Jaime L. Frías

Folic acid for the prevention of neural tube defects

The American Academy of Pediatrics endorses the US Public Health Service (USPHS) recommendation that all women capable of becoming pregnant consume 400 μg of folic acid daily to prevent neural tube defects (NTDs). Studies have demonstrated that periconceptional folic acid supplementation can prevent 50% or more of NTDs such as spina bifida and anencephaly. For women who have previously had an NTD-affected pregnancy, the Centers for Disease Control and Prevention (CDC) recommends increasing the intake of folic acid to 4000 μg per day beginning at least 1 month before conception and continuing through the first trimester. Implementation of these recommendations is essential for the primary prevention of these serious and disabling birth defects. Because fewer than 1 in 3 women consume the amount of folic acid recommended by the USPHS, the Academy notes that the prevention of NTDs depends on an urgent and effective campaign to close this prevention gap.

Orofacial clefts in the National Birth Defects Prevention Study, 1997-2004.

Orofacial clefts are among the most common types of birth defects, but their clinical presentation has not been well described in a geographically diverse US population. To describe the birth prevalence and phenotype of nonsyndromic clefts, we used data from the National Birth Defects Prevention Study (NBDPS), a multi‐site, population‐based, case‐control study aimed at identifying genetic and environmental risk factors for birth defects. Included in the study were infants born during 1997–2004 with a cleft lip (CL), cleft lip with cleft palate (CLP), or cleft palate (CP). Infants with clefts associated with recognized single‐gene disorders, chromosome abnormalities, holoprosencephaly, or amniotic band sequence were excluded. A total of 3,344 infants with nonsyndromic orofacial clefts were identified, including 751 with CL, 1,399 with CLP, and 1,194 with CP, giving birth prevalence estimates of 0.3, 0.5, and 0.4/1,000 live births, respectively. Among infants with CLP where cleft laterality was specified, about twice as many had unilateral vs. bilateral involvement, while for CL there were over 10 times as many with unilateral versus bilateral involvement. Involvement was most often left‐sided. About one‐quarter of infants with CP had Pierre Robin sequence. Over 80% of infants had an isolated orofacial cleft. Among infants with CL or CLP, heart, limb, and other musculoskeletal defects were most commonly observed, while heart, limb, and central nervous system defects were most common among infants with CP. Better understanding of the birth prevalence and phenotype may help guide clinical care as well as contribute to an improved understanding of pathogenesis. Published 2009 Wiley‐Liss, Inc.

Priorities for Future Public Health Research in Orofacial Clefts

The National Center on Birth Defects and Developmental Disabilities at the Centers for Disease Control and Prevention conducted a workshop in January 2006, entitled “Prioritizing a Research Agenda for Orofacial Clefts.” The goals of the meeting were to review existing research on orofacial clefts (OFCs), identify gaps in knowledge that need additional public health research, and develop a prioritized research agenda that can help guide future public health research. Experts in the field of epidemiology, public health, genetics, psychology, speech pathology, dentistry, and health economics participated to create the research agenda. Research gaps identified by the participants for additional public health research included: the roles of maternal nutrition, obesity, and diabetes in the etiology of OFCs; psychosocial outcomes for children with OFCs; the quality of life for families and children with OFCs; and the health care costs of OFCs. To create the research agenda, the participants prioritized the research gaps by public health importance, feasibility, and outcomes of interest. This report summarizes the workshop.

Setting a public health research agenda for Down syndrome: Summary of a meeting sponsored by the Centers for Disease Control and Prevention and the National Down Syndrome Society†‡§

On November 8–9, 2007, a meeting entitled “Setting a Public Health Research Agenda for Down Syndrome” was held to review current knowledge, identify gaps, and develop priorities for future public health research related to Down syndrome. Participants included experts in clinical and molecular genetics, pediatrics, cardiology, psychiatry, psychology, neuroscience, epidemiology, and public health. Participants were asked to identify key public health research questions and discuss potential strategies that could be used to address those questions. The following were identified as priority areas for future public health research: identification of risk and preventive factors for physical health and cognitive outcomes, focusing on understanding the reasons for previously recognized disparities; improved understanding of comorbid conditions, including their prevalence, clinical variability, natural history, and optimal methods for their evaluation and treatment; better characterization of the natural history of cognition, language, and behavior; identification of mental health comorbidities and of risk and protective factors for their development; identification of strategies to improve enrollment in research studies; development of strategies for conveying up‐to‐date information to parents and health professionals; identification of interventions to improve cognition, language, mental health, and behavior; understanding the impact of educational and social services and supports; identification of improved methods for diagnosis of and interventions for Alzheimer disease; and understanding the effects of different types of health care on outcomes. Participants strongly supported the development of population‐based resources for research studies and resources useful for longitudinal studies. This agenda will be used to guide future public health research on Down syndrome. Published 2008 Wiley‐Liss, Inc.

