Risk Of Oral Clefts Research Articles

First-trimester nonsystemic corticosteroid use and the risk of oral clefts in Norway

PurposeExposure of pregnant mice to corticosteroids can produce oral clefts in offspring. Although data in humans are more mixed, recent reports have suggested that dermatologic steroids are associated with oral clefts. MethodsWe investigated maternal first-trimester exposure to corticosteroids (focusing on dermatologic uses) and oral clefts in offspring using two population-based studies. The Norway Cleft Study (1996–2001) is a national case-control study including 377 infants with cleft lip ± palate (CLP), 196 infants with cleft palate only (CPO), and 763 controls. The Norwegian Mother and Child Cohort Study (MoBa, 1998–2008) is a national birth cohort including 123 infants with CLP, 61 infants with CPO, and 551 controls. ResultsIn the case-control study, there was the suggestion of an association of dermatologic corticosteroids with both CLP (adjusted OR [aOR], 2.3; 95% confidence interval [CI], 0.71–7.7) and CPO (aOR, 3.4; CI, 0.87–13). There was no evidence of this association in the cohort data (odds ratio for CLP, 1.2; CI, 0.50–2.8 and odds ratio for CPO, 1.0; CI, 0.30–3.4), although exposure to dermatologic steroids was less specifically ascertained. There were no associations with other types of corticosteroids. ConclusionsOur data add to the suggestive but inconsistent findings for this association.

Topiramate use in pregnancy and the birth prevalence of oral clefts

First marketed in the USA in 1996, topiramate (TPM) is an antiepileptic drug later approved for migraine prophylaxis, and in 2012 for weight loss in combination with phentermine. Some studies indicate an elevated prevalence of oral cleft (OC) in infants exposed to TPM in utero. We evaluated the association between TPM use in early pregnancy and the risk of OC. This retrospective cohort study used 1997-2011 automated data from four sources: HealthCore and OptumInsight (commercial insurance claims), Truven Health (Medicaid claims), and Kaiser Permanente Northern California Region (electronic medical records). We compared the prevalence of OCs in infants of women exposed to TPM in the first trimester (TPM cohort) with the prevalence in infants of women formerly exposed to TPM or other antiepileptic drugs (formerly exposed [FE] cohort) and infants of women with similar medical profiles (SMPs) to the TPM cohort that were not exposed to TPM (SMP cohort). To control for confounding, we used stratification and standardization for individual variables and propensity score deciles. The birth prevalence of OCs was 0.36% (7/1945) in the TPM cohort, 0.14% (20/13 512) in the FE cohort, and 0.07% (9/13 614) in the SMP cohort. Standardized by site, the prevalence ratio (PR) for TPM versus FE was 2.5 (95% CI: 1.0-6.0) and for TPM versus SMP was 5.4 (95% CI: 2.0-14.6). Adjustment for covariates one at a time or by propensity score yielded similar results. Consistent with other recent epidemiologic research, first-trimester TPM exposure was associated with an elevated birth prevalence of OC.

Use of Corticosteroids in Early Pregnancy is Not Associated With Risk of Oral Clefts and Other Congenital Malformations in Offspring

Corticosteroids are commonly used to treat inflammatory diseases. There is conflicting evidence regarding the association of corticosteroid use in pregnancy and congenital malformations in offspring. We conducted a prevalence study of 83,043 primiparous women who gave birth to a live-born singleton in northern Denmark, in 1999-2009. Through medical registries, we identified prescriptions for corticosteroids, congenital malformations, and covariates. Furthermore, we summarized the literature on this topic. Overall, 1449 women (1.7%) used inhaled or oral corticosteroids from 30 days before conception throughout the first trimester. Oral cleft in the offspring was recorded for 1 of the users (0.08%) and 145 of the nonusers (0.2%), prevalence odds ratio (OR) 0.47 [95% confidence interval (CI), 0.07-3.34]. The prevalence OR for congenital malformations overall was 1.02 (95% CI, 0.79-1.32). According to published studies, the use of corticosteroids in early pregnancy was associated with congenital malformations overall with relative estimates ranging from 0.8 (95% CI, 0.4-1.7) to 2.1 (95% CI, 0.5-9.6). For oral clefts, the ORs ranged from 0.6 (95% CI, 0.2-1.7) to 5.2 (95% CI, 1.5-17.1). We found no evidence of an association between use of corticosteroids in early pregnancy and risk of congenital malformations in offspring.

