Are Children Born with Birth Defects at Increased Risk of Injuries in Early Childhood?

OBJECTIVE: To investigate the extent to which children with birth defects experience differential likelihood of various injuries and injury-related hospitalizations in early childhood. STUDY DESIGN: The Florida Birth Defects Registry was used to identify infants born 2006-2010 with select birth defects. Injury matrices were used to detect injuries in inpatient, ambulatory, and emergency department admissions for each infant up to their third birthday. χ2tests were used to compare sociodemographic and perinatal characteristics of children, by presence of an injury-related hospital admission. Adjusted multivariable logistic and zero-inflated negative binomial regression models were used to investigate birth defect and injury associations and related hospital use. RESULTS: We observed a 21% (99% CI: 1.16-1.27) increased odds of injury in children with birth defects. All birth defect subgroups had a statistically significantly increased odds of injury (excluding chromosomal defects), with adjusted ORs ranging from 1.19 to 1.40. The combination of birth defects and injuries resulted in 40% (99% CI: 1.36-1.44) more frequent injury-related hospital visits and a 3-fold (99% CI: 2.76-2.96) increase in time spent receiving inpatient medical care. Over 30% of children with critical congenital heart defects had an injury-related hospital admission. CONCLUSIONS: Children born with specific birth defects are at increased likelihood of various injuries during early life. Although the magnitude of this increased likelihood varied by the mechanism by which the injury occurred, the location of the injury, and the type of birth defect, our study findings support a direct association between birth defects and injuries in early life.

Evaluation of the Sensitivity and Accuracy of Birth Defects Indicators on the 2003 Revision of the U.S. Birth Certificate: Has Data Quality Improved?

BACKGROUND: The 2003 revision of the U.S. Birth Certificate was restricted to birth defects readily identifiable at birth. Despite being the lone source of birth defects cases in some studies, we lack population-based information on the quality of birth defects data from the most recent revision of the birth certificate. METHODS: We linked birth certificate data to confirmed cases from the Florida Birth Defects Registry (FBDR) to assess the sensitivity and positive predictive value (PPV) of birth defects indicators on the birth certificate. Descriptive statistics and log-binomial regression were used to examine variation in data quality measures by defect type and other characteristics. We also evaluated the contribution of birth certificates as a case ascertainment source for the FBDR. RESULTS: Sensitivity of the birth certificate was poor (19.1%) with variation across defects ranging from 55% for anencephaly and 54% for gastroschisis, to <10% for other defects. PPV was better (87.1%) and ranged from >93% for orofacial clefts and gastroschisis to <55% for anencephaly and limb reduction defects. We also observed variation in data quality across maternal, infant, and hospital characteristics. Of cases identified by the birth certificate and not any other FBDR data source, 54.9% were false-positive diagnoses. CONCLUSIONS: Efforts to restrict the 2003 revision of the birth certificate to defects identifiable at birth have not improved the likelihood that birth certificates will identify infants born with those defects. We do not recommend the use of birth certificates as a source of birth defects data without case verification strategies.

Using state and provincial surveillance programs to reduce risk of recurrence of neural tube defects in the United States and Canada: A missed opportunity?

BACKGROUND: Once a woman has had a fetus or infant affected with a neural tube defect (NTD), the risk of recurrence is approximately 3%. This risk can be significantly reduced by folic acid supplement consumption during the periconceptional period; however, this requires women at risk to be adequately informed about the appropriate dosage and timing of supplement intake before planning another pregnancy. As birth defects surveillance programs are tasked with identifying and documenting NTD-affected pregnancies and births, they are in a unique position to support recurrence prevention activities. METHODS: In 2015, we surveyed state and provincial birth defects surveillance programs to assess their NTD recurrence prevention activities. The online survey was sent to programs in 52 United States (U.S.) jurisdictions and all 13 provinces and territories in Canada. Findings were compared with a similar survey conducted in 2005 among U.S. programs. RESULTS: In 2015, of the 44 U.S. and Canadian surveillance programs that responded, only 9 programs (7 U.S. and 2 Canadian) reported currently having activities specifically directed toward preventing NTD recurrence. Compared with a 2005 survey of U.S. programs, the number of U.S. programs working on NTD recurrence prevention decreased by almost 50% (from 13 to 7 programs). CONCLUSION: The number of birth defects surveillance programs with NTD recurrence prevention activities has decreased over the past decade due to a range of barriers, most notably a lack of resources. However, while some recurrence prevention activities require part-time staff, other activities could be accomplished using minimal resources. Birth Defects Research (Part A) 106:875-880, 2016.© 2016 Wiley Periodicals, Inc.

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. © 2016 Wiley Periodicals, Inc.

National population-based estimates for major birth defects, 2016-2020.

