Rachel E. Rutkowski

Maternal Pre‐Pregnancy Body Mass Index and Risk of Selected Birth Defects: Evidence of a Dose–Response Relationship

BACKGROUNDnThis study investigates the relationship between maternal pre-pregnancy body mass index (BMI) and 26 birth defects identified through the Florida Birth Defects Registry.nnnMETHODSnPre-pregnancy BMI (kg/m(2)) was categorised into underweight (<18.5), normal weight (18.5-24.9), overweight (25.0-29.9), and obese (≥30.0) among Florida resident mothers without pre-gestational diabetes who gave birth to singleton infants from March 2004 through December 2009. Obesity was classified as obese I (30.0-34.9), obese II (35.0-39.9), and obese III (≥40.0). Logistic regression was used to calculate the adjusted odds ratios and 95% confidence interval, representing the association between pre-pregnancy BMI and each of the 26 specific birth defects (and an any birth defect composite). Models were adjusted for maternal age, race/ethnicity, education, smoking, marital status, and nativity.nnnRESULTSnThe livebirth prevalence of any birth defect increased with increasing BMI, from 3.9% among underweight women to 5.3% among obese III women (Pu2009<u20090.001). Results show a direct dose-response relationship between maternal pre-pregnancy BMI and 10 defects under study (cleft palate without cleft lip, diaphragmatic hernia, hydrocephalus without spina bifida, hypoplastic left heart syndrome, pulmonary valve atresia and stenosis, pyloric stenosis, rectal and large intestinal atresia/stenosis, transposition of great arteries, tetralogy of Fallot, and ventricular septal defects) and the any birth defect category. Conversely, gastroschisis exhibited a statistically significant inverse relationship with pre-pregnancy BMI.nnnCONCLUSIONSnThis study provides evidence of the increasing risk of birth defect-affected pregnancy with increasing pre-pregnancy obesity. Reducing pre-pregnancy obesity, even among obese women, may reduce the occurrence of birth defects.

The Association Between Race/Ethnicity and Major Birth Defects in the United States, 1999–2007

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

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

BACKGROUNDnCongenital microcephaly has been linked to maternal Zika virus infection. However, ascertaining infants diagnosed with microcephaly can be challenging.nnnMETHODSnThirty 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.nnnRESULTSnThe 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.nnnCONCLUSIONnDifferences 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.

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

BACKGROUNDnThe 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.nnnMETHODSnWe 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.nnnRESULTSnSensitivity 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.nnnCONCLUSIONSnEfforts 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.

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

BACKGROUNDnGastrointestinal 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.nnnMETHODSnAs 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.nnnRESULTSnPooling 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.nnnCONCLUSIONSnThese 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.

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.

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

ObjectivenPublic 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.nnnMethodsnWe 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.nnnResultsnThe 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.nnnConclusionnOur 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.

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.

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

BACKGROUNDnOnce 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.nnnMETHODSnIn 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.nnnRESULTSnIn 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).nnnCONCLUSIONnThe 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.