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.

Evaluating the proportion of isolated cases among a spectrum of birth defects in a population-based registry.

INTRODUCTION: Because the etiology and outcomes of birth defects may differ by the presence vs. absence of co-occurring anomalies, epidemiologic studies often attempt to classify cases into isolated versus non-isolated groupings. This report describes a computer algorithm for such classification and presents results using data from the Texas Birth Defects Registry (TBDR). METHODS: Each of the 1,041 birth defects coded by the TBDR was classified as chromosomal, syndromic, minor, or "needs review" by a group of three clinical geneticists. A SAS program applied those classifications to each birth defect in a case (child/fetus), and then hierarchically combined them to obtain one summary classification for each case, adding isolated and multiple defect categories. The program was applied to 136,121 cases delivered in 2012-2017. RESULTS: Of total cases, 49% were classified by the platform as isolated (having only one major birth defect). This varied widely by birth defect; of those examined, the highest proportion classified as isolated was found in pyloric stenosis (87.6%), whereas several cardiovascular malformations had low proportions, including tricuspid valve atresia/stenosis (2.3%). DISCUSSION: This is one of the first and largest attempts to identify the proportion of isolated cases across a broad spectrum of birth defects, which can inform future epidemiologic and genomic studies of these phenotypes. Our approach is designed for easy modification for use with any birth defects coding system and category definitions, allowing scalability for different studies or birth defects registries, which often do not have resources for individual clinical review of all case records.

Contribution of Preterm Birth to Mortality Among Neonates with Birth Defects.

OBJECTIVE: To estimate the proportion of neonatal mortality risk attributable to preterm delivery among neonates with birth defects. STUDY DESIGN: Using a statewide cohort of live born infants from the Texas Birth Defects Registry (1999-2014 deliveries), we estimated the population attributable fraction and 95% CI of neonatal mortality (death <28 days) attributable to prematurity (birth at <37 weeks vs ≥37 weeks) for 31 specific birth defects. To better understand the overall population burden, analyses were repeated for all birth defects combined. RESULTS: Our analyses included 169 148 neonates with birth defects, of which 40 872 (24.2%) were delivered preterm. The estimated proportion of neonatal mortality attributable to prematurity varied by birth defect, ranging from 12.5% (95% CI: 8.7-16.1) for hypoplastic left heart syndrome to 71.9% (95% CI: 41.1-86.6) for anotia or microtia. Overall, the proportion was 51.7% (95% CI: 49.4-54.0) for all birth defects combined. CONCLUSIONS: A large proportion of deaths among neonates with birth defects are attributable to preterm delivery. Our results highlight differences in this burden across common birth defects. Our findings may be helpful for prioritizing future work focused on better understanding the etiology of prematurity among neonates with birth defects and the mechanisms by which prematurity contributes to neonatal mortality in this population.

Survival of infants and children born with severe microcephaly, Texas, 1999-2015.

BACKGROUND: Severe microcephaly is a brain reduction defect where the delivery head circumference is <3rd percentile for gestational age and sex with subsequent lifelong morbidities. Our objective was to evaluate survival among 2,704 Texas infants with severe microcephaly delivered 1999-2015. METHODS: Infants with severe microcephaly from the Texas Birth Defects Registry were linked to death certificates and the national death index. Survival estimates, hazard ratios (HR) and confidence intervals (CI) were calculated using the Kaplan-Meier method and Cox proportional hazards models stratified by presence versus absence of co-occurring defects. RESULTS: We identified 496 deaths by age 4 years; most (42.9%) occurred in the neonatal period, and another 39.9% died by 1 year of age. Overall infant survival was 84.8%. Lowest infant survival subgroups included those with chromosomal/syndromic conditions (66.1%), very preterm deliveries (63.9%), or co-occurring critical congenital heart defects (44.0%). Among infants with severe microcephaly and a chromosomal/syndromic co-occurring defect, the risk of death was nearly three-fold higher among those with: proportionate microcephaly (i.e., small baby overall), relative to non-proportionate (HR = 2.84, 95% CI = 2.17-3.71); low-birthweight relative to normal (HR = 2.72, 95% CI = 1.92-3.85); critical congenital heart defects (CCHD) relative to no CCHD (HR = 2.90, 95% CI = 2.20-3.80). Trisomies were a leading underlying cause of death (27.5%). CONCLUSIONS: Overall, infants with severe microcephaly had high 4-year survival rates which varied by the presence of co-occurring defects. Infants with co-occurring chromosomal/syndromic anomalies have a higher risk of death by age one than those without any co-occurring birth defects.

