Vitamin D during pregnancy

Studies in pregnant women across the US, Northern Europe and the Middle East have shown that 26–90% of them are deficient in vitamin D, defined as a concentration of the vitamin D metabolite calcidiol (25(OH)D₃) below 20 ng/ml. Vitamin D levels during pregnancy are linked to many aspects of both maternal and child health. A number of observational studies have described the effects of vitamin D status on normal placenta formation and the course of pregnancy, the incidence of complications including pre-eclampsia, gestational diabetes, as well as the mode and time of delivery. Many studies also reference the impact of normal vitamin D levels on fetal development, including skeletal size and mineralization, but also on the incidence of disease in the later years of childhood.[1]

Impact of vitamin D on pregnancy

Several studies have confirmed that ensuring optimal calcidiol levels reduces the risk of a number of complications in the mother during pregnancy, while in the child it reduces the risk of developmental abnormalities in the prenatal period and a number of post-birth diseases. [1]

Pre-eclampsia

Pre-eclampsia is a multiple organ disease, manifested, among other things, by an increase in blood pressure (>140/90 mmHg), in women after 20 weeks of gestation; its incidence is estimated at around 3–8%. Although its etiology is very complex, it has been shown to occur more frequently in pregnant women with vitamin D deficiency. Its occurrence is associated with decreased levels of vascular endothelial growth factor (VEGF) and increased release of pro-inflammatory cytokines. Since the expression of genes for VEGF and cytokines remains under a strong modulatory impact of vitamin D, this may explain the effect of its deficiency on the occurrence of pre-eclampsia. [2, 3] A prospective study involving 274 pregnant women followed from 16 weeks of gestation to delivery showed that all women who developed pre-eclampsia had low 25(OH)D₃ concentrations at the start of pregnancy, and that subsequent supplementation had no effect on reducing its risk. A drop in 25(OH)D₃ levels below 20 ng/ml was associated with a twofold increase in the risk of pre-eclampsia. Furthermore, newborns of mothers with pre-eclampsia were twice as likely to have low 25(OH)D₃ levels (less than 15 ng/ml). The authors emphasize that vitamin D deficiency may be an independent risk factor for pre-eclampsia, and vitamin D supplementation in early pregnancy should have a significant impact on reducing the risk of this complication. [2, 4]

Gestational diabetes

There is a growing body of evidence supporting the role of vitamin D in maintaining normal glucose homeostasis. Low 25(OH)D₃ levels have been confirmed to be associated with insulin resistance and impaired insulin secretion. [5] It has been demonstrated that pregnant women with gestational diabetes mellitus had 25(OH)D₃ levels inversely correlated with glucose levels, either fasting or during a glucose tolerance test, and with glycosylated hemoglobin levels, indicating poorer glycemic control in vitamin D deficiency. [6] A cross-sectional study involving 741 pregnant women found an association between low vitamin D levels and the incidence of gestational diabetes. [7] The occurrence of severe vitamin D deficiency was found to be almost twice as common in women with gestational diabetes (44 vs. 23.5%). A relationship between vitamin D levels and the degree of insulin resistance has also been shown. [8] However, administration of the active vitamin D metabolite calcitriol (1,25(OH)D₃) to women with gestational diabetes did not affect glycaemia or insulin resistance. [9] There are also studies in which this association is inconclusive, however, other population groups or excessive body weight, which are not always taken into account, may be an interference in the assessment. [2]

Impact of vitamin D on normal child development

Ensuring adequate vitamin D levels is very important from the first days of a baby’s life.

Impact on skeletal development and birth weight

Vitamin D plays a role in fetal growth by regulating calcium homeostasis and parathyroid hormone levels. [10] Severe hypovitaminosis D in a pregnant woman causes the child to develop rickets while still in fetal development, which manifests clinically after birth. [2] It has been demonstrated that newborns of mothers with low vitamin D status had significantly larger fontanel diameters. [7] Numerous studies also indicate an association between pregnant women’s 25(OH)D₃ concentrations and neonatal birth weight and length, as well as growth rate during the first year of life. [11] A comparison of neonatal growth parameters with maternal milk and vitamin D intake during pregnancy showed an association between vitamin D intake during pregnancy and birth weight; each additional 40 IU (1 μg) of vitamin D intake by the mother resulted in an 11 g increase in birth weight. [12] A study of 108 pregnant women and their offspring found a significant association between umbilical cord 25(OH)D ₃ concentrations and head circumference at 3 and 6 months after birth. [14] Javaid et al. showed that children of mothers with vitamin D deficiency in late pregnancy, studied at the age of 9 years, had lower bone mineral density of the total body and lumbar spine compared to the population average for their sex and age. [14] This indicates the long-term effects of fetal vitamin D deficiency on subsequent child development.

