NINDS Health Equity Strategic Planning Process Overview, High-Level Recommendations, and Guide.

Neurologic mortality is increasing in the United States and is occurring in an inequitable manner. There is a major need for innovative research strategies to eliminate these inequities. In 2020, the National Institute of Neurological Disorders and Stroke (NINDS) embarked on a health equity strategic planning process, which culminated in a 3-day public workshop and research recommendations provided by a working group of its National Advisory Neurological Disorders and Stroke Council (NANDSC WG) to the NINDS. This Neurology® supplement is dedicated to the NINDS health equity strategic planning process. As cochairs of the NANDS WG, we developed this summary to provide an overview of the process and a guide for navigating this special issue. Detailed recommendations from the NANDS WG are distributed throughout various articles in this supplement and supported with extensive commentary on the state of the science in health equity. Consolidated high-level recommendations from this process are presented at the end of this article.

The Lives Lost to Inequities: Avertable Deaths From Neurologic Diseases in the Past Decade.

BACKGROUND AND OBJECTIVES: Mortality rates for neurologic diseases are increasing in the United States, with large disparities across geographical areas and populations. Racial and ethnic populations, notably the non-Hispanic (NH) Black population, experience higher mortality rates for many causes of death, but the magnitude of the disparities for neurologic diseases is unclear. The objectives of this study were to calculate mortality rates for neurologic diseases by race and ethnicity and-to place this disparity in perspective-to estimate how many US deaths would have been averted in the past decade if the NH Black population experienced the same mortality rates as other groups. METHODS: Mortality rates for deaths attributed to neurologic diseases, as defined by the International Classification of Diseases, were calculated for 2010 to 2019 using death and population data obtained from the Centers for Disease Control and Prevention and the US Census Bureau. Avertable deaths were calculated by indirect standardization: For each calendar year of the decade, age-specific death rates of NH White persons in 10 age groups were multiplied by the NH Black population in each age group. A secondary analysis used Hispanic and NH Asian populations as the reference groups. RESULTS: In 2013, overall age-adjusted mortality rates for neurologic diseases began increasing, with the NH Black population experiencing higher rates than NH White, NH American Indian and Alaska Native, Hispanic, and NH Asian populations (in decreasing order). Other populations with higher mortality rates for neurologic diseases included older adults, the male population, and adults older than 25 years without a high school diploma. The gap in mortality rates for neurologic diseases between the NH Black and NH White populations widened from 4.2 individuals per 100,000 in 2011 to 7.0 per 100,000 in 2019. Over 2010 to 2019, had the NH Black population experienced the neurologic mortality rates of NH White, Hispanic, or NH Asian populations, 29,986, 88,407, or 117,519 deaths, respectively, would have been averted. DISCUSSION: Death rates for neurologic diseases are increasing. Disproportionately higher neurologic mortality rates in the NH Black population are responsible for a large number of excess deaths, making research and policy efforts to address the systemic causes increasingly urgent.

Establishing Sickle Cell Disease Stroke Prevention Teams in Africa is Feasible: Program Evaluation Using the RE-AIM Framework.

We used the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework to evaluate a Stroke Prevention Team's readiness to prevent strokes in children with sickle cell anemia living in northern Nigeria. The NIH sponsored Stroke Prevention Trial in Nigeria included a goal of a sustainable stroke prevention program. The program's 1-year reach for transcranial Doppler screening was 14.7% (4710/32,000) of which 6.0% (281/4710) had abnormal velocities (≥200 cm/s). All participants with abnormal transcranial Doppler velocities were started on hydroxyurea (effectiveness). The leaders of all 5 hospitals agreed to adopt the program. After 1 year, program-implementation and maintenance rates were 100%, demonstrating the program's feasibility and short-term sustainability.

Hydroxyurea for primary stroke prevention in children with sickle cell anaemia in Nigeria (SPRING): a double-blind, multicentre, randomised, phase 3 trial.