Prevalence and Clustering of Congenital Heart Defects Among Boys With Hypospadias.

Importance: Hypospadias is a common birth defect of the male urinary tract that may be isolated or may co-occur with other structural malformations, including congenital heart defects (CHDs). The risk for co-occurring CHDs among boys with hypospadias remains unknown, which limits screening and genetic testing strategies. Objective: To characterize the risk of major CHDs among boys born with hypospadias. Design, Setting, and Participants: This retrospective cohort study used data from population-based birth defect surveillance programs on all male infants born in 11 US states from January 1, 1995, to December 31, 2014. Statistical analysis was performed from September 2, 2020, to March 25, 2022. Exposure: Hypospadias. Main Outcomes and Measures: Demographic and diagnostic data were obtained from 2 active state-based birth defect surveillance programs for primary analyses, the Texas Birth Defects Registry and the Arkansas Reproductive Health Monitoring System, with validation among 9 additional states in the National Birth Defects Prevention Network (NBDPN). Birth defect diagnoses were identified using the British Pediatric Association coding for hypospadias (exposure) and major CHDs (primary outcomes). Maternal covariates and birth year were also abstracted from the vital records. Poisson regression was used to estimate adjusted prevalence ratios and 95% CIs for major CHDs within Texas and Arkansas and combined using inverse variance-weighted meta-analysis. Findings were validated using the NBDPN. Results: Among 3.7 million pregnancies in Texas and Arkansas, 1485 boys had hypospadias and a co-occurring CHD. Boys with hypospadias were 5.8 times (95% CI, 5.5-6.1) more likely to have a co-occurring CHD compared with boys without hypospadias. Associations were observed for every specific CHD analyzed among boys with hypospadias, occurred outside of chromosomal anomalies, and were validated in the NBDPN. An estimated 7.024% (95% CI, 7.020%-7.028%) of boys with hypospadias in Texas and 5.503% (95% CI, 5.495%-5.511%) of boys with hypospadias in Arkansas have a co-occurring CHD. In addition, hypospadias severity and maternal race and ethnicity were independently associated with the likelihood for hypospadias to co-occur with a CHD; boys in Texas with third-degree (ie, more severe) hypospadias were 2.7 times (95% CI, 2.2-3.4) more likely than boys with first-degree hypospadias to have a co-occurring CHD, with consistent estimates in Arkansas (odds ratio, 2.7; 95% CI, 1.4-5.3), and boys with hypospadias born to Hispanic mothers in Texas were 1.5 times (95% CI, 1.3-1.8) more likely to have a co-occurring CHD than boys with hypospadias born to non-Hispanic White mothers. Conclusions and Relevance: In this cohort study, boys with hypospadias had a higher prevalence of CHDs than boys without hypospadias. These findings support the need for consideration of additional CHD screening programs for boys born with hypospadias.

Trisomy 13 and 18-Prevalence and mortality-A multi-registry population based analysis.

The aim of the study is to determine the prevalence, outcomes, and survival (among live births [LB]), in pregnancies diagnosed with trisomy 13 (T13) and 18 (T18), by congenital anomaly register and region. Twenty-four population- and hospital-based birth defects surveillance registers from 18 countries, contributed data on T13 and T18 between 1974 and 2014 using a common data-reporting protocol. The mean total birth prevalence (i.e., LB, stillbirths, and elective termination of pregnancy for fetal anomalies [ETOPFA]) in the registers with ETOPFA (n = 15) for T13 was 1.68 (95% CI 1.3-2.06), and for T18 was 4.08 (95% CI 3.01-5.15), per 10,000 births. The prevalence varied among the various registers. The mean prevalence among LB in all registers for T13 was 0.55 (95%CI 0.38-0.72), and for T18 was 1.07 (95% CI 0.77-1.38), per 10,000 births. The median mortality in the first week of life was 48% for T13 and 42% for T18, across all registers, half of which occurred on the first day of life. Across 16 registers with complete 1-year follow-up, mortality in first year of life was 87% for T13 and 88% for T18. This study provides an international perspective on prevalence and mortality of T13 and T18. Overall outcomes and survival among LB were poor with about half of live born infants not surviving first week of life; nevertheless about 10% survived the first year of life. Prevalence and outcomes varied by country and termination policies. The study highlights the variation in screening, data collection, and reporting practices for these conditions.

