The modern clinical features of effective prevention of gestational and fetal pathology




vitamin and mineral supplementation, folic acid, metafolin, vitamin D, iron supplementation, iodine supplementation, pregnancy, congenital fetal anomalies, maternal anemia, preterm birth, preeclampsia


Aim of the literature review: to evaluate the prophylactic clinical effect of oral vitamin and mineral supplementation (VMS) in pregnancy on perinatal and neonatal outcomes.

Materials and methods. Authors were searched Cochrane Review, WHO platform, clinical guidelines, and reference lists of retrieved studies on Medline. All prospective randomized controlled trials evaluating VMS with folic acid, vitamin D, iron, iodine, vitamin A, ω-3 long chain polyunsaturated fatty acids, zinc, calcium, vitamin E and C during pregnancy and its effects on pregnancy outcomes were eligible, irrespective of language or the publication status of trials. Trial reports that were published as abstracts were eligible.

Results. Complex using of VMS led to reduction in congenital fetal anomalies, maternal anemia. Authors did not find an important effect on results of perinatal and neonatal mortality. VMS in pregnancy probably led to slightly fewer stillbirths, prevent of gestational diabetes, a reduction in babies considered low birth weight, and slight led to a reduction in babies considered small gestational age. Authors were observed a little or no difference for other maternal, fetal and infant outcomes: preeclampsia, maternal mortality, miscarriage, autism, and spinal cord tumor for infant. VMS probably led to reduction in very early preterm births, although there was no difference identified in induction of labor for post-term pregnancies, and no impact on the rates of cesarean sections. Authors didn’t find any information that VMS increases rates cases of macrosomia. There were no cases of side effects of VMS in optimal doses on mother, fetus and child. Аuthors were unable to assess a number of prespecified, clinically important outcomes due to insufficient or non-available data.

Conclusions. Аuthors findings suggest a positive preventive impact of VMS with folic acid, vitamin D, iron, iodine, zinc, vitamin A, ω-3 fatty acids on several birth outcomes (congenital fetal anomalies, maternal anemia, stillbirths, low birth weight, and preterm birth). No important benefits or harms of VMS were found for mortality outcomes (perinatal and neonatal mortality). These findings may provide some basis to guide the replacement of monocomponent supplements with complex VMS for pregnant women residing in Ukraine.

Author Biographies

D. G. Konkov, National Pirogov Memorial Medical University, Vinnytsia

MD, professor, Obstetrics and Gynecology Department No. 1

V. V. Klivak, National Pirogov Memorial Medical University, Vinnytsia

PhD, associate professor, Obstetrics and Gynecology Department No. 2

O. A. Taran, National Pirogov Memorial Medical University, Vinnytsia

MD, professor, Department of Obstetrics and Gynecology No. 1

O. B. Lastovetska, National Pirogov Memorial Medical University, Vinnytsia

Graduate student, Department of Obstetrics and Gynecology No. 2,


ACOG Committee on Obstetric Practice. “ACOG Committee Opinion No. 495: Vitamin D: Screening and supplementation during pregnancy.” Obstet Gynecol 118 (2011): 197–8.

Baczynska-Strzecha, M., Kalinka, J. “Assessment of correlation between vitamin D level and prevalence of preterm births in the population of pregnant women in Poland.” Int J Occup Med Environ Health 30 (2017): 933–41.

Bailey, R.L., West, K.P. Jr., Black, R.E. “The epidemiology of global micronutrient deficiencies.” Ann Nutr Metab 66.2 (2015): 22–33.

Bialy, L., Fenton, T., Shulhan-Kilroy, J., et al. “Vitamin D supplementation to improve pregnancy and perinatal outcomes: an overview of 42 systematic reviews.” BMJ Open 10 (2020): e032626.

Borzenko, I., Konkov, D., Kondratova, I., et al. “Influence of endotheliopathy of spiral arteries on placental ischemia.” Georgian Med News 11.296 (2019): 131–4.

Bulavenko, O.V., Tatarchuk, T.F., Konkov, D.G., Furman, O.V. “The modern strategies of clinical management of vitamin D deficiency in practices of the obstetrician gynecologist.” Reproductive endocrinology 1.39 (2018): 38–44.

Businge, C.B., Longo-Mbenza, B., Kengne, A.P. “The prevalence of insufficient iodine intake in pregnancy in Africa: protocol for a systematic review and meta-analysis.” Syst Rev 8.1 (2019): 209.

Chandyo, R.K., Ulak, M., Kvestad, I., et al. “The effects of vitamin B12 supplementation in pregnancy and postpartum on growth and neurodevelopment in early childhood: Study Protocol for a Randomized Placebo Controlled Trial.” BMJ Open 7 (2017): e016434.

