Iron, Vitamin D Status Predict Maternal Mental Health During Pregnancy

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Iron and vitamin D status during the second trimester predicted maternal depression symptoms during the third trimester.

Maternal iron and vitamin D status may play an important role in influencing mental health during pregnancy, according to findings from a secondary analysis of the Alberta Pregnancy Outcomes and Nutrition (APrON) cohort study.1

Results showed an adequate maternal status of iron and vitamin D during the second trimester was related to less maternal depression symptoms during the third trimester, with further analysis suggesting scores differed based on the combined adequacy of both micronutrients during midpregnancy.1

“​​Evidence related to the potential combined impact of maternal iron and vitamin D status on pregnancy-related health outcomes is limited, despite an emergence of studies reporting mechanistic interactions between their biological pathways,” wrote Catherine Field, PhD, professor in the agricultural, food and nutritional science department at the University of Alberta, and colleagues.1

Despite a growing body of evidence supporting the importance of adequate nutrition in pregnancy, an estimated 20%-30% of pregnant women worldwide suffer from vitamin deficiency. The combined impact of maternal iron and vitamin D status on pregnancy-related health outcomes is limited, and even less is known about their impact on prenatal or postpartum depression symptoms, highlighting an important gap in research.2

The APrON cohort study set out to address these uncertainties and included pregnant participants and their children from Calgary and Edmonton, Canada, between 2009 and 2012. Individuals were eligible for inclusion if they were > 16 years of age, could read and write in English, and intended to reside in Calgary or Edmonton throughout gestation and to 3 months postpartum.1

One of the primary aims of the APrON cohort study was to examine the association between nutrient status in pregnancy and postpartum with maternal mental health. In this secondary analysis, investigators sought to explore the individual and combined associations of maternal iron and vitamin D status during and after pregnancy on depression symptoms among participants.1

The occurrence of gestational medical conditions was determined through patient responses to questionnaires at several pregnancy visits. Iron and vitamin D intake from supplements was estimated via Supplemental Intake Questionnaires by self-report and converted into an estimated daily supplement intake for different micronutrients. Maternal venous blood samples were drawn at each study visit, which occurred ≤ 3 times during pregnancy and at multiple time points during the postpartum period.1

Iron biomarkers, including serum ferritin, soluble transferrin receptor, and hepcidin, were measured using immunoassays and vitamin D metabolites were quantified using liquid chromatography with tandem mass spectroscopy. Investigators conceptualized 4 categories of maternal iron and vitamin D status during the second trimester based on concentrations of serum ferritin and total 25-hydoxyvitamin D.1

Additionally, Maternal Edinburgh Postnatal Depression Scale (EPDS) scores during the third trimester (n = 1920) and 3 months postpartum (n = 1822) were obtained to assess maternal depression symptoms.1

Investigators noted most participants were married or cohabiting with a partner, highly educated, and had a household income >$70,000. The majority self-identified as White and 53% were pregnant with their first child. Most of the pregnant individuals consumed iron and vitamin D supplements during each trimester of pregnancy.1

Upon analysis, greater second trimester maternal concentrations of serum ferritin (β, -0.8; 95% confidence interval [CI], -1.5 to -0.01), hepcidin (β, -0.5; 95% CI, -0.9 to -0.2), and 25hydroxyvitamin D3 (β, -0.01; 95% CI, -0.02 to -0.004) predicted lower maternal EPDS scores during the third trimester. Investigators did not observe any relationships between maternal soluble transferrin receptor, soluble transferrin receptor to serum ferritin ratio, or 3-epi-25hydroxyvitamin D3 with third trimester EPDS scores or between maternal biomarkers and EPDS scores at 3 months postpartum.1

Compared with pregnant participants who were iron replete, defined as serum ferritin ≥15 μg/L) and vitamin D replete, defined as 25-hydroxyvitamin D ≥75 nmol/L, EPDS scores were significantly higher when iron status was low (serum ferritin <15 μg/L) and vitamin D was replete (P = .044) or when iron and vitamin D (25-hydroxyvitamin D <75 nmol/L) were both low (P = .024).1

“This investigation is one of the first to report on the combined adequacy of maternal iron and vitamin D status during pregnancy and its impact on maternal depression. The novelty of this work reinforces the need to ask similar questions in other pregnant populations,” investigators concluded.1


  1. Evanchuk JL, Kozyrskyj A, Vaghef-Mehrabani E, et al. Maternal Iron and Vitamin D Status during the Second Trimester Is Associated with Third Trimester Depression Symptoms among Pregnant Participants in the APrON Cohort. J Nutr. 2024;154(1):174-184. doi:10.1016/j.tjnut.2023.10.029
  2. Mousa A, Naqash A, Lim S. Macronutrient and Micronutrient Intake during Pregnancy: An Overview of Recent Evidence. Nutrients. 2019;11(2):443. Published 2019 Feb 20. doi:10.3390/nu11020443