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Background: Most studies evaluating neurocognitive outcomes in children with congenital heart defects (CHD) have focused on high-risk patients or used specialized, resource-intensive testing. To determine the association of CHD with academic outcomes and compare outcomes according to the severity of CHD, we linked state educational records with a birth defects registry and birth certificates.Methods and Results: We performed a retrospective cohort study using data from the North Carolina Birth Defects Monitoring Program, North Carolina Department of Public Instruction, and North Carolina Department of Health and Human Services vital records. We performed logistic regression, adjusting for maternal education, race/ethnicity, enrollment in public pre-Kindergarten, and gestational age, to determine the association of CHD with not meeting standards on reading and math end-of-grade examinations in third grade in 2006 to 2012. Of 5624 subjects with CHD and 10 832 with no structural birth defects, 2807 (50%) and 6355 (59%) were linked, respectively. Children with CHD had 1.24× the odds of not meeting standards in either reading or math (95% confidence interval, 1.12-1.37), with 44.6% of children with CHD not meeting standards in at least one of these areas compared with 37.5% without CHD. Although children with both critical and noncritical CHD had poorer outcomes, those with critical CHD were significantly more likely to receive exceptional services compared with the noncritical group (adjusted odds ratio, 1.46; 95% confidence interval, 1.15-1.86).Conclusions: Children with all types of CHD have poorer academic outcomes compared with their peers. Evaluation for exceptional services should be considered in children with any type of CHD. [ABSTRACT FROM AUTHOR]

The article presents a study comparing the academic outcomes between children with orofacial cleft (OFC) and children without major birth defects. The study involved a random sample of mothers of children aged 5-12 years with isolated OFC identified by the North Carolina Birth Defects Monitoring Program (NCBDMP) and unaffected children. It finds that most children with OFC are successful in school but may be more likely to have poorer academic outcomes than their peers without birth defects.

Abstract: This study examines associations between area-level socioeconomic factors and the birth defect gastroschisis in order to further our understanding of the etiology of this condition. Specifically, this study explores how measuring socioeconomic conditions at different geographic scales affect the results of statistical models. A population-based case-control study of resident live births was conducted using data from the North Carolina Birth Defect Monitoring Program and the North Carolina composite linked birth files from 1998 through 2004. Neighborhood conditions potentially related to gastroschisis (poverty, unemployment, education, and racial composition) were measured using Census 2000 data and aggregated to several geographic scales. The Brown–Forsythe test of homogeneity of variance was used to select the neighborhood size by examining the effect of neighborhood size on variation in gastroschisis rates. To examine our assumptions about neighborhood size and neighborhood effects on gastroschisis, we estimated a series of logistic regression and multilevel logistic regression models. The Brown–Forsythe test suggested an optimal neighborhood size with a circular radius of approximately 2500 m, which was supported by the statistical analysis. Results indicate a weak association between living in a neighborhood characterized by high poverty and unemployment and an elevated risk of a gastroschisis-affected pregnancy after adjusting for individual-level risk factors. Cross-level interactions indicate that women in low poverty neighborhoods who do not rely on Medicaid have a significantly lower risk of gastroschisis. The choice of neighborhood scale influences model results suggesting that socioeconomic processes may influence health outcomes variably at different scales. [Copyright &y& Elsevier]

Objective: To examine the timeliness of primary cleft surgery, mean age at which surgery occurred, and factors associated with timely cleft surgery among children with orofacial clefts (OFCs). Design: Retrospective study of children with OFC using North Carolina vital statistics, birth defects registry, and Medicaid files. Participants/Patients: Medicaid-enrolled North Carolina resident children with OFC born from 1995 to 2002. Main Outcome Measures: Proportion of children who underwent primary cleft surgery within 18 months of life, mean age when surgery occurred, and factors associated with timely surgery. Results: 406 children with OFC were continuously enrolled in Medicaid during the first 2 years of life. Overall, 78.1% of children had surgery within 18 months. About 90% of children with cleft lip (CL), 58.0% of children with cleft palate (CP), and 89.6% of children with cleft lip and palate (CLP) received timely cleft surgery; the mean age at which surgery occurred was 5 months. Children whose mothers received maternity care coordination, received prenatal care at a local health department, or lived in the southeastern or northeastern region of the state were more likely to receive timely cleft surgery. Conclusion: Most children with OFC in North Carolina born during this time period received primary cleft surgery within 18 months of life, but this varied by maternal demographics and other factors. [ABSTRACT FROM AUTHOR]

