Maternal Folic Acid Intake and Risk of Nonsyndromic Orofacial Clefts: A Hospital-Based Case–Control Study in Bangalore, India

2019 ◽  
Vol 57 (6) ◽  
pp. 678-686
Author(s):  
Vivienne J. Mendonca

Background: Orofacial clefts are the most common congenital anomaly worldwide. Cleft etiology appears to be multifactorial, with genetic and environmental components. Although periconceptional folic acid supplementation has been shown to be protective for neural tube defects, current evidence for its role in cleft prevention is mixed with few studies from low- and middle-income countries. Aim: To investigate the association between periconceptional folic acid intake and incidence of nonsyndromic orofacial clefts among infants in Bangalore, India. Methods: A hospital-based case–control study (106 cases, 212 controls) utilizing a questionnaire to collect data on prenatal supplements, dietary folate, and potentially confounding factors. Multivariate logistic regression analysis was used to assess relationships between folic acid supplementation and all nonsyndromic clefts, and in separate analyses for cleft lip and/or palate (CL/P) and cleft palate (CP), adjusting for statistically significant variables. Results: A statistically significant protective association was found for separate folic acid supplements (not combined with iron or multivitamins) taken in the periconceptional period and all clefts combined (adjusted odds ratio [OR]: 0.62, 95% confidence interval [CI], 0.45-0.86) and CL/P (adjusted OR: 0.57; 95% CI, 0.38-0.86). Higher levels of dietary folate were found to be associated with a reduced risk for all clefts (adjusted OR: 0.98, 95% CI, 0.96-0.99), CL/P (adjusted OR: 0.98, 95% CI, 0.96-0.99), and CP (adjusted OR: 0.96, 95% CI, 0.93-0.99). Conclusion: This study provides limited evidence for a protective association of periconceptional folic acid supplementation with nonsyndromic orofacial clefts. The low proportion of mothers taking folic acid supplements in the periconceptional period highlights the need for increased education and awareness regarding prenatal nutrition.

2021 ◽  
Author(s):  
Wenli Xu ◽  
Ling Yi ◽  
Changfei Deng ◽  
Ziling Zhao ◽  
Tianjin Zhou ◽  
...  

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 negatively 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 significant (aOR = 0.52, 95% CI: 0.30–0.90), but the statistical power seemed weak due to limited number of NsCP cases. 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.


Author(s):  
Yanji Qu ◽  
Shao Lin ◽  
Jian Zhuang ◽  
Michael S. Bloom ◽  
Maggie Smith ◽  
...  

Background Maternal folic acid supplementation (FAS) reduces the risk of neural tube defects in offspring. However, its effect on congenital heart disease (CHDs), especially on the severe ones remains uncertain. This study aimed to assess the individual and joint effect of first‐trimester maternal FAS and multivitamin use on CHDs in offspring. Methods and Results This is a case‐control study including 8379 confirmed CHD cases and 6918 controls from 40 healthcare centers of 21 cities in Guangdong Province, China. Adjusted odds ratios (aORs) of FAS and multivitamin use between CHD cases (overall and specific CHD phenotypes) and controls were calculated by controlling for parental confounders. The multiplicative interaction effect of FAS and multivitamin use on CHDs was estimated. A significantly protective association was detected between first‐trimester maternal FAS and CHDs among offspring (aOR, 0.69; 95% CI, 0.62–0.76), but not for multivitamin use alone (aOR, 1.42; 95% CI, 0.73–2.78). There was no interaction between FAS and multivitamin use on CHDs ( P =0.292). Most CHD phenotypes benefited from FAS (aORs ranged from 0.03–0.85), especially the most severe categories (ie, multiple critical CHDs [aOR, 0.16; 95% CI, 0.12–0.22]) and phenotypes (ie, single ventricle [aOR, 0.03; 95% CI, 0.004–0.21]). Conclusions First‐trimester maternal FAS, but not multivitamin use, was substantially associated with lower risk of CHDs, and the association was strongest for the most severe CHD phenotypes. We recommend that women of childbearing age should supplement with folic acid as early as possible, ensuring coverage of the critical window for fetal heart development to prevent CHDs.


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