Maternal factor effect on the infants with cleft lip and cleft palate: A case–control study

Objective To investigate the association between smoking and orofacial clefts in the United Kingdom. Design Case-control study in which the mother's exposure to tobacco smoke was assessed by a structured interview. Setting Scotland and the Manchester and Merseyside regions of England. Participants One hundred ninety children born with oral cleft between September 1, 1997, and January 31, 2000, and 248 population controls, matched with the cases on sex, date of birth, and region. Main Outcome Measure Cleft lip with or without cleft palate and cleft palate. Results There was a positive association between maternal smoking during the first trimester of pregnancy and both cleft lip with or without cleft palate (odds ratio 1.9, 95% confidence interval 1.1 to 3.1) and cleft palate (odds ratio 2.3, 95% confidence interval 1.3 to 4.1). There was evidence of a dose-response relationship for both types of cleft. An effect of passive smoking could not be excluded in mothers who did not smoke themselves. Conclusion The small increased risk for cleft lip with or without cleft palate in the offspring of women who smoke during pregnancy observed in this study is in line with previous evidence. In contrast to some previous studies, an increased risk was also apparent for cleft palate. In these U.K. data, there was evidence of a dose-response effect of maternal smoking for both types of cleft. The data were compatible with a modest effect of maternal passive smoking, but the study lacked statistical power to detect or exclude such an effect with confidence. It may be useful to incorporate information on the effects of maternal smoking on oral clefts into public health campaigns on the consequences of maternal smoking.

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Association between selected essential trace element concentrations in umbilical cord and risk for cleft lip with or without cleft palate: A case-control study

The Science of The Total Environment ◽

10.1016/j.scitotenv.2019.01.171 ◽

2019 ◽

Vol 661 ◽

pp. 196-202 ◽

Cited By ~ 7

Author(s):

Wenli Ni ◽

Wenlei Yang ◽

Jinhui Yu ◽

Zhiwen Li ◽

Lei Jin ◽

...

Keyword(s):

Cleft Palate ◽

Trace Element ◽

Umbilical Cord ◽

Cleft Lip ◽

Case Control Study ◽

Case Control ◽

Essential Trace Element ◽

Element Concentrations ◽

Control Study

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First trimester exposure to ambient gaseous air pollutants and risk of orofacial clefts: a case–control study in Changsha, China

BMC Oral Health ◽

10.1186/s12903-021-01876-7 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Wen Jiang ◽

Wanqin Xie ◽

Bin Ni ◽

Haiyan Zhou ◽

Zhiyu Liu ◽

...

Keyword(s):

Particulate Matter ◽

Cleft Palate ◽

Air Pollutants ◽

Cleft Lip ◽

Case Control Study ◽

First Trimester ◽

Case Control ◽

Orofacial Clefts ◽

First Trimester Of Pregnancy ◽

Control Study

Abstract Background A growing body of studies have investigated the association between air pollution exposure during early pregnancy and the risk of orofacial clefts, but these studies put more emphasis on particulate matter and reported inconsistent results, while research on the independent effects of gaseous air pollutants on orofacial clefts has been quite inadequate, especially in China. Methods A case–control study was conducted in Changsha, China from 2015 to 2018. A total of 446 cases and 4460 controls were included in the study. Daily concentrations of CO, NO2, SO2, O3, PM2.5 and PM10 during the first trimester of pregnancy were assigned to each subject using the nearest monitoring station method. Multivariate logistic regression models were applied to evaluate the associations of monthly average exposure to gaseous air pollutants with orofacial clefts and its subtypes before and after adjusting for particulate matter. Variance inflation factors (VIFs) were used to determine if the effects of gaseous air pollutants could be independent of particulate matter. Results Increase in CO, NO2 and SO2 significantly increased the risk of cleft lip with or without cleft palate (CL/P) in all months during the first trimester of pregnancy, with aORs ranging from 1.39 to 1.48, from 1.35 to 1.61 and from 1.22 to 1.35, respectively. The risk of cleft palate only (CPO) increased with increasing NO2 exposure levels in the first trimester of pregnancy, with aORs ranging from 1.60 to 1.66. These effects sustained and even exacerbated after adjusting for particulate matter. No significant effect of O3 was observed. Conclusions Our study suggested that maternal exposure to CO, NO2, and SO2 during the first trimester of pregnancy might contribute to the development of orofacial clefts, and the associations were potentially independent of particulate matter.

