Search

Objective: To determine the accuracy and reliability of remotely directed and interpreted ultrasound (teleultrasound) as compared with standard in-person ultrasound for the detection of fetal anomalies, and to determine participants' satisfaction with teleultrasound., Study Design: This was a single-center, randomized (1:1) noninferiority study. Individuals referred to the maternal-fetal medicine (MFM) ultrasound clinic were randomized to standard in-person ultrasound and counseling or teleultrasound and telemedicine counseling. The primary outcome was major fetal anomaly detection rate (sensitivity). All ultrasounds were performed by registered diagnostic medical sonographers and interpretations were done by a group of five MFM physicians. After teleultrasound was completed, the teleultrasound patients filled out a satisfaction survey using a Likert scale. Newborn data were obtained from the newborn record and statewide birth defect databases., Results: Of 300 individuals randomized in each group, 294 were analyzed in the remotely interpreted teleultrasound group and 291 were analyzed in the in-person ultrasound group. The sensitivity of sonographic detection of 28 anomalies was 82.14% in the control group and of 20 anomalies in the telemedicine group, it was 85.0%. The observed difference in sensitivity was 0.0286, much smaller than the proposed noninferiority limit of 0.05. Specificity, negative predictive value, positive predictive value, and accuracy were more than 94% for both groups. Patient satisfaction was more than 95% on all measures, and there were no significant differences in patient satisfaction based on maternal characteristics., Conclusion: Teleultrasound is not inferior to standard in-person ultrasound for the detection of fetal anomalies. Teleultrasound was uniformly well received by patients, regardless of demographics. These key findings support the continued expansion of telemedicine services., Key Points: · For detection of major anomalies, teleultrasound is comparable to standard ultrasound.. · Teleultrasound was well accepted by patients.. · Teleultrasound use should be expanded.., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: Few studies have evaluated associations between birth defects and risk of pediatric cancers by age of attainment. Therefore, we assessed the risk of cancer among children with and without birth defects by age at attainment., Methods: We examined cancer risk in children ≤14 years with and without birth defects born between 1996 and 2011 by linking data from the Arkansas Reproductive Health Monitoring System, Arkansas Central Cancer Registry, and birth certificates. Age of attainment for cancer was calculated as person-years from birth to cancer diagnosis, death, or end of study period, whichever occurred first. Using Cox proportional hazards models, we evaluated associations by attained age groups (<1, 1-4, 5-9, and 10-14 years) between: (1) groups of birth defects (any, chromosomal, and non-chromosomal) and any cancer; (2) non-chromosomal birth defects by organ system and any cancer; and (3) non-chromosomal birth defects and subtypes of cancer., Results: In the cohort of 629,086 children, 23,341 (3.7%) children had birth defects and 1,037 (0.2%) children had cancer. For children with non-chromosomal birth defects, specifically cardiovascular and genitourinary, highest risk of any cancer was observed in first year of life (Hazard Ratio [HR] 18.5; 95% confidence interval [CI] 10.1-33.8). For children with chromosomal birth defects, increased cancer risk was observed among those 1-4 years-old (HR 20.0; 95% CI 8.3-48.4)., Conclusion: Overall, cancer risk among children with birth defects was highest among those <5 years-old. Our findings, consistent with previous studies, may inform surveillance strategies for children with birth defects., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Birth defects are established risk factors for childhood cancer. Nonetheless, cancer epidemiology in children with birth defects is not well characterized., Methods: Using data from population-based registries in 4 US states, this study compared children with cancer but no birth defects (n = 13,111) with children with cancer and 1 or more nonsyndromic birth defects (n = 1616). The objective was to evaluate cancer diagnostic characteristics, including tumor type, age at diagnosis, and stage at diagnosis., Results: Compared with the general population of children with cancer, children with birth defects were diagnosed with more embryonal tumors (26.6% vs 18.7%; q < 0.001), including neuroblastoma (12.5% vs 8.2%; q < 0.001) and hepatoblastoma (5.0% vs 1.3%; q < 0.001), but fewer hematologic malignancies, including acute lymphoblastic leukemia (12.4% vs 24.4%; q < 0.001). In age-stratified analyses, differences in tumor type were evident among children younger than 1 year and children 1 to 4 years old, but they were attenuated among children 5 years of age or older. The age at diagnosis was younger in children with birth defects for most cancers, including leukemia, lymphoma, astrocytoma, medulloblastoma, ependymoma, embryonal tumors, and germ cell tumors (all q < 0.05)., Conclusions: The results indicate possible etiologic heterogeneity in children with birth defects, have implications for future surveillance efforts, and raise the possibility of differential cancer ascertainment in children with birth defects., Lay Summary: Scientific studies suggest that children with birth defects are at increased risk for cancer. However, these studies have not been able to determine whether important tumor characteristics, such as the type of tumor diagnosed, the age at which the tumor is diagnosed, and the degree to which the tumor has spread at the time of diagnosis, are different for children with birth defects and children without birth defects. This study attempts to answer these important questions. By doing so, it may help scientists and physicians to understand the causes of cancer in children with birth defects and diagnose cancer at earlier stages when it is more treatable., (© 2020 American Cancer Society.)

