Population-based Birth Defects Registry Research Articles

Direct potable reuse and birth defects prevalence in Texas: An augmented synthetic control method analysis of data from a population-based birth defects registry.

Direct potable reuse (DPR) involves adding purified wastewater that has not passed through an environmental buffer into a water distribution system. DPR may help address water shortages and is approved or is under consideration as a source of drinking water for several water-stressed population centers in the United States, however, there are no studies of health outcomes in populations who receive DPR drinking water. Our objective was to determine whether the introduction of DPR for certain public water systems in Texas was associated with changes in birth defect prevalence. We obtained data on maternal characteristics for all live births and birth defects cases regardless of pregnancy outcome in Texas from 2003 to 2017 from the Texas Birth Defects Registry and birth and fetal death records. The ridge augmented synthetic control method was used to model changes in birth defect prevalence (per 10,000 live births) following the adoption of DPR by four Texas counties in mid-2013, with county-level data on maternal age, percent women without a high school diploma, percent who identified as Hispanic/Latina or non-Hispanic/Latina Black, and rural-urban continuum code as covariates. There were nonstatistically significant increases in prevalence of all birth defects collectively (average treatment effect in the treated = 53.6) and congenital heart disease (average treatment effect in the treated = 287.3) since June 2013. The estimated prevalence of neural tube defects was unchanged. We estimated nonstatistically significant increases in birth defect prevalence following the implementation of DPR in four West Texas counties. Further research is warranted to inform water policy decisions.

Prevalence and descriptive epidemiology of choanal atresia and stenosis in Texas, 1999-2018.

Choanal atresia and stenosis are common causes of congenital nasal obstruction, but their epidemiology is poorly understood. Compared to bilateral choanal atresia/stenosis, unilateral choanal atresia/stenosis is generally diagnosed later and might be under-ascertained in birth defect registries. Data from the population-based Texas Birth Defects Registry and Texas vital records, 1999-2018, were used to assess the prevalence of choanal atresia/stenosis. Poisson regression models were used to evaluate associations with infant and maternal characteristics in two analytic groups: isolated choanal atresia/stenosis (n = 286) and isolated, bilateral choanal atresia/stenosis (n = 105). The overall prevalence of choanal atresia/stenosis was 0.92/10,000, and the prevalence of isolated choanal atresia/stenosis was 0.37/10,000 livebirths. Variables associated with choanal atresia/stenosis in one or both analytic groups included infant sex, pregnancy plurality, maternal race/ethnicity, maternal age, and maternal residence on the Texas-Mexico border. In general, adjusted prevalence ratios estimated from the two analytic groups were in the same direction but tended to be stronger in the analyses restricted to isolated, bilateral defects. Epidemiologic studies of isolated choanal atresia/stenosis should consider focusing on cases with bilateral defects, and prioritizing analyses of environmental, social, and structural factors that could account for the association with maternal residence on the Texas-Mexico border.

Prevalence of congenital anomalies according to maternal race and ethnicity, Texas, 1999-2018.

Few studies of congenital anomalies provide prevalence estimates stratified by maternal race/ethnicity. We sought to determine whether the prevalence of a broad spectrum of anomalies varies among offspring of women from different race/ethnic groups. We obtained information on cases with anomalies from the population-based Texas Birth Defects Registry, and denominator data on livebirths among Texas residents during 1999-2018 from the Texas Center for Health Statistics. We estimated the prevalence ratio (PR) and 95% confidence interval (CI) of N = 145 anomalies among offspring of Hispanic and non-Hispanic Black relative to non-Hispanic White women using Poisson regression, adjusting for maternal age, education, body mass index, and previous livebirths. We performed a two-stage analysis with a Bonferroni-adjusted p < 1.7 × 10-4 in the initial screening phase to identify anomalies with statistically significant variation. There were 7,698,768 livebirths and 1,187,385 anomalies diagnosed in 368,393 cases. The prevalence of any monitored congenital anomaly was similar among offspring of non-Hispanic White (referent), non-Hispanic Black (PR 0.98, CI 0.96-1.00), and Hispanic (PR 0.95, CI 0.93-0.96) women. We observed statistically significant racial/ethnic variation for 42 anomalies. Marked differences were observed when comparing offspring of non-Hispanic Black to non-Hispanic White women with respect to polydactyly (PR 4.38, CI 4.07-4.72), pyloric stenosis (PR 0.34, CI 0.29-0.40), and aortic valve atresia/stenosis (PR 0.51, CI 0.36-0.72). Birth prevalence of many major congenital anomalies varies by maternal race and ethnicity. While the reasons for these differences are likely multifactorial, a thorough understanding of racial and ethnic disparities is useful to stimulate etiologic research.

