Birth Defects Registry Research Articles

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.

Educational attainment of children with congenital heart disease in the United Kingdom.

Educational attainment in children with congenital heart disease (CHD) within the UK has not been reported, despite the possibility of school absences and disease-specific factors creating educational barriers. Children were prospectively recruited to the Born in Bradford birth cohort between March 2007 and December 2010. Diagnoses of CHD were identified through linkage to the congenital anomaly register and independently verified by clinicians. Multivariable regression accounted for relevant confounders. Our primary outcome was the odds of 'below expected' attainment in maths, reading, and writing at ages 4-11 years.Educational records of 139 children with non-genetic CHD were compared with 11188 age-matched children with no major congenital anomaly. Children with CHD had significantly higher odds of 'below expected' attainment in maths at age 4-5 years [odds ratio (OR) 1.64, 95% confidence interval (CI) 1.07-2.52], age 6-7 (OR 2.03, 95% CI 1.32-3.12), and age 10-11 (OR 2.28, 95% CI 1.01-5.14). Odds worsened with age, with similar results for reading and writing. The odds of receiving special educational needs support reduced with age for children with CHD relative to controls [age 4-5: OR 4.84 (2.06-11.40); age 6-7: OR 3.65 (2.41-5.53); age 10-11: OR 2.73 (1.84-4.06)]. Attainment was similar for children with and without exposure to cardio-pulmonary bypass. Lower attainment was strongly associated with the number of pre-school hospital admissions. Children with CHD have lower educational attainment compared with their peers. Deficits are evident from school entry and increase throughout primary school.

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.

Leveraging automated approaches to categorize birth defects from abstracted birth hospitalization data.

The Surveillance for Emerging Threats to Pregnant People and Infants Network (SET-NET) collects data abstracted from medical records and birth defects registries on pregnant people and their infants to understand outcomes associated with prenatal exposures. We developed an automated process to categorize possible birth defects for prenatal COVID-19, hepatitis C, and syphilis surveillance. By employing keyword searches, fuzzy matching, natural language processing (NLP), and machine learning (ML), we aimed to decrease the number of cases needing manual clinician review. SET-NET captures International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM) codes and free text describing birth defects. For unstructured data, we used keyword searches, and then conducted fuzzy matching with a cut-off match score of ≥90%. Finally, we employed NLP and ML by testing three predictive models to categorize birth defect data. As of June 2023, 8326 observations containing data on possible birth defects were submitted to SET-NET. The majority (n = 6758 [81%]) were matched to an ICD-10-CM code and 1568 (19%) were unable to be matched. Through keyword searches and fuzzy matching, we categorized 1387/1568 possible birth defects. Of the remaining 181 unmatched observations, we correctly categorized 144 (80%) using a predictive model. Using automated approaches allowed for categorization of 99.6% of reported possible birth defects, which helps detect possible patterns requiring further investigation. Without employing these analytic approaches, manual review would have been needed for 1568 observations. These methods can be employed to quickly and accurately sift through data to inform public health responses.

Meconium Concentrations of Pesticides and Risk of Hypospadias: A Case-Control Study in Brittany, France.

Hypospadias is a male genital tract defect for which an increase in prevalence has been documented over the last few decades. A role for environmental risk factors is suspected, including prenatal exposure to pesticides. To study the risk of hypospadias in association with multiple pesticide measurements in meconium samples. The Brittany Registry of Congenital Anomalies (France) conducted a case-control study between 2012 and 2018. Cases were hypospadias, ascertained by a pediatrician and a pediatric surgeon, excluding genetic conditions, following European Surveillance of Congenital Anomalies guidelines (N = 69). Controls (N = 135) were two male infants without congenital anomaly born after each case in the same maternity unit. Mothers in the maternity units completed a self-administered questionnaire, we collected medical data from hospital records, and medical staff collected meconium samples. We performed chemical analysis of 38 pesticides (parent compound and/or metabolite) by UHPLC/MS/MS following strict quality assurance/quality control criteria and blind to case-control status. We carried out logistic regression accounting for frequency-matching variables and major risk factors. Among the 38 pesticides measured, 16 (42%) were never detected in the meconium samples, 18 (47%) were in <5% of samples, and 4 (11%) in ≥5% of the samples. We observed an association between the detection of fenitrothion in meconium and the risk of hypospadias (OR = 2.6 [1.0-6.3] with n cases = 13, n controls = 21), but not the other pesticides. Our small study provides a robust assessment of fetal exposure. Fenitrothion's established antiandrogenic activities provide biologic plausibility for our observations. Further studies are needed to confirm this hypothesis.