Study of selected birth defects among American Indian/Alaska Native population: A multi-state population-based retrospective study, 1999-2007.

BACKGROUND: Higher prevalence of selected birth defects has been reported among American Indian/Alaska Native (AI/AN) newborns. We examine whether known risk factors for birth defects explain the higher prevalence observed for selected birth defects among this population. METHODS: Data from 12 population-based birth defects surveillance systems, covering a birth population of 11 million from 1999 to 2007, were used to examine prevalence of birth defects that have previously been reported to have elevated prevalence among AI/ANs. Prevalence ratios (PRs) were calculated for non-Hispanic AI/ANs and any AI/ANs (regardless of Hispanic ethnicity), adjusting for maternal age, education, diabetes, and smoking, as well as type of case-finding ascertainment surveillance system. RESULTS: After adjustment, the birth prevalence of two of seven birth defects remained significantly elevated among AI/ANs compared to non-Hispanic whites (NHWs): anotia/microtia was almost threefold higher, and cleft lip +/- cleft palate was almost 70% higher compared to NHWs. Excluding AI/AN subjects who were also Hispanic had only a negligible impact on adjusted PRs. CONCLUSIONS: Additional covariates accounted for some of the elevated birth defect prevalences among AI/ANs compared to NHWs. Exclusion of Hispanic ethnicity from the AI/AN category had little impact on birth defects prevalences in AI/ANs. NHWs serve as a viable comparison group for analysis. Birth defects among AI/ANs require additional scrutiny to identify modifiable risk and protective factors.

Pre-Zika descriptive epidemiology of microcephaly in Texas, 2008-2012.

BACKGROUND: There are limited population-based studies on microcephaly. We characterized the epidemiology of microcephaly in Texas during a 5-year period (2008-2012), prior to the Zika epidemic in the Western hemisphere (2015). The associations of suspected risk factors were compared across four clearly defined case groups. METHODS: Data from the Texas Birth Defects Registry were used to calculate the prevalence of congenital microcephaly and crude and adjusted prevalence ratios using Poisson regression. Twelve maternal and infant factors were assessed across case groups, which included total (explained + unexplained), explained (e.g., syndromic), unexplained, and severe unexplained microcephaly (head circumference <3rd percentile). RESULTS: The birth prevalence for total and total severe microcephaly were 14.7 and 4.8 per 10,000 livebirths, respectively. For explained and unexplained cases, significantly elevated risks were noted for mothers who were older (35+), less educated (≤12 years), diabetic (pre-pregnancy or gestational), or had a preterm delivery. Unlike explained cases, however, mothers who were non-White or smoked had an increased risk for unexplained microcephaly. Furthermore, young maternal age (<20), multiparity, and higher BMI reduced the risk for unexplained microcephaly. For severe unexplained cases, the risk profile was similar to that for all unexplained cases-with the exception of null associations noted for diabetes and birth year. CONCLUSIONS: We found that risk patterns for microcephaly varied across case groupings. Risk factors included maternal race/ethnicity, age, and smoking during pregnancy. Among severe unexplained cases, notable positive associations were seen among mothers who were non-Hispanic Black or less educated, while inverse associations were noted for obesity.

Original Findings and Updated Meta-Analysis for the Association Between Maternal Diabetes and Risk for Congenital Heart Disease Phenotypes.

Maternal diabetes is associated with congenital heart defects (CHDs) as a group, but few studies have assessed risk for specific CHD phenotypes. We analyzed these relationships using data from the Texas Birth Defects Registry and statewide vital records for deliveries taking place in 1999-2009 (n = 48,249 cases). We used Poisson regression to calculate prevalence ratios for the associations between maternal diabetes (pregestational or gestational) and each CHD phenotype, adjusting for potential confounders. Analyses were repeated by type of diabetes. To address the potential for misclassification bias, we performed logistic regression, using malformed controls. We also conducted meta-analyses, combining our estimates of the association between pregestational diabetes and each CHD phenotype with previous estimates. The prevalence of every CHD phenotype was greater among women with pregestational diabetes than among nondiabetic women. Most of these differences were statistically significant (adjusted prevalence ratios = 2.47-13.20). Associations were slightly attenuated for many CHD phenotypes among women with gestational diabetes. The observed associations did not appear to be the result of misclassification bias. In our meta-analysis, pregestational diabetes was significantly associated with each CHD phenotype. These findings contribute to a better understanding of the teratogenic effects of maternal diabetes and improved counseling for risk of specific CHD phenotypes.

