Search

BACKGROUND Birth defects are established risk factors for childhood cancer. Nonetheless, cancer epidemiology in children with birth defects is not well characterized. METHODS Using data from population-based registries in 4 US states, this study compared children with cancer but no birth defects (n = 13,111) with children with cancer and 1 or more nonsyndromic birth defects (n = 1616). The objective was to evaluate cancer diagnostic characteristics, including tumor type, age at diagnosis, and stage at diagnosis. RESULTS Compared with the general population of children with cancer, children with birth defects were diagnosed with more embryonal tumors (26.6% vs 18.7%; q

Primary congenital glaucoma (PCG) and anterior segment defects (ASDs) are rare ocular malformations diagnosed early in life which can cause blindness. Pathogenic variants in several genes have been linked to these conditions, but little is known about nongenetic risk factors. We investigated the association between maternal nutrition and PCG and ASDs in the National Birth Defects Prevention Study, a large population-based, multicenter case-control study of major birth defects in the United States. Mothers of cases (n = 152) and control infants without a birth defect (n = 9,178) completed an interview which included a food frequency questionnaire capturing usual dietary intake in the year before pregnancy. Maternal nutrition was assessed through individual nutrient intake, calculating a Diet Quality Index for Pregnancy (DQI-P) score for each mother, and using latent class analysis to empirically derive four dietary patterns. We calculated adjusted odds ratios (aORs) and 95% confidence intervals (CI) using logistic regression. The results for individual nutrients varied, with some having an inverse or U-shaped pattern of association with increasing intake. The DQI-P was not associated with risk of PCG and ASDs (aOR 0.91; CI 0.49-1.66, highest vs. lowest quartile). The dietary pattern analysis suggested lower odds among women with a Prudent and Mexican dietary pattern (aOR 0.82, 95% CI 0.52-1.29; aOR 0.80, 95% CI 0.36-1.78, respectively) compared to those with a Western dietary pattern. We found that higher intake of some nutrients and certain dietary patterns may be inversely associated with PCG and ASDs, though caution is urged due to imprecision of estimates.

Objective:Children with orofacial clefts (OFCs) may experience poor reading proficiency, learning disabilities, and academic underachievement. We examined the association between nonsyndromic (NS) OFCs and end-of-grade (EOG) performance in reading and math from third through eighth grade in a sample subgroup.Participants:We identified a cohort of 559 children with NS-OFCs and 6822 children without birth defects, classifying cleft type by cleft lip alone, with or without cleft alveolar ridge (CL); cleft lip with cleft palate (CL+P); and cleft palate only (CP).Main Outcome Measures:Using logistic regression, we estimated the odds of not meeting grade-level standards among children with NS-OFCs compared to unaffected peers. Using longitudinal analyses, we estimated the odds of not meeting grade-level standards and average change in test scores through eighth grade.Results:Children with NS-OFCs were 1.22 (95% CI: 0.96, 1.83) times as likely not to meet grade-level standards in reading compared to unaffected peers. The effect was similar for math (OR: 1.17; 95% CI: 0.92, 1.48). Children with CL+P were 1.33 (95% CI: 0.86, 1.83) and 1.74 (95% CI: 1.19, 2.56) times as likely not to meet grade-level standard in reading and in both subjects, respectively, compared to unaffected peers. The average rate of change in both scores was similar for children with and without OFCs.Conclusions:Poor academic performance appears greatest for children with CL+P, a finding compatible with previous observations and hypothesized mechanisms associating orofacial clefts with subtle abnormalities in brain development. Academic performance monitoring and referral for academic assistance is warranted.

BACKGROUND: Antecedents for infantile hypertrophic pyloric stenosis (IHPS) vary across studies; therefore, we conducted a multistate, population-based retrospective study of the prevalence and descriptive epidemiology of IHPS in the United States (US). METHODS: Data for IHPS cases (n = 29,554) delivered from 1999–2010 and enumerated from 11 US population-based birth defect surveillance programs, along with data for live births (n = 14,707,418) delivered within the same birth period and jurisdictions, were analyzed using Poisson regression to estimate IHPS prevalence per 10,000 live births. Additional data on deliveries from 1999–2005 from seven of these programs were analyzed using multivariable logistic regression to estimate adjusted prevalence ratios (aPR)s and 95% confidence intervals (CI)s for selected infant and parental characteristics. RESULTS: Overall, IHPS prevalence from 1999–2010 was 20.09 (95% CI = 19.87, 20.32) per 10,000 live births, with statistically significant increases from 2003–2006 and decreases from 2007–2010. Compared to their respective referents, aPRs were higher in magnitude for males, preterm births, and multiple births, but lower for birth weights

An ideal dexmedetomidine protocol has yet to be determined for standing sedation in horses. It was hypothesized that an IV bolus followed by CRI dexmedetomidine would have a quicker increase in plasma concentrations compared with repeated IM injections. In a crossover design, eight adult, female horses were randomly placed into two groups: the CRI group (IV bolus dexmedetomidine at 0.005 mg/kg followed by a CRI at 0.01 mg/kg/h for 15 min then 0.005 mg/kg/h for 60 min) and the IM group (dexmedetomidine at 0.01 mg/kg, followed by 0.005 mg/kg in 30-min intervals for 60 min). Clearance and elimination half-life were 134 ± 67.4 ml/kg/min and 44.3 ± 26.3 min, respectively, in the CRI group, and apparent clearance and half-life were 412 ± 306 ml/kg/min (Cl/F) and 38.9 ± 18.6 min, respectively, in the IM group. Analgesia was evaluated using mechanical pressure threshold. Intravenous dexmedetomidine produced faster onset of sedation and increased pressure threshold compared with IM administration. Individual horses had a large variability in dexmedetomidine plasma concentrations between CRI and IM administration. The odds of a decreased GI motility following IV administration was 12.34 times greater compared with IM administration.

