Oral Clefts, Transforming Growth Factor Alpha Gene Variants, and Maternal Smoking: A Population-based Case-Control Study in Denmark, 1991-1994

Objective: Infants born in Maryland between June 1992 and June 1996 were used in a case-control study of nonsyndromic oral clefts to test for effects of maternal smoking and a polymorphic genetic marker at the transforming growth factor alpha (TGFA) locus, both of which have been reported to be risk factors for these common birth defects. Design and Setting: Cases were infants with an oral cleft ascertained through three comprehensive treatment centers, with additional ascertainment through a registry of birth defects maintained by the Maryland Health Department. Controls were healthy infants. Medical history information on infants and mothers were collected, along with DNA samples Patients, Participants: Among 286 cases contacted (72% ascertainment), there were 192 nonsyndromic isolated oral clefts (106 M; 86 F) available for this case-control study. Main Outcome Measures: The largest group of 149 Caucasian nonsyndromic cases and 86 controls was used to test for association with maternal smoking and genotype at the Taq1 polymorphism in TGFA. Results: While this modest sample had limited statistical power to detect gene-environment interaction, there was a significant marginal Increase In risk of having an oral cleft If the mother smoked (odds ratio = 1.75, 95%CI = 1.01 to 3.02). We could not demonstrate statistical interaction between maternal smoking and TGFA genotype in this study, however, and the observed increase in the C2 allele among cases was not statistically significant. Conclusions: We could not confirm either the reported association between oral clefts and TGFA genotype or its interaction with maternal smoking. However, these data do show an increased risk if the mother smoked during pregnancy, and this effect was greatest among infants with a bilateral cleft and no close family history of clefts.

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The contribution of maternal epilepsy and its treatment to the etiology of oral clefts: A population based case-control study

Genetic Epidemiology ◽

10.1002/gepi.1370110404 ◽

1994 ◽

Vol 11 (4) ◽

pp. 343-351 ◽

Cited By ~ 34

Author(s):

Ahmad R. Abrishamchian ◽

Muin J. Khoury ◽

Eugenia E. Calle

Keyword(s):

Case Control Study ◽

Population Based ◽

Case Control ◽

Oral Clefts ◽

Control Study

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Maternal Periconceptional Folic Acid Supplementation and the Risk of Non-Syndromic Oral Clefts in Offspring: A Population-Based Case-Control Study in Chengdu, China

10.21203/rs.3.rs-136950/v1 ◽

2021 ◽

Author(s):

Wenli Xu ◽

Ling Yi ◽

Changfei Deng ◽

Ziling Zhao ◽

Tianjin Zhou ◽

...

Keyword(s):

Folic Acid ◽

Cleft Palate ◽

Statistical Power ◽

Case Control Study ◽

Population Based ◽

Folic Acid Supplementation ◽

Case Control ◽

Oral Clefts ◽

Acid Supplementation ◽

Control Study

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.

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