Zika virus infection during pregnancy can cause congenital brain and eye abnormalities and is associated with neurodevelopmental abnormalities (1-3). In areas of the United States that experienced local Zika virus transmission, the prevalence of birth defects potentially related to Zika virus infection during pregnancy increased in the second half of 2016 compared with the first half (4). To update the previous report, CDC analyzed population-based surveillance data from 22 states and territories to estimate the prevalence of birth defects potentially related to Zika virus infection, regardless of laboratory evidence of or exposure to Zika virus, among pregnancies completed during January 1, 2016-June 30, 2017. Jurisdictions were categorized as those 1) with widespread local transmission of Zika virus; 2) with limited local transmission of Zika virus; and 3) without local transmission of Zika virus. Among 2,004,630 live births, 3,359 infants and fetuses with birth defects potentially related to Zika virus infection during pregnancy were identified (1.7 per 1,000 live births, 95% confidence interval [CI] = 1.6-1.7). In areas with widespread local Zika virus transmission, the prevalence of birth defects potentially related to Zika virus infection during pregnancy was significantly higher during the quarters comprising July 2016-March 2017 (July-September 2016 = 3.0; October-December 2016 = 4.0; and January-March 2017 = 5.6 per 1,000 live births) compared with the reference period (January-March 2016) (1.3 per 1,000). These findings suggest a fourfold increase (prevalence ratio [PR] = 4.1, 95% CI = 2.1-8.4) in birth defects potentially related to Zika virus in widespread local transmission areas during January-March 2017 compared with that during January-March 2016, with the highest prevalence (7.0 per 1,000 live births) in February 2017. Population-based birth defects surveillance is critical for identifying infants and fetuses with birth defects potentially related to Zika virus regardless of whether Zika virus testing was conducted, especially given the high prevalence of asymptomatic disease. These data can be used to inform follow-up care and services as well as strengthen surveillance.

BACKGROUND: As maternal fever affects approximately 6-8% of early pregnancies, it is important to expand upon previous observations of an association between maternal fever and birth defects. METHODS: We analyzed data from the National Birth Defects Prevention Study, a multistate, case-control study of major structural birth defects. Telephone interviews were completed by mothers of cases (n = 17,162) and controls (n = 10,127). Using multivariable logistic regression, we assessed the association between maternal self-report of cold or flu with fever and cold or flu without fever during early pregnancy and 30 categories of non-cardiac birth defects. RESULTS: Maternal report of cold or flu with fever was significantly associated with 8 birth defects (anencephaly, spina bifida, encephalocele, cleft lip with or without cleft palate, colonic atresia/stenosis, bilateral renal agenesis/hypoplasia, limb reduction defects, and gastroschisis) with elevated adjusted odds ratios ranging from 1.2 to 3.7. Maternal report of cold or flu without fever was not associated with any of the birth defects studied. CONCLUSIONS: This study adds to the evidence that maternal fever during early pregnancy is associated with an increased risk for selected birth defects. Elevated associations were limited to mothers who reported a fever, suggesting that it is fever that contributes to the excess risk rather than illnesses associated with it. However, fever may also serve as a marker for more severe infections.

BACKGROUND: Population-based birth defects surveillance is a core public health activity in the United States (U.S.); however, the lack of national data quality standards has limited the use of birth defects surveillance data across state programs. Development of national standards will facilitate data aggregation and utilization across birth defects surveillance programs in the U.S. METHODS: Based on national standards for other U.S. public health surveillance programs, existing National Birth Defects Prevention Network (NBDPN) guidelines for conducting birth defects surveillance, and information from birth defects surveillance programs regarding their current data quality practices, we developed 11 data quality measures that focused on data completeness (n = 5 measures), timeliness (n = 2), and accuracy (n = 4). For each measure, we established tri-level performance criteria (1 = rudimentary, 2 = essential, 3 = optimal). In January 2014, we sent birth defects surveillance programs in each state, District of Columbia, Puerto Rico, Centers for Disease Control and Prevention (CDC), and the U.S. Department of Defense Birth and Infant Health Registry an invitation to complete a self-administered NBDPN Standards Data Quality Assessment Tool. The completed forms were electronically submitted to the CDC for analyses. RESULTS: Of 47 eligible population-based surveillance programs, 45 submitted a completed assessment tool. Two of the 45 programs did not meet minimum inclusion criteria and were excluded; thus, the final analysis included information from 43 programs. Average scores for four of the five completeness performance measures were above level 2. Conversely, the average scores for both timeliness measures and three of the four accuracy measures were below level 2. Surveillance programs using an active case-finding approach scored higher than programs using passive case-finding approaches for the completeness and accuracy measures, whereas their average scores were lower for timeliness measures. CONCLUSIONS: This initial, nation-wide assessment of data quality across U.S. population-based birth defects surveillance programs highlights areas for improvement. Using this information to identify strengths and weaknesses, the birth defects surveillance community, working through the NBDPN, can enhance and implement a consistent set of standards that can promote uniformity and enable surveillance programs to work towards improving the potential of these programs.