No major differences in perinatal and maternal outcomes between uninterrupted embryo culture in time-lapse system and conventional embryo culture.

Is embryo culture in a closed time-lapse system associated with any differences in perinatal and maternal outcomes in comparison to conventional culture and spontaneous conception? There were no significant differences between time-lapse and conventional embryo culture in preterm birth (PTB, <37 weeks), low birth weight (LBW, >2500 g) and hypertensive disorders of pregnancy for singleton deliveries, the primary outcomes of this study. Evidence from prospective trials evaluating the safety of time-lapse incubation for clinical use show similar embryo development rates, implantation rates, and ongoing pregnancy and live birth rates when compared to conventional incubation. Few studies have investigated if uninterrupted culture can alter risks of adverse perinatal outcomes presently associated with IVF when compared to conventional culture and spontaneous conceptions. This study is a Swedish population-based retrospective registry study, including 7379 singleton deliveries after fresh embryo transfer between 2013 and 2018 from selected IVF clinics. Perinatal outcomes of singletons born from time-lapse-cultured embryos were compared to singletons from embryos cultured in conventional incubators and 71 300 singletons from spontaneous conceptions. Main perinatal outcomes included PTB and LBW. Main maternal outcomes included hypertensive disorders of pregnancy (pregnancy hypertension and preeclampsia). From nine IVF clinics, 2683 singletons born after fresh embryo transfer in a time-lapse system were compared to 4696 singletons born after culture in a conventional incubator and 71 300 singletons born after spontaneous conception matched for year of birth, parity, and maternal age. Patient and treatment characteristics from IVF deliveries were cross-linked with the Swedish Medical Birth Register, Register of Birth Defects, National Patient Register and Statistics Sweden. Children born after sperm and oocyte donation cycles and after Preimplantation Genetic testing cycles were excluded. Odds ratio (OR) and adjusted OR were calculated, adjusting for relevant confounders. In the adjusted analyses, no significant differences were found for risk of PTB (adjusted OR 1.11, 95% CI 0.87-1.41) and LBW (adjusted OR 0.86, 95% CI 0.66-1.14) or hypertensive disorders of pregnancy; preeclampsia and hypertension (adjusted OR 0.99, 95% CI 0.67-1.45 and adjusted OR 0.98, 95% CI 0.62-1.53, respectively) between time-lapse and conventional incubation systems. A significantly increased risk of PTB (adjusted OR 1.31, 95% CI 1.08-1.60) and LBW (adjusted OR 1.36, 95% CI 1.08-1.72) was found for singletons born after time-lapse incubation compared to singletons born after spontaneous conceptions. In addition, a lower risk for pregnancy hypertension (adjusted OR 0.72 95% CI 0.53-0.99) but no significant difference for preeclampsia (adjusted OR 0.87, 95% CI 0.68-1.12) was found compared to spontaneous conceptions. Subgroup analyses showed that some risks were related to the day of embryo transfer, with more adverse outcomes after blastocyst transfer in comparison to cleavage stage transfer. This study is retrospective in design and different clinical strategies may have been used to select specific patient groups for time-lapse versus conventional incubation. The number of patients is limited and larger datasets are required to obtain more precise estimates and adjust for possible effect of additional embryo culture variables. Embryo culture in time-lapse systems is not associated with major differences in perinatal and maternal outcomes, compared to conventional embryo culture, suggesting that this technology is an acceptable alternative for embryo incubation. The study was financed by a research grant from Gedeon Richter. There are no conflicts of interest for all authors to declare. N/A.

