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Effect of maternal vitamin D status on risk of adverse birth outcomes: a systematic review and dose–response meta-analysis of observational studies

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Abstract

Purpose

Accumulating evidence suggests that vitamin D deficiency increases the risk of adverse perinatal outcomes. However, the dose–response relationship between maternal vitamin D status and adverse birth outcomes remains unclear. Focusing on prospective observational studies, we aimed to explore the dose–response relationship of vitamin D status with the risk of low birth weight (LBW), macrosomia (MA), preterm birth (PTB), small for gestational age (SGA), and intrauterine growth restriction (IUGR).

Methods

Databases including PubMed, Embase, Scopus, and Web of Science were used up to 19 January 2021 to search for observational studies that fulfilled criteria as follows: cohort studies, case–cohort studies, or nested case–control studies. Random-effects models were used to pool relative risks (RRs) and 95% confidence intervals (CIs) in the observational studies.

Results

A total of 72 publications were included in this systematic review and 71 in the meta-analysis. Maternal 25-hydroxyvitamin D (25(OH)D) concentrations were inversely associated with the risk of LBW (RR: 0.65; 95% CI 0.48–0.86), PTB (RR: 0.67; 95% CI 0.57–0.79), and SGA (RR: 0.61; 95% CI 0.49–0.76) in the highest versus lowest meta-analysis, but not associated with MA and IUGR. Linear dose–response analysis showed that each 25 nmol/L increase in 25(OH)D was associated with a 6% and 10% reduction in the risk of PTB (RR: 0.94; 95% CI 0.90–0.98) and SGA (RR: 0.90; 95% CI 0.84–0.97), respectively.

Conclusion

Our study suggests that a sufficient vitamin D status during pregnancy is protective against the risk of LBW, PTB, and SGA.

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Availability of data and materials

All data generated or analyzed during this study are included in this article and its additional files.

Code availability

Not applicable.

Abbreviations

CLIA:

Chemiluminescent immunoassay

ECLIA:

Electrochemical luminescence immunoassay

EIA:

Enzyme immunoassay

ELISA:

Enzyme-linked immunosorbent assay

FFQ:

Food frequency questionnaire

HPLC:

High-performance liquid chromatography

IUGR:

Intrauterine growth restriction

LBW:

Low birth weight

LC–MS:

Liquid chromatography–mass spectrometry

MA:

Macrosomia

NOS:

Newcastle Ottawa scale

PTB:

Preterm birth

RIA:

Radioimmunoassay

RR:

Relative risk

SGA:

Small for gestational age

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Acknowledgements

We would like to thank all members of our research team for their engagement and the original authors of the included studies for their excellent work.

Funding

This research was supported by the National Natural Science Foundation of China (LH, No.81773426, No. 82173513) and the Joint Foundation of the Health Commission of Hubei Province (HY, WJ2018H0139).

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Authors and Affiliations

  1. Hubei Key Laboratory of Food Nutrition and Safety and the Ministry of Education (MOE) Key Laboratory of Environment and Health, School of Public Health, Department of Nutrition and Food Hygiene, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, Hubei, People’s Republic of China

    Rui Zhao, Leilei Zhou, Shanshan Wang, Xuefeng Yang & Liping Hao

  2. Department of Obstetrics, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China

    Heng Yin

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  1. Rui Zhao
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Contributions

RZ and LH designed the study; RZ, SW, and LZ researched the databases; RZ, LZ, and SW collected data; RZ and LZ analyzed the data; RZ drafted the manuscript; HY, XY, and LH critically revised the manuscript. All authors have read and approved the final manuscript.

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Correspondence to Liping Hao.

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Zhao, R., Zhou, L., Wang, S. et al. Effect of maternal vitamin D status on risk of adverse birth outcomes: a systematic review and dose–response meta-analysis of observational studies. Eur J Nutr 61, 2881–2907 (2022). https://doi.org/10.1007/s00394-022-02866-3

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