Maternal Antihypertensive Medication Use and Congenital Heart Defects: Updated Results From the National Birth Defects Prevention Study.

Previous NBDPS (National Birth Defects Prevention Study) findings from 1997 to 2003 suggested that maternal antihypertensive use was associated with congenital heart defects (CHDs). We re-examined associations between specific antihypertensive medication classes and specific CHDs with additional NBDPS data from 2004 to 2011. After excluding mothers missing hypertension information or who reported pregestational diabetes mellitus, a multiple birth, or antihypertensive use but no hypertension, we compared self-reported maternal exposure data on 10 625 CHD cases and 11 137 nonmalformed controls. We calculated adjusted odds ratios [95% confidence intervals] to estimate the risk of specific CHDs associated with antihypertensive use during the month before conception through the third month of pregnancy, controlling for maternal age, race/ethnicity, body mass index, first trimester cigarette smoking, and NBDPS site. Overall, 164 (1.5%) case mothers and 102 (0.9%) control mothers reported early pregnancy antihypertensive use for their hypertension. We observed increased risk of 4 CHD phenotypes, regardless of antihypertensive medication class reported: coarctation of the aorta (2.50 [1.52-4.11]), pulmonary valve stenosis (2.19 [1.44-3.34]), perimembranous ventricular septal defect (1.90 [1.09-3.31]), and secundum atrial septal defect (1.94 [1.36-2.79]). The associations for these phenotypes were statistically significant for mothers who reported ß-blocker use or renin-angiotensin system blocker use; estimates for other antihypertensive medication classes were generally based on fewer exposed cases and were less stable but remained elevated. Our results support and expand on earlier NBDPS findings that antihypertensive medication use may be associated with increased risk of specific CHDs, although we cannot completely rule out confounding by underlying disease characteristics.

Copy number variants in a population-based investigation of Klippel-Trenaunay syndrome.

Klippel-Trenaunay syndrome (KTS) is a rare congenital vascular disorder that is thought to occur sporadically; however, reports of familial occurrence suggest a genetic component. We examined KTS cases to identify novel, potentially causal copy number variants (CNVs). We identified 17 KTS cases from all live-births occurring in New York (1998-2010). Extracted DNA was genotyped using Illumina microarrays and CNVs were called using PennCNV software. CNVs selected for follow-up had ≥10 single nucleotide polymorphisms (SNPs) and minimal overlap with in-house controls or controls from the Database of Genomic Variants. We identified 15 candidate CNVs in seven cases; among them a deletion in two cases within transcripts of HDAC9, a histone deacetylase essential for angiogenic sprouting of endothelial cells. One of them also had a duplication upstream of SALL3, a transcription factor essential for embryonic development that inhibits DNMT3A, a DNA methyltransferase responsible for embryonic de novo DNA methylation. Another case had a duplication spanning ING5, a histone acetylation regulator active during embryogenesis. We identified rare genetic variants related to chromatin modification which may have a key role in regulating vascular development during embryogenesis. Further investigation of their implications in the pathogenesis of KTS is warranted. © 2016 Wiley Periodicals, Inc.

Maternal autoimmune disease and birth defects in the National Birth Defects Prevention Study.

BACKGROUND: Little is known about the association between maternal autoimmune disease or its treatment and the risk of birth defects. We examined these associations using data from the National Birth Defects Prevention Study, a multi-site, population-based, case-control study. METHODS: Analyses included 25,116 case and 9897 unaffected control infants with estimated delivery dates between 1997 and 2009. Information on autoimmune disease, medication use, and other pregnancy exposures was collected by means of telephone interview. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for birth defects with five or more exposed cases; crude ORs and exact 95% CIs were estimated for birth defects with three to four exposed cases. RESULTS: Autoimmune disease was reported by 373 mothers (279 case and 94 control mothers). The majority of birth defects evaluated were not associated with autoimmune disease; however, a statistically significant association between maternal autoimmune disease and encephalocele was observed (OR, 4.64; 95% CI, 1.95-11.04). Eighty-two mothers with autoimmune disease used an immune modifying/suppressing medication during pregnancy; this was associated with encephalocele (OR, 7.26; 95% CI, 1.37-24.61) and atrial septal defects (OR, 3.01; 95% CI, 1.16-7.80). CONCLUSION: Our findings suggest maternal autoimmune disease and treatment are not associated with the majority of birth defects, but may be associated with some defects, particularly encephalocele. Given the low prevalence of individual autoimmune diseases and the rare use of specific medications, we were unable to examine associations of specific autoimmune diseases and medications with birth defects. Other studies are needed to confirm these findings. Birth Defects Research (Part A) 106:950-962, 2016. © 2016 Wiley Periodicals, Inc.