Abstract: Examining the geographic distribution of birth defects can be useful in exploratory etiologic research. Identification of clusters of certain defects may uncover possible environmental or socio-economic risk factors and assist with the generation of hypotheses about underlying causes of these conditions. In North Carolina, the prevalence of gastroschisis, a serious abdominal wall defect, has increased over the past decade and anecdotal evidence from clinicians suggests the possibility of clustering of this condition. This study uses a spatial scan statistic to identify the location and extent of clusters of gastroschisis births in North Carolina between 1999 and 2004. Data on cases of gastroschisis were obtained from the North Carolina Birth Defect Monitoring Program (NCBDMP) and control births were chosen from all resident live births without birth defects contained in the North Carolina composite linked birth files. The clusters were controlled for five major risk factors (maternal age, race, parity, Medicaid status, maternal smoking) to ensure that the clusters were not artifacts of unequal population distribution. Results indicate a localized cluster of gastroschisis in the rural southern Piedmont of North Carolina which persists even after controlling for all major risk factors. Adjusting for these risk factors shifted the location of the cluster substantially, demonstrating the importance of adjusting for underlying population distribution. Since clusters persisted after adjusting for individual-level risk factors, environmental contaminants may explain the excess of gastroschisis cases. This study is among the first to assess spatial clustering of gastroschisis using GIS methods. This study also demonstrates the importance of controlling for covariates in spatial analysis and illustrates the usefulness of the spatial scan statistic in exploratory etiologic research. [Copyright &y& Elsevier]

Objective: North Carolina has several programs that identify high-risk women and children for needed services, including the Child Service Coordination Program (CSCP). This study determines CSCP referral rates among infants with orofacial clefts (OFCs) and predictors of CSCP referral. We hypothesized receiving Medicaid and maternity care coordination (MCC) services increases the likelihood of CSCP referral. Design and Setting: For births between 1999 and 2002, data were matched from North Carolina Vital Statistics, Health Services Information System (MCC and CSCP data), and North Carolina Birth Defects Monitoring Program. Multi- variate analysis was used to determine crude and adjusted odds ratios for sociodemographic variables to predict CSCP referral. Participants: A total of 644 mothers of live-born infants with OFCs in North Carolina were identified. Results: About 45% of infants with OFCs were referred to the CSCP. Infants of mothers who were at least 30 years of age and mothers who had more than a high school education were significantly less likely to be referred to the CSCP. Compared with infants with OFCs whose mothers did not receive Medicaid, mothers who received Medicaid were 1.9 times more likely to be referred to the CSCP, and mothers who received Medicaid and MCC services were 2.3 times more likely. Conclusions: Receipt of Medicaid and MCC services and receipt of Medicaid alone were positively associated with CSCP referral. Future studies should examine the effects of the duration of MCC services and factors related to the timeliness of CSCP referral. [ABSTRACT FROM AUTHOR]

Assesses the impact that folic acid public health initiatives have had on spina bifida rates among sociodemographic subpopulations in North Carolina using the data from the North Carolina Birth Defects Monitoring Program. Variation of the magnitude of the decline; Subgroups for which targeted educational activities are most needed; Overall trend in the spina bifida prevalence during 1995 to 1999.

Objectives: The purpose of this study is to examine the trends in multiple deliveries in North Carolina and assess their effect on the rates of low birth weight, fetal mortality, and infant mortality. Methods: Using North Carolina vital statistics files, trends in multiple births, categorized by race, maternal age, and birth weight, were examined for the period 1980–1997. A partitioning method was used to estimate the contribution of maternal age distribution and age-specific multiple birth rates to the overall increase in multiple births, and the contribution of the changing multiple birth rate to observed trends in low birth weight and fetal and infant mortality. Results: Between 1980 and 1997, the state's multiple birth rate increased by 40%. Most of the increase was due to a rise in the age-specific multiple birth rates, rather than a shift in the maternal age distribution. The increase in the multiple birth rate accounted for a substantial proportion of the increase in low birth weight among Whites and Blacks. The rise in multiple births also hindered further declines in fetal and infant mortality during this time. Conclusions: Multiple births are an increasingly important contributor to perinatal outcomes, and warrant greater consideration in research aimed at evaluating trends in low birth weight and infant mortality. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Gastroschisis is a congenital anomaly that has been reported to be increasing in frequency. The objective of this study was to determine the birth prevalence of gastroschisis using two large databases. STUDY DESIGN: We reviewed data from a statewide database and a national database from a neonatal health care provider, abstracting cases of gastroschisis. RESULTS: In North Carolina, the birth prevalence of gastroschisis increased from 1.96 per 10,000 births in 1997 to 4.49 per 10,000 births in 2000 (p = 0.0007). The overall increase was almost entirely because of the increase in infants born to mothers less than 20 years old. Among infants receiving care from the national neonatal provider, the prevalence of gastroschisis increased from 2.9 per 1000 patients in 1997 to five per 1000 patients in 2001 (p = 0.044). CONCLUSION: The birth prevalence of gastroschisis is increasing in North Carolina, and this trend may be occurring nationally. The rapid change in the birth prevalence in the subset of population most at risk for gastroschisis implicates environmental or pharmacologic teratogens rather than changing population characteristics as a causal factor in the development of gastroschisis. [ABSTRACT FROM AUTHOR]

A study of trends in maternal mortality from 1963 to 1992 in North Carolina shows that during the period 1973-1977, when legal abortion first became available, the maternal mortality ratio (maternal deaths per 100,000 live births) for deaths related to induced-abortion was almost 85% lower than the ratio during the previous five-year period. The decrease in abortion-related mortality had a substantial impact on the overall maternal mortality ratio during this period, accounting for about 46% of the total decline in maternal deaths. After 1977, the maternal mortality ratio for induced abortion declined to less than one death per 100,000 live births, while the mortality ratio for all other obstetric causes leveled offal about 10 deaths per 100,000 live births. [ABSTRACT FROM AUTHOR]

