Point Prevalence Estimates of Activity-Limiting Long-term Symptoms Among United States Adults ≥1 Month After Reported Severe Acute Respiratory Syndrome Coronavirus 2 Infection, 1 November 2021.

BACKGROUND: Although most adults infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) fully recover, a proportion have ongoing symptoms, or post-COVID conditions (PCC), after infection. The objective of this analysis was to estimate the number of United States (US) adults with activity-limiting PCC on 1 November 2021. METHODS: We modeled the prevalence of PCC using reported infections occurring from 1 February 2020 to 30 September 2021, and population-based, household survey data on new activity-limiting symptoms ≥1 month following SARS-CoV-2 infection. From these data sources, we estimated the number and proportion of US adults with activity-limiting PCC on 1 November 2021 as 95% uncertainty intervals, stratified by sex and age. Sensitivity analyses adjusted for underascertainment of infections and uncertainty about symptom duration. RESULTS: On 1 November 2021, at least 3.0-5.0 million US adults, or 1.2%-1.9% of the US adult population, were estimated to have activity-limiting PCC of ≥1 month's duration. Population prevalence was higher in females (1.4%-2.2%) than males. The estimated prevalence after adjusting for underascertainment of infections was 1.7%-3.8%. CONCLUSIONS: Millions of US adults were estimated to have activity-limiting PCC. These estimates can support future efforts to address the impact of PCC on the US population.

Congenital Heart Defects in the United States: Estimating the Magnitude of the Affected Population in 2010.

BACKGROUND: Because of advancements in care, there has been a decline in mortality from congenital heart defects (CHDs) over the past several decades. However, there are no current empirical data documenting the number of people living with CHDs in the United States. Our aim was to estimate the CHD prevalence across all age groups in the United States in the year 2010. METHODS: The age-, sex-, and severity-specific observed prevalence of CHDs in Québec, Canada, in the year 2010 was assumed to equal the CHD prevalence in the non-Hispanic white population in the United States in 2010. A race-ethnicity adjustment factor, reflecting differential survival between racial-ethnic groups through 5 years of age for individuals with a CHD and that in the general US population, was applied to the estimated non-Hispanic white rates to derive CHD prevalence estimates among US non-Hispanic blacks and Hispanics. Confidence intervals for the estimated CHD prevalence rates and case counts were derived from a combination of Taylor series approximations and Monte Carlo simulation. RESULTS: We estimated that ≈2.4 million people (1.4 million adults, 1 million children) were living with CHDs in the United States in 2010. Nearly 300 000 of these individuals had severe CHDs. CONCLUSIONS: Our estimates highlight the need for 2 important efforts: planning for health services delivery to meet the needs of the growing population of adults with CHD and the development of surveillance data across the life span to provide empirical estimates of the prevalence of CHD across all age groups in the United States.

Red Blood Cell Folate Insufficiency among nonpregnant Women of Childbearing age in Guatemala 2009 to 2010: Prevalence and predicted Neural Tube Defects risk.

BACKGROUND: The World Health Organization recently released recommendations stating that red blood cell (RBC) folate concentrations should be above 400 ng/L (906 nmol/L) for optimal prevention of folate-sensitive neural tube defects (NTDs). The objective of this study was to determine the distribution of folate insufficiency (FI) (<906 nmol/L) and potential risk of NTDs based on RBC folate concentrations among nonpregnant women of child-bearing age in Guatemala. METHODS: A national and regional multistage cluster probability survey was completed during 2009 to 2010 among Guatemalan women of child-bearing age 15 to 49 years of age. Demographic and health information and blood samples for RBC folate analyses were collected from 1473 women. Prevalence rate ratios of FI and predicted NTD prevalence were estimated based on RBC folate concentrations comparing subpopulations of interest. RESULTS: National FI prevalence was 47.2% [95% confidence interval, 43.3-51.1] and showed wide variation by region (18-81%). In all regions, FI prevalence was higher among indigenous (27-89%) than among nonindigenous populations (16-44%). National NTD risk based on RBC folate concentrations was estimated to be 14 per 10,000 live births (95% uncertainty interval, 11.1-18.6) and showed wide regional variation (from 11 NTDS in the Metropolitan region to 26 NTDs per 10,000 live births in the Norte region). CONCLUSION: FI remains a common problem in populations with limited access to fortified products, specifically rural, low income, and indigenous populations. However, among subpopulations that are most likely to have fortified food, the prevalence of FI is similar to countries with well-established fortification programs. Birth Defects Research (Part A) 106:587-595, 2016. © 2016 Wiley Periodicals, Inc.