Maternal cigarette, alcohol, and coffee consumption in relation to risk of clubfoot.

BACKGROUND: Clubfoot is associated with maternal cigarette smoking in several studies, but it is not clear if this association is confined to women who smoke throughout the at-risk period. Maternal alcohol and coffee drinking have not been well studied in relation to clubfoot. METHODS: The present study used data from a population-based case-control study of clubfoot conducted in Massachusetts, New York, and North Carolina from 2007 to 2011. Mothers of 646 isolated clubfoot cases and 2037 controls were interviewed about pregnancy events and exposures, including the timing and frequency of cigarette smoking, alcohol intake, and coffee drinking. RESULTS: More mothers of cases than controls reported smoking during early pregnancy (28.9% vs. 19.1%). Of women who smoked when they became pregnant, those who quit in the month after a first missed period had a 40% increase in clubfoot risk and those who continued to smoke during the next 3 months had more than a doubling in risk, after controlling for demographic factors, parity, obesity, and specific medication exposures. Adjusted odds ratios for women who drank >3 servings of alcohol or coffee per day throughout early pregnancy were 2.38 and 1.77, respectively, but the numbers of exposed women were small and odds ratios were unstable. CONCLUSIONS: Clubfoot risk appears to be increased for offspring of women who smoke cigarettes, particularly those who continue smoking after pregnancy is recognisable, regardless of amount. For alcohol and coffee drinkers, suggested increased risks were only observed in higher levels of intake.

Population-based study to determine mortality in spina bifida: New York State Congenital Malformations Registry, 1983 to 2006.

BACKGROUND: The lifetime risk of death among individuals with spina bifida is 10-times higher compared with the general population. A population-based analysis on cause-specific mortality among individuals spina bifida is lacking. METHODS: Using statewide, population-based New York Congenital Malformations Registry, we examined all births between years 1983 and 2006, and identified 1988 births with spina bifida and 10,951 births with congenital hypertrophic pyloric stenosis (CHPS). We linked registry records to birth and death files from vital records, and determined age- and cause-specific mortality for isolated and multiple spina bifida, and compared the findings with the less fatal CHPS. RESULTS: Mortality in spina bifida is significantly high compared with CHPS (16.9% vs. 0.96%, respectively). The probability of survival in spina bifida was lower compared with CHPS. A majority of the deaths in spina bifida occurred in infants within the first year of birth; however, an increased risk of death persisted in young adulthood for both isolated and multiple cases of spina bifida. The common causes of death in children with spina bifida were hydrocephalus, infections, cardiac anomalies, pneumonia, and pulmonary embolism; while infections, heart or kidney failure, injuries and neoplasms contributed to deaths in adults. CONCLUSION: We conclude that mortality in spina bifida is a large concern, and individuals living with the defect require improved clinical care for lethal medical complications. Primary prevention of spina bifida through mandatory folic acid fortification remains as the best strategy to reduce both disability and mortality associated with this defect across the world.

Analysis of polychlorinated biphenyls and organochlorine pesticides in archived dried blood spots and its application to track temporal trends of environmental chemicals in newborns.

Dried blood spots (DBS) collected from infants shortly after birth for the newborn screening program (NSP) in the United States are valuable resources for the assessment of exposure to environmental chemicals in newborns. The NSP was debuted as a public health program in the United States in the 1960s; and the DBS samples collected over a period of time can be used in tracking temporal trends in exposure to environmental chemicals by newborns. In this study, polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) were measured in DBS samples collected from newborns in Upstate New York from 1997 to 2011 by gas chromatography-high resolution mass spectrometry (GC-HRMS). Twelve PCBs and two OCPs were found in DBS samples at a detection rate above 50% (n=51). The mean whole blood concentration of ΣPCBs (sum of 12 congeners) over the 15-year period was 1.06 ng/mL, followed by p,p'-DDE (0.421 ng/mL) and HCB (0.065 ng/mL). The measured concentrations of PCBs and p,p'-DDE in infants'blood were comparable to those reported in cord blood, suggesting maternal/trans-placental transfer of these compounds from mothers to fetuses. The concentrations of ΣPCBs and p,p'-DDE in blood samples of infants decreased significantly between 1997 and 2001, and no significant reduction was found thereafter. This observation is consistent with the trends reported for these chemicals in other human tissues in the United States.

