Antifungal medication use during early pregnancy and the risk of congenital heart defects in the National Birth Defects Prevention Study, 1997-2011.

BACKGROUND: Fungal infections are common among pregnant people. Recent studies suggest positive associations between oral antifungals used to treat fungal infections and congenital heart defects (CHDs). METHODS: We estimated associations between first trimester antifungal use and 20 major, specific CHDs using data from the National Birth Defects Prevention Study (NBDPS), a multi-site, case-control study that included pregnancies with estimated delivery dates from October 1997 through December 2011. Infants with CHDs ("cases") were ascertained from 10 birth defect surveillance programs. Live born infants without major birth defects ("controls") were randomly selected from birth records or hospital discharge lists. First trimester antifungal use was self-reported via maternal interview. We estimated adjusted odds ratios (AORs) and 95% confidence intervals (CIs) using logistic regression with Firth's penalized likelihood. RESULTS: First trimester antifungal use was reported by 148/11,653 (1.3%) case and 123/11,427 (1.1%) control participants. We estimated AORs for 12 CHDs; six had AORs >1.5 (tetralogy of Fallot, double outlet right ventricle with transposition of the great arteries [DORV-TGA], atrioventricular septal defect, hypoplastic left heart syndrome, pulmonary atresia, muscular ventricular septal defect), and one (pulmonary valve stenosis) had an AOR <0.7. All CIs included the null, except for DORV-TGA. CONCLUSIONS: First trimester antifungal use was rare. We observed some positive associations for several specific CHDs in our analysis, although the CIs largely included the null. Results do not support a large increase in risk, but smaller increases in risk for certain CHD cannot be ruled out.

Delayed entry into prenatal care among women with pre-pregnancy health conditions, National Birth Defects Prevention Study, 1997-2011.

First trimester entry into prenatal care is recommended for all women, and especially women with pre-pregnancy conditions. Our objective was to determine whether women with pre-pregnancy conditions were at lower risk of entry after the first trimester (delayed entry) into prenatal care than women without a pre-pregnancy health condition. We used data from 10,890 participants in the National Birth Defects Prevention Study who delivered liveborn infants without birth defects. Women reported pre-pregnancy conditions and timing of entry into prenatal care during a computer-assisted telephone interview. Multivariable logistic regression analyses were conducted to evaluate whether having a pre-pregnancy condition was associated with delayed entry into prenatal care compared to women without pre-pregnancy conditions. Approximately 13% of women reported delayed entry into prenatal care, and 18% of women reported a pre-pregnancy condition. Delayed entry into prenatal care was not associated with pre-pregnancy cardiometabolic or neurologic conditions. Women with thyroid conditions were less likely to report delayed entry into prenatal care (prevalence odds ratio (OR), 95% confidence interval (CI): 0.55 [0.32, 0.94]), but women with hematologic and respiratory conditions were more likely to report delayed entry into prenatal care (OR: 1.95 [1.00, 3.82] and 1.27 [0.95, 1.72], respectively), compared to those without any chronic conditions. Future research investigating the success of early prenatal care among women with thyroid conditions could identify ways to reduce delayed prenatal care among women with other pre-pregnancy conditions.

A genome-wide association study of obstructive heart defects among participants in the National Birth Defects Prevention Study.

Obstructive heart defects (OHDs) share common structural lesions in arteries and cardiac valves, accounting for ~25% of all congenital heart defects. OHDs are highly heritable, resulting from interplay among maternal exposures, genetic susceptibilities, and epigenetic phenomena. A genome-wide association study was conducted in National Birth Defects Prevention Study participants (Ndiscovery  = 3978; Nreplication  = 2507), investigating the genetic architecture of OHDs using transmission/disequilibrium tests (TDT) in complete case-parental trios (Ndiscovery_TDT  = 440; Nreplication_TDT  = 275) and case-control analyses separately in infants (Ndiscovery_CCI  = 1635; Nreplication_CCI  = 990) and mothers (case status defined by infant; Ndiscovery_CCM  = 1703; Nreplication_CCM  = 1078). In the TDT analysis, the SLC44A2 single nucleotide polymorphism (SNP) rs2360743 was significantly associated with OHD (pdiscovery  = 4.08 × 10-9 ; preplication  = 2.44 × 10-4 ). A CAPN11 SNP (rs55877192) was suggestively associated with OHD (pdiscovery  = 1.61 × 10-7 ; preplication  = 0.0016). Two other SNPs were suggestively associated (p < 1 × 10-6 ) with OHD in only the discovery sample. In the case-control analyses, no SNPs were genome-wide significant, and, even with relaxed thresholds ( × discovery < 1 × 10-5 and preplication < 0.05), only one SNP (rs188255766) in the infant analysis was associated with OHDs (pdiscovery  = 1.42 × 10-6 ; preplication  = 0.04). Additional SNPs with pdiscovery < 1 × 10-5 were in loci supporting previous findings but did not replicate. Overall, there was modest evidence of an association between rs2360743 and rs55877192 and OHD and some evidence validating previously published findings.

