stratification of randomisation from 9.0 10.4 g/dL (mild) and 6.5-8.9 g/dL (moderate) to ≥9.0 g/dL and <9.0 g/dL. • Change of the Hb cut off used to determine if rescue red blood cell (RBC) transfusion was allowed from <6.9 g/dL to ≤6.9 g/dL to align with exclusion criterion 14. • Specification that if the subject was in daily treatment for e.g. allergy or asthma, this was not considered as premedication and could be continued also before administration of iron isomaltoside.

• Deletion of the planned analysis of soluble transferrin receptor since it was not possible to establish collaboration with an external laboratory regarding this analysis. • Specification that a research bio-bank was to be established at the Department of Clinical Biochemistry, Hvidovre University Hospital, for storage of the hepcidin samples. • Replacement of a specific list of adverse drug reactions (ADRs) for iron isomaltoside with a reference to the current version of the Investigator's Brochure (IB) for iron isomaltoside, and specification that the current version of the IB for iron isomaltoside (instead of a specific version) should always be used to assess if a serious adverse reaction (SAR) was considered a suspected unexpected SAR in order to ensure that the newest data were available. • Change of trial population to not only include subjects with iron deficiency anaemia (IDA) but also subjects with iron deficiency (ID) without anaemia. The protocol title and several sections have been changed accordingly. • Change of primary objective from ‘evaluate and compare the effect of IV iron isomaltoside to a fixed dose of oral iron administered as tablet ferrous fumarate with ascorbic acid as correction of anaemia in pregnant women who have IDA after 4 weeks of standard treatment’ to ‘evaluate the effect of IV iron isomaltoside compared to a fixed dose of oral iron administered as tablet ferrous fumarate with ascorbic acid as avoidance of developing/having IDA throughout the duration of the trial in pregnant women who have ID after 4 weeks of standard oral treatment’. • Change of the primary endpoint from ‘Hb ≥11.0 g/dL at any time point within 6 weeks after beginning of treatment with trial drugs’ to ‘Hb ≥11.0 g/dL (≥6.8 mmol/L) at all post baseline time points’ including statistical analysis of the primary endpoint. • Deletion of the secondary endpoint ‘Time to response (achieve an Hb ≥11.0 g/dL)’.

• Change of sample size from 140 to 200 subjects including change of the sample size calculation. • Change of inclusion criterion 2 from ‘Pregnancy at gestational age 14 (+2 weeks)’ to ‘Pregnancy at gestational age 14+0 – 19+0’. • Change of inclusion criterion 3 from ‘Hb ≤10.5 g/dL (6.5 mmol/L) and ferritin <30 μg/L after 4 weeks of standard treatment in a clinical setting’ to ‘Ferritin <30 μg/L (0-29 μg/L) after 4 weeks of standard treatment in a clinical setting’. • Merge of the screening and baseline visits and deletion of eligibility laboratory assessments. • Change of exclusion criteria 1, 7, and 8 to be based on history/known condition and clinical assessment instead of biochemical assessment. • Rewording of exclusion criteria 10, 11, and 12 in order to incorporate that the screening and baseline visits were merged. • Change of Hb intervals used for stratification of randomisation from ≥9.0 g/dL and <9.0 g/dL to <11 g/dL and ≥11 g/dL. • Change of the Hb requirement for when an additional dose of IV iron isomaltoside was allowed at weeks 6 and/or 12 from ≤10.5 g/dL (6.5 mmol/L) to Hb <11 g/dL (<6.8 mmol/L). • Change of definition of per protocol (PP) population in relation to RBC transfusion: Any RBC transfusion after randomisation should lead to exclusion from the PP population instead of only RBC transfusion before week 6.

• Change of the endpoint on AEs of special interest from ‘Number of AEs of special interest (i.e. hypersensitivity symptoms defined in Standardised Medical Dictionary for Regulatory Activities Query (SMQ) terms (including four additional terms) for definition of hypersensitivity events and specific gastrointestinal symptoms (constipation, diarrhoea, flatulence, nausea, vomiting, abdominal pain, dyspepsia, dysgeusia, and stool discoloration) at pre-specified time points in relation to administration of trial drug)’ to ‘Number of AEs of special interest (i.e. hypersensitivity symptoms defined in SMQ terms (including four additional terms) and specific gastrointestinal symptoms (constipation, diarrhoea, flatulence, nausea, vomiting, abdominal pain, dyspepsia, dysgeusia, and stool discoloration) observed at any time during the trial in both treatment groups’. • Change of inclusion criterion 2 from ‘Pregnancy at gestational age 14+0 – 19+0’ to ‘‘Pregnancy at gestational age 14+0 – 21+0’. • Specification that all symptoms of hypersensitivity were to be collected during the trial period. • Specification that intake of oral iron was only allowed if it was included in multivitamins. Thus, oral iron as supplement per se was not allowed. • Change of the statistical analysis of restless legs syndrome (RLS) to a repeated measures logistic regression model with treatment, visit, stratum, and treatment by visit interaction as fixed effects and baseline value as covariate since RLS is a binary endpoint.

• Specification that the final subject visit was defined as the week 18 visit, time of contact to health care facility due to onset of labour, or time of decision to induce labour, and that AEs were to be collected up until one of the criteria for final subject visit was fulfilled. • Specification that all 4 questions related to RLS must be answered ‘yes’ for RLS to be present. • Change of the reference document for iron isomaltoside from the current IB to the current Summary Product of Characteristics (SmPC), since iron isomaltoside is approved in Denmark and the dosing in the trial was within the approved label. • Specification that subjects with a good clinical practice (GCP) deviation of clinical or statistical significance were also to be excluded from the PP population. • Addition of statistical analysis for hypophosphatemia and exploratory endpoints. • Specification of statistical analyses for the secondary endpoints and for the safety analyses. • Specification that statistical analyses of secondary endpoints were to be performed including all data points/events and only including data points/events up to the time point where an additional dose of IV iron isomaltoside was received. • Expansion of the section on protocol deviations.

• Addition of the endpoint ‘Incidence of hypophosphatemia (defined as s phosphate <2 mg/dL) at any time post-baseline to week 18)’. • Change of the endpoint ‘Reason for the additional IV iron isomaltoside dose (intolerance, non-compliance, lack of effect)’ to ‘Reason for the additional IV iron isomaltoside dose (non-compliance, lack of effect)’. • Change of the endpoint ‘Number of subjects who received 1 or more allogenic RBC transfusions and the number of units of RBC-transfused per transfused subject from baseline to 7 days postpartum (medical record follow-up)’ to ‘Number of subjects who received 1 or more allogenic RBC-transfusions and the number of units of RBC-transfused per transfused subject from baseline to final subject visit’. • Change of the endpoint ‘Compliance to treatment: at baseline in the IV group and at weeks 6 and 18 in oral group’ to ‘Compliance to treatment: at baseline in the IV group and by pill count at weeks 6 and 18 in oral group’. • Further specification and definition of the exploratory endpoints collected from the medical records of the mother and the newborn from the final subject visit until 7 days postpartum. • Specification that 200 subjects should be randomised. • Specification of the method for pill count at week 6. • Deletion of ‘Any drug, which potentially yields a decrease in oral iron absorption (e.g. tetracycline, antacids, and cholestyramine)’ from the list of prohibited medication and replacement with an advice not to use any drug, which potentially yielded a decrease in oral iron absorption (e.g. tetracycline, antacids, and cholestyramine) if possible. • Specification of overdose in the oral treatment group as a dose > + 10 %.