A multi-ethnic genome-wide association study identifies novel loci for non-syndromic cleft lip with or without cleft palate on 2p24.2, 17q23 and 19q13.

Orofacial clefts (OFCs), which include non-syndromic cleft lip with or without cleft palate (CL/P), are among the most common birth defects in humans, affecting approximately 1 in 700 newborns. CL/P is phenotypically heterogeneous and has a complex etiology caused by genetic and environmental factors. Previous genome-wide association studies (GWASs) have identified at least 15 risk loci for CL/P.

A Genome-wide Association Study of Nonsyndromic Cleft Palate Identifies an Etiologic Missense Variant in GRHL3.

Cleft palate (CP) is a common birth defect occurring in 1 in 2,500 live births. Approximately half of infants with CP have a syndromic form, exhibiting other physical and cognitive disabilities. The other half have nonsyndromic CP, and to date, few genes associated with risk for nonsyndromic CP have been characterized.

Birth Outcomes of Children Born to Women with Rheumatoid Arthritis.

Aim: The aim of the study was to estimate the possible risk of adverse birth outcomes of children born to mothers with rheumatoid arthritis (RA).

Methods: The dataset of large population-based Hungarian Case-Control Surveillance System of Congenital Abnormalities from 1980-1996 was evaluated including 22,843 cases with congenital abnormalities and 38,151 matched controls without any defect.

Results: 36 cases (0.

Maternal factors in the origin of infantile hypertrophic pyloric stenosis: A population-based case-control study.

In most patients affected by isolated infantile hypertrophic pyloric stenosis (IHPS) the etiology is largely unknown. Thus, the aim of this study was to estimate possible maternal risk factors in the origin of IHPS. The study samples included 241 cases with IHPS, 357 matched controls and 38,151 population controls without any defect in the population-based large dataset of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-1996.

Maternal factors in the origin of isolated anorectal malformations - a population-based case-control study.

Objective: In most patients affected by isolated anorectal malformation (IARM), the etiology is unknown. Thus, the aim of this study was to analyze the possible role of maternal risk factors in the origin of IARM.

Methods: The study samples included 231 cases with IARM, 361 matched and 38 151 population controls without any defect in the population-based large dataset of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-1996.

Birth outcomes of patients with isolated anorectal malformations: A population-based case-control study.

In most patients affected by isolated anorectal malformation (IARM) the etiology is largely unknown. Thus, the aim of our project was to analyze possible risk factors for IARM. In the first step, birth outcomes of cases with IARM were analyzed on the basis of maternal socio-demographic variables, and these data are presented in this paper.

Folic acid in pregnant women associated with reduced prevalence of severe congenital heart defects in their children: a national population-based case-control study.

Objective: Previous Hungarian intervention trials have shown an association between periconceptional folic-acid-containing multivitamin supplementation and significantly reduced risk of congenital heart defects (CHDs). These findings were confirmed in observational multivitamin studies in the USA, and studies in the Netherlands and China regarding folic acid. The objective of this observational population-based study was to estimate the possible preventive effect of folic acid supplementation for different CHDs during their critical period of development.

Ear Infection in Isolated Cleft Lip: Etiological Implications.

Background And Hypothesis: Chronic ear infections are a common occurrence in children with orofacial clefts involving the secondary palate. Less is known about the middle ear status of individuals with isolated clefts of the lip, although several studies have reported elevated rates of ear infection in this group. The purpose of this retrospective study was to test the hypothesis that chronic ear infections occur more frequently in isolated cleft lip cases (n = 94) compared with controls (n = 183).

Birth outcomes of male and female patients with infantile hypertrophic pyloric stenosis--a population-based case-control study.

Objective: Most of the patients are affected by isolated infantile hypertrophic pyloric stenosis (IHPS) beyond the polygenic predisposition, the other factors in the multifactorial etiology are largely unknown. The main characteristic of IHPS is the robust male predominance, thus the aim of this study was to analyze birth outcomes in males and females whether they are different or not.