Maternal hereditary hemolytic anemia and birth defects in the National Birth Defects Prevention Study.

OBJECTIVES: Hereditary hemolytic anemia (HHA) results from genetic mutations that cause red blood cell abnormalities. Little research exists on the relationship between HHA and birth defects. Using data from the National Birth Defects Prevention Study (NBDPS), we described characteristics of HHA-exposed women and estimated associations between HHA during pregnancy and specific birth defects. METHODS: The NBDPS was a population-based, case-control study of major birth defects and included pregnancies with estimated delivery dates from October 1997 through December 2011. Participants were ascertained from hospital discharge lists or birth defect registries at 10 sites. Trained interviewers collected information about pregnancy exposures via telephone questionnaire. We described characteristics among HHA-exposed women and calculated crude odds ratios and exact 95% confidence intervals for defects with ≥3 exposed cases. RESULTS: Among 31 HHA-exposed women (28 cases/3 controls), 13 (42%) reported sickle cell anemia, 17 (55%) reported thalassemia, and one (3%) reported hereditary spherocytosis. The average age at delivery for HHA-exposed case women was 27.3 years (range: 17-38). The majority (82%) of HHA-exposed case women reported additional conditions during pregnancy, including hypertension, genitourinary infections, and respiratory illnesses. Additionally, 93% of case women reported using medication during pregnancy. Among the 28 cases, 18 (64%) had isolated birth defects. The defects with ≥3 exposed cases were anencephaly, atrial septal defect, gastroschisis, and cleft palate. Except for anencephaly, the 95% confidence intervals for all estimates were close to or included the null. CONCLUSION: This hypothesis-generating study adds to the sparse literature on the association between HHA and birth defects.

Testing and Validating Semi-automated Approaches to the Occupational Exposure Assessment of Polycyclic Aromatic Hydrocarbons.

INTRODUCTION: When it is not possible to capture direct measures of occupational exposure or conduct biomonitoring, retrospective exposure assessment methods are often used. Among the common retrospective assessment methods, assigning exposure estimates by multiple expert rater review of detailed job descriptions is typically the most valid, but also the most time-consuming and expensive. Development of screening protocols to prioritize a subset of jobs for expert rater review can reduce the exposure assessment cost and time requirement, but there is often little data with which to evaluate different screening approaches. We used existing job-by-job exposure assessment data (assigned by consensus between multiple expert raters) from a large, population-based study of women to create and test screening algorithms for polycyclic aromatic hydrocarbons (PAHs) that would be suitable for use in other population-based studies. METHODS: We evaluated three approaches to creating a screening algorithm: a machine-learning algorithm, a set of a priori decision rules created by experts based on features (such as keywords) found in the job description, and a hybrid algorithm incorporating both sets of criteria. All coded jobs held by mothers of infants participating in National Birth Defects Prevention Study (NBDPS) (n = 35,424) were used in developing or testing the screening algorithms. The job narrative fields considered for all approaches included job title, type of product made by the company, main activities or duties, and chemicals or substances handled. Each screening approach was evaluated against the consensus rating of two or more expert raters. RESULTS: The machine-learning algorithm considered over 30,000 keywords and industry/occupation codes (separate and in combination). Overall, the hybrid method had a similar sensitivity (87.1%) as the expert decision rules (85.5%) but was higher than the machine-learning algorithm (67.7%). Specificity was best in the machine-learning algorithm (98.1%), compared to the expert decision rules (89.2%) and hybrid approach (89.1%). Using different probability cutoffs in the hybrid approach resulted in improvements in sensitivity (24-30%), without the loss of much specificity (7-18%). CONCLUSION: Both expert decision rules and the machine-learning algorithm performed reasonably well in identifying the majority of jobs with potential exposure to PAHs. The hybrid screening approach demonstrated that by reviewing approximately 20% of the total jobs, it could identify 87% of all jobs exposed to PAHs; sensitivity could be further increased, albeit with a decrease in specificity, by adjusting the algorithm. The resulting screening algorithm could be applied to other population-based studies of women. The process of developing the algorithm also provides a useful illustration of the strengths and potential pitfalls of these approaches to developing exposure assessment algorithms.