Medication use in pregnancy in relation to the risk of isolated clubfoot in offspring.

Clubfoot, a common major structural malformation, develops early in gestation. Epidemiologic studies have identified higher risks among boys, first-born children, and babies with a family history of clubfoot, but studies of risks associated with maternal exposures are lacking. We conducted the first large-scale, population-based, case-control study of clubfoot with detailed information on maternal medication use in pregnancy. Study subjects were ascertained from birth defect registries in Massachusetts, New York, and North Carolina during 2007-2011. Cases were 646 mothers of children with clubfoot without other major structural malformations (i.e., isolated clubfoot); controls were mothers of 2,037 children born without major malformations. Mothers were interviewed within 12 months of delivery about medication use, including product, timing, and frequency. Odds ratios were estimated for exposure to 27 medications in pregnancy months 2-4 after adjustment for study site, infant sex, first-born status, body mass index (weight (kg)/height (m)(2)), and smoking. Odds ratios were less than 1.20 for 14 of the medications; of the remainder, most odds ratios were only slightly elevated (range, 1.21-1.66), with wide confidence intervals. The use of antiviral drugs was more common in clubfoot cases than in controls (odds ratio = 4.22, 95% confidence interval: 1.52, 11.73). Most of these results are new findings and require confirmation in other studies.

Descriptive and risk factor analysis for choanal atresia: The National Birth Defects Prevention Study, 1997-2007.

Choanal atresia causes serious posterior nasal obstruction. This defect is the leading cause of nasal surgery in newborns, although its etiology is largely unknown. Data from the National Birth Defects Prevention Study, a population-based case-control study, were used to examine associations between maternal self-reports of exposures and occurrence of choanal atresia in their offspring. Overall, 117 case and 8350 control mothers with deliveries from 1997 through 2007 provided telephone interview reports of pre-pregnancy (one year before conception) and periconceptional (one month before through three months after conception) exposures. The exposures analyzed were pre-pregnancy dietary intake, pre-pregnancy and periconceptional caffeine consumption, and periconceptional cigarette smoking, alcohol drinking, and medication use. Independent associations between each exposure and all choanal atresia cases combined (n = 117) and isolated choanal atresia cases (those without additional unrelated major defects; n = 61) were examined. Odds ratios (ORs), both unadjusted (uORs) and adjusted (aORs) for potential confounders, and 95% confidence intervals (CIs) were estimated using unconditional logistic regression analysis. For all choanal atresia cases combined, positive associations were observed with maternal pre-pregnancy intake in the highest quartile for vitamin B-12 (aOR = 1.9; CI = 1.1,3.1), zinc (aOR = 1.7; CI = 1.0,3.1), and niacin (aOR = 1.8; CI = 1.0,3.1), and intake in the lowest quartile for methionine (aOR = 1.6; CI = 1.0,2.6) and vitamin D (aOR = 1.6; CI = 1.0,2.4) compared to intake in the two intermediate quartiles combined. Further, a positive association was observed with periconceptional use of thyroid medications (uOR = 2.6; CI = 1.0,6.3) compared to no use of such medications. Among isolated choanal atresia cases, negative associations were observed for pantothenic acid (aOR = 0.4; CI = 0.2,0.9) and fat (aOR = 0.5; 95% CI = 0.2,1.0) intake in the lowest quartile compared to that in the intermediate quartiles, and positive associations were observed for periconceptional cigarette smoking (aOR = 2.3; CI = 1.1,4.7) compared to no smoking and pre-pregnancy daily coffee intake of 3 or more cups (aOR = 2.5; CI = 1.1,5.6) compared to intake of less than 1 cup per day. The positive association for periconceptional exposure to thyroid medications also persisted for isolated choanal atresia cases (uOR = 4.0; CI = 1.1,11.2). Because of the large number of associations tested, these findings may be due to chance. Alternatively, they may contribute new hypotheses regarding the etiology of choanal atresia; thus, requiring replication in additional studies.

