Preeclampsia Onset, Days to Delivery, and Autism Spectrum Disorders in Offspring: Clinical Birth Cohort Study.

BACKGROUND: Maternal preeclampsia is associated with a risk of autism spectrum disorders (ASD) in offspring. However, it is unknown whether the increased ASD risk associated with preeclampsia is due to preeclampsia onset or clinical management of preeclampsia after onset, as clinical expectant management of preeclampsia allows pregnant women with this complication to remain pregnant for potentially weeks depending on the onset and severity. Identifying the risk associated with preeclampsia onset and exposure provides evidence to support the care of high-risk pregnancies and reduce adverse effects on offspring. OBJECTIVE: This study aimed to fill the knowledge gap by assessing the ASD risk in children associated with the gestational age of preeclampsia onset and the number of days from preeclampsia onset to delivery. METHODS: This retrospective population-based clinical cohort study included 364,588 mother-child pairs of singleton births between 2001 and 2014 in a large integrated health care system in Southern California. Maternal social demographic and pregnancy health data, as well as ASD diagnosis in children by the age of 5 years, were extracted from electronic medical records. Cox regression models were used to assess hazard ratios (HRs) of ASD risk in children associated with gestational age of the first occurrence of preeclampsia and the number of days from first occurrence to delivery. RESULTS: Preeclampsia occurred in 16,205 (4.4%) out of 364,588 pregnancies; among the 16,205 pregnancies, 2727 (16.8%) first occurred at <34 weeks gestation, 4466 (27.6%) first occurred between 34 and 37 weeks, and 9012 (55.6%) first occurred at ≥37 weeks. Median days from preeclampsia onset to delivery were 4 (IQR 2,16) days, 1 (IQR 1,3) day, and 1 (IQR 0,1) day for those first occurring at <34, 34-37, and ≥37 weeks, respectively. Early preeclampsia onset was associated with greater ASD risk (P=.003); HRs were 1.62 (95% CI 1.33-1.98), 1.43 (95% CI 1.20-1.69), and 1.23 (95% CI 1.08-1.41), respectively, for onset at <34, 34-37, and ≥37 weeks, relative to the unexposed group. Within the preeclampsia group, the number of days from preeclampsia onset to delivery was not associated with ASD risk in children; the HR was 0.995 (95% CI 0.986-1.004) after adjusting for gestational age of preeclampsia onset. CONCLUSIONS: Preeclampsia during pregnancy was associated with ASD risk in children, and the risk was greater with earlier onset. However, the number of days from first preeclampsia onset to delivery was not associated with ASD risk in children. Our study suggests that ASD risk in children associated with preeclampsia is not increased by expectant management of preeclampsia in standard clinical practice. Our results emphasize the need to identify effective approaches to preventing the onset of preeclampsia, especially during early pregnancy. Further research is needed to confirm if this finding applies across different populations and clinical settings.

Neighborhood Disadvantage and Autism Spectrum Disorder in a Population With Health Insurance.