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Nested Case-Control Study of One-Carbon Metabolites in Mid-Pregnancy and Risks of Cleft Lip With and Without Cleft Palate

Pediatric Research ◽

10.1203/pdr.0b013e3181b9b544 ◽

2009 ◽

Vol 66 (5) ◽

pp. 501-506 ◽

Cited By ~ 20

Author(s):

Gary M Shaw ◽

Stein Emil Vollset ◽

Suzan L Carmichael ◽

Wei Yang ◽

Richard H Finnell ◽

...

Keyword(s):

Cleft Palate ◽

Cleft Lip ◽

Case Control Study ◽

Case Control ◽

Nested Case Control ◽

Control Study

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The functional variant of NTN1 contributes to the risk of nonsyndromic cleft lip with or without cleft palate

European Journal of Human Genetics ◽

10.1038/s41431-019-0549-4 ◽

2019 ◽

Vol 28 (4) ◽

pp. 453-460

Author(s):

Dandan Li ◽

Guirong Zhu ◽

Shu Lou ◽

Lan Ma ◽

Chi Zhang ◽

...

Keyword(s):

Cleft Palate ◽

Cleft Lip ◽

Genome Wide Association Study ◽

Case Control Study ◽

Cleft Lip And Palate ◽

Case Control ◽

Orofacial Cleft ◽

Enhancer Activity ◽

Increased Risk ◽

Control Study

AbstractPrevious genome-wide association study of nonsyndromic cleft lip with or without cleft palate (NSCL/P) identified a susceptible variant (rs4791774). We hypothesized that the functional single nucleotide polymorphism (SNP) may be in linkage disequilibrium with this lead SNP. The potential functional SNP (rs4791331) was identified by bioinformatic analysis. A case–control study with 891 orofacial cleft cases and 830 controls was designed to investigate its association with orofacial cleft. The allele-specific DNA-protein binding preference was predicted by JASPAR database. Cell proliferation, cycle and apoptosis, luciferase activity and netrin-1 (NTN1) expression were examined after transfection with the rs4791331 C/T vector in HEK-293 and HEPM cell lines. Forty-six lip tissues of NSCL/P patients were collected to detect NTN1 expression. ntn1a knockout zebrafish models were generated by CRISPR/Cas9 and observed with micro-CT. In the case–control study, the rs4791331-T allele was associated with an increased risk of nonsyndromic orofacial cleft (OR = 1.41, 95% CI = 1.19–1.68), as well as the subgroups cleft lip only (OR = 1.46, 95% CI = 1.14–1.87) and cleft lip and palate (OR = 1.58, 95% CI = 1.27–1.96). The T allele of rs4791331 exhibited anti-apoptotic effects and promoted cell cycle progression at the G1/S transition. Decreased enhancer activity and reduced NTN1 expression following transfection of the T allele were observed. Carriers of the CT/TT genotypes showed significantly lower expression of NTN1 than CC carriers. The ntn1a−/− zebrafish showed relatively wider intermaxillary fissures. These results indicate that rs4791331 (C > T) disrupted motif binding and led to abnormal expression of NTN1, which may be involved in the development of NSCL/P.

