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.

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.

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.

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.

Proportion of selected congenital heart defects attributable to recognized risk factors.

PURPOSE: To assess the contribution of multiple risk factors for two congenital heart defects-hypoplastic left heart syndrome (HLHS) and tetralogy of Fallot (TOF). METHODS: We used data from the National Birth Defects Prevention Study (1997-2011) to estimate average adjusted population attributable fractions for several recognized risk factors, including maternal prepregnancy overweight-obesity, pregestational diabetes, age, and infant sex. RESULTS: There were 594 cases of isolated simple HLHS, 971 cases of isolated simple TOF, and 11,829 controls in the analysis. Overall, 57.0% of HLHS cases and 37.0% of TOF cases were estimated to be attributable to risk factors included in our model. Among modifiable HLHS risk factors, maternal prepregnancy overweight-obesity accounted for the largest proportion of cases (6.5%). Among modifiable TOF risk factors, maternal prepregnancy overweight-obesity and maternal age of 35 years or older accounted for the largest proportions of cases (8.3% and 4.3%, respectively). CONCLUSIONS: Approximately half of HLHS cases and one-third of TOF cases were estimated to be attributable to risk factors included in our models. Interventions targeting factors that can be modified may help reduce the risk of HLHS and TOF development. Additional research into the etiology of HLHS and TOF may reveal other modifiable risk factors that might contribute to primary prevention efforts.

Estimating the Number of Pregnant Women Infected With Zika Virus and Expected Infants With Microcephaly Following the Zika Virus Outbreak in Puerto Rico, 2016.

IMPORTANCE: Zika virus (ZIKV) infection during pregnancy is a cause of congenital microcephaly and severe fetal brain defects, and it has been associated with other adverse pregnancy and birth outcomes. OBJECTIVE: To estimate the number of pregnant women infected with ZIKV in Puerto Rico and the number of associated congenital microcephaly cases. DESIGN, SETTING, AND PARTICIPANTS: We conducted a modeling study from April to July 2016. Using parameters derived from published reports, outcomes were modeled probabilistically using Monte Carlo simulation. We used uncertainty distributions to reflect the limited information available for parameter values. Given the high level of uncertainty in model parameters, interquartile ranges (IQRs) are presented as primary results. Outcomes were modeled for pregnant women in Puerto Rico, which currently has more confirmed ZIKV cases than any other US location. EXPOSURE: Zika virus infection in pregnant women. MAIN OUTCOMES AND MEASURES: Number of pregnant women infected with ZIKV and number of congenital microcephaly cases. RESULTS: We estimated an IQR of 5900 to 10 300 pregnant women (median, 7800) might be infected during the initial ZIKV outbreak in Puerto Rico. Of these, an IQR of 100 to 270 infants (median, 180) may be born with microcephaly due to congenital ZIKV infection from mid-2016 to mid-2017. In the absence of a ZIKV outbreak, an IQR of 9 to 16 cases (median, 12) of congenital microcephaly are expected in Puerto Rico per year. CONCLUSIONS AND RELEVANCE: The estimate of 5900 to 10 300 pregnant women that might be infected with ZIKV provides an estimate for the number of infants that could potentially have ZIKV-associated adverse outcomes. Including baseline cases of microcephaly, we estimated that an IQR of 110 to 290 total cases of congenital microcephaly, mostly attributable to ZIKV infection, could occur from mid-2016 to mid-2017 in the absence of effective interventions. The primary limitation in this analysis is uncertainty in model parameters. Multivariate sensitivity analyses indicated that the cumulative incidence of ZIKV infection and risk of microcephaly given maternal infection in the first trimester were the primary drivers of both magnitude and uncertainty in the estimated number of microcephaly cases. Increased information on these parameters would lead to more precise estimates. Nonetheless, the results underscore the need for urgent actions being undertaken in Puerto Rico to prevent congenital ZIKV infection and prepare for affected infants.

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.

Specific SSRIs and birth defects: Bayesian analysis to interpret new data in the context of previous reports.