Importance: Family socioeconomic status has been associated with autism spectrum disorder (ASD) diagnoses. Less is known regarding the role of neighborhood disadvantage in the United States, particularly when children have similar access to health insurance. Objective: To evaluate the association between neighborhood disadvantage and the diagnosis of ASD and potential effect modification by maternal and child demographic characteristics. Design, Setting, and Participants: This cohort study examined a retrospective birth cohort from Kaiser Permanente Southern California (KPSC), an integrated health care system. Children born in 2001 to 2014 at KPSC were followed up through KPSC membership records. Electronic medical records were used to obtain an ASD diagnosis up to December 31, 2019, or the last follow-up. Data were analyzed from February 2022 to September 2023. Exposure: Socioeconomic disadvantage at the neighborhood level, an index derived from 7 US census tract characteristics using principal component analysis. Main Outcomes and Measures: Clinical ASD diagnosis based on electronic medical records. Associations between neighborhood disadvantage and ASD diagnosis were determined by hazard ratios (HRs) from Cox regression models adjusted for birth year, child sex, maternal age at delivery, parity, severe prepregnancy health conditions, maternal race and ethnicity, and maternal education. Effect modification by maternal race and ethnicity, maternal education, and child sex was assessed. Results: Among 318 372 mothers with singleton deliveries during the study period, 6357 children had ASD diagnoses during follow-up; their median age at diagnosis was 3.53 years (IQR, 2.57-5.34 years). Neighborhood disadvantage was associated with a higher likelihood of ASD diagnosis (HR, 1.07; 95% CI, 1.02-1.11, per IQR = 2.70 increase). Children of mothers from minoritized racial and ethnic groups (African American or Black, Asian or Pacific Islander, Hispanic or Latinx groups) had increased likelihood of ASD diagnosis compared with children of White mothers. There was an interaction between maternal race and ethnicity and neighborhood disadvantage (difference in log-likelihood = 21.88; P < .001 for interaction under χ24); neighborhood disadvantage was only associated with ASD among children of White mothers (HR, 1.17; 95% CI, 1.09-1.26, per IQR = 2.00 increase). Maternal education and child sex did not significantly modify the neighborhood-ASD association. Conclusions and Relevance: In this study, children residing in more disadvantaged neighborhoods at birth had higher likelihood of ASD diagnosis among a population with health insurance. Future research is warranted to investigate the mechanisms behind the neighborhood-related disparities in ASD diagnosis, alongside efforts to provide resources for early intervention and family support in communities with a higher likelihood of ASD.

Maternal obesity, diabetes, preeclampsia, and asthma during pregnancy and likelihood of autism spectrum disorder with gastrointestinal disturbances in offspring.

LAY ABSTRACT: Autism spectrum disorder is heterogeneous and often accompanied by co-occurring conditions. Previous studies have shown that maternal health conditions during pregnancy including obesity, diabetes, preeclampsia, and asthma were associated with increased likelihood of autism. However, little has been done examining the likelihood associated with autism with co-occurring conditions. This study assessed these maternal health conditions in relationship to autism and gastrointestinal disturbances, a common co-occurring condition in children diagnosed with autism. Data included 308,536 mother-child pairs from one integrated health care system with comprehensive electronic medical records. Among the study cohort, 5,131 (1.7%) children had a diagnosis of autism by age 5. Gastrointestinal disturbances were present in 35.4% of children diagnosed with autism and 25.1% of children without autism diagnoses. Our results showed that each of the four maternal health conditions during pregnancy was associated with increased likelihood of gastrointestinal disturbances, autism without gastrointestinal disturbances, and autism with gastrointestinal disturbances. For all four maternal health conditions, the association was greatest for likelihood of autism with gastrointestinal disturbances. Given that children diagnosed with autism are more likely to have gastrointestinal disturbances and over 80% of gastrointestinal disturbances in this cohort were diagnosed prior to autism diagnosis, this study suggests that there may be common biological pathways between autism and gastrointestinal disturbances impacted by these maternal exposures. Future studies are warranted to assess associations between different exposures and autism with other co-occurring conditions to increase our understanding of autism heterogeneity.

Ambient air pollution and COVID-19 incidence during four 2020-2021 case surges.