Increasing Prevalence of Gastroschisis--14 States, 1995-2012.

Gastroschisis is a serious congenital defect in which the intestines protrude through an opening in the abdominal wall. Gastroschisis requires surgical repair soon after birth and is associated with an increased risk for medical complications and mortality during infancy. Reports from multiple surveillance systems worldwide have documented increasing prevalence of gastroschisis since the 1980s, particularly among younger mothers; however, since publication of a multistate U.S. report that included data through 2005, it is not known whether prevalence has continued to increase. Data on gastroschisis from 14 population-based state surveillance programs were pooled and analyzed to assess the average annual percent change (AAPC) in prevalence and to compare the prevalence during 2006-2012 with that during 1995-2005, stratified by maternal age and race/ethnicity. The pooled data included approximately 29% of U.S. births for the period 1995-2012. During 1995-2012, gastroschisis prevalence increased in every category of maternal age and race/ethnicity, and the AAPC ranged from 3.1% in non-Hispanic white (white) mothers aged <20 years to 7.9% in non-Hispanic black (black) mothers aged <20 years. These corresponded to overall percentage increases during 1995-2012 that ranged from 68% in white mothers aged <20 years to 263% in black mothers aged <20 years. Gastroschisis prevalence increased 30% between the two periods, from 3.6 per 10,000 births during 1995-2005 to 4.9 per 10,000 births during 2006-2012 (prevalence ratio = 1.3, 95% confidence interval [CI]: 1.3-1.4), with the largest increase among black mothers aged <20 years (prevalence ratio = 2.0, 95% CI: 1.6-2.5). Public health research is urgently needed to identify factors contributing to this increase.

Racial disparities in heterotaxy syndrome.

BACKGROUND: Heterotaxy syndrome (HTX) is a constellation of defects including abnormal organ lateralization and often including congenital heart defects. HTX has widely divergent population-based estimates of prevalence, racial and ethnic predominance, and mortality in current literature. METHODS: The objective of this study was to use a population-based registry to investigate potential racial and ethnic disparities in HTX. Using the Texas Birth Defects Registry, we described clinical features and mortality of HTX among infants delivered from 1999 to 2006. We calculated birth prevalence and crude prevalence (cPR) ratios for infant sex, maternal diabetes, and sociodemographic factors. RESULTS: A total of 353 HTX cases were identified from 2,993,604 births (prevalence ratio = 1.18 per 10,000 live births. HTX prevalence was approximately 70% higher among infants of Hispanic and non-Hispanic black mothers and 28% higher among female infants (cPR = 1.28; 95% confidence interval,1.04-1.59). There was a twofold higher female preponderance for infants of mothers who were non-Hispanic white or black. Mothers with diabetes were three times more likely to have a child with HTX compared with nondiabetics (cPR = 3.13; 95% confidence interval, 2.12-4.45). Among nondiabetics, HTX cases were 86% more likely to have a Hispanic mother and 72% a non-Hispanic black mother. First-year mortality for live born children with HTX was 30.9%. CONCLUSION: This study represents one of the largest population-based studies of HTX to date, with a novel finding of higher rates of HTX among Hispanic infants of mostly Mexican origin, as well as among female infants of only non-Hispanic white and black mothers. These findings warrant further investigation.

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

OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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. LEVEL OF EVIDENCE: II.

The association between race/ethnicity and major birth defects in the United States, 1999-2007.