Critical congenital heart defects (CCHD) occur in approximately two of every 1,000 live births. Newborn screening provides an opportunity for reducing infant morbidity and mortality. In September 2011, the U.S. Department of Health and Human Services (HHS) Secretary endorsed the recommendation that critical congenital heart defects be added to the Recommended Uniform Screening Panel (RUSP) for all newborns. In 2014, CDC collaborated with the American Academy of Pediatrics (AAP) Division of State Government Affairs and the Newborn Screening Technical Assistance and Evaluation Program (NewSTEPs) to assess states' actions for adopting newborn screening for CCHD. Forty-three states have taken action toward newborn screening for CCHD through legislation, regulations, or hospital guidelines. Among those 43, 32 (74%) are collecting or planning to collect CCHD screening data; however, the type of data collected by CCHD newborn screening programs varies by state. State mandates for newborn screening for CCHD will likely increase the number of newborns screened, allowing for the possibility of early identification and prevention of morbidity and mortality. Data collection at the state level is important for surveillance, monitoring of outcomes, and evaluation of state CCHD newborn screening programs.

In 2011, statewide newborn screening programs for critical congenital heart defects began in the United States, and subsequently screening has been implemented widely. In this review, we focus on data reports and collection efforts related to both prenatal diagnosis and newborn screening. Defect-specific, maternal, and geographic factors are associated with variations in prenatal detection, so newborn screening provides a population-wide safety net for early diagnosis. A new web-based repository is collecting information on newborn screening program policies, quality indicators related to screening programs, and specific case-level data on infants with these defects. Birth defects surveillance programs also collect data about critical congenital heart defects, particularly related to diagnostic timing, mortality, and services. Individuals from state programs, federal agencies, and national organizations will be interested in these data to further refine algorithms for screening in normal newborn nurseries, neonatal intensive care settings, and other special populations; and ultimately to evaluate the impact of screening on outcomes.

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.

BACKGROUND: Little is known about population-based maternal, child, and system characteristics associated with high hospital resource use for children with orofacial clefts (OFC) in the US. METHODS: This was a statewide, population-based, retrospective observational study of children with OFC born between 1998 and 2006, identified by the Florida Birth Defects Registry whose records were linked with longitudinal hospital discharge records. We stratified the descriptive results by cleft type [cleft lip with cleft palate, cleft lip, and cleft palate] and by isolated versus nonisolated OFC (accompanied by other coded major birth defects). We used Poisson regression to analyze associations between selected characteristics and high hospital resource use (≥90(th) percentile of estimated hospitalized days and inpatient costs) for birth, postbirth, and total hospitalizations initiated before age 2 years. RESULTS: Our analysis included 2,129 children with OFC. Infants who were born low birth weight (<2500 grams) were significantly more likely to have high birth hospitalization costs for CLP (adjusted prevalence ratio: 1.6 [95% confidence interval: 1.0-2.7]), CL (adjusted prevalence ratio: 3.0 [95% confidence interval: 1.1-8.1]), and CP (adjusted prevalence ratio: 2.3 [95% confidence interval: 1.3-4.0]). Presence of multiple birth defects was significantly associated with a three- to eleven-fold and a three- to nine-fold increase in the prevalence of high costs and number of hospitalized days, respectively; at birth, postbirth before age 2 years and overall hospitalizations. CONCLUSION: Children with cleft palate had the greatest hospital resources use. Additionally, the presence of multiple birth defects contributed to greater inpatient days and costs for children with OFC.

BACKGROUND: Adverse associations between maternal pesticide exposure and neural tube defects (NTDs) have been suggested but not consistently observed. This study used data from the multisite National Birth Defects Prevention Study to examine associations between maternal periconceptional (1 month preconception through 2 months postconception) occupational pesticide exposure and NTDs. METHODS: Mothers of 502 NTD cases and 2950 unaffected live-born control infants with estimated delivery dates from 1997 through 2002 were included. Duration, categorical intensity scores, and categorical frequency scores for pesticide classes (e.g., insecticides) were assigned using a modified, literature-based job-exposure matrix and maternal-reported occupational histories. Adjusted odds ratios (aORs) and 95% confidence intervals were estimated based on fitted multivariable logistic regression models that described associations between maternal periconceptional occupational pesticide exposure and NTDs. The aORs were estimated for pesticide exposure (any [yes/no] and cumulative exposure [intensity x frequency x duration] to any pesticide class, each pesticide class, or combination of pesticide classes) and all NTD cases combined and NTD subtypes. RESULTS: Positive, but marginally significant or nonsignificant, aORs were observed for exposure to insecticides + herbicides for all NTD cases combined and for spina bifida alone. Similarly, positive aORs were observed for any exposure and cumulative exposure to insecticides + herbicides + fungicides and anencephaly alone and encephalocele alone. All other aORs were near unity. CONCLUSION: Pesticide exposure associations varied by NTD subtype and pesticide class. Several aORs were increased, but not significantly. Future work should continue to examine associations between pesticide classes and NTD subtypes using a detailed occupational pesticide exposure assessment and examine pesticide exposures outside the workplace.

