Pharmacokinetics and pharmacodynamics of intravenous continuous rate infusion and repeated intramuscular administration of dexmedetomidine in standing horses.

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.

Cancer diagnostic profile in children with structural birth defects: An assessment in 15,000 childhood cancer cases.

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 < 0.001), including neuroblastoma (12.5% vs 8.2%; q < 0.001) and hepatoblastoma (5.0% vs 1.3%; q < 0.001), but fewer hematologic malignancies, including acute lymphoblastic leukemia (12.4% vs 24.4%; q < 0.001). In age-stratified analyses, differences in tumor type were evident among children younger than 1 year and children 1 to 4 years old, but they were attenuated among children 5 years of age or older. The age at diagnosis was younger in children with birth defects for most cancers, including leukemia, lymphoma, astrocytoma, medulloblastoma, ependymoma, embryonal tumors, and germ cell tumors (all q < 0.05). CONCLUSIONS: The results indicate possible etiologic heterogeneity in children with birth defects, have implications for future surveillance efforts, and raise the possibility of differential cancer ascertainment in children with birth defects. LAY SUMMARY: Scientific studies suggest that children with birth defects are at increased risk for cancer. However, these studies have not been able to determine whether important tumor characteristics, such as the type of tumor diagnosed, the age at which the tumor is diagnosed, and the degree to which the tumor has spread at the time of diagnosis, are different for children with birth defects and children without birth defects. This study attempts to answer these important questions. By doing so, it may help scientists and physicians to understand the causes of cancer in children with birth defects and diagnose cancer at earlier stages when it is more treatable.

Risk factors for primary congenital glaucoma in the National Birth Defects Prevention Study.

Primary congenital glaucoma (PCG) is a rare but serious birth defect. Genetic mutations have been implicated in the development of PCG, but little is known about nongenetic risk factors. This study investigates potential risk factors for PCG in the National Birth Defects Prevention Study (NBDPS), a large population-based case-control study of major birth defects in the United States. The analysis includes case infants with PCG (N = 107) and control infants without birth defects (N = 10,084) enrolled in NBDPS from birth years 2000-2011. Pregnancy/infant clinical characteristics, demographics, and parental health history were collected through maternal interview. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were computed to examine associations with all PCG cases and isolated PCG cases without other major malformations. Associations with all the cases included term low birth weight (<2,500 g; aOR = 2.80, CI 1.59-4.94), non-Hispanic black maternal race/ethnicity (aOR = 2.42, CI 1.42-4.13), maternal history of seizure (aOR = 2.73, CI 1.25-5.97), maternal antihypertensive use (aOR = 3.60, CI 1.52-8.53), and maternal sexually transmitted infection (aOR = 2.75, CI 1.17-6.44). These factors were also associated with isolated PCG, as was maternal use of nonsteroidal anti-inflammatory drugs (aOR = 2.70, CI 1.15-6.34). This study is among the first to examine a wide array of potential risk factors for PCG in a population-based sample.

Sharp transection of the suspensory ligament as an alternative to digital strumming during canine ovariohysterectomy.

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.

Academic Achievement Among Children With Nonsyndromic Orofacial Clefts : A Population-Based Study.

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.

Baseline Prevalence of Birth Defects Associated with Congenital Zika Virus Infection - Massachusetts, North Carolina, and Atlanta, Georgia, 2013-2014.

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.

Survival of children with trisomy 13 and trisomy 18: A multi-state population-based study.

Trisomy 13 (T13) and trisomy 18 (T18) are among the most prevalent autosomal trisomies. Both are associated with a very high risk of mortality. Numerous instances, however, of long-term survival of children with T13 or T18 have prompted some clinicians to pursue aggressive treatment instead of the traditional approach of palliative care. The purpose of this study is to assess current mortality data for these conditions. This multi-state, population-based study examined data obtained from birth defect surveillance programs in nine states on live-born infants delivered during 1999-2007 with T13 or T18. Information on children's vital status and selected maternal and infant risk factors were obtained using matched birth and death certificates and other data sources. The Kaplan-Meier method and Cox proportional hazards models were used to estimate age-specific survival probabilities and predictors of survival up to age five. There were 693 children with T13 and 1,113 children with T18 identified from the participating states. Among children with T13, 5-year survival was 9.7%; among children with T18, it was 12.3%. For both trisomies, gestational age was the strongest predictor of mortality. Females and children of non-Hispanic black mothers had the lowest mortality. Omphalocele and congenital heart defects were associated with an increased risk of death for children with T18 but not T13. This study found survival among children with T13 and T18 to be somewhat higher than those previously reported in the literature, consistent with recent studies reporting improved survival following more aggressive medical intervention for these children. © 2015 Wiley Periodicals, Inc.