OBJECTIVES: We investigated the relationship between race/ethnicity and 27 major birth defects. METHODS: We pooled data from 12 population-based birth defects surveillance systems in the United States that included 13.5 million live births (1 of 3 of US births) from 1999 to 2007. Using Poisson regression, we calculated prevalence estimates for each birth defect and 13 racial/ethnic groupings, along with crude and adjusted prevalence ratios (aPRs). Non-Hispanic Whites served as the referent group. RESULTS: American Indians/Alaska Natives had a significantly higher and 50% or greater prevalence for 7 conditions (aPR = 3.97; 95% confidence interval [CI] = 2.89, 5.44 for anotia or microtia); aPRs of 1.5 to 2.1 for cleft lip, trisomy 18, and encephalocele, and lower, upper, and any limb deficiency). Cubans and Asians, especially Chinese and Asian Indians, had either significantly lower or similar prevalences of these defects compared with non-Hispanic Whites, with the exception of anotia or microtia among Chinese (aPR = 2.08; 95% CI = 1.30, 3.33) and Filipinos (aPR = 1.90; 95% CI = 1.10, 3.30) and tetralogy of Fallot among Vietnamese (aPR = 1.60; 95% CI = 1.11, 2.32). CONCLUSIONS: This is the largest population-based study to our knowledge to systematically examine the prevalence of a range of major birth defects across many racial/ethnic groups, including Asian and Hispanic subgroups. The relatively high prevalence of birth defects in American Indians/Alaska Natives warrants further attention.

The utility of the National Death Index as a supplemental data source in ascertaining 5-year mortality among Texas heterotaxy cases.

INTRODUCTION: The Texas Birth Defects Registry (TBDR) is an active surveillance system which covers all pregnancy outcomes and routinely links birth defects cases to in-state vital records. This study describes the value of using the National Death Index (NDI) data to supplement Texas state death certificates from vital records for a birth defects survival analysis. METHODS: The cohort for this study were live-born cases with heterotaxy, a complex birth defect, delivered to Texas residents between 1999 and 2006, with a 5-year follow-up period for survival determination. Cases were linked to their Texas birth and death certificates, if present. Any live-born case that did not link to a Texas death certificate was sent to the NDI to search for any deaths that occurred. RESULTS: We identified 366 heterotaxy cases that were live-born in delivery years 1999-2006, 134 of which were linked to a Texas death certificate. The 232 remaining cases were sent to the NDI to search for a death certificate not found previously. This resulted in only 2 additional out-of-state deaths. DISCUSSION: Future quantification of NDI yields for birth defects survival studies would assist with further assessing the efficacy of utilizing the NDI for capturing early childhood mortality in states that routinely link to in-state death certificates.

Prevalence and correlates of gastroschisis in 15 states, 1995 to 2005.

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

Body mass index and birth defects: Texas, 2005-2008.

Texas ranks 12th nationally in the proportion of adult residents who are obese; approximately 67 % of Texans are overweight or obese. Studies indicate that obesity is related to an increased risk for birth defects; however, small sample sizes have limited the scope of birth defects investigated, and only four levels of body mass index (BMI) are typically explored. Using six BMI levels, we evaluated the association between maternal BMI and birth defects in a population-based registry covering ~1.6 million births. Texas birth defect cases were linked to 2005-2008 vital records. Maternal BMI was calculated using self-reported prepregnancy weight and height from the vital record and categorized as follows: underweight (BMI <18.5), normal weight (BMI 18.5-24.9), overweight (BMI 25-29.9), class I obese (BMI 30-34.9), class II obese (BMI 35-39.9) and class III obese (BMI ≥40). Prevalence ratios for specific birth defects for maternal BMI categories were estimated by using normal weight as the referent, adjusted for maternal age and race/ethnicity, and stratified by maternal diabetes status. Risk for certain birth defects increased with increasing BMI (i.e., atrial and ventricular septal defects, pulmonary valve atresia, patent ductus arteriosus, and clubfoot). Risk for birth defects was substantially increased among some obese mothers (BMI ≥30) (e.g., spina bifida, tetralogy of Fallot, cleft lip with or without cleft palate, hypospadias, and epispadias). Conversely, mothers with higher BMI had a lower risk for having an infant or fetus with gastroschisis (aPR = 0.35; 95 % CI = 0.12, 0.80). Given the increased risk for birth defects associated with obesity, preconception counseling should emphasize the importance of maintaining normal weight.

Trends in survival among children with Down syndrome in 10 regions of the United States.

