Mary K. Ethen

Prenatal Diagnosis, Birth Location, Surgical Center, and Neonatal Mortality in Infants With Hypoplastic Left Heart Syndrome

Background— Most studies have not demonstrated improved survival after prenatal diagnosis of critical congenital heart disease, including hypoplastic left heart syndrome (HLHS). However, the effect of delivery near a cardiac surgical center (CSC), the recommended action after prenatal diagnosis, on HLHS mortality has been poorly investigated. Methods and Results— Using Texas Birth Defects Registry data, 1999 through 2007, which monitored >3.4 million births, we investigated the association between distance (calculated driving time) from birth center to CSC and neonatal mortality in 463 infants with HLHS. Infants with extracardiac birth defects or genetic disorders were excluded. The associations between prenatal diagnosis, CSC HLHS volume, and mortality were also examined. Neonatal mortality in infants born <10 minutes from a CSC was 21.0%, 10 to 90 minutes 25.2%, and >90 minutes 39.6% (P for trend <0.001). Prenatal diagnosis alone was not associated with improved survival (P=0.14). In multivariable analysis, birth >90 minutes from a CSC remained associated with increased mortality (odds ratio, 2.03; 95% confidence interval, 1.19–3.45), compared with <10 minutes. In subanalysis, birth >90 minutes from a CSC was associated with higher pretransport mortality (odds ratio, 6.69; 95% confidence interval, 2.52–17.74) and birth 10 to 90 minutes with higher presurgical mortality (odds ratio, 4.45; 95% confidence interval, 1.17–17.00). Higher surgical mortality was associated with lower CSC HLHS volume (odds ratio per 10 patients, 0.88; 95% confidence interval, 0.84–0.91). Conclusions— Infants with HLHS born far from a CSC have increased neonatal mortality, and most of this mortality is presurgical. Efforts to improve prenatal diagnosis of HLHS and subsequent delivery near a large volume CSC may significantly improve neonatal HLHS survival.

Mortality in First 5 Years in Infants With Functional Single Ventricle Born in Texas, 1996 to 2003

Background— Infants with functional single ventricle have a high risk of death during the early years of life. Studies have reported improvement in postoperative survival, but they do not include preoperative deaths or those occurring before transfer. The purpose of this population-based study was to estimate 5-year survival in infants with functional single ventricle, to define factors associated with survival, and to estimate improvement in outcome. Methods and Results— Patients with hypoplastic left heart syndrome, pulmonary atresia intact ventricular septum, single ventricle, and tricuspid atresia born in 1996 to 2003 were identified from the Texas Birth Defects Registry and linked to state and national birth and death vital records. We examined the effects of defect type, birth era, birth weight, gestational age, maternal race/ethnicity, extracardiac anomalies, sex, and maternal age and education on survival. Five-year survival varied by defect type: hypoplastic left heart syndrome, 38.0% (95% confidence interval, 32.6 to 43.5); single ventricle, 56.1% (95% confidence interval, 49.9 to 61.7); pulmonary atresia intact ventricular septum, 55.7% (95% confidence interval, 45.8 to 64.4); and tricuspid atresia, 74.6% (95% confidence interval, 62.4 to 83.4). The presence of extracardiac defects increased the adjusted risk of death by 84%. Non-Hispanic blacks had an adjusted risk of death that was 41% higher than that for non-Hispanic whites, and Hispanics had a 26% higher risk. Patients born in 2001 to 2003 had a 47% lower risk than those born in 1996 to 2000. Conclusions— This population-based study demonstrates significant improvement in overall 5-year survival, particularly in cases of hypoplastic left heart syndrome and single ventricle. Additional studies are needed to determine the factors causing racial/ethnic and regional differences in outcome.

