Motivated by population-based geocoded data for Iowa stillbirths and live births delivered during 2005-2011, we sought to identify spatio-temporal variation of stillbirth risk. Our high-quality data consisting of point locations of these delivery events allows use of a Bayesian Poisson point process approach to evaluate the spatial pattern of events. With this large epidemiologic dataset, we implemented the integrated nested Laplace approximation (INLA) to fit the conditional formulation of the point process via a Bayesian hierarchical model and empirically showed that INLA, compared to Markov chain Monte Carlo (MCMC) sampling, is an attractive approach. Furthermore, we modeled the temporal variability in stillbirth to better understand how stillbirths are geographically linked over the seven-year study period and demonstrate the similarity between the conditional formulation of the spatio-temporal model and a log Gaussian Cox process governed by discrete space-time random fields. After controlling for important features of the data, the Bayesian temporal relative risk maps identified areas of increasing and decreasing stillbirth risk over the birth period, which may warrant further public health investigation in the regions identified.

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 <2,500 g. The aPRs for all cases increased with decreasing parental age, maternal education, and maternal parity, but decreased for parental race/ethnicity other than non-Hispanic White. Estimates restricted to isolated cases or stratified by infant sex were similar to those for all cases.
Conclusions: This study covers one of the largest samples and longest temporal period examined for IHPS in the US. Similar to findings reported in Europe, estimates suggest that IHPS prevalence has decreased recently in the US. Additional analyses supported associations with several infant and parental characteristics.

Motivated by the paucity of high-quality stillbirth surveillance data and the spatial analysis of such data, we describe the pattern of stillbirth events as a step toward increased understanding of risk factors which can better guide future measures to mitigate these events. A challenge in such an analysis is that some mothers experience stillbirth events from independent pregnancies within a defined study period. To account for these dependencies, we parameterize our model to include a maternal contextual effect and broaden the appeal of Bayesian Poisson point process modeling to quantify excess stillbirth risk while considering a form of a log-Gaussian Cox process. In the presence of extra unobserved spatial variation in risk, we demonstrate a pragmatic methodologic strategy to model the risk surface in relation to covariates and that there is a variance-bias trade-off associated with the use of a maternal contextual effect. We applied our strategy to the spatial distribution of stillbirth in Iowa during the years 2005–2011 using data obtained from an active, statewide public health surveillance program. We identified areas of excess risk for further investigation based on model components that captured important features of the data.

Purpose: To examine maternal smoking and body mass index (BMI) interactions in contributing to risk of oral clefts.
Methods: We studied 4935 cases and 10,557 controls from six population-based studies and estimated a pooled logistic regression of individual-level data, controlling for study fixed effects and individual-level risk factors.
Results: We found a significant negative smoking-BMI interaction, with cleft risk with smoking generally declining with higher BMI. For all clefts combined, the odds ratio for smoking was 1.61 (95% confidence interval [CI]: 1.39-1.86) at BMI 17 (underweight), 1.47 (95% CI: 1.34-1.62) at BMI 22 (normal weight), 1.35 (95% CI: 1.22-1.48) at BMI 27 (overweight), 1.21 (95% CI: 1.04-1.41) at BMI 33 (obese), and 1.13 (95% CI: 0.92-1.38) at BMI 37 (very obese). A negative interaction was also observed for isolated clefts and across cleft types but was more pronounced for cleft lip only and cleft palate only.
Conclusions: Our findings suggest that the risk of oral clefts associated with maternal smoking is largest among underweight mothers, although the smoking-BMI interaction is strongest for cleft lip only and cleft palate only. BMI was not protective for the effects of smoking; a clinically relevant increase in smoking-related cleft risk was still present among heavier women.