The use of health care databases for surveillance of congenital anomalies: A EUROlinkCAT study

Abstract Background Although health care databases were not designed for research or surveillance, they are increasingly used by researchers to investigate the epidemiology of congenital anomalies (CAs). Identifying specific CAs that can be accurately identified in hospital databases and those that are poorly recorded will enable surveillance of CAs. We evaluated the accuracy and the quality of the coding of CAs in hospital databases compared to EUROCAT data. Methods The EUROlinkCAT project linked data from eleven EUROCAT registries I eight countries to electronic hospital databases. The coding of specific CAs in hospital databases was compared to the codes in the EUROCAT registries (gold standard). For birth years 2010-2014 all linked live birth CA cases and all children identified in the hospital databases with a CA code were analysed. Registries calculated sensitivity and Positive Predictive Value (PPV) for 17 selected CAs. Pooled estimates for sensitivity and PPV were then calculated for each anomaly using random effects meta-analyses. Results Most registries linked more than 85% of their cases to hospital data. Gastroschisis, cleft lip with or without cleft palate and Down syndrome were recorded in hospital databases with high accuracy (sensitivity and PPV &amp;gt;85%). Hypoplastic left heart syndrome, spina bifida, Hirschsprung's disease, omphalocele and cleft palate showed high sensitivity (&amp;gt;85%), but low or heterogeneous PPV, indicating that hospital data were complete but may contain false positives. The remaining anomaly subgroups showed low or heterogeneous sensitivity and PPV, indicating that the information in the hospital database was incomplete and of variable validity. Conclusions Electronic health care databases cannot replace CA registries, although they can be used as an additional ascertainment source for CA registries. CA registries are still the most appropriate data source to study the epidemiology of CAs. Key messages • European hospital databases can accurately record a limited number of anomalies that are visible at birth, diagnosed prenatally and/or require hospitalisation or surgery in the first year of life. • Additional data sources are needed to capture all children with CAs as hospital databases have limited information or codes to identify pregnancies that result in termination for fetal anomaly.

Prevalence of neural tube defects in England prior to the mandatory fortification of non-wholemeal wheat flour with folic acid: a population-based cohort study

ObjectivesTo determine the baseline trends in the total birth prevalence of neural tube defects (NTDs) in England (2000–2019) to enable the impact of folic acid fortification of non-wholemeal wheat flour...

Survival of neonates, infants, and children with birth defects: a population-based study in Texas, 1999–2018

Birth defects are a leading cause of neonatal, infant, and childhood mortality, but recent population-based survival estimates for a spectrum in the U.S. are lacking. Using the statewide Texas Birth Defects Registry (1999-2017 births) and vital records linkage to ascertain deaths, we conducted Kaplan-Meier analyses to estimate survival probabilities at 1, 7, and 28 days, and 1, 5, and 10 years. We evaluated survival in the full cohort of infants with any major defect and for 30 specific conditions. One-year survival analyses were stratified by gestational age, birth year, and case classification. Among 246,394 live-born infants with any major defect, the estimated survival probabilities were 98.9% at 1 day, 95.0% at 1 year, and 93.9% at 10 years. Ten-year survival varied by condition, ranging from 36.9% for holoprosencephaly to 99.3% for pyloric stenosis. One-year survival was associated with increasing gestational age (e.g., increasing from 46.9% at <28 weeks to 95.8% at ≥37 weeks for spina bifida). One-year survival increased in more recent birth years for several defect categories (e.g., increasing from 86.0% among 1999-2004 births to 93.1% among 2014-2017 births for unilateral renal agenesis/dysgenesis) and was higher among infants with an isolated defect versus those with multiple defects. This study describes short- and long-term survival outcomes from one of the largest population-based birth defect registries in the world and highlights improved survival over time for several conditions. Our results may lend insight into future healthcare initiatives aimed at reducing mortality in this population. This study was funded in part by a Centers for Disease Control and Prevention (CDC) birth defects surveillance cooperative agreement with the Texas Department of State Health Services and Health Resources and Services Administration (HRSA) Block Grant funds.

Risk factors for mortality in infancy and childhood in children with major congenital anomalies: A European population-based cohort study.