: ObjectiveTo examine the association between health care services variables and pregnancy-related death using a contemporary geographically defined population and enhanced methods for case identification.: MethodsThis is a population-based, case-control study from North Carolina for the 7-year period 1992–1998. Pregnancy-related deaths after a live birth (n = 118) were identified after review of pregnancy-associated deaths (n = 400) ascertained from death certificate codes and linkage of birth and death files. Controls (n = 3697) were randomly selected from all registered live births for the same 7-year period and were not matched with cases. This sample size was sufficient to ensure that the standard errors for subgroup prevalences were less than 1%. The associations between pregnancy-related death and health care services were explored with univariate and multivariable regression analysis.: ResultsNeither maternity care coordination nor nutritional services were protective. There was no association with source of care, private versus public. The adjusted odds ratio (OR) for pregnancy-related death associated with cesarean delivery was 3.9 (95% confidence interval [CI] 2.5, 6.1). The adjusted OR for pregnancy-related death associated with the receipt of prenatal care was 0.2 (95% CI 0.1, 0.6).: ConclusionRemoving barriers to and actively promoting use of prenatal care services and decreasing the rate of cesarean deliveries could decrease the number of pregnancy-related deaths. [Copyright &y& Elsevier]

Introduction: Children with Congenital Heart Defects (CHD) may be at risk for poor academic performance in elementary school. Cumulative episodes of care among children with CHD may impact neurocognitive outcomes. We examined the association between the number of episodes of care and third-grade academic performance among children with CHD. Methods: We identified children with CHD from electronic medical records between 1/1/2008 and 12/31/2013 among five North Carolina (NC) tertiary care centers. We classified children by CHD type (severe disease, shunt lesion, valve disease, other) and matched subjects to the NC Department of Public Instruction educational records. We calculated the number of episodes of care by adding inpatient and outpatient visits from the EMR in the follow up period prior to administering the EOG. We estimated the odds of failing third-grade reading or math end of grade (EOG) tests among children with CHD who had episodes of care >50th percentile compared to children ≤50th percentile using logistic regression controlling for maternal education, race/ethnicity, and gestational age. We also estimated the average change in the developmental scale score using linear regression for the same comparison group. The inability to demonstrate proficiency in NC grade level standards was considered a failing score. Results: A total of 425 children with CHD had third-grade EOG scores. Of these, 57% were male and 45% of children had a severe CHD, 30% had a shunt lesion, and 21% had valve disease. The median number of episodes of care was 4 (range: 1-60). Children with number of visits above the 50th percentile (>4 visits) had 2.09 (95% CI: 1.04,4.21) greater odds of failing the math EOG compared to children at or below the 50th percentile (1-4 visits). The third- grade math developmental scale score declined by 1.54 points (p<0.008) for every 10 episodes of care. There was no statistically significant effect of episodes of care on third grade reading performance. Conclusions: Children with CHD in NC with number of episodes of care above the 50th percentile, may be at risk for delays in third-grade academic performance. Additional services may be required to improve academic success in this population. [ABSTRACT FROM AUTHOR]

Background: Improved pediatric congenital heart disease (CHD) outcomes have led to rapid growth of the adult CHD population. There are few contemporary studies examining causes of death (COD) in adults with CHD. Methods: Patients with CHD with a healthcare encounter between 2008-2013 at one of five tertiary care centers in North Carolina (NC) were identified by ICD-9 code. Those aged ≥ 20 yrs who could be linked to a NC death certificate between 2008-2016 were included. Mean age of death (AOD) & underlying COD were analyzed, with stratification by lesion severity (severe, shunt, valve). Results: A total of 629 adults met inclusion criteria. The mean AOD was 64.2 yrs. Those with severe CHD (n=157, 25%), shunts (n=202, 32%) & valvular lesions (n=174, 28%) had a mean AOD of 46.0, 65.0 & 73.3 yrs, respectively. The most common COD among all adults were cancer (14%), CHD (14%), ischemic heart disease (11%), infection (8%) & lung disease (7%); 43% died from any cardiovascular (CV) disease with 33% of CV deaths due to CHD. The most common COD among those with severe CHD were CHD (41%), cancer (9%) & heart failure (8%); 60% died from CV disease with 68% of CV deaths due to CHD. For those with shunts, the most common COD were ischemic heart disease (15%), cancer (15%) & lung disease (10%); 42% died from CV disease with 21% of CV deaths due to CHD. The most common COD among those with valvular CHD were cancer (17%), ischemic heart disease (11%) & lung disease (9%); 34% died from CV disease with 8% of CV deaths due to CHD. Among those who died during the study period, the odds of death due to CV disease vs. other causes was 2.6 times higher in those with severe CHD compared to non-severe disease (95% CI for OR 1.8-3.2, P<0.0001) and the odds of death due to CHD vs. other causes was 14 times higher in those with severe CHD compared to non-severe disease (95% CI for OR 8.1-23.4, P<0.0001). Conclusions: In those without severe disease, the lifespan of adults with CHD is approaching that of the general population as reported by the CDC. The most common COD differ based on lesion severity, with CHD being most common only among those with severe disease. Among patients with non-severe CHD, the most common COD are similar to the general population. Understanding COD in adults with CHD can lead to improved, targeted preventive care. [ABSTRACT FROM AUTHOR]

