Maternal Smoking during Early Pregnancy, GSTP1 and EPHX1 Variants, and Risk of Isolated Orofacial Clefts

2007 ◽  
Vol 44 (4) ◽  
pp. 366-373 ◽  
Author(s):  
Dorian Ramirez ◽  
Edward J. Lammer ◽  
David M. Iovannisci ◽  
Cecile Laurent ◽  
Richard H. Finnell ◽  
...  
Keyword(s):  
Cleft Palate ◽  
Maternal Smoking ◽  
Cleft Lip ◽  
Detoxification Enzymes ◽  
Glutathione S Transferase ◽  
Orofacial Clefts ◽  
Functional Polymorphisms ◽  
Increased Risk ◽  
Cleft Lip Palate ◽  
Isolated Cleft Palate

Objective: To examine the interactions between four fetal xenobiotic metabolizing gene polymorphisms, maternal cigarette smoking, and risk for oral cleft defects. Design and Participants: California population–based case-control study of 431 infants born with isolated orofacial clefts and 299 nonmalformed controls. Main Outcome Measures: Infants were genotyped for functional polymorphisms of the detoxification enzymes microsomal epoxide hydrolase-1 (EPHX1 T→C [Tyr113His], and A→G [His139Arg]), and glutathione-S transferase Pi-1 (GSTP1 A→G [Ile105Val] and C→T [Ala114Val]), and risks for cleft outcomes were measured for gene only and gene-maternal smoking effects. Results: Although smoking was associated with an increased risk for isolated cleft lip ± palate, we found no independent associations of genotypes of EPHX1-codon 113 or GSTP1-codon 105 polymorphisms for either isolated cleft lip ± palate or isolated cleft palate. The heterozygote genotype for the EPHX1-codon 139 polymorphism was associated with an increased risk of isolated cleft palate (odds ratio = 1.6 [95% confidence interval, 1.0 to 2.6]). Infant EPHX1 and GTSP1 polymorphic variants did not appreciably alter the risks for clefts associated with maternal smoking, nor were any EPHX1 combined genotype-specific risks found. Infant genotypes of the GSTP1-codon 105 polymorphism, combined with glutathione-S-transferase-μ-1 null genotypes, did not appreciably alter the risk of orofacial clefts. Conclusions: Our results suggest that genetic variation of the detoxification enzymes EPHX1 and GSTP1 did not increase the risks of orofacial clefting, nor do they influence the risks associated with maternal smoking.

Smoking and Orofacial Clefts: A United Kingdom–Based Case-Control Study

2004 ◽  
Vol 41 (4) ◽  
pp. 381-386 ◽  
Author(s):  
J. Little ◽  
A. Cardy ◽  
M. T. Arslan ◽  
M. Gilmour ◽  
P. A. Mossey ◽  
...  
Keyword(s):  
Confidence Interval ◽  
Cleft Palate ◽  
Odds Ratio ◽  
Maternal Smoking ◽  
Cleft Lip ◽  
Case Control Study ◽  
Case Control ◽  
Orofacial Clefts ◽  
Increased Risk ◽  
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.

Children with Cleft Lip/Palate and Mental Retardation: A Subpopulation of Cleft-Craniofacial Team Patients

1993 ◽  
Vol 30 (6) ◽  
pp. 548-556 ◽  
Author(s):  
Ronald P. Strauss ◽  
Hillary Broder
Keyword(s):  
African American ◽  
Mental Retardation ◽  
Cleft Palate ◽  
Special Needs ◽  
Cleft Lip ◽  
Cleft Lip Palate ◽  
Caucasian Patients ◽  
Isolated Cleft Palate ◽  
Impaired Speech ◽  
Clinic Population

This study compares a subpopulation of persons with cleft lip/palate who have mental retardation (n = 56) to those with normal learning (n = 420), at a large university-based cleft-craniofacial center. Many of the patients Identified as having mental retardation in this sample have the diagnosis of isolated cleft palate (46.8%). Nearly half (46.3%) of the patients with mental retardation were found to have multiple anomalies, syndromes or associated medical findings. Common findings included cardiopulmonary defects, seizures, and deviations in head size. In this clinic population, mental retardation was found more commonly among African-American patients with clefts, than among Caucasian patients with clefts. Higher rates of facial disfiguration and impaired speech were found in patients with clefts and mental retardation. This research demonstrates that among a population of persons with cleft lip and/or cleft palate, there is a subpopulation of children who also have mental retardation. Craniofacial-cleft teams will need to develop strategies to address the special needs of this group of patients.