The National Birth Defects Prevention Network (NBDPN) published the first Congenital Malformations Surveillance Report in 1997 and has annually released a report since 2000 that contains state-specific population-based data on major birth defects and a directory describing data collection information for population-based birth defects surveillance programs in the United States. The birth defects in these reports have included conditions affecting major organs of the central nervous, eye, ear, cardiovascular, orofacial, gastrointestinal, genitourinary, and musculoskeletal systems, as well as other disorders, including trisomies and amniotic band sequence. | In 2014, the NBDPN released an updated list of major birth defects as part of its national standards development for birth defects surveillance. The criteria used to guide deliberations for inclusion on the reportable list were: (1) public health importance; (2) accuracy of diagnosis; (3) amenable to prevention/intervention; (4) state of knowledge; (5) structural malformations, diagnosed within the first year of life; and (6) ability to separate into syndromic/nonsyndromic. For example, the NBDPN list now includes all 12 critical congenital heart defects (CCHDs) that are primary and secondary targets of pulse oximetry screening as a result of the addition of CCHD to the U.S. Recommended Universal Screening Panel for newborns (Mahle et al., 2012). Other noncardiac conditions that were added include clubfoot, cloacal exstrophy, craniosynostosis, deletion 22q11.2, holoprosencephaly, small intestinal atresia/stenosis, and Turner syndrome. These additions were balanced with the removal of several conditions, including: amniotic bands, aniridia, congenital hip dislocation, epispadias, fetus or newborn affected by maternal alcohol use, Hirschsprung disease (congenital megacolon), hydrocephalus, microcephalus, patent ductus arterious, and pyloric stenosis. Additional modifications to the list resulted in the regrouping of some conditions. Upper and lower limb deficiencies were collapsed into all limb deficiencies, while cleft lip with or without cleft palate was separated into cleft lip alone and cleft lip with cleft palate. Finally, obstructive genitourinary defect was limited to just the reporting of congenital posterior urethral valves. Table 1 presents the new reported list of birth defects and their diagnostic codes (International Classification of Diseases, 9th Revision, Clinical Modification [ICD-9-CM]; and Centers for Disease Control and Prevention/British Pediatric Association Classification of Diseases [CDC/BPA]).

BACKGROUND: Hypospadias is a frequent birth defect with three phenotypic subtypes. With data from the National Birth Defects Prevention Study, a large, multi-state, population-based, case-control study, we compared risk factors for second and third degree hypospadias. METHODS: A wide variety of data on maternal and pregnancy-related risk factors for isolated second and third degree hypospadias was collected by means of computer-assisted telephone interviews to identify potential etiological differences between the two phenotypes. Logistic regression was used to calculate odds ratios including a random effect by study center. RESULTS: In total, 1547 second degree cases, 389 third degree cases, and 5183 male controls were included in our study. Third degree cases were more likely to have a non-Hispanic black or Asian/Pacific Islander mother, be delivered preterm, have a low birth weight, be small for gestational age, and be conceived with fertility treatments than second degree cases and controls. Associations with both second and third degree hypospadias were observed for maternal age, family history, parity, plurality, and hypertension during pregnancy. Risk estimates were generally higher for third degree hypospadias except for family history. CONCLUSION: Most risk factors were associated with both or neither phenotype. Therefore, it is likely that the underlying mechanism is at least partly similar for both phenotypes. However, some associations were different between second and third degree hypospadias, and went in opposite directions for second and third degree hypospadias for Asian/Pacific Islander mothers. Effect estimates for subtypes of hypospadias may be over- or underestimated in studies without stratification by phenotype.

BACKGROUND: Our objective was to examine differences in hospital resource usage for children with Down syndrome by age and the presence of other birth defects, particularly severe and nonsevere congenital heart defects (CHDs). METHODS: This was a retrospective, population-based, statewide study of children with Down syndrome born 1998 to 2007, identified by the Florida Birth Defects Registry (FBDR) and linked to hospital discharge records for 1 to 10 years after birth. To evaluate hospital resource usage, descriptive statistics on number of hospitalized days and hospital costs were calculated. Results were stratified by isolated Down syndrome (no other coded major birth defect); presence of severe and nonsevere CHDs; and presence of major FBDR-eligible birth defects without CHDs. RESULTS: For 2552 children with Down syndrome, there were 6856 inpatient admissions, of which 68.9% occurred during the first year of life (infancy). Of the 2552 children, 31.7% (n = 808) had isolated Down syndrome, 24.0% (n = 612) had severe CHDs, 36.3% (n = 927) had nonsevere CHDs, and 8.0% (n = 205) had a major FBDR-eligible birth defect in the absence of CHD. Infants in all three nonisolated DS groups had significantly higher hospital costs compared with those with isolated Down syndrome. From infancy through age 4, children with severe CHDs had the highest inpatient costs compared with children in the other sub-groups. CONCLUSION: Results support findings that for children with Down syndrome the presence of other anomalies influences hospital use and costs, and children with severe CHDs have greater hospital resource usage than children with other CHDs or major birth defects without CHDs.

OBJECTIVES: We investigated the relationship between race/ethnicity and 27 major birth defects. METHODS: We 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. RESULTS: American 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). CONCLUSIONS: This 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.

