Congenital Malformations Registry - Summary Report, 2008

Section VII: Current Publications

  1. Agopian AJ, Lupo PJ, Herdt-Losavio ML, Langlois PH, Rocheleau CM, Mitchell LE, and the National Birth Defects Prevention Study. Differences in folic acid use, prenatal care, smoking, and drinking in early pregnancy by occupation. Prev Med 2012;55(4):341-345. DOI:10.1016/j.ypmed.2012.07.015.

    Several occupational groups were identified in which women were more likely to smoke, consume alcohol, not use folic acid, or not have prenatal care during early pregnancy. Discovery of these associations identifies high-risk occupational groups that could be targeted for health promotion activities (e.g., workplace interventions). Better understanding of characteristics that motivate high-risk behaviors could further inform workplace health promotion activities. The development of successful workplace health promotion strategies that reduce the prevalence of high-risk behaviors could both improve maternal and child health and reduce healthcare costs.

  2. Browne ML, Carter TC, Kay DM, Kuehn D, Brody LC, Romitti PA, Liu A, Caggana M, Druschel CM, Mills JL. Evaluation of genes involved in limb development, angiogenesis, and coagulation as risk factors for congenital limb deficiencies. Am J Med Genet A 2012 Oct;158A(10):2463-72.

    Genotypes were obtained for 132 SNPs in genes involved in limb development (SHH, WNT7A, FGF4, FGF8, FGF10, TBX3, TBX5, SALL4, GREM1, GDF5, CTNNB1, EN1, CYP26A1, CYP26B1), angiogenesis (VEGFA, HIF1A, NOS3), and coagulation (F2, F5, MTHFR). Our data suggest that common variants in FGF10 increase the risk for a wide range of non-syndromic limb deficiencies. We also observed suggestive evidence for associations with SNPs in other genes including CYP26B1 and WNT7A.

  3. Carter TC, Kay DM, Browne ML, Liu A, Romitti PA, Kuehn D, Conley MR, Caggana M, Druschel CM, Brody LC, Mills JL. Anorectal atresia and Variants at Predicted Regulatory Sites in Candidate Genes. Ann Hum Gene 2012; Epub ahead of print.

    Variants predicted to affect transcription factor binding, splicing, and DNA methylation in WNT3A, PCSK5, TCF4, MKKS, GLI2, HOXD12, and BMP4 were associated with anorectal atresia based on a nominal P value < 0.05. Our results for MKKS support previously suggested associations with anorectal malformations. Our findings suggest that more research is needed to determine whether altered GLI2 and BMP4 expression is important in anorectal atresia in humans.

  4. Carter TC, Kay DM, Browne ML, Liu A, Romitti PA, Kuehn D, Conley MR, Caggana M, Druschel CM, Brody LC, Mills JL. Hirschsprung's disease and variants in genes that regulate enteric neural crest cell proliferation, migration and differentiation. J Hum Genet 2012 Aug;57(8):485-93.

    Hirschsprung's disease (HSCR) results from failed colonization of the embryonic gut by enteric neural crest cells (ENCCs); colonization requires RET proto-oncogene (RET) signaling. Our population-based study identified novel RET variants in HSCR cases and showed that common RET variants may not contribute to HSCR in all race/ethnic groups. The findings for HOXB5 and PHOX2B provide supportive evidence that genes regulating ENCC proliferation, migration and differentiation could be risk factors for HSCR.

  5. Caton AR. Exploring the seasonality of birth defects in the New York State Congenital Malformations Registry. Birth Defects Res A Clin Mol Teratol 2012;94:424-37.

    We aimed to determine whether the occurrence of birth defects varied by month of conception using the population-based New York State Congenital Malformations Registry (CMR). We merged live birth certificates (n = 2,044,091) with CMR records for mothers residing in New York State, excluding New York City, for the years 1992 through 2006.

    Of 42 groups examined in the 15-year period, 24 (57%) had at least one statistically significant test result, suggesting a trend or seasonal variation. Congenital cataract, pulmonary valve atresia/stenosis, coarctation of aorta, biliary atresia, and renal agenesis or hypoplasia had at least three significant tests. These results may help to generate hypotheses about environmental factors that vary by season for further studies.

  6. Chen L, Bell EM, Browne ML, Druschel CM, Romitti PA, Schmidt RJ, Burns TL, Moslehi R, Olney RS; and the National Birth Defects Prevention Study. Maternal caffeine consumption and risk of congenital limb deficiencies. Birth Defects Res A Clin Mol Teratol 2012: Epub ahead of print.

    A weak increased risk of congenital limb deficiencies was associated with maternal dietary caffeine consumption in this study; however, risk did not vary by amount of caffeine consumed.

  7. Ciafaloni E, Fox DJ, Pandya S, Westfield CP, Puzhankara S, Romitti PA, Mathews KD, Miller TM, Matthews DJ, Miller LA, Cunniff C, Druschel CD, Moxley RT. Delayed Diagnosis in Duchenne Muscular Dystrophy: Data from the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet). J Pediatr 2009;155:380-5.