Abstract 13983: Reproductive Health Counseling and Experiences Among Females With Congenital Heart Defects: Results From the Congenital Heart Survey to Recognize Outcomes, Needs, and Well-Being

Introduction: The American Heart Association (AHA) recommends clinicians discuss reproductive health with women with congenital heart defects (CHD) beginning in adolescence due to their unique pregnancy and contraceptive needs. Therefore, we assessed reproductive health counseling and experiences among women with CHD, and differences by CHD severity. Methods: Women with CHD ages 19 to 38 years, identified in active, population-based birth defects registries from Arkansas, Arizona, and Atlanta, GA, completed the Congenital Heart Survey To Recognize Outcomes, Needs, and well-beinG (CH STRONG) from 2016 to 2019, including questions about reproductive health counseling, concerns and experiences. Prevalence estimates standardized to all CH STRONG-eligible women and adjusted prevalence ratios (aPR), calculated with multivariable Poisson regression, assessed differences by CHD severity. Results: Of 765 female respondents, 40.7% were 19-24 years, 66.7% were non-Hispanic white, and 67.7% had &gt; high school education. Overall, 21.3% received CHD-specific contraceptive counseling, 28.3% pregnancy counseling, and 12.8% advice to avoid pregnancy (Fig). Women with severe, compared to non-severe CHD, were more likely to receive clinician counseling about safe contraception (aPR=3.0, 95% confidence interval [CI]: 2.2-4.0), pregnancy (aPR=3.5, 95% CI: 2.7-4.6), and advice to avoid pregnancy (aPR=4.3, 95% CI: 2.9-6.5), and they were more likely to be concerned about their ability to have children (aPR=1.4, 95% CI: 1.1-1.8) and delay/avoid pregnancy (aPR=2.2, 95% CI: 1.5-3.2). No differences were seen in ever being pregnant (aPR=0.83, 95% CI: 0.6-1.1). Conclusions: Results suggest most women with CHD are not receiving AHA-recommended reproductive health counseling. Almost one in three women with severe CHD received clinician advice to avoid pregnancy, although AHA guidelines state pregnancy is contraindicated for few women with CHD.

An epidemiologic study of penoscrotal transposition by maternal characteristics using data from the Texas birth defects registry.

Penoscrotal transposition (PST) is an uncommon urogenital malformation in which the penis is mal-positioned to be inferior to the scrotum. The purpose of this study was to explore PST risk by maternal characteristics and to describe co-occurring congenital abnormalities in the Texas Birth Defects Registry (TBDR). We conducted a population-based descriptive study examining occurrence of PST in the TBDR between 1999 and 2019. The primary outcome variable was PST diagnosis during infancy. Descriptive variables included maternal age, education, and race/ethnicity. Prevalence ratios (PRs) were calculated within each maternal variable category using Poisson regression. Counts and percentages of cases with select co-occurring congenital abnormalities were also calculated. Overall, 251 infants had PST, providing a prevalence of 0.61/10,000 live male births (95% CI: 0.53-0.68). PST prevalence was significantly lower among infants of mothers who had lower educational attainment (<high school vs. >high school), who were younger (<25 vs. 25-34), and who were Hispanic (vs. non-Hispanic White) and was significantly higher among older mothers (35+ vs. 25-39). Hypospadias was the most common co-occurring genitourinary anomaly, affecting close to 70% of cases. To our knowledge, this is the first investigation exploring the prevalence of PST in a population-based birth defects registry. Our findings help to understand the risk for PST among select maternal demographic characteristics and may assist in generating hypotheses about the underlying etiology of this condition for future work.