Association between maternal occupational exposure to polycyclic aromatic hydrocarbons and rare birth defects of the face and central nervous system.

BACKGROUND: Previous studies suggested associations between maternal smoking, a source of exposure to polycyclic aromatic hydrocarbons (PAHs) and other chemicals, and central nervous system and face birth defects; however, no previous studies have evaluated maternal occupational PAH exposure itself. METHODS: Jobs held in the periconceptional period were retrospectively assigned for occupational PAH exposures. Associations between maternal occupational PAH exposure and selected rare defects of the face (cataracts, microphthalmia, glaucoma, microtia, and choanal atresia) and central nervous system (holoprosencephaly, hydrocephaly, cerebellar hypoplasia, and Dandy-Walker malformation) were evaluated using data from the National Birth Defects Prevention Study, a population-based case-control study in the United States. Crude and adjusted odds ratios (ORs) with 95% confidence intervals were calculated to estimate associations between each evaluated defect and PAH exposure using multivariable logistic regression. RESULTS: Food and beverage serving, as well as cooks and food preparation occupations, were among the most frequent jobs held by exposed mothers. Cataracts, microtia, microphthalmia, and holoprosencephaly were significantly associated with PAH exposure with evidence of dose-response (P-values for trend ≤.05). Hydrocephaly was associated with any PAH exposure, but not significant for trend. Sensitivity analyses that reduced possible sources of exposure misclassification tended to strengthen associations. CONCLUSIONS: This is the first population-based case-control study to evaluate associations between maternal occupational PAH exposures and these rare birth defects of the central nervous system and face.

Maternal surgery and anesthesia during pregnancy and risk of birth defects in the National Birth Defects Prevention Study, 1997-2011.

BACKGROUND: There is little recent research on the teratogenicity of maternal anesthesia exposure. We used National Birth Defects Prevention Study data to describe surgical procedures conducted during pregnancy and to estimate the risk of birth defects associated with periconceptional anesthesia exposure. METHODS: We used logistic regression to assess associations between general and local anesthesia for surgery during the periconceptional period and specific birth defects. We calculated odds ratios and 95% confidence intervals for 25 birth defects with at least five exposed cases (11,501 controls, 24,337 cases), adjusted for maternal race/ethnicity, age, body mass index, periconceptional exposure to X-ray, CT, or radionuclide scans, and study site. RESULTS: The most commonly reported procedures were dental, dermatologic, and cervical cerclage procedures, regardless of gestational timing. Overall, 226 case and 73 control women reported periconceptional general anesthesia; 230 case and 89 control women reported periconceptional local anesthesia. Women who reported general or local anesthesia were disproportionately non-Hispanic white and were more likely to report periconceptional opioid use and at least one periconceptional X-ray/CT/radionuclide scan. Women who reported general anesthesia were also more likely to report periconceptional injury. We did not observe any significant associations between either type of anesthesia exposure and the birth defects studied. Odds ratios were generally close to null and imprecise. CONCLUSIONS: Our study population reported a wide range of surgical procedures during pregnancy, requiring both general and local anesthesia. Our findings suggest that periconceptional anesthesia is not strongly associated with the birth defects assessed in this study.

Maternal antihypertensive medication use and selected birth defects in the National Birth Defects Prevention Study.