Geographic distribution of live births with tetralogy of Fallot in North Carolina 2003 to 2012.

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.

Maternal residential exposure to agricultural pesticides and birth defects in a 2003 to 2005 North Carolina birth cohort.

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 (<10(th) , 10-50(th) , 50-90(th) , and >90(th) 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.

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

BACKGROUND: Congenital microcephaly has been linked to maternal Zika virus infection. However, ascertaining infants diagnosed with microcephaly can be challenging. METHODS: Thirty birth defects surveillance programs provided data on infants diagnosed with microcephaly born 2009 to 2013. The pooled prevalence of microcephaly per 10,000 live births was estimated overall and by maternal/infant characteristics. Variation in prevalence was examined across case finding methods. Nine programs provided data on head circumference and conditions potentially contributing to microcephaly. RESULTS: The pooled prevalence of microcephaly was 8.7 per 10,000 live births. Median prevalence (per 10,000 live births) was similar among programs using active (6.7) and passive (6.6) methods; the interdecile range of prevalence estimates was wider among programs using passive methods for all race/ethnicity categories except Hispanic. Prevalence (per 10,000 live births) was lowest among non-Hispanic Whites (6.5) and highest among non-Hispanic Blacks and Hispanics (11.2 and 11.9, respectively); estimates followed a U-shaped distribution by maternal age with the highest prevalence among mothers <20 years (11.5) and ≥40 years (13.2). For gestational age and birth weight, the highest prevalence was among infants <32 weeks gestation and infants <1500 gm. Case definitions varied; 41.8% of cases had an HC ≥ the 10th percentile for sex and gestational age. CONCLUSION: Differences in methods, population distribution of maternal/infant characteristics, and case definitions for microcephaly can contribute to the wide range of observed prevalence estimates across individual birth defects surveillance programs. Addressing these factors in the setting of Zika virus infection can improve the quality of prevalence estimates. Birth Defects Research (Part A) 106:972-982, 2016. © 2016 Wiley Periodicals, Inc.

Hypospadias and maternal exposure to atrazine via drinking water in the National Birth Defects Prevention study.

BACKGROUND: Hypospadias is a relatively common birth defect affecting the male urinary tract. It has been suggested that exposure to endocrine disrupting chemicals might increase the risk of hypospadias by interrupting normal urethral development. METHODS: Using data from the National Birth Defects Prevention Study, a population-based case-control study, we considered the role of maternal exposure to atrazine, a widely used herbicide and potential endocrine disruptor, via drinking water in the etiology of 2nd and 3rd degree hypospadias. We used data on 343 hypospadias cases and 1,422 male controls in North Carolina, Arkansas, Iowa, and Texas from 1998-2005. Using catchment level stream and groundwater contaminant models from the US Geological Survey, we estimated atrazine concentrations in public water supplies and in private wells. We assigned case and control mothers to public water supplies based on geocoded maternal address during the critical window of exposure for hypospadias (i.e., gestational weeks 6-16). Using maternal questionnaire data about water consumption and drinking water, we estimated a surrogate for total maternal consumption of atrazine via drinking water. We then included additional maternal covariates, including age, race/ethnicity, parity, and plurality, in logistic regression analyses to consider an association between atrazine and hypospadias. RESULTS: When controlling for maternal characteristics, any association between hypospadias and daily maternal atrazine exposure during the critical window of genitourinary development was found to be weak or null (odds ratio for atrazine in drinking water = 1. 00, 95 % CI = 0.97 to 1.03 per 0.04 µg/day increase; odds ratio for maternal consumption = 1.02, 95 % CI = 0.99 to 1.05; per 0.05 µg/day increase). CONCLUSIONS: While the association that we observed was weak, our results suggest that additional research into a possible association between atrazine and hypospadias occurrence, using a more sensitive exposure metric, would be useful.