Prescriptions for insulin and insulin analogues in children with and without major congenital anomalies: a data linkage cohort study across six European regions

Are children with major congenital anomalies more likely to develop diabetes requiring insulin therapy, as indicated by prescriptions for insulin, than children without congenital anomalies? The aim of this study is to evaluate prescription rates of insulin/insulin analogues in children aged 0–9 years with and without major congenital anomalies. A EUROlinkCAT data linkage cohort study, involving six population-based congenital anomaly registries in five countries. Data on children with major congenital anomalies (60,662) and children without congenital anomalies (1,722,912), the reference group, were linked to prescription records. Birth cohort and gestational age were examined. The mean follow-up for all children was 6.2 years. In children with congenital anomalies aged 0–3 years, 0.04 per 100 child-years (95% CIs 0.01–0.07) had > 1 prescription for insulin/insulin analogues compared with 0.03 (95% CIs 0.01–0.06) in reference children, increasing ten-fold by age 8–9 years. The risk of > 1 prescription for insulin/insulin analogues aged 0–9 years in children with non-chromosomal anomalies (RR 0.92, 95% CI 0.84–1.00) was similar to that of reference children. However, children with chromosomal anomalies (RR 2.37, 95% CI 1.91–2.96), and specifically children with Down syndrome (RR 3.44, 95% CIs 2.70–4.37), Down syndrome with congenital heart defects (RR 3.86, 95% CIs 2.88–5.16) and Down syndrome without congenital heart defects (RR 2.78, 95% CIs 1.82–4.27), had a significantly increased risk of > 1 prescription for insulin/insulin analogues aged 0–9 years compared to reference children. Female children had a reduced risk of > 1 prescription aged 0–9 years compared with male children (RR 0.76, 95% CI 0.64–0.90 for children with congenital anomalies and RR 0.90, 95% CI 0.87–0.93 for reference children). Children without congenital anomalies born preterm (< 37 weeks) were more likely to have > 1 insulin/insulin analogue prescription compared to term births (RR 1.28, 95% CIs 1.20–1.36).Conclusion: This is the first population-based study using a standardised methodology across multiple countries. Males, children without congenital anomalies born preterm and those with chromosomal anomalies had an increased risk of being prescribed insulin/insulin analogues. These results will help clinicians to identify which congenital anomalies are associated with an increased risk of developing diabetes requiring insulin therapy and allow them to reassure families of children who have non-chromosomal anomalies that their risk is similar to that of the general population.What is Known:• Children and young adults with Down syndrome have an increased risk of diabetes requiring insulin therapy.• Children born prematurely have an increased risk of developing diabetes requiring insulin therapy.What is New:• Children with non-chromosomal anomalies do not have an increased risk of developing diabetes requiring insulin therapy compared to children without congenital anomalies.• Female children, with or without major congenital anomalies, are less likely to develop diabetes requiring insulin therapy before the age of 10 compared to male children.

Prevalence of vascular disruption anomalies and association with young maternal age: A EUROCAT study to compare the United Kingdom with other European countries.

Younger mothers are at a greater risk of having a pregnancy with gastroschisis and the risk is higher in the United Kingdom than other European countries. Gastroschisis is thought to be a vascular disruption anomaly and the aim of this study was to analyze the prevalence of other possible vascular disruption anomalies to determine whether both the younger maternal age and the UK associations also occur with these anomalies. All pregnancies with anomalies considered potentially due to vascular disruption from January 1, 2005 to December 31, 2017 from 26 European population-based congenital anomaly registries who were members of EUROCAT were analyzed. Multilevel models were used to allow for differences between registries when analyzing associations with maternal age, year of birth and whether the registry was in the United Kingdom. There were 5,220 cases with potential vascular disruption anomalies, excluding chromosomal and genetic conditions, with a prevalence of 8.85 per 10,000 births in the United Kingdom and 5.44 in the other European countries. The prevalence per 10,000 births of gastroschisis (4.45 vs. 1.56) and congenital constriction bands (0.83 vs. 0.42) was significantly higher in the United Kingdom, even after adjusting for maternal age. However, transverse limb reduction defects had a similar prevalence (2.16 vs. 2.14 per 10,000). The expected increased prevalence in younger mothers was observed for vascular disruption anomalies overall and for the individual anomalies: gastroschisis and congenital constriction bands. Vascular disruption anomalies that had an increased risk for younger mothers (such as gastroschisis) had a higher maternal age standardized prevalence in the United Kingdom, while vascular disruption anomalies with weaker associations with younger mothers (such as transverse limb reduction defects) did not have an increased prevalence in the United Kingdom, which may indicate a different etiology for these anomalies.

Interpregnancy interval and prevalence of selected birth defects: A multistate study.