Background Little is known about the contemporary mortality experience among adults with congenital heart disease (CHD). The objectives of this study were to assess the age at death, presence of cardiovascular comorbidities, and most common causes of death among adults with CHD in a contemporary cohort within the United States. Methods and Results Patients with CHD who had a healthcare encounter between 2008 and 2013 at 1 of 5 comprehensive CHD centers in North Carolina were identified by International Classification of Diseases, Ninth Revision ( ICD-9 ), code. Only patients who could be linked to a North Carolina death certificate between 2008 and 2016 and with age at death ≥20 years were included. Median age at death and underlying cause of death based on death certificate data were analyzed. The prevalence of acquired cardiovascular risk factors was determined from electronic medical record data. Among the 629 included patients, the median age at death was 64.2 years. Those with severe CHD (n=157, 25%), shunts (n=202, 32%), and valvular lesions (n=174, 28%) had a median age at death of 46.0, 65.0, and 73.3 years, respectively. Cardiovascular death was most common in adults with severe CHD (60%), with 40% of those deaths caused by CHD. Malignancy and ischemic heart disease were the most common causes of death in adults with nonsevere CHD. Hypertension and hyperlipidemia were common comorbidities among all CHD severity groups. Conclusions The most common underlying causes of death differed by lesion severity. Those with severe lesions most commonly died from underlying CHD, whereas those with nonsevere disease more commonly died from non-CHD causes.

Background: North Carolina's Infant-Toddler Program (NC ITP) provides Early Intervention (EI) services from birth to age three for children at risk for developmental delays. This study examined referral patterns by clinical and sociodemographic characteristics among infants with birth defects and infants born extremely preterm (gestational age < 27 weeks) or extremely low birthweight (<1,000 g)., Methods: A retrospective cohort of North Carolina resident births from 2012 to 2014 was matched to data from the North Carolina Birth Defects Monitoring Program and NC ITP records. A total of 2,463 infants with eligible birth defects and 2,118 extremely preterm or low birthweight infants were identified. Adjusted odds ratios and 95% confidence intervals from multivariable logistic regression models were used to analyze differences in referral by sociodemographic and clinical factors. Referrals resulting in enrollment were also examined., Results: About 70% of infants with eligible birth defects and 85% of extremely premature infants were referred to the NC ITP. Geographic region, maternal race/ethnicity, maternal and infant enrollment in Medicaid, and hospital level of care at delivery were associated with referral among both at-risk groups. Among infants with birth defects, maternal age, education, and marital status were also associated with referral, as well as gestational age, birthweight, and the presence of multiple anomalies. Of the infants with referrals, over 80% in each group were subsequently enrolled., Conclusions: Many of the sociodemographic and clinical factors examined were associated with EI referral. These findings can be used to address coverage gaps and improve referral and enrollment rates for at-risk infants., (© 2019 Wiley Periodicals, Inc.)

Background: Previously we observed elevated odds ratios (ORs) for total pesticide exposure and 10 birth defects: three congenital heart defects and structural defects affecting the gastrointestinal, genitourinary and musculoskeletal systems. This analysis examines association of those defects with exposure to seven commonly applied pesticide active ingredients., Methods: Cases were live-born singleton infants from the North Carolina Birth Defects Monitoring Program linked to birth records for 2003-2005; noncases served as controls (total n = 304,906). Pesticide active ingredient exposure was assigned using a previously constructed metric based on crops within 500 m of residence, dates of pregnancy, and likely chemical application dates for each pesticide-crop combination. ORs (95% CI) were estimated with logistic regression for categories of exposure compared to unexposed. Models were adjusted for maternal race/ethnicity, age at delivery, education, marital status, and smoking status., Results: Associations varied by birth defect and pesticide combinations. For example, hypospadias was positively associated with exposures to 2,4-D (OR 50th to <90th percentile : 1.39 [1.18, 1.64]), mepiquat (OR 50th to <90th percentile : 1.10 [0.90, 1.34]), paraquat (OR 50th to <90th : 1.14 [0.93, 1.39]), and pendimethalin (OR 50th to <90th : 1.21 [1.01, 1.44]), but not S-metolachlor (OR 50th to <90th : 1.00 [0.81, 1.22]). Whereas atrial septal defects were positively associated with higher levels of exposure to glyphosate, cyhalothrin, S-metolachlor, mepiquat, and pendimethalin (ORs ranged from 1.22 to 1.35 for 50th to <90th exposures, and 1.72 to 2.09 for >90th exposures); associations with paraquat were null or inconsistent (OR 50th to <90th: 1.05 (0.87, 1.27)., Conclusion: Our results suggest differing patterns of association for birth defects with residential exposure to seven pesticide active ingredients in North Carolina., (© 2018 Wiley Periodicals, Inc.)