BACKGROUND: There are limited data on the relationship between antihypertensive medication use in early pregnancy and risk of birth defects. METHODS: Using data from the National Birth Defects Prevention Study, we examined associations between specific antihypertensive medication classes and 28 noncardiac birth defects. We analyzed self-reported data on 17,038 case and 11,477 control pregnancies with estimated delivery dates during 1997-2011. We used multivariable logistic regression to estimate odds ratios (ORs) and 95% confidence intervals, adjusted for maternal age, race/ethnicity, body mass index, parity, pregestational diabetes, and study site, for associations between individual birth defects and antihypertensive medication use during the first trimester of pregnancy. We compared risk among women reporting early pregnancy antihypertensive medication use to normotensive women. RESULTS: Hypertensive women who reported early pregnancy antihypertensive medication use were more likely to be at least 35 years old, non-Hispanic Black, obese, multiparous, and to report pregestational diabetes than normotensive women. Compared to normotensive women, early pregnancy antihypertensive medication use was associated with increased risk of small intestinal atresia (adjusted OR 2.4, 95% CI 1.2-4.7) and anencephaly (adjusted OR 1.9, 95% CI 1.0-3.5). Risk of these defects was not specific to any particular medication class. CONCLUSIONS: Maternal antihypertensive medication use was not associated with the majority of birth defects we analyzed, but was associated with an increased risk for some birth defects. Because we cannot entirely rule out confounding by the underlying hypertension and most ORs were based on small numbers, the increased risks observed should be interpreted with caution.

Metformin in the first trimester and risks for specific birth defects in the National Birth Defects Prevention Study.

BACKGROUND: We assessed associations between first-trimester metformin use for pregestational diabetes and specific major birth defects. METHODS: We compared risks associated with first-trimester metformin use by diabetic women to nondiabetic women on no diabetes medication; we calculated crude odds ratios by exact logistic regression and adjusted by inverse probability weighting. Confounding by diabetes was assessed by comparing risks for metformin-exposed diabetic women to those for insulin-exposed diabetics and nondiabetics treated with metformin for subfertililty. RESULTS: Among 9,279 nonmalformed controls and 24,375 malformed cases, diabetics who used metformin (with or without insulin) had increased adjusted odds ratios (aORs) for several birth defects associated with diabetes. However, women treated with metformin for subfertility had aORs similar to or lower than those for diabetic metformin users, and many approximated the null. For atrial septal defect secundum, anorectal defects, and limb reduction defects, the estimates for metformin when used for subfertility were 2-3-fold. CONCLUSION: While metformin use for diabetes was associated with an increased risk of many birth defects, when metformin was used for subfertility most defects had aORs that approximated the null, while only three defects had modestly increased aORs, two of which had lower confidence bounds that included the null. Our study does not suggest that metformin poses an appreciable risk for major birth defects, but further studies are necessary.

Maternal Hypertension, Antihypertensive Medication Use, and Small for Gestational Age Births in the National Birth Defects Prevention Study, 1997-2011.

Background Small for gestational age (SGA) birth is associated with poor long-term health outcomes. It is unclear whether maternal antihypertensive medication increases risk of SGA independently of maternal hypertension. Methods We analyzed associations between maternal hypertension and antihypertensive medication use and SGA among non-malformed singleton controls in the National Birth Defects Prevention Study. We defined SGA as birthweight < 10th percentile for a given gestational age, sex, race/ethnicity, and parity. We included 1045 SGA and 10,019 non-SGA births. We used logistic regression to calculate adjusted odds ratios (AORs) and 95% confidence intervals (CIs). We assessed interaction between hypertension, antihypertensive use, and maternal race/ethnicity and age. Results Overall, 122 (11.7%) SGA and 892 (8.9%) non-SGA mothers reported hypertension and 21 (2.0%) SGA and 154 (1.5%) non-SGA mothers reported antihypertensive use. The most commonly reported medications were centrally-acting antiadrenergics, ß-blockers, calcium channel blockers, and diuretics. Compared to normotensive pregnancies, maternal hypertension, regardless of treatment (AOR, 1.49 [95% CI, 1.20, 1.86]), and untreated maternal hypertension [AOR, 1.46 (95% CI, 1.15, 1.86)] were associated with SGA. We observed a positive, but not significant, association between antihypertensive use and SGA. SGA risk varied by maternal race/ethnicity, being highest among Hispanic mothers, and age, being highest among mothers ≥ 35 years, but statistical tests for interaction were not significant. Conclusions Consistent with the literature, our findings suggest that maternal hypertension slightly increases SGA risk. We did not observe an appreciably increased SGA risk associated with antihypertensive medication use beyond that of the underlying maternal hypertension.

Associations between Maternal Water Consumption and Birth Defects in the National Birth Defects Prevention Study (2000-2005).