Pattern of Cleft Lip and Palate in Hospital-Based Population in Saudi Arabia: Retrospective Study

2008 ◽  
Vol 45 (6) ◽  
pp. 592-596 ◽  
Author(s):  
Aziza Aljohar ◽  
Kandasamy Ravichandran ◽  
Shazia Subhani
Keyword(s):  
Saudi Arabia ◽  
Cleft Palate ◽  
Cleft Lip ◽  
Cleft Lip And Palate ◽  
Tertiary Care ◽  
Positive Family History ◽  
Care Hospital ◽  
Associated Anomalies ◽  
Cleft Lip Palate ◽  
Isolated Cleft Palate

Objective: To report the patterns of cleft lip and/or cleft palate in Saudi Arabia from data collected at a tertiary care hospital. Design and Setting: King Faisal Specialist Hospital and Research Center, Riyadh. Patients: All the cleft lip and/or cleft palate patients registered in the Cleft Lip/Palate and Craniofacial Anomalies Registry from June 1999 to December 2005. Results: Retrospectively, 807 cases of cleft lip and/or palate were registered. There were 451 boys and 356 girls. Cleft lip and palate was more common (387) than isolated cleft palate (294) and isolated cleft lip (122). Boys predominated in cleft lip and palate and cleft lip; whereas, girls predominated in isolated cleft palate, with boy to girl ratios of 1.6:1, 1.2:1, and 0.9:1 for cleft lip and/or palate, isolated cleft lip, and isolated cleft palate, respectively. The Riyadh region had more cases (32.0%) than the Asir (15.6%) and Eastern (14.6%) regions. Parents of 439 individuals had consanguineous marriages. A positive family history of cleft was seen in 224 cases. Of 238 cases with associated anomalies, 91 had congenital heart disease. Of the children with isolated cleft palate, 40.5% had associated anomalies, whereas only 23.0% of the children with isolated cleft lip or cleft lip and palate had associated malformations. Conclusion: The pattern of cleft observed in this study does not differ significantly from those reported in the literature for Arab populations.

scholarly journals Incidence of Orofacial Clefts in Kumasi, Ghana

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
P. Agbenorku ◽  
M. Yore ◽  
K. A. Danso ◽  
C. Turpin
Keyword(s):  
Cleft Palate ◽  
Congenital Anomalies ◽  
Cleft Lip ◽  
Cleft Lip And Palate ◽  
Orofacial Clefts ◽  
Female Ratio ◽  
Live Births ◽  
Male Female Ratio ◽  
Cleft Lip Palate ◽  
History Of

Background. Cleft lip and cleft palate are among the most common orofacial congenital anomalies. This study is to establish Orofacial Clefts Database for Kumasi, Ghana, with a view to extend it to other cities in future to obtain a national orofacial anomaly database. Methods. A descriptive prospective survey was carried out at eleven selected health facilities in Kumasi. Results. The total number of live births recorded was 27,449. Orofacial anomalies recorded were 36, giving an incidence of 1.31/1000 live births or 1 in 763 live births. The mean maternal age of cleft lip/palate babies was 29.85 years (range 18–40 years). The male : female ratio for the orofacial anomalies babies was 1.3 : 1; the male : female ratio was 0.5 : 1 in the cleft lip group, 1.3 : 1 in the cleft lip and palate group, and 4 : 1 in the cleft palate group. The majority of clefts were unilateral (69.4%, n=25), with females (n=14) outnumbering males (n=11). A family history of cleft was recorded with five babies (13.9%). Associated congenital anomalies were recorded in seven (19.4%) cleft lips and/or palates. Conclusion. The incidence of 1 in 763 live births found in this study indicates that cleft lip/palate is a common congenital anomaly in Kumasi.