Background Little is known about the contemporary mortality experience among adults with congenital heart disease (CHD). The objectives of this study were to assess the age at death, presence of cardiovascular comorbidities, and most common causes of death among adults with CHD in a contemporary cohort within the United States. Methods and Results Patients with CHD who had a healthcare encounter between 2008 and 2013 at 1 of 5 comprehensive CHD centers in North Carolina were identified by International Classification of Diseases, Ninth Revision ( ICD‐9 ), code. Only patients who could be linked to a North Carolina death certificate between 2008 and 2016 and with age at death ≥20 years were included. Median age at death and underlying cause of death based on death certificate data were analyzed. The prevalence of acquired cardiovascular risk factors was determined from electronic medical record data. Among the 629 included patients, the median age at death was 64.2 years. Those with severe CHD (n=157, 25%), shunts (n=202, 32%), and valvular lesions (n=174, 28%) had a median age at death of 46.0, 65.0, and 73.3 years, respectively. Cardiovascular death was most common in adults with severe CHD (60%), with 40% of those deaths caused by CHD. Malignancy and ischemic heart disease were the most common causes of death in adults with nonsevere CHD. Hypertension and hyperlipidemia were common comorbidities among all CHD severity groups. Conclusions The most common underlying causes of death differed by lesion severity. Those with severe lesions most commonly died from underlying CHD, whereas those with nonsevere disease more commonly died from non‐CHD causes.

Background There is a persistent, unexplained disparity in sex ratio among childhood cancer cases, whereby males are more likely to develop most cancers. This male predominance is also seen for most birth defects, which are strongly associated with risk of childhood cancer. We conducted mediation analysis to estimate whether the increased risk of cancer among males is partially explained by birth defect status. Methods We used a population-based birth cohort with linked data from birth certificates, birth defects registries, and cancer registries from Arkansas, Michigan, North Carolina, and Texas. We conducted counterfactual mediation analysis to estimate the natural direct and indirect effects of sex on cancer risk, modeling birth defect status as mediator. State; birth year; plurality; and maternal race and ethnicity, age, and education were considered confounders. We conducted separate analyses limited to cancers diagnosed younger than 1 year of age. Results Our dataset included 10 181 074 children: 15 110 diagnosed with cancer, 539 567 diagnosed with birth defects, and 2124 co-occurring cases. Birth defect status mediated 38% of the association between sex and cancer overall. The proportion mediated varied by cancer type, including acute myeloid leukemia (93%), neuroblastoma (35%), and non-Hodgkin lymphoma (6%). Among children younger than 1 year of age at cancer diagnosis, the proportion mediated was substantially higher (82%). Conclusions Our results suggest that birth defects mediate a statistically significant proportion of the relationship between sex and childhood cancer. The proportion mediated varied by cancer type and diagnosis age. These findings improve our understanding of the causal pathway underlying male sex as a risk factor for childhood cancer.

The science of transitional states of consciousness is reviewed. Despite intensive study, determining the subjective experience of animals during transitional states of consciousness remains inherently limited. Until better assessment tools become available, behavior-based observations, such as loss of righting reflex/loss of posture, remain among our most useful guides to the onset of unconsciousness in animals. To minimize potential animal suffering and to ensure a truly unconscious state is unambiguously achieved, a state of general anesthesia relying on gamma amino butyric acid type A agonists or N-methyl-d-aspartate antagonist agents continues to be a necessary component of the companion animal euthanasia process.

Background A substantial proportion of infants born with tetralogy of Fallot (TOF) die in infancy. A better understanding of the heterogeneity associated with TOF, including extracardiac malformations and chromosomal anomalies is vital to stratifying risk and optimizing outcomes during infancy. Methods Using the North Carolina Birth Defects Monitoring Program, infants diagnosed with TOF and born between 2003 and 2012 were included. Kaplan-Meier survival curves were used to estimate cumulative 1-year mortality, stratified by the presence of concomitant birth defects (BDs) and chromosomal anomalies. Multivariable logistic regression was used to estimate the direct effect of each concomitant BD, after adjusting for all others. Results A total of 496 infants with TOF were included, and 15% (n = 76) died. The number of concomitant BD systems was significantly associated with the risk of death at 1-year, p

Background Congenital microcephaly has been linked to maternal Zika virus infection. However, ascertaining infants diagnosed with microcephaly can be challenging. Methods Thirty birth defects surveillance programs provided data on infants diagnosed with microcephaly born 2009 to 2013. The pooled prevalence of microcephaly per 10,000 live births was estimated overall and by maternal/infant characteristics. Variation in prevalence was examined across case finding methods. Nine programs provided data on head circumference and conditions potentially contributing to microcephaly. Results The pooled prevalence of microcephaly was 8.7 per 10,000 live births. Median prevalence (per 10,000 live births) was similar among programs using active (6.7) and passive (6.6) methods; the interdecile range of prevalence estimates was wider among programs using passive methods for all race/ethnicity categories except Hispanic. Prevalence (per 10,000 live births) was lowest among non-Hispanic Whites (6.5) and highest among non-Hispanic Blacks and Hispanics (11.2 and 11.9, respectively); estimates followed a U-shaped distribution by maternal age with the highest prevalence among mothers

Background Geographic variation in congenital heart disease is not well-described. This study uses geographic information systems (GIS) to describe the spatial epidemiology of tetralogy of Fallot (TOF), in North Carolina (NC) and to compare travel time for cases to congenital heart centers in NC. Methods Using the NC Birth Defects Monitoring Program database, live births with TOF born between 2003 and 2012 were identified. Birth certificates provided demographic variables. A denominator of live births/zip code was obtained from the NC live births database. ArcGIS® software was used to illustrate TOF prevalence by zip code, and SatScanTM was used to identify spatial clusters of TOF cases and to identify changes in cluster location over time. Driving time to each of five NC congenital heart centers was predicted based on road systems information. Results A total of 496 infants were born with TOF between 2003 and 2012. The prevalence was 4.2/10,000 live births. A large cluster (330 zip codes, 306 cases) was identified in northeastern NC. Average driving time for each case to closest congenital heart center was: University of North Carolina 37 min, Vident Medical Center 64 min, Duke University 58 min, Carolina's Medical Center 89 min, and Wake Forest Baptist Health 57 min. Overall, average predicted driving time to the nearest congenital heart center was 61 min. Conclusion Approximately 50 infants/year were born with TOF in NC. One cluster was identified. Further study is necessary to explore potential explanations for the observed case cluster. As interest in regionalization of congenital heart surgery grows, GIS and spatial analysis can become increasingly useful tools for health care planning. Birth Defects Research (Part A) 106:881-887, 2016. © 2016 Wiley Periodicals, Inc.

