Maternal risk factors for oral clefts: A case-control study

Introduction: A cleft lip with or without a cleft palate is one of the major congenital anomalies observed in newborns. This study explored the risk factors for oral clefts in Gorgan, Northern Iran. Materials and Methods: This hospital-based case-control study was performed in three hospitals in Gorgan, Northern Iran between April 2006 and December 2009. The case group contained 33 newborns with oral clefts and the control group contained 63 healthy newborns. Clinical and demographic factors, including date of birth, gender of the newborns, type of oral cleft, consanguinity of the parents, parental ethnicity, and the mother's parity, age, education and intake of folic acid were recorded for analysis. Results: A significant association was found between parity higher than 2 and the risk of an oral cleft (OR= 3.33, CI 95% [1.20, 9.19], P> 0.02). According to ethnicity, the odds ratio for oral clefts was 0.87 in Turkmens compared with Sistani people (CI 95% [0.25, 2.96]) and 1.11 in native Fars people compared with Sistani people (CI 95% [0.38, 3.20]). A lack of folic acid consumption was associated with an increased risk of oral clefts but this was not statistically significant (OR = 1.42, CI 95% [0.58, 3.49]). There were no significant associations between sex (OR boy/girl = 0.96, CI 95% [0.41, 2.23]), parent familial relations (OR = 1.07, CI 95% [0.43, 2.63]), mother's age and oral clefts. Conclusions: The results of this study indicate that higher parity is significantly associated with an increased risk of an oral cleft, while Fars ethnicity and a low intake of folic acid increased the incidence of oral clefts but not significantly

Spatial Epidemiology of Birth Defects in the United States and the State of Utah Using Geographic Information Systems and Spatial Statistics

Oral clefts are the most common form of birth defects in the United States (US) and the State of Utah has among the highest prevalence of oral clefts in the nation. The overall objective of this dissertation was to examine the spatial distribution of oral clefts and their linkage with a broad range of demographic, behavioral, social, economic, and environmental risk factors through the application of Geographic Information Systems (GIS) and spatial statistics. Using innovative linked micromaps plots, we investigated the geographic patterns of oral clefts occurrence from 1998 to 2002 and their relationships with maternal smoking rates and proportion of American Indians and Alaskan Natives (AIAN) at large scales across the US. The findings indicated higher oral clefts occurrence in the southwest and the midwest and lower occurrence in the east. Furthermore, these spatial patterns were significantly related to the smoking rates and AIAN. Then at the small area level, hierarchical Bayesian models were built to examine the spatial variation in oral clefts risk in the State of Utah from 1995 to 2004 and to assess association with mothers using tobacco, mothers consuming alcohol during pregnancy, and the proportion of mothers with no high school diploma. Next, multi-scalar spatial clustering and cluster techniques were used to test the hypothesis whether there was spatial clustering of oral clefts anywhere in the State of Utah and whether there were statistically significant local clusters with elevated oral cleft cases. Results generally revealed modest spatial variation in oral clefts risk in the State of Utah, with no pronounced spatial clustering, indicating environmental exposures are unlikely plausible cause of oral clefts. However, a few notable areas within Tri-County Local Health District, Provo/Brigham Young University, and North Orem had a tendency toward elevated oral clefts cases. Investigation of the maternal characteristics of these potential clusters supports the hypotheses that maternal smoking, lower education level, and family history are possible causes of oral clefts. Throughout this dissertation, we demonstrated how birth defects data collected by state and local surveillance systems coupled with GIS and spatial statistics methods can be useful in exploratory etiologic research of birth defects

The effects of oral clefts on hospital use throughout the lifespan

<p>Abstract</p> <p>Background</p> <p>Oral clefts are one of the most common birth defects worldwide. They require multiple healthcare interventions and add significant burden on the health and quality of life of affected individuals. However, not much is known about the long term effects of oral clefts on health and healthcare use of affected individuals. In this study, we evaluate the effects of oral clefts on hospital use throughout the lifespan.</p> <p>Methods</p> <p>We estimate two-part regression models for hospital admission and length of stay for several age groups up to 68 years of age. The study employs unique secondary population-based data from several administrative inpatient, civil registration, demographic and labor market databases for 7,670 individuals born with oral clefts between 1936 and 2002 in Denmark, and 220,113 individuals without oral clefts from a 5% random sample of the total birth population from 1936 to 2002.</p> <p>Results</p> <p>Oral clefts significantly increase hospital use for most ages below 60 years by up to 233% for children ages 0-10 years and 16% for middle age adults. The more severe cleft forms (cleft lip with palate) have significantly larger effects on hospitalizations than less severe forms.</p> <p>Conclusions</p> <p>The results suggest that individuals with oral clefts have higher hospitalization risks than the general population throughout most of the lifespan.</p