Analysis of Potential Oral Cleft Risk Factors in the Kosovo Population

The aim of this study was to analyze the association of potential risk factors such as positive family cleft history, smoking, use of drugs during pregnancy, and parental age with oral clefts in offspring within the Kosovo population. We conducted a population-based case-control study of live births in Kosovo from 1996 to 2005. Using a logistic regression model, 244 oral cleft cases were compared with 488 controls. We have excluded all syndromic clefts. Heredity increases the risk of clefts in newborns [odds ratio (OR) = 8.25, 95% confidence interval (CI) 3.12-23.52]. Clefts were also associated with smoking (OR = 1.87, 95% CI 0.75-4.08), use of drugs during pregnancy (OR = 2.25, 95% CI 0.82-5.12), increasing maternal age (OR = 1.83, 95% CI 1.42-2.49), and increasing paternal age (OR = 1.3, 95% CI 1.2- 1.4). We found heredity to be the most important factor for cleft occurrence in Kosovar newborns. Another significant potential risk factor for occurrence of clefts is the parental age. We found the use of drugs and smoking during pregnancy to be less significant.

Maternal Snuff Use and Smoking and the Risk of Oral Cleft Malformations - A Population-Based Cohort Study

ObjectiveTo determine if maternal use of snuff (containing high levels of nicotine, low levels of nitrosamines and no combustion products) is associated with an increased risk of oral cleft malformations in the infant and whether cessation of snuff use or smoking before the antenatal booking influences the risk.MethodA population-based cohort study was conducted on all live born infants, recorded in the Swedish Medical Birth Register from 1999 through 2009 (n = 1 086 213). Risks of oral clefts were evaluated by multivariate logistic regression analyses (using adjusted odds ratios, with 95% confidence intervals [CI]).ResultsAmong 975 866 infants that had information on maternal tobacco use, 1761 cases of oral clefts were diagnosed. More than 50% of the mothers who used snuff or smoked three months prior pregnancy stopped using before the antenatal booking. Almost 8% of the mothers were smoking at the antenatal booking and 1,1% of the mothers used snuff. Compared with infants of non-tobacco users, the adjusted odds ratios (95% CI) of any oral cleft for infants of mothers who continued to use snuff or to smoke were 1.48 [1.00–2.21] and 1.19 [1.01–1.41], respectively. In contrast, in infants of mothers who stopped using snuff or stopped smoking before the antenatal booking, the corresponding risks were not increased (adjusted odds ratios [95% CI] were 0.71 [0.44–1.14] and 0.88 [0.73–1.05], respectively).ConclusionMaternal snuff use or smoking in early pregnancy is associated with an increased risk of oral clefts. Infants of mothers who stopped using snuff or stopped smoking before the antenatal booking had no increased risk of oral cleft malformations. Oral snuff or other sources of nicotine should not be recommended as an alternative for smoke-cessation during pregnancy.

Significant association of MTHFD1 1958G>A single nucleotide polymorphism with nonsyndromic cleft lip and palate in Indian population.

