Maternal periconceptional folic acid supplementation reduced risks of non-syndromic oral clefts in offspring

Wenli Xu,Wenli Xu,Longrong Ran,Changfei Deng,Ling Yi,Li Dai,Li Dai,Ziling Zhao,Tianjin Zhou,Gang Zhang,Gang Zhang,Ziling Zhao,Changfei Deng,Hanmin Liu,Hanmin Liu,Shunxia Zhao,Zhihong Ren

doi:10.1038/s41598-021-91825-9

Abstract

Maternal periconceptional folic acid supplementation (FAS) has been documented to be associated with decreased risk of nonsyndromic oral clefts (NsOC). However, the results remain inconclusive. In this population-based case–control study of 807 singletons affected by NsOC and 8070 healthy neonates who were born between October 2010 and September 2015 in Chengdu, China, we examined the association of maternal FAS with the risk of nonsyndromic cleft lip with or without cleft palate (NsCL/P), and cleft palate (NsCP). Unconditional logistic regression analysis was used to estimate the crude and adjusted odds ratios (ORs) and 95% confidential intervals (CI). Significant associations were found between maternal periconceptional FAS and decreased risk of NsCL/P (aOR = 0.41, 95% CI 0.33–0.51). This protective effect was also detected for NsCL (aOR = 0.42, 95% CI 0.30–0.58) and NsCLP (aOR = 0.41, 95% CI 0.31–0.54). Both maternal FAS started before and after the last menstrual period (LMP) were inversely associated with NsCL/P (before LMP, aOR = 0.43, 95% CI 0.33–0.56; after LMP, aOR = 0.41, 95% CI 0.33–0.51). The association between NsCP and maternal FAS initiating before LMP was also found (aOR = 0.52, 95% CI 0.30–0.90). The findings suggest that maternal periconceptional FAS can reduce the risk of each subtype of NsCL/P in offspring, while the potential effect on NsCP needs further investigations.

Highlights

Maternal periconceptional folic acid supplementation (FAS) has been documented to be associated with decreased risk of nonsyndromic oral clefts (NsOC)
Females were identified as risk factors of nonsyndromic cleft palate (NsCP) (Supplementary Table 1). In this population-based case–control study, we demonstrated that maternal periconceptional FAS was associated with a reduced risk of overall NsCL/P, and the reduced risk varied by cleft subtype and supplementation initiation timing
We did not identify the preventive effect of periconceptional FAS for NsCP, whereas we observed a significant association between maternal FAS started before last menstrual period (LMP) and NsCP, suggesting that earlier or longer supplementation may be protective

Summary

Introduction

Maternal periconceptional folic acid supplementation (FAS) has been documented to be associated with decreased risk of nonsyndromic oral clefts (NsOC). In this population-based case–control study of 807 singletons affected by NsOC and 8070 healthy neonates who were born between October 2010 and September 2015 in Chengdu, China, we examined the association of maternal FAS with the risk of nonsyndromic cleft lip with or without cleft palate (NsCL/P), and cleft palate (NsCP). The information regarding maternal folic use, prenatal exposures, perinatal health care and birth outcomes are prospectively collected by the Chengdu Maternal and Infant Health Surveillance system (CMIHS) These data allowed us to examine additional effect of maternal FAS on NsOC subtypes by performing a population-based case–control study

Methods

Results

Conclusion