Racial/Ethnic Disparities in Risk of Early Childhood Mortality Among Children With Congenital Heart Defects

BACKGROUND: Infants with congenital heart defects (CHDs) have increased risk of childhood morbidity and mortality. However, little is known about racial/ethnic differences in early childhood mortality. PATIENTS AND METHODS: We conducted a retrospective cohort study with data from the Texas Birth Defect Registry on 19 530 singleton, live-born infants with a CHD and born January 1, 1996, to December 31, 2003, to non-Hispanic (NH) white, NH black, and Hispanic women. Texas Birth Defect Registry data were linked to Texas death records and the National Death Index to ascertain deaths between January 1, 1996, and December 31, 2005. Kaplan-Meier survival estimates were computed, and hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated from multivariable Cox-proportional hazard regression models to determine the effect of maternal race/ethnicity on mortality for selected CHD phenotypes. RESULTS: After adjusting for covariates, compared with NH white children, NH black children had increased early childhood mortality risk for transposition of the great arteries (HR: 2.04 [95% CI: 1.40–2.97]), tetralogy of Fallot (HR: 1.85 [95% CI: 1.09–3.12]), pulmonary valve atresia without ventricular septal defect (VSD) (HR: 2.60 [95% CI: 1.32–5.12]), VSD (HR: 1.56 [95% CI: 1.19–2.03]), and atrial septal defect (HR: 1.34 [95% CI: 1.08–1.66]). Hispanic children had higher mortality risk for pulmonary valve atresia without VSD (HR: 1.76 [95% CI: 1.06–2.91]) and hypoplastic left heart syndrome (HR: 1.51 [95% CI: 1.13–2.02]). CONCLUSIONS: We provide evidence that supports racial/ethnic disparities in early childhood mortality among infants with CHDs. Identifying infants with the greatest risk of early childhood mortality will facilitate development of interventions and policies to mitigate these risks.

Survival of children with trisomy 13 and trisomy 18: A multi-state population-based study.

Trisomy 13 (T13) and trisomy 18 (T18) are among the most prevalent autosomal trisomies. Both are associated with a very high risk of mortality. Numerous instances, however, of long‐term survival of children with T13 or T18 have prompted some clinicians to pursue aggressive treatment instead of the traditional approach of palliative care. The purpose of this study is to assess current mortality data for these conditions. This multi‐state, population‐based study examined data obtained from birth defect surveillance programs in nine states on live‐born infants delivered during 1999–2007 with T13 or T18. Information on childrens vital status and selected maternal and infant risk factors were obtained using matched birth and death certificates and other data sources. The Kaplan–Meier method and Cox proportional hazards models were used to estimate age‐specific survival probabilities and predictors of survival up to age five. There were 693 children with T13 and 1,113 children with T18 identified from the participating states. Among children with T13, 5‐year survival was 9.7%; among children with T18, it was 12.3%. For both trisomies, gestational age was the strongest predictor of mortality. Females and children of non‐Hispanic black mothers had the lowest mortality. Omphalocele and congenital heart defects were associated with an increased risk of death for children with T18 but not T13. This study found survival among children with T13 and T18 to be somewhat higher than those previously reported in the literature, consistent with recent studies reporting improved survival following more aggressive medical intervention for these children.

Gastroschisis prevalence in Texas 1999-2003.

BACKGROUND The worldwide prevalence of gastroschisis is increasing. Maternal age, race/ethnicity, and place of residence have been associated with increased risk. METHODS We obtained descriptive characteristics of mothers of infants with gastroschisis and mothers of all live births from the Texas Birth Defects Registry and Texas vital records for 1999-2003. We calculated prevalence, crude prevalence ratios, and prevalence ratios adjusted for maternal age, parity, education, race/ethnicity, and geographic entity (Mexican border proximity, urban/rural residence, health service region, and county). RESULTS We observed 764 cases of gastroschisis among 1,827,317 live births, for a prevalence of 4.18 per 10,000 births (95% confidence interval 3.88-4.48). Prevalence increased during 1999-2003 (p for trend <0.02). Infants of young and nulliparous mothers were at greatest risk in crude analyses. Other characteristics associated with increased risk were 12 or fewer years of education, border residence, and Hispanic ethnicity. Black mothers were at lower risk. When adjusted for maternal age, race/ethnicity, education, parity, and residence, we found that border residence, educational level, and Hispanic race/ethnicity were no longer significant, but young mothers and nulliparous mothers remained at higher risk, and blacks at reduced risk. Differences in prevalence observed between regions and counties largely disappeared when adjusted for maternal factors. No significant difference between urban and rural residence was found. CONCLUSION The prevalence of gastroschisis increased in Texas during 1999-2003. Black mothers were at lower risk, and Hispanic mothers were at no greater risk than whites. No differences were found between urban/rural or border/nonborder residents.