Chiavarini, M., Naldini, G., Fabiani, R. “Maternal folate intake and risk of childhood brain and spinal cord tumors: A systematic review and meta-analysis.” Neuroepidemiology 51.1–2 (2018): 82–95.

Czeizel, A.E. “Primary prevention of neural-tube defects and some other major congenital abnormalities: recommendations for the appropriate use of folic acid during pregnancy.” Paediatr Drugs 2.6 (2000): 437–49.

Czeizel, A.E., Dudas, I., Vereczkey, A., et al. “Folate deficiency and folic acid supplementation: the prevention of neural-tube defects and congenital heart defects.” Heart Defects Nutrients 5.11 (2013): 4760–75.

Duckworth, S., Mistry, H.D., Chappell, L.C. “Vitamin supplementation in pregnancy.” The Obstetrician & Gynaecologist 14 (2012): 175–8.

American College of Obstetricians and Gynecologists. “Early pregnancy loss. ACOG Practice Bulletin No. 200.” Obstet Gynecol 132 (2018): e197–207.

Curtis, E.M., Moon, R.J., Harvey, N.C., Cooper, C. “Maternal vitamin D supplementation during pregnancy.” British Medical Bulletin 126.1 (2018): 57–77.

FAO; IFAD; WHO; WFP; UNICEF. The State of Food Security and Nutrition in the World 2019. Safeguarding against Economic Slowdowns and Downturns. FAO. Rome (2019).

Flood-Nichols, S.K., Tinnemore, D., Huang, R.R., et al. “Vitamin D deficiency in early pregnancy.” PLoS One 10 (2015): e0123763.

Gallo, S., McDermid, J.M., Al-Nimr, R.I., et al. “Vitamin D Supplementation during Pregnancy: An Evidence Analysis Center Systematic Review and Meta-Analysis.” Journal of the Academy of Nutrition and Dietetics 120.5 (2020): 898–924.

Gernand, A.D., Schulze, K.J., Stewart, C.P., et al. “Micronutrient deficiencies in pregnancy worldwide: health effects and prevention.” Nat Rev Endocrinol 12 (2016): 274–89.

Gowachirapant, S., Jaiswal, N., Melse-Boonstra, A., et al. “Effect of iodine supplementation in pregnant women on child neurodevelopment: A randomised, double-blind, placebo-controlled trial.” Lancet Diabetes Endocrinol 5 (2017): 853–63.

Harding, K.B., Peña-Rosas, J.P., Webster, A.C., et al. “Iodine supplementation for women during the preconception, pregnancy and postpartum period.” Cochrane Database Syst Rev 3 (2017): CD011761.

Higgins, J.P.T, Churchill, R., Chandler, J., Cumpston, M.S., eds. Cochrane Handbook for Systematic Reviews of Interventions version 5.2.0 (updated June 2017). Chapter 8: Assessing risk of bias in included studies. Cochrane (2017). Available from: [].

Hofmeyr, G.J., Lawrie, T.A., Atallah, A.N., et al. “Calcium suppl ementation during pregnancy for preventing hypertensive disorders and related problems.” Cochrane Database Syst Rev 3 (2014): CD001059.

Alberta Health Services (Canada). Nutrition Giudeline Diabetes in Pregnancy. Available from: [].

Iglesias Vázquez, L., Canals, J., Arija, V. “Review and meta-analysis found that prenatal folic acid was associated with a 58% reduction in autism but had no effect on mental and motor development.” Acta Paediatr 108.4 (2019):600–10.

Keats, E.C., Haider, B.A., Tam, E., Bhutta, Z.A. “Multiple-micronutrient supplementation for women during pregnancy.” Cochrane Database Syst Rev 3 (2019): CD004905.

Konkov, D.G., Piskun, A.O., Taran, O.A., Kostur, G.V. “Specialties of hystomorphometrical changes in placenta of women with early and late preeclampsia.” Wiadomości Lekarskie 73.1 (2020): 151–5.

Lastovetska, O.B., Bulavenko, O.V., Konkov, D.G., Buran, V.V. “Effectiveness of the preventive use of folic acid and a complex with active folates in women with MTHFR C677T genetic polymorphism who had a history of embryonic loss.” Reproductive endocrinology 3.53 (2020): 55–60.

Li, H., Ma, J., Huang, R., et al. “Prevalence of vitamin D deficiency in the pregnant women: an observational study in Shanghai, China.” Arch Public Health 78 (2020): 31.

McCauley, M.E., van den Broek, N., Dou, L., Othman, M. “Vitamin A supplementation during pregnancy for maternal and newborn outcomes.” Cochrane Database Syst Rev 10 (2015): CD008666.

Middleton, P., Gomersall, J.C., Gould, J.F., et al. “Omega-3 fatty acid addition during pregnancy.” Cochrane Database Syst Rev 11 (2018): CD003402.