IRF6 AP-2a binding site promoter polymorphism is associated with oral clefts in Latvia

OBJECTIVE: To evaluate the association between AXIN2, CDH1 and IRF6 with oral clefts in a cohort from Latvia. MATERIAL AND METHODS: 283 unrelated individuals, 93 born with isolated oral clefts and 190 individuals born without any structural abnormalities were evaluated. Cleft type and dental anomalies outside the cleft area were determined by clinical examination. Four SNPs were selected for this study: rs2240308 and rs11867417 in AXIN2; rs9929218 in CDH1; and rs642961 in IRF6. Genotypes were determined by polymerase chain reaction using the Taqman assay method from a genomic DNA sample extracted from whole blood. Allele and genotype frequencies were compared between individuals born with or without oral clefts using the PLINK program. RESULTS: Tooth agenesis was the most frequent dental anomaly found among individuals born with oral clefts (N=10; frequency 10.8%). The allele A in the IRF6 marker rs642961 was associated with all combined types of oral clefts (OR=1.74; CI 95% 1.07-2.82) and with cases with cleft lip with or without cleft palate (OR=1.88, CI 95% 1.15-3.01; p=0.007). CONCLUSIONS: The IRF6 AP-2a binding site promoter polymorphism is associated with isolated oral clefts in Latvia.publishersversionPeer reviewe

Incidence of cleft lip and palate in Gorgan - Northern Iran: An epidemiological study

Objective: Cleft lip with or without cleft palate is the most common orofacial congenital anomaly among live births. This study was carried out to determine the incidence rate of oral clefting in Gorgan, Northern Iran during 2004-2009. Methods: This descriptive hospital-based study was performed on 35,009 live newborns in Dezyani Hospital in Gorgan, Northern Iran during 2004-2009. All newborns were screened for oral clefts. Data including birth date, gender, type of oral clefts, parents' consanguinity, parental ethnicity and presence of other congenital anomalies were recorded for analysis. Result: The overall incidence rate of oral clefts during this 6-year period was 1.05 per 1000, or 1 per 946 live births. The incidence of cleft lip and isolated cleft palate was 0.08 and 0.37 per 1,000 live births, respectively. The ratio for different cleft types was 1:7:4 (CL: CLP: CP). The incidence of oral clefting was 1.2 per 1,000 male births and 0.86 per 1,000 female births (RR=1.40; 95% CI: 0.73-2.71). According to parental ethnicity, the incidence of oral clefting was 0.7, 1.7 and 1.26 per 1,000 in Native Fars, Turkman and Sistani, respectively. The relative risk for oral clefting in Turkman to native Fars group was 2.56 (p<0.02). In this study, 56.7% of clefts were CL+P, 8.1% were CL and 35.1% of cases were CP. CP was more common among girls (54%) than among boys (46%) but CL was more common among boys. Conclusion: The results showed that the incidence of oral clefts in the study population as being 1.05 per 1,000 live births, which has increased from 0.97 per 1,000 live births reported in an earlier study in this area. © OMSB, 2012

Assessing the association between hypoxia during craniofacial development and oral clefts

