A population-based case-control study investigated the association between maternal exposure to air pollutants, carbon monoxide, nitrogen dioxide, ozone, sulfur dioxide, and particulate matter <10 μm ...in aerodynamic diameter during weeks 3–8 of pregnancy and the risk of selected cardiac birth defects and oral clefts in livebirths and fetal deaths between 1997 and 2000 in seven Texas counties. Controls were frequency matched to cases on year of birth, vital status, and maternal county of residence at delivery. Stationary monitoring data were used to estimate air pollution exposure. Logistic regression models adjusted for covariates available in the vital record. When the highest quartile of exposure was compared with the lowest, the authors observed positive associations between carbon monoxide and tetralogy of Fallot (odds ratio = 2.04, 95% confidence interval: 1.26, 3.29), particulate matter <10 μm in aerodynamic diameter and isolated atrial septal defects (odds ratio = 2.27, 95% confidence interval: 1.43, 3.60), and sulfur dioxide and isolated ventricular septal defects (odds ratio = 2.16, 95% confidence interval: 1.51, 3.09). There were inverse associations between carbon monoxide and isolated atrial septal defects and between ozone and isolated ventricular septal defects. Evidence that air pollution exposure influences the risk of oral clefts was limited. Suggestive results support a previously reported finding of an association between ozone exposure and pulmonary artery and valve defects.
Use of topiramate in pregnancy and risk of oral clefts Margulis, Andrea V., MD, ScD; Mitchell, Allen A., MD; Gilboa, Suzanne M., PhD ...
American journal of obstetrics and gynecology,
11/2012, Letnik:
207, Številka:
5
Journal Article
Recenzirano
Odprti dostop
Objective The objective of this study was to evaluate the association between the use of monotherapy topiramate in pregnancy and cleft lip with or without cleft palate (CL/P) in the offspring. Study ...Design Data from the Slone Epidemiology Center Birth Defects Study (BDS) from 1997 to 2009 and the National Birth Defects Prevention Study (NBDPS) from 1997 to 2007 were analyzed. Conditional logistic regression was used to compare the first-trimester use of topiramate monotherapy to no antiepileptic drug use during the periconceptional period between the mothers of infants with CL/P and the mothers of controls for each study separately and in pooled data. Results The BDS contained 785 CL/P cases and 6986 controls; the NBDPS contained 2283 CL/P cases and 8494 controls. The odds ratios (exact 95% confidence intervals) for the association between topiramate use and CL/P were 10.1 (1.1-129.2) in the BDS, 3.6 (0.7-20.0) in the NBDPS, and 5.4 (1.5-20.1) in the pooled data. Conclusion First-trimester use of topiramate may be associated with CL/P.
Diabetes mellitus and birth defects Correa, Adolfo, MD, PhD; Gilboa, Suzanne M., PhD; Besser, Lilah M., MPH ...
American journal of obstetrics and gynecology,
09/2008, Letnik:
199, Številka:
3
Journal Article, Conference Proceeding
Recenzirano
Odprti dostop
Objective The purpose of this study was to examine associations between diabetes mellitus and 39 birth defects. Study Design This was a multicenter case-control study of mothers of infants who were ...born with (n = 13,030) and without (n = 4895) birth defects in the National Birth Defects Prevention Study (1997-2003). Results Pregestational diabetes mellitus (PGDM) was associated significantly with noncardiac defects (isolated, 7/23 defects; multiples, 13/23 defects) and cardiac defects (isolated, 11/16 defects; multiples, 8/16 defects). Adjusted odds ratios for PGDM and all isolated and multiple defects were 3.17 (95% CI, 2.20-4.99) and 8.62 (95% CI, 5.27-14.10), respectively. Gestational diabetes mellitus (GDM) was associated with fewer noncardiac defects (isolated, 3/23 defects; multiples, 3/23 defects) and cardiac defects (isolated, 3/16 defects; multiples, 2/16 defects). Odds ratios between GDM and all isolated and multiple defects were 1.42 (95% CI, 1.17-1.73) and 1.50 (95% CI, 1.13-2.00), respectively. These associations were limited generally to offspring of women with prepregnancy body mass index ≥25 kg/m2. Conclusion PGDM was associated with a wide range of birth defects; GDM was associated with a limited group of birth defects.