Choanal atresia causes serious posterior nasal obstruction. This defect is the leading cause of nasal surgery in newborns, although its etiology is largely unknown. Data from the National Birth Defects Prevention Study, a population-based case-control study, were used to examine associations between maternal self-reports of exposures and occurrence of choanal atresia in their offspring. Overall, 117 case and 8350 control mothers with deliveries from 1997-2007 provided telephone interview reports of pre-pregnancy (one year before conception) and periconceptional (one month before through three months after conception) exposures. Exposures analyzed were pre-pregnancy dietary intake, pre-pregnancy and periconceptional caffeine consumption, and periconceptional cigarette smoking, alcohol drinking, and medication use. Independent associations between each exposure and all choanal atresia cases combined (n=117) and isolated choanal atresia cases (those without additional unrelated major defects; n=61) were examined. Odds ratios (ORs), both unadjusted (uORs) and adjusted (aORs) for potential confounders, and 95% confidence intervals (CI)s were estimated using unconditional logistic regression analysis. For all choanal atresia cases combined, positive associations were observed with maternal pre-pregnancy intake in the highest quartile for vitamin B-12 (aOR=1.9; CI=1.1,3.1), zinc (aOR=1.7; CI=1.0,3.1), and niacin (aOR=1.8; CI=1.0,3.1), and intake in the lowest quartile for methionine (aOR=1.6; CI=1.0,2.6) and vitamin D (aOR=1.6; CI=1.0,2.4) compared to intake in the two intermediate quartiles combined. Further, a positive association was observed with periconceptional use of thyroid medications (uOR=2.6; CI=1.0,6.3) compared to no use of such medications. Among isolated choanal atresia cases, negative associations were observed for pantothenic acid (aOR=0.4; CI=0.2,0.9) and fat (aOR=0.5; 95% CI=0.2,1.0) intake in the lowest quartile compared to that in the intermediate quartiles, and positive associations were observed for periconceptional cigarette smoking (aOR=2.3; CI=1.1,4.7) compared to no smoking and pre-pregnancy daily coffee intake of 3 or more cups (aOR=2.5; CI=1.1,5.6) compared to intake of less than 1 cup per day. The positive association for periconceptional exposure to thyroid medications also persisted for isolated choanal atresia cases (uOR=4.0; CI=1.1,11.2). Because of the large number of associations tested, these findings may be due to chance. Alternatively, they may contribute new hypotheses regarding the etiology of choanal atresia; thus, requiring replication in additional studies.

IMPORTANCE: Critical congenital heart disease (CCHD) was added to the Recommended Uniform Screening Panel for Newborns in the United States in 2011. Many states have recently adopted or are considering requirements for universal CCHD screening through pulse oximetry in birth hospitals. Limited previous research is directly applicable to the question of how many US infants with CCHD might be identified through screening. OBJECTIVES: To estimate the proportion of US infants with late detection of CCHD (&gt;3 days after birth) based on existing clinical practice and to investigate factors associated with late detection. DESIGN, SETTING, AND PARTICIPANTS: Descriptive and multivariable analysis. Data were obtained from a multisite population-based study of birth defects in the United States, the National Birth Defects Prevention Study (NBDPS). We included all live-born infants with estimated dates of delivery from January 1, 1998, through December 31, 2007, and nonsyndromic, clinically verified CCHD conditions potentially detectable through screening via pulse oximetry. MAIN OUTCOMES AND MEASURES: The main outcome measure was the proportion of infants with late detection of CCHD through echocardiography or at autopsy under the assumption that universal screening at birth hospitals might reduce the number of such late diagnoses. Secondary outcome measures included prevalence ratios for associations between selected demographic and clinical factors and late detection of CCHD. RESULTS: Of 3746 live-born infants with nonsyndromic CCHD, late detection occurred in 1106 (29.5% [95% CI, 28.1%-31.0%]), including 6 (0.2%) (0.1%-0.4%) first receiving a diagnosis at autopsy more than 3 days after birth. Late detection varied by CCHD type from 9 of 120 infants (7.5% [95% CI, 3.5%-13.8%]) with pulmonary atresia to 497 of 801 (62.0% [58.7%-65.4%]) with coarctation of the aorta. In multivariable analysis, late detection varied significantly by CCHD type and study site, and infants with extracardiac defects were significantly less likely to have late detection of CCHD (adjusted prevalence ratio, 0.58 [95% CI, 0.49-0.69]). CONCLUSIONS AND RELEVANCE: We estimate that 29.5% of live-born infants with nonsyndromic CCHD in the NBDPS received a diagnosis more than 3 days after birth and therefore might have benefited from routine CCHD screening at birth hospitals. The number of infants in whom CCHD was detected through screening likely varies by several factors, including CCHD type. Additional population-based studies of screening in practice are needed.

The prevalence of trisomy 21 has been reported to differ by race-ethnicity, however, the results are inconsistent and the cause of the differences is unknown. Using data from 1996 to 2005 from the Metropolitan Atlanta Congenital Defects Program (MACDP), we analyzed the use of prenatal cytogenetic testing and the subsequent use of elective termination among pregnancies affected with any MACDP-eligible birth defect and trisomy 21, by maternal race-ethnicity. We then examined whether these factors could explain the observed differences in the prevalence of trisomy 21 among race-ethnicity groups. Among all pregnancies with birth defects, prenatal cytogenetic testing as well as elective terminations after an abnormal prenatal cytogenetic test result were observed less frequently among Hispanic women than among non-Hispanic white women (odds ratio [OR] 0.66, 95% confidence interval [CI] 0.56-0.78, respectively). In pregnancies affected by trisomy 21, both the Hispanic and the non-Hispanic black populations had more live births (89.5% and 77.8%, respectively) and fewer elective terminations (5.7% and 15.2%, respectively) compared to the non-Hispanic white population (63.0% live births, 32.3% elective terminations). After adjusting for elective terminations, non-Hispanic white mothers had a higher live birth prevalence of trisomy 21 compared to non-Hispanic black (OR 0.64, 95% CI 0.54-0.76) or Hispanic mothers (OR 0.69, 95% CI 0.55-0.86). Overall, our data suggest that factors associated with decisions made about the use of prenatal testing, and about pregnancy management after testing, might play a large role in the race-ethnicity differences observed in the live birth prevalence of trisomy 21.