Laterality defects in the national birth defects prevention study (1998-2007): birth prevalence and descriptive epidemiology.

Little is known epidemiologically about laterality defects. Using data from the National Birth Defects Prevention Study (NBDPS), a large multi‐site case‐control study of birth defects, we analyzed prevalence and selected characteristics in children born with laterality defects born from 1998 to 2007. We identified 517 nonsyndromic cases (378 heterotaxy, 73.1%; 139 situs inversus totalis [SIT], 26.9%) resulting in an estimated birth prevalence of 1.1 per 10,000 live births (95% confidence interval 1.0–1.2). Prevalence did not differ significantly across sites, over time, or by inclusion of pregnancy termination. Laterality defects were more common among preterm cases compared to term cases, and in children born to mothers who were non‐white or younger than 20 years compared to white mothers or those age 25–29 years. The distribution of associated cardiac and extra‐cardiac defects, excluding the expected heterotaxy anomalies, varied by type of laterality defect. Cases with heterotaxy were significantly more likely than those with SIT to have double outlet right ventricle, atrioventricular canal defects, pulmonary stenosis, non‐tetralogy of Fallot pulmonary atresia with ventricular septal defect, totally and partially anomalous pulmonary venous return; also more likely to have orofacial clefts, esophageal atresia, bowel atresias, and omphalocele, though not reaching statistical significance. Relatively more common among cases with SIT were Dandy‐Walker malformation, anotia/microtia, and limb deficiency. The similarity in the demographic characteristics of heterotaxy and SIT supports the hypothesis that they are part of a continuum of abnormal left‐right axis patterning. These findings on laterality defects may help guide clinical care, future research, and prevention strategies.

Maternal age and prevalence of isolated congenital heart defects in an urban area of the United States

Although maternal age has been associated with a number of birth defects in several reports, the literature on the association of maternal age with isolated congenital heart defect (CHD) phenotypes has been limited. We evaluated CHD prevalence based on a cohort of 5,289 infants and fetuses with isolated CHDs born during the period 1968–2005 and ascertained by the Metropolitan Atlanta Congenital Defects Program (MACDP) among residents of five central counties in Atlanta. For our denominator, we obtained information on births to residents of the same counties from vital records (nu2009=u20091,301,143). We calculated prevalence ratios for 23 CHD phenotypes by several maternal age categories, using the group 25–29 years of age as a reference group. We used Poisson regression models to estimate adjusted prevalence ratios (aPRs) and 95% confidence intervals (CIs), controlling for maternal race, infant sex, and birth cohort. A maternal age of 35 years or older was associated with an increased prevalence for several CHD phenotypes: laterality defects (aPRu2009=u20092.06; CI 1.22–3.48), all conotruncal defects (aPRu2009=u20091.30; CI 1.03–1.65), and specifically for dextro‐transposition of the great arteries (aPRu2009=u20091.65; CI 1.10–2.48), coarctation of the aorta (aPRu2009=u20091.54; CI 1.10–2.16), ventricular septal defects (aPRu2009=u20091.20; CI 1.06–1.36), and atrial septal defects (aPRu2009=u20091.36; CI 1.05–1.77). Our findings suggest that the birth prevalence of specific isolated CHDs varies with maternal age. Further studies are warranted to corroborate these observations, taking into account potential confounding by known modifiable risk factors. Published 2011 Wiley‐Liss, Inc.

Congenital Heart Defects and Major Structural Noncardiac Anomalies, Atlanta, Georgia, 1968 to 2005

OBJECTIVEnTo identify the proportion of major structural noncardiac anomalies identified with congenital heart defects (CHDs).nnnSTUDY DESIGNnRecords of infants with CHDs in the Metropolitan Atlanta Congenital Defects Program who were born during the period 1968 through 2005 were classified as having isolated, syndromic, multiple CHD (ie, having an unrecognized pattern of multiple congenital anomalies or a recognized pattern of multiple congenital anomalies of unknown etiology), or laterality defects. Frequencies of associated noncardiac anomalies were obtained.nnnRESULTSnWe identified 7984 live-born and stillborn infants and fetuses with CHDs. Among them, 5695 (71.3%) had isolated, 1080 (13.5%) had multiple, 1048 (13.1%) had syndromic, and 161 (2.0%) had laterality defects. The percentage of multiple congenital anomalies was highest for case with atrial septal defects (18.5%), cardiac looping defects (17.2%), and conotruncal defects (16.0%), and cases with atrioventricular septal defects represented the highest percentages of those with syndromic CHDs (66.7%).nnnCONCLUSIONSnIncluding those with syndromes and laterality defects, 28.7% of case infants with CHDs had associated major noncardiac malformations. Thus, infants with CHDs warrant careful examination for the presence of noncardiac anomalies.