Objectives: Nonsyndromic cleft lip and palate (NSCLP) is genetically distinct from those with syndromic clefts, and accounts for ~70% of cases with Oral clefts. Folate, or vitamin B9, is an essential nutrient in our diet. Allelic variants in genes involved in the folate pathway might be expected to have an impact on risk of oral clefts. Given the key role of methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) in folate metabolism, it would be of significant interest to assess its role in NSCLP etiology. Study Design: The present study aims at examining the association between MTHFD1 1958G>A polymorphism and NSCLP risk by conducting a case-control study in south Indian population. Our sample comprised of 142 cases with nonsyndromic clefts and 141 controls without clefts or family history of clefting. The MTHFD1 1958G>A polymorphism was genotyped using PCR-RFLP. Results: An increased risk was found for the heterozygous 1958GA (OR=2.44; P=0.020) and homozygous 1958AA (OR=2.45; P=0.012) genotypes in the children. When the dominant model (AG+AA vs GG) was applied the risk remained the same as co-dominant model, but the level of significance increased (OR=2.44; P=0.002). Conclusions: The results indicated the MTHFD1 1958G>A polymorphism to be one of the important genetic determinants of NSCLP risk in South Indian subjects. Key words:MTHFD1, orofacial cleft, SNP, genetics.

Lack of association between IRF6 polymorphisms and nonsyndromic oral clefts in South Indian population

Objective: This present study is aimed to investigate the association between interferon regulatory factor 6 (IRF6), single nucleotide polymorphisms (SNPs), and nonsyndromic cleft lip without without cleft palate (NSCLP) in the South Indian population. Subject and Methods: For this study, 190 unrelated NSCLP patients and 189 controls without clefts were genotyped with rs2235371 (V2741) and rs642961 SNPs using PCR-RFLP. The associations between NSCLP groups and IRF6 gene polymorphisms, as well as haplotypes, were analyzed using chi-squared test and 95% confidence interval (95%CI) of the odds ratios were calculated with the control groups as reference. Results: For controls, the minor allele frequencies of both variants, V2741 and rs642961, were 7.1% and 21.1%, respectively. Genotype data for both variants in control and cleft groups follow the Hardy Weinberg Equilibrium. Between cases with NSCLP and controls, the two SNPs showed no differences in frequencies of the genotypes or alleles. The pairwise linkage disequilibrium (LD) values (D’=1 and r2=0.027) between V2741 and rs642961 revealed that these two SNPs are not in strong LD. Haplotype G-T showed a significantly reduced risk for oral clefts (p<0.001) and haplotype A-T increased the risk for oral clefts (p=0.043). Gene-gene interaction showed that the higher risk group contains more GG-CC combination of cases that the controls, but this model was not significantly associated with cleft status (p=0.136) Conclusion: In conclusion, while IRF6 is strongly associated in other populations, this study demonstrated that variants in IRF6 may play a role in NSCLP in a South Indian population, but other genes are expected to play a role in this population as well.

Evaluating the effects of maternal exposure to benzene, toluene, ethyl benzene, and xylene on oral clefts among offspring in Texas: 1999–2008

There is evidence from previous studies that maternal occupational exposure to hazardous air pollutants (HAPs) 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. Data on 6045 nonsyndromic isolated oral cleft cases (3915 cleft lip with or without cleft palate [CL ± P] and 2130 nonsyndromic 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 (BTEX) separately and the risk of oral clefts in offspring. High estimated maternal exposure to benzene was not associated with oral clefts, compared with low estimated exposure (CL ± P 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. In our study, there was no evidence that maternal exposure to environmental levels of BTEX was associated with oral clefts.