Community socioeconomic disadvantage and the survival of infants with congenital heart defects.

OBJECTIVES: We examined the association between survival of infants with severe congenital heart defects (CHDs) and community-level indicators of socioeconomic status. METHODS: We identified infants born to residents of Arizona, New Jersey, New York, and Texas between 1999 and 2007 with selected CHDs from 4 population-based, statewide birth defect surveillance programs. We linked data to the 2000 US Census to obtain 11 census tract-level socioeconomic indicators. We estimated survival probabilities and hazard ratios adjusted for individual characteristics. RESULTS: We observed differences in infant survival for 8 community socioeconomic indicators (P < .05). The greatest mortality risk was associated with residing in communities in the most disadvantaged deciles for poverty (adjusted hazard ratio [AHR] = 1.49; 95% confidence interval [CI] = 1.11, 1.99), education (AHR = 1.51; 95% CI = 1.16, 1.96), and operator or laborer occupations (AHR = 1.54; 95% CI = 1.16, 1.96). Survival decreased with increasing numbers of indicators that were in the most disadvantaged decile. Community-level mortality risk persisted when we adjusted for individual-level characteristics. CONCLUSIONS: The increased mortality risk among infants with CHDs living in socioeconomically deprived communities might indicate barriers to quality and timely care at which public health interventions might be targeted.

Prevention of orofacial clefts caused by smoking: implications of the Surgeon General's report.

BACKGROUND: According to the 2014 Surgeon General's Report, smoking in early pregnancy can cause orofacial clefts. We sought to examine the implications of this causal link for the potential prevention of orofacial clefts in the United States. METHODS: Using published data on the strength of the association between orofacial clefts and smoking in early pregnancy and the prevalence of smoking at the start of pregnancy, we estimated the attributable fraction for smoking as a cause of orofacial clefts. We then used the prevalence of orofacial clefts in the United States to estimate the number of orofacial clefts that could be prevented in the United States each year by eliminating exposure to smoking during early pregnancy. We also estimated the financial impact of preventing orofacial clefts caused by maternal smoking based on a published estimate of attributable healthcare costs through age 10 for orofacial clefts. RESULTS: The estimated attributable fraction of orofacial clefts caused by smoking in early pregnancy was 6.1% (95% uncertainty interval 4.4%, 7.7%). Complete elimination of smoking in early pregnancy could prevent orofacial clefts in approximately 430 infants per year in the United States, and could save an estimated $40.4 million in discounted healthcare costs through age 10 for each birth cohort. CONCLUSION: Understanding the magnitude of the preventable burden of orofacial clefts related to maternal smoking could help focus smoking cessation efforts on women who might become pregnant.

Using bayesian models to assess the effects of under-reporting of cannabis use on the association with birth defects, national birth defects prevention study, 1997-2005.

