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Maternal first trimester iron status and its association with obstetric and perinatal outcomes

  • Obstetrics and Gynecology
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Abstract

Purpose

To assess the following in singleton pregnant women: (1) associations between first trimester iron deficiency and obstetric and perinatal outcomes, (2) overall first trimester iron status and (3) post-treatment iron status after intensified iron supplementation.

Methods

A prospective cohort study was conducted with linkage of first trimester hemoglobin and plasma ferritin with obstetric and perinatal data from a hospital database. Blood sample data were obtained from a Danish University Hospital. The cohort was divided into groups according to ferritin and hemoglobin: (1) iron-deficient anemic (ferritin < 30 ng/mL and Hb < 110 g/L), (2) iron-deficient non-anemic (ferritin < 30 ng/mL and Hb ≥ 110 g/L), and (3) iron-replete non-anemic (ferritin 30–200 ng/mL and Hb ≥ 110 g/L). Obstetric and perinatal outcomes in each iron-deficient group were compared to the iron-replete non-anemic group using multivariable logistic regression. The effect of 4 weeks intensified iron supplementation on hemoglobin and ferritin was assessed by groupwise comparisons.

Results

The cohort comprised 5763 singleton pregnant women, of which 14.2% had non-anemic iron deficiency, and 1.2% had iron-deficiency anemia. Compared to iron-replete non-anemic women, iron-deficient anemic women had a higher risk of gestational diabetes (aOR 3.8, 95% CI 1.4–9.0), and iron-deficient non-anemic women had a higher risk of stillbirth (aOR 4.0, 95% CI 1.0–14.3). In group 1 and 2, 81.5% and 67.7% remained iron-deficient after intensified iron supplementation.

Conclusion

Iron-deficiency anemia was associated with gestational diabetes, and non-anemic iron deficiency with stillbirth, although risk estimates were imprecise due to few events. Iron deficiency was present in 15.4% and often persisted despite 4 weeks intensified iron supplementation.

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Availability of data and material

Requests on data access can be made through contact with the corresponding author. Data may be accessed upon reasonable request and after review and approval by the Danish Data Protection Agency and the Danish Patient Safety Authority.

Code availability

The code (R) will be available from the corresponding author upon reasonable request.

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Acknowledgements

We acknowledge and are thankful for the data management support from Steen Christian Rasmussen, MSc, MPH.

Funding

This study has been covered solely by internal funding.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Copenhagen University Hospital Hvidovre, Kettegaard Allé 30, 2650, Hvidovre, Denmark

    Rebecka Hansen, Veronika Markova Sommer, Charlotte Holm & Lone Krebs

  2. Fertility Department, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark

    Anne Lærke Spangmose & Anja Pinborg

  3. Fetal Medicine Unit, Department of Obstetrics and Gynecology, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark

    Finn Stener Jørgensen

  4. Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

    Finn Stener Jørgensen, Lone Krebs & Anja Pinborg

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  1. Rebecka Hansen
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Contributions

RH, ALS, VMS, CH, LK and AP were involved in the conception and design of the study. RH and VMS carried out data collection. RH and ALS performed data analyses. RH drafted the manuscript. All authors were involved in the interpretation of the data and reviewed and approved the final manuscript.

Corresponding author

Correspondence to Rebecka Hansen.

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Conflict of interest

When the study was conducted, Rebecka Hansen and Veronika Markova Sommer were investigators and Charlotte Holm primary investigator for a clinical trial sponsored by Pharmacosmos A/S. As investigators, Rebecka Hansen and Veronika Markova Sommer had salary costs funded by Pharmacosmos A/S. Rebecka Hansen and Charlotte Holm have served on advisory boards for Pharmacosmos A/S. However, Pharmacosmos A/S did not play any role or had any influence on this cohort study. Only the named authors had influence on the study design, conduct, analysis, interpretation and the manuscript. The authors have no additional conflicts of interest to declare.

Ethics approval

The study was approved by the Danish Data Protection Agency (J. No.: AHH-2017-031, I-suite number: 05349) and the Danish Patient Safety Authority (J. No.: 3-3013-2410/1). According to Danish legislation, informed written consent from patients is not required for this specific type of study. The reporting of the study adhered to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines.

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Hansen, R., Spangmose, A.L., Sommer, V.M. et al. Maternal first trimester iron status and its association with obstetric and perinatal outcomes. Arch Gynecol Obstet 306, 1359–1371 (2022). https://doi.org/10.1007/s00404-022-06401-x

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