BACKGROUND: Air pollution exposure may make people more vulnerable to COVID-19 infection. However, previous studies in this area mostly focused on infection before May 2020 and long-term exposure. OBJECTIVE: To assess both long-term and short-term exposure to air pollution and COVID-19 incidence across four case surges from 03/1/2020 to 02/28/2021. METHODS: The cohort included 4.6 million members from a large integrated health care system in southern California with comprehensive electronic medical records (EMR). COVID-19 cases were identified from EMR. Incidence of COVID-19 was computed at the census tract-level among members. Prior 1-month and 1-year averaged air pollutant levels (PM2.5, NO2, and O3) at the census tract-level were estimated based on hourly and daily air quality data. Data analyses were conducted by each wave: 3/1/2020-5/31/2020, 6/1/202-9/30/2020, 10/1/2020-12/31/2020, and 1/1/2021-2/28/2021 and pooled across waves using meta-analysis. Generalized linear mixed effects models with Poisson distribution and spatial autocorrelation were used with adjustment for meteorological factors and census tract-level social and health characteristics. Results were expressed as relative risk (RR) per 1 standard deviation. RESULTS: The cohort included 446,440 COVID-19 cases covering 4609 census tracts. The pooled RRs (95% CI) of COVID-19 incidence associated with 1-year exposures to PM2.5, NO2, and O3 were 1.11 (1.04, 1.18) per 2.3 µg/m3,1.09 (1.02, 1.17) per 3.2 ppb, and 1.06 (1.00, 1.12) per 5.5 ppb respectively. The corresponding RRs (95% CI) associated with prior 1-month exposures were 1.11 (1.03, 1.20) per 5.2 µg/m3 for PM2.5, 1.09 (1.01, 1.17) per 6.0 ppb for NO2 and 0.96 (0.85, 1.08) per 12.0 ppb for O3. CONCLUSION: Long-term PM2.5 and NO2 exposures were associated with increased risk of COVID-19 incidence across all case surges before February 2021. Short-term PM2.5 and NO2 exposures were also associated. Our findings suggest that air pollution may play a role in increasing the risk of COVID-19 infection.

Asthma Disease Status, COPD, and COVID-19 Severity in a Large Multiethnic Population.

BACKGROUND: Current studies of asthma history on coronavirus disease 2019 (COVID-19) outcomes are limited and lack consideration of disease status. OBJECTIVE: To conduct a population-based study to assess asthma disease status and chronic obstructive pulmonary disease (COPD) in relation to COVID-19 severity. METHODS: Patients diagnosed with COVID-19 (n = 61,338) in a large, diverse integrated health care system were identified. Asthma/COPD history, medication use, and covariates were extracted from electronic medical records. Asthma patients were categorized into those with and without clinical visits for asthma 12 or fewer months prior to COVID-19 diagnosis and labeled as active and inactive asthma, respectively. Primary outcomes included COVID-19-related hospitalizations, intensive respiratory support (IRS), and intensive care unit admissions within 30 days, and mortality within 60 days after COVID-19 diagnosis. Logistic and Cox regression were used to relate COVID-19 outcomes to asthma/COPD history. RESULTS: The cohort was 53.9% female and 66% Hispanic and had a mean age of 43.9 years. Patients with active asthma had increased odds of hospitalization, IRS, and intensive care unit admission (odds ratio 1.47-1.66; P < .05) compared with patients without asthma or COPD. No increased risks were observed for patients with inactive asthma. Chronic obstructive pulmonary disease was associated with increased risks of hospitalization, IRS, and mortality (odds ratio and hazard ratio 1.27-1.67; P < .05). Among active asthma patients, those using asthma medications had greater than 25% lower odds for COVID-19 outcomes than those without medication. CONCLUSIONS: Patients with asthma who required clinical care 12 or fewer months prior to COVID-19 or individuals with COPD history are at increased risk for severe COVID-19 outcomes. Proper medication treatment for asthma may lower this risk.

Types of diabetes during pregnancy and longitudinal BMI in offspring from birth to age 10 years.

OBJECTIVE: To examine longitudinal BMI trajectory from birth to age 10 years in a clinical cohort after exposure to maternal pre-existing type 1 (T1D), type 2 (T2D), gestational diabetes managed with or without anti-diabetes medication, and no diabetes during pregnancy. METHODS: Data included 218 227 singleton children born in 2008-2015 from a population-based integrated healthcare system; 537 exposed to maternal T1D, 7836 to T2D, 6982 to medicated GDM and 12 576 to unmedicated GDM. Differences in BMI over time among groups were assessed by non-linear mixed-effects models adjusting for covariates. RESULTS: Children's BMI was significantly lower 6-months after birth for all diabetes exposed groups compared to no diabetes. Beginning at approximately age 2.5 years, BMI was significantly higher for T1D, T2D and medicated GDM groups compared to the no diabetes group. At age 3, the growth pattern started separating with highest BMI in T1D and T2D groups, followed by medicated GDM, unmedicated GDM, and the no diabetes groups. By age 7, BMI was significantly higher for the unmedicated GDM group compared to the no diabetes group. Adjusted BMI was generally comparable between T1D and T2D groups for all ages. Starting at age 5, T1D, T2D and medicated GDM groups had BMI greater than one SD over the BMI in the no diabetes group. CONCLUSION: In a clinical cohort with standard diabetes management approaches, a hierarchical BMI growth pattern exists in offspring exposed to different types of diabetes during pregnancy after adjusting for important covariates, starting as early as age 3 years.

