Öz
Objective: Maternal nutrition is increasingly recognized as a modifiable determinant of fetal cardiovascular development. Experimental and epidemiological studies suggest that iron deficiency may contribute to congenital heart disease, but data focusing on ventricular septal defect (VSD) remain limited. This study aimed to evaluate the association between maternal iron status and isolated perimembranous VSD in offspring.
Materials and Methods: This single-center retrospective case–control study included mothers of 41 infants younger than one year with isolated perimembranous VSD and 38 control mothers whose infants had no structural heart disease after echocardiographic evaluation. Maternal laboratory parameters were retrieved from electronic medical records, and the earliest available results were used for analysis. Evaluated parameters included hemoglobin, ferritin, vitamin B12, folate, and 25-hydroxyvitamin D. Group comparisons were performed using the Mann–Whitney U test or chi-square test, as appropriate. Binary logistic regression was used to assess independent associations with VSD, and receiver operating characteristic analysis was performed for ferritin.
Results: Maternal ferritin levels were significantly lower in the VSD group than in controls (median 25.8 [IQR 15.5–52.0] vs 57.9 [IQR 21.3–79.3] ng/mL, p=0.012), whereas maternal hemoglobin, vitamin B12, folate, and vitamin D levels did not differ significantly. In multivariable logistic regression adjusted for maternal age, hemoglobin, vitamin B12, and folate, ferritin remained independently associated with VSD (OR 0.83 per 10-ng/mL increase, 95% CI 0.72–0.96, p=0.012). Ferritin showed moderate discriminative ability for VSD (AUC 0.665, 95% CI 0.537–0.781).
Conclusion: Lower maternal ferritin levels were associated with isolated perimembranous VSD in offspring, independent of hemoglobin levels. These findings suggest that reduced maternal iron stores may be relevant to fetal septal development and warrant confirmation in prospective studies with measurements obtained during early pregnancy.
Kaynakça
- Kalisch-Smith JI, Ved N, Szumska D, Munro J, Troup M, Harris SE, et al. Maternal iron deficiency perturbs embryonic cardiovascular development in mice. Nat Commun. 2021;12(1):3025. https://doi.org/10.1038/s41467-021-23660-5
- Lewkowitz AK, Tuuli MG. Identifying and treating iron deficiency anemia in pregnancy. JAMA Netw Open. 2024;7(8):e223223. https://doi.org/10.1001/jamanetworkopen.2024.3223
- Dolk H, McCullough N, Callaghan S, Casey F, Craig B, Given J, et al. Risk factors for congenital heart disease: The Baby Hearts Study, a population-based case-control study. PLoS One. 2020;15(2):e0227908. https://doi.org/10.1371/journal.pone.0227908
- Jenkins KJ, Correa A, Feinstein JA, Botto L, Britt AE, Daniels SR, et al. Noninherited risk factors and congenital cardiovascular defects: current knowledge. Circulation. 2007;115(23):2995-3014. https://doi.org/10.1161/CIRCULATIONAHA.106.183216
- Mires S, Caputo M, Overton T, Skerritt C. Maternal micronutrient deficiency and congenital heart disease risk: a systematic review of observational studies. Birth Defects Res. 2022;114(16):1079-91. https://doi.org/10.1002/bdr2.2072
- Georgieff MK. Iron deficiency in pregnancy. Am J Obstet Gynecol. 2020;223(4):516-524. https://doi.org/10.1016/j.ajog.2020.03.006