Background: Epidemiologic studies involving birth defects are extremely sensitive to phenotype accuracy and precision. We devised a case review and classification protocol for a project to study school achievement in children with idiopathic, nonsyndromic orofacial clefts to improve the reliability of phenotypic classification from the statewide birth defects registry., Methods: Surveillance-program abstraction data and medical records at the birth or treating hospitals were used when available. Exclusion criteria included: median cleft lip; Tessier cleft; premaxillary agenesis; presence of a recognizable syndrome, phenotype, association, or sequence (other than Robin sequence); clefts with other malformations not considered to be normal or common variants in the newborn; and cases with documented or suspected genetic or teratogenic causes., Results: Of 712 children identified with orofacial clefts, 153 were excluded, leaving 559 nonsyndromic orofacial cleft cases of unknown cause in the final study. These cases were grouped into the following clinically meaningful types: cleft lip with or without cleft alveolus; cleft lip and cleft palate; and cleft palate only. This review and classification process resulted in the elimination of 21.5% of the original cohort of identified cases, with most exclusions being due to suspected syndromic associations., Conclusion: Verbatim descriptions of the clinical findings are critical for accurate classification of diagnoses. This review process improved the precision of orofacial cleft phenotype classification for our study. Precision would have been further improved if all of the cases had verbatim descriptions of diagnoses and all medical records could have been reviewed by the classification team., (© 2015 Wiley Periodicals, Inc.)

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., (© 2014 John Wiley & Sons Ltd.)

Background: Little is known about the barriers faced by families of children with birth defects in obtaining healthcare. We examined reported perceived barriers to care and satisfaction with care among mothers of children with orofacial clefts., Methods: In 2006, a validated barriers to care mail/phone survey was administered in North Carolina to all resident mothers of children with orofacial clefts born between 2001 and 2004. Potential participants were identified using the North Carolina Birth Defects Monitoring Program, an active, state-wide, population-based birth defects registry. Five barriers to care subscales were examined: pragmatics, skills, marginalization, expectations, and knowledge/beliefs. Descriptive and bivariate analyses were conducted using chi-square and Fisher's exact tests. Results were stratified by cleft type and presence of other birth defects., Results: Of 475 eligible participants, 51.6% (n = 245) responded. The six most commonly reported perceived barriers to care were all part of the pragmatics subscale: having to take time off work (45.3%); long waits in the waiting rooms (37.6%); taking care of household responsibilities (29.7%); meeting other family members' needs (29.5%); waiting too many days for appointments (27.0%); and cost (25.0%). Most respondents (72.3%, 175/242) felt "very satisfied" with their child's cleft care., Conclusion: Although most participants reported being satisfied with their child's care, many perceived barriers to care were identified. Due to the limited understanding and paucity of research on barriers to care for children with birth defects, including orofacial clefts, additional research on barriers to care and factors associated with them are needed., (© 2014 Wiley Periodicals, Inc.)

Background: Hypospadias is a relatively common birth defect affecting the male urinary tract. We explored the etiology of hypospadias by examining its spatial distribution in North Carolina and the spatial clustering of residuals from individual and environmental risk factors., Methods: We used data collected by the North Carolina Birth Defects Monitoring Program from 2003 to 2005 to estimate local Moran's I statistics to identify geographic clustering of overall and severe hypospadias, using 995 overall cases and 16,013 controls. We conducted logistic regression and local Moran's I statistics on standardized residuals to consider the contribution of individual variables (maternal age, maternal race/ethnicity, maternal education, smoking, parity, and diabetes) and environmental variables (block group land cover) to this clustering., Results: Local Moran's I statistics indicated significant clustering of overall and severe hypospadias in eastern central North Carolina. Spatial clustering of hypospadias persisted when controlling for individual factors, but diminished somewhat when controlling for environmental factors. In adjusted models, maternal residence in a block group with more than 5% crop cover was associated with overall hypospadias (odds ratio = 1.22; 95% confidence interval = 1.04-1.43); that is living in a block group with greater than 5% crop cover was associated with a 22% increase in the odds of having a baby with hypospadias. Land cover was not associated with severe hypospadias., Conclusion: This study illustrates the potential contribution of mapping in generating hypotheses about disease etiology. Results suggest that environmental factors including proximity to agriculture may play some role in the spatial distribution of hypospadias. Birth Defects Research (Part A) 100:887-894, 2014. © 2014 Wiley Periodicals, Inc., (© 2014 Wiley Periodicals, Inc.)

We evaluate the use of three different exposure metrics to estimate maternal agricultural pesticide exposure during pregnancy. Using a geographic information system-based method of pesticide exposure estimation, we combine data on crop density and specific pesticide application amounts/dates to create the three exposure metrics. For illustration purposes, we create each metric for a North Carolina cohort of pregnant women, 2003-2005, and analyze the risk of congenital anomaly development with a focus on metric comparisons. Based on the results, and the need to balance data collection efforts/computational efficiency with accuracy, the metric which estimates total chemical exposure using application dates based on crop-specific earliest planting and latest harvesting information is preferred. Benefits and drawbacks of each metric are discussed and recommendations for extending the analysis to other states are provided.