Maternal Common Cold or Fever During Pregnancy and the Risk of Orofacial Clefts in the Offspring: A Systematic Review and Meta-analysis

2021 ◽  
pp. 105566562110676
Author(s):  
Fang-ping Shi ◽  
Ying-ying Huang ◽  
Qiao-qun Dai ◽  
Yu-lu Chen ◽  
Hai-yin Jiang ◽  
...  
Keyword(s):  
Cleft Palate ◽  
Common Cold ◽  
Cleft Lip ◽  
Meta Analysis ◽  
Case Control Studies ◽  
Orofacial Clefts ◽  
Random Effects Models ◽  
Relative Risks ◽  
Increased Risk ◽  
The Common

The common cold and/or an associated fever during pregnancy have/has been suspected to harm the developing fetus. We sought possible correlations between a maternal common cold or fever during pregnancy and the risk of orofacial clefts in the offspring. We systematically searched PubMed and Embase using appropriate keywords, and we checked the reference lists of retrieved articles. We used random-effects models to estimate overall relative risks. Incidence of orofacial clefts. We included 13 case-control studies. Modest but statistically significant associations were found between a maternal common cold and cleft lip with or without a cleft palate (CL/CP) (odds ratio [OR] 2.17; 95% confidence interval [CI] 1.66–2.83) and a cleft palate only (CPO) (OR 3.08; 95% CI 1.5–6.34). Furthermore, maternal fever was also associated with an increased risk of CL/CP (OR 1.91, 95% CI 1.3–2.8) and CPO (OR 1.48, 95% CI 0.83–2.63) in the offspring. Further analyses of maternal influenza (alone) yielded similar results. Although evidence of heterogeneity should be carefully evaluated, our findings suggest that maternal common cold or fever during pregnancy may be associated with a greater risk of CL/CP or CPO in the offspring. Future cohort studies using valid assessments of maternal common cold exposure during pregnancy that consider the severity of fever are needed to clarify the contribution of maternal common cold or fever status to the risk of orofacial clefts in children.

scholarly journals Maternal cigarette smoking before or during pregnancy increases the risk of birth congenital anomalies: a population-based retrospective cohort study of 12 million mother-infant pairs

BMC Medicine ◽  
2022 ◽  
Vol 20 (1) ◽  
Author(s):  
Lili Yang ◽  
Huan Wang ◽  
Liu Yang ◽  
Min Zhao ◽  
Yajun Guo ◽  
...  
Keyword(s):  
Cigarette Smoking ◽  
Cleft Palate ◽  
Congenital Anomalies ◽  
Maternal Smoking ◽  
Cleft Lip ◽  
First Trimester ◽  
Vital Statistics ◽  
Third Trimester ◽  
Maternal Cigarette Smoking ◽  
Increased Risk

Abstract Background The associations of maternal cigarette smoking with congenital anomalies in offspring have been inconsistent. This study aimed to clarify the associations of the timing and intensity of maternal cigarette smoking with 12 subtypes of birth congenital anomalies based on a nationwide large birth cohort in the USA. Methods We used nationwide birth certificate data from the US National Vital Statistics System during 2016–2019. Women reported the average daily number of cigarettes they consumed 3 months before pregnancy and in each subsequent trimester during pregnancy. Twelve subtypes of congenital anomalies were identified in medical records. Poisson regression analysis was used to estimate the risk ratios (RRs) with 95% confidence intervals (CIs) for 12 subtypes of congenital anomalies associated with the timing (i.e., before pregnancy, and during three different trimesters of pregnancy) and intensity (i.e., number of cigarettes consumed per day) of maternal cigarette smoking. Results Among the 12,144,972 women included, 9.3% smoked before pregnancy and 7.0%, 6.0%, and 5.7% in the first, second, and third trimester, respectively. Maternal smoking before or during pregnancy significantly increased the risk of six subtypes of birth congenital anomalies (i.e., congenital diaphragmatic hernia, gastroschisis, limb reduction defect, cleft lip with or without cleft palate, cleft palate alone, and hypospadias), even as low as 1–5 cigarettes per day. The adjusted RRs (95% CIs) for overall birth congenital anomalies (defined as having any one of the congenital malformations above significantly associated with maternal cigarette smoking) among women who smoked 1–5, 6–10, and ≥ 11 cigarettes per day before pregnancy were 1.31 (1.22–1.41), 1.25 (1.17–1.33), and 1.35 (1.28–1.43), respectively. Corresponding values were 1.23 (1.14–1.33), 1.33 (1.24–1.42), 1.33 (1.23–1.43), respectively, for women who smoked cigarettes in the first trimester; 1.32 (1.21–1.44), 1.36 (1.26–1.47), and 1.38 (1.23–1.54), respectively, for women who smoked cigarettes in the second trimester; and 1.33 (1.22–1.44), 1.35 (1.24–1.47), and 1.35 (1.19–1.52), respectively, for women who smoked cigarettes in the third trimester. Compared with women who kept smoking before and throughout pregnancy, women who never smoked had significantly lower risk of congenital anomalies (RR 0.77, 95% CI 0.73–0.81), but women who smoked before pregnancy and quitted during each trimester of pregnancy had no reduced risk (all P > 0.05). Conclusions Maternal smoking before or during pregnancy increased the risk of several birth congenital anomalies, even as low as 1–5 cigarettes per day. Maternal smokers who stopped smoking in the subsequent trimesters of pregnancy were still at an increased risk of birth congenital anomalies. Our findings highlighted that smoking cessation interventions should be implemented before pregnancy.