Both short and long interpregnancy intervals (IPIs) have been associated with adverse birth outcomes. We undertook a multistate study to describe the prevalence of selected birth defects by IPI. We obtained data from nine population-based state birth defects registries for singleton live births in 2000-2009 among mothers with a previous live birth identified through birth certificates. IPI was calculated as the difference between prior birthdate and start of the current pregnancy (conception date). We estimated prevalence of selected defects per 10,000 live births and prevalence ratios (PRs) with 95% confidence intervals (CIs) overall and stratified by maternal age at previous birth and race/ethnicity. Primary analyses focused on short IPI < 6 months and long IPI ≥ 60 months compared to 18-23 months (referent). Sensitivity analyses limited to active-surveillance states and those with<10% missing IPI. Among 5,147,962 eligible births, 6.3% had short IPI while 19.8% had long IPI. Compared to referent, prevalence with short IPI was elevated for gastroschisis (3.7, CI: 3.0-4.5 vs. 2.0, CI: 1.6-2.4) and with both short and long IPI for tetralogy of Fallot (short: 3.4, 2.8-4.2 long: 3.8, 3.4-4.3 vs. 2.7, 2.3-3.2) and cleft lip ± palate (short: 9.9, 8.8-11.2 long: 9.2, 8.5-9.8 vs. 8.4, 7.6-9.2). Stratified analyses identified additional associations, including elevated prevalence of anencephaly with short IPI in younger mothers and limb defects with long IPI in those ages 25-34 at prior birth. Sensitivity analyses showed similar results. In this population-based study, we observed increased prevalence of several birth defects with short and long IPI.

Epidemiology of Pierre-Robin sequence in Europe: A population-based EUROCAT study.

Pierre Robin sequence (PRS) is a rare congenital anomaly. Respiratory disorders and feeding difficulties represent the main burden. The aim of this study was to investigate the epidemiology of PRS using a cohort of cases from EUROCAT, the European network of population-based registries of congenital anomalies. We analysed cases of PRS born in the period 1998-2017 collected by 29 population-based congenital anomaly registries in 17 different countries. We calculated prevalence estimates, prenatal detection rate, survival up to 1week, and proportions of associated anomalies. The effect of maternal age was tested using a Poisson regression model. Out of 11669155 surveyed births, a total of 1294 cases of PRS were identified. The estimate of the overall prevalence was 12.0 per 100000 births (95% CI 9.9, 14.5). There was a total of 882 (68.2%) isolated cases, and the prevalence was 7.8 per 100000 births (95% CI 6.7, 9.2). A total of 250 cases (19.3%) were associated with other structural congenital anomalies, 77 cases (6.0%) were associated with chromosomal anomalies and 77 (6.0%) with genetic syndromes. The prenatal detection rate in isolated cases was 12.0% (95% CI 9.8, 14.5) and increased to 16.0% (95% CI 12.7, 19.7) in the sub-period 2008-2017. The prevalence rate ratio of non-chromosomal cases with maternal age ≥35 was higher than in cases with maternal age <25 for total (PRR 1.26, 95% CI 1.05, 1.51) and isolated cases (PRR 1.33, 95% CI 1.00, 1.64). Survival of chromosomal cases (94.2%) and multiple anomaly cases (95.3%) were lower than survival of isolated cases (99.4%). This epidemiological study using a large series of cases of PRS provides insights into the epidemiological profile of PRS in Europe. We observed an association with higher maternal age, but further investigations are needed to test potential risk factors for PRS.

Abstract PR03: Sex ratio disparities and the risk of childhood cancer: Evaluating the mediating effect of birth defects among 15,000 childhood cancer cases