Background: Congenital limb deficiencies (CLDs) are a relatively common group of birth defects whose etiology is mostly unknown. Recent studies suggest maternal air pollution exposure as a potential risk factor., Aim: To investigate the relationship between ambient air pollution exposure during early pregnancy and offspring CLDs., Methods: The study population was identified from the National Birth Defects Prevention Study, a population-based multi-center case-control study, and consisted of 615 CLD cases and 5,701 controls with due dates during 1997 through 2006. Daily averages and/or maxima of six criteria air pollutants (particulate matter <2.5 μm [PM 2.5 ], particulate matter <10 μm [PM 10 ], nitrogen dioxide [NO 2 ], sulfur dioxide [SO 2 ], carbon monoxide [CO], and ozone [O 3 ]) were averaged over gestational weeks 2-8, as well as for individual weeks during this period, using data from EPA air monitors nearest to the maternal address. Logistic regression was used to estimate odds ratios (aORs) and 95% confidence intervals (CIs) adjusted for maternal age, race/ethnicity, education, and study center. We estimated aORs for any CLD and CLD subtypes (i.e., transverse, longitudinal, and preaxial). Potential confounding by co-pollutant was assessed by adjusting for one additional air pollutant. Using the single pollutant model, we further investigated effect measure modification by body mass index, cigarette smoking, and folic acid use. Sensitivity analyses were conducted restricting to those with a residence closer to an air monitor., Results: We observed near-null aORs for CLDs per interquartile range (IQR) increase in PM 10 , PM 2.5 , and O 3 . However, weekly averages of the daily average NO 2 and SO 2 , and daily max NO 2 , SO 2 , and CO concentrations were associated with increased odds of CLDs. The crude ORs ranged from 1.03 to 1.12 per IQR increase in these air pollution concentrations, and consistently elevated aORs were observed for CO. Stronger associations were observed for SO 2 and O 3 in subtype analysis (preaxial). In co-pollutant adjusted models, associations with CO remained elevated (aORs: 1.02-1.30); but aORs for SO 2 and NO 2 became near-null. The aORs for CO remained elevated among mothers who lived within 20 km of an air monitor. The aORs varied by maternal BMI, smoking status, and folic acid use., Conclusion: We observed modest associations between CLDs and air pollution exposures during pregnancy, including CO, SO 2 , and NO 2 , though replication through further epidemiologic research is warranted., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: The National Birth Defects Prevention Study (NBDPS) is a multisite, population-based, case-control study of genetic and nongenetic risk factors for major structural birth defects. Eligible women had a pregnancy affected by a birth defect or a liveborn child without a birth defect between 1997 and 2011. They were invited to complete a telephone interview to collect pregnancy exposure data and were mailed buccal cell collection kits to collect specimens from themselves, their child (if living), and their child's father. Over 23,000 families representing more than 30 major structural birth defects provided DNA specimens., Methods: To evaluate their utility for exome sequencing (ES), specimens from 20 children with colonic atresia were studied. Evaluations were conducted on specimens collected using cytobrushes stored and transported in open versus closed packaging, on native genomic DNA (gDNA) versus whole genome amplified (WGA) products and on a library preparation protocol adapted to low amounts of DNA., Results: The DNA extracted from brushes in open packaging yielded higher quality sequence data than DNA from brushes in closed packaging. Quality metrics of sequenced gDNA were consistently higher than metrics from corresponding WGA products and were consistently high when using a low input protocol., Conclusions: This proof-of-principle study established conditions under which ES can be applied to NBDPS specimens. Successful sequencing of exomes from well-characterized NBDPS families indicated that this unique collection can be used to investigate the roles of genetic variation and gene-environment interaction effects in birth defect etiologies, providing a valuable resource for birth defect researchers., (© 2019 Wiley Periodicals, Inc.)