Maternal bereavement in the antenatal period and oral cleft in the offspring

Is maternal bereavement (emotional stress) due to loss of a close relative in the antenatal period associated with the risk of oral cleft in the offspring? Our study suggests prenatal maternal bereavement is associated with an increased risk of oral cleft in the offspring, especially when the bereavement was due to a sudden death or death of a child. The aetiology of oral cleft is unknown but includes both genetic and environmental causes. We performed a population-based cohort study based on several national registers in Denmark from 1978 to 2008. Our final study population consisted of 1 771 663 children. Of these 35 118 (2%) were born to mothers who experienced bereavement in the exposure window from 1 year before pregnancy to the end of the first trimester. In total, 3043 children were diagnosed with a cleft; 968 with cleft lip, 1206 with cleft lip and palate and 869 with a cleft palate. For overall bereavement the prevalence was 1.7 per 1 000 live born in the unexposed children and 2.2 per 1 000 live born in the exposed children. Overall, maternal bereavement due to the death of a close relative from 1 year before conception to the end of the first trimester was associated with a significantly increased risk of oral cleft [odds ratio (OR): 1.28, 95% confidence interval (CI): 1.01; 1.61). When mothers lost a relative due to a sudden death, the risk of oral cleft in the offspring was higher (OR: 1.76, 95% CI: 1.06; 2.94). Losing a relative in the time period before pregnancy and during the first trimester showed a tendency to an increased risk. The risk increase was 77% when the mother was bereaved due to sudden death and the estimation was robust in different analytical strategies. It is a limitation that we only studied live born children, but most children with isolated oral cleft would survive their pregnancy and birth. Since oral cleft are rare and despite the large study population, we still had a relatively small number of cases, which results in limited power to detect small differences. We did not have actual measurements of the maternal cortisol concentration, but we believe that bereavement due to death of a close relative produces a strong stress reaction in most people. Also we did not have the opportunity to adjust for intake of folic acid and use of anti-depressant; however, analysis in a subset of the data showed no difference in these intakes between exposed and unexposed mothers. With this study we add a large-scale human cohort study to the body of literature on stress and birth defects. Our study is in agreement with previously published results and can be generalized to similar populations like the native Danish population. Severe stress may be added to the list of potential causes for oral cleft.

Exposure During Pregnancy to Glycol Ethers and Chlorinated Solvents and the Risk of Congenital Malformations

Exposure to solvents during pregnancy has long been suspected of increasing the risk of congenital malformations, but the lack of prospective assessment of specific solvent exposures has prevented definitive conclusions. In a cohort of 3421 pregnant women in Brittany (2002-2006), occupational solvent exposure was assessed from self-report during pregnancy and from a job-exposure matrix. Congenital malformations were diagnosed among live births, stillbirths, and medical pregnancy terminations. In a nested case-control sample, urinary concentrations of 10 metabolites of glycol ethers and chlorinated solvents were measured in maternal samples collected during early pregnancy (n = 79 cases, 580 controls). Dose-response trends linked occupational solvent exposure (both self-reported and based on a job-exposure matrix) to the risk of major congenital malformations--especially oral clefts, urinary tract malformations, and male genital malformations. Detection of some glycol ether metabolites and trichloroacetic acid in urine was associated with increased risks of oral clefts and of urinary tract and limb defects. This prospective study, using three independent methods of exposure assessment, suggests several specific associations between solvent exposure during early pregnancy and congenital malformations. Results based on urinary biomarkers, although limited by small numbers, identify work situations that require further investigation.

Discussion: ‘Topiramate in pregnancy and risk of oral clefts,’ by Margulis et al

In the roundtable that follows, clinicians discuss a study published in this issue of the Journal in light of its methodology, relevance to practice, and implications for future research. Article discussed: Margulis AV, Mitchell AA, Gilboa SM, et al; National Birth Defects Prevention Study. Use of topiramate in pregnancy and risk of oral clefts. Am J Obstet Gynecol 2012;207:405.e1-7.

Med Check

Med Check

Maternal Exposure to Amoxicillin and the Risk of Oral Clefts

Prior studies have suggested an increased risk of oral clefts after exposure to amoxicillin in early pregnancy, but findings have been inconsistent. Among participants in the Slone Epidemiology Center Birth Defects Study from 1994 to 2008, we identified 877 infants with cleft lip with/without cleft palate and 471 with cleft palate alone. Controls included 6952 nonmalformed infants. Mothers were interviewed about demographic, reproductive and medical factors, and details of medication use. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) associated with use of amoxicillin in the first trimester using conditional logistic regression and adjusting for known risk factors for oral clefts, as well as for infections, fever, and concomitant treatments. In the control group, 2.1% of women had used amoxicillin in the first trimester. Maternal use of amoxicillin was associated with an increased risk of cleft lip with/without cleft palate (adjusted OR = 2.0 [95% confidence interval = 1.0-4.1]), with an OR of 4.3 (1.4-13.0) for third-gestational-month use. Risks were not elevated for use of other penicillins or cephalosporins. For cleft palate, the OR for first-trimester amoxicillin was 1.0 (0.4-2.3) with an OR of 7.1 (1.4-36) for third-gestational month use. Amoxicillin use in early pregnancy may be associated with an increased risk of oral clefts.