Objectives: To examine trajectories in academic achievement for children with oral clefts versus unaffected classmates and explore predictors of persistently low achievement among children with oral clefts.
Design: Longitudinal cohort study of academic achievement in a population-based sample.
Setting and participants: Children born from 1983 through 2003 with oral clefts were identified from the Iowa Registry for Congenital and Inherited Disorders and matched to unaffected classmates by sex, school/school district and month and year of birth.
Main outcome measures: Academic achievement was measured from Iowa Testing Programs data. Outcomes included achievement scores in reading, language and mathematics.
Results: Academic achievement data were available for 586 children with oral clefts and 1873 unaffected classmates. Achievement trajectories were stable for both groups. Children with oral clefts were more likely than their classmates to be classified into persistent low achievement trajectories, including when adjusting for socioeconomic differences: OR=1.63, 95% CI 1.23 to 2.16 for reading; OR=1.73, 95% CI 1.29 to 2.31 for language; OR=1.45, 95% CI 1.05 to 1.99 for math. Predictors of low achievement were cleft palate only (vs other cleft types), adolescent mothers, low maternal education and less frequent use of prenatal care.
Conclusions: Most children have steady academic trajectories and children with oral clefts are at greater risk for persistent low achievement in school than unaffected classmates. These findings support the need for routine, early screening for academic deficits in this population. Cleft palate only, low parental education and adolescent mothers are associated with increased risk for persistent low achievement.

Objective: To compare academic achievement in children with oral-facial clefts (OFC) with their unaffected siblings.
Methods: 256 children with OFC were identified from the Iowa Registry for Congenital and Inherited Disorders, and 387 unaffected siblings were identified from birth certificates. These data were linked to Iowa Testing Programs achievement data. We compared academic achievement in children with OFC with their unaffected siblings using linear regression models, adjusted for potential confounders. In post hoc analyses, we explored modifiers of siblings’ academic performance.
Results: Achievement scores were similar between children with OFC and their siblings. Children with cleft palate only were significantly more likely to use special education than their unaffected siblings. Siblings’ academic achievement was inversely related to distance in birth order and age from the affected child.
Conclusion: Children with OFC and their siblings received similar achievement scores. Younger siblings, in particular, may share a vulnerability to poor academic outcomes.

Objective: To examine self-reported mental health status and aggravation level in mothers of children with isolated oral clefts.
Methods: Population-based sample of children (aged 4 to 9 years) with isolated oral clefts was enumerated from births from 1998 through 2003 in Arkansas, Iowa, and New York State. Mothers of 294 children completed the Mental Health Inventory 5-item questionnaire and Aggravation in Parenting Scale. The Mental Health Inventory and Aggravation in Parenting Scale scores, stratified by poor (Mental Health Inventory ≤ 67) and better (Mental Health Inventory > 67) mental health status or high (Aggravation in Parenting Scale ≤ 11), moderate (Aggravation in Parenting Scale = 12 to 15) and low (Aggravation in Parenting Scale = 16) aggravation, were compared by selected maternal and child characteristics. Mean scores for each instrument and proportion of mothers with poor mental health or high aggravation were compared with those reported in the National Survey of American Families.
Results: Mean scores for each instrument and proportion of mothers with poor mental health or high aggravation differed little from published data. Mothers with poor mental health tended to be less educated, to have lower household incomes, and to rate their health and their child’s health lower than those in better mental health. Mothers with high aggravation tended to have lower household incomes, to have more children, and to rate their health and their child’s health lower than those with moderate or low aggravation.
Conclusions: Mothers of affected children were not more likely to experience poor mental health or high aggravation compared with published data; however, sociodemographic characteristics were associated with maternal psychosocial adaptation. Brief screeners for mental health and parenting administered during routine appointments may facilitate identifying at-risk caregivers.