OBJECTIVE: Critical congenital heart disease (CCHD) was recently added to the U.S. Recommended Uniform Screening Panel for newborns. This evaluation aimed to estimate screening time and hospital cost per newborn screened for CCHD using pulse oximetry as part of a public health economic assessment of CCHD screening. METHODS: A cost survey and time and motion study were conducted in well-newborn and special/intensive care nurseries in a random sample of seven birthing hospitals in New Jersey, where the state legislature mandated CCHD screening in 2011. The sample was stratified by hospital facility level, hospital birth census, and geographic location. At the time of the evaluation, all hospitals had conducted CCHD screening for at least four months. RESULTS: Mean screening time per newborn was 9.1 (standard deviation = 3.4) minutes. Hospitals' total mean estimated cost per newborn screened was $14.19 (in 2011 U.S. dollars), consisting of $7.36 in labor costs and $6.83 in equipment and supply costs. CONCLUSIONS: This federal agency-state health department collaborative assessment is the first state-level analysis of time and hospital costs for CCHD screening using pulse oximetry conducted in the U.S. Hospitals' cost per newborn screened for CCHD with pulse oximetry is comparable with cost estimates of existing newborn screening tests. Hospitals' equipment costs varied substantially based on the pulse oximetry technology employed, with lower costs among hospitals that used reusable screening sensors. In combination with estimates of screening accuracy, effectiveness, and avoided costs, information from this evaluation suggests that CCHD screening is cost-effective.

BACKGROUND: We investigated whether maternal exposure to cigarette smoke was associated with omphalocoele and whether periconceptional folic acid modified the association. METHODS: We analysed data from the National Birth Defects Prevention Study on omphalocoele case (n = 301) and control (n = 8135) mothers for infants born from 1997 through 2007. Mothers who reported active smoking or exposure to second-hand smoke during the periconceptional period (1 month before conception to 3 months after) were considered exposed. Those who reported use of folic acid supplements during the same period were considered supplement users. Odds ratios and 95% confidence intervals were estimated using multivariable logistic regression adjusted for alcohol use, preconception body mass index, and race/ethnicity. RESULTS: One hundred fifteen (38.2%) case and 2592 (31.9%) control mothers reported exposure to cigarette smoke during the periconceptional period. Adjusted odds ratios [95% confidence intervals] were 1.19 [0.94, 1.53] for any smoke exposure, 0.87 [0.54, 1.40] for active smoking, 1.38 [1.00, 1.90] for second-hand smoke exposure, and 1.16 [0.80, 1.67] for both exposures combined. No dose-response relationship was observed. Folic acid-containing supplements did not reduce the risk for omphalocoele among women with active or second-hand smoke exposure. CONCLUSIONS: Self-reported active maternal smoking, with or without exposure to second-hand smoke, during the periconceptional period was not associated with omphalocoele. In contrast, there was a possible association with periconceptional exposure to second-hand smoke.

PURPOSE: The aim of this study was to describe the methods, cases, and initial results of a pilot project using existing public health data collection programs (birth defect surveillance or newborn screening) to conduct long-term follow-up of children with metabolic disorders. METHODS: California, Iowa, New York, and Utah expanded birth defect surveillance or newborn screening programs to collect long-term follow-up data on 19 metabolic disorders. Data elements to monitor health status and services delivered were identified, and record abstraction and data linkages were conducted. Children were followed up through to the age of 3 years. RESULTS: A total of 261 metabolic cases were diagnosed in 1,343,696 live births (19.4 cases/100,000; 95% confidence interval = 17.1-21.8). Four deaths were identified. Children with fatty acid oxidation disorders had a higher percentage of health service encounters compared with children with other disorders of at least one health service encounter (hospitalization, emergency room, metabolic clinic, genetic service provider, or social worker) except for hospitalizations; children with organic acid disorders had a higher percentage of at least one hospitalization during their third year of life than children with other disorders. CONCLUSION: Existing public health data programs can be leveraged to conduct population-based newborn screening long-term follow-up. This approach is flexible according to state needs and resources. These data will enable the states in assessing health burden, assuring access to services, and supporting policy development.

BACKGROUND: Congenital limb deficiencies (LD)s are characterised by the failure or disruption in formation of limbs or digits. Epidemiological research on maternal exposure to cigarette smoke and LDs is inconclusive. METHODS: Data from the National Birth Defects Prevention Study were used to examine LDs and maternal exposure to active or passive cigarette smoke. Mothers of LD case (n = 906) and unaffected control (n = 8352) pregnancies from October 1997 through December 2007 reported on exposure type and quantity. Logistic regression was used to estimate adjusted odds ratio (OR) and 95% confidence interval [95% CI]; interactions with folic acid (FA) intake were tested. RESULTS: For any LD, ORs were elevated for active (1.24 [95% CI 1.01, 1.53]), passive (home) (1.28 [95% CI 1.03, 1.59]), and 'active and passive' (1.34 [95% CI 1.05, 1.70]) exposures. The ORs for longitudinal LDs were elevated for passive (home) (1.62 [95% CI 1.14, 2.31]) and 'active and passive' (1.62 [95% CI 1.09, 2.41]) exposures. The OR for pre-axial LDs were elevated for any (1.39 [95% CI 1.01, 1.90]), active (1.53 [95% CI 1.03, 2.29]), passive (home) (1.82 [95% CI 1.23, 2.69]), and 'active and passive' (1.87 [95% CI 1.20, 2.92]) exposures. For lower limbs, ORs were elevated for passive (home) (1.44 [95% CI 1.01, 2.04]) and smoking 15 or more cigarettes/day (2.25 [95% CI 1.27, 3.97]). Interactions showed that ORs for any passive smoke exposure were 0.43 and 0.59 higher in the absence of FA intake for any and terminal transverse LDs. CONCLUSIONS: Maternal active smoking and exposure to passive cigarette smoke emerged as a potential teratogen that affects limb and digit formation. FA was not found to mitigate the impact.