Maternal Gestational Diabetes and Type 2 Diabetes During Pregnancy and Risk of Childhood Asthma in Offspring.

OBJECTIVE: To examine maternal preexisting type 2 diabetes (T2D) and gestational diabetes mellitus (GDM) on risk of childhood asthma. STUDY DESIGN: This retrospective birth cohort study included 97 554 singletons born in 2007-2011 within hospitals from a single integrated healthcare system. Children were prospectively followed from age 5 until December 31, 2017, using electronic medical records. Relative risks of childhood asthma associated with maternal diabetes in utero were estimated by hazard ratios using Cox regression adjusting for potential confounders. RESULTS: There were 3119 children (3.2%) who were exposed to preexisting T2D and 9836 (10.1%) to GDM. Among mothers with GDM, 3380 (34.4%) were dispensed antidiabetic medication during pregnancy. During a median of 7.6 years (IQR, 6.3-9.0 years) after birth, 15 125 children (15.5%) were diagnosed with asthma after age 5. Maternal diabetes interacted with maternal asthma history to affect child's asthma risk (P = .05). Among children without maternal asthma (n = 89 487), the adjusted hazard ratios for childhood asthma were 1.21 (95% CI, 1.08-1.36; P < .001) for exposure to T2D, 1.12 (95% CI, 1.01-1.25; P = .04) for GDM requiring antidiabetic medications, and 1.01 (95% CI, 0.93-1.10; P = .82) for GDM not requiring medications compared with no diabetes during pregnancy. The corresponding hazard ratios were 1.53 (95% CI, 1.19-1.96; P < .001), 1.11 (95% CI, 0.65-1.46; P = .44), and 0.84 (95% CI, 0.66-1.08; P = .17) among children without maternal asthma (n = 8067). Gestational age at GDM diagnosis was not associated with childhood asthma (P = .27). CONCLUSIONS: The risk of childhood asthma was predominately observed for exposure to preexisting T2D, small for GDM requiring medication, and not increased for GDM not requiring medication during pregnancy, compared with no diabetes during pregnancy.

Attention-Deficit Hyperactivity Disorder Risk: Interaction Between Parental Age and Maternal History of Attention-Deficit Hyperactivity Disorder.

OBJECTIVE: To assess the interaction between maternal attention-deficit/hyperactivity disorder (ADHD) history and young parental age on child's ADHD risk. METHODS: The study included 321,272 singleton children born between 1995 and 2012 from hospitals within a single integrated health care organization. The children were prospectively followed up through electronic medical record systems from birth until the first date of the following: date of clinical diagnosis of ADHD, last date of continuous health plan membership, death due to any cause, or December 31, 2017. Risks of ADHD associated with a maternal history of ADHD before pregnancy and young parental age were assessed by using Cox regression adjusting for potential confounders. RESULTS: The children were followed up for a median (interquartile range) of 8.9 (6.2, 13.6) years from birth. Among them, 5.1% had ADHD diagnosis, 1.8% had a maternal history of ADHD before the pregnancy, and 4.4% had mothers <20 years and 2.3% had fathers <20 years at date of birth. The hazard ratio (HR) of ADHD in children associated with parental age <20 years varied by maternal history of ADHD (p < 0.005 for both multiplicative and additive interactions). For children without a maternal history of ADHD, the HR associated with at least 1 parent <20 years was 1.14 (95% confidence interval 1.04-1.24). However, for children with a maternal history of ADHD, the HR associated with at least 1 parent <20 years was 1.92 (95% confidence interval 1.31-2.82). CONCLUSION: High ADHD risk in offspring associated with young parenthood was predominantly observed among children with a maternal history of ADHD.