Background and objective: Previous studies of academic achievement of children with oral clefts have mostly relied on small, clinic-based samples prone to ascertainment bias. In the first study in the United States to use a population-based sample with direct assessment, we evaluated the academic achievement of children with oral clefts relative to their classmates.
Methods: Children born with isolated oral clefts in Iowa from 1983 to 2003 were identified from the Iowa Registry for Congenital and Inherited Disorders and matched to unaffected classmates by gender, school/school district, and month and year of birth. Academic achievement was assessed by using standardized tests of academic progress developed by the Iowa Testing Programs. Iowa Testing Programs data were linked to birth certificates for all children. Regression models controlled for household demographic and socioeconomic factors. The analytical sample included 588 children with clefts contributing 3735 child-grade observations and 1874 classmates contributing 13 159 child-grade observations.
Results: Children with oral clefts had lower scores than their classmates across all domains and school levels, with a 5-percentile difference in the overall composite score. Children with clefts were approximately one-half grade level behind their classmates and had higher rates of academic underachievement and use of special education services by 8 percentage points. Group differences were slightly lower but remained large and significant after adjusting for many background characteristics.
Conclusions: Children with oral clefts underperformed across all academic areas and grade levels compared with their classmates. The results support a model of early testing and intervention among affected children to identify and reduce academic deficits.

Objectives: This study examined the behavioral health of young children with oral clefts, and effects of satisfaction with facial appearance, cleft team care, number of cleft-related surgeries, and socioeconomic status (SES).
Subjects and methods: The study included a population-based sample of 104 children aged 2-12 years with isolated oral clefts from the state of Iowa. Behavior was evaluated with the Child Behavior Checklist or the Pediatric Behavior Scale 30, depending on age, compared with normative samples.
Results: Risks of behavioral problems were not significantly different from normative samples except for higher inattention/hyperactivity risks at age 6-12 years. Low satisfaction with facial appearance was associated with behavioral problems in all domains, except aggression. Team-care effects were not associated with behavioral problems. Number of cleft-related surgeries was associated with increased anxiety/depression and somatic symptom risks. Higher SES was associated with reduced inattention/hyperactivity, aggressive/oppositional behavior, and somatic symptoms.
Conclusions: Most children with oral clefts may have similar behavioral health outcomes to unaffected children, except for increased inattention/hyperactivity risks at older ages. However, low satisfaction with facial appearance, increased exposure to surgeries, and lower SES may significantly increase behavioral problems. Also, the findings emphasize the need to study the representation of behavioral health professionals on cleft teams and access to behavioral health care.

Background: Data from Iowa fetal death certificates (FDCs) suggest that reportable stillbirths (unintended fetal deaths ≥ 20 weeks gestation and/or weighing ≥ 350 grams) occur in about 1 in 200 deliveries. In 2005, the Iowa Department of Public Health and the Iowa Registry for Congenital and Inherited Disorders (IRCID) collaborated with other state stakeholders to establish the Iowa Stillbirth Surveillance Project. The goal of this project was to use population-based, active surveillance methodologies to identify reportable stillbirths delivered by Iowa residents since January 1, 2000.
Methods: To conduct stillbirth surveillance, the IRCID expanded its existing public health authority and electronic abstract application for birth defects surveillance. The expanded application was piloted using a random sample (n = 250 of 989) of FDCs reported from January 2000 through December 2004.
Results: IRCID procedures for active case finding and medical record abstraction verified 192 (76.8%) as reportable stillbirths. Stillbirths not verified as reportable were due to findings of elective terminations (n = 30), live births (n = 3), induced deliveries (n = 2), and FDC entries for gestational age and/or delivery weight that were either inaccurately recorded (n = 13) or accurately recorded but did not meet Iowa FDC reporting criteria (n = 9); medical records for one FDC were unavailable. Infant malformations were more common among unverified stillbirths, whereas the cause of death due to maternal-related conditions was higher among verified stillbirths.
Conclusions: These results suggest that over-reporting limits the use of FDCs as a primary ascertainment source for stillbirth surveillance in Iowa. Continued expansion of the IRCID active surveillance methodologies to monitor stillbirths in Iowa is recommended.