BACKGROUND: Critical congenital heart disease (CCHD) was recently added to the U.S. Recommended Uniform Screening Panel for newborns. States considering screening requirements may want more information about the potential impact of screening. This study examined potentially avoidable mortality among infants with late detected CCHD and assessed whether late detection was associated with increased hospital resource use during infancy. METHODS: This was a state-wide, population-based, observational study of infants with CCHD (n = 3603) born 1998 to 2007 identified by the Florida Birth Defects Registry. We examined 12 CCHD conditions that are targets of newborn screening. Late detection was defined as CCHD diagnosis after the birth hospitalization. Deaths potentially avoidable through screening were defined as those that occurred outside a hospital following birth hospitalization discharge and those that occurred within 3 days of an emergency readmission. RESULTS: For 23% (n = 825) of infants, CCHD was not detected during the birth hospitalization. Death occurred among 20% (n = 568/2,778) of infants with timely detected CCHD and 8% (n = 66/825) of infants with late detected CCHD, unadjusted for clinical characteristics. Potentially preventable deaths occurred in 1.8% (n = 15/825) of infants with late detected CCHD (0.4% of all infants with CCHD). In multivariable models adjusted for selected characteristics, late CCHD detection was significantly associated with 52% more admissions, 18% more hospitalized days, and 35% higher inpatient costs during infancy. CONCLUSION: Increased CCHD detection at birth hospitals through screening may lead to decreased hospital costs and avoid some deaths during infancy. Additional studies conducted after screening implementation are needed to confirm these findings.

Experimental data indicate that gestational exposures to estrogenic compounds impact risk of hypospadias. We examined whether risk of hypospadias (i.e., a congenital malformation in which the opening of the penile urethra occurs on the ventral side of the penis) was associated with maternal intake of phytoestrogens, given their potential impact on estrogen metabolism. The analysis included data on mothers of 1,250 hypospadias cases and 3,118 controls who delivered their infants from 1997 to 2005 and participated in the National Birth Defects Prevention Study, a multistate, population-based, case-control study. After adjustment for several covariates, high intakes of daidzein, genistein, glycetin, secoisolariciresinol, total isoflavones, total lignans, and total phytoestrogens were associated with reduced risks; odds ratios comparing intakes ≥90th percentile with intakes between the 11th and 89th percentiles ranged from 0.6 to 0.8. For example, the odds ratio for total phytoestrogen intake was 0.7 (95% confidence interval: 0.5, 1.0). This study represents the first large-scale analysis of phytoestrogen intake and hypospadias. The observed associations merit investigation in additional populations before firm conclusions can be reached.

This population-based U.S. study investigated the association between major musculoskeletal malformations and periconceptional maternal occupational pesticide exposure for a wide range of occupations. We conducted a multi-site case-control analysis using data from the National Birth Defects Prevention Study among employed women with due dates from October 1, 1997 through December 31, 2002. Cases included 871 live-born, stillborn, or electively terminated fetuses with isolated craniosynostosis, gastroschisis, diaphragmatic hernia, or transverse limb deficiencies. Controls included 2857 live-born infants without major malformations. Using self-reported maternal occupational information, an industrial hygienist used a job-exposure matrix and expert opinion to evaluate the potential for exposure to insecticides, herbicides or fungicides for each job held during one month pre-conception through three months post-conception. Exposures analyzed included any exposure (yes/no) to pesticides, to insecticides only, to both insecticides and herbicides (I+H) and to insecticides, herbicides and fungicides (I+H+F). We used logistic regression to evaluate the association between exposures and defects, controlling for infant and maternal risk factors. Occupational exposure to I+H+F was associated with gastroschisis among infants of women aged 20 years or older (adjusted odds ratio [aOR]=1.88; 95% confidence interval [CI]: 1.16-3.05), but not for women under age 20 (aOR=0.48; 95% CI: 0.20-1.16). We found no significant associations for the other defects. Additional research is needed to validate these findings in a separate population.

OBJECTIVES:Clinical evidence indicates newborn critical congenital heart disease (CCHD) screening through pulse oximetry is lifesaving. In 2011, CCHD was added to the US Recommended Uniform Screening Panel for newborns. Several states have implemented or are considering screening mandates. This study aimed to estimate the cost-effectiveness of routine screening among US newborns unsuspected of having CCHD. METHODS: We developed a cohort model with a time horizon of infancy to estimate the inpatient medical costs and health benefits of CCHD screening. Model inputs were derived from new estimates of hospital screening costs and inpatient care for infants with late-detected CCHD, defined as no diagnosis at the birth hospital. We estimated the number of newborns with CCHD detected at birth hospitals and life-years saved with routine screening compared with no screening. RESULTS: Screening was estimated to incur an additional cost of $6.28 per newborn, with incremental costs of $20 862 per newborn with CCHD detected at birth hospitals and $40 385 per life-year gained (2011 US dollars). We estimated 1189 more newborns with CCHD would be identified at birth hospitals and 20 infant deaths averted annually with screening. Another 1975 false-positive results not associated with CCHD were estimated to occur, although these results had a minimal impact on total estimated costs. CONCLUSIONS: This study provides the first US cost-effectiveness analysis of CCHD screening in the United States could be reasonably cost-effective. We anticipate data from states that have recently approved or initiated CCHD screening will become available over the next few years to refine these projections.