A range of health effects, including adverse pregnancy outcomes, have been associated with exposure to ambient concentrations of particulate matter (PM) and ozone (O3). The objective of this study was to determine whether maternal exposure to fine particulate matter (PM2.5) and O3 during pregnancy is associated with the risk of term low birthweight and small for gestational age infants in both single and co-pollutant models. Term low birthweight and small for gestational age were determined using all birth certificates from North Carolina from 2003 to 2005. Ambient air concentrations of PM2.5 and O3 were predicted using a hierarchical Bayesian model of air pollution that combined modeled air pollution estimates from the EPA׳s Community Multi-Scale Air Quality (CMAQ) model with air monitor data measured by the EPA׳s Air Quality System. Binomial regression, adjusted for multiple potential confounders, was performed. In adjusted single-pollutant models for the third trimester, O3 concentration was positively associated with small for gestational age and term low birthweight births [risk ratios for an interquartile range increase in O3: 1.16 (95% CI 1.11, 1.22) for small for gestational age and 2.03 (95% CI 1.80, 2.30) for term low birthweight]; however, inverse or null associations were observed for PM2.5 [risk ratios for an interquartile range increase in PM2.5: 0.97 (95% CI 0.95, 0.99) for small for gestational age and 1.01 (95% CI 0.97, 1.06) for term low birthweight]. Findings were similar in co-pollutant models and linear models of birthweight. These results suggest that O3 concentrations in both urban and rural areas may be associated with an increased risk of term low birthweight and small for gestational age births., (Published by Elsevier Inc.)

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., (© The Author 2014. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Few studies have examined the potential relationship between air pollution and birth defects. The objective of this study was to investigate whether maternal exposure to particulate matter (PM2.5 ) and ozone (O3 ) during pregnancy is associated with birth defects among women living throughout North Carolina., Methods: Information on maternal and infant characteristics was obtained from North Carolina birth certificates and health service data (2003-2005) and linked with information on birth defects from the North Carolina Birth Defects Monitoring Program. The 24-hr PM2.5 and O3 concentrations were estimated using a hierarchical Bayesian model of air pollution generated by combining modeled air pollution predictions from the U.S. Environmental Protection Agency's Community Multi-Scale Air Quality model with air monitor data from the Environmental Protection Agency's Air Quality System. Maternal residence was geocoded and assigned pollutant concentrations averaged over weeks 3 to 8 of gestation. Binomial regression was performed and adjusted for potential confounders., Results: No association was observed between either PM2.5 or O3 concentrations and most birth defects. Positive effect estimates were observed between air pollution and microtia/anotia and lower limb deficiency defects, but the 95% confidence intervals were wide and included the null., Conclusion: Overall, this study suggested a possible relationship between air pollution concentration during early pregnancy and certain birth defects (e.g., microtia/anotia, lower limb deficiency defects), although this study did not have the power to detect such an association. The risk for most birth defects does not appear to be affected by ambient air pollution., (Copyright © 2013 Wiley Periodicals, Inc.)

Background: Information on travel distance and time to care for children with birth defects is lacking. We examined factors associated with travel distance and time to cleft care among children with orofacial clefts., Methods: In 2006, a mail/phone survey was administered in English and Spanish to all resident mothers of children with orofacial clefts born 2001 to 2004 and identified by the North Carolina birth defects registry. We analyzed one-way travel distance and time and the extent to which taking a child to care was a problem. We used multivariable logistic regression to examine the association between selected sociodemographic factors and travel distance (≤60 miles and >60 miles) and time (≤60 min and >60 min) to cleft care., Results: Of 475 eligible participants, 51.6% (n = 245) responded. Of the respondents, 97.1% (n = 238) were the child's biological mother. Approximately 83% (n = 204) of respondents were non-Hispanic White; 33.3% (n = 81) were college educated; and 50.0% (n = 115) had private health insurance. One-way mean and median travel distances were 80 and 50 miles, respectively (range, 0-1058 miles). One-way mean and median travel times were 92 and 60 min, respectively (range, 5 min to 8 hr). After adjusting for selected sociodemographics, travel distance varied significantly by maternal education, child's age, and cleft type. Travel time varied significantly by child's age. Approximately 67% (n = 162) reported taking their child to receive care was not a problem., Conclusion: Approximately 48% of respondents traveled > 1 hr to receive cleft care. Increasing access to care may be important for improving health outcomes among this population., (Copyright © 2013 Wiley Periodicals, Inc.)