Congenital idiopathic talipes equinovarus (ITEV), also known as clubfoot, is a well-recognized foot deformity. To date, prevalence estimates and descriptive data reported for ITEV have varied due to differences in study methodology. Using population-based surveillance data collected by the Iowa Registry for Congenital and Inherited Disorders, we examined isolated ITEV births delivered from 1997 through 2005 and compared to live births in Iowa during the same time period. An overall prevalence was calculated for live, singleton full-term births only. Prevalence odds ratios (POR)s and 95% confidence intervals (CI)s were examined for selected infant and parental characteristics. The prevalence of isolated ITEV was 11.4 per 10,000 live, singleton full-term births (95% CI = 10.3, 12.6), with no significant variation in prevalence during the study period. Increased PORs were found for males (POR 1.8; 95% CI = 1.5, 2.3) and maternal smoking during pregnancy (POR = 1.5, 95% CI = 1.2, 1.9); low birth weight (<2,500 g) showed an increase among females (POR = 3.2, 95% CI = 1.5, 6.9) but not males (POR = 0.9, 95% CI = 0.3, 2.8). Elevated, but non-significant, PORs were found for season of birth, maternal education, and trimester prenatal care was initiated; decreased PORs were found for fetal presentation, maternal race/ethnicity, parity, area of residence, and parental age at delivery. Our study of a well-defined, homogenous sample suggested that prevalence of isolated ITEV in Iowa was similar to that reported in other population-based studies and provided support for some, but not all, previously reported associations with infant and parental characteristics. More detailed, longitudinal studies of isolated ITEV are recommended.

In summary, mothers of children with microtia were generally satisfied with the care provided, although a need for increased access to an organized specialty care team, improved interactions with healthcare professionals, and a lack of hearing aids were identified. Despite the modest number of participants, our study is the first population-based assessment to measure the baseline needs among parents of children with microtia. Continued follow-up of this sample might provide additional insights into postoperative care and outcomes experienced by these children.

Maternal smoking is a recognized risk factor for orofacial clefts. Maternal or fetal pharmacogenetic variants are plausible modulators of this risk. In this work, we studied 5,427 DNA samples, including 1,244 from subjects in Denmark and Iowa with facial clefting and 4,183 from parents, siblings, or unrelated population controls. We examined 25 single-nucleotide polymorphisms in 16 genes in pathways for detoxification of components of cigarette smoke, to look for evidence of gene-environment interactions. For genes identified as related to oral clefting, we studied gene-expression profiles in fetal development in the relevant tissues and time intervals. Maternal smoking was a significant risk factor for clefting and showed dosage effects, in both the Danish and Iowan data. Suggestive effects of variants in the fetal NAT2 and CYP1A1 genes were observed in both the Iowan and the Danish participants. In an expanded case set, NAT2 continued to show significant overtransmission of an allele to the fetus, with a final P value of .00003. There was an interaction between maternal smoking and fetal inheritance of a GSTT1-null deletion, seen in both the Danish (P=.03) and Iowan (P=.002) studies, with a Fisher’s combined P value of <.001, which remained significant after correction for multiple comparisons. Gene-expression analysis demonstrated expression of GSTT1 in human embryonic craniofacial tissues during the relevant developmental interval. This study benefited from two large samples, involving independent populations, that provided substantial power and a framework for future studies that could identify a susceptible population for preventive health care.

Background: While the number of women entering the work force has grown, so has the importance of investigating occupational reproductive hazards. The objective of this study was to examine the concordance between maternal-assessed and industrial hygienist-assessed exposure to four classes of occupational agents – video display terminals, paints, solvents, and agricultural chemicals.
Methods: Case (n=87) and control (n=102) mothers who participated in a population-based study of orofacial clefts provided occupational histories and exposure (yes/no) to selected classes of agents for the one-year period prior to their child’s delivery. Two industrial hygienists reviewed the occupational histories and assigned mothers an exposure status for each class of agent. Using industrial hygienist-assessed exposure as the “gold standard”, sensitivity and specificity of maternal reports were calculated for each class of agent. Kappa statistics were calculated for the study population to account for chance agreement between the two exposure assessment methods.
Results: Sensitivity estimates for cases were the highest for video display terminals (77%) and lowest for agricultural chemicals (14%). Respective estimates for controls were 74% and 14%. Specificity estimates tended to be high for both groups. Kappa values ranged from 0.16-0.45.
Conclusions: With regard to the classes of agents examined, these data suggest screening questions alone may not be the preferred method of obtaining occupational exposure histories, even when the time period of interest is fairly short and recent.