Background/objectives: In this report, the National Birth Defects Prevention Network (NBDPN) examines and compares gastroschisis and omphalocele for a recent 5-year birth cohort using data from 30 population-based birth defect surveillance programs in the United States., Methods: As a special call for data for the 2019 NBDPN Annual Report, state programs reported expanded data on gastroschisis and omphalocele for birth years 2012-2016. We estimated the overall prevalence (per 10,000 live births) and 95% confidence intervals (CI) for each defect as well as by maternal race/ethnicity, maternal age, infant sex, and case ascertainment methodology utilized by the program (active vs. passive). We also compared distribution of cases by maternal and infant factors and presence/absence of other birth defects., Results: The overall prevalence estimates (per 10,000 live births) were 4.3 (95% CI: 4.1-4.4) for gastroschisis and 2.1 (95% CI: 2.0-2.2) for omphalocele. Gastroschisis was more frequent among young mothers (<25 years) and omphalocele more common among older mothers (>40 years). Mothers of infants with gastroschisis were more likely to be underweight/normal weight prior to pregnancy and mothers of infants with omphalocele more likely to be overweight/obese. Omphalocele was twice as likely as gastroschisis to co-occur with other birth defects., Conclusions: This report highlights important differences between gastroschisis and omphalocele. These differences indicate the importance of distinguishing between these defects in epidemiologic assessments. The report also provides additional data on co-occurrence of gastroschisis and omphalocele with other birth defects. This information can provide a basis for future research to better understand these defects., (Published 2019. This article is a U.S. Government work and is in the public domain in the USA.)

Background: With their unique history of exposure to extensive nuclear testing between 1946 and 1958, descendants of Marshall Island residents may have underappreciated genetic abnormalities, increasing their risk of birth defects., Methods: We conducted a retrospective cohort study of resident women with at least one singleton live birth between 1997 and 2013 in northwest Arkansas using state birth certificate data linked to data from the Arkansas Reproductive Health Monitoring System, a statewide birth defects registry. We calculated unadjusted and adjusted prevalence ratios (PR) and 95% confidence intervals (CI) from modified Poisson regression analyses for non-Hispanic (NH) whites, NH-blacks, Hispanics and Marshallese, using NH-whites as the reference group., Results: Of the 91,662 singleton births during the study period, 2,488 were to Marshallese women. Due to the relatively small number of Marshallese births, we could not calculate prevalence estimates for some defects. Marshallese infants had higher rates of congenital cataracts (PR = 9.3; 95% CI: 3.1, 27.9). Although the number of defects was low, Marshallese infants also had higher rates of truncus arteriosus (PR = 44.0; 95% CI: 2.2, 896.1)., Conclusions: Marshallese infants may have increased risk of specific birth defects, but estimates are unstable because of small sample size so results are inconclusive. Larger population-based studies would allow for further investigation of this potential risk among Marshallese infants., (© 2019 Wiley Periodicals, Inc.)

Background: Previous studies demonstrate that infant and childhood mortality differ among children with birth defects by maternal race/ethnicity, but limited mortality information is published for Hispanic ethnic subgroups., Methods: We performed a retrospective cohort study using data for children with birth defects born to Hispanic mothers during 1999-2007 from 12 population-based state birth defects surveillance programs. Deaths were ascertained through multiple sources. Survival probabilities were estimated by the Kaplan-Meier method. Cox proportional hazards regression was used to examine the effect of clinical and demographic factors on mortality risk., Results: Among 28,497 Hispanic infants and children with major birth defects, 1-year survival was highest for infants born to Cuban mothers at 94.6% (95% confidence intervals [CI] 92.7-96.0) and the lowest for Mexicans at 90.2% (95% CI 89.7-90.6; p < .0001). For children aged up to 8 years, survival remained highest for Cuban Americans at 94.1% (95% CI 91.8-95.7) and lowest for Mexican Americans at 89.2% (95% CI 88.7-89.7; p = .0002). In the multivariable analysis using non-Hispanic White as the reference group, only infants and children born to Mexican mothers were noted to have a higher risk of mortality for cardiovascular defects., Conclusions: This analysis provides a better understanding of survival and mortality for Hispanic infants and children with selected birth defects. The differences found in survival, particularly the highest survival rates for Cuban American children and lowest for Mexican American children with birth defects, underscores the importance of assessing Hispanic ethnic subgroups, as differences among subgroups appear to exist., (© 2017 Wiley Periodicals, Inc.)