BACKGROUND: Studies on associations between periconceptional cannabis exposure and birth defects have mainly relied on self-reported exposure. Therefore, the results may be biased due to under-reporting of the exposure. The aim of this study was to quantify the potential effects of this form of exposure misclassification. METHODS: Using multivariable logistic regression, we re-analysed associations between periconceptional cannabis use and 20 specific birth defects using data from the National Birth Defects Prevention Study from 1997-2005 for 13 859 case infants and 6556 control infants. For seven birth defects, we implemented four Bayesian models based on various assumptions concerning the sensitivity of self-reported cannabis use to estimate odds ratios (ORs), adjusted for confounding and under-reporting of the exposure. We used information on sensitivity of self-reported cannabis use from the literature for prior assumptions. RESULTS: The results unadjusted for under-reporting of the exposure showed an association between cannabis use and anencephaly (posterior OR 1.9 [95% credible interval (CRI) 1.1, 3.2]) which persisted after adjustment for potential exposure misclassification. Initially, no statistically significant associations were observed between cannabis use and the other birth defect categories studied. Although adjustment for under-reporting did not notably change these effect estimates, cannabis use was associated with esophageal atresia (posterior OR 1.7 [95% CRI 1.0, 2.9]), diaphragmatic hernia (posterior OR 1.8 [95% CRI 1.1, 3.0]), and gastroschisis (posterior OR 1.7 [95% CRI 1.2, 2.3]) after correction for exposure misclassification. CONCLUSIONS: Under-reporting of the exposure may have obscured some cannabis-birth defect associations in previous studies. However, the resulting bias is likely to be limited.

Impact of time to maternal interview on interview responses in the National Birth Defects Prevention Study.

Prenatal exposures often are assessed using retrospective interviews. Time from exposure to interview may influence data accuracy. We investigated the association of time to interview (TTI) with aspects of interview responses in the National Birth Defects Prevention Study, a population-based case-control study of birth defects in 10 US states. Mothers completed a computer-assisted telephone interview 1.5-24 months after their estimated date of delivery. Proxy metrics for interview quality were whether certain exposures were reported, whether the start month of reported medication use or illness was reported, or whether responses were missing. Interaction by case status was assessed. Interviews were completed with 30,542 mothers (22,366 cases and 8,176 controls) who gave birth between 1997 and 2007. Mothers of cases were interviewed later than were mothers of controls (11.7 months vs. 9.5 months, respectively). In adjusted analyses, having a TTI that was greater than 6 months was associated with only a few aspects of interview responses (e.g., start month of pseudoephedrine use). Interaction by case-control status was observed for some exposures; mothers of controls had a greater reduction in interview quality with increased TTI in these instances (e.g., report of morning sickness, start month of acetaminophen use and ibuprofen use). The results suggest that TTI might impact interview responses; however, the impact may be minimal and specific to the type of exposure.

Current estimate of Down Syndrome population prevalence in the United States.

OBJECTIVE: To calculate a reliable estimate of the population prevalence of Down syndrome in the US. STUDY DESIGN: The annual number of births of infants with Down syndrome were estimated by applying published birth prevalence rates of Down syndrome by maternal age to US data from the Centers for Disease Control and Prevention for the years for which births by maternal age were available (1940-2008). Death certificate data for persons with Down syndrome were available for the years 1968-2007. We estimated the number of people with Down syndrome on January 1, 2008, using a life table approach based on proportions of deaths by age. Monte Carlo sampling was used to create 90% uncertainty intervals (UIs) for our estimates. RESULTS: We estimated the January 1, 2008, population prevalence of Down syndrome as approximately 250700 (90% UI, 185900-321700) based on proportions of deaths by age from the most recent 2 years (2006-2007) of death certificate data. This estimate corresponds to a prevalence of 8.27 people with Down syndrome per 10000 population (90% UI, 6.14-10.62). CONCLUSION: Our estimate of Down syndrome prevalence is roughly 25%-40% lower than estimates based solely on current birth prevalence. The results presented here can be considered a starting point for facilitating policy and services planning for persons with Down syndrome.

Estimate of the potential impact of folic acid fortification of corn masa flour on the prevention of neural tube defects.