Abstract Background: There is a persistent yet unexplained disparity in the sex ratio among childhood cancer cases, whereby males are more likely to develop several cancers. These patterns are also seen for most birth defects, which are strongly associated with the risk of childhood cancer. We conducted a mediation analysis to estimate whether birth defect status mediates the association between sex and childhood cancer risk. Methods: We linked data from birth, birth defects, and cancer registries to obtain a population-based birth cohort including births from 1992-2013 in Arkansas, Michigan, North Carolina, and Texas. We obtained birth defects diagnoses, including chromosomal and nonchromosomal defects, from statewide, population-based birth defects registries. We focused on “major” defects as defined by the National Birth Defects Prevention Network and the National Birth Defects Prevention Study. Cancer diagnoses that occurred prior to age 18 years were obtained from state cancer registries. We obtained data on child’s sex, birth weight, gestational age, maternal race/ethnicity, maternal age, and plurality from birth records. We conducted counterfactual mediation analysis to estimate the direct and indirect effects of sex on risk of childhood cancer, modeling sex as the exposure, birth defect status as the mediator, and cancer type as the outcome. State, maternal race/ethnicity (white, black, other), maternal age (continuous), and plurality (singleton vs. multiple) were considered potential mediator-outcome confounders. Due to lower success rates of linkage to birth records among adolescent cancer cases, we conducted a sensitivity analysis limiting to cancers diagnosed at age &amp;lt; 5 years. Results: Our dataset included 10,181,074 children (5,208,379 males; 4,972,695 females), including 15,110 with cancer diagnoses (8044 males; 7066 females), 539,567 children with birth defects diagnoses (320,666 males; 218,901 females), and 2,124 co-occurring cases (children with both cancer and one or more birth defect diagnosis: 1,186 males; 938 females). We observed mediation of the association between sex and childhood cancer overall by birth defect status (proportion mediated [PM]: 38%). In analyses of specific cancer types, we observed variation of the estimated proportion mediated among several cancers, including hepatoblastoma (PM: 33%), neuroblastoma (PM: 35%), non-Hodgkin lymphoma (PM: 6%), and soft tissue sarcomas (PM: 25%). In analysis of children age &amp;lt; 5 years at cancer diagnosis, we observed similar results. Conclusions: Our results suggest that birth defects mediate a significant proportion of the overall relationship between sex and childhood cancer. While approximately 60% of the male excess in childhood cancer cases remains unexplained, these findings add to our understanding of the causal pathway of male sex as a risk factor for childhood cancer. Additional studies are under way to characterize the biology underlying these observations. This abstract is also being presented as Poster A66. Citation Format: Erin L. Marcotte, Jeremy M. Schraw, Tania A. Desrosiers, Wendy N. Nembhard, Peter H. Langlois, Mark A. Canfield, Robert E. Meyer, Sharon E. Plon, Philip Lupo. Sex ratio disparities and the risk of childhood cancer: Evaluating the mediating effect of birth defects among 15,000 childhood cancer cases [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr PR03.

Association Between Birth Defects and Cancer Risk Among Children and Adolescents in a Population-Based Assessment of 10 Million Live Births

Birth defects affect approximately 1 in 33 children. Some birth defects are known to be strongly associated with childhood cancer (eg, trisomy 21 and acute leukemia). However, comprehensive evaluations of childhood cancer risk in those with birth defects have been limited in previous studies by insufficient sample sizes. To identify specific birth defect-childhood cancer (BD-CC) associations and characterize cancer risk in children by increasing number of nonchromosomal birth defects. This multistate, population-based registry linkage study pooled statewide data on births, birth defects, and cancer from Texas, Arkansas, Michigan, and North Carolina on 10 181 074 children born from January 1, 1992, to December 31, 2013. Children were followed up to 18 years of age for a diagnosis of cancer. Data were retrieved between September 26, 2016, and September 21, 2017, and data analysis was performed from September 2, 2017, to March 21, 2019. Birth defects diagnoses (chromosomal anomalies and nonchromosomal birth defects) recorded by statewide, population-based birth defects registries. Cancer diagnosis before age 18 years, as recorded in state cancer registries. Cox regression models were used to generate hazard ratios (HRs) and 95% CIs to evaluate BD-CC associations and the association between number of nonchromosomal defects and cancer risk. Compared with children without any birth defects, children with chromosomal anomalies were 11.6 (95% CI, 10.4-12.9) times more likely to be diagnosed with cancer, whereas children with nonchromosomal birth defects were 2.5 (95% CI, 2.4-2.6) times more likely to be diagnosed with cancer before 18 years of age. An increasing number of nonchromosomal birth defects was associated with a corresponding increase in the risk of cancer. Children with 4 or more major birth defects were 5.9 (95% CI, 5.3-6.4) times more likely to be diagnosed with cancer compared with those without a birth defect. In the analysis of 72 specific BD-CC patterns, 40 HRs were statistically significant (adjusted P < .05) after accounting for multiple comparisons. Cancers most frequently associated with nonchromosomal defects were hepatoblastoma and neuroblastoma. Several significant and novel associations were observed between specific birth defects and cancers. Among children with nonchromosomal birth defects, the number of major birth defects diagnosed was significantly and directly associated with cancer risk. These findings could inform clinical treatment for children with birth defects and may elucidate mechanisms that lead to these complex outcomes.