Preterm birth and young maternal age are known risk factors for infant and childhood mortality. There is limited knowledge of the impact of these risk factors in children born with major congenital anomalies (CAs), who have inherently higher risks of death compared with other children. To investigate the risk factors for mortality up to age 10 years in children born with specific major CAs. This population-based cohort study involved 150,198 livebirths from 1995 to 2014 in 13 European CA registries linked to mortality data. Cox proportional hazards models estimated the association of gestational age, maternal age and child's sex with death <1 year and 1-9 years for the whole cohort and by CA subgroup. Hazard ratios (HR) from each registry were pooled using multivariate meta-analysis. Preterm birth had a dose-response association with mortality; compared with infants born at 37+ weeks gestation, those born at <28, 28-31 and 32-36 weeks had 14.88 (95% CI 12.57, 17.62), 8.39 (95% CI 7.16, 9.85) and 3.88 (95% CI 3.40, 4.43) times higher risk of death <1 year, respectively. The corresponding risks at 1-9 years were 4.99 (95% CI 2.94, 8.48), 3.09 (95% CI 2.28, 4.18) and 2.04 (95% CI 1.69, 2.46) times higher, respectively. Maternal age <20 years (versus 20-34 years) was a risk factor for death <1 year (HR 1.30, 95% CI 1.09, 1.54) and 1-9 years (HR 1.58, 95% CI 1.19, 2.10). Females had 1.22 (95% CI 1.07, 1.39) times higher risk of death between 1 and 9 years than males. Preterm birth was associated with considerably higher infant and childhood mortality in children with CAs, comparable to estimates reported elsewhere for the background population. Additional risk factors included young maternal age and female sex. Information on risk factors could benefit clinical care and guide counselling of parents following CA diagnoses.

Pediatric cancer incidence among individuals with overgrowth syndromes and overgrowth features: A population-based assessment in seven million children.

Overgrowth syndromes (e.g., Beckwith-Wiedemann) are associated with an increased risk of pediatric cancer, although there are few population-based estimates of risk. There are also limited studies describing associations between other overgrowth features (e.g., hepatosplenomegaly) and pediatric cancer. Therefore, cancer risk among children with these conditions was evaluated with data from a large, diverse population-based registry linkage study. This study includes all live births in Texas during the years 1999-2017. Children with overgrowth features and syndromes were identified from the Texas Birth Defects Registry; children with cancer were identified by linkage to the Texas Cancer Registry. Cox regression models were used to estimate the hazard ratio (HR) and 95% confidence interval (CI) for the association between each overgrowth syndrome/feature and cancer, which were adjusted for infant sex and maternal age. In the total birth cohort (n=6,997,422), 21,207 children were identified as having an overgrowth syndrome or feature. Children with Beckwith-Wiedemann syndrome were 42 times more likely to develop pediatric cancer (95% CI, 24.20-71.83), with hepatoblastoma being the most common, followed by Wilms tumor. The presence of any isolated overgrowth feature was associated with increased cancer risk (HR, 4.70; 95% CI, 3.83-5.77); associations were strongest for hepatosplenomegaly (HR, 23.04; 95% CI, 13.37-39.69) and macroglossia (HR, 11.18; 95% CI, 6.35-19.70). This population-based assessment confirmed prior findings that children with either overgrowth syndromes or features were significantly more likely to develop cancer. Overall, this study supports recommendations for cancer surveillance in children with these conditions and may also inform future research into cancer etiology.

Understanding the medical complexity of children and young people with life-limiting conditions in Wales using linked, routinely collected healthcare data

ObjectivesTo better understand the complexity and healthcare needs of children and young people in Wales with life-limiting or life threatening conditions to better plan and target healthcare services. Previous attempts to quantify complexity have required primary data collection; this is not feasible at scale, use of existing data is preferred. MethodsRoutinely collected healthcare and administrative data were linked: primary care data, hospital care data sets, cancer and congenital anomaly registries, paediatric intensive care audit data and death records. Children and young people with life-limiting conditions were identified using a previously developed diagnostic framework. Previous work on conceptualising medical complexity across eight domains was operationalised for the first time using the wide range of available data, with scores across five domains and a total complexity score. The relationship between the complexity score, healthcare use, stage of condition and category of condition was explored. ResultsChildren and young people with life-limiting conditions showed the full range of medical complexity scores, from zero to five, with distributions varying across age groups with increasing complexity at greater ages. Distributions also varied across categories of condition, with congenital and oncology conditions, although among the most prevalent, exhibiting lower medical complexity. Nonetheless, all conditions showed a range of complexities – there were no conditions for which all individuals were either high or low complexity. Complexity scores were correlated with stage of condition and healthcare use and may be used to identify groups likely to have higher healthcare demand or greater risk of clinical instability. While life-limiting conditions were more prevalent in areas of higher deprivation, there was no association between deprivation and medical complexity. ConclusionAssessment of medical complexity from routinely-collected data can be useful in better understanding a population and in targeting and planning care, without requiring additional data collection. This can help to design resilient services that prepare for changing needs and aid targeting of limited resources.