BACKGROUND: Water and water-based beverages constitute a major part of daily fluid intake for pregnant women, yet few epidemiologic studies have investigated the role of water consumption on birth outcomes. METHODS: We used data from the National Birth Defects Prevention Study to conduct a case-control study investigating associations between maternal water consumption during pregnancy and birth defects (BD). We used interview data on water consumption during the first trimester of pregnancy in 14,454 cases (major BDs n ≥ 50) and 5,063 controls. Total water consumption was analyzed as a continuous variable and in quartiles. We evaluated the role of dietary quality and sugar sweetened beverage consumption. Logistic regression models were used to assess effects of water consumption on risk of BDs with adjustment for relevant covariates. RESULTS: Mean daily maternal water consumption among controls was 4.4 eight-ounce glasses. We observed decreases in estimated risk associated with increases in water consumption for several BDs, including neural tube defects (spina bifida), oral clefts (cleft lip), musculoskeletal defects (gastroschisis, limb deficiencies), and congenital heart defects (hypoplastic left heart syndrome, right-sided obstructions, pulmonary valve stenosis). Our results were generally unchanged when an indicator for overall dietary quality was included; however, there was evidence of effect measure modification by heavy consumption of sugar-sweetened beverages for some defects, but not all. CONCLUSION: These analyses suggest the importance of sufficient water consumption during early pregnancy, above and beyond it being a marker of higher diet quality. Additional analyses are warranted to understand the biological mechanism for this association. Birth Defects Research 109:193-202, 2017. © 2016 Wiley Periodicals, Inc.

Genetic variation affects congenital heart defect susceptibility in offspring exposed to maternal tobacco use.

BACKGROUND: Congenital heart defects (CHDs) are among the most prevalent and serious birth defects, occurring in 8 to 10 of every 1000 live births in the United States. Epidemiologic studies have reported an association between CHDs and maternal smoking, but it remains unknown how genes impact the susceptibility of offspring to CHDs in the presence of maternal tobacco use. METHODS: Using data from 403 case- and 219 control-parental triads enrolled in the National Birth Defects Prevention Study between 1998 and 2008, we investigated the association between CHDs and maternal and infant genetic variants involved in the tobacco metabolism and DNA repair pathways among mothers who smoked prenatally. RESULTS: The maternal genotypes of single nucleotide polymorphisms in the excision repair cross-complementation group 1 (ERCC1), poly (ADP-ribose) polymerase 2 (PARP2), and ERCC5 genes were identified to be significantly associated with the occurrence of CHDs in the presence of maternal tobacco use. Our analysis also revealed a moderate association between the infant genotypes of polymorphisms in the O-sialoglycoprotein endopeptidase (OSGEP) gene and increased risk of CHDs among mothers who smoked. CONCLUSION: Our study provides evidence that maternal and infant polymorphisms within the ERCC1, PARP2, ERCC5, and OSGEP genes are associated with CHD risk in the presence of maternal tobacco use. These results may provide insight into the susceptibility of having a pregnancy affected by CHDs among women who smoke.

Detecting gene-environment interactions in human birth defects: Study designs and statistical methods.

BACKGROUND: The National Birth Defects Prevention Study (NBDPS) contains a wealth of information on affected and unaffected family triads, and thus provides numerous opportunities to study gene-environment interactions (G×E) in the etiology of birth defect outcomes. Depending on the research objective, several analytic options exist to estimate G×E effects that use varying combinations of individuals drawn from available triads. METHODS: In this study, we discuss important considerations in the collection of genetic data and environmental exposures. RESULTS: We will also present several population- and family-based approaches that can be applied to data from the NBDPS including case-control, case-only, family-based trio, and maternal versus fetal effects. For each, we describe the data requirements, applicable statistical methods, advantages, and disadvantages. CONCLUSION: A range of approaches can be used to evaluate potentially important G×E effects in the NBDPS. Investigators should be aware of the limitations inherent to each approach when choosing a study design and interpreting results.

Detecting maternal-fetal genotype interactions associated with conotruncal heart defects: a haplotype-based analysis with penalized logistic regression.