Clubfoot is a common structural malformation, occurring in approximately 1/1,000 live births. Previous studies of sociodemographic and pregnancy-related risk factors have been inconsistent, with the exception of the strong male preponderance and association with primiparity. Hypotheses for clubfoot pathogenesis include fetal constraint, Mendelian-inheritance, and vascular disruption, but its etiology remains elusive. We conducted a population-based case-control study of clubfoot in North Carolina, Massachusetts, and New York from 2007 to 2011. Mothers of 677 clubfoot cases and 2,037 non-malformed controls were interviewed within 1 year of delivery about socio-demographic and reproductive factors. Cases and controls were compared for child's sex, maternal age, education, cohabitation status, race/ethnicity, state, gravidity, parity, body mass index (BMI), and these pregnancy-related conditions: oligohydramnios, breech delivery, bicornuate uterus, plural birth, early amniocentesis (<16 weeks), chorionic villous sampling (CVS), and plural gestation with fetal loss. Odds ratios (ORs) and 95% confidence intervals (CIs) were adjusted for state. Cases were more likely to be male (OR: 2.7; 2.2-3.3) and born to primiparous mothers (1.4; 1.2-1.7) and mothers with BMI ≥30 kg/m(2) (1.4; 1.1-1.8). These associations were greatest in isolated and bilateral cases. ORs for the pregnancy-related conditions ranged from 1.3 (breech delivery) to 5.6 (early amniocentesis). Positive associations with high BMI were confined to cases with a marker of fetal constraint (oligohydramnios, breech delivery, bicornuate uterus, plural birth), inheritance (family history in 1st degree relative), or vascular disruption (early amniocentesis, CVS, plural gestation with fetal loss). Pathogenetic factors associated with obesity may be in the causal pathway for clubfoot., (Copyright © 2013 Wiley Periodicals, Inc.)

Objective: To estimate the birth prevalence and 7-year case-fatality rate of peripartum cardiomyopathy for a statewide population by applying the National Institutes of Health Workshop on Peripartum Cardiomyopathy definition, including echocardiographic criteria for left ventricular dysfunction., Methods: This was an epidemiologic study of residents of North Carolina experiencing an obstetric delivery or a pregnancy-related death before delivery in 2002 through 2003 including 235,599 live births. Potential cases were identified from International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM), pregnancy and cardiovascular codes followed by medical record review, and from the state pregnancy-related mortality file. Only women meeting the established definition including echocardiographic criteria for left ventricular dysfunction and women with diagnoses at autopsy were included. The state death file and the U.S. Social Security Death Index were searched for the years 2002 through 2010 for all cases., Results: A total of 740 potential cases from 70 hospitals were identified from discharge ICD-9-CM codes. The medical records for 698 (94.3%) were located and reviewed. Seventy-eight met inclusion criteria. An additional seven women had diagnoses only at autopsy. The birth prevalence was 1 case for every 2,772 live births or 3.61 cases per 10,000 live births (95% confidence interval 2.88-4.46). The 7-year case-fatality rate was 16.5% (95% confidence interval 10--25.9%). Black non-Hispanic women experienced an almost fourfold increased prevalence and fatality compared with white women. Women older than age 35 years had the highest prevalence., Conclusions: The racial disparity in both birth prevalence and case-fatality is striking; one in six women died within 7 years., Level of Evidence: II.

Background: National data on health care use among children with special needs are limited and do not address children with spina bifida (SB). One recent study examined health care costs during 2003 among privately insured individuals with SB. Our objective was to compare health care use and expenditures among publicly insured children with SB to children without a major birth defect and among children with SB with and without hydrocephalus., Methods: Data from the North Carolina Birth Defects Monitoring Program and Medicaid were linked to identify continuously enrolled children with SB (case children) and children without a major birth defect (control children) born from 1995 to 2002. Medicaid expenditures per child for medical, inpatient, outpatient, dental, well-child care, developmental/behavioral services, and home health for those aged 0 to 4 years old were calculated for case and control children and for case children with and without hydrocephalus., Results: Of 373 case children who survived infancy, 205 (55%) were enrolled in Medicaid. Expenditures were assessed for 144 case and 5674 control children aged 0 to 4 years old continuously enrolled in Medicaid. During infancy, mean expenditure was $33,135 per child with SB and $3900 per unaffected child. The biggest relative expenditures were for developmental/behavioral services (82 times higher for case than control child [$1401 vs. $17]) and home health services (20 times higher [$821 vs. $41]). Average expenditure for an infant with SB and hydrocephalus was 2.6 times higher than an infant with SB without hydrocephalus ($40,502 vs. $15,699)., Conclusions: Expenditure comparisons by SB subtype are important for targeting health care resources., (Copyright © 2011 Wiley Periodicals, Inc.)

Objective: To examine the timeliness of primary cleft surgery, mean age at which surgery occurred, and factors associated with timely cleft surgery among children with orofacial clefts (OFCs)., Design: Retrospective study of children with OFC using North Carolina vital statistics, birth defects registry, and Medicaid files., Participants/patients: Medicaid-enrolled North Carolina resident children with OFC born from 1995 to 2002., Main Outcome Measures: Proportion of children who underwent primary cleft surgery within 18 months of life, mean age when surgery occurred, and factors associated with timely surgery., Results: 406 children with OFC were continuously enrolled in Medicaid during the first 2 years of life. Overall, 78.1% of children had surgery within 18 months. About 90% of children with cleft lip (CL), 58.0% of children with cleft palate (CP), and 89.6% of children with cleft lip and palate (CLP) received timely cleft surgery; the mean age at which surgery occurred was 5 months. Children whose mothers received maternity care coordination, received prenatal care at a local health department, or lived in the southeastern or northeastern region of the state were more likely to receive timely cleft surgery., Conclusion: Most children with OFC in North Carolina born during this time period received primary cleft surgery within 18 months of life, but this varied by maternal demographics and other factors.