Birth Defects in Offspring of Adolescent and Young Adults with a History of Cancer: A Population-Based Study of 27,000 Women.

We examined birth defects in offspring of adolescent and young adult (AYA) women with a history of cancer (age 15-39 years at diagnosis). We identified AYA women diagnosed with cancer between January 1, 1999, and December 31, 2015 using population-based data from the Texas Cancer Registry; data were linked with live birth and fetal death certificates through December 31, 2016 to identify singleton births to AYA women after diagnosis. Birth defects in offspring through age 12 months were ascertained from the Texas Birth Defects Registry. We estimated risk of birth defects in offspring of AYA women and women without cancer (matched 3:1 by maternal race/ethnicity, maternal age, and offspring year of birth) and compared risk using log binomial regression models. There were 6,882 singleton births to AYA women after diagnosis. Common cancer types were thyroid (28.9%), lymphoma (12.5%), and breast (10.7%). Risk of any birth defect was higher in offspring of AYA women (6.0%) compared with offspring of women without cancer [n = 20,646; 4.8%; risk ratio (RR) 1.24; 95% confidence interval (CI), 1.11-1.38]. Risk of eye or ear (RR, 1.39; 95% CI, 1.03-1.90), heart and circulatory (RR, 1.32; 95% CI, 1.09-1.60), genitourinary (RR, 1.38; 95% CI, 1.12-1.69), and musculoskeletal (RR, 1.37; 95% CI, 1.13-1.66) defects was also higher. Risk of birth defects was elevated in liveborn and stillborn offspring of AYA women. Although birth defects are rare, AYA women making decisions about pregnancy and prenatal care should receive appropriate counseling and surveillance.

Risk factors for admission and length of stay in hospital for children with and without congenital anomalies: A EUROlinkCAT study

ObjectiveTo explore risk factors for hospital admission, and length of stay (LOS) in hospital, among children with congenital anomalies (CAs) and reference children without CAs in Europe.&#x0D; MethodA European population-based data-linkage cohort study was conducted including children with CAs (born 1995-2014) registered in seven EUROCAT CA registries and children without CAs (reference children) living in the same geographical areas. Data on hospitalisation and LOS (1995-2015) for all children aged &lt;1 year and 1-4 years were obtained by linkage to hospital discharge databases.&#x0D; The effects of birth cohort, sex, gestational age, maternal age, multiple birth and socioeconomic status on risk of admission and LOS were estimated using Cox’s Proportional Hazards and negative binomial regression models. Random effects meta-analysis and quantile estimation methods were used to pool the estimates.&#x0D; ResultsA total of 79,036 children with CAs and 2,016,042 reference children were linked to hospital records. Children with CAs born pre-term (&lt;32 weeks) were more than twice as likely to be admitted (adj. HR 2.35, 95% CI 1.45-3.80) and had almost 8 times longer stays (adj. IRR 7.95, 95% CI 6.12-10.33) compared to children with CAs born at term. Reference children were almost six times as likely to be admitted (adj. HR 5.87, 95% CI 3.10-11.09), and had almost 50 times longer stays (adj. IRR 49.49, 30.92-79.21) compared to reference children born at term. Children with CAs and reference children born preterm were also at increased risk of admission at 1-4 years of age, although the effect was less than for children aged &lt;1 year.&#x0D; ConclusionThe impact of risk factors for admission to hospital and LOS were similar between children with CAs and reference children but the impact was often greater in reference children. This study highlights the value of linking to hospital discharge records to obtain population-based information on morbidity for counselling parents.

Prediction of Preterm Birth among Infants with Orofacial Cleft Defects.