Background Using the National Birth Defects Prevention Network (NBDPN) annual data report, U.S. national prevalence estimates for major birth defects are developed based on birth cohort 2010-2014. Methods Data from 39 U.S. population-based birth defects surveillance programs (16 active case-finding, 10 passive case-finding with case confirmation, and 13 passive without case confirmation) were used to calculate pooled prevalence estimates for major defects by case-finding approach. Fourteen active case-finding programs including at least live birth and stillbirth pregnancy outcomes monitoring approximately one million births annually were used to develop national prevalence estimates, adjusted for maternal race/ethnicity (for all conditions examined) and maternal age (trisomies and gastroschisis). These calculations used a similar methodology to the previous estimates to examine changes over time. Results The adjusted national birth prevalence estimates per 10,000 live births ranged from 0.62 for interrupted aortic arch to 16.87 for clubfoot, and 19.93 for the 12 critical congenital heart defects combined. While the birth prevalence of most birth defects studied remained relatively stable over 15 years, an increasing prevalence was observed for gastroschisis and Down syndrome. Additionally, the prevalence for atrioventricular septal defect, tetralogy of Fallot, omphalocele, and trisomy 18 increased in this period compared to the previous periods. Active case-finding programs generally had higher prevalence rates for most defects examined, most notably for anencephaly, anophthalmia/microphthalmia, trisomy 13, and trisomy 18. Conclusion National estimates of birth defects prevalence provide data for monitoring trends and understanding the impact of these conditions. Increasing prevalence rates observed for selected conditions warrant further examination.

Simple Summary Carbon dioxide is commonly used for stunning animals prior to killing. It allows several animals to be killed at once, reduces the need for handling, and is a reliable method. However, research in laboratory rodents, poultry, and pigs has indicated that it causes considerable aversion at concentrations above ambient conditions. Currently, there are no available alternatives with desirable characteristics. This manuscript describes a list of research priorities to find and implement the use of alternative methods or agents to improve animal welfare. Abstract The use of carbon dioxide (CO2) for stunning and killing animals is considered to compromise welfare due to air hunger, anxiety, fear, and pain. Despite decades of research, no alternatives have so far been found that provide a safe and reliable way to induce unconsciousness in groups of animals, and also cause less distress than CO2. Here, we revisit the current and historical literature to identify key research questions that may lead to the identification and implementation of more humane alternatives to induce unconsciousness in mice, rats, poultry, and pigs. In addition to the evaluation of novel methods and agents, we identify the need to standardise the terminology and behavioural assays within the field. We further reason that more accurate measurements of consciousness state are needed and serve as a central component in the assessment of suffering. Therefore, we propose a roadmap toward improving animal welfare during end-of-life procedures.

OBJECTIVE: To investigate first-year survival of infants born with spina bifida, and examine the association of maternal prepregnancy body mass index (BMI) with infant mortality. METHODS: This is a retrospective cohort study of 1,533 liveborn infants with nonsyndromic spina bifida with estimated dates of delivery from 1998 to 2011 whose mothers were eligible for the National Birth Defects Prevention Study (NBDPS). NBDPS data were linked to death records to conduct survival analyses. Kaplan–Meier survival functions estimated mortality risk over the first year of life. Cox proportional hazards models estimated hazard ratios (HRs) for maternal prepregnancy BMI categorized as underweight (

Background Birth defects are responsible for a large proportion of disability and infant mortality. Exposure to a variety of pesticides have been linked to increased risk of birth defects. Methods We conducted a case–control study to estimate the associations between a residence-based metric of agricultural pesticide exposure and birth defects. We linked singleton live birth records for 2003 to 2005 from the North Carolina (NC) State Center for Health Statistics to data from the NC Birth Defects Monitoring Program. Included women had residence at delivery inside NC and infants with gestational ages from 20 to 44 weeks (n = 304,906). Pesticide exposure was assigned using a previously constructed metric, estimating total chemical exposure (pounds of active ingredient) based on crops within 500 meters of maternal residence, specific dates of pregnancy, and chemical application dates based on the planting/harvesting dates of each crop. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals for four categories of exposure ( 90th percentiles) compared with unexposed. Models were adjusted for maternal race, age at delivery, education, marital status, and smoking status. Results We observed elevated ORs for congenital heart defects and certain structural defects affecting the gastrointestinal, genitourinary and musculoskeletal systems (e.g., OR [95% confidence interval] [highest exposure vs. unexposed] for tracheal esophageal fistula/esophageal atresia = 1.98 [0.69, 5.66], and OR for atrial septal defects: 1.70 [1.34, 2.14]). Conclusion Our results provide some evidence of associations between residential exposure to agricultural pesticides and several birth defects phenotypes. Birth Defects Research (Part A) 106:240–249, 2016. © 2016 Wiley Periodicals, Inc.