BACKGROUND: In high-income countries, standard care for primary stroke prevention in children with sickle cell anaemia and abnormal transcranial Doppler velocities results in a 92% relative risk reduction of strokes but mandates initial monthly blood transfusion. In Africa, where regular blood transfusion is not feasible for most children, we tested the hypothesis that initial moderate-dose compared with low-dose hydroxyurea decreases the incidence of strokes for children with abnormal transcranial Doppler velocities. METHODS: SPRING is a double-blind, parallel-group, randomised, controlled, phase 3 trial of children aged 5-12 years with sickle cell anaemia with abnormal transcranial Doppler velocities conducted at three teaching hospitals in Nigeria. For randomisation, we used a permuted block allocation scheme with block sizes of four, stratified by sex and site. Allocation was concealed from all but the pharmacists and statisticians. Participants were assigned in a 1:1 ratio to low-dose (10 mg/kg per day) or moderate-dose (20 mg/kg per day) oral hydroxyurea taken once daily with monthly clinical evaluation and laboratory monitoring. The primary outcome was initial stroke or transient ischaemic attack, centrally adjudicated. The secondary outcome was all-cause hospitalisation. We used the intention-to-treat population for data analysis. The trial was stopped early for futility after a planned minimum follow-up of 3·0 years to follow-up for participants. This trial was registered with ClinicalTrials.gov, number NCT02560935. FINDINGS: Between Aug 2, 2016, and June 14, 2018, 220 participants (median age 7·2 years [IQR 5·5-8·9]; 114 [52%] female) were randomly allocated and followed for a median of 2·4 years (IQR 2·0-2·8). All participants were Nigerian and were from the following ethnic groups: 179 (82%) people were Hausa, 25 (11%) were Fulani, and 16 (7%) identified as another ethnicity. In the low-dose hydroxyurea group, three (3%) of 109 participants had strokes, with an incidence rate of 1·19 per 100 person-years and in the moderate-dose hydroxyurea group five (5%) of 111 had strokes with an incidence rate of 1·92 per 100 person-years (incidence rate ratio 0·62 [95% CI 0·10-3·20], p=0·77). The incidence rate ratio of hospitalisation for any reason was 1·71 (95% CI 1·15-2·57, p=0·0071), with higher incidence rates per 100 person-years in the low-dose group versus the moderate-dose group (27·43 vs 16·08). No participant had hydroxyurea treatment stopped for myelosuppression. INTERPRETATION: Compared with low-dose hydroxyurea therapy, participants treated with moderate-dose hydroxyurea had no difference in the stroke incidence rate. However, secondary analyses suggest that the moderate-dose group could lower incidence rates for all-cause hospitalisations. These findings provide an evidence-based guideline for the use of low-dose hydroxyurea therapy for children with sickle cell anaemia at risk of stroke. FUNDING: National Institute of Neurological Disorders and Stroke.

Primary prevention of stroke in children with sickle cell anemia in sub-Saharan Africa: rationale and design of phase III randomized clinical trial.

Strokes in children with sickle cell anemia (SCA) are associated with significant morbidity and premature death. Primary stroke prevention in children with SCA involves screening for abnormal transcranial Doppler (TCD) velocity coupled with regular blood transfusion therapy for children with abnormal velocities, for at least one year. However, in Africa, where the majority of children with SCA live, regular blood transfusions are not feasible due to inadequate supply of safe blood, cost, and the reluctance of caregivers to accept transfusion therapy for their children. We describe the Primary Prevention of Stroke in Children with Sickle Cell Disease in Nigeria Trial [StrokePreventioninNigeria (SPRING) trial, NCT02560935], a three-center double-blinded randomized controlled Phase III clinical trial to 1) determine the efficacy of moderate fixed-dose (20 mg/kg/day) versus low fixed-dose (10 mg/kg/day) hydroxyurea therapy for primary stroke prevention; 2) determine the efficacy of moderate fixed-dose hydroxyurea for decreasing the incidence of all cause-hospitalization (pain, acute chest syndrome, infection, other) compared to low fixed-dose hydroxyurea. We will test the primary hypothesis that there will be a 66% relative risk reduction of strokes in children with SCA and abnormal TCD measurements, randomly allocated, for a minimum of three years to receive moderate fixed-dose versus low fixed-dose hydroxyurea (total n = 220). The results of this trial will advance the care of children with SCA in sub-Saharan Africa, while improving research capacity for future studies to prevent strokes in children with SCA.

Asymptomatic SARS-CoV-2 Infection in Household Contacts of a Healthcare Provider, Wuhan, China.

We found that all 5 asymptomatic household contacts of a Wuhan, China, physician with coronavirus disease had severe acute respiratory syndrome coronavirus 2 detected by PCR. The index patient and 2 contacts also had abnormal chest computed tomography scans. Asymptomatic infected household contacts of healthcare workers with coronavirus disease might be underrecognized.