Racial/ethnic differences in survival of United States children with birth defects: a population-based study.

OBJECTIVES: To examine racial/ethnic-specific survival of children with major birth defects in the US. STUDY DESIGN: We pooled data on live births delivered during 1999-2007 with any of 21 birth defects from 12 population-based birth defects surveillance programs. We used the Kaplan-Meier method to calculate cumulative survival probabilities and Cox proportional hazards models to estimate mortality risk. RESULTS: For most birth defects, there were small-to-moderate differences in neonatal (<28 days) survival among racial/ethnic groups. However, compared with children born to non-Hispanic white mothers, postneonatal infant (28 days to <1 year) mortality risk was significantly greater among children born to non-Hispanic black mothers for 13 of 21 defects (hazard ratios [HRs] 1.3-2.8) and among children born to Hispanic mothers for 10 of 21 defects (HRs 1.3-1.7). Compared with children born to non-Hispanic white mothers, a significantly increased childhood (≤ 8 years) mortality risk was found among children born to Asian/Pacific Islander mothers for encephalocele (HR 2.6), tetralogy of Fallot, and atrioventricular septal defect (HRs 1.6-1.8) and among children born to American Indian/Alaska Native mothers for encephalocele (HR 2.8), whereas a significantly decreased childhood mortality risk was found among children born to Asian/Pacific Islander mothers for cleft lip with or without cleft palate (HR 0.6). CONCLUSION: Children with birth defects born to non-Hispanic black and Hispanic mothers carry a greater risk of mortality well into childhood, especially children with congenital heart defect. Understanding survival differences among racial/ethnic groups provides important information for policy development and service planning.

What we don't know can hurt us: Nonresponse bias assessment in birth defects research.

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.

Next steps for birth defects research and prevention: The birth defects study to evaluate pregnancy exposures (BD-STEPS).

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.

Issues involved in the phenotypic classification of orofacial clefts ascertained through a state birth defects registry for the North Carolina Cleft Outcomes Study.

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.

Maternal cigarette, alcohol, and coffee consumption in relation to risk of clubfoot.

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.

Assessed occupational exposure to chlorinated, aromatic and Stoddard solvents during pregnancy and risk of fetal growth restriction.

OBJECTIVES: 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. METHODS: 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 birthweight<10th 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. RESULTS: 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). CONCLUSIONS: 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.

Academic outcomes of children with isolated orofacial clefts compared with children without a major birth defect.

OBJECTIVE: To compare academic outcomes between children with orofacial cleft (OFC) and children without major birth defects. DESIGN AND SETTING: In 2007-2008, we mailed questionnaires to a random sample of mothers of school-aged children with OFC and mothers of children without major birth defects (comparison group). The questionnaire included Likert-scale, closed-ended, and open-ended questions from validated instruments. We conducted bivariate and multivariable analyses on parent-reported educational outcomes and bivariate analyses on parent-reported presence of related medical conditions between children with isolated OFC and unaffected children. PATIENTS/PARTICIPANTS: A random sample of 504 parents of children with OFCs born 1996-2002 (age 5-12 years) were identified by the North Carolina Birth Defects Monitoring Program. A random sample of 504 parents of children without birth defects born 1996-2002 was selected from North Carolina birth certificates. Of the 289 (28.7%) respondents, we analyzed 112 children with isolated OFC and 138 unaffected children. MAIN OUTCOME MEASURES: Letter grades, school days missed, and grade retention. RESULTS: Parents of children with isolated OFC reported more developmental disabilities and hearing and speech problems among their children than comparison parents. Children with isolated OFC were more likely to receive lower grades and miss more school days than unaffected children. Because of the low response rate, results should be interpreted cautiously. CONCLUSION: Children with isolated OFC may have poorer academic outcomes during elementary school than their unaffected peers. Future studies are needed to confirm these results and determine whether these differences persist in later grades.

Medication use in pregnancy in relation to the risk of isolated clubfoot in offspring.

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.

The association between race/ethnicity and major birth defects in the United States, 1999-2007.

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.