Breastfeeding Persistence at 6 Months: Trends and Disparities from 2008 to 2015.

OBJECTIVE: To assess trends and disparities in breastfeeding by maternal characteristics (race and ethnicity, age at delivery, obesity, parity, and level of education) and the relative importance among these for breastfeeding at 6 months. STUDY DESIGN: This retrospective birth cohort study included 195 861 live singleton children born at 32-42 weeks of gestation from 2008 to 2015 within a single integrated healthcare system. All children had healthcare coverage during the first year of life. Maternal characteristics and breastfeeding status at 6 months of age were extracted from electronic medical records. Trends over time of any breastfeeding ≥6 months were evaluated for the 5 maternal characteristics. Robust Poisson regression models were used to estimate breastfeeding rate differences associated with each of the 5 characteristics. The relative importance among them associated with breastfeeding ≥6 months was assessed by comparing model quasi-likelihood information criteria. RESULTS: Rates of breastfeeding ≥6 months significantly increased overall and among groups defined by the maternal characteristics. However, there was little improvement over time in closing disparities associated with maternal race and ethnicity, age at delivery, prepregnancy obesity status, and level of education. Education level contributed to the greatest disparity in breastfeeding ≥6 months. Maternal age was the second factor, followed by prepregnancy obesity and maternal race and ethnicity. CONCLUSIONS: Breastfeeding outreach programs focusing on women with less than a college education, women <25 years old, and women from non-Hispanic black or Hispanic race and ethnicity may help to reduce disparities and improve breastfeeding persistence rates within integrated healthcare systems.

Recruitment results among families contacted for an obesity prevention intervention: the Obesity Prevention Tailored for Health Study.

BACKGROUND: Overweight and obesity are serious threats to health and increase healthcare utilization and costs. The Obesity Prevention Tailored for Health (OPT) study was designed to test the effectiveness of a family-based intervention targeting diet and physical activity. We describe the results of efforts to recruit parents and children enrolled in a large managed-care organization into the OPT study. METHODS: Parents with 10- to 12-year-old children were randomly selected from the membership of Kaiser Permanente Southern California, a large integrated health plan, and contacted between June 2010 and November 2011. We describe recruitment outcomes and compare characteristics of parents and children who did and did not participate. Information was collected from calls with parents and through the administrative and electronic medical records of the health plan. RESULTS: Of the 4,730 parents contacted, 16.1% expressed interest in participation (acceptors), 28.8% declined participation (refusers), 4.7% were ineligible, and, even after multiple attempts, we were unable to reach 50.4%. Slightly less than half of the acceptors (n = 361) were ultimately randomized to receive either the OPT program plus usual care or usual care alone (7.6% of all parents initially contacted). There were not any significant differences between acceptors who were or were not randomized. Overall, we found that acceptors were more likely to be female parents, have overweight/obese children, and higher utilization of outpatient visits by parents and children compared with refusers and those we were unable to reach. We found no differences in recruitment outcomes by body mass index or comorbidity score of the parents, level of physical activity of the parents and children, education of the parents, or household income. CONCLUSIONS: Recruiting parents and children into an obesity prevention program in a healthcare setting proved to be challenging and resource-intensive. Barriers and incentives for participation in obesity prevention programs need to be identified and addressed. Concern for the weight of their children may motivate parents to participate in family-based lifestyle interventions; however, the healthcare setting may be more relevant to weight-related treatment than to primary prevention. TRIAL REGISTRATION NUMBER: ISRCTN06248443, 30 January 2014.

OBAYA (obesity and adverse health outcomes in young adults): feasibility of a population-based multiethnic cohort study using electronic medical records.

BACKGROUND: Although obesity is a risk factor for many