BACKGROUND: Hispanics in the US have a higher prevalence of neural tube defect (NTD) -affected pregnancies than non-Hispanic whites, and lower median total folic acid (FA) intake. FA fortification of corn masa flour (CMF) is a policy-level intervention for NTD prevention; however, the impact on NTD prevalence has not been estimated. METHODS: We developed a model to estimate the percentage reduction in prevalence of spina bifida and anencephaly (NTDs) that could occur with FA fortification of CMF. Model inputs included estimates of the percentage reduction in United States NTD prevalence attributed to FA fortification of enriched cereal grain products (1995-1996 vs. 1998-2002), the increase in median FA intake after enriched cereal grain product fortification, and the estimated increase in median FA intake that could occur with CMF fortification at the same level as enriched cereal grain products (140 µg/100 g). We used Monte Carlo simulation to quantify uncertainty. We stratified analyses by racial/ethnic group and rounded results to the nearest 10. RESULTS: We estimated CMF fortification could prevent 30 Hispanic infants from having spina bifida (95% uncertainty interval: 0, 80) and 10 infants from having anencephaly (95% uncertainty interval: 0, 40) annually. The estimated impact among non-Hispanic whites and blacks was smaller. CONCLUSION: CMF fortification with FA could prevent from 0 to 120 infants, with the most likely value of approximately 40, from having spina bifida or anencephaly among Hispanics, the population most likely to benefit from the proposed intervention. While this estimated reduction is unlikely to be discernible using current birth defect surveillance methods, it still suggests an important benefit to the target population.

Association between maternal age and birth defects of unknown etiology: United States, 1997-2007.

BACKGROUND: Birth defects affect 3% of babies born, and are one of the leading causes of infant mortality. Both younger and older maternal age may pose increased risks for certain birth defects. This study assessed the relationship between maternal age at the estimated delivery date and the risk for birth defects. METHODS: Data were obtained from the National Birth Defects Prevention Study, a population-based case-control study including mothers across 10 states. Maternal age was stratified into six categories: <20, 20 to 24, 25 to 29, 30 to 34, 35 to 39, and ≥40 years, and also analyzed as a continuous variable. Logistic regression models adjusted formaternal race/ethnicity, education, body mass index (BMI), folic acid use, smoking, gravidity, and parental age difference were used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs). RESULTS: For maternal age <20 years, associations with total anomalous pulmonary venous return (aOR, 2.3; 95% CI, 1.3-4.0), amniotic band sequence (aOR, 2.4; 95% CI, 1.5-3.8), and gastroschisis (aOR, 6.1; 95% CI, 4.8-8.0) were observed. For the ≥40 year age group, associations with several cardiac defects, esophageal atresia (aOR, 2.9; 95% CI, 1.7-4.9), hypospadias (aOR, 2.0; 95% CI, 1.4-3.0), and craniosynostosis (aOR, 1.6; 95% CI, 1.1-2.4) were observed. Results using maternal age as a continuous variable were consistent with those that used categorized maternal age. CONCLUSION: Elucidating risk factors specific to women ateither extreme of maternal age may offer prevention opportunities. All women should be made aware of prevention opportunities, such as folic acid supplementation, to reduce the occurrence of birth defects.

Parent-reported prevalence of autism spectrum disorders in US-born children: an assessment of changes within birth cohorts from the 2003 to the 2007 National Survey of Children's Health.

The prevalence of autism spectrum disorders (ASD) from the 2007 National Survey of Children's Health (NSCH) was twice the 2003 NSCH estimate for autism. From each NSCH, we selected children born in the US from 1990 to 2000. We estimated autism prevalence within each 1-year birth cohort to hold genetic and non-genetic prenatal factors constant. Prevalence differences across surveys thus reflect survey measurement changes and/or external identification effects. In 2003, parents were asked whether their child was ever diagnosed with autism. In 2007, parents were asked whether their child was ever diagnosed with an ASD and whether s/he currently had an ASD. For the 1997-2000 birth cohorts (children aged 3-6 years in 2003 and 7-10 years in 2007), relative increases between 2003 autism estimates and 2007 ASD estimates were 200-600 %. For the 1990-1996 birth cohorts (children aged 7-13 years in 2003) increases were lower; nonetheless, differences between 2003 estimates and 2007 "ever ASD" estimates were >100 % for 6 cohorts and differences between 2003 estimates and 2007 "current ASD" estimates were >80 % for 3 cohorts. The magnitude of most birth cohort-specific differences suggests continuing diagnosis of children in the community played a sizable role in the 2003-2007 ASD prevalence increase. While some increase was expected for 1997-2000 cohorts, because some children have later diagnoses coinciding with school entry, increases were also observed for children ages ≥ 7 years in 2003. Given past ASD subtype studies, the 2003 "autism" question might have missed a modest amount (≤ 33 %) of ASDs other than autistic disorder.