Background: There is a persistent yet unexplained disparity in the sex ratio among childhood cancer cases, whereby males are more likely to develop several cancers. These patterns are also seen for most birth defects, which are strongly associated with the risk of childhood cancer. We conducted a mediation analysis to estimate whether birth defect status mediates the association between sex and childhood cancer risk. Methods: We linked data from birth, birth defects, and cancer registries to obtain a population-based birth cohort including births from 1992-2013 in Arkansas, Michigan, North Carolina, and Texas. We obtained birth defects diagnoses, including chromosomal and nonchromosomal defects, from statewide, population-based birth defects registries. We focused on “major” defects as defined by the National Birth Defects Prevention Network and the National Birth Defects Prevention Study. Cancer diagnoses that occurred prior to age 18 years were obtained from state cancer registries. We obtained data on child’s sex, birth weight, gestational age, maternal race/ethnicity, maternal age, and plurality from birth records. We conducted counterfactual mediation analysis to estimate the direct and indirect effects of sex on risk of childhood cancer, modeling sex as the exposure, birth defect status as the mediator, and cancer type as the outcome. State, maternal race/ethnicity (white, black, other), maternal age (continuous), and plurality (singleton vs. multiple) were considered potential mediator-outcome confounders. Due to lower success rates of linkage to birth records among adolescent cancer cases, we conducted a sensitivity analysis limiting to cancers diagnosed at age < 5 years. Results: Our dataset included 10,181,074 children (5,208,379 males; 4,972,695 females), including 15,110 with cancer diagnoses (8044 males; 7066 females), 539,567 children with birth defects diagnoses (320,666 males; 218,901 females), and 2,124 co-occurring cases (children with both cancer and one or more birth defect diagnosis: 1,186 males; 938 females). We observed mediation of the association between sex and childhood cancer overall by birth defect status (proportion mediated [PM]: 38%). In analyses of specific cancer types, we observed variation of the estimated proportion mediated among several cancers, including hepatoblastoma (PM: 33%), neuroblastoma (PM: 35%), non-Hodgkin lymphoma (PM: 6%), and soft tissue sarcomas (PM: 25%). In analysis of children age < 5 years at cancer diagnosis, we observed similar results. Conclusions: Our results suggest that birth defects mediate a significant proportion of the overall relationship between sex and childhood cancer. While approximately 60% of the male excess in childhood cancer cases remains unexplained, these findings add to our understanding of the causal pathway of male sex as a risk factor for childhood cancer. Additional studies are under way to characterize the biology underlying these observations. This abstract is also being presented as Poster A66. Citation Format: Erin L. Marcotte, Jeremy M. Schraw, Tania A. Desrosiers, Wendy N. Nembhard, Peter H. Langlois, Mark A. Canfield, Robert E. Meyer, Sharon E. Plon, Philip Lupo. Sex ratio disparities and the risk of childhood cancer: Evaluating the mediating effect of birth defects among 15,000 childhood cancer cases [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr PR03.

Population reduction or eradication of domestic or non-domestic species may be required to address their impacts on the environment, other species, or human interests. Firearms are often used to accomplish these practical management objectives, and there is increased concern that the methods used may compromise animal welfare. We document the accuracy and humaneness of gunshot placement to the brain and cervical vertebrae of Philippine deer (Rusa marianna) on Guam during depopulation activities as a model for meeting AVMA standards of euthanasia under field conditions (e.g., animal is not in hand). Deer were shot with a .223 caliber rifle from 10-125 m and approached immediately (

OBJECTIVES: To examine the first-year survival of infants with congenital heart defects (CHDs) and investigate the potential role of socioeconomic and demographic factors on survival. METHODS: Subjects included 15 533 infants with CHDs born between 2004 and 2013 ascertained by the NC Birth Defects Monitoring Program. We classified CHDs into the following 3 groups: critical univentricular (n = 575), critical biventricular (n = 1494), and noncritical biventricular (n = 13 345). We determined vital status and age at death through linkage to state vital records and used geocoded maternal residence at birth to obtain census information for study subjects. We calculated Kaplan–Meier survival estimates by maternal and infant characteristics and derived hazard ratios from Cox proportional hazard models for selected exposures. RESULTS: Among all infants with CHDs, there were 1289 deaths (8.3%) in the first year. Among infants with univentricular defects, 61.6% (95% confidence interval [CI]: 57.7%–65.7%) survived. Survival among infants with univentricular defects was considerably better for those whose fathers were ≥35 years old (71.6%; 95% CI: 63.8%–80.3%) compared with those whose fathers were younger (59.7%; 95% CI: 54.6%–65.2%). Factors associated with survival among infants with any biventricular defect included maternal education, race and/or ethnicity, marital status, and delivery at a heart center. The hazard of infant mortality was greatest among non-Hispanic African American mothers. CONCLUSIONS: Survival among infants with critical univentricular CHDs was less variable across sociodemographic categories compared with survival among infants with biventricular CHDs. Sociodemographic differences in survival among infants with less severe CHDs reinforces the importance of ensuring culturally effective pediatric care for at-risk infants and their families.

BACKGROUND Children with nonsyndromic orofacial clefts (NS OFCs) may require exceptional children's (EC) services for academic delays. We examined EC service use of children with and without NS OFCs in NC in elementary school. METHODS We included 559 children with NS OFCs and 6,822 children without birth defects who had NC educational records. We estimated prevalence ratios, trends in enrollment, and characteristics of eligibility classification using descriptive statistics and logistic regression by cleft subtype and race/ethnicity. We estimated the odds of third grade retention by EC enrollment using logistic regression with inverse probability of treatment weights. RESULTS Children with NS OFCs were 3.02 (95% CI: 2.50, 3.64) times as likely to receive third grade special education (SE) services compared to unaffected peers. The prevalence odds was highest among children with CL+P (OR: 4.61, 95% CI: 3.49, 6.09) declining by 54% by fifth grade. The prevalence odds of SE for white children was approximately 1.50 times that for African American children in fourth and fifth grades. Approximately 33% of children with NS OFCs within each racial/ethnic group received SE in third grade. African American children were twice as likely to receive services under specific learning disability. Children with NS OFCs receiving EC services were 44% (OR: 0.56; 95% CI: 0.13, 2.38) less likely to be retained in third grade compared to children with NS OFCs who were not receiving services. CONCLUSIONS Children with NS OFCs are more likely to receive SE services in elementary school compared to their unaffected peers. The eligibility category differed by racial/ethnic group.