Bridging the childhood epilepsy treatment gap in northern Nigeria (BRIDGE): Rationale and design of pre-clinical trial studies.

Epilepsy is the most common serious childhood neurological disorder. In the low- and middle-income countries (LMICs) of Africa, children with epilepsy suffer increased morbidity and mortality compared to their counterparts in high-income countries, and the majority do not receive treatment - the childhood epilepsy treatment gap. Reports of the childhood epilepsy treatment gap in Africa are likely underestimates; most surveys do not include several common childhood seizure types, including most types of non-convulsive epilepsy. Efforts to scale up childhood epilepsy care services in the LMICs of Africa must contend with a shortage of physicians and diagnostic technology [e.g., electroencephalograms (EEGs)]. One pragmatic solution is to integrate epilepsy care into primary care by task-shifting to community health extension workers. The aims of this project (BRIDGE) are to: 1) train, develop, and pilot task-shifted epilepsy care teams; 2) develop and pilot innovative childhood epilepsy screening and diagnostic paradigms adapted to the local Hausa language/culture in Kano, northern Nigeria; and, 3) quantify and map the childhood epilepsy treatment gap, using geographic information systems (GIS), to target limited resources to areas of greatest need. Task-shifted teams will diagnose and manage childhood epilepsy using an innovative epilepsy screening tools and diagnostic and management paradigms in environments with limited EEG access. If validated and demonstrated efficacious in clinical trials, this project can be taken to scale across broader areas of west Africa's LMICs that share language and culture. BRIDGE has the potential to enhance access to basic childhood epilepsy care and establish the foundation for childhood epilepsy clinical trials in west Africa.

The International Childhood Cancer Cohort Consortium (I4C): A research platform of prospective cohorts for studying the aetiology of childhood cancers.

BACKGROUND: Childhood cancer is a rare but leading cause of morbidity and mortality. Established risk factors, accounting for <10% of incidence, have been identified primarily from case-control studies. However, recall, selection and other potential biases impact interpretations particularly, for modest associations. A consortium of pregnancy and birth cohorts (I4C) was established to utilise prospective, pre-diagnostic exposure assessments and biological samples. METHODS: Eligibility criteria, follow-up methods and identification of paediatric cancer cases are described for cohorts currently participating or planning future participation. Also described are exposure assessments, harmonisation methods, biological samples potentially available for I4C research, the role of the I4C data and biospecimen coordinating centres and statistical approaches used in the pooled analyses. RESULTS: Currently, six cohorts recruited over six decades (1950s-2000s) contribute data on 388 120 mother-child pairs. Nine new cohorts from seven countries are anticipated to contribute data on 627 500 additional projected mother-child pairs within 5 years. Harmonised data currently includes over 20 "core" variables, with notable variability in mother/child characteristics within and across cohorts, reflecting in part, secular changes in pregnancy and birth characteristics over the decades. CONCLUSIONS: The I4C is the first cohort consortium to have published findings on paediatric cancer using harmonised variables across six pregnancy/birth cohorts. Projected increases in sample size, expanding sources of exposure data (eg, linkages to environmental and administrative databases), incorporation of biological measures to clarify exposures and underlying molecular mechanisms and forthcoming joint efforts to complement case-control studies offer the potential for breakthroughs in paediatric cancer aetiologic research.

Using daily excessive concentration hours to explore the short-term mortality effects of ambient PM2.5 in Hong Kong.

We developed a novel indicator, daily excessive concentration hours (DECH), to explore the acute mortality impacts of ambient fine particulate matter pollution (PM2.5) in Hong Kong. The DECH of PM2.5 was calculated as daily concentration-hours >25 µg/m3. We applied a generalized additive models to quantify the association between DECH and mortality with adjustment for potential confounders. The results showed that the DECH was significantly associated with mortality. The excess mortality risk for an interquartile range (565 µg/m3*hours) increase in DECH of PM2.5 was 1.65% (95% CI: 1.05%, 2.26%) for all natural mortality at lag 02 day, 2.01% (95% CI: 0.82%, 3.21%) for cardiovascular mortality at lag 03 days, and 1.41% (95% CI: 0.34%, 2.49%) for respiratory mortality at lag 2 day. The associations remained consistent after adjustment for gaseous air pollutants (daily mean concentration of SO2, NO2 and O3) and in alternative model specifications. When compared to the mortality burden of daily mean PM2.5, DECH was found to be a relatively conservative indicator. This study adds to the evidence by showing that daily excessive concentration hours of PM2.5 might be a new predictor of mortality in Hong Kong.