OBJECTIVE: This study examined changes in survival among children with Down syndrome (DS) by race/ethnicity in 10 regions of the United States. A retrospective cohort study was conducted on 16,506 infants with DS delivered during 1983-2003 and identified by 10 US birth defects monitoring programs. Kaplan-Meier survival probabilities were estimated by select demographic and clinical characteristics. Adjusted hazard ratios (aHR) were estimated for maternal and infant characteristics by using Cox proportional hazard models. RESULTS: The overall 1-month and 1-, 5-, and 20-year survival probabilities were 98%, 93%, 91%, and 88%, respectively. Over the study period, neonatal survival did not improve appreciably, but survival at all other ages improved modestly. Infants of very low birth weight had 24 times the risk of dying in the neonatal period compared with infants of normal birth weight (aHR 23.8; 95% confidence interval [CI] 18.4-30.7). Presence of a heart defect increased the risk of death in the postneonatal period nearly fivefold (aHR 4.6; 95% CI 3.9-5.4) and continued to be one of the most significant predictors of mortality through to age 20. The postneonatal aHR among non-Hispanic blacks was 1.4 (95% CI 1.2-1.8) compared with non-Hispanic whites and remained elevated by age 10 (2.0; 95% CI 1.0-4.0). CONCLUSIONS: The survival of children born with DS has improved and racial disparities in infant survival have narrowed. However, compared with non-Hispanic white children, non-Hispanic black children have lower survival beyond infancy. Congenital heart defects are a significant risk factor for mortality through age twenty.

Association between thyroxine levels at birth and choanal atresia or stenosis among infants in Texas, 2004-2007.

BACKGROUND: The causes of choanal atresia or stenosis (CA) are largely unknown. Infant thyroxine (T(4) ) levels collected during newborn screening may be proxy measures for a risk factor present during the critical period of development. Therefore, we conducted a case-control study to examine the association between newborn T(4) levels and CA. METHODS: Data for cases with CA and controls were obtained from the Texas Birth Defects Registry for the period of 2004 to 2007. Information on infant T(4) levels at birth was obtained from the Texas Newborn Screening Program. Controls (n = 3570) were drawn from unaffected births in Texas for the same period and frequency matched to cases (n = 69) on year of birth, then linked to the newborn screening database. Logistic regression was used to evaluate the association between continuous and categorical infant T(4) levels and nonsyndromic CA. RESULTS: After adjustment for gestational age and year of birth, infant T(4) levels were inversely associated with CA (adjusted odds ratio [AOR], 0.85; 95% confidence interval [CI], 0.80-0.90). We observed a linear trend (p < 0.001) across quartiles of T(4) ; compared to infants with low levels, AORs for CA were 0.50 (95% CI, 0.28-0.91), 0.39 (95% CI, 0.20-0.75), and 0.15 (95% CI, 0.06-0.40) for infants with medium-to-low, medium, and high levels, respectively. CONCLUSIONS: Our findings suggest a role of low thyroid hormone levels in the development of CA, or that low newborn T(4) levels are potential proxy measures of a risk factor present during the critical period. Birth Defects Research (Part A), 2012.

The association between neonatal thyroxine and craniosynostosis, Texas, 2004-2007.

BACKGROUND: Craniosynostosis (CS), a structural anomaly characterized by premature fusion of cranial sutures, occurs in 1 in 2000 live births. Associations of CS with the thyroid have been reported. Neonatal thyroid hormone (T4) is evaluated nationally at birth by the Newborn Screening Program (NBS). This study evaluated the relationship between NBS T4 levels and craniosynostosis. METHODS: Live-born singleton babies born in 2004 through 2007 were identified through the Texas Birth Defects Registry (499 cases) and Texas Bureau of Vital Statistics (3570 controls) and successfully linked to analyte data available in the Texas NBS Database. Cases were classified based on the absence of other major defects (isolated cases, n = 382) and suture(s) involved. Mean T4 levels were compared between controls and cases (overall and stratified by classification). T4 levels were stratified by quintiles to evaluate differences between cases and controls within quintiles. The diagnostic utility of NBS T4 was evaluated using receiver operator characteristic (ROC) curves. RESULTS: Mean T4 levels were lower in isolated cases (16.89 µg/dl) than in controls (17.77 µg/dl; p = 0.0004). This trend persisted for sagittal (16.69 µg/dl; p = 0.002) and metopic (16.83 µg/dl; p = 0.042) CS. When stratified by quintiles, 54% of isolated lambdoid CS were in the first quintile compared to controls (p = 0.012). ROC area under the curve (AUC) was approximately 0.55 for all classifications except lambdoid (AUC = 0.73). CONCLUSION: NBS T4 levels were slightly lower among cases with nearly half of all lambdoid CS having T4 levels in the lowest quintile. However, overall NBS T4 levels are not suitable for potential screening or diagnostic application.