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Orofacial clefts in the newborn and environmental and occupational parental exposures: a case-control study in Rio de Janeiro, Brazil

Revista Brasileira de Saúde Materno Infantil ◽

10.1590/s1519-38292003000400005 ◽

2003 ◽

Vol 3 (4) ◽

pp. 401-409 ◽

Cited By ~ 4

Author(s):

Isabel Cristina G Leite ◽

Francisco José Roma Paumgartten ◽

Sérgio Koifman

Keyword(s):

Cleft Palate ◽

Vector Control ◽

Cleft Lip ◽

Case Control Study ◽

Occupational Exposures ◽

Case Control ◽

Base Case ◽

Orofacial Clefts ◽

Agricultural Pesticides ◽

Control Study

OBJECTIVES: to evaluate risk factors involving environmental and occupational parental exposures associated with occurrence of orofacial clefts in a group of Brazilian children. METHODS: a secondary base case-control study was conducted with 274 cases of cleft lip with or without cleft palate (CL±P) and cleft palate only, with 548 controls (1:2). The authors analyzed residential proximity to industrial areas, exposure to commercial insecticides, agricultural pesticides, and vector control spraying, as well as various occupational exposures. The results were obtained by conditional regression analysis. RESULTS: proximity to industrial installations as a risk factor (OR = 3,32; 95%CI: 2,18-5,05) for all orofacial clefts, as well as the combined use of household insecticides and urban vector control pesticide spraying (OR = 5,73; 95%CI: 2,51-11,28). A group of maternal occupations heavily associated with orofacial clefts was domestic services (OR = 2,89; 95%CI: 1,76-4,86). CONCLUSIONS: solvents are frequently associated with CL ± P and that they are contained in numerous industrial products and household cleaning products, the results pertaining to occupational exposure become plausible. Other associations such as the routine use of domestic insecticides require further specific research for confirmation of the hypothesis.

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A Mutation in RYK is a Genetic Factor for Nonsyndromic Cleft Lip and Palate

The Cleft Palate-Craniofacial Journal ◽

10.1597/04-145.1 ◽

2006 ◽

Vol 43 (3) ◽

pp. 310-316 ◽

Cited By ~ 18

Author(s):

Akira Watanabe ◽

Sadanori Akita ◽

Nguyen Thi Duc Tin ◽

Nagato Natsume ◽

Yoko Nakano ◽

...

Keyword(s):

Single Nucleotide Polymorphisms ◽

Cleft Palate ◽

Missense Mutation ◽

Cleft Lip ◽

Case Control Study ◽

Case Control ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Transmission Disequilibrium ◽

Control Study

Objective The RYK, EPHB2, and EPHB3 genes are attractive candidates for cleft lip and/or palate and cleft palate only pathogenesis. Both the Ryk-deficient mouse and Ephb2/Ephb3 (genes for interaction molecules with RYK) double-mutant mouse show cleft palate. Setting Mutation searches for RYK, EPHB2, and EPHB3 were carried out in a large number of Japanese and Vietnamese patients with cleft lip and/or palate and cleft palate only. Case-control study and transmission disequilibrium tests were performed also, using three single nucleotide polymorphisms within a linkage disequilibrium block in RYK. Seven haplotypes were constructed from the single nucleotide polymorphisms. Results A missense mutation, 1355G>A (Y452C), in RYK was identified in one Vietnamese patient with cleft lip and/or palate. This mutation was not found among 1646 Vietnamese, Japanese, and Caucasians, including 354 cleft lip and/ or palate and cleft palate only patients. Colony formation assay using NIH3T3 cells transfected with mutant cDNA revealed that mutant RYK had significantly reduced protein activity, compared with those with wild-type RYK, implying that the transformation ability of RYK is depleted by this mutation. Although a case-control study and transmission disequilibrium tests on three individual single nucleotide polymorphisms provided no evidence for association with oral clefts, a case-control study on one rare haplotype suggested a positive association in Japanese patients with cleft lip and/or palate and cleft palate only. No mutations in EPHB2 and EPHB3 were found in any patients examined. Conclusion The findings suggested that a missense mutation, 1355G>A, and one rare single nucleotide polymorphisms haplotype may play a role in the development of cleft lip and/or palate in the Vietnamese, and cleft lip and/ or palate and cleft palate only in the Japanese.

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