Maternal occupational exposure and oral clefts in offspring

BackgroundPrevious studies suggest that periconceptional maternal occupational exposure to solvents and pesticides increase the risk of oral clefts in the offspring. Less is known about the effect of occupational exposure to metals, dust, and gases and fumes on development of oral clefts.MethodsThis case-malformed control study used data from a population-based birth defects registry (Eurocat) of children and foetuses born in the Northern Netherlands between 1997 and 2013. Cases were defined as non-syndromic oral clefts. The first control group had chromosomal/monogenic defects, and the second control group was defined as non-chromosomal/non-monogenic malformed controls. Maternal occupational exposure was estimated through linkage of mothers’ occupation with a community-based Job Exposure Matrix (JEM). Multivariate logistic regression was used to estimate the effect of occupational exposures. Odds ratios were adjusted (aORs) for relevant confounders.ResultsA total of 387 cases, 1135 chromosomal and 4352 non-chromosomal malformed controls were included in this study. Prevalence of maternal occupational exposures to all agents was 43.9% and 41.0%/37.7% among cases and controls, respectively. Oral clefts had significantly increased ORs of maternal occupational exposure to pesticides (aOR = 1.7, 95% confidence interval [CI] 1.0–3.1) and dust (aOR = 1.3, 95% CI 1.1–1.6) when using non-chromosomal controls. Subgroup analysis for CL(P) stratified by gender showed a significantly increased risk for male infants exposed to ‘other solvents’ and exposure to mineral dust for female infants.ConclusionOur study showed that maternal occupational exposure to pesticides and dust are risk factors for oral clefts in the offspring. Larger studies are needed to confirm this finding.

Changing trends in the prevalence of anencephaly in Liaoning province of Northeast China from 2006-2015: data from a population-based birth defects registry.

The goal of this study was to assess the prevalence and trends of anencephaly on the basis of a large population-based cases identified by the Liaoning Birth Defects Registry, which included 14 cities over a 10-year period. Anencephaly prevalence, percent change, average changeand the contribution rates of each city were calculated. Statistical analysis was undertaken on the basis of a Poisson regression model. A total of 1600 anencephaly cases were collected during the observational period (4.92/10,000 live births). On average, the prevalence decreased 10.15% each year; this overall time trend was statistically significant (P<0.01). The top three leading cities were Huludao (10.33 per 10,000 live births), Chaoyang (8.56 per 10,000 live births) and Fuxin (6.36 per 10,000 live births). In contrast, Anshan (2.64 per 10,000 live births), Dalian (2.79 per 10,000 live births) and Yingkou (3.46 per 10,000 live births) were the cities with the lowest prevalence. Of note, significantly decreasing trends were observed in half of these cities (n=7). Additionally, Benxi, Yingkou and Dalian were the major cities contributing to over one third of the decreasing trend in Liaoning province. In conclusion, this study provided evidence of the decreasing prevalence of anencephaly from 2006 to 2015 in Liaoning province. In the future, prevention efforts should be strengthened to further reduce the risk of anencephaly in areas with high rates.

Use of hierarchical models to analyze European trends in congenital anomaly prevalence.

Surveillance of congenital anomalies is important to identify potential teratogens. Despite known associations between different anomalies, current surveillance methods examine trends within each subgroup separately. We aimed to evaluate whether hierarchical statistical methods that combine information from several subgroups simultaneously would enhance current surveillance methods using data collected by EUROCAT, a European network of population-based congenital anomaly registries. Ten-year trends (2003 to 2012) in 18 EUROCAT registries over 11 countries were analyzed for the following groups of anomalies: neural tube defects, congenital heart defects, digestive system, and chromosomal anomalies. Hierarchical Poisson regression models that combined related subgroups together according to EUROCAT's hierarchy of subgroup coding were applied. Results from hierarchical models were compared with those from Poisson models that consider each congenital anomaly separately. Hierarchical models gave similar results as those obtained when considering each anomaly subgroup in a separate analysis. Hierarchical models that included only around three subgroups showed poor convergence and were generally found to be over-parameterized. Larger sets of anomaly subgroups were found to be too heterogeneous to group together in this way. There were no substantial differences between independent analyses of each subgroup and hierarchical models when using the EUROCAT anomaly subgroups. Considering each anomaly separately, therefore, remains an appropriate method for the detection of potential changes in prevalence by surveillance systems. Hierarchical models do, however, remain an interesting alternative method of analysis when considering the risks of specific exposures in relation to the prevalence of congenital anomalies, which could be investigated in other studies. Birth Defects Research (Part A) 106:480-10, 2016. © 2016 Wiley Periodicals, Inc.