Influencing clinical practice regarding the use of antiepileptic medications during pregnancy: modeling the potential impact on the prevalences of spina bifida and cleft palate in the United States.

Selected antiepileptic drugs (AEDs) increase the risk of birth defects. To assess the impact of influencing AED prescribing practices on spina bifida and cleft palate we searched the literature for estimates of the association between valproic acid or carbamazepine use during pregnancy and these defects and summarized the associations using meta-analyses. We estimated distributions of the prevalence of valproic acid and carbamazepine use among women of childbearing age based on analyses of four data sets. We estimated the attributable fractions and the number of children born with each defect that could be prevented annually in the United States if valproic acid and carbamazepine were not used during pregnancy. The summary odds ratio estimate for the association between valproic acid and spina bifida was 11.9 (95% uncertainty interval (UI): 4.0-21.2); for valproic acid and cleft palate 5.8 (95% UI: 3.3-9.5); for carbamazepine and spina bifida 3.6 (95% UI: 1.3-7.8); and for carbamazepine and cleft palate 2.4 (95% UI: 1.1-4.5) in the United States. Approximately 40 infants (95% UI: 10-100) with spina bifida and 35 infants (95% UI: 10-70) with cleft palate could be born without these defects each year if valproic acid were not used during pregnancy; 5 infants (95% UI: 0-15) with spina bifida and 5 infants (95% UI: 0-15) with cleft palate could be born without these defects each year if carbamazepine were not used during pregnancy. This modeling approach could be extended to other medications to estimate the impact of translating pharmacoepidemiologic data to evidence-based prenatal care practice.

Differences in Head Impact Exposures Between Youth Tackle and Flag Football Games and Practices: Potential Implications for Prevention Strategies.

BACKGROUND: Interventions designed to reduce the risk for head impacts and concussion in youth football have increased over the past decade; however, understanding of the role of regular game play on head impact exposure among youth tackle and flag football athletes is currently limited. PURPOSE: To explore head impact exposure among youth tackle and flag football athletes (age range, 6-14 years) during both practices and games. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: Using the Vector MouthGuard sensor, the authors collected head impact data from 524 tackle and flag youth football athletes over the course of a football season. Quantities of interest were estimated from regression models using Bayesian methods. RESULTS: For impacts ≥10g, a tackle football athlete had an estimated 17.55 (95% CI, 10.78-28.96) times more head impacts per practice compared with a flag football athlete (6.85 [95% CI, 6.05-7.76] and 0.39 [95% CI, 0.24-0.62] head impacts, respectively). Additionally, a tackle football athlete had an estimated 19.48 (95% CI, 12.74-29.98) times more head impacts per game compared with a flag football athlete (13.59 [95% CI, 11.97-15.41] and 0.70 [95% CI, 0.46-1.05] head impacts, respectively). Among tackle football athletes, the estimated average impact rate was 6.51 (95% CI, 5.75-7.37) head impacts during a practice and 12.97 (95% CI, 11.36-14.73) impacts during a game, resulting in 2.00 (95% CI, 1.74-2.29) times more ≥10g head impacts in games versus practices. Tackle football athletes had 2.06 (95% CI, 1.80-2.34) times more high-magnitude head impacts (≥40g) during a game than during a practice. On average, flag football athletes experienced an estimated 0.37 (95% CI, 0.20-0.60) head impacts during a practice and 0.77 (95% CI, 0.53-1.06) impacts during a game, resulting in 2.06 (95% CI, 1.29-3.58) times more ≥10g head impacts in games versus practices. Because of model instability caused by a large number of zero impacts for flag football athletes, a comparison of high-magnitude head impacts is not reported for practices or games. CONCLUSION: This study provides a characterization of the head impact exposure of practices and games among a large population of youth tackle and flag football athletes aged 6 to 14 years. These findings suggest that a greater focus on game-based interventions, such as fair play interventions and strict officiating, may be beneficial to reduce head impact exposures for youth football athletes.