Risk-adjusted prolonged length of stay as an alternative outcome measure for pediatric congenital cardiac surgery.

BACKGROUND: Morbid events after pediatric congenital cardiac surgery are increasingly used for better outcome measurement and quality comparisons. This study was undertaken to evaluate the relationship between a hospital's risk-adjusted prevalence of prolonged postoperative length of stay (PLOS) and its risk-adjusted mortality rate to investigate whether PLOS can serve as an appropriate quality measure for pediatric congenital cardiac surgery. METHODS: Risk-adjusted prevalence of prolonged PLOS for 12 programs in New York State was estimated using data from 4,776 operations in the New York State pediatric Cardiac Surgery Reporting System (2006-2009). We used logistic regression analysis to adjust for case mix and patient risk factors. The hospital-level correlation between risk-adjusted prolonged PLOS and risk-adjusted mortality rates was examined using Spearman correlation coefficient analysis. RESULTS: Risk-adjusted prevalence of prolonged PLOS ranged from 7.48% to 36.52% for pediatric cardiac programs in New York State during the study period. The Spearman correlation test showed a strong positive relationship between a hospital's risk-adjusted prolonged PLOS and mortality rate (r = 0.83; p = 0.0008). CONCLUSIONS: Prolonged PLOS can be used in lieu of risk-adjusted mortality rates when it is not practical to use mortality rates owing to low case volume or decreasing mortality rates of some procedures.

Periconceptional maternal alcohol consumption and neural tube defects.

BACKGROUND: Neural tube defects (NTD)s, which occur when the neural tube fails to close during early gestation, are some of the most common birth defects worldwide. Alcohol is a known teratogen and has been shown to induce NTDs in animal studies, although most human studies have failed to corroborate these results. Using data from the National Birth Defects Prevention Study, associations between maternal reports of periconceptional (1 month prior through 2 months postconception) alcohol consumption and NTDs were examined. METHODS: NTD cases and unaffected live born control infants, delivered from 1997 through 2005, were included. Interview reports of alcohol consumption (quantity, frequency, variability, and type) were obtained from 1223 case mothers and 6807 control mothers. Adjusted odds ratios (aOR)s and 95% confidence intervals were estimated using multivariable logistic regression analysis. RESULTS: For all NTDs combined, most aORs for any alcohol consumption, one or more binge episodes, and different type(s) of alcohol consumed were near unity or modestly reduced (≥ 0.7 < aOR ≤ 1.1) and were not statistically significant. Findings were similar for individual NTD subtypes. CONCLUSIONS: These findings suggest no elevated association between maternal periconceptional alcohol consumption and NTDs. Underreporting of alcohol consumption, due to negative social stigma associated with alcohol consumption during pregnancy, and limited reports for mothers with early pregnancy loss of a fetus with an NTD may have affected the estimated odds ratios. Future studies should aim to increase sample sizes for less prevalent subtypes, reduce exposure misclassification, and improve ascertainment of fetal deaths and elective terminations.

A genome-wide association study identifies susceptibility loci for nonsyndromic sagittal craniosynostosis near BMP2 and within BBS9.

Sagittal craniosynostosis is the most common form of craniosynostosis, affecting approximately one in 5,000 newborns. We conducted, to our knowledge, the first genome-wide association study for nonsyndromic sagittal craniosynostosis (sNSC) using 130 non-Hispanic case-parent trios of European ancestry (NHW). We found robust associations 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) and rs10262453, P = 3.50 × 10(-14)) in an independent NHW population of 172 unrelated probands with sNSC and 548 controls. Both BMP2 and BBS9 are genes with roles in skeletal development that warrant functional studies to further understand the etiology of sNSC.

Evaluation of genes involved in limb development, angiogenesis, and coagulation as risk factors for congenital limb deficiencies.