Prevalence, Correlates, and Outcomes of Omphalocele in the United States, 1995-2005.

To examine the trends in the prevalence, epidemiologic correlates, and 1-year survival of omphalocele using 1995-2005 data from the National Birth Defects Prevention Network in the United States. We examined 2,308 cases of omphalocele over 11 years from 12 state population-based birth defects registries. We used Poisson regression to estimate prevalence and risk factors for omphalocele and Kaplan-Meier survival curves and Cox proportional hazards regression to estimate survival patterns and hazard ratios, respectively, to examine isolated compared with nonisolated cases. Birth prevalence of omphalocele was 1.92 per 10,000 live births with no consistent trend over time. Neonates with omphalocele were more likely to be male (prevalence ratio 1.22, 95% confidence interval [CI] 1.12-1.34), born to mothers 35 years of age or older (prevalence ratio 1.77, 95% CI 1.54-2.04) and younger than 20 years (prevalence ratio 1.34, 95% CI 1.14-1.56), and of multiple births (prevalence ratio 2.22, 95% CI 1.85-2.66). The highest proportion of neonates with omphalocele had congenital heart defects (32%). The infant mortality rate was 28.7%, with 75% of those occurring in the first 28 days. The best survival was for isolated cases and the worst for neonates with chromosomal defects (hazard ratio 7.75, 95% CI 5.40-11.10) and low-birth-weight neonates (hazard ratio 7.51, 95% CI 5.86-9.63). Prevalence of omphalocele has remained constant from 1995 to 2005. Maternal age (younger than 20 years and 35 years or older), multiple gestation, and male sex are important correlates of omphalocele, whereas co-occurrence with chromosomal defects and very low birth weight are consistent determinants of 1-year survival among these neonates. II.

Major congenital anomalies in babies born with Down syndrome: a EUROCAT population-based registry study.

Previous studies have shown that over 40% of babies with Down syndrome have a major cardiac anomaly and are more likely to have other major congenital anomalies. Since 2000, many countries in Europe have introduced national antenatal screening programs for Down syndrome. This study aimed to determine if the introduction of these screening programs and the subsequent termination of prenatally detected pregnancies were associated with any decline in the prevalence of additional anomalies in babies born with Down syndrome. The study sample consisted of 7,044 live births and fetal deaths with Down syndrome registered in 28 European population-based congenital anomaly registries covering seven million births during 2000-2010. Overall, 43.6% (95% CI: 42.4-44.7%) of births with Down syndrome had a cardiac anomaly and 15.0% (14.2-15.8%) had a non-cardiac anomaly. Female babies with Down syndrome were significantly more likely to have a cardiac anomaly compared to male babies (47.6% compared with 40.4%, P < 0.001) and significantly less likely to have a non-cardiac anomaly (12.9% compared with 16.7%, P < 0.001). The prevalence of cardiac and non-cardiac congenital anomalies in babies with Down syndrome has remained constant, suggesting that population screening for Down syndrome and subsequent terminations has not influenced the prevalence of specific congenital anomalies in these babies.

Barriers to care for children with orofacial clefts in North Carolina.

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. 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. 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. 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.