To develop risk prediction models for preterm birth among infants with orofacial clefts. Data from the Texas Birth Defects Registry for infants with orofacial clefts born between 1999-2014 were used to develop preterm birth predictive models. Logistic regression was used to consider maternal and infant characteristics, and internal validation of the final model was performed using bootstrapping methods. The area under the curve (AUC) statistic was generated to assess model performance, and separate predictive models were built and validated for infants with cleft lip and cleft palate alone. Several secondary analyses were conducted among subgroups of interest. State-wide, population-based Registry data. 6774 infants with orofacial clefts born in Texas between 1999-2014. Preterm birth among infants with orofacial clefts. The final predictive model performed modestly, with an optimism-corrected AUC of 0.67 among all infants with orofacial clefts. The optimism-corrected models for cleft lip (with or without cleft palate) and cleft palate alone had similar predictive capability, with AUCs of 0.66 and 0.67, respectively. Secondary analyses had similar results, but the model among infants with delivery prior to 32 weeks demonstrated higher optimism-corrected predictive capability (AUC = 0.74). This study provides a first step towards predicting preterm birth risk among infants with orofacial clefts. Identifying pregnancies affected by orofacial clefts at the highest risk for preterm birth may lead to new avenues for improving outcomes among these infants.

Exome sequencing findings in children with annular pancreas.

Annular pancreas (AP) is a congenital defect of unknown cause in which the pancreas encircles the duodenum. Theories include abnormal migration and rotation of the ventral bud, persistence of ectopic pancreatic tissue, and inappropriate fusion of the ventral and dorsal buds before rotation. The few reported familial cases suggest a genetic contribution. We conducted exome sequencing in 115 affected infants from the California birth defects registry. Seven cases had a single heterozygous missense variant in IQGAP1, five of them with CADD scores >20; seven other infants had a single heterozygous missense variant in NRCAM, five of them with CADD scores >20. We also looked at genes previously associated with AP and found two rare heterozygous missense variants, one each in PDX1 and FOXF1. IQGAP1 and NRCAM are crucial in cell polarization and migration. Mutations result in decreased motility which could possibly cause the ventral bud to not migrate normally. To our knowledge, this is the first study reporting a possible association for IQGAP1 and NRCAM with AP. Our findings of rare genetic variants involved in cell migration in 15% of our population raise the possibility that AP may be related to abnormal cell migration.

Population-based prevalence and trend of birth defects in Costa Rica from 2000 to 2019.

We aimed to analyze the prevalence and trend of birth defects (BDs) in Costa Rica, where BDs are the second leading cause of infant and under-five mortality. A descriptive analysis of selected BDs prevalence and trends from 2000 to 2019 was performed, based on data from the Costa Rican Birth Defects Register Center, the national BDs surveillance system with coverage of 98% of live births in the country. We used Joinpoint regression to identify any calendar year where a significant change in trend occurred; the annual percent change (APC) and the average annual percent change (AAPC) were determined. Marginal means and prevalence ratios by subperiod (2000-2009 as referent and 2010-2019) were estimated using Poisson regression, and compared using Wald's chi-square tests (alpha ≤0.05). From 2000 to 2019, BDs occurred in 2.3% of live births (95% CI: 2.3-2.4); 73% of which were major BDs. Males presented a significantly higher prevalence (sex ratio 1.13 males/females). The trend showed an AAPC of +3.7 (p < .05) with two joinpoints, 2005 and 2013. A significant APC (+11.3) was observed during 2005-2013, within the context of improvements in the surveillance system, such as the increase in the reporting age, and the incorporation of other data sources in addition to maternity hospitals. Most of the BDs groups presented a significant upward trend. The highest AAPC was observed for the respiratory system (+11.7), congenital heart defects (+9.5), and nervous system (+8.5). The BDs present a clear upward trend in the last two decades due, among other things, to a significant improvement in the surveillance system.