Methods: The study samples included 241 cases with IHPS, 357 matched, and 38,151 population controls without any defect in the population-based large dataset of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-1996.

Maternal factors in the origin of isolated oesophageal atresia: A population-based case-control study.

Background: In most patients affected by isolated oesophageal atresia (IOA) the etiology is largely unknown. Thus, the aim of this study was to analyze potential risk factors in mothers.

Methods: The study samples included 221 cases with IOA, 356 matched and 38,151 population controls without any defect in the population-based dataset of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980 to 1996.

Paroxysmal supraventricular tachycardia in pregnant women and birth outcomes of their children: a population-based study.

The aim of the study was to estimate the possible association of pregnant women with paroxysmal supraventricular tachycardia (PSVT) with the possible risk for adverse birth outcomes, particularly different congenital abnormalities (CAs) in their children. Prospectively and medically recorded PSVT was evaluated in 103 pregnant women who later had offspring with CA (case group) and 149 pregnant women who later delivered newborn infants without CA (control group) and matched to cases in the population-based data set of the Hungarian Case-Control Surveillance System of Congenital Abnormalities, 1980-1996. Of 252 pregnant women with PSVT, 115 (45.

Identification of functional variants for cleft lip with or without cleft palate in or near PAX7, FGFR2, and NOG by targeted sequencing of GWAS loci.

Although genome-wide association studies (GWASs) for nonsyndromic orofacial clefts have identified multiple strongly associated regions, the causal variants are unknown. To address this, we selected 13 regions from GWASs and other studies, performed targeted sequencing in 1,409 Asian and European trios, and carried out a series of statistical and functional analyses. Within a cluster of strongly associated common variants near NOG, we found that one, rs227727, disrupts enhancer activity.

No increases in the rate of undescended testis in Hungary during the last 50 years: A population-based study.

Undescended testis (cryptorchidism) is a common structural birth defect, i.e. congenital abnormality of the male genital organs and increasing trend in its birth prevalence was reported in some countries.

Sex ratio of congenital abnormalities in the function of maternal age: a population-based study.

Maternal age effect is well-known in the origin of numerical chromosomal aberrations and some isolated congenital abnormalities (CAs). The sex ratio (SR), i.e.

Possible preventive effect of high doses of folic acid for isolated hypospadias: a national population-based case-control study.

Hypospadias is a common structural birth defect (congenital abnormality) of the male genital organ. The objective of this study was to test the hypothesis regarding the possible preventive effect of folic acid for isolated hypospadias (IH). Folic acid use was compared in 3,038 cases with IH and 24,814 male controls without any defects in the national population-based Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-1996.

Distribution of maternal age and birth order groups in cases with unclassified multiple congenital abnormalities according to the number of component abnormalities: a national population-based case-control study.

Background: Multiple congenital abnormalities are caused by chromosomal aberrations, mutant major genes and teratogens. A minor proportion of these patients are identified as syndromes but the major part belonging to the group of unclassified multiple CAs (UMCAs). The main objective of this study was to evaluate the maternal age and birth order in pregnant women who had offspring affected with UMCA.

Higher risk of orofacial clefts in children born to mothers with angina pectoris: a population-based case-control study.

Previously an unexpected association of maternal angina pectoris (MAP) during pregnancy with a higher risk of orofacial clefts in their children was found. There were three objectives of this study: (i) to evaluate the validity of MAP-diagnoses in the previous study and the recent history of mothers with MAP in a follow-up study; (ii) to estimate the prevalence of other congenital abnormalities in the offspring of mothers with MAP; and (iii) to analyze the possible effect of confounders for the risk of orofacial clefts. The large dataset of population-based Hungarian Case-Control Surveillance System of Congenital Abnormalities, 1980-1996 was evaluated including 22 843 cases with congenital abnormalities and 38 151 controls without any defect.