Head Impact Exposures Among Youth Tackle and Flag American Football Athletes.

BACKGROUND: Promoted as a safer alternative to tackle football, there has been an increase in flag football participation in recent years. However, examinations of head impact exposure in flag football as compared with tackle football are currently limited. HYPOTHESIS: Tackle football athletes will have a greater number and magnitude of head impacts compared with flag football athletes. STUDY DESIGN: Cohort study. LEVEL OF EVIDENCE: Level 4. METHODS: Using mouthguard sensors, this observational, prospective cohort study captured data on the number and magnitude of head impacts among 524 male tackle and flag football athletes (6-14 years old) over the course of a single football season. Estimates of interest based on regression models used Bayesian methods to estimate differences between tackle and flag athletes. RESULTS: There were 186,239 head impacts recorded during the study. Tackle football athletes sustained 14.67 (95% CI 9.75-21.95) times more head impacts during an athletic exposure (game or practice) compared with flag football athletes. Magnitude of impact for the 50th and 95th percentile was 18.15g (17.95-18.34) and 52.55g (51.06-54.09) for a tackle football athlete and 16.84g (15.57-18.21) and 33.51g (28.23-39.08) for a flag football athlete, respectively. A tackle football athlete sustained 23.00 (13.59-39.55) times more high-magnitude impacts (≥40g) per athletic exposure compared with a flag football athlete. CONCLUSION: This study demonstrates that youth athletes who play tackle football are more likely to experience a greater number of head impacts and are at a markedly increased risk for high-magnitude impacts compared with flag football athletes. CLINICAL RELEVANCE: These results suggest that flag football has fewer head impact exposures, which potentially minimizes concussion risk, making it a safer alternative for 6- to 14-year-old youth football athletes.

Estimation of the contribution of non-assisted reproductive technology ovulation stimulation fertility treatments to US singleton and multiple births.

Infertility treatments that include ovulation stimulation, both assisted reproductive technologies (ARTs) and non-ART ovulation stimulation, are associated with increased risks of multiple birth and concomitant sequelae and adverse outcomes, even among singletons. While a US surveillance system for ART-induced births is ongoing, no population-based tracking system exists for births resulting from non-ART treatments. The authors developed a multistage model to estimate the uncertain proportion of US infants born in 2005 who were conceived by using non-ART ovulation treatments. Using published surveillance data, they estimated proportions of US multiple births conceived naturally and by ART and assumed that the remainder were conceived with non-ART treatments. They used Bayesian meta-analyses to summarize published clinical studies on the multiple-gestation risk associated with non-ART ovulation treatments, applied a fetal survival factor, and used this multiple-birth risk estimate and their own estimate of the proportion of US multiple births attributable to non-ART ovulation stimulation to estimate the total (and, through subtraction, singleton) proportion of infants conceived with such treatments. On the basis of the model, the authors estimate that 4.6% of US infants born in 2005 (95% uncertainty range: 2.8%-7.1%) resulted from non-ART ovulation treatments. Notably, this figure is 4 times greater than the ART contribution.

Systematic Review and Bayesian Meta-analysis of the Dose-response Relationship between Folic Acid Intake and Changes in Blood Folate Concentrations.