- Means RT. Iron deficiency and iron deficiency anemia: implications and impact in pregnancy, fetal development, and early childhood parameters. Nutrients. 2020;12(2):447. https://doi.org/10.3390/nu12020447
- Zhang J, Li Q, Song Y, Fang L, Alsharari Z, Huang L, et al. Nutritional factors for anemia in pregnancy: a systematic review with meta-analysis. Front Public Health. 2022;10:1041136. https://doi.org/10.3389/fpubh.2022.1041136
- Zhao B, Sun M, Wu T, Li J, Shi H, Wei Y. The association between maternal anemia and neonatal anemia: a systematic review and meta-analysis. BMC Pregnancy Childbirth. 2024;24(1):683. https://doi.org/10.1186/s12884-024-06832-1
- Daru J, Allotey J, Peña-Rosas JP, Khan KS. Serum ferritin thresholds for the diagnosis of iron deficiency in pregnancy: a systematic review. Transfus Med. 2017;27(3):167-74. https://doi.org/10.1111/tme.12408
- Zaffran S, Kelly RG. New developments in the second heart field. Differentiation. 2012;84(1):17-24. https://doi.org/10.1016/j.diff.2012.03.003
- Nakajima Y. Retinoic acid signaling in heart development. Genesis. 2019;57(7-8):e23300. https://doi.org/10.1002/dvg.23300
- Nair M, Drakesmith CW, Smith M, Bankhead CR, Sparrow DB. Maternal anaemia and congenital heart disease in offspring: a case-control study using linked electronic health records in the United Kingdom. BJOG. 2025;132(8):1139-46. https://doi.org/10.1111/1471-0528.18150
- Qaddour R, Alsayed R. Relationship between maternal iron status and the risk of congenital heart defects: a case-control study. J Int Med Res. 2025;53(7):3000605251356004. https://doi.org/10.1177/03000605251356004
- Hacettepe Üniversitesi Nüfus Etütleri Enstitüsü. 2018 Türkiye Nüfus ve Sağlık Araştırması. Ankara: T.C. Cumhurbaşkanlığı Strateji ve Bütçe Başkanlığı ve TÜBİTAK; 2019.
- Alkaya DU, Öztürk B, Ülker AY, Bozlak S, Öztürk E, Dedeoğlu R, et al. Congenital heart defects and outcome in a large cohort of Down syndrome: a single-center experience from Turkey. Turk Arch Pediatr. 2023;58(5):473-9. https://doi.org/10.5152/TurkArchPediatr.2023.23041
- Bull MJ, Saal HM, Braddock SR, Enns GM, Gruen JR, Perrin JM, et al. Health supervision for children with Down syndrome. Pediatrics. 2011;128(2):393-406. https://doi.org/10.1542/peds.2011-1605
- Patterson AJ, Zhang L. Hypoxia and fetal heart development. Curr Mol Med. 2010;10(7):653-66. https://doi.org/10.2174/156652410792630643
- Obianeli C, Afifi K, Stanworth S, Churchill D. Iron deficiency anaemia in pregnancy: a narrative review from a clinical perspective. Diagnostics (Basel). 2024;14(20):2306. https://doi.org/10.3390/diagnostics14202306
- World Health Organization. WHO guideline on use of ferritin concentrations to assess iron status in individuals and populations. Geneva: World Health Organization; 2020.
- Pavord S, Daru J, Prasannan N, Robinson S, Stanworth S, Girling J. UK guidelines on the management of iron deficiency in pregnancy. Br J Haematol. 2020;188(6):819-30. https://doi.org/10.1111/bjh.16221
- Quezada-Pinedo HG, Jaddoe VWV, Gaillard R, Duijts L, van Rijn BB, Reiss IKM, et al. Maternal hemoglobin and iron status in early pregnancy and childhood cardiac outcomes. Clin Nutr. 2024;43(9):1997-2004. https://doi.org/10.1016/j.clnu.2024.07.009
Telif hakkı ve lisans
Telif hakkı © 2026 Yazar(lar). Açık erişimli bu makale, orijinal çalışmaya uygun şekilde atıfta bulunulması koşuluyla, herhangi bir ortamda veya formatta sınırsız kullanım, dağıtım ve çoğaltmaya izin veren Creative Commons Atıf Lisansı (CC BY) altında dağıtılmıştır.