OBJECTIVE: To follow up on previously reported associations between periconceptional use of selective serotonin reuptake inhibitors (SSRIs) and specific birth defects using an expanded dataset from the National Birth Defects Prevention Study. DESIGN: Bayesian analysis combining results from independent published analyses with data from a multicenter population based case-control study of birth defects. SETTING: 10 centers in the United States. PARTICIPANTS: 17,952 mothers of infants with birth defects and 9857 mothers of infants without birth defects, identified through birth certificates or birth hospitals, with estimated dates of delivery between 1997 and 2009. EXPOSURES: Citalopram, escitalopram, fluoxetine, paroxetine, or sertraline use in the month before through the third month of pregnancy. Posterior odds ratio estimates were adjusted to account for maternal race/ethnicity, education, smoking, and prepregnancy obesity. MAIN OUTCOME MEASURE: 14 birth defects categories that had associations with SSRIs reported in the literature. RESULTS: Sertraline was the most commonly reported SSRI, but none of the five previously reported birth defects associations with sertraline was confirmed. For nine previously reported associations between maternal SSRI use and birth defect in infants, findings were consistent with no association. High posterior odds ratios excluding the null value were observed for five birth defects with paroxetine (anencephaly 3.2, 95% credible interval 1.6 to 6.2; atrial septal defects 1.8, 1.1 to 3.0; right ventricular outflow tract obstruction defects 2.4, 1.4 to 3.9; gastroschisis 2.5, 1.2 to 4.8; and omphalocele 3.5, 1.3 to 8.0) and for two defects with fluoxetine (right ventricular outflow tract obstruction defects 2.0, 1.4 to 3.1 and craniosynostosis 1.9, 1.1 to 3.0). CONCLUSIONS: These data provide reassuring evidence for some SSRIs but suggest that some birth defects occur 2-3.5 times more frequently among the infants of women treated with paroxetine or fluoxetine early in pregnancy.

Assessing the association between natural food folate intake and blood folate concentrations: a systematic review and Bayesian meta-analysis of trials and observational studies.

Folate is found naturally in foods or as synthetic folic acid in dietary supplements and fortified foods. Adequate periconceptional folic acid intake can prevent neural tube defects. Folate intake impacts blood folate concentration; however, the dose-response between natural food folate and blood folate concentrations has not been well described. We estimated this association among healthy females. A systematic literature review identified studies (1 1992-3 2014) with both natural food folate intake alone and blood folate concentration among females aged 12-49 years. Bayesian methods were used to estimate regression model parameters describing the association between natural food folate intake and subsequent blood folate concentration. Seven controlled trials and 29 observational studies met the inclusion criteria. For the six studies using microbiologic assay (MA) included in the meta-analysis, we estimate that a 6% (95% Credible Interval (CrI): 4%, 9%) increase in red blood cell (RBC) folate concentration and a 7% (95% CrI: 1%, 12%) increase in serum/plasma folate concentration can occur for every 10% increase in natural food folate intake. Using modeled results, we estimate that a natural food folate intake of ≥ 450 µg dietary folate equivalents (DFE)/day could achieve the lower bound of an RBC folate concentration (~ 1050 nmol/L) associated with the lowest risk of a neural tube defect. Natural food folate intake affects blood folate concentration and adequate intakes could help women achieve a RBC folate concentration associated with a risk of 6 neural tube defects/10,000 live births.

Assessing the association between the methylenetetrahydrofolate reductase (MTHFR) 677C>T polymorphism and blood folate concentrations: a systematic review and meta-analysis of trials and observational studies.