OBJECTIVE To compare time efficiency and nociceptive input between digital strumming (DS) and sharp transection (ST) of the suspensory ligament during ovariohysterectomy (OVH). STUDY DESIGN Randomized controlled trial. ANIMALS 30 adult female dogs. METHODS Dogs were randomly assigned to ST or DS procedures. Measures of nociception were assessed through measurements of preoperative and intraoperative heart rate during manipulation of the suspensory ligament. Measures of pain were assessed through preoperative and postoperative pain scores by using the short form Glasgow Composite Pain Scale. Time efficiency was measured through total surgical time and the time to release each suspensory ligament. RESULTS After body weight was accounted for, the total surgical time was 1.1 minutes (P = .06) faster for ST than for DS, and each additional kilogram of body weight increased total surgical time by 0.1 minutes (P = .02). Digital strumming had 30.6-fold greater odds of taking greater than 1 minute compared with ST (P = .001). The heart rate from baseline to peak was 7.4 beats per minute lower in the ST group than in the DS group (P = .06). No complications were observed, and there was no difference in postoperative pain scores between treatments. CONCLUSION Sharp transection was faster and generated less intraoperative acceleration in heart rate but did not differ in postoperative outcomes compared with DS. CLINICAL SIGNIFICANCE Sharp transection is a viable alternative to DS for breakdown of the suspensory ligament during canine OVH. Sharp transection may improve surgical efficiency, especially when performing large volumes in the spay/neuter setting and could influence veterinary student training.

Background Higher prevalence of selected birth defects has been reported among American Indian/Alaska Native (AI/AN) newborns. We examine whether known risk factors for birth defects explain the higher prevalence observed for selected birth defects among this population. Methods Data from 12 population-based birth defects surveillance systems, covering a birth population of 11 million from 1999 to 2007, were used to examine prevalence of birth defects that have previously been reported to have elevated prevalence among AI/ANs. Prevalence ratios (PRs) were calculated for non-Hispanic AI/ANs and any AI/ANs (regardless of Hispanic ethnicity), adjusting for maternal age, education, diabetes, and smoking, as well as type of case-finding ascertainment surveillance system. Results After adjustment, the birth prevalence of two of seven birth defects remained significantly elevated among AI/ANs compared to non-Hispanic whites (NHWs): anotia/microtia was almost threefold higher, and cleft lip +/- cleft palate was almost 70% higher compared to NHWs. Excluding AI/AN subjects who were also Hispanic had only a negligible impact on adjusted PRs. Conclusions Additional covariates accounted for some of the elevated birth defect prevalences among AI/ANs compared to NHWs. Exclusion of Hispanic ethnicity from the AI/AN category had little impact on birth defects prevalences in AI/ANs. NHWs serve as a viable comparison group for analysis. Birth defects among AI/ANs require additional scrutiny to identify modifiable risk and protective factors.

The crux of Dr. Harcombe’s critique is her assertion that our study design was inappropriate for our research objective, which was to investigate whether maternal carbohydrate restriction before conception was associated with neural tube defects (NTDs) in the National Birth Defects Prevention Study (NBDPS), a population-based case-control study of birth defects (Desrosiers, Siega-Riz, Mosley, Meyer, & The National Birth Defects Prevention Study, 2018). In her Letter, Dr. Harcombe claims that our study is fundamentally flawed because “cases should have been women who restrict carbohydrates and the controls should have been women who don’t and the outcome measure should have been NTD-affected pregnancies.” Despite her confusing (mis)use of the terms case and control, what Dr. Harcombe appears to be describing is a cohort study.

We appreciate Dr. Camacho’s interest in our article (Desrosiers, Siega-Riz, Mosley, Meyer, & National Birth Defects Prevention Study, 2018), and welcome the opportunity to respond. As Dr. Camacho emphasizes, the association between folic acid and neural tube defects (NTDs) is well established (Viswanathan et al., 2017). What is less certain are factors potentially related to folate insufficiency among women of reproductive age, and even more so, among women who meet the U.S. Preventative Health Task Force’s recommendation of 0.4–0.8 mg/day of supplemental folic acid (Tinker, Hamner, Qi, & Crider, 2015; US Preventive Services Task Force, 2017). Understanding the reasons for folate insufficiency could help prevent some cases of birth defects in the future and is thus a worthy research pursuit. One theory expressed in the literature is whether avoidance of carbohydrate-rich foods such as enriched grains (fortified with folic acid) and beans (high in natural folate) could lead to meaningful reductions in folate status, which could in turn lead to an increased risk for some women of having an NTD-affected pregnancy (Mills, 2017; Quinlivan & Gregory, 2007).

BACKGROUND Folic acid fortification significantly reduced the prevalence of neural tube defects (NTDs) in the United States. The popularity of "low carb" diets raises concern that women who intentionally avoid carbohydrates, thereby consuming fewer fortified foods, may not have adequate dietary intake of folic acid. METHODS To assess the association between carbohydrate intake and NTDs, we analyzed data from the National Birth Defects Prevention Study from 1,740 mothers of infants, stillbirths, and terminations with anencephaly or spina bifida (cases), and 9,545 mothers of live born infants without a birth defect (controls) conceived between 1998 and 2011. Carbohydrate and folic acid intake before conception were estimated from food frequency questionnaire responses. Restricted carbohydrate intake was defined as ≤5th percentile among controls. Odds ratios were estimated with logistic regression and adjusted for maternal race/ethnicity, education, alcohol use, folic acid supplement use, study center, and caloric intake. RESULTS Mean dietary intake of folic acid among women with restricted carbohydrate intake was less than half that of other women (p

Background: Epidemiologic studies involving birth defects are extremely sensitive to phenotype accuracy and precision. We devised a case review and classification protocol for a project to study school achievement in children with idiopathic, nonsyndromic orofacial clefts to improve the reliability of phenotypic classification from the statewide birth defects registry. Methods: Surveillance-program abstraction data and medical records at the birth or treating hospitals were used when available. Exclusion criteria included: median cleft lip; Tessier cleft; premaxillary agenesis; presence of a recognizable syndrome, phenotype, association, or sequence (other than Robin sequence); clefts with other malformations not considered to be normal or common variants in the newborn; and cases with documented or suspected genetic or teratogenic causes. Results: Of 712 children identified with orofacial clefts, 153 were excluded, leaving 559 nonsyndromic orofacial cleft cases of unknown cause in the final study. These cases were grouped into the following clinically meaningful types: cleft lip with or without cleft alveolus; cleft lip and cleft palate; and cleft palate only. This review and classification process resulted in the elimination of 21.5% of the original cohort of identified cases, with most exclusions being due to suspected syndromic associations. Conclusion: Verbatim descriptions of the clinical findings are critical for accurate classification of diagnoses. This review process improved the precision of orofacial cleft phenotype classification for our study. Precision would have been further improved if all of the cases had verbatim descriptions of diagnoses and all medical records could have been reviewed by the classification team. Birth Defects Research (Part A) 103:899–903, 2015. © 2015 Wiley Periodicals, Inc.