Background: We evaluated selected birth defects over a 9-year period to assess prevalence trends by selected maternal and infant factors., Methods: Data were pooled from 11 population-based birth defects surveillance programs in the United States for children born between 1999 and 2007. Overall prevalence, as well as 3-year interval prevalence, was calculated for 26 specific birth defects, stratified by maternal age, maternal race/ethnicity, and infant sex. Average annual percent change (AAPC) was calculated for each birth defect. Poisson regression was used to determine change in AAPC, and joinpoint regression to identify breakpoints and changes in slope for prevalence of each defect over time., Results: Between 1999 and 2001 and 2005 and 2007, four birth defects increased by 10% or more: coarctation of the aorta (17%), gastroschisis (83%), omphalocele (11%), and Down syndrome (10%). Among mothers <20 years of age, the gastroschisis AAPC increased 10.1% overall and, cross-classified by maternal race/ethnicity, the AAPC for mothers <20 years increased 9.2%, 25.7%, and 7.7% among non-Hispanic white (NHW), non-Hispanic black (NHB), and Hispanic mothers, respectively. A small increase in Down syndrome (AAPC 4.4%) was found for NHB mothers ≥35 years., Conclusion: No significant trends in prevalence were identified for most birth defects. Gastroschisis prevalence increased significantly among NHW and NHB mothers <20 years of age, with the greatest increases in NHB mothers. Prevalence of Down syndrome among NHB mothers ≥35 years also increased slightly. Stratified results may suggest avenues of research in birth defect etiology and in evaluating prevention efforts. Birth Defects Research 109:1442-1450, 2017.© 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Background: Gastrointestinal defects are a phenotypically and etiologically diverse group of malformations. Despite their combined prevalence and clinical impact, little is known about the epidemiology of these birth defects. Therefore, the objective of the 2017 National Birth Defects Prevention Network (NBDPN) data brief was to better describe the occurrence of gastrointestinal defects., Methods: As part of the 2017 NBDPN annual report, 28 state programs provided additional data on gastrointestinal defects for the period 2010-2014. Counts and prevalence estimates (per 10,000 live births) were calculated overall and by demographic characteristics for (1) biliary atresia; (2) esophageal atresia/tracheoesophageal fistula; (3) rectal and large intestinal atresia/stenosis; and (4) small intestinal atresia/stenosis. Additionally, we explored the frequency of these malformations co-occurring with other structural birth defects., Results: Pooling data from all participating registries, the prevalence estimates were: 0.7 per 10,000 live births for biliary atresia (713 cases); 2.3 per 10,000 live births for esophageal atresia/tracheoesophageal fistula (2,472 cases); 4.2 per 10,000 live births for rectal and large intestinal atresia/stenosis (4,334 cases); and 3.4 per 10,000 live births for small intestinal atresia/stenosis (3,388 cases). Findings related to co-occurring birth defects were especially notable for esophageal atresia/tracheoesophageal fistula, rectal and large intestinal atresia/stenosis, and small intestinal atresia/stenosis, where the median percentage of non-isolated cases was 53.9%, 45.5%, and 50.6%, respectively., Conclusions: These population-based prevalence estimates confirm some previous studies, and provide a foundation for future epidemiologic studies of gastrointestinal defects. Exploring the genetic and environmental determinants of these malformations may yield new clues into their etiologies., (© 2017 Wiley Periodicals, Inc.)