BACKGROUND: The methylenetetrahydrofolate reductase (MTHFR) 677C>T polymorphism is a risk factor for neural tube defects. The T allele produces an enzyme with reduced folate-processing capacity, which has been associated with lower blood folate concentrations. OBJECTIVE: We assessed the association between MTHFR C677T genotypes and blood folate concentrations among healthy women aged 12-49 y. DESIGN: We conducted a systematic review of the literature published from January 1992 to March 2014 to identify trials and observational studies that reported serum, plasma, or red blood cell (RBC) folate concentrations and MTHFR C677T genotype. We conducted a meta-analysis for estimates of percentage differences in blood folate concentrations between genotypes. RESULTS: Forty studies met the inclusion criteria. Of the 6 studies that used the microbiologic assay (MA) to measure serum or plasma (S/P) and RBC folate concentrations, the percentage difference between genotypes showed a clear pattern of CC > CT > TT. The percentage difference was greatest for CC > TT [S/P: 13%; 95% credible interval (CrI): 7%, 18%; RBC: 16%; 95% CrI: 12%, 20%] followed by CC > CT (S/P: 7%; 95% CrI: 1%, 12%; RBC: 8%; 95% CrI: 4%, 12%) and CT > TT (S/P: 6%; 95% CrI: 1%, 11%; RBC: 9%; 95% CrI: 5%, 13%). S/P folate concentrations measured by using protein-binding assays (PBAs) also showed this pattern but to a greater extent (e.g., CC > TT: 20%; 95% CrI: 17%, 22%). In contrast, RBC folate concentrations measured by using PBAs did not show the same pattern and are presented in the Supplemental Material only. CONCLUSIONS: Meta-analysis results (limited to the MA, the recommended population assessment method) indicated a consistent percentage difference in S/P and RBC folate concentrations across MTHFR C677T genotypes. Lower blood folate concentrations associated with this polymorphism could have implications for a population-level risk of neural tube defects.

Diabetes and congenital heart defects: a systematic review, meta-analysis, and modeling project.

CONTEXT: Maternal pregestational diabetes (PGDM) is a risk factor for development of congenital heart defects (CHDs). Glycemic control before pregnancy reduces the risk of CHDs. A meta-analysis was used to estimate summary ORs and mathematical modeling was used to estimate population attributable fractions (PAFs) and the annual number of CHDs in the U.S. potentially preventable by establishing glycemic control before pregnancy. EVIDENCE ACQUISITION: A systematic search of the literature through December 2012 was conducted in 2012 and 2013. Case-control or cohort studies were included. Data were abstracted from 12 studies for a meta-analysis of all CHDs. EVIDENCE SYNTHESIS: Summary estimates of the association between PGDM and CHDs and 95% credible intervals (95% CrIs) were developed using Bayesian random-effects meta-analyses for all CHDs and specific CHD subtypes. Posterior estimates of this association were combined with estimates of CHD prevalence to produce estimates of PAFs and annual prevented cases. Ninety-five percent uncertainty intervals (95% UIs) for estimates of the annual number of preventable cases were developed using Monte Carlo simulation. Analyses were conducted in 2013. The summary OR estimate for the association between PGDM and CHDs was 3.8 (95% CrI=3.0, 4.9). Approximately 2670 (95% UI=1795, 3795) cases of CHDs could potentially be prevented annually if all women in the U.S. with PGDM achieved glycemic control before pregnancy. CONCLUSIONS: Estimates from this analysis suggest that preconception care of women with PGDM could have a measureable impact by reducing the number of infants born with CHDs.

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.

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.

Population red blood cell folate concentrations for prevention of neural tube defects: Bayesian model.

OBJECTIVE: To determine an optimal population red blood cell (RBC) folate concentration for the prevention of neural tube birth defects. DESIGN: Bayesian model. SETTING: Data from two population based studies in China. PARTICIPANTS: 247,831 participants in a prospective community intervention project in China (1993-95) to prevent neural tube defects with 400 µg/day folic acid supplementation and 1194 participants in a population based randomized trial (2003-05) to evaluate the effect of folic acid supplementation on blood folate concentration among Chinese women of reproductive age. INTERVENTION: Folic acid supplementation (400 µg/day). MAIN OUTCOME MEASURES: Estimated RBC folate concentration at time of neural tube closure (day 28 of gestation) and risk of neural tube defects. RESULTS: Risk of neural tube defects was high at the lowest estimated RBC folate concentrations (for example, 25.4 (95% uncertainty interval 20.8 to 31.2) neural tube defects per 10,000 births at 500 nmol/L) and decreased as estimated RBC folate concentration increased. Risk of neural tube defects was substantially attenuated at estimated RBC folate concentrations above about 1000 nmol/L (for example, 6 neural tube defects per 10,000 births at 1180 (1050 to 1340) nmol/L). The modeled dose-response relation was consistent with the existing literature. In addition, neural tube defect risk estimates developed using the proposed model and population level RBC information were consistent with the prevalence of neural tube defects in the US population before and after food fortification with folic acid. CONCLUSIONS: A threshold for "optimal" population RBC folate concentration for the prevention of neural tube defects could be defined (for example, approximately 1000 nmol/L). Population based RBC folate concentrations, as a biomarker for risk of neural tube defects, can be used to facilitate evaluation of prevention programs as well as to identify subpopulations at elevated risk for a neural tube defect affected pregnancy due to folate insufficiency.