We conducted a population-based case-control study of single nucleotide polymorphisms (SNPs) in selected genes to find common variants that play a role in the etiology of limb deficiencies (LDs). Included in the study were 389 infants with LDs of unknown cause and 980 unaffected controls selected from all births in New York State (NYS) for the years 1998-2005. We used cases identified from the NYS Department of Health (DOH) Congenital Malformations Registry. 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). Genotype call rates were >97% and SNPs were tested for departure from Hardy-Weinberg expectations by race/ethnic subgroups. For each SNP, odds ratios (OR)s and confidence intervals (CI)s were estimated and corrected for multiple comparisons for all LDs combined and for LD subtypes. Among non-Hispanic white infants, associations between FGF10 SNPs rs10805683 and rs13170645 and all LDs combined were statistically significant following correction for multiple testing (OR = 1.99; 95% CI = 1.43-2.77; uncorrected P = 0.000043 for rs10805683 heterozygous genotype, and OR = 2.37; 95% CI = 1.48-3.78; uncorrected P = 0.00032 for rs13170645 homozygous minor genotype). We also observed suggestive evidence for associations with SNPs in other genes including CYP26B1 and WNT7A. Animal studies have shown that FGF10 induces formation of the apical ectodermal ridge and is necessary for limb development. Our data suggest that common variants in FGF10 increase the risk for a wide range of non-syndromic limb deficiencies.

Hirschsprung's disease and variants in genes that regulate enteric neural crest cell proliferation, migration and differentiation.

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. We sequenced RET to identify coding and splice-site variants in a population-based case group and we tested for associations between HSCR and common variants in RET and candidate genes (ASCL1, homeobox B5 (HOXB5), L1 cell adhesion molecule (L1CAM), paired-like homeobox 2b (PHOX2B), PROK1 and PROKR1) chosen because they are involved in ENCC proliferation, migration and differentiation in animal models. We conducted a nested case-control study of 304 HSCR cases and 1215 controls. Among 38 (12.5%) cases with 34 RET coding and splice-site variants, 18 variants were previously unreported. We confirmed associations with common variants in HOXB5 and PHOX2B but the associations with variants in ASCL1, L1CAM and PROK1 were not significant after multiple comparisons adjustment. RET variants were strongly associated with HSCR (P-values between 10(-3) and 10(-31)) but this differed by race/ethnicity: associations were absent in African-Americans. Our population-based study not only identified novel RET variants in HSCR cases, it 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.

Associations between periconceptional alcohol consumption and craniosynostosis, omphalocele, and gastroschisis.

BACKGROUND: Alcohol consumption during pregnancy is known to be associated with certain birth defects, but the risk of other birth defects is less certain. The authors examined associations between maternal alcohol consumption during pregnancy and craniosynostosis, omphalocele, and gastroschisis among participants in the National Birth Defects Prevention Study, a large, multicenter case-control study. METHODS: A total of 6622 control infants and 1768 infants with birth defects delivered from 1997-2005 were included in the present analysis. Maternal alcohol consumption was assessed as any periconceptional consumption (1 month prepregnancy through the third pregnancy month), and by quantity-frequency, duration, and beverage type. Alcohol consumption throughout pregnancy was explored for craniosynostosis since the period of development may extend beyond the first trimester. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated using unconditional logistic regression analysis. OR were adjusted for age, race/ethnicity, and state of residence at time of infant's birth. Gastroschisis OR were also adjusted for periconceptional smoking. RESULTS: Periconceptional alcohol consumption and craniosynostosis showed little evidence of an association (OR = 0.92; CI: 0.78-1.08), but alcohol consumption in the second (OR = 0.65; CI: 0.47-0.92) and third trimesters (OR = 0.68; CI: 0.49-0.95) was inversely associated with craniosynostosis. Periconceptional alcohol consumption was associated with omphalocele (OR = 1.50; CI: 1.15-1.96) and gastroschisis (OR = 1.40; CI: 1.17-1.67). CONCLUSIONS: Results suggest that maternal periconceptional alcohol consumption is associated with omphalocele and gastroschisis, and second and third trimester alcohol consumption are inversely associated with craniosynostosis.

Long-term follow-up of children with confirmed newborn screening disorders using record linkage.

BACKGROUND: Long-term follow-up of children identified through newborn screening is a critical process of data collection and analysis for advancing the public health understanding of the health outcomes and service uptake of the affected children. This article describes first steps toward the long-term follow-up of newborn screening children with confirmed disorders through records linkage using population-based administrative data. METHODS: The study cohort consisted of children born in 2006-2007 with confirmed disorders identified through newborn screening. Deterministic data linkage methods were used for record matching. RESULTS: The cohort was followed up to 2 years after birth by matching to data sources including vital records, hospital discharges, the Congenital Malformations Registry, and Early Intervention to monitor service utilization, comorbidities, and mortality of the affected children. Of 1215 children with confirmed conditions identified through newborn screening, 25 deaths (2.1%) were identified, 86.1% used hospital (in- or outpatient) services, 36.1% were enrolled in the Congenital Malformations Registry, and 19.9% used the services of the Early Intervention program during the 2-year follow-up period. CONCLUSIONS: Long-term follow-up of children with disorders identified through newborn screening can be initiated by using existing administrative data. This method is an inexpensive, cost-effective. and efficient approach for periodical assessment of services utilization, the efficiency of service delivery, and health outcomes for affected individuals.