    Multistate, population-based data was used to identify key factors contributing to delay in diagnosis of males with Duchenne muscular dystrophy (DMD) without known family history. In this group of boys, first signs or symptoms was noted at a mean age of 2.5 years, and concerns resulted in primary care provider evaluation of the child at a mean age of 3.6 years. The mean age for the first creatine kinase blood tests was 4.7 years and mean age at definitive diagnosis was 4.9 years. There is a delay of about 2.5 years between onset of DMD symptoms and time of diagnosis, unchanged over the previous two decades. This delay results in lost opportunities for timely genetic counseling and initiation of corticosteroid treatment. Based on these findings, recommendations were made that primary care practitioners check creatine kinase early when evaluating boys with unexplained developmental delays.

  8. Desrosiers TA, Herring AH, Shapira SK, Luben TJ, Hooiveld M, Herdt-Losavio ML, Lin S, Olshan AF and the National Birth Defects. Paternal occupation and birth defects in offspring: Findings from the National Birth Defects Prevention Study. Accepted by Occup Environ Med 2012; 69:534-542. DOI:10.1136/oemed-2011-100372.

    This large population-based study was conducted to explore the relation between multiple paternal occupations and over 60 types of birth defects using Bayesian analytic methods that specifically address the statistical challenges associated with analysis of sparsely distributed data across numerous exposures and outcomes. Results from this study indicate that paternal work in a number of occupations may be associated with an increased prevalence of various birth defects in offspring. Findings can be used to inform future investigation of specific paternal occupations found to be associated with birth defects or to generate hypotheses about chemical or physical exposures and exposure mixtures common to such occupations.

  9. Lin S, Munsie JP, Herst-Losavio M, Druschel CM, Campbell KC, Browne ML. Maternal asthma medication use and the risk of selected birth defects. Pediatrics 2 012; 129: e317-e324. DOI: 10.1542/peds.2010-2660.

    This study found no significant associations between maternal periconceptional use of asthma medications and risks of neural tube defects, some musculoskeletal defects (limb deficiency and diaphragmatic hernia), and small intestinal atresia. It suggests, however, that maternal asthma medication use may increase the risk of esophageal atresia, anorectal atresia, and omphalocele. Although the magnitudes of the associations were moderate (ORs ranged from 2.14 to 4.26), we cannot disentangle the effects of asthma severity and related hypoxia from those attributable to medication use, nor can we rule out the possibility that these findings are attributable to bias or chance. The current clinical guidelines and specific recommendations for aggressive asthma management during pregnancy should remain unchanged. Additional studies with detailed data on asthma severity and treatment and a large sample are recommended to clarify whether our findings are attributable to maternal use of asthma medication, asthma severity, or chance alone.

  10. Mills JL, Carter TC, Kay DM, Browne ML, Brody LC, Liu A, Romitti PA, Caggana M, Druschel CM. Folate and vitamin B12-related genes and risk for omphalocele. Hum Genet 2012 May;131(5):739-46.

    Both taking folic acid-containing vitamins around conception and consuming food fortified with folic acid have been reported to reduce omphalocele rates. We examined single nucleotide polymorphisms (SNPs) known to be important in folate, vitamin B12, or choline. We observed associations between omphalocele and transcobalamin receptor (TCblR) and transporter (TCN2) SNPs and a betaine-homocysteine S-methyltransferase (BHMT) SNP. These results suggests that disruption of methylation reactions, in which folate, vitamin B12, and homocysteine play critical parts, may be a risk factor for omphalocele. Our data, if confirmed, suggest that supplements containing both folic acid and vitamin B12 may be beneficial in preventing omphaloceles.

  11. Van Zutphen AR, Lin S, Fletcher BA, Hwang SA. A population-based case-control study of extreme summer temperature and birth defects. Environ Health Perspect 2012 Oct;120:1443-9.

    To determine whether pregnancies are potentially vulnerable to the weather extremes anticipated with climate change, we evaluated the relationship between extreme summer temperature and birth defects in a population-based case-control study by linking the New York State Congenital Malformations Registry to birth certificates for the years 1992-2006.

    Among 6,422 cases and 59,328 controls that shared at least 1 week of the critical period in summer, we found positive and consistent associations between multiple heat indicators during the relevant developmental window and congenital cataracts which should be confirmed with other data sources.

  12. Wang Y, Kennedy J, Caggana M, Zimmerman R, Thomas S, Berninger J, Harris K, Green NS, Oyeku S, Hulihan M, Grant AM, Grosse SD. Sickle cell disease incidence among newborns in New York State by maternal race/ethnicity and nativity. Genet Med 2012; published online on September 27, 2012.

    This study provides the first US estimates of sickle cell disease incidence by maternal nativity. Newborns of non-Hispanic black mothers accounted for 86% of sickle cell disease cases whereas newborns of Hispanic mothers accounted for 12% of cases. The estimated incidence was 1:230 live births for non-Hispanic black mothers, 1:2,320 births for Hispanic mothers, and 1:41,647 births for non-Hispanic white mothers. Newborns of foreign-born non-Hispanic black mothers had a twofold higher incidence of sickle cell disease than those born to US-born non-Hispanic black mothers (P < 0.001). Such findings identify at-risk populations and inform outreach activities that promote ongoing, high-quality medical management to affected children.