Objective: North Carolina has several programs that identify high-risk women and children for needed services, including the Child Service Coordination Program (CSCP). This study determines CSCP referral rates among infants with orofacial clefts (OFCs) and predictors of CSCP referral. We hypothesized receiving Medicaid and maternity care coordination (MCC) services increases the likelihood of CSCP referral., Design and Setting: For births between 1999 and 2002, data were matched from North Carolina Vital Statistics, Health Services Information System (MCC and CSCP data), and North Carolina Birth Defects Monitoring Program. Multivariate analysis was used to determine crude and adjusted odds ratios for sociodemographic variables to predict CSCP referral., Participants: A total of 644 mothers of live-born infants with OFCs in North Carolina were identified., Results: About 45% of infants with OFCs were referred to the CSCP. Infants of mothers who were at least 30 years of age and mothers who had more than a high school education were significantly less likely to be referred to the CSCP. Compared with infants with OFCs whose mothers did not receive Medicaid, mothers who received Medicaid were 1.9 times more likely to be referred to the CSCP, and mothers who received Medicaid and MCC services were 2.3 times more likely., Conclusions: Receipt of Medicaid and MCC services and receipt of Medicaid alone were positively associated with CSCP referral. Future studies should examine the effects of the duration of MCC services and factors related to the timeliness of CSCP referral.

Purpose: African-American women have a 2- to 4-fold increased risk of pregnancy-related death compared with Caucasian women. We conducted this study to determine if differences in a combination of socioeconomic and medical risk factors may explain this racial disparity in pregnancy-related death., Methods: Pregnancy-related deaths of African-American (N=60) and Caucasian (N=47) women were identified from review of pregnancy-associated deaths (N=400) ascertained through cause of death on death certificates, electronic linkage of birth and death files, and review of the hospital discharge database for the State of North Carolina, during the period between 1992 and 1998. Controls (N=3404) were randomly selected from all live births for the same 7-year period. Logistic regression was used to model the association between race and pregnancy-related death., Results: The unadjusted odds ratio (OR) for pregnancy-related death for African-Americans compared with Caucasians was 3.07 (95% confidence interval [CI], 2.08, 4.54). After controlling for gestational age at delivery, maternal age, income, hypertension, and receipt of prenatal care, African-American race remained a significant predictor variable (OR 2.65 [95% CI 1.73, 4.07])., Conclusions: Our analysis confirms that there is a strong association between race and pregnancy-related death, even after adjusting for potential predictors and confounders.

The preterm delivery rate in North Carolina is consistently higher than the national average. However, recent reports suggest that singleton preterm delivery rates for non-Hispanic Whites are increasing while those for non-Hispanic African Americans are decreasing. To study this pattern further, the authors examined data on singleton non-Hispanic White and non-Hispanic African-American births in 1989 and 1999 by using North Carolina vital statistics data. They found that the frequency of preterm delivery rose 1.1% (8.5% to 9.6%) among non-Hispanic Whites but declined 1.4% (17.9% to 16.5%) among non-Hispanic African Americans over the same time period. For both subgroups, a bimodal distribution of birth weights was apparent among preterm births at 28-31 weeks of gestation. The second peak with its cluster of normal-weight infants was more prominent among non-Hispanic African Americans in 1989 than in 1999. To reduce the potential for bias due to misclassification of infant gestational age, frequencies of preterm delivery of infants who weighed less than 2,500 g were calculated. Unlike the original analysis, this calculation showed that preterm delivery increased for both subgroups. A number of non-Hispanic African-American births classified as preterm were apparently term births mistakenly assigned short gestational ages. Such misclassification was more frequent in 1989 than in 1999, inflating 1989 preterm delivery rates.

Previous studies have documented a decline in neural tube defects (NTDs) in the United States after the addition of folic acid to enriched grain products and other folic acid initiatives. The decrease generally has been greater for spina bifida than for other NTDs. However, the extent to which the decline varies by maternal sociodemographic characteristics has not been examined. In this study data from the North Carolina Birth Defects Monitoring Program, a statewide, population-based birth defect surveillance program, were used to assess the impact that folic acid public health initiatives have had on spina bifida rates among various sociodemographic subpopulations in North Carolina. This report covers data from 1995 through 1999. The overall prevalence of spina bifida decreased by 27.2% during 1995-1996 and 1998-1999 (p = 0.014). The magnitude of the decline varied considerably by sociodemographic characteristics of the mother. The decline was greatest among mothers who were aged > or = 30 years (prevalence ratio [PR] = 0.53), who had more than a high school education (PR = 0.57), whose prenatal care was not paid by Medicaid (PR = 0.67), and who were non-Hispanic white (PR = 0.72). Geographically the decrease in the western and Piedmont regions of the state was almost threefold that occurring in the eastern region. The decline in spina bifida after fortification varied considerably by sociodemographic subpopulations. More effort is needed to target folic acid education programs at disadvantaged populations.