BACKGROUND Nonresponse bias assessment is an important and underutilized tool in survey research to assess potential bias due to incomplete participation. This study illustrates a nonresponse bias sensitivity assessment using a survey on perceived barriers to care for children with orofacial clefts in North Carolina. METHODS Children born in North Carolina between 2001 and 2004 with an orofacial cleft were eligible for inclusion. Vital statistics data, including maternal and child characteristics, were available on all eligible subjects. Missing ‘responses’ from nonparticipants were imputed using assumptions based on the distribution of responses, survey method (mail or phone), and participant maternal demographics. RESULTS Overall, 245 of 475 subjects (51.6%) responded to either a mail or phone survey. Cost as a barrier to care was reported by 25.0% of participants. When stratified by survey type, 28.3% of mail respondents and 17.2% of phone respondents reported cost as a barrier. Under various assumptions, the bias-adjusted estimated prevalence of cost as barrier to care ranged from 16.1% to 30.0%. Maternal age, education, race, and marital status at time of birth were not associated with subjects reporting cost as a barrier. CONCLUSION As survey response rates continue to decline, the importance of assessing the potential impact of nonresponse bias has become more critical. Birth defects research is particularly conducive to nonresponse bias analysis, especially when birth defect registries and birth certificate records are used. Future birth defect studies which use population-based surveillance data and have incomplete participation could benefit from this type of nonresponse bias assessment. Birth Defects Research (Part A) 103:603–609, 2015. © 2015 Wiley Periodicals, Inc.

Previous experimental and epidemiological research suggests that maternal exposure to some organic solvents during pregnancy may increase the risk of fetal growth restriction (FGR). We evaluated the association between expert-assessed occupational solvent exposure and risk of small for gestational age (SGA) infants in a population-based sample of women in the National Birth Defects Prevention Study.We analysed data from 2886 mothers and their infants born between 1997 and 2002. Job histories were self-reported. Probability of exposure to six chlorinated, three aromatic and one petroleum solvent was assessed by industrial hygienists. SGA was defined as birthweight10th centile of birthweight-by-gestational age in a national reference. Logistic regression was used to estimate ORs and 95% CIs to assess the association between SGA and exposure to any solvent(s) or specific solvent classes, adjusting for maternal age and education.Approximately 8% of infants were SGA. Exposure prevalence to any solvent was 10% and 8% among mothers of SGA and non-SGA infants, respectively. Among women with ≥ 50% probability of exposure, we observed elevated but imprecise associations between SGA and exposure to any solvent(s) (1.71; 0.86 to 3.40), chlorinated solvents (1.70; 0.69 to 4.01) and aromatic solvents (1.87; 0.78 to 4.50).This is the first population-based study in the USA to investigate the potential association between FGR and assessed maternal occupational exposure to distinct classes of organic solvents during pregnancy. The potential associations observed between SGA and exposure to chlorinated and aromatic solvents are based on small numbers and merit further investigation.

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).

The study objective was to compare butorphanol pharmacokinetics and physiologic effects following intravenous and subcutaneous administration in horses. Ten adult horses received 0.1 mg/kg butorphanol by either intravenous or subcutaneous injections, in a randomized crossover design. Plasma concentrations of butorphanol were measured at predetermined time points using highly sensitive liquid chromatography-tandem mass spectrometry assay (LC-MS/MS). Demeanor and physiologic variables were recorded. Data were analyzed with multivariate mixed-effect model on ranks (P ≤ 0.05). For subcutaneous injection, absorption half-life and peak plasma concentration of butorphanol were 0.10 ± 0.07 h and 88 ± 37.4 ng/mL (mean ± SD), respectively. Bioavailability was 87%. After intravenous injection, mean ± SD butorphanol steady-state volume of distribution and clearance was 1.2 ± 0.96 L/kg and 0.65 ± 0.20 L/kg/h, respectively. Terminal half-lives for butorphanol were 2.31 ± 1.74 h and 5.29 ± 1.72 h after intravenous and subcutaneous administrations. Subcutaneous butorphanol reached and maintained target plasma concentrations >10 ng/mL for 2 ± 0.87 h (Mean ± SD), with less marked physiologic and behavioral effects compared to intravenous injection. Subcutaneous butorphanol administration is an acceptable alternative to the intravenous route in adult horses.

Background Clubfoot is associated with maternal cigarette smoking in several studies, but it is not clear if this association is confined to women who smoke throughout the at-risk period. Maternal alcohol and coffee drinking have not been well studied in relation to clubfoot. Methods The present study used data from a population-based case–control study of clubfoot conducted in Massachusetts, New York, and North Carolina from 2007 to 2011. Mothers of 646 isolated clubfoot cases and 2037 controls were interviewed about pregnancy events and exposures, including the timing and frequency of cigarette smoking, alcohol intake, and coffee drinking. Results More mothers of cases than controls reported smoking during early pregnancy (28.9% vs. 19.1%). Of women who smoked when they became pregnant, those who quit in the month after a first missed period had a 40% increase in clubfoot risk and those who continued to smoke during the next 3 months had more than a doubling in risk, after controlling for demographic factors, parity, obesity, and specific medication exposures. Adjusted odds ratios for women who drank >3 servings of alcohol or coffee per day throughout early pregnancy were 2.38 and 1.77, respectively, but the numbers of exposed women were small and odds ratios were unstable. Conclusions Clubfoot risk appears to be increased for offspring of women who smoke cigarettes, particularly those who continue smoking after pregnancy is recognisable, regardless of amount. For alcohol and coffee drinkers, suggested increased risks were only observed in higher levels of intake.