BACKGROUND: We provide updated crude and adjusted prevalence estimates of major birth defects in the United States for the period 2016-2020. METHODS: Data were collected from 13 US population-based surveillance programs that used active or a combination of active and passive case ascertainment methods to collect all birth outcomes. These data were used to calculate pooled prevalence estimates and national prevalence estimates adjusted for maternal race/ethnicity for all conditions, and maternal age for trisomies and gastroschisis. Prevalence was compared to previously published national estimates from 1999 to 2014. RESULTS: Adjusted national prevalence estimates per 10,000 live births ranged from 0.63 for common truncus to 18.65 for clubfoot. Temporal changes were observed for several birth defects, including increases in the prevalence of atrioventricular septal defect, tetralogy of Fallot, omphalocele, trisomy 18, and trisomy 21 (Down syndrome) and decreases in the prevalence of anencephaly, common truncus, transposition of the great arteries, and cleft lip with and without cleft palate. CONCLUSION: This study provides updated national estimates of selected major birth defects in the United States. These data can be used for continued temporal monitoring of birth defects prevalence. Increases and decreases in prevalence since 1999 observed in this study warrant further investigation.

Risk of Cardiovascular Disease After COVID-19 Diagnosis Among Adults With and Without Diabetes.

Background Growing evidence suggests incident cardiovascular disease (CVD) may be a long-term outcome of COVID-19 infection, and chronic diseases, such as diabetes, may influence CVD risk associated with COVID-19. We evaluated the postacute risk of CVD >30 days after a COVID-19 diagnosis by diabetes status. Methods and Results We included adults ≥20 years old with a COVID-19 diagnosis from March 1, 2020 through December 31, 2021 in a retrospective cohort study from the IQVIA PharMetrics Plus insurance claims database. A contemporaneous control group comprised adults without recorded diagnoses for COVID-19 or other acute respiratory infections. Two historical control groups comprised patients with or without an acute respiratory infection. Cardiovascular outcomes included cerebrovascular disorders, dysrhythmia, inflammatory heart disease, ischemic heart disease, thrombotic disorders, other cardiac disorders, major adverse cardiovascular events, and any CVD. The total sample comprised 23 824 095 adults (mean age, 48.4 years [SD, 15.7 years]; 51.9% women; mean follow-up, 8.5 months [SD, 5.8 months]). In multivariable Cox regression models, patients with a COVID-19 diagnosis had a significantly greater risk of all cardiovascular outcomes compared with patients without a diagnosis of COVID-19 (hazard ratio [HR], 1.66 [1.62-1.71], with diabetes; HR, 1.75 [1.73-1.78], without diabetes). Risk was attenuated but still significant for the majority of outcomes when comparing patients with COVID-19 to both historical control groups. Conclusions In patients with COVID-19 infection, postacute risk of incident cardiovascular outcomes is significantly higher than among controls without COVID-19, regardless of diabetes status. Therefore, monitoring for incident CVD may be essential beyond the first 30 days after a COVID-19 diagnosis.

Proportion of critical congenital heart defects attributable to unhealthy prepregnancy body mass index among women with live births in Florida, 2005-2016.

BACKGROUND: Associations between maternal prepregnancy body mass index (BMI) and congenital heart defects have been reported, however, the proportion of critical congenital heart defects (CCHDs) attributable to unhealthy prepregnancy BMI has not been determined. Our objective was to investigate the association between maternal prepregnancy BMI and CCHDs. METHODS: The Florida Birth Defects Registry was used to identify infants with CCHDs born between 2005-2016. Birth certificate data were used to define the source population and identify perinatal and socio-demographic characteristics. BMI values were categorized as underweight (<18.5), normal weight (18.5-24.9), overweight (25.0-29.9), obese I (30.0-34.9), obese II (35.0-39.9), and obese III (≥40.0). Multi-predictor logistic regression models were used to estimate adjusted odds ratios (aORs) and 99% confidence intervals representing the association between maternal prepregnancy BMI and CCHDs. Adjusted population attributable fractions (PAFs) for the aORs were calculated. RESULTS: We observed a significantly increased risk of "any CCHD" in infants born to women at any level of obesity. Among the 12 CCHDs examined, 5 showed a significantly increased risk among mothers in the two highest obesity levels (II & III). Approximately 8% of all CCHDs may be attributed to suboptimal maternal prepregnancy BMI, with the highest total individual CCHD PAFs for pulmonary valve atresia (21.7%) and total anomalous pulmonary venous return (12.8%). CONCLUSIONS: Women with suboptimal prepregnancy BMI are at increased odds of having a child born with a CCHD. We found evidence of a direct dose-response relationship between prepregnancy BMI and odds for CCHD; with variation by CCHD subtype.

Evaluating the impact of expanding the number of diagnosis codes reported in inpatient discharge databases on the counts and rates of birth defects.