Impact on immunity

The impact of vitamin D on immune system activity has been very well documented. [15] Vitamin D is believed to reduce the risk of respiratory tract infection through immunomodulation as a result of processes such as decreased chemokine production, inhibition of dendritic cell activation and changes in T cell activation. Observational studies have shown that low vitamin D levels in women during pregnancy were correlated with low levels in newborns, which was associated with an increase in the incidence of acute lower respiratory tract infections in infancy and wheezing during the first five years of life. [16] Adequate vitamin D levels have also been demonstrated to reduce the risk of sepsis, which may be related to the vitamin’s impact on increasing levels of cathelicidin, an important cofactor of antimicrobial activity.

Impact on the development of the nervous system

A number of studies have pointed to the impact of vitamin D on brain development in early life. Vitamin D deficiency in mother and offspring can cause some developmental difficulties in early life, including problems with learning, memory and concentration. There is also evidence of increased lateral ventricular volume and altered neuronal expression of genes involved in dopamine- and glucocorticoid-related pathways, suggesting autism and schizophrenia-like disorders. [17] A systematic review on prenatal nutrients and their impact on emotional development in childhood and the development of mental illness at a later stage has shown that adequate levels of vitamins A and D reduce the risk of schizophrenia and other mental illnesses in later life in the offspring. The risk of a child developing schizophrenia is higher with the lower the postnatal 25(OH)D₃ level. It is estimated that a proper prenatal vitamin D supply could prevent 43.6% of schizophrenia cases. [18] A growing body of literature also suggests that higher serum 25(OH)D₃ concentrations, both during fetal life and in early life, may reduce the risk of autism. [19] Vitamin D also plays an important role in hypoxia and ischemia of the brain in newborns. Children born to mothers with vitamin D deficiency were more likely to develop cerebral hypoxia and ischemia during birth. [19]

Summary

Vitamin D deficiency in pregnant women and their children is an important health problem with serious consequences for the health of both. Multiple academic studies confirm that ensuring optimal levels during pregnancy prevents many complications. Many studies emphasize that it is important to ensure adequate levels before or at the beginning of pregnancy, as supplementation does not work if there are health complications.

References

1. Zimmer M, Sieroszewski P, Oszukowski P et al. Ginekologia i Perinatologia Praktyczna 2020;5(4):170-181.
2. Misiorowska J, Misiorowski W. Postępy Nauk Medycznych, t. XXVII, nr 12, 2014
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4. Bodnar LM, Catov JM, Simhan HN et al. J Clin Endocrinol Metab 2007; 92: 3517- 3522
5. Dudek-Makuch M. Rola witaminy D w patomechanizmie chorób metabolicznych. Niedobór witaminy D a cukrzyca. https://chc.com.pl/rola-witaminy-d-w-patomechanizmie-chorob-metabolicznych-niedobor-witaminy-d-a-cukrzyca/
6. Lau SL, Gunton JE, Athayde NP et al. Med J Aust 2011; 194(7): 334-337.
7. Maghbooli Z, Hossein-Nezhad A et al. Diabetes Metab Res Rev 2007.
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11. Scholl TO, Chen X. Early Hum Dev 2009; 85(4): 231-234.
12. Mannion CA, Gray-Donald K, Koski KG. CMAJ. 2006 Apr 25;174(9):1273-7.
13. Pawley N, Bishop NJ. Am J Clin Nutr. 2004 Dec;80(6 Suppl):1748S-51S.
14. Javaid MK, Crozier SR, Harvey NC et al. Lancet 2006; 367(9504): 36-43
15. Dudek-Makuch M. https://chc.com.pl/rola-witaminy-d-w-prawidlowym-funkcjonowaniu-ukladu-nerwowego/
16. Camargo CA Jr, Ingham T, Wickens K, et al. 2011 Jan;127(1):e180-7.
17. Yates NJ, Tesic D, Feindel KW et al. J Endocrinol. 2018;237(2):73-85.
18. Freedman R, Hunter SK, Hoffman MC et al. Am J Psychiatry. 2018;175(7):607-619
19. Cannell JJ, Grant WB. Dermatoendocrinol. 2013, 1;5(1):199-204.

BIOGRAPHICAL NOTE

Marlena Dudek-Makuch, PhD (Pharm.), MSc, has 20 years of professional experience in phytochemical and biological research, and scientific information (assistant professor at the Department of Pharmacognosy, Poznań University of Medical Sciences). She is an author of research and review papers on the isolation and identification of compounds of plant origin, and evaluation of their biological activity. Since 2015, she has been teaching a postgraduate course in “Herbs in practice and therapy”. She is currently a member of the Regulatory Department, R&D Division, at CHC. In her position, she is in charge of preparing expert reports (clinical, non-clinical) for medicinal products, clinical reports for OTC switches, clinical assessments of medical devices, pharmacovigilance activities for medical devices, and safety assessment of plant-based raw materials used in medicinal products, medical devices, and dietary supplements.