No abstract

Our study revealed that drinking during pregnancy is fairly common, three times the levels reported in surveys that ask only about drinking during the month before the survey. Women who binge drink before pregnancy are at particular risk for drinking after becoming pregnant. Sexually active women of childbearing ages who drink alcohol should be advised to use reliable methods to prevent pregnancy, plan their pregnancies, and stop drinking before becoming pregnant.

Purpose: The population-based National Down Syndrome Project combined epidemiological and molecular methods to study congenital heart defects in Down syndrome. Methods: Between 2000 and 2004, six sites collected DNA, clinical, and epidemiological information on parents and infants. We used logistic regression to examine factors associated with the most common Down syndrome-associated heart defects. Results: Of 1469 eligible infants, major cardiac defects were present in 44%; atrioventricular septal defect (39%), secundum atrial septal defect (42%), ventricular septal defect (43%), and tetralogy of Fallot (6%). Atrioventricular septal defects showed the most significant sex and ethnic differences with twice as many affected females (odds ratio, 1.93; 95% confidence interval, 1.40 -2.67) and, compared with whites, twice as many blacks (odds ratio, 2.06; 95% confidence interval, 1.32-3.21) and half as many Hispanics (odds ratio, 0.48; 95% confidence interval, 0.30 -0.77). No associations were found with origin of the nondisjunction error or with the presence of gastrointestinal defects. Conclusions: Sex and ethnic differences exist for atrioventricular septal defects in Down syndrome.Identification of genetic and environmental risk factors associated with these differences is essential to our understanding of the etiology of congenital heart defects. The National Down Syndrome Project (NDSP) seeks to investigate the etiology and phenotypic consequences of trisomy 21 Down syndrome (DS). 1 Aside from the universal findings of mental retardation and hypotonia, congenital heart defects (CHDs) are arguably the most important clinical sequelae of an extra chromosome 21. In 1998 the Atlanta Down syndrome Project (ADSP), a forerunner of the NDSP, reported that 41% of newborns with DS were born with one or more major heart defects, including atrioventricular septal defect (AVSD), secundum atrial septal defect (ASDII), ventricular septal defect (VSD), and tetralogy of Fallot (TOF). 2 Findings from the ADSP and other recent population-based studies of DS and CHDs 2-5 are summarized in Table 1.With the birth prevalence of major DS-associated CHDs well established by multiple studies using modern diagnostic methods, attention can now be directed toward understanding the etiology of these defects. Not only do infants with DS have a higher rate of CHDs than do infants without DS, but one defect, the AVSD, is particularly characteristic. To understand the etiology of CHDs in DS and of AVSD specifically, both genetic and environmental determinants must be explored. For example, several recent reports have suggested that the distribution of CHDs in DS varies by ethnicity (race/ethnicity), 6 -13 but most population-based studies have not had broad ethnic representation (Table 1). Drawing on our experience with the ADSP, we designed the multicenter NDSP to explore possible CHD risk factors singly and in combination. The NDSP is one of the largest population-based studies of CHDs in DS and the first to assemble clinical, demographic, a...

There is a delay of about 2.5 years between onset of DMD symptoms and the time of definitive diagnosis, unchanged over the previous 2 decades. This delay results in lost opportunities for timely genetic counseling and initiation of corticosteroid treatment. We recommend checking creatine kinase early in the evaluation of boys with unexplained developmental delay.

OBJECTIVE To identify trends in the prevalence and epidemiologic correlates of gastroschisis using a large population-based sample with cases identified by the National Birth Defects Prevention Network over the course of an 11-year period. METHODS This study examined 4,713 cases of gastroschisis occurring in 15 states during 1995–2005, using public use natality data sets for denominators. Multivariable Poisson regression was used to identify statistically significant risk factors, and Joinpoint regression analyses were conducted to assess temporal trends in gastroschisis prevalence by maternal age and race and ethnicity. RESULTS Results show an increasing temporal trend for gastroschisis (from 2.32 per 10,000 to 4.42 per 10,000 live births). Increasing prevalence of gastroschisis has occurred primarily among younger mothers (11.45 per 10,000 live births among mothers younger than age 20 years compared with 5.35 per 10,000 among women aged 20 to 24 years). In the multivariable analysis, using non-Hispanic whites as the referent group, non-Hispanic black women had the lowest risk of having a gastroschisis-affected pregnancy (prevalence ratio 0.42, 95% confidence interval [CI] 0.37–0.48), followed by Hispanics (prevalence ratio 0.86, 95% CI 0.81–0.92). Gastroschisis prevalence did not differ by newborn sex. CONCLUSIONS Our findings demonstrate that the prevalence of gastroschisis has been increasing since 1995 among 15 states in the United States, and that higher rates of gastroschisis are associated with non-Hispanic white maternal race and ethnicity, and maternal age younger than 25 years (particularly younger than 20 years of age).

OBJECTIVE To estimate prevalence of childhood-onset Duchenne and Becker muscular dystrophies (DBMD) in 6 sites in the United States by race/ethnicity and phenotype (Duchenne muscular dystrophy [DMD] or Becker muscular dystrophy [BMD]). METHODS In 2002, the Centers for Disease Control and Prevention established the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet) to conduct longitudinal, population-based surveillance and research of DBMD in the United States. Six sites conducted active, multiple-source case finding and record abstraction to identify MD STARnet cases born January 1982 to December 2011. We used cross-sectional analyses to estimate prevalence of DBMD per 10 000 boys, ages 5 to 9 years, for 4 quinquennia (1991–1995, 1996–2000, 2001–2005, and 2006–2010) and prevalence per 10 000 male individuals, ages 5 to 24 years, in 2010. Prevalence was also estimated by race/ethnicity and phenotype. RESULTS Overall, 649 cases resided in an MD STARnet site during $1 quinquennia. Prevalence estimates per 10 000 boys, ages 5 to 9 years, were 1.93, 2.05, 2.04, and 1.51, respectively, for 1991–1995, 1996–2000, 2001–2005, and 2006–2010. Prevalence tended to be higher for Hispanic individuals than non-Hispanic white or black individuals, and higher for DMD than BMD. In 2010, prevalence of DBMD was 1.38 per 10 000 male individuals, ages 5 to 24 years. CONCLUSIONS We present population-based prevalence estimates for DBMD in 6 US sites. Prevalence differed by race/ethnicity, suggesting potential cultural and socioeconomic influences in the diagnosis of DBMD. Prevalence also was higher for DMD than BMD. Continued longitudinal surveillance will permit us to examine racial/ethnic and socioeconomic differences in treatment and outcomes for MD STARnet cases.

Sagittal craniosynostosis is the most common form of craniosynostosis, affecting approximately one of 5,000 newborns. We conducted the first genome-wide association study (GWAS) for non-syndromic sagittal craniosynostosis (sNSC) using 130 non-Hispanic white (NHW) case-parent trios. Robust associations were observed in a 120 kb region downstream of BMP2, flanked by rs1884302 (P = 1.13 × 10−14; odds ratio [OR] = 4.58) and rs6140226 (P = 3.40 × 10−11; OR = 0.24) and within a 167 kb region of BBS9 between rs10262453 (P = 1.61 × 10−10; OR=0.19) and rs17724206 (P = 1.50 × 10−8; OR = 0.22). We replicated the associations to both loci [rs1884302 (P = 4.39 × 10−31); rs10262453 (P = 3.50 × 10−14)] in an independent NHW population of 172 unrelated sNSC probands and 548 controls. Both BMP2 and BBS9 are genes with a role in skeletal development warranting functional studies to further understand the etiology of sNSC.

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