Caffeine, selected metabolic gene variants, and risk for neural tube defects.

BACKGROUND: Investigations of maternal caffeine intake and neural tube defects (NTDs) have not considered genetic influences. Caffeine metabolism gene effects were examined in the National Birth Defects Prevention Study. METHODS: Average daily caffeine was summed from self-reported coffee, tea, soda, and chocolate intake for mothers of 768 NTD cases, and 4143 controls delivered from 1997 to 2002. A subset of 306 NTD and 669 control infants and their parents were genotyped for CYP1A2*1F, NAT2 481C>T, and NAT2 590G>A. CYP1A2*1F was classified by fast or slow oxidation status, and NAT2 variants were categorized into rapid or slow acetylation status. Case-control logistic regression analyses, family-based transmission/disequilibrium tests and log-linear analyses, and hybrid log-linear analyses were conducted to produce odds ratios (ORs) or relative risks (RRs) and 95% confidence intervals (CIs) for caffeine intake and maternal and infant gene variants, and to examine interaction effects. RESULTS: NTDs were independently associated with infant slow NAT2 acetylator status (RR, 2.00; 95% CI, 1.10-3.64) and maternal CYP1A2*1F fast oxidation status (OR, 1.49; 95% CI, 1.10-2.03). Mothers who consumed caffeine, oxidized CYP1A2*1F quickly, and acetylized NAT2 slowly had a nonsignificantly elevated estimated risk for an NTD-affected pregnancy (OR, 3.10; 95% CI, 0.86-11.21). Multiplicative interaction effects were observed between maternal caffeine and infant CYP1A2*1F fast oxidizer status (p(interaction) = 0.03). CONCLUSIONS: The association identified between maternal CYP1A2*1F fast oxidation status and NTDs should be examined further in the context of the other substrates of CYP1A2. Maternal caffeine and its metabolites may be associated with increased risk for NTD-affected pregnancies in genetically susceptible subgroups.

Characteristics of pregnant illicit drug users and associations between cannabis use and perinatal outcome in a population-based study.

BACKGROUND: According to the 2004 National Survey on Drug Use and Health, 4.6% of American women reported use of an illicit drug during pregnancy. Previous studies on illicit drug use during pregnancy and perinatal outcomes showed inconsistent results. METHODS: This population-based study included mothers who delivered live-born infants without birth defects between 1997 and 2004 and completed interviews for the National Birth Defects Prevention Study (response rate 69%; n=5871). Prevalence of self-reported illicit drug use (specifically cannabis, cocaine, and stimulants) during pregnancy and its associations with demographic and social factors were assessed. We used multivariable linear and logistic regression analyses to study the associations of cannabis use with birth weight and gestational age. RESULTS: The prevalence of reported illicit drug use during pregnancy was 3.6% (standard error 0.24). Pregnant users of cannabis, cocaine, and stimulants were younger, had a lower level of education and lower household income, and were less likely to have used folic acid in the periconceptional period than nonusers. Illicit drug users were also more likely to have used alcohol and tobacco. After adjustment for confounding, cannabis use was not associated with mean birth weight or gestational age or with low birth weight or preterm delivery. CONCLUSION: Women who report use of illicit drugs during pregnancy differ in demographic and socioeconomic background from nonusers. Reported cannabis use does not seem to be associated with low birth weight or preterm birth.

Increased prevalence of renal and urinary tract anomalies in children with Down syndrome.