Symptoms of anxiety and depression during pregnancy and their association with low birth weight in Chinese women: a nested case control study.

This study is a nested case control study from a population-based cohort study conducted in Wuhan, China. The aim is to estimate the association between symptoms of depression during pregnancy (DDP), anxiety during pregnancy(ADP), and depression with anxiety during pregnancy (DADP) and low birth weight (LBW) and to examine the extent to which preterm birth (PTB) moderates these associations. Logistic regression analyses were used to model associations between DDP, ADP, and DADP and LBW. Models were stratified by the presence or absence of PTB to examine moderating effects. From the cohort study, 2853 had a LBW baby (cases); 5457 pregnant women served as controls. Women with DDP or ADP only were not at higher risk of having a LBW baby, but DADP was associated with increased risk of LBW (crude OR 1.41, 95% CI 1.17-1.70; adjusted OR 1.29, 95% CI 1.07-1.57), and the significant association was particularly evident between DADP and LBW in PTB, but not in full-term births. Our data suggests that DADP is related to an increased risk of LBW and that this association is most present in PTBs.

Prenatal and postnatal exposure to pet ownership, blood pressure, and hypertension in children: the Seven Northeastern Cities study.

OBJECTIVE: There is little information about how exposure to pets impacts blood pressure (BP) in children. The objective of the present study was to investigate the association between pet exposure and BP in children. METHODS: A total of 9354 children, aged 5-17 years, from 24 elementary schools and 24 middle schools in the Seven Northeastern Cities were evaluated during 2012-2013. BP measurements were taken using a mercury sphygmomanometer. Hypertension in children was defined as having an average DBP or SBP in the 95th percentile or higher for the child's sex, age, and height. RESULTS: Overall, 2127 of the 9354 participants (22.7%) had current exposures to pets, with 989 of all participants having dogs (10.6%). Pet exposure was negatively associated with hypertension and BP in men and women. Keeping dogs in the home was related to a significantly lower prevalence of hypertension in men [adjusted odds ratio (aOR) = 0.68; 95% confidence interval (CI): 0.49-0.94] and women (aOR = 0.66; 95% CI: 0.48-0.90). When the analysis was stratified by sex, in-utero exposure to pets was negatively associated with hypertension in men (aOR = 0.66; 95% CI: 0.45-0.97), and the associations with lower BP strengthened with higher levels of current pet exposure. As for BP, the associations between pet exposure and DBP were detected more in women; estimated decreases in mean DBP was 1.10 mmHg (95% CI: -1.75 to -0.45) for current pet exposure. CONCLUSION: Pet ownership reduces the odds of hypertension and elevated BP in children.

Editorial brain malformation surveillance in the Zika era.

The current surveillance systems for congenital microcephaly are necessary to monitor the impact of Zika virus (ZIKV) on the developing human brain, as well as the ZIKV prevention efforts. However, these congenital microcephaly surveillance systems are insufficient. Abnormalities of neuronal differentiation, development and migration may occur among infants with normal head circumference who have intrauterine exposure to ZIKV. Therefore, surveillance for congenital microcephaly does not ascertain many of the infants seriously impacted by congenital ZIKV infection. Furthermore, many infants with normal head circumference and with malformations of the brain cortex do not have clinical manifestations of their congenital malformations until several months to many years after birth, when they present with clinical manifestations such as seizures/epilepsy, developmental delays with or without developmental regression, and/or motor impairment. In response to the ZIKV threat, public health surveillance systems must be enhanced to ascertain a wide variety of congenital brain malformations, as well as their clinical manifestations that lead to diagnostic brain imaging. Birth Defects Research (Part A) 106:869-874, 2016. © 2016 The Authors Birth Defects Research Part A: Clinical and Molecular Teratology Published by Wiley Periodicals, Inc.

Long-term exposure to urban air pollution and lung cancer mortality: A 12-year cohort study in Northern China.