Objectives: To evaluate the association between hypoxia during embryo development and oral clefts in an animal model, and to evaluate the association between polymorphisms in the HIF-1A gene with oral clefts in human families. Material and Methods: The study with the animal model used zebrafish embryos at 8 hours post-fertilization submitted to 30% and 50% hypoxia for 24 hours. At 5 days post-fertilization, the larvae were fixed. The cartilage structures were stained to evaluate craniofacial phenotypes. The family-based association study included 148 Brazilian nuclear families with oral clefts. The association between the genetic polymorphisms rs2301113 and rs2057482 in HIF-1A with oral clefts was tested. We used real time PCR genotyping approach. ANOVA with Tukey's post-test was used to compare means. The transmission/disequilibrium test was used to analyze the distortion of the inheritance of alleles from parents to their affected offspring. Results: For the hypoxic animal model, the anterior portion of the ethmoid plate presented a gap in the anterior edge, forming a cleft. The hypoxia level was associated with the severity of the phenotype (p&lt;0.0001). For the families, there was no under-transmitted allele among the affected progeny (p&gt;0.05). Conclusion: Hypoxia is involved in the oral cleft etiology, however, polymorphisms in HIF-1A are not associated with oral clefts in humans

Maternal Dietary Patterns and Risk of Isolated Cleft Birth Defects in Utah - A Case-Control Study

Inadequate maternal nutrition during pregnancy has been suggested as a risk factor for oral cleft birth defects including the major groupings of cleft lip with or without cleft palate (CL/P), and cleft palate alone (CP). Few studies have analyzed overall dietary patterns in relation to development of oral clefts. The purpose of this study is to examine the statistical associations between maternal dietary pattern scores and risk of oral clefts in Utah. Data collected from the Utah Oral Cleft Study was used as a starting point. New variables were formed to define maternal dietary patterns using the SPSS statistical analysis program. Derived dietary pattern variables were compared among mothers of Utah children with oral clefts (445 cases) and mothers of unaffected children (410 controls); these included scores based on intake of the following groups of foods: fruits, vegetables, whole grains, low‐fat dairy foods, and an overall diet score based on the DASH dietary intervention studies. Logistic regression analyses were used to estimate the risk of oral clefts by quintile of the food group and DASH scores while controlling for the potential confounding effects of maternal age, education, smoking and alcohol use during pregnancy, and multivitamin use during pregnancy. Logistic regression analysis indicated a 40% reduction in risk of oral clefts (CL/P and CP combined) (OR=0.60) in mothers in the highest vs. lowest quintile of whole grain intake. The iii DASH dietary score was not significantly associated with risk of oral clefts. Periconceptional exposure to tobacco smoke and education levels were also associated with risk of CL/P. Periconceptional dietary intake of whole grains may significantly reduce incidence of isolated CLP in the offspring

Birth Defects Res A Clin Mol Teratol

BACKGROUNDThere is evidence from previous studies that maternal occupational exposure to hazardous air pollutants is positively associated with oral clefts, however, studies evaluating the association between residential exposure to these toxicants and oral clefts are lacking. Therefore, our goal was to conduct a case-control study examining the association between estimated maternal residential exposure to benzene, toluene, ethyl benzene, and xylene (BTEX) and the risk of oral clefts among offspring.METHODSData on 6,045 non-syndromic isolated oral cleft cases (3,915 cleft lip with or without cleft palate [CL\uc2\ub1P] and 2,130 non-syndromic isolated cleft palate [CP] cases) delivered between 1999 and 2008 were obtained from the Texas Birth Defects Registry. The control group was a sample of unaffected live births, frequency matched to cases on year of birth. Census tract-level estimates of annual average exposures were obtained from the U.S. Environmental Protection Agency 2005 Hazardous Air Pollutant Exposure Model (HAPEM5) for each pollutant and assigned to each subject based on maternal residence during pregnancy. Logistic regression was used to assess the relationship between estimated maternal exposure to each pollutant (benzene, toluene, ethyl benzene, and xylene) separately and the risk of oral clefts in offspring.RESULTSHigh estimated maternal exposure to benzene was not associated with oral clefts, compared with low estimated exposure (CL\uc2\ub1P adjusted OR=0.95; 95% CI=0.81-1.12; CP adjusted OR=0.85; 95% CI=0.67-1.09). Similar results were seen for the other pollutants.CONCLUSIONIn our study, there was no evidence that maternal exposure to environmental levels of BTEX was associated with oral clefts.1R03DE02173901A1/DE/NIDCR NIH HHS/United StatesR03 DE021739/DE/NIDCR NIH HHS/United StatesU01DD000494/DD/NCBDD CDC HHS/United States2014-08-01T00:00:00Z23893927PMC377149