Use of topiramate in pregnancy and risk of oral clefts

The objective of this study was to evaluate the association between the use of monotherapy topiramate in pregnancy and cleft lip with or without cleft palate (CL/P) in the offspring. Data from the Slone Epidemiology Center Birth Defects Study (BDS) from 1997 to 2009 and the National Birth Defects Prevention Study (NBDPS) from 1997 to 2007 were analyzed. Conditional logistic regression was used to compare the first-trimester use of topiramate monotherapy to no antiepileptic drug use during the periconceptional period between the mothers of infants with CL/P and the mothers of controls for each study separately and in pooled data. The BDS contained 785 CL/P cases and 6986 controls; the NBDPS contained 2283 CL/P cases and 8494 controls. The odds ratios (exact 95% confidence intervals) for the association between topiramate use and CL/P were 10.1 (1.1-129.2) in the BDS, 3.6 (0.7-20.0) in the NBDPS, and 5.4 (1.5-20.1) in the pooled data. First-trimester use of topiramate may be associated with CL/P.

Utilization of Topiramate During Pregnancy and Risk of Birth Defects

To evaluate the risk of oral cleft and major congenital malformation occurrence in infants born to women exposed to topiramate in their first trimester of pregnancy compared with women who used other anti-epileptic drugs or those with disease states in which topiramate may have been used. Sourced from patients' pharmacy and medical claims from 2002 through 2010, this study identified infants born from mothers exposed to topiramate (n = 870) and other anti-epileptic drugs (n = 3615) in the first trimester of pregnancy. First trimester exposure was based on prescription dispensing dates and days supplied relative to infant birth date, accounting for premature delivery. Infants born to women with migraine without epilepsy (n = 26,865), women with epilepsy (n = 2607), and women with diabetes mellitus (n = 13,062), as well as randomly sampled women (n = 99,761), were used for comparison. Topiramate use was excluded from all groups with the exception of the topiramate and random sample cohorts. Non-anti-epileptic drug teratogens were excluded from each cohort (except random sample). Unadjusted relative risks and 95% confidence intervals for topiramate vs each comparator were calculated. Risks >1 indicate a higher risk with topiramate vs comparator, whereas risks <1 indicate a lower risk with topiramate vs comparator. The frequency of oral clefts was 0.23% for topiramate use, 0.17% for other anti-epileptic drug use (topiramate vs comparator relative risk = 1.39 [95% confidence interval: 0.28-6.85]), 0.16% for migraineurs (1.47 [0.36-6.06]), 0.31% for epileptics (0.75 [0.16-3.52]), 0.26% for diabetics (0.88 [0.21-3.67]), and 0.16% for the random sample (1.44 [0.36-5.81]). The frequency of major congenital malformations was 4.33% for topiramate use, 3.21% for other anti-epileptic drugs (1.33 [0.92-1.90]), 3.79% for migraineurs (1.12 [0.81-1.55]), 4.33% for epileptics (0.98 [0.68-1.41]), 6.58% for diabetics (0.65 [0.47-0.89]), and 3.77% for the random sample (1.13 [0.82-1.55]). This retrospective study quantified the association between topiramate exposure during pregnancy and the risk of oral cleft or major congenital malformations, and suggested little or no increase in risk in comparison with exposure to other anti-epileptic drugs or to disease states, such as migraine, epilepsy, or diabetes. However, small numbers of events limit the strength of inferences.