Objective: Public health surveillance programs worldwide implement a variety of case-finding strategies, and many rely at least in part on International Classification of Diseases (ICD)-based diagnostic codes in administrative and clinical databases. Over time, state- and national-level hospital discharge databases have been expanding the number of reported diagnosis code fields. This study aimed to evaluate the impact of these expansions on frequencies and rates of major birth defects, and the classification of birth defects as isolated vs multiple. Methods: We used state-level 2006-2013 Florida Birth Defects Registry data and 2009-2012 data from a nationally representative database (Kids' Inpatient Database). We generated data under different scenarios by varying the number of diagnosis code fields available, and comparing counts and rates of major birth defects generated under each scenario. Results: The expansion from 10 to 31 diagnosis code fields improved ascertainment by preventing the loss of 1 in every 40 birth defect cases with defect-related diagnoses appearing only in code positions 11 to 31. Although there was variation by birth defect, the largest impact of the expansion tended to occur for less severe birth defects diagnosed in sicker infants. When restricting to fewer codes, not only were fewer cases diagnosed, but more were classified as being isolated due to the inability to capture co-occurring defects. Conclusion: Our findings encourage additional research for other health outcomes in patients of all ages. Other disease registries rely at least in part on diagnostic codes documented by healthcare providers in their case-finding activities, irrespective of ascertainment protocols, making routine investigation of these databases essential.

Identifying Algorithms to Improve the Accuracy of Unverified Diagnosis Codes for Birth Defects.

OBJECTIVES: We identified algorithms to improve the accuracy of passive surveillance programs for birth defects that rely on administrative diagnosis codes for case ascertainment and in situations where case confirmation via medical record review is not possible or is resource prohibitive. METHODS: We linked data from the 2009-2011 Florida Birth Defects Registry, a statewide, multisource, passive surveillance program, to an enhanced surveillance database with selected cases confirmed through medical record review. For each of 13 birth defects, we calculated the positive predictive value (PPV) to compare the accuracy of 4 algorithms that varied case definitions based on the number of diagnoses, medical encounters, and data sources in which the birth defect was identified. We also assessed the degree to which accuracy-improving algorithms would affect the Florida Birth Defects Registry's completeness of ascertainment. RESULTS: The PPV generated by using the original Florida Birth Defects Registry case definition (ie, suspected cases confirmed by medical record review) was 94.2%. More restrictive case definition algorithms increased the PPV to between 97.5% (identified by 1 or more codes/encounters in 1 data source) and 99.2% (identified in >1 data source). Although PPVs varied by birth defect, alternative algorithms increased accuracy for all birth defects; however, alternative algorithms also resulted in failing to ascertain 58.3% to 81.9% of cases. CONCLUSIONS: We found that surveillance programs that rely on unverified diagnosis codes can use algorithms to dramatically increase the accuracy of case finding, without having to review medical records. This can be important for etiologic studies. However, the use of increasingly restrictive case definition algorithms led to a decrease in completeness and the disproportionate exclusion of less severe cases, which could limit the widespread use of these approaches.

Assessing the Impact of Different Race-Bridging Algorithms on the Reported Rate of Birth Defects.

INTRODUCTION: In Florida prior to 2004, the birth certificate only allowed parents to identify themselves as 1 race. The birth certificate was subsequently revised in 2004, allowing parents to identify with more than 1 race. This inconsistency in data collection methods can greatly impact the results of race-specific time trend analyses. Race-bridging techniques have been developed to reassign multiple race responses to single race categories. This investigation aimed to compare race-specific birth defect rates calculated in 2 ways: (1) the current method: treating those selecting multiple race categories as though they selected Other race, and (2) the bridged method: attempting to classify those selecting multiple categories into the category they would have selected if they could only pick 1 race. METHODS: Data from the Florida Office of Vital Statistics and the Florida Birth Defects Registry were used to examine rates of selected birth defects by race among births to non-Hispanic mothers from 2005 to 2014. Rates of selected birth defects were calculated and compared for the following race groups: white, black, American Indian/Alaska Native (AIAN), and Asian/Pacific Islander (API) using the following 6 bridging methods: (1) no bridging method, (2) largest group, whole allocation, (3) smallest group, whole allocation, (4) largest group other than white, (5) equal fractions, fractional allocation, and (6) reported fractions, fractional allocation. RESULTS: The differences in birth defect rates comparing the current method to the recalculated bridged-race population depends on the bridging method used. Using largest group, whole-allocation, the total population of white, black, and API races increased, whereas the total number of AIAN remained unaffected. Using the smallest group or largest group other than white, whole-allocation, the total population of black, API, and AIAN increased, resulting in decreased birth defect rates. Lastly, using equal fractions or reported fractions, fractional allocation we found an increase in the live birth count for each race and a corresponding decrease in birth defect rates. DISCUSSION: Race-bridging techniques may be useful when reviewing race-specific rates over time, or to account for the lack of comparability of race/ethnic classification in birth defect studies, particularly national studies combining data from different states. However, determining the best race-bridging technique warrants further investigation on larger populations and on other health outcomes.