The threshold for population-level optimal red blood cell (RBC) folate concentration among women of reproductive age for the prevention of neural tube defects has been estimated at 906 nmol/L; however, the dose-response relationship between folic acid intake and blood folate concentrations is uncharacterized. To estimate the magnitude of blood folate concentration increase in response to specific dosages of folic acid under steady-state conditions (as could be achieved with food fortification), a systematic review of the literature and meta-analysis was conducted. Of the 14,002 records we identified, 533 were selected for full-text review, and data were extracted from 108 articles. The steady-state concentrations (homeostasis) of both serum/plasma and RBC folate concentrations were estimated using a Bayesian meta-analytic approach and one-compartment physiologically-based pharmacokinetic models. RBC folate concentrations increased 1.78 fold (95% credible interval (CI): 1.66, 1.93) from baseline to steady-state at 375⁻570 µg folic acid/day, and it took a median of 36 weeks of folic acid intake (95% CI: 27, 52) to achieve steady-state RBC folate concentrations. Based on regression analysis, we estimate that serum/plasma folate concentrations increased 11.6% (95% CI: 8.4, 14.9) for every 100 µg/day folic acid intake. These results will help programs plan and monitor folic acid fortification programs.

Perinatal outcomes of twin births conceived using assisted reproduction technology: a population-based study.

BACKGROUND: Approximately 18% of multiple births in the USA result from assisted reproduction technology (ART). Although many studies comparing ART and naturally conceived twins report no difference in risks for perinatal outcomes, others report slight to moderate positive or protective associations. METHODS: We selected twin deliveries with and without indication of ART from Massachusetts live birth-infant death records from 1997 to 2000 linked to the US ART surveillance system. The sample was restricted to deliveries by mothers with increased socioeconomic status, private health insurance and intermediate/plus prenatal care use. Our final sample included 1446 and 2729 ART and non-ART twin deliveries, respectively. Odds ratios (OR) for associations between ART and perinatal outcomes were adjusted for maternal demographic factors, smoking, prenatal care and hospital care level. RESULTS: ART twin deliveries were less likely than non-ART to be very preterm (adjusted OR 0.75; 95% confidence interval 0.58-0.97) or include a very low birthweight (<1500 g) infant (0.75; 0.58-0.95) or infant death (0.55; 0.35-0.88). In stratified analyses, these findings were observed among primiparous deliveries, but there were no risk differences among multiparous ART and non-ART twin deliveries. CONCLUSIONS: ART treatment was not a risk factor for adverse perinatal outcome, and risks for several outcomes were somewhat lower among ART twin deliveries. Nonetheless, ART is strongly associated with twinning and twins remain a high-risk group, relative to singletons. Promoting singleton gestation in assisted conception is an important strategy for reducing adverse outcomes.

Modeling the impact of folic acid fortification and supplementation on red blood cell folate concentrations and predicted neural tube defect risk in the United States: have we reached optimal prevention?

Background: The US CDC and the Institute of Medicine recommend that women capable of becoming pregnant consume ≥400 µg synthetic folic acid/d to prevent neural tube defects (NTDs). The United States has 3 sources of folic acid: fortified enriched cereal grain products (ECGPs), fortified ready-to-eat (RTE) cereals, and dietary supplements. Objective: Our objectives were as follows: 1) to estimate the usual daily folic acid intake and distributions of red blood cell (RBC) folate concentrations among women consuming folic acid from different sources; 2) to assess the usual daily total folic acid intake associated with optimal RBC folate concentrations for NTD prevention; 3) to predict NTD prevalence; and 4) to estimate the number of preventable folate-sensitive NTDs. Design: NHANES data (2007-2012) for nonpregnant women of reproductive age (12-49 y) were used to estimate usual daily intakes of synthetic folic acid and natural food folate. We applied existing models of the relation between RBC folate concentrations and NTD risk to predict NTD prevalence. Results: Based on the distribution of overall RBC folate concentrations (4783 women), the predicted NTD prevalence was 7.3/10,000 live births [95% uncertainty interval (UI): 5.5-9.4/10,000 live births]. Women consuming folic acid from ECGPs as their only source had lower usual daily total folic acid intakes (median: 115 µg/d; IQR: 79-156 µg/d), lower RBC folate concentrations (median: 881 nmol/L; IQR: 704-1108 nmol/L), and higher predicted NTD prevalence (8.5/10,000 live births; 95% UI: 6.4-10.8/10,000 live births) compared with women consuming additional folic acid from diet or supplements. If women who currently consume folic acid from ECGPs only (48% of women) consumed additional folic acid sources, 345 (95% UI: 0-821) to 701 (95% UI: 242-1189) additional NTDs/y could be prevented. Conclusions: This analysis supports current recommendations and does not indicate any need for higher intakes of folic acid to achieve optimal NTD prevention. Ensuring 400 µg/d intake of folic acid prior to pregnancy has the potential to increase the number of babies born without an NTD.