Contribution of Preterm Birth to Mortality Among Neonates With Birth Defects

ABSTRACT Birth defects are an important cause of death among infants who die within their first year. Among other complications associated with birth defects, mothers are at higher risk for preterm delivery, which is also associated with infant mortality. Some previous research has shown that in a population of infants with birth defects, those born at term are 3 to 4 times more likely to survive as their preterm peers. This study aimed to clarify the relationship between birth defects, infant mortality, and preterm birth using the population attributable fraction (PAF), examining the mortality risk attributable to preterm birth in infants with birth defects. Data for this study came from the Texas Birth Defects Registry, which includes live births, still births, and pregnancy terminations with a structural birth defect or chromosomal abnormality. The sample included live-born infants with 1 or more major birth defects between January 1, 1999 and December 31, 2014. Exclusion criteria were infants with a chromosomal abnormality or diagnosed syndrome, infants missing data on gestational age or with a gestational age less than 24 weeks, and anencephaly. The final sample included 169,148 infants; of these, 40,872 were preterm (&lt;37 weeks), 128,276 were term, and 2715 died as neonates. Distributions of maternal and infant characteristics were significantly different between the 2 groups (P &lt; 0.01), with more mothers of preterm infants experiencing diabetes, hypertension, multiple gestation pregnancies, or cesarean delivery. In addition, more preterm infants had multiple birth defects or congenital heart defects than their term peers. Analysis of the data included estimates of PAF for infant mortality risk attributed to 31 different birth defects, with results ranging from 12.5% to 71.9%. Highest PAF estimates were observed for anotia or microtia (71.9%; CI, 41.1–86.6), hypospadias (69.4%; CI, 53.9–79.7), talipes equinovarus (69.4%; CI, 60.0–76.6), and stenosis or atresia of the large intestine, rectum, or anal canal (69.1%; CI, 56.3–78.1). On the other hand, lowest PAF estimates included hypoplastic left heart syndrome (12.5%; CI, 8.7–16.1), coarctation of the aorta (19.7%; CI, 9.8–28.4), diaphragmatic hernia (23.8%; CI, 19.2–28.2), and holoprosencephaly (26.0%; CI, 14.5–35.9). For each defect associated with a higher PAF, a large percentage of infant deaths were those born preterm. Infants with defects that had a high PAF estimate were 11.4–17.8 times more likely to die if born preterm than term, and those with a low PAF estimate were only 1.9–2.3 times more likely to die if born preterm as opposed to full term. Overall, analysis showed that 51.7% of neonatal mortality in infants with birth defects is attributable to preterm birth. Stratified analyses performed to reduce confounders showed similar results. The relationship between birth defects and other factors contributing to preterm delivery and infant mortality is complex, and thus this study is unable to fully characterize these relationships. The associations revealed in this analysis indicate that preterm birth is a significant contributor to infant mortality in infants with birth defects, and further research can more fully characterize this association by attempting interventions both to mitigate preterm birth and to reduce infant mortality after preterm birth. Further research might also focus on particular types of birth defects and how rates of preterm birth might be reduced in specific cases of either infant or maternal risks.

Associated anomalies in Pierre Robin sequence.

Pierre Robin sequence (PRS) is frequently co-occurring with other non-PRS congenital anomalies. The types and the prevalence of anomalies co-occurring with PRS vary in the reported studies. The aims of this report was to study the types and the prevalence of the anomalies co-occurring with PRS in a well-studied population northeastern France. The types and the prevalence of anomalies co-occurring in cases with PRS were ascertained in all terminations of pregnancy, stillbirths and live births in 387,067 births occurring consecutively during the period 1979-2007 in the area covered by our registry of congenital anomalies which is population-based, 89 cases of PRS were registered during the study period with a prevalence of 2.29 per 10,000 births, 69.7% of the cases had associated non-PRS anomalies. Chromosomal abnormalities were present in 10 (11.2%) cases including three 22 q11.2 deletion. Non-chromosomal recognizable conditions were diagnosed in 27 cases (30.3%) including 10 Stickler syndrome, 8 Treacher Collins syndrome, 3 cases with short stature and 6 other syndromes. Multiple congenital anomalies (MCA) were present in 25 cases (28.1%). The most frequent MCA were in the ear, face and neck (35 out of 98 anomalies, 35.7%), cardiovascular (18 anomalies, 18.4%), musculoskeletal (11 anomalies, 11.2%), central nervous (7 anomalies, 7.1%), urinary (6 anomalies, 6.1%), and eye (6 anomalies, 6.1%) system. The high prevalence of associated anomalies justifies a thorough screening for other congenital anomalies in cases with PRS.