RERE deficiency contributes to the development of orofacial clefts in humans and mice

2021 ◽  
Author(s):  
Bum Jun Kim ◽  
Hitisha P Zaveri ◽  
Peter N Kundert ◽  
Valerie K Jordan ◽  
Tiana M Scott ◽  
...  
Keyword(s):  
Cleft Palate ◽  
Cleft Lip ◽  
Neurodevelopmental Disorder ◽  
Mouse Embryos ◽  
Deletion Syndrome ◽  
Orofacial Clefts ◽  
Orofacial Clefting ◽  
Increased Risk ◽  
The Brain ◽  
Human And Mouse

AbstractDeletions of chromosome 1p36 are the most common telomeric deletions in humans and are associated with an increased risk of orofacial clefting. Deletion/phenotype mapping, combined with data from human and mouse studies, suggests the existence of multiple 1p36 genes associated with orofacial clefting including SKI, PRDM16, PAX7 and GRHL3. The arginine–glutamic acid dipeptide (RE) repeats gene (RERE) is located in the proximal critical region for 1p36 deletion syndrome and encodes a nuclear receptor co-regulator. Pathogenic RERE variants have been shown to cause neurodevelopmental disorder with or without anomalies of the brain, eye or heart (NEDBEH). Cleft lip has previously been described in one individual with NEDBEH. Here we report the first individual with NEDBEH to have a cleft palate. We confirm that RERE is broadly expressed in the palate during mouse embryonic development, and we demonstrate that the majority of RERE-deficient mouse embryos on C57BL/6 background have cleft palate. We go on to show that ablation of Rere in cranial neural crest (CNC) cells, mediated by a Wnt1-Cre, leads to delayed elevation of the palatal shelves and cleft palate and that proliferation of mesenchymal cells in the palatal shelves is significantly reduced in Rereflox/flox; Wnt1-Cre embryos. We conclude that loss of RERE function contributes to the development of orofacial clefts in individuals with proximal 1p36 deletions and NEDBEH and that RERE expression in CNC cells and their derivatives is required for normal palatal development.

scholarly journals Trends in Enteral Access Placement Among Patients With Oral Clefts: Evaluation of 46 617 Patient Admissions

2018 ◽  
Vol 56 (1) ◽  
pp. 21-30
Author(s):  
Thanapoom Boonipat ◽  
Nicholas S. Adams ◽  
Allen L. Shoemaker ◽  
Robert J. Mann ◽  
John W. Polley ◽  
...  
Keyword(s):  
Cleft Palate ◽  
Enteral Feeding ◽  
Cleft Lip ◽  
Cleft Lip And Palate ◽  
Complication Rates ◽  
Oral Clefts ◽  
Patient Admissions ◽  
Increased Risk ◽  
Enteral Access ◽  
Isolated Cleft Palate