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.

Socioeconomic status, child enrichment factors, and cognitive performance among preschool-age children: results from the Follow-Up of Growth and Development Experiences study.

Lower cognitive performance is associated with poorer health and functioning throughout the lifespan and disproportionately affects children from lower socioeconomic status (SES) populations. Previous studies reporting positive associations between child home enrichment and cognitive performance generally had a limited distribution of SES. We evaluated the associations of SES and child enrichment with cognitive performance in a population with a wide range of SES, particularly whether enrichment attenuates associations with SES. Children were sampled from a case-control study of small-for-gestational-age (SGA) conducted in a public hospital serving a low SES population (final n=198) and a private hospital serving a middle-to-high SES population (final n=253). SES (maternal education and income) and perinatal factors (SGA, maternal smoking and drinking) were obtained from maternal birth interview. Five child home enrichment factors (e.g. books in home) and preschool attendance were obtained from follow-up interview at age 4.5 years. Cognitive performance was assessed with the Differential Ability Scales (DAS), a standardized psychometric test administered at follow-up. SES and enrichment scores were created by combining individual factors. Analyses were adjusted for perinatal factors. Children from the public birth hospital had a significantly lower mean DAS general cognitive ability (GCA) score than children born at the private birth hospital (adjusted mean difference -21.4, 95% CI: -24.0, -18.7); this was substantially attenuated by adjustment for individual SES, child enrichment factors, and preschool attendance (adjusted mean difference -5.1, 95% CI: -9.5, -0.7). Individual-level SES score was associated with DAS score, beyond the general SES effect associated with hospital of birth. Adjustment for preschool attendance and home enrichment score attenuated the association between individual SES score and adjusted mean DAS-GCA among children born at both of the hospitals. The effect of being in the lower compared to the middle tertile of SES score was reduced by approximately a quarter; the effect of being in the upper compared to the middle tertile of SES score was reduced by nearly half, but this comparison was possible only for children born at the private hospital. A child's individual SES was associated with cognitive performance within advantaged and disadvantaged populations. Child enrichment was associated with better cognitive performance and attenuated the SES influence. Health care providers should reinforce guidelines for home enrichment and refer children with delays to early intervention and education, particularly children from disadvantaged populations.

Population attributable fractions for three perinatal risk factors for autism spectrum disorders, 2002 and 2008 autism and developmental disabilities monitoring network.

PURPOSE: Numerous studies establish associations between adverse perinatal outcomes/complications and autism spectrum disorder (ASD). There has been little assessment of population attributable fractions (PAFs). METHODS: We estimated average ASD PAFs for preterm birth (PTB), small for gestational age (SGA), and Cesarean delivery (CD) in a U.S. population. Average PAF methodology accounts for risk factor co-occurrence. ASD cases were singleton non-Hispanic white, non-Hispanic black, and Hispanic children born in 1994 (n = 703) or 2000 (n = 1339) who resided in 48 U.S. counties included within eight Autism and Developmental Disabilities Monitoring Network sites. Cases were matched on birth year, sex, and maternal county of residence, race-ethnicity, age, and education to 20 controls from U.S. natality files. RESULTS: For the 1994 cohort, average PAFs were 4.2%, 0.9%, and 7.9% for PTB, SGA, and CD, respectively. The summary PAF was 13.0% (1.7%-19.5%). For the 2000 cohort, average PAFs were 2.0%, 3.1%, and 6.7% for PTB, SGA, and CD, respectively, with a summary PAF of 11.8% (7.5%-15.9%). CONCLUSIONS: Three perinatal risk factors notably contribute to ASD risk in a U.S. population. Because each factor represents multiple etiologic pathways, PAF estimates are best interpreted as the proportion of ASD attributable to having a suboptimal perinatal environment resulting in PTB, SGA, and/or CD.