Background: The birth defects component of the Western Australian Register for Developmental Anomalies (WARDA-BD) was evaluated to assess its efficiency, effectiveness, and data quality., Methods: WARDA-BD was evaluated using the Centers for Disease Control and Prevention Guidelines for Evaluating Public Health Surveillance Systems and Data Quality Standards from the National Birth Defects Prevention Network. The evaluation included interviews with Register staff, local community organizations, parents, clinicians, and researchers; process observation; and secondary data analyses., Results: WARDA-BD is a statutory, statewide, population-based surveillance system established in 1980 that monitors approximately 30,000 births annually. Identification of eligible cases is for children up to age 6 years through active and passive ascertainment methods from multiple sources including birth, death, and hospitalization data; antenatal ultrasonography; hospital unit logs; medical records; fetal medicine departments; cytogenetic laboratories; specialty clinics; and pediatric surgery and pathology departments. Defect diagnoses are verified and coded using the 5-digit British Paediatric Association extension of the International Classification of Disease, Ninth Revision system. Register staff monitor Register data for completeness and accuracy resulting in high quality data with a low percentage of missing items., Conclusion: Strengths of WARDA-BD include high data quality, timeliness, representativeness, stable funding, active community engagement, and high staff retention. Its data were used in numerous epidemiologic investigations resulting in >325 peer-reviewed publications. Potential weaknesses include the limited number of variables collected and low visibility. Although WARDA-BD uses labor intensive case ascertainment and quality assurance and control processes, the Register provides accurate and essential data for stakeholders. Birth Defects Research (Part A) 106:894-904, 2016. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Background: The Birth Defects Study To Evaluate Pregnancy exposureS (BD-STEPS) is a population-based, multi-Center case-control study of modifiable risk factors for selected birth defects in the United States. BD-STEPS is the second major research effort of the Centers for Birth Defects Research and Prevention, which extends and expands the initial research effort, the National Birth Defects Prevention Study (NBDPS)., Methods: BD-STEPS focuses on 17 categories of structural birth defects selected based on severity, prevalence, consistent ascertainment, and previous findings that warrant additional research. Cases are identified through existing birth defects surveillance programs; controls are from vital records or birth hospital logs from the same catchment area. BD-STEPS uses a standardized computer-assisted telephone interview to collect information from case and control mothers on topics including demographics, health conditions, and medication use. Following the maternal interview, selected Centers request permission to sample residual newborn screening blood spots from state repositories for genetic analyses. New components planned for BD-STEPS include linkages with external datasets and use of online questionnaires to collect in-depth information on selected exposures., Results: BD-STEPS extends NBDPS by continuing to collect data on many exposures that were assessed in NBDPS, allowing data from both studies to be combined and providing an unprecedented sample size to analyze rare exposures. BD-STEPS expands upon NBDPS by collecting more detailed information on existing exposures as well as new exposures., Conclusion: The goal of BD-STEPS is to provide women and healthcare providers with information they need to make decisions to promote the healthiest pregnancy possible., (© 2015 Wiley Periodicals, Inc.)

Objectives: To examine racial/ethnic-specific survival of children with major birth defects in the US., Study Design: We pooled data on live births delivered during 1999-2007 with any of 21 birth defects from 12 population-based birth defects surveillance programs. We used the Kaplan-Meier method to calculate cumulative survival probabilities and Cox proportional hazards models to estimate mortality risk., Results: For most birth defects, there were small-to-moderate differences in neonatal (<28 days) survival among racial/ethnic groups. However, compared with children born to non-Hispanic white mothers, postneonatal infant (28 days to <1 year) mortality risk was significantly greater among children born to non-Hispanic black mothers for 13 of 21 defects (hazard ratios [HRs] 1.3-2.8) and among children born to Hispanic mothers for 10 of 21 defects (HRs 1.3-1.7). Compared with children born to non-Hispanic white mothers, a significantly increased childhood (≤ 8 years) mortality risk was found among children born to Asian/Pacific Islander mothers for encephalocele (HR 2.6), tetralogy of Fallot, and atrioventricular septal defect (HRs 1.6-1.8) and among children born to American Indian/Alaska Native mothers for encephalocele (HR 2.8), whereas a significantly decreased childhood mortality risk was found among children born to Asian/Pacific Islander mothers for cleft lip with or without cleft palate (HR 0.6)., Conclusion: Children with birth defects born to non-Hispanic black and Hispanic mothers carry a greater risk of mortality well into childhood, especially children with congenital heart defect. Understanding survival differences among racial/ethnic groups provides important information for policy development and service planning., (Copyright © 2015 Elsevier Inc. All rights reserved.)

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., (© 2010 Wiley-Liss, Inc.)

Anophthalmia and microphthalmia (A/M) are rare birth defects affecting up to 2 per 10,000 live births. These conditions are manifested by the absence of an eye or reduced eye volumes within the orbit leading to vision loss. Although clinical case series suggest a strong genetic component in A/M, few systematic investigations have been conducted on potential genetic contributions owing to low population prevalence. To overcome this challenge, we utilized DNA samples and data collected as part of the National Birth Defects Prevention Study (NBDPS). The NBDPS employed multi-center ascertainment of infants affected by A/M. We performed exome sequencing on 67 family trios and identified numerous genes affected by rare deleterious nonsense and missense variants in this cohort, including de novo variants. We identified 9 nonsense changes and 86 missense variants that are absent from the reference human population (Genome Aggregation Database), and we suggest that these are high priority candidate genes for A/M. We also performed literature curation, single cell transcriptome comparisons, and molecular pathway analysis on the candidate genes and performed protein structure modeling to determine the potential pathogenic variant consequences on PAX6 in this disease.