Objective Preconception care for women with diabetes can reduce the occurrence of adverse birth outcomes. We aimed to estimate the preconception care (PCC)–preventable health and cost burden of ...adverse birth outcomes associated with diagnosed and undiagnosed pregestational diabetes mellitus (PGDM) in the United States. Study Design Among women of reproductive age (15-44 years), we estimated age- and race/ethnicity-specific prevalence of diagnosed and undiagnosed diabetes. We applied age and race/ethnicity-specific pregnancy rates, estimates of the risk reduction from PCC for 3 adverse birth outcomes (preterm birth, major birth defects, and perinatal mortality), and lifetime medical and lost productivity costs for children with those outcomes. Using a probabilistic model, we estimated the reduction in adverse birth outcomes and costs associated with universal PCC compared with no PCC among women with PGDM. We did not assess maternal outcomes and associated costs. Results We estimated 2.2% of US births are to women with PGDM. Among women with diagnosed diabetes, universal PCC might avert 8397 (90% prediction interval PI, 5252-11,449) preterm deliveries, 3725 (90% PI, 3259-4126) birth defects, and 1872 (90% PI, 1239-2415) perinatal deaths annually. Associated discounted lifetime costs averted for the affected cohort of children could be as high as $4.3 billion (90% PI, 3.4-5.1 billion) (2012 US dollars). PCC among women with undiagnosed diabetes could yield an additional $1.2 billion (90% PI, 951 million-1.4 billion) in averted cost. Conclusion Results suggest a substantial health and cost burden associated with PGDM that could be prevented by universal PCC, which might offset the cost of providing such care.
MicroRNAs (miRNAs) contribute to both neuronal and immune cell fate, but their involvement in intertissue communication remained unexplored. The brain, via vagal secretion of acetylcholine (ACh), ...suppresses peripheral inflammation by intercepting cytokine production; therefore, we predicted that microRNAs targeting acetylcholinesterase (AChE) can attenuate inflammation. Here, we report that inflammatory stimuli induced leukocyte overexpression of the AChE-targeting miR-132. Injected locked nucleic acid (LNA)-modified anti-miR-132 oligonucleotide depleted miR-132 amounts while elevating AChE in mouse circulation and tissues. In transfected cells, a mutated 3′UTR miR-132 binding site increased AChE mRNA expression, whereas cells infected with a lentivirus expressing pre-miR-132 showed suppressed AChE. Transgenic mice overexpressing 3′UTR null AChE showed excessive inflammatory mediators and impaired cholinergic anti-inflammatory regulation, in spite of substantial miR-132 upregulation in brain and bone marrow. Our findings identify the AChE mRNA-targeting miR-132 as a functional regulator of the brain-to-body resolution of inflammation, opening avenues for study and therapeutic manipulations of the neuro-immune dialog.
Diabetes is associated with an increased risk for many birth defects and is likely to have an increasing impact on birth defect prevalence because of the rise in diabetes in the United States in ...recent decades. One of the first analyses in which specific birth defects were assessed for their relationship with both pregestational and gestational diabetes used data from the initial 6 years of the National Birth Defects Prevention Study. That analysis reported strong associations for pregestational diabetes with several birth defects, but few exposures among some of the less common birth defects led to unstable estimates with wide confidence intervals. Since that analysis, the study continued to collect data for another 8 years, including information on approximately 19,000 additional cases and 6900 additional controls.
Our objective was to use data from the National Birth Defects Prevention Study, the largest population-based birth defects case-control study in the United States, to provide updated and more precise estimates of the association between diabetes and birth defects, including some defects not previously assessed.
We analyzed data on deliveries from October 1997 through December 2011. Mothers of case and control infants were interviewed about their health conditions and exposures during pregnancy, including diagnosis of pregestational (type 1 or type 2) diabetes before the index pregnancy or gestational diabetes during the index pregnancy. Using logistic regression, we separately assessed the association between pregestational and gestational diabetes with specific categories of structural birth defects for which there were at least 3 exposed case infants. For birth defect categories for which there were at least 5 exposed case infants, we calculated odds ratios adjusted for maternal body mass index, age, education, race/ethnicity, and study site; for defect categories with 3 or 4 exposed cases, we calculated crude odds ratios.