Nonsyndromic congenital heart defects (CHDs) develop during embryogenesis as a result of a complex interplay between environmental exposures, genetics, and epigenetic causes. Genetic factors associated with CHDs may be attributed to either independent effects of maternal or fetal genes, or the intergenerational interactions between maternal and fetal genes. Detecting gene-by-gene interactions underlying complex diseases is a major challenge in genetic research. Detecting maternal-fetal genotype (MFG) interactions and differentiating them from the maternal/fetal main effects has presented additional statistical challenges due to correlations between maternal and fetal genomes. Traditionally, genetic variants are tested separately for maternal/fetal main effects and MFG interactions on a single-locus basis. We conducted a haplotype-based analysis with a penalized logistic regression framework to dissect the genetic effect associated with the development of nonsyndromic conotruncal heart defects (CTD). Our method allows simultaneous model selection and effect estimation, providing a unified framework to differentiate maternal/fetal main effect from the MFG interaction effect. In addition, the method is able to test multiple highly linked SNPs simultaneously with a configuration of haplotypes, which reduces the data dimensionality and the burden of multiple testing. By analyzing a dataset from the National Birth Defects Prevention Study (NBDPS), we identified seven genes (GSTA1, SOD2, MTRR, AHCYL2, GCLC, GSTM3, and RFC1) associated with the development of CTDs. Our findings suggest that MFG interactions between haplotypes in three of seven genes, GCLC, GSTM3, and RFC1, are associated with nonsyndromic conotruncal heart defects.

Maternal-fetal metabolic gene-gene interactions and risk of neural tube defects.

Single-gene analyses indicate that maternal genes associated with metabolic conditions (e.g., obesity) may influence the risk of neural tube defects (NTDs). However, to our knowledge, there have been no assessments of maternal-fetal metabolic gene-gene interactions and NTDs. We investigated 23 single nucleotide polymorphisms among 7 maternal metabolic genes (ADRB3, ENPP1, FTO, LEP, PPARG, PPARGC1A, and TCF7L2) and 2 fetal metabolic genes (SLC2A2 and UCP2). Samples were obtained from 737 NTD case-parent triads included in the National Birth Defects Prevention Study for birth years 1999-2007. We used a 2-step approach to evaluate maternal-fetal gene-gene interactions. First, a case-only approach was applied to screen all potential maternal and fetal interactions (n = 76), as this design provides greater power in the assessment of gene-gene interactions compared to other approaches. Specifically, ordinal logistic regression was used to calculate the odds ratio (OR) and 95% confidence interval (CI) for each maternal-fetal gene-gene interaction, assuming a log-additive model of inheritance. Due to the number of comparisons, we calculated a corrected p-value (q-value) using the false discovery rate. Second, we confirmed all statistically significant interactions (q < 0.05) using a log-linear approach among case-parent triads. In step 1, there were 5 maternal-fetal gene-gene interactions with q < 0.05. The "top hit" was an interaction between maternal ENPP1 rs1044498 and fetal SLC2A2 rs6785233 (interaction OR = 3.65, 95% CI: 2.32-5.74, p = 2.09×10(-8), q=0.001), which was confirmed in step 2 (p = 0.00004). Our findings suggest that maternal metabolic genes associated with hyperglycemia and insulin resistance and fetal metabolic genes involved in glucose homeostasis may interact to increase the risk of NTDs.

Maternal reporting of prenatal ultrasounds among women in the National Birth Defects Prevention Study.

BACKGROUND: Increased availability and usage of ultrasound screening have led to improved identification of fetal structural abnormalities prenatally. Few population-based studies have been published on prenatal detection for structural birth defects in the United States. The aim of this study is to determine the frequency of maternal reporting of abnormal prenatal ultrasounds for selected birth defects and to investigate associated maternal characteristics. METHODS: Participants included 4013 mothers enrolled in the National Birth Defects Prevention Study who carried a fetus with at least one of 14 structural birth defects between 1997 and 2004. Frequencies of abnormal prenatal ultrasounds were based on maternal report and computed for isolated and multiple defects. Associations between maternal characteristics and abnormal prenatal ultrasounds were assessed using logistic regression. RESULTS: Overall, 46% of participants reported an abnormal ultrasound. Infants with omphalocele, anencephaly, gastroschisis, and renal agenesis were more likely to have abnormal prenatal ultrasounds than those with cleft and limb abnormalities. Hispanic women were less likely to report abnormal prenatal ultrasounds of birth defects than Caucasians, as were women who had a body mass index ≥ 30 kg/m(2) compared with those with a normal body mass index. CONCLUSION: Of the 14 selected birth defects in this study, less than half were reported by mothers of affected infants to have had an abnormal ultrasound during pregnancy. The frequency of reporting abnormal prenatal ultrasounds varies by type of defect, maternal race/ethnicity, and maternal body mass index status.