PURPOSE: To investigate associations between maternal use of common medications and herbals during early pregnancy and risk for hypospadias in male infants. METHODS: We used data from the National Birth Defects Prevention Study, a multi-site, population-based, case-control study. We analyzed data from 1537 infants with second-degree or third-degree isolated hypospadias and 4314 live-born male control infants without major birth defects, with estimated dates of delivery from 1997 to 2007. Exposure was reported use of prescription or over-the-counter medications or herbal products, from 1 month before to 4 months after conception. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were estimated using multivariable logistic regression, adjusting for maternal age, race/ethnicity, education, pre-pregnancy body mass index, previous live births, maternal subfertility, study site, and year. RESULTS: We assessed 64 medication and 24 herbal components. Maternal uses of most components were not associated with an increased risk of hypospadias. Two new associations were observed for venlafaxine (aOR 2.4; 95%CI 1.0, 6.0) and progestin-only oral contraceptives (aOR 1.9; 95%CI 1.1, 3.2). The previously reported association for clomiphene citrate was confirmed (aOR 1.9; 95%CI 1.2, 3.0). Numbers were relatively small for exposure to other specific patterns of fertility agents, but elevated aORs were observed for the most common of them. CONCLUSIONS: Overall, findings were reassuring that hypospadias is not associated with most medication components examined in this analysis. New associations will need to be confirmed in other studies. Increased risks for hypospadias associated with various fertility agents raise the possibility of confounding by underlying subfertility. (Copyright (c) 2013 John Wiley & Sons, Ltd.)

BACKGROUND: Neural tube defects (NTD)s, which occur when the neural tube fails to close during early gestation, are some of the most common birth defects worldwide. Alcohol is a known teratogen and has been shown to induce NTDs in animal studies, although most human studies have failed to corroborate these results. Using data from the National Birth Defects Prevention Study, associations between maternal reports of periconceptional (1 month prior through 2 months postconception) alcohol consumption and NTDs were examined. METHODS: NTD cases and unaffected live born control infants, delivered from 1997 through 2005, were included. Interview reports of alcohol consumption (quantity, frequency, variability, and type) were obtained from 1223 case mothers and 6807 control mothers. Adjusted odds ratios (aOR)s and 95% confidence intervals were estimated using multivariable logistic regression analysis. RESULTS: For all NTDs combined, most aORs for any alcohol consumption, one or more binge episodes, and different type(s) of alcohol consumed were near unity or modestly reduced (≥0.7<aOR≤1.1) and were not statistically significant. Findings were similar for individual NTD subtypes. CONCLUSIONS: These findings suggest no elevated association between maternal periconceptional alcohol consumption and NTDs. Underreporting of alcohol consumption, due to negative social stigma associated with alcohol consumption during pregnancy, and limited reports for mothers with early pregnancy loss of a fetus with an NTD may have affected the estimated odds ratios. Future studies should aim to increase sample sizes for less prevalent subtypes, reduce exposure misclassification, and improve ascertainment offetal deaths and elective terminations. (Birth Defects Research (Part A), 2013. (c) 2013 Wiley Periodicals, Inc.)

Since 1997, the National Birth Defects Prevention Network (NBDPN), in collaboration with the Centers for Disease Control and Prevention (CDC), has published data on major birth defects affecting the central nervous, eye, ear, cardiovascular, orofacial, gastrointestinal, genitourinary, and musculoskeletal systems, as well as trisomies, amniotic bands, and fetal alcohol syndrome, from population-based birth defects surveillance programs in the United States. Annually, the NBDPN Data Committee issues a data request to population-based birth defects programs for data on 47 major birth defects; the specific defects with accompanying diagnostic codes are detailed in Appendix 1 on page 10. This year’s report containing data from 41 population-based birth defects surveillance programs for births occurring from January 1, 2005, through December 31, 2009, is available as a supplement on pages. The data are presented by racial/ethnic groups for all defects and additionally by maternal age for triso-mies 13, 18, and 21. | To calculate prevalence, programs were also asked to provide the number of total live births and male live births for each calendar year submitted. The standard method for calculating birth defects prevalence is to divide the number of cases (birth defect for any pregnancy outcome) by total live births for the catchment area and then multiply by 10,000 to obtain the prevalence per 10,000 live births; Mason et al. (2005) provide further detail and rationale for this approach. This methodology is used for all defects except hypospadias, which is calculated using a denominator of total male live births. An attempt was made to standardize both the submitted data and presentation of state surveillance data, however, differences in the way programs collect and report birth defects data are listed in the footnotes of the accompanying tables and may be referenced in the program directories on pages S121-S169 (online). Some programs were able to only provide data for selected years, were unable to report counts and prevalence by race/ethnicity, or were unable to provide data for each specific defect requested due to differences in the coding systems (i.e., International Classification of Diseases, 9th Revision, Clinical Modification [ICD-9-CM] vs CDC/British Pediat-ric Association [BPA]) Classification of Diseases used to classify birth defects.