Pregestational diabetes was reported by 0.6% of mothers of control infants (71 of 11,447) and 2.5% of mothers of case infants (775 of 31,007). Gestational diabetes during the index pregnancy was reported by 4.7% of mothers of control infants (536 of 11,447) and 5.3% of mothers of case infants (1,653 of 31,007). Pregestational diabetes was associated with strong, statistically significant odds ratios (range, 2.5–80.2) for 46 of 50 birth defects considered. The largest odds ratio was observed for sacral agenesis (adjusted odds ratio, 80.2; 95% confidence interval, 46.1–139.3). A greater than 10-fold increased risk was also observed for holoprosencephaly (adjusted odds ratio, 13.1; 95% confidence interval, 7.0–24.5), longitudinal limb deficiency (adjusted odds ratio, 10.1; 95% confidence interval, 6.2–16.5), heterotaxy (adjusted odds ratio, 12.3; 95% confidence interval, 7.3–20.5), truncus arteriosus (adjusted odds ratio, 14.9; 95% confidence interval, 7.6–29.3), atrioventricular septal defect (adjusted odds ratio, 10.5; 95% confidence interval, 6.2–17.9), and single ventricle complex (adjusted odds ratio, 14.7; 95% confidence interval, 8.9–24.3). For gestational diabetes, statistically significant odds ratios were fewer (12 of 56) and of smaller magnitude (range, 1.3– 2.1; 0.5 for gastroschisis).
Pregestational diabetes is associated with a markedly increased risk for many specific births defects. Because glycemic control before pregnancy is associated with a reduced risk for birth defects, ongoing quality care for persons with diabetes is an important opportunity for prevention.
Objective The purpose of this study was to examine associations between prepregnancy body mass index (BMI) and congenital heart defects (CHDs). Study Design These analyses included case infants with ...CHDs (n = 6440) and liveborn control infants without birth defects (n = 5673) enrolled in the National Birth Defects Prevention Study (1997-2004). Results Adjusted odds ratios for all CHDs combined were 1.16 (95% confidence interval CI, 1.05–1.29), 1.15 (95% CI, 1.00–1.32), and 1.31 (95% CI, 1.11–1.56) for overweight status, moderate obesity, and severe obesity, respectively. Phenotypes associated with elevated BMI (≥25.0 kg/m2 ) were conotruncal defects (tetralogy of Fallot), total anomalous pulmonary venous return, hypoplastic left heart syndrome, right ventricular outflow tract (RVOT) defects (pulmonary valve stenosis), and septal defects (secundum atrial septal defect). Conclusion These results corroborated those of previous studies and suggested new associations between obesity and conotruncal defects and RVOT defects.
As of June 16, 2020, the coronavirus disease 2019 (COVID-19) pandemic has resulted in 2,104,346 cases and 116,140 deaths in the United States.* During pregnancy, women experience immunologic and ...physiologic changes that could increase their risk for more severe illness from respiratory infections (1,2). To date, data to assess the prevalence and severity of COVID-19 among pregnant U.S. women and determine whether signs and symptoms differ among pregnant and nonpregnant women are limited. During January 22-June 7, as part of COVID-19 surveillance, CDC received reports of 326,335 women of reproductive age (15-44 years) who had positive test results for SARS-CoV-2, the virus that causes COVID-19. Data on pregnancy status were available for 91,412 (28.0%) women with laboratory-confirmed infections; among these, 8,207 (9.0%) were pregnant. Symptomatic pregnant and nonpregnant women with COVID-19 reported similar frequencies of cough (>50%) and shortness of breath (30%), but pregnant women less frequently reported headache, muscle aches, fever, chills, and diarrhea. Chronic lung disease, diabetes mellitus, and cardiovascular disease were more commonly reported among pregnant women than among nonpregnant women. Among women with COVID-19, approximately one third (31.5%) of pregnant women were reported to have been hospitalized compared with 5.8% of nonpregnant women. After adjusting for age, presence of underlying medical conditions, and race/ethnicity, pregnant women were significantly more likely to be admitted to the intensive care unit (ICU) (aRR = 1.5, 95% confidence interval CI = 1.2-1.8) and receive mechanical ventilation (aRR = 1.7, 95% CI = 1.2-2.4). Sixteen (0.2%) COVID-19-related deaths were reported among pregnant women aged 15-44 years, and 208 (0.2%) such deaths were reported among nonpregnant women (aRR = 0.9, 95% CI = 0.5-1.5). These findings suggest that among women of reproductive age with COVID-19, pregnant women are more likely to be hospitalized and at increased risk for ICU admission and receipt of mechanical ventilation compared with nonpregnant women, but their risk for death is similar. To reduce occurrence of severe illness from COVID-19, pregnant women should be counseled about the potential risk for severe illness from COVID-19, and measures to prevent infection with SARS-CoV-2 should be emphasized for pregnant women and their families.
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