Cohort evidence that links long-term exposures to air pollution and mortality comes largely from the United States and European countries. We investigated the relationship between long-term exposures to particulate matter <10µm in diameter (PM10), nitrogen dioxide (NO2), and sulfur dioxide (SO2) and mortality of lung cancer in Northern China. A cohort of 39,054 participants were followed during 1998-2009. Annual average concentrations for PM10, NO2, and SO2 were determined based on data collected from central monitoring stations. Lung cancer deaths (n=140) were obtained from death certificates, and hazard ratios (HRs) were estimated using Cox proportional hazards models, adjusting for age, gender, BMI, education, marital status, smoking status, passive smoking, occupation, alcohol consumption, etc. Each 10mg/m(3) increase in PM10 concentrations was associated with a 3.4%-6.0% increase in lung cancer mortality in the time-varying exposure model and a 4.0%-13.6% increase in the baseline exposure model. In multi-pollutant models, the magnitude of associations was attenuated, most strongly for PM10. The association was different in men and women, also varying across age categories and different smoking status. Substantial differences exist in the risk estimates for participants based on assignment method for air pollution exposure.

Racial disparity in the association between body mass index and self-reported asthma in children: a population-based study.

OBJECTIVE: To examine the racial disparity in the association between obesity and asthma in US children and adolescents. METHODS: This study was based on a nationally representative, random-digit-dial sample of US households with children less than 18 years of age from the National Survey of Children's Health in 2011/2012 and 2007. The study sample included 88,668 children ages 10-17 with data on body mass index (BMI), parental reporting of asthma diagnosis, and potential confounders. Multiple logistic regression analysis was performed to estimate the crude and adjusted odds ratios stratified by child race/ethnicity. RESULTS: The prevalence of overweight was 15.2% and obesity was 14.1%. Self-reported asthma diagnosis was 16.7% in our study sample. Obese children were 51% more likely to have asthma compared to normal weight children after controlling for child's sex, child age, socioeconomic status, environmental tobacco smoke (ETS), and neighborhood conditions. Our study also shows that the strength of this association varied by race/ethnicity after stratification. Being male, being non-Hispanic Black or Multi-racial, below the Federal Poverty Level, ETS and having detracting neighborhood elements were also significantly associated with higher odds of having a self-reported asthma diagnosis. CONCLUSION: We observed a racial difference in the association between BMI and asthma in US children. Our findings have significant public health implications and may help public health practitioners to target children and adolescents at higher risk of prevention and intervention efforts.

Ambient air pollution and preterm birth: A prospective birth cohort study in Wuhan, China.

IMPORTANCE: Although studies in western countries suggest that ambient air pollution is positively associated with adverse pregnancy outcomes, the upper levels of pollutant exposures have been relatively low, thus eroding confidence in the conclusions. Meanwhile, in Asia, where upper levels of exposure have been greater, there have been limited studies of the association between air pollution and adverse pregnancy outcomes. OBJECTIVE: The primary objective was to evaluate whether high levels of pollution, including particulate matter pollution with a mass median aerodynamic diameter of less than 2.5 µm (PM2.5) and 10 µm (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), ozone (O3), and carbon monoxide (CO) are related to increased occurrence of preterm birth (PTB). METHODS: We conducted a population-based study in Wuhan, China in a cohort of 95,911 live births during a two-year period from 2011 to 2013. The exposure was estimated based on daily mean concentrations of pollutants estimated using the pollutants' measurements from the nine closest monitors. Logistic regressions were performed to determine the relationships between exposure to each of the pollutants during different pregnancy periods and PTB while controlling for key covariates. RESULTS: We found 3% (OR=1.03; 95% CI: 1.02, 1.05), 2% (OR=1.02; 95% CI: 1.02, 1.03), 15% (OR=1.15; 95% CI: 1.11, 1.19), and 5% (OR=1.05; 95% CI: 1.02, 1.07) increases in risk of PTB with each 5-µg/m(3) increase in PM2.5 and PM10 concentrations, 100-µg/m(3) increase in CO concentrations, and 10-µg/m(3) increase in O3 concentrations, respectively. There was negligible evidence for associations for SO2 and NO2. The effects from two-pollutant models were similar to the estimated effects from single pollutant models. No critical exposure windows were identified consistently: the strongest effect for PTB was found in the second trimester for PM2.5, PM10, and CO, but for SO2 it was in the first trimester, second month, and third month. For NO2 it was in the first trimester and second month, and for O3, the third trimester. CONCLUSION: Findings reveal an association between air pollutants and PTB. However, more toxicological studies and prospective cohort studies with improved exposure assessments are needed to establish causality related to specific pollutants.