O’Callaghan, K.M., Hennessy, Á., Hull, G.L.J., et al. “Estimation of the maternal vitamin D intake that maintains circulating 25-hydroxyvitamin D in late gestation at a concentration sufficient to keep umbilical cord sera 25-30 nmol/L: A dose-response, double-blind, randomized placebo-controlled trial in pregnant women at northern latitude.” Am J Clin Nutr 108 (2018): 77–91.

Ota, E., Mori, R., Middleton, P., et al. “Zinc supplementation for improving pregnancy and infant outcome.” Cochrane Database Syst Rev 2 (2015): CD000230.

Pena, H.R., de Lima, M.C., Brandt, K.G., et al. “Influence of preeclampsia and gestational obesity in maternal and newborn levels of vitamin D.” BMC Pregnancy Childbirth 15 (2015): 112.

Pena-Rosas, J.P., De-Regil, L.M., Garcia-Casal, M.N., Dowswell, T. “Daily oral iron supplementation during pregnancy.” Cochrane Database Syst Rev 7 (2015): CD004736.

Plana-Ripoll, O., Parner, E., Olsen, J., Li, J. “Severe stress following bereavement during pregnancy and risk of pregnancy loss: results from a population-based cohort study.” J Epidemiol Community Health 70 (2016): 424–9.

Royal Australian and New Zealand College of Obstetricians and Gynaecologists. Pre-pregnancy Counselling. RANZCOG (2017): 11 p.

Wilson, R.L., Gummow, J.A., McAninch, D., et al. “Vitamin and mineral supplementation in pregnancy: evidence to practice.” Journal of Pharmacy Practice and Research 48 (2018): 186–92.

Richard, K., Holland, O., Landers, K., et al. “Review: Effects of maternal micronutrient supplementation on placental function.” Placenta 54 (2017): 38–44.

Roberts, C.T. “IFPA Award in Placentology Lecture: complicated interactions between genes and the environment in placentation, pregnancy outcome and long term health.” Placenta 31 (2010): S47–53.

Rostami, M., Tehrani, F.R., Simbar, M., et al. “Effectiveness of prenatal vitamin D deficiency screening and treatment program: A stratified randomized field trial.” J Clin Endocrinol Metab 103 (2018): 2936–48.

Roth, D.E., Morris, S.K., Zlotkin, S., et al. “Vitamin D supplementation in pregnancy and lactation and infant growth.” N Engl J Med 379 (2018): 535–46.

Sablok, A., Batra, A., Thariani, K., et al. “Supplementation of vitamin D in pregnancy and its correlation with feto-maternal outcome.” Clin Endocrinol 83 (2015): 536–41.

Smith, D., Hornstra, J., Rocha, M., et al. “Folic acid impairs the uptake of 5-Methyltetrahydrofolate in human umbilical vascular endothelial cells.” J Cardiovasc Pharmacol 70.4 (2017): 271–5.

Smith, E.R., Shankar, A.H., Wu, L.S., et al. “Modifiers of the effect of maternal multiple micronutrient supplementation on stillbirth, birth outcomes, and infant mortality: A meta-analysis of individual patient data from 17 randomised trials in low-income and middle-income countries.” Lancet Glob Health 5 (2017): e1090–e1100.

Srinivasan, K., Thomas, S., Anand, S., et al. “Vitamin B-12 supplementation during pregnancy and early lactation does not affect neurophysiologic outcomes in children aged 6 years.” The Journal of Nutrition 150.7 (2020): 1951–7.

Sudfeld, C.R., Smith, E.R. “New Evidence Should Inform WHO Guidelines on Multiple Micronutrient Supplementation in Pregnancy.” J Nutr 149 (2019): 359–61.

Vandevijvere, S., Amsalkhir, S., Van Oyen, H., Moreno-Reyes, R. “High prevalence of vitamin D deficiency in pregnant women: a national cross-sectional survey.” PLoS One 7 (2012): e43868.

World Health Organization. WHO Recommendations on antenatal care for a positive pregnancy experience. Executive summary. Geneva. WHO (2016). Available from: [].

Wilson, R.L., Gummow, J.A., McAninch, D., et al. “Vitamin and mineral supplementation in pregnancy: evidence to practice.” Journal of Pharmacy Practice and Research 48 (2018):186–92.

World Health Organization. Vitamin D supplementation during pregnancy (2019). Available from: [].

Xiao, J.P., Zang, J., Pei, J.J., et al. “Low maternal vitamin D status during the second trimester of pregnancy: a cross-sectional study in Wuxi, China.” PLoS One 10 (2015): e0117748.

Zhang, T., Sun, Y., Chen, Z., Li, T. “Traditional and molecular chromosomal abnormality analysis of products of conception in spontaneous and recurrent miscarriage.” BJOG 125 (2018): 414–20.





Pregnancy and childbirth