OBJECTIVE: The goal was to investigate the prevalence of renal and urinary tract anomalies (RUTAs) in a Down syndrome (DS) population. METHODS: Data were obtained from the New York State Congenital Malformation Registry (NYS-CMR) in this retrospective cohort study. The occurrence of RUTAs was assessed for children with and without DS who were born in NYS between 1992 and 2004. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for each malformation. RESULTS: Between 1992 and 2004, 3832 children with DS and 3 411 833 without DS were born in NYS. The prevalence of RUTAs in the DS population was 3.2%, compared with 0.7% in the NYS population (OR: 4.5 [95% CI: 3.8 -5.4]). Children with DS had significantly increased risks of anterior urethral obstruction (OR: 29.7 [95% CI: 4.0 -217.7]), cystic dysplastic kidney (OR: 4.5 [95% CI: 1.5-14.1]), hydronephrosis (OR: 8.7 [95% CI: 6.8 -11.0]), hydroureter (OR: 8.5 [95% CI: 3.5-20.4]), hypospadias (OR: 2.0 [95% CI: 1.4 -2.9]), posterior urethral valves (OR: 7.1 [95% CI: 1.8 -28.8]), prune belly syndrome (OR: 11.9 [95% CI: 1.6 - 85.4]), and renal agenesis (OR: 5.4 [95% CI: 2.8 -10.4]). There was no significantly increased risk of ectopic kidney (OR: 1.6 [95% CI: 0.2-11.2]) or ureteropelvic junction obstruction (OR: 1.4 [95% CI: 0.2-9.9]) in the DS population. CONCLUSION: Children with DS have significantly increased risks of RUTAs.

Maternal caffeine consumption and risk of neural tube defects.

BACKGROUND: Animal studies demonstrate teratogenic effects of caffeine, whereas human studies are inconclusive. METHODS: Associations between maternal caffeine consumption and neural tube defects (NTDs) by type of NTD (anencephaly, spina bifida, or encephalocele) were examined using data from the National Birth Defects Prevention Study (NBDPS). Total average daily caffeine from coffee, tea, soda, and chocolate consumption during the year before pregnancy was estimated for 768 mothers of infants with NTDs and 4143 mothers of infants without birth defects who gave birth during 1997 through 2002. Periconceptional use of caffeine-containing medications was evaluated separately. Adjusted odds ratios (OR) and 95% confidence intervals (CI) associated with consumption of total caffeine and each caffeine source were estimated from logistic regression models. RESULTS: Positive associations were observed between spina bifida and total caffeine consumption (OR 1.4; 95% CI: 1.1-1.9) and each caffeine source except caffeinated tea, which showed a negative association with spina bifida (OR 0.7; 95% CI: 0.6-0.9). Associations with modestly increased risk of NTDs and encephalocele were also observed. The association between caffeine consumption and anencephaly differed by maternal race/ethnicity. No dose effects were found. CONCLUSIONS: Additional studies should confirm whether women who consume caffeine are at increased risk for pregnancies complicated by NTDs.

Racial disparities in mortality among infants with Dandy-Walker syndrome.

BACKGROUND: Congenital malformations are the major cause of infant mortality in the United States, but their contribution to overall racial disparity--a major public health concern--is poorly understood. We sought to estimate the contribution of a congenitally acquired central nervous system lesion, Dandy-Walker Syndrome (DWS), to black-white disparity in infant mortality. METHODS: Data were obtained from the New York State Congenital Malformations Registry, an ongoing population-based validated surveillance system. We compared black to white infants with respect to infant, neonatal, and postneonatal mortality using Cox proportional hazards regression models. RESULTS: A total of 196 live-born neonates were diagnosed with DWS in the state from 1992 to 2005 inclusive. Of these, 53 were non-Hispanic black and 76 were non-Hispanic white. Neonatal mortality was similar for non-Hispanic blacks and non-Hispanic whites (adjusted hazards ratio [AHR], 1.42; 95% CI, 0.52-3.82), but non-Hispanic blacks had an 8-fold increased risk for postneonatal mortality (AHR, 8.26; 95% CI, 2.08-32.72). Adjustment for fetal growth and other maternal and infant characteristics resulted in a 10-fold increased risk of mortality for non-Hispanic black infants as compared to non-Hispanic whites. By contrast, adjustment for preterm birth attenuated the risk, but non-Hispanic black infants were still more than 6 times as likely to die during the postneonatal period than non-Hispanic whites (AHR, 6.36, 95% CI, 1.52-26.60). CONCLUSION: DWS has one of the largest black-white disparities in postneonatal survival. This underscores the importance of evaluating racial disparities in infant mortality by specific conditions in order to formulate targeted interventions to reduce disparities.