Objective: It is well known that patients with oral clefts have challenges with feeding. Enteral feeding access, in the form of gastrostomy, is often utilized to supplement or replace oral intake. Although commonly performed, these procedures have reported complication rates as high as 83%. We intend to discover rates of enteral access in patients with oral clefts and report-related outcomes. Design: The Healthcare Cost Utilization Project Kids’ Inpatient Database from 2000 to 2012 was analyzed using patients with oral clefts and enteral access procedures. The χ2 test was used for univariate analyses of proportions, and linear regression was used to analyze trends. Multivariate logistic regression was used to analyze odds ratios. Results: Of the 46 617 patient admissions included, 14.6% had isolated cleft lip (CL), 51.7% cleft lip and palate (CLP), and 43.7% isolated cleft palate. The rates of enteral access in the oral cleft population increased from 3.7% in 2000 to 5.8% in 2012 ( P < .001). Increased rates were identified in patients with ( P = .019) and without ( P < .001) complex conditions. A significant increase in the rate of enteral access was seen in patients with CLP ( P < .001) and isolated cleft palate ( P < .001). No difference was seen in the isolated CL group ( P = .096). Patients with complex conditions were at a 4.4-fold increased risk and those admitted to urban, teaching hospitals were at a 4.7-fold risk of enteral access placement. Conclusions: The rates for enteral feeding access increased significantly from 2000 to 2012. The reasons for the increased incidence are unclear. Invasive enteral access procedures have been shown to have a multitude of complications. Careful patient selection should be done before placement of invasive enteral access.

Maternal Drug Use and Infant Cleft Lip/Palate with Special Reference to Corticoids

2003 ◽  
Vol 40 (6) ◽  
pp. 624-628 ◽  
Author(s):  
Bengt Källén
Keyword(s):  
Drug Use ◽  
Cleft Palate ◽  
Early Pregnancy ◽  
Cleft Lip ◽  
First Trimester ◽  
Orofacial Cleft ◽  
Orofacial Clefts ◽  
Maternal Drug Use ◽  
Median Cleft ◽  
Cleft Lip Palate

Objective To study the association between maternal drug use in early pregnancy and orofacial cleft in the infant. Design Register analysis based on prospectively collected information. Patients All delivered women in Sweden July 1, 1995, through December 31, 2001. Main outcome measure Presence of orofacial cleft in infant. Results Prospective information on maternal drug use during the first trimester, as reported in early pregnancy, was studied in 1142 infants with orofacial clefts, isolated or with other malformations, excluding chromosome anomalies. Any drug use was not associated with clefts (odds ratio [OR] = 0.98, 95% confidence interval [95% CI] = 0.85 to 1.13), with isolated clefts (OR = 0.92) with isolated median cleft palate (OR = 1.03, 95% CI = 0.79 to 1.36) or with isolated cleft lip with or without cleft palate (OR = 0.86, 95% CI = 0.71 to 1.05). Reported use of multivitamins, folic acid, or B12 was not associated with a decrease in orofacial cleft risk (OR = 1.00, 95% CI = 0.63 to 1.52). ORs above 2 were seen for some drugs: sulfasalazine, naproxen, and anticonvulsants, but only a few exposed cases occurred. An association between glucocorticoid use and infant cleft was indicated and seemed to be strongest for median cleft palate. Conclusion Maternal drug use seems to play only a small role for the origin of orofacial clefts, at least in Sweden.

scholarly journals Deep orofacial phenotyping of population-based infants with isolated cleft lip and isolated cleft palate

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Mimi Yow ◽  
Nuno V. Hermann ◽  
Yuan Wei ◽  
Agneta Karsten ◽  
Sven Kreiborg
Keyword(s):  
Cleft Palate ◽  
Cleft Lip ◽  
Population Based ◽  
Tooth Agenesis ◽  
Orofacial Clefts ◽  
Dental Epithelium ◽  
Pre Treatment ◽  
Isolated Cleft Palate ◽  
Dental Maturity ◽  
Deep Phenotyping

AbstractIsolated orofacial clefts (OFC) are common with poorly understood aetiology. Heterogeneous phenotypes and subphenotypes confound aetiological variant findings. To improve OFC phenome understanding, population-based, consecutive, pre-treatment infants with isolated unilateral cleft lip (UCL, n = 183) and isolated cleft palate (CP, n = 83) of similar ancestry were grouped for deep phenotyping. Subphenotypes stratified by gender and cleft severity were evaluated for primary dental malformations and maturation using radiographs. We found that cleft severity and tooth agenesis were inadequate to distinguish heterogeneity in infants with UCL and CP. Both groups featured slow dental maturity, significantly slower in males and the UCL phenotype. In 32.8% of infants with UCL, supernumerary maxillary lateral incisors were present on the cleft lip side, but not in infants with CP, suggesting a cleft dental epithelium and forme fruste cleft dentoalveolus of the UCL subphenotype. The findings underscored the importance of deep phenotyping to disclose occult OFC subphenotypes.

Sign in / Sign up

Export Citation Format

Share Document