Newer anticonvulsants: Lamotrigine, topiramate and gabapentin

BACKGROUND The second generation antiepileptic drugs (AEDs), which include lamotrigine, topiramate, and gabapentin, have been introduced during the past 20 years. Because the newer AEDs differ in their pharmacokinetics from the first generation AEDs, it is hoped that the second generation AEDs will be less teratogenic. METHODS The findings in pregnancy cohorts and case-control studies concerning lamotrigine, topiramate and gabapentin-exposed pregnancies have been analyzed. RESULTS The rate of all malformations in lamotrigine monotherapy-exposed pregnancies has been between 2.0 and 5.6%, in comparison to baseline rates of 1.1 to 3.6% in two unexposed comparison groups. Compared to reference populations, a higher risk (0.4%) of isolated oral clefts has been observed in one cohort of 1562 lamotrigine-exposed pregnancies, but the risk was lower (0.1%) in other studies. In topiramate-exposed pregnancies, the rate of all malformations has been 4.2 to 4.9%, with an increase in oral clefts with and without other anomalies. The limited information available now for gabapentin has shown no evidence of teratogenicity. Concerning other developmental effects of these drugs, young children exposed to lamotrigine in utero have shown no deficits in cognitive function. Prenatal exposure to topiramate has been associated with an elevated frequency of small size for gestational age newborns. CONCLUSIONS The information available suggests an increased risk of oral clefts in infants exposed to topiramate, and perhaps lamotrigine, early in pregnancy, and of growth retardation for topiramate-exposed infants. Larger sample sizes are needed to clarify the questions that have been raised.

Maternal risk factors for oral clefts: a case-control study.

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. 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. 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. 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.

Case–control studies for identifying novel teratogens

The case-control study design offers an operationally efficient approach to measuring an association between an exposure and an outcome, especially when the outcome is rare, as is true for specific birth defects. For example, instead of following 50,000 pregnant women to have sufficient statistical power to identify a doubling in risk of oral clefts associated with a common exposure (e.g., cigarette smoking), 75 cases and 3 controls per case could be studied with equal statistical power. Examples of case sources include hospital or clinical series, or birth defect registries. For validity, control subjects should represent the population base of the cases, which can be difficult to identify for non-population-based case groups. Case-control studies typically rely on retrospective exposure measurement, which presents a major challenge and sets up the possibility of recall bias. Approaches are discussed to keep sources of bias to a minimum, including recall, non-differential information, and selection biases. Case-control studies can play an important role in this process for both hypothesis-generation and hypothesis-testing of potential teratogens. Examples of case-control studies and their contributions to the field are presented. © 2011 Wiley-Liss, Inc.

Risk of Oral Clefts in Twins

Small studies have indicated that twinning increases the risk of oral cleft. We used data from a Danish national population-based cohort study to investigate whether twinning was associated with isolated oral cleft, and to estimate the twin probandwise concordance rate and heritability. Twins (207 affected/130,710) and singletons (7766 affected/4,798,526) born from 1936 through 2004 in Denmark were ascertained by linkage among the Danish Facial Cleft Database, the Danish Twin Registry, and the Civil Registration System. We computed oral cleft prevalence and prevalence proportion ratio for twins versus singletons, stratified for 3 subphenotypes. Probandwise concordance rates and heritability for twins were estimated for 2 phenotypes--cleft lip with or without cleft palate (CL/P) and cleft palate (CP). The prevalence of oral cleft was 15.8 per 10,000 twins and 16.6 per 10,000 singletons (prevalence proportion ratio = 0.95; 95% confidence interval = 0.83-1.1). This prevalence was similar for monozygotic and dizygotic twins. The probandwise concordance rate was higher for CL/P for monozygotic twins than for dizygotic twins (50% vs. 8%, respectively). A similar contrast was present for CP. Recurrence risk for both types of clefts was greater in dizygotic twins than in non-twin siblings. Heritability estimates were above 90% for both CL/P and CP. No excess risk of oral cleft could be demonstrated for twins compared with singletons. The concordance rates and heritability estimates for both types of clefts show a strong genetic component.

High Oral Cleft Risk Reported for Topiramate

High Oral Cleft Risk Reported for Topiramate