Effect of Acculturation and Distance From Cardiac Center on Congenital Heart Disease Mortality

BACKGROUND AND OBJECTIVE: Despite improvements in congenital heart disease (CHD) survival over the past 4 decades, ethnic disparities persist. Several studies have shown higher postoperative CHD adjusted mortality in black and Hispanic children. Others noted that non–English-speaking language at home was associated with appointment noncompliance, which the parents attributed to misunderstanding and living too far from a health center. The purpose of this study was to determine the effect of home distance to a cardiac center, or having a Latin American–born parent, on first-year mortality in infants with severe CHD. METHODS: Infants with severe CHD, having an estimated first-year mortality >25%, born 1996–2003, were identified from the Texas Birth Defects Registry and linked to state and national vital records. We examined the effects of defect type; birth weight; gestational age; extracardiac anomalies; infant gender; maternal race/ethnicity, marital status, and education; residence in a Texas county bordering Mexico; home distance to cardiac center; and parental birth country on first-year survival. RESULTS: Overall first-year survival was 59.9%, and no race/ethnic differences were noted; however, survival was significantly (P < .05) lower for Hispanic infants with hypoplastic left heart syndrome. Neither home distance to a cardiac center nor parental birth country was related to first-year survival; however, survival was noted to be lower in Texas counties bordering Mexico, counties that have high rates of poverty. CONCLUSIONS: Further studies are needed to determine if these disparities in survival of infants with severe CHD are attributable to delays in referral to a cardiac center.

Population-based microcephaly surveillance in the United States, 2009 to 2013: An analysis of potential sources of variation

BACKGROUND Congenital microcephaly has been linked to maternal Zika virus infection. However, ascertaining infants diagnosed with microcephaly can be challenging. METHODS Thirty birth defects surveillance programs provided data on infants diagnosed with microcephaly born 2009 to 2013. The pooled prevalence of microcephaly per 10,000 live births was estimated overall and by maternal/infant characteristics. Variation in prevalence was examined across case finding methods. Nine programs provided data on head circumference and conditions potentially contributing to microcephaly. RESULTS The pooled prevalence of microcephaly was 8.7 per 10,000 live births. Median prevalence (per 10,000 live births) was similar among programs using active (6.7) and passive (6.6) methods; the interdecile range of prevalence estimates was wider among programs using passive methods for all race/ethnicity categories except Hispanic. Prevalence (per 10,000 live births) was lowest among non-Hispanic Whites (6.5) and highest among non-Hispanic Blacks and Hispanics (11.2 and 11.9, respectively); estimates followed a U-shaped distribution by maternal age with the highest prevalence among mothers <20 years (11.5) and ≥40 years (13.2). For gestational age and birth weight, the highest prevalence was among infants <32 weeks gestation and infants <1500 gm. Case definitions varied; 41.8% of cases had an HC ≥ the 10th percentile for sex and gestational age. CONCLUSION Differences in methods, population distribution of maternal/infant characteristics, and case definitions for microcephaly can contribute to the wide range of observed prevalence estimates across individual birth defects surveillance programs. Addressing these factors in the setting of Zika virus infection can improve the quality of prevalence estimates. Birth Defects Research (Part A) 106:972-982, 2016.

Racial/ethnic disparities in timing of death during childhood among children with congenital heart defects