© 2014 The Authors Birth Defects Research Part A: Clinical and Molecular Teratology Published by Wiley Periodicals, Inc.

Our objective was to examine the relationship between estimated maternal exposure to pesticides in public drinking water and the risk of congenital heart defects (CHD). We used mixed-effects logistic regression to analyze data from 18,291 nonsyndromic cases with heart defects from the Texas Birth Defects Registry and 4414 randomly-selected controls delivered in Texas from 1999 through 2005. Water district-level pesticide exposure was estimated by linking each maternal residential address to the corresponding public water supply district’s measured atrazine levels. We repeated analyses among independent subjects from the National Birth Defects Prevention Study (NBDPS) (1620 nonsyndromic cases with heart defects and 1335 controls delivered from 1999 through 2005). No positive associations were observed between high versus low atrazine level and eight CHD subtypes or all included heart defects combined. These findings should be interpreted with caution, in light of potential misclassification and relatively large proportions of subjects with missing atrazine data. Thus, more consistent and complete monitoring and reporting of drinking water contaminants will aid in better understanding the relationships between pesticide water contaminants and birth defects.

Background: Clefts of the lip and/or palate (CL/P) carry a social stigma that often causes psychosocial stress. The purpose of this study was to consider the association of cleft phenotype and age with self-reported aspects of psychosocial stress. Methods: Children with nonsyndromic CL/P and unaffected children born between 1997 and 2003 were identified through the North Carolina Birth Defects Monitoring Program and North Carolina birth records, respectively. The psychosocial concerns of children with CL/P were assessed via a 29-question subset of a larger survey. Responses were analyzed according to school age and cleft phenotype (cleft lip with/without cleft alveolus, CL ± A; cleft palate only, CP; or cleft lip with cleft palate, CL + P). Results: Surveys were returned for 176 children with CL/P and 333 unaffected children. When compared with unaffected children, responses differed for CL ± A in 4/29 questions, for CP in 7/29 questions, and for CL + P in 8/29 questions (P < 0.05). When stratified by school age, children with CL/P in elementary, middle, and high school differed from unaffected children by 1/29, 7/29, and 2/29 questions, respectively. Middle school–aged children with CL/P were more affected by aesthetic concerns, bullying, and difficulties with friendship, and social interaction. Children with CL + P reported more severe aesthetic-related concerns than children with CL ± A or CP but experienced similar speech-related distress as children with CP only. Conclusion: Social implications associated with CL/P are most pronounced during middle school, and less so during elementary and high school. This information identifies areas of social improvement aimed at reducing the stigma of CL/P.

We aimed to compare antinociceptive effects of IV infusions of morphine (M), morphine-lidocaine (ML), or morphine-lidocaine-ketamine (MLK) combined, in a mild-to-moderate pain model in dogs. Eighteen adult hounds were heavily sedated with IV morphine (0.2 mg/kg) and dexmedetomidine to undergo thoracic skin incisions. After reversal, dogs were randomly assigned to receive loading doses of lidocaine and ketamine (MLK), lidocaine and saline (ML), or equivalent volume of saline (M), followed by 18 hr constant infusions of morphine (0.12 mg/kg/hr), lidocaine (3 mg/kg/hr) and ketamine (0.6 mg/kg/hr); morphine (0.12 mg/kg/hr) and lidocaine (3 mg/kg/hr); or morphine (0.12 mg/kg/hr), respectively. Pain was assessed with Short Form Glasgow Composite Measure Pain Scale and mechanical nociception with von Frey filaments (VFFS). Data were analyzed with linear mixed model on ranks. Independently of treatment, Short Form Glasgow Composite Measure Pain Scale was significantly higher than baseline for 24 hr (p < .0001), while VFFS was significantly lower than baseline for 48 hr post-recovery (p < .0001), with no difference between MLK and M groups. The ML group recorded significantly lower VFFS (p = .02) than the M group for the entire study. In conclusion, there was no significant analgesic difference between MLK and M alone.

Zika virus infection during pregnancy can cause serious brain abnormalities, but the full range of adverse outcomes is unknown (1). To better understand the impact of birth defects resulting from Zika virus infection, the CDC surveillance case definition established in 2016 for birth defects potentially related to Zika virus infection* (2) was retrospectively applied to population-based birth defects surveillance data collected during 2013-2014 in three areas before the introduction of Zika virus (the pre-Zika years) into the World Health Organization's Region of the Americas (Americas) (3). These data, from Massachusetts (2013), North Carolina (2013), and Atlanta, Georgia (2013-2014), included 747 infants and fetuses with one or more of the birth defects meeting the case definition (pre-Zika prevalence = 2.86 per 1,000 live births). Brain abnormalities or microcephaly were the most frequently recorded (1.50 per 1,000), followed by neural tube defects and other early brain malformations† (0.88), eye abnormalities without mention of a brain abnormality (0.31), and other consequences of central nervous system (CNS) dysfunction without mention of brain or eye abnormalities (0.17). During January 15-September 22, 2016, the U.S. Zika Pregnancy Registry (USZPR) reported 26 infants and fetuses with these same defects among 442 completed pregnancies (58.8 per 1,000) born to mothers with laboratory evidence of possible Zika virus infection during pregnancy (2). Although the ascertainment methods differed, this finding was approximately 20 times higher than the proportion of one or more of the same birth defects among pregnancies during the pre-Zika years. These data demonstrate the importance of population-based surveillance for interpreting data about birth defects potentially related to Zika virus infection.