Periconceptional folic acid associated with an increased risk of oral clefts relative to non-folate related malformations in the Northern Netherlands: a population based case-control study

Periconceptional folic acid has been associated with a reduced risk of neural tube defects, but findings on its effect in oral clefts are largely inconclusive. This case-control study assesses the effects of periconceptional folic acid on cleft risk, using complementary data from the Dutch Oral Cleft Registry and a population-based birth defects registry (Eurocat) of children and foetuses born in the Northern Netherlands between 1997 and 2009. Cases were live-born infants with non-syndromic clefts (n = 367) and controls were infants or foetuses with chromosomal/syndromal (n = 924) or non-folate related anomalies (n = 2,021). We analyzed type/timing/duration of supplement use related to traditional cleft categories as well as to their timing (early/late embryonic periods) and underlying embryological processes (fusion/differentiation defects). Consistent supplement use during the aetiologically relevant period (weeks 0-12 postconception) was associated with an increased risk of clefts (adjusted odds ratio 1.72, 95% confidence interval 1.19-2.49), especially of cleft lip/alveolus (3.16, 1.69-5.91). Further analysis systematically showed twofold to threefold increased risks for late differentiation defects-mainly clefts of the lip/alveolus-with no significant associations for early/late fusion defects. Effects were attributable to folic acid and not to other multivitamin components, and inclusion of partial use (not covering the complete aetiologically relevant period) generally weakened associations. In conclusion, this study presents several lines of evidence indicating that periconceptional folic acid in the Northern Netherlands is associated with an increased risk of clefts, in particular of cleft lip/alveolus. This association is strengthened by the specificity, consistency, systematic pattern, and duration of exposure-response relationship of our findings, underlining the need to evaluate public health strategies regarding folic acid and to further investigate potential adverse effects.

External birth defects in Southern Vietnam: a population-based study at the grassroots level of health care in Binh Thuan Province.

BackgroundThere currently exists no data on birth defects from population-based studies in Vietnam. Our study's aim was to assess external birth defect (EBD) prevalence among live newborns in Binh Thuan Province in Vietnam with the help of health workers at all levels of the health system.MethodsA 2-month training session for 452 health professionals (HP) practicing delivery care in 127 Commune Health Stations (CHS) and in 12 provincial or district hospitals (DH) was setup in 2006. After a successful 6-month pilot study, a one-year registry of EBDs was established in 2008. All live newborns were screened for EBDs within 24 hours after birth in all DH obstetric departments and in all CHSs. Trained local HPs collected information by filling out a predesigned form and by photographing the affected newborn. EBDs were coded using the International Classification of Diseases system-10, Clinical Modification. The study was repeated in 2010.ResultsThroughout 2010, out of a total of 13,954 newborns, 84 cases with one or more EBDs were reported, representing an overall prevalence rate of 60.2 per 10,000 live births. The most common groups of EBDs were limbs (27.2/10,000), orofacial clefts (20.1/10,000) and the central nervous system (7.9/10,000).ConclusionsThis first population-based study in Vietnam, which required coordination efforts at the local level, provides baseline prevalences of external birth defects. Data on EBDs from this study in southern Vietnam may be useful for setting up a regional population-based registry of birth defects in Vietnam.

Trends in the prevalence, risk and pregnancy outcome of multiple births with congenital anomaly: a registry‐based study in 14 European countries 1984–2007

To assess the public health consequences of the rise in multiple births with respect to congenital anomalies. Descriptive epidemiological analysis of data from population-based congenital anomaly registries. Fourteen European countries. A total of 5.4 million births 1984-2007, of which 3% were multiple births. Cases of congenital anomaly included live births, fetal deaths from 20 weeks of gestation and terminations of pregnancy for fetal anomaly. Prevalence rates per 10,000 births and relative risk of congenital anomaly in multiple versus singleton births (1984-2007); proportion prenatally diagnosed, proportion by pregnancy outcome (2000-07). Proportion of pairs where both co-twins were cases. Prevalence of congenital anomalies from multiple births increased from 5.9 (1984-87) to 10.7 per 10,000 births (2004-07). Relative risk of nonchromosomal anomaly in multiple births was 1.35 (95% CI 1.31-1.39), increasing over time, and of chromosomal anomalies was 0.72 (95% CI 0.65-0.80), decreasing over time. In 11.4% of affected twin pairs both babies had congenital anomalies (2000-07). The prenatal diagnosis rate was similar for multiple and singleton pregnancies. Cases from multiple pregnancies were less likely to be terminations of pregnancy for fetal anomaly, odds ratio 0.41 (95% CI 0.35-0.48) and more likely to be stillbirths and neonatal deaths. The increase in babies who are both from a multiple pregnancy and affected by a congenital anomaly has implications for prenatal and postnatal service provision. The contribution of assisted reproductive technologies to the increase in risk needs further research. The deficit of chromosomal anomalies among multiple births has relevance for prenatal risk counselling.