BACKGROUND Infants with congenital heart defects (CHD) have increased risk of morbidity and mortality. Little is known about racial/ethnic differences in timing of death during childhood. Our intent was to investigate racial/ethnic differences in mortality for CHDs during specific time periods in childhood. METHODS Texas Birth Defect Registry data were used for a retrospective cohort study with 30,015 singleton infants with a CHD, born January 1, 1999, to December 31, 2007, to non-Hispanic (NH) white, NH-black, or Hispanic women. Texas Birth Defect Registry data were linked to Texas death records to ascertain death. Kaplan-Meier survival probabilities and multivariable Cox-proportional hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated. RESULTS NH-blacks and Hispanics with specific CHDs had increased mortality during the postneonatal period and early childhood. NH-blacks had increased postneonatal mortality compared with NH-whites for transposition of the great arteries (HR = 2.4; 95% CI, 1.5-4.0), pulmonary valve atresia without ventricular septal defect (HR = 4.1; 95% CI, 1.7-9.7), Ebsteins anomaly (HR = 8.6; 95 CI, 1.2-61.1), hypoplastic left heart syndrome (HR = 2.1; 95% CI, 1.2-3.7), coarctation of the aorta (HR = 2.1; 95% CI, 1.2-3.5), ventricular septal defect (HR = 2.1; 95% CI, 1.6-2.8), and atrial septal defect (HR = 1.4; 95% CI, 1.1-1.8). Hispanics had increased postneonatal mortality risk for tetralogy of Fallot (HR = 2.0; 95% CI, 1.1-3.5). Racial/ethnic increases in mortality risk were also observed during infancy and childhood. CONCLUSION Racial/ethnic differences in mortality were most notably observed during the postneonatal period and early childhood. Future studies should assess factors associated with this disparity in mortality risk for infants with CHDs.

Age at Referral and Mortality From Critical Congenital Heart Disease

BACKGROUND AND OBJECTIVE: Newborn pulse oximetry screening is recommended to promote early referral of neonates with critical congenital heart disease (CCHD) and reduce mortality; however, the impact of late referral on mortality is not well defined. The purpose of this population-based study was to describe the association between timing of referral to a cardiac center and mortality in 2360 liveborn neonates with CCHD. METHODS: Neonates with CCHD born before pulse oximetry screening (1996–2007) were selected from the Texas Birth Defects Registry and linked to state birth and death records. Age at referral was ascertained from date of first cardiac procedure at a cardiac center. Logistic and Cox proportional hazards regression models were used to estimate factors associated with late referral and mortality; the Kaplan-Meier method was used to estimate 3-month survival. RESULTS: Median age at referral was 1 day (25th–75th percentile: 0–6 days). Overall, 27.5% (649 of 2360) were referred after age 4 days and 7.5% (178 of 2360) had no record of referral. Neonatal mortality was 18.1% (277 of 1533) for those referred at 0 to 4 days of age, 9.0% (34 of 379) for those referred at 5 to 27 days of age, and 38.8% (69 of 178) for those with no referral. No improvement in age at referral was found across the 2 eras within 1996–2007. CONCLUSIONS: A significant proportion of neonates with CCHD experienced late or no referral to cardiac specialty centers, accounting for a significant number of the deaths. Future population-based studies are needed to determine the benefit of pulse oximetry screening on mortality and morbidity.

Mortality among infants with birth defects: Joint effects of size at birth, gestational age, and maternal race/ethnicity.

BACKGROUND We examined the separate and joint effects of gestational age, size at birth and maternal race/ethnicity on early childhood survival among 48,391 singleton infants with major birth defects. METHODS Texas Birth Defects Registry data were linked to death records and the National Death Index to ascertain deaths. Gestational age categories were preterm or term birth; size at birth included small for gestational age (SGA), appropriate for gestational age (AGA), and large for gestational age (LGA). Kaplan-Meier survival estimates were calculated, and Cox-proportional hazards models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI) to determine risk of death after adjusting for covariates. RESULTS Overall, relative to non-Hispanic (NH) -whites, NH-blacks, and Hispanics had a 51 and 10% greater risk of death during early childhood, respectively. Compared to NH-whites born term and AGA (survival = 97%), Hispanic children born SGA and preterm had the greatest risk of death (HR(a) = 6.1; 95% CI, 5.2, 7.2) and the lowest early childhood survival (76%), followed by SGA preterm NH-blacks (HR(a) = 4.8; 95% CI, 3.6, 6.5; survival = 81%) and SGA preterm NH-whites (HR(a) = 4.5; 95% CI, 3.7, 5.6; survival = 83%). Children born LGA at term had no increased risk of mortality regardless of maternal race/ethnicity. CONCLUSIONS The joint effect of gestational age and size at birth had greatest impact on childhood mortality. Additional population based studies are needed to better understand causes of racial/ethnic disparities in mortality among children with birth defects.