A substantial proportion of infants born with tetralogy of Fallot (TOF) die in infancy. A better understanding of the heterogeneity associated with TOF, including extracardiac malformations and chromosomal anomalies is vital to stratifying risk and optimizing outcomes during infancy.Using the North Carolina Birth Defects Monitoring Program, infants diagnosed with TOF and born between 2003 and 2012 were included. Kaplan-Meier survival curves were used to estimate cumulative 1-year mortality, stratified by the presence of concomitant birth defects (BDs) and chromosomal anomalies. Multivariable logistic regression was used to estimate the direct effect of each concomitant BD, after adjusting for all others.A total of 496 infants with TOF were included, and 15% (n = 76) died. The number of concomitant BD systems was significantly associated with the risk of death at 1-year, p 0.0001. Specifically, the risk of mortality was 8% among infants with TOF with or without additional cardiac defects, 16% among infants with TOF and 1 extracardiac BD system, 19% among infants with 2 extracardiac BD systems, and 39% among infants with ≥ 3 extracardiac BD systems. After adjustment, concomitant eye and gastrointestinal defects were significantly associated increased with 1-year mortality, odds ratio 2.83 (95% confidence interval, 1.08-7.32) and odds ratio 4.43 (95% confidence interval, 1.57, 12.45), respectively. Infants with trisomy 13 or trisomy 18 were also significantly more likely to die, p 0.0001.Both concomitant BDs and genetic anomalies increase the risk of mortality among infants with TOF. Future studies are needed to identify the underlying genetic and socioeconomic risk factors for high-risk TOF infants. Birth Defects Research 109:1154-1165, 2017. © 2017 Wiley Periodicals, Inc.

Background— Most studies evaluating neurocognitive outcomes in children with congenital heart defects (CHD) have focused on high-risk patients or used specialized, resource-intensive testing. To determine the association of CHD with academic outcomes and compare outcomes according to the severity of CHD, we linked state educational records with a birth defects registry and birth certificates. Methods and Results— We performed a retrospective cohort study using data from the North Carolina Birth Defects Monitoring Program, North Carolina Department of Public Instruction, and North Carolina Department of Health and Human Services vital records. We performed logistic regression, adjusting for maternal education, race/ethnicity, enrollment in public pre-Kindergarten, and gestational age, to determine the association of CHD with not meeting standards on reading and math end-of-grade examinations in third grade in 2006 to 2012. Of 5624 subjects with CHD and 10 832 with no structural birth defects, 2807 (50%) and 6355 (59%) were linked, respectively. Children with CHD had 1.24× the odds of not meeting standards in either reading or math (95% confidence interval, 1.12–1.37), with 44.6% of children with CHD not meeting standards in at least one of these areas compared with 37.5% without CHD. Although children with both critical and noncritical CHD had poorer outcomes, those with critical CHD were significantly more likely to receive exceptional services compared with the noncritical group (adjusted odds ratio, 1.46; 95% confidence interval, 1.15–1.86). Conclusions— Children with all types of CHD have poorer academic outcomes compared with their peers. Evaluation for exceptional services should be considered in children with any type of CHD.

Background Little is known about the barriers faced by families of children with birth defects in obtaining healthcare. We examined reported perceived barriers to care and satisfaction with care among mothers of children with orofacial clefts.

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.

A range of health effects, including adverse pregnancy outcomes, have been associated with exposure to ambient concentrations of particulate matter (PM) and ozone (O3). The objective of this study was to determine whether maternal exposure to fine particulate matter (PM2.5) and O3 during pregnancy is associated with the risk of term low birthweight and small for gestational age infants in both single and co-pollutant models. Term low birthweight and small for gestational age were determined using all birth certificates from North Carolina from 2003 to 2005. Ambient air concentrations of PM2.5 and O3 were predicted using a hierarchical Bayesian model of air pollution that combined modeled air pollution estimates from the EPA׳s Community Multi-Scale Air Quality (CMAQ) model with air monitor data measured by the EPA׳s Air Quality System. Binomial regression, adjusted for multiple potential confounders, was performed. In adjusted single-pollutant models for the third trimester, O3 concentration was positively associated with small for gestational age and term low birthweight births [risk ratios for an interquartile range increase in O3: 1.16 (95% CI 1.11, 1.22) for small for gestational age and 2.03 (95% CI 1.80, 2.30) for term low birthweight]; however, inverse or null associations were observed for PM2.5 [risk ratios for an interquartile range increase in PM2.5: 0.97 (95% CI 0.95, 0.99) for small for gestational age and 1.01 (95% CI 0.97, 1.06) for term low birthweight]. Findings were similar in co-pollutant models and linear models of birthweight. These results suggest that O3 concentrations in both urban and rural areas may be associated with an increased risk of term low birthweight and small for gestational age births.

Clubfoot, a common major structural malformation, develops early in gestation. Epidemiologic studies have identified higher risks among boys, first-born children, and babies with a family history of clubfoot, but studies of risks associated with maternal exposures are lacking. We conducted the first large-scale, population-based, case-control study of clubfoot with detailed information on maternal medication use in pregnancy. Study subjects were ascertained from birth defect registries in Massachusetts, New York, and North Carolina during 2007-2011. Cases were 646 mothers of children with clubfoot without other major structural malformations (i.e., isolated clubfoot); controls were mothers of 2,037 children born without major malformations. Mothers were interviewed within 12 months of delivery about medication use, including product, timing, and frequency. Odds ratios were estimated for exposure to 27 medications in pregnancy months 2-4 after adjustment for study site, infant sex, first-born status, body mass index (weight (kg)/height (m)(2)), and smoking. Odds ratios were less than 1.20 for 14 of the medications; of the remainder, most odds ratios were only slightly elevated (range, 1.21-1.66), with wide confidence intervals. The use of antiviral drugs was more common in clubfoot cases than in controls (odds ratio = 4.22, 95% confidence interval: 1.52, 11.73). Most of these results are new findings and require confirmation in other studies.

apid methods for on-site swine depopulation are re-quired in the event of an animal health emergency in North America. The term animal health emergency, as used in this context, includes a wide range of poten-tial situations such as disease outbreaks, contamination with chemicals (eg, dioxin) or radionuclides (eg, cesi-um-137), and adverse animal welfare conditions creat-ed by transportation restrictions that severely limit feed deliveries and animal movement. As described by the AVMA, mass depopulation refers to methods by which large numbers of animals must be destroyed quickly and efficiently with as much consideration given to the welfare of the animals as practicable, but where the cir -cumstances and tasks facing those performing depopu-lation are understood to be extenuating.