Characteristics of boys with the so-called true undescended testis diagnosed at the third postnatal month--a population-based case-control study.

Objective: Undescended testis (cryptorchidism) is a common congenital abnormality of male genital organs diagnosed at birth followed with frequent postnatal descensus. However, the so-called isolated true undescended testis (ITUT) diagnosed at the third postnatal month seems to be an independent defect-entity, and this hypothesis was planned to confirm or reject in the study.

Method: The evaluation of birth outcomes and maternal socio-demographic data of cases with ITUT in the population-based large dataset of the Hungarian Congenital Abnormality Registry.

Possible association of first and high birth order of pregnant women with the risk of isolated congenital abnormalities in Hungary - a population-based case-matched control study.

Objective: In epidemiological studies at the estimation of risk factors in the origin of specified congenital abnormalities in general birth order (parity) is considered as confounder. The aim of this study was to analyze the possible association of first and high (four or more) birth order with the risk of congenital abnormalities in a population-based case-matched control data set.

Study Design: The large dataset of the Hungarian Case-Control Surveillance of Congenital Abnormalities included 21,494 cases with different isolated congenital abnormality and their 34,311 matched controls.

Risk and protective factors in the origin of atrial septal defect secundum--national population-based case-control study.

The aim of this study was to assess the risk factors in the origin of lethal or surgically corrected isolated atrial septal defect secundum. The population-based Hungarian Case-Control Surveillance of Congenital Abnormalities (conducted between 1980 and 1996) comprised 472 atrial septal defect secundum cases, 678 matched controls and 38,151 available controls without any defects; in addition, 21,022 malformed controls with other isolated defects. Medically recorded chronic disorders in the prenatal maternity logbook were evaluated, while acute maternal diseases, drug treatments and pregnancy supplements were analyzed on the basis of both prospective medically recorded data and retrospective maternal information.

Birth outcomes of cases with conotruncal defects of heart - a population-based case-control study.

Objective: The aim of this study was to evaluate the birth outcomes of cases with four types of conotruncal defects (CTDs), i.e. common truncus, transposition of great arteries, tetralogy of Fallot and double-outlet right ventricle.

Pregnancy complications in the mothers who delivered boys with isolated hypospadias - a population-based case-control study.

Objective: The evaluation of pregnancy complications of mothers who delivered boys with isolated hypospadias (IHS) to estimate their roles in the higher rate of low birthweight and preterm birth in cases with IHS.

Methods: The incidence of prospectively and medically recorded pregnancy complications in the prenatal maternity logbook was compared in the mothers of 3038 cases with IHS and their 4981 matched controls, in addition, 24 814 population male controls without any defects in the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-1996.

Results: The well-known higher rate of preterm birth and mainly of low birthweight was confirmed in cases with IHS.

Association of young and advanced age of pregnant women with the risk of isolated congenital abnormalities in Hungary - a population-based case-matched control study.

Objective: To analyze the possible association of maternal age with the risk of all congenital abnormalities (CAs) in a population-based large case-matched control data set.

Methods: The Hungarian Case-Control Surveillance of Congenital Abnormalities included 21,494 cases with isolated CA and their 34,311 matched controls. First the distribution of maternal age groups in 24 CA-groups and their matched controls was compared.

Possible association of maternal factors with the higher risk of isolated true undescended testis: A population-based case-control study.

The objective of the study was to evaluate the possible association of maternal factors with the risk of isolated true undescended testis (ITUT) diagnosed at the third postnatal month because our knowledge is limited regarding the origin of ITUT. Acute and chronic diseases with related drug treatments were compared in the mothers of 2052 cases with ITUT, 24,814 male controls without any defects and 12,082 malformed male controls with other isolated defects in the population-based large dataset of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-1996. Prospective medically recorded endometriosis before conception of the study pregnancy in the mothers of 39 cases was associated with a higher risk of ITUT in their sons (odds ratio (OR) with 95% confidence interval [CI]: 2.