BACKGROUND: Animal studies have shown that high doses of caffeine might cause congenital limb deficiencies (LDs); however, no epidemiologic studies have explored this relation. METHODS: This case-control study assessed associations between maternal dietary caffeine and congenital LDs using data from the National Birth Defects Prevention Study (NBDPS), with 844 LD cases and 8069 controls from 1997 to 2007. Caffeine intakes from beverages (coffee, tea, and soda) and chocolate combined and by beverage type were examined. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were estimated for subtypes of isolated LDs (no additional major anomalies) and LDs with other major anomalies separately, comparing the odds of 10 to <100, 100 to <200, 200 to <300, and 300+ mg/day total caffeine intake to 0 to <10 mg/day. RESULTS: All total dietary caffeine intake categories of 10 mg/day and above were marginally associated with odds of all isolated LDs combined (aOR, 1.4-1.7), isolated longitudinal LDs (aOR, 1.2-1.6), and isolated transverse LDs (aOR, 1.3-1.8) compared to the lowest intake category. A dose-response pattern for total dietary caffeine intake was not observed. CONCLUSIONS: A weak increased risk of congenital LDs associated with maternal dietary caffeine consumption was observed in this study; however, risk did not vary by amount of caffeine consumed. (Birth Defects Research (Part A), 2012. (c) 2012 Wiley Periodicals, Inc.)

Newborn screening for critical congenital heart defects, added in September 2011 to the Recommended Uniform Screening Panel in the United States, is a new public health priority and has particular relevance for state birth defects surveillance programs. In this commentary, we review the background to potential involvement by birth defects programs with screening, and detail key questions that these programs can evaluate: (1) health outcomes after newborn screening among affected children; (2) missed primary targets of screening (i.e., affected children who were not screened or had false-negative screens); (3) burden and screening accuracy for secondary targets; (4) the role of altitude, sociodemographic characteristics, and other special circumstances; (5) the contribution of prenatal and clinical diagnoses before newborn screening; and (6) costs and service utilization. To address these issues, monitoring programs will need to pay particular attention to: (1) data sources and quality; (2) timeliness; (3) long-term follow-up for comprehensive outcomes; (4) reporting standards; and (5) state and national program coordination. Although some aspects of involvement with these screening programs will require new partnerships and paradigm shifts in birth defects program operations, the visibility of these screening programs among stakeholders will also provide birth defects programs with new opportunities to demonstrate their usefulness. (Birth Defects Research (Part A), (c) 2012 Wiley Periodicals, Inc.)

BACKGROUND: We examined whether hypospadias was associated with several aspects of the diet, including intake of animal products, intake of several nutrients and food groups related to a vegetarian diet and oestrogen metabolism, and diet quality. METHODS: The study included deliveries from 1997 to 2005 that were part of the National Birth Defects Prevention Study. Diet was assessed by food frequency questionnaire during maternal telephone interviews, and two diet quality indices were developed based on existing indices. Analyses included 1250 cases with second- or third-degree hypospadias (urethra opened at the penile shaft, scrotum or perineum) and 3118 male, liveborn, non-malformed controls. All odds ratios (OR) and 95% confidence intervals [CI] were estimated from logistic regression models that included several potential confounders, including energy intake. RESULTS: Intake of animal products was not associated with hypospadias; for example, the adjusted OR for any vs. no intake of meat was 1.0 [95% CI 0.6, 1.6]. Frequency of intake of meat or other animal products was also not associated with hypospadias, nor was intake of iron or several nutrients that are potentially related to oestrogen metabolism. Diet quality was also not associated with hypospadias; the OR for diet quality in the highest vs. lowest quartile for the two diet quality indices were 1.0 [95% CI 0.6, 1.6] and 0.9 [95% CI 0.7, 1.1]. CONCLUSION: This large study does not support an association of a vegetarian diet or worse diet quality with hypospadias.

OBJECTIVES: Approximately 4% to 12% of pregnant women have asthma; few studies have examined the effects of maternal asthma medication use on birth defects. We examined whether maternal asthma medication use during early pregnancy increased the risk of selected birth defects. METHODS: National Birth Defects Prevention Study data for 2853 infants with 1 or more selected birth defects (diaphragmatic hernia, esophageal atresia, small intestinal atresia, anorectal atresia, neural tube defects, omphalocele, or limb deficiencies) and 6726 unaffected control infants delivered from October 1997 through December 2005 were analyzed. Mothers of cases and controls provided telephone interviews of medication use and additional potential risk factors. Exposure was defined as maternal periconceptional (1 month prior through the third month of pregnancy) asthma medication use (bronchodilator or anti-inflammatory). Associations between maternal periconceptional asthma medication use and individual major birth defects were estimated by using adjusted odds ratios (aOR) and 95% confidence intervals (95%CI). RESULTS: No statistically significant associations were observed for maternal periconceptional asthma medication use and most defects studied; however, positive associations were observed between maternal asthma medication use and isolated esophageal atresia (bronchodilator use: aOR = 2.39, 95%CI = 1.23, 4.66), isolated anorectal atresia (anti-inflammatory use: aOR=2.12, 95%CI=1.09, 4.12), and omphalocele (bronchodilator and anti-inflammatory use: aOR=4.13, 95%CI=1.43, 11.95). CONCLUSIONS: Positive associations were observed for anorectal atresia, esophageal atresia, and omphalocele and maternal periconceptional asthma medication use, but not for other defects studied. It is possible that observed associations may be chance findings or may be a result of maternal asthma severity and related hypoxia rather than medication use.