Population-based birth defects data in the United States, 2010-2014: A focus on gastrointestinal defects.

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.

Improving the Completeness of Ascertainment in Florida's Birth Defects Surveillance Program: The Impact of Adding Infant Death and Emergency Department Data.

INTRODUCTION: The Florida Birth Defects Registry (FBDR) relies predominantly on a statewide, population-based, passive surveillance system constructed by linking together multiple administrative and clinical databases. With funding limitations and data restrictions a reality in public health, it is imperative for disease registries to have ongoing evaluation of existing and new data sources. This study quantifies the impact of expanding the FBDR case ascertainment net to include infant death certificates (IDCs) and emergency department (ED) discharge data on the reported prevalence of birth defects. METHODS: Between 2008 and 2011, the FBDR identified cases using various data sources: inpatient and outpatient discharge data (2008-2011), Regional Perinatal Intensive Care Center data (2008), Early Steps program data (2008), IDCs (2009-2011), and ED data (2010-2011). Using hypothetical reconstructions of the FBDR, we examined the overall and unique contribution of each data source in identifying infants with birth defects. This permitted evaluation of a changing FBDR data source mix during the 4-year study period. The effect of adding both IDCs and ED data was investigated by constructing the 2010-2011 FBDR with and without these data sources, and then comparing frequencies and prevalence rates across each scenario. Analyses were conducted for all FBDR cases and for specific birth defect categories; improvements in ascertainment were assessed across sociodemographic and perinatal characteristics. RESULTS: Overall, IDCs captured 3.4% of all infants with at least 1 birth defect studied, ED data captured 3.9% of the cases, and together the 2 data sources captured 7.2%. However, IDCs uniquely identified 0.8% of all cases, ED data uniquely identified 0.7% of all cases, and collectively they identified only 1.4% of cases that would otherwise have been missed. The unique contribution of IDC and ED data to case identification varied by defect and across sociodemographic and perinatal subgroups, with the largest impact among infants with anencephalus (64.7%), trisomy 13 (52.0%), trisomy 18 (22.2%), and encephalocele (13.3%), or those who were born weighing less than 1,500 grams or less than 32 weeks' gestation, or whose mothers' education was eighth grade or less. DISCUSSION: Although their unique contribution is small when all defects are considered together, IDCs and ED data contribute cases that would otherwise have been disproportionately lost and are thus an important addition to surveillance activities. The FBDR continues to strive to create a comprehensive, accurate, and efficient statewide birth defects surveillance system.

Evaluating Difficult Decisions in Public Health Surveillance: Striking the Right Balance between Timeliness and Completeness.

INTRODUCTION: State-based surveillance programs play a key role in birth defects planning, prevention, education, support, and research activities. High-quality data are essential to all of these functions, and a key indicator of quality is timeliness. The Florida Birth Defects Registry (FBDR)-one of the largest population-based state registries in the United States-faces challenges with timeliness, as evidenced by its 18-month lag time. The goal of this study was to determine if the timeliness of the FBDR could be improved without significantly reducing the completeness of birth defect ascertainment. METHODS: Using 2006-2011 data from the FBDR, we first investigated the timing of diagnosis of birth defects by estimating the effect of different periods of follow-up on prevalence rates reported by the FBDR. We achieved this through retrospective reconstructions of the FBDR under 5 different scenarios with progressively narrower follow-up windows for each infant, and by comparing recalculated rates to the rate of the current FBDR with 1 year of follow-up. We then considered scenarios in which the time lag used to construct the FBDR was reduced (15, 12, 9, and 6 months) by using less data (from 7 to 4 quarters). Recalculated rates were again compared to the current FBDR constructed with 2 years of data and an 18-month lag. Analyses were performed overall and for 44 specific defects. RESULTS: During the 6-year study period, the FBDR identified more than 27,000 infants with a defect detected during the first year of life. Restricting follow-up from 1 year to 9 months would only result in a loss of 1.4% of cases. Cutting follow-up in half to 6 months would miss 3.2% of cases, although there was significant variation across defects. Improving timeliness had a small impact on completeness of ascertainment. Overall, compiling the FBDR with only 6 quarters of Florida Agency for Health Care Administration data (as opposed to 8 quarters) would improve timeliness by approximately 6 months, resulting in a registry that is 99.4% complete. DISCUSSION: Six-to-nine month improvements in timeliness were achievable with a minimal sacrifice in completeness (0.6%-1.7%). Efforts to enhance data quality through the assessment of timeliness and completeness indicators are not unique to birth defects surveillance programs. Other programs, particularly those with similar passive case ascertainment protocols, can use our findings to consider a more timely release of registry data, or to design similar investigations of their own.