Estimating the numbers of pregnant women infected with Zika virus and infants with congenital microcephaly in Colombia, 2015-2017.

BACKGROUND: Colombia experienced a Zika virus (ZIKV) outbreak in 2015-2016. To assist with planning for medical and supportive services for infants affected by prenatal ZIKV infection, we used a model to estimate the number of pregnant women infected with ZIKV and the number of infants with congenital microcephaly from August 2015 to August 2017. METHODS: We used nationally reported cases of symptomatic ZIKV disease among pregnant women and information from the literature on the percent of asymptomatic infections to estimate the number of pregnant women with ZIKV infection occurring August 2015-December 2016. We then estimated the number of infants with congenital microcephaly expected to occur August 2015-August 2017. To compare to the observed counts of infants with congenital microcephaly due to all causes reported through the national birth defects surveillance system, the model was time limited to produce estimates for February-November 2016. FINDINGS: We estimated 1140-2160 (interquartile range [IQR]) infants with congenital microcephaly in Colombia, during August 2015-August 2017, whereas 340-540 infants with congenital microcephaly would be expected in the absence of ZIKV. Based on the time limited version of the model, for February-November 2016, we estimated 650-1410 infants with congenital microcephaly in Colombia. The 95% uncertainty interval for the latter estimate encompasses the 476 infants with congenital microcephaly reported during that approximate time frame based on national birth defects surveillance. INTERPRETATION: Based on modeled estimates, ZIKV infection during pregnancy in Colombia could lead to 3-4 times as many infants with congenital microcephaly in 2015-2017 as would have been expected in the absence of the ZIKV outbreak. FUNDING: This publication was made possible through support provided by the Bureau for Global Health, U.S. Agency for International Development under the terms of an Interagency Agreement with Centers for Disease Control and Prevention.

Risk of bacterial meningitis in children with cochlear implants.

BACKGROUND: In June 2002, the Food and Drug Administration received reports of bacterial meningitis in patients with cochlear implants for treatment of hearing loss. Implants that included a positioner (a wedge inserted next to the implanted electrode to facilitate transmission of the electrical signal by pushing the electrode against the medial wall of the cochlea) were voluntarily recalled in the United States in July 2002. METHODS: We identified patients with meningitis and conducted a cohort study and a nested case-control investigation involving 4264 children who had received cochlear implants in the United States between January 1, 1997, and August 6, 2002, and who were less than six years of age when they received the implants. We calculated the incidence of meningitis in the cohort and assessed risk factors for meningitis among patients and among 199 controls, using data from interviews with parents and abstracted from medical records. RESULTS: We identified 26 children with bacterial meningitis. The incidence of meningitis caused by Streptococcus pneumoniae was 138.2 cases per 100,000 person-years--more than 30 times the incidence in a cohort of the same age in the general U.S. population. Postimplantation bacterial meningitis was strongly associated with the use of an implant with a positioner (odds ratio, 4.5 [95 percent confidence interval, 1.3 to 17.9], with adjustment for medical, surgical, and environmental factors) and with the joint presence of radiographic evidence of a malformation of the inner ear and a cerebrospinal fluid leak (adjusted odds ratio, 9.3 [95 percent confidence interval, 1.2 to 94.5]). The incidence of meningitis among patients who had received an implant with a positioner remained higher than the incidence among those whose implants did not have a positioner for the duration of follow-up (24 months from the time of implantation). CONCLUSIONS: Parents and health care providers should ensure that all children who receive cochlear implants are appropriately vaccinated and are then monitored and treated promptly for any bacterial infections after receiving the implant.