Risk factors for non-syndromic holoprosencephaly in the National Birth Defects Prevention Study†‡§

Holoprosencephaly (HPE) is a complex structural brain anomaly that results from incomplete cleavage of the forebrain. The prevalence of HPE at birth is low, and risk factors have been difficult to identify. Using data from a large multi‐state population‐based case‐control study, we examined risk factors for non‐syndromic HPE. Data from maternal telephone interviews were available for 74 infants with HPE and 5871 controls born between 1997 and 2004. Several characteristics and exposures were examined, including pregnancy history, medical history, maternal diet and use of nutritional supplements, medications, tobacco, alcohol, and illegal substances. We used χ2‐tests and logistic regression (excluding women with pre‐existing diabetes) to examine associations with HPE. Except for diet (year before pregnancy) and sexually transmitted infections (STIs) (throughout pregnancy), most exposures were examined for the time period from the month before to the third month of pregnancy. HPE was found to be associated with pre‐existing diabetes (χ2u2009=u20096.0; Pu2009=u20090.01), aspirin use [adjusted odds ratio (aOR)u2009=u20093.4; 95% confidence interval (CI) 1.6–6.9], lower education level (aORu2009=u20092.5; 95%CI 1.1–5.6), and use of assisted reproductive technologies (ART) (crude ORu2009=u20094.2; 95%CI 1.3–13.7). Consistent maternal folic acid use appeared to be protective (aORu2009=u20090.4; 95%CI 0.2–1.0), but the association was of borderline statistical significance. While some of these findings support previous observations, other potential risk factors identified warrant further study. Published 2010 Wiley‐Liss, Inc.

Priorities for public health research on craniosynostosis: Summary and recommendations from a Centers for Disease Control and Prevention‐sponsored meeting

On June 8–9, 2006, the National Center on Birth Defects and Developmental Disabilities at the Centers for Disease Control and Prevention held a meeting entitled “Prioritizing a Public Health Research Agenda for Craniosynostosis”. The meeting goals were to review current knowledge in the area, discuss research gaps, and identify future priorities for public health research. Participants with a broad range of expertise (including clinical and molecular genetics, cranial morphology, epidemiology, pediatrics, psychology, public health, and surgery) contributed to the development of the research agenda. Meeting participants were asked to consider public health significance and feasibility when identifying areas of priority for future public health research. Participants identified several priorities, including the need to better delineate the prevalence and phenotype of craniosynostosis (CS); to identify factors important in the causation of CS (including potentially modifiable environmental risk factors as well as genes involved in isolated CS and gene–gene and gene–environment interactions); and to better understand short‐ and long‐term outcomes of CS (e.g., surgical, neurocognitive and neuropsychological outcomes, psychological adjustment, and social relationships) and issues related to clinical care that could affect those outcomes. The need for improved collaboration among clinical treatment centers and standardization of data collection to address these priorities was emphasized. These priorities will be used to guide future public health research on CS.

Use of special education services by children with orofacial clefts.

BACKGROUNDnOur objective was to evaluate the use of special education services by children with orofacial clefts (OFCs).nnnMETHODSnWe linked the birth certificates of children born from 1982-2001 in five counties of metropolitan Atlanta to a population-based birth defects surveillance system to identify children with OFCs, and to the special education files for the school years 1992-2004 to identify children who used special education services. The special education data contained exceptionalities and services rendered for each school year. Prevalence ratios (PRs) and 95% CIs were calculated. The data were stratified by race/ethnicity, maternal education, type of OFC, and the presence of associated major malformations. In addition, we assessed the age at which special education began and the amount of time spent receiving services.nnnRESULTSnOf the 777 children with OFCs, 201 (26%) were in special education at least 1 year compared with 8% of the children who had no major birth defects, yielding a PR of 3.2 (95% CI: 2.9-3.6). The most common exceptionality or service for children with an OFC was speech and language services. Compared with children with no birth defects, children with an OFC were four times more likely to be in this exceptionality (PR 3.8; 95% CI: 3.3-4.3). After excluding children in speech and language services, children with OFCs were still more likely to use special education services (PR 2.4; 95% CI: 1.7-3.2).nnnCONCLUSIONSnChildren with OFCs used special education services more often than children without birth defects. This information can help in planning for future population needs.