Ambient Air Pollution and Adverse Pregnancy Outcomes in Wuhan, China.

Background: Several recent studies have suggested that maternal exposures to air pollution and temperature extremes might contribute to low birth weight (LBW), preterm birth (PTB), and other outcomes that can adversely affect infant health. At the time the current study began, most other studies had been conducted in the United States or Europe. Dr. Zhengmin Qian proposed to extend work he had done on ambient particulate air pollution and daily mortality in Wuhan, China (Qian et al. 2010), as part of the HEIsponsored Public Health and Air Pollution in Asia program, to study adverse birth outcomes. Wuhan is the capital city of Hubei province, has a large population of about 6.4 million within the urban study area, experiences temperature extremes, and generally has higher air pollution levels than those observed in the United States and Europe, thus providing a good opportunity to explore questions about air pollution and health. Approach: Qian and colleagues planned a cohort and nested case­control design with four specific aims, examining whether increased exposures to air pollutants (PM2.5, PM10, SO2, NO2, O3, and CO) during vulnerable pregnancy periods were associated with increased rates of PTB, LBW (<2500 g), or intrauterine growth retardation (IUGR, defined as having a birth weight below the 10th percentile of singleton live births in Wuhan) after adjusting for major risk factors and whether the associations were confounded by copollutant exposures, affected by residual confounding, or modified by temperature extremes, socioeconomic status (SES), or secondhand smoke (SHS) exposure. The cohort study included 95,911 births that occurred from June 10, 2011, to June 9, 2013, and met typical prespecified inclusion criteria used in other birth outcome studies. The case­control study included 3146 cases (PTB, LBW, or both, but not IUGR) and 4263 controls (matched to the cases by birth month) for whom investigators were able to complete home visits and questionnaires. The investigators obtained air pollution and daily weather data for August 2010 to June 2013 from nine monitoring stations representing background air pollution sites in seven Wuhan inner-city districts. Only two of these stations provided PM2.5 data. For the cohort study, the investigators assigned exposures to mothers according to the daily mean concentrations from the monitor nearest the residential community in which the mother lived at the time of the birth. For the case­control study, they assigned exposures based on the inverse distance weighted average of daily mean concentrations from the three nearest monitors, for all but PM2.5 for which the method was not specified. They also collected data on various factors that might confound or modify the impact of the pollutants on the adverse outcomes, including data collected in the cohort from mothers at the time of delivery and, in the case­control study, from questionnaires administered to mothers. In the case­control study, covariates representing SES (as indicated by the mother's educational attainment and household income) and SHS exposures were of particular interest. The primary statistical analyses of the pollutant associations with PTB, LBW, and IUGR were conducted using logistic regression models. In the cohort study, exposures during the pregnancy period of interest (full term, trimesters, and selected months) were included as continuous variables. In the case­control study, the exposures were modeled as binary variables (i.e., above or below the median pollutant concentrations). Numerous sensitivity analyses were conducted. Results and interpretation: Although originally planning a nested case­control study, the investigators encountered challenges that led them to analyze the cohort and case­control studies using different ways of assigning exposures and characterizing them in their statistical models. These decisions precluded direct comparisons between the sets of results, making it difficult to answer the questions about residual confounding that nested case­control studies are designed to answer. The odds ratios from the two study designs using different exposures also have different interpretations. Still, one can ask whether the sets of findings were qualitatively consistent with each other or with those of similar studies. There were some similarities. Both studies suggested that increased PM(2.5), PM(10), CO, and O(3) exposures over the full pregnancy were associated with small increases in the odds of PTB (the case­control study also showed an association with NO2) and that increased PM(2.5) exposures were associated with significantly increased odds of LBW. However, most of the other pollutants had no effect on LBW, except CO in the cohort study and O(3) in the case­control study, both of which increased the odds of LBW. The exposures over the entire pregnancy were generally associated with decreased odds of IUGR. Adjustments for potential confounders were greatest for the delivery covariates. The investigators found no systematic association of any of these outcomes with particular trimesters or months, another result that differed from those of some other studies. They found little evidence that their main results were confounded or modified by the presence of copollutants, although with the exception of O3, most of the pollutants were highly correlated, making it difficult to disentangle the effects of individual pollutants. Could the two sets of data be analyzed in a more comparable way, as in a standard nested case­control study? At the Committee's request, the investigators reanalyzed the case­control data using the same exposures and models as in the cohort study. The results were strikingly different from those using the inverse distance weighted exposures, modeled as binary variables ­ the pollutants had either no effect or an apparent beneficial effect on PTB and LBW. The Committee was not convinced by the explanations offered for these differences, leaving the reasons for them unresolved. Conclusions: This study set out to answer important questions about the effects of air pollution exposure on three measures of adverse birth outcomes ­ LBW, PTB, and IUGR ­ in a large cohort of mothers and newborns in Wuhan, China. Given the cohort size, high pollution levels and temperatures, and detailed covariate data, the investigators were well poised to address these questions. They sought to pattern their work on other studies of birth outcomes, were very responsive to Committee questions, and provided many additional analyses and explanations. In the Committee's view, however, the study was unable to address with confidence several of its specific aims. Most important, the differences in results when the case­control data were analyzed with different exposure metrics remain unexplained, raising concerns about the ability to draw conclusions from subsequent analyses assessing residual confounding and effect modification by temperature extremes, SES, and SHS exposure. Consequently, any individual findings from the cohort and case­control studies should be considered suggestive rather than conclusive, and should be interpreted carefully together.

Poor sleep quality associated with high risk of hypertension and elevated blood pressure in China: results from a large population-based study.

Little information is available concerning the association between sleep quality and blood pressure (BP) in Chinese individuals. This study evaluated the association between sleep quality, as determined by the Pittsburgh sleep quality index (PSQI), and hypertension in a rural Chinese population. Using a multistage cluster and random sampling method, a representative sample of 9404 adults aged 20-93 years in northeastern China was selected from 2012 to 2013. Sleep quality was assessed by PSQI, and trained observers measured BP. A sleep disorder (SD) was diagnosed for any participant with a score of 6 or greater. Overall, 1218 male participants (25.53%) and 1261 female participants (27.22%) were defined as having SDs. Compared with the normal subjects, participants with hypertension had higher global PSQI scores and subscores in all elements. The odds ratios (ORs) of hypertension, systolic hypertension and diastolic hypertension among participants with SDs were 2.38 (95% confidence interval (CI): 2.13-2.65), 2.52 (95% CI: 2.26-2.80) and 1.93 (95% CI: 1.74-2.14) in contrast to the reference group, respectively. The risk for hypertension in poor sleepers with subscores over 0 in all of the elements was significantly increased, with ORs ranging from 1.16 (95% CI: 1.04-2.30) to 3.88 (95% CI: 1.24-12.16). The global PSQI score and its components were associated with hypertension and high BP.

Parental Body Mass Index, Gestational Weight Gain, and Risk of Macrosomia: a Population-Based Case-Control Study in China.

BACKGROUND: The prevalence of macrosomia has risen markedly worldwide, including in China, during the past two decades. Few epidemiological studies, however, have investigated the risk factors for macrosomia in China. This study was designed to investigate the associations between parental anthropometric characteristics, gestational weight gain (GWG), and risk of macrosomia in China. METHODS: This population-based, case-control study in Wuhan, China, included a total of 6341 subjects (870 cases and 5471 controls). Multivariable logistic regression was conducted to calculate odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Mothers or fathers who were overweight or obese before pregnancy had an elevated risk of giving birth to a macrosomic infant compared with their normal weight counterparts. Women with GWG above the Institute of Medicine (IOM) recommendation had an adjusted OR of 6.09 [95% CI 5.04, 7.35] for delivering a macrosomic infant compared with women who had GWG within the IOM recommendation. When stratified by maternal pre-pregnancy body mass index (BMI), women who were underweight or normal weight before pregnancy were observed to have a higher risk of macrosomia birth associated with greater GWG. CONCLUSIONS: Parental pre-pregnancy overweight/obesity and excessive GWG during pregnancy were highly associated with macrosomia. The association with GWG was most pronounced in mothers who had a normal or underweight pre-pregnancy BMI. Weight control efforts before pregnancy for mothers and fathers as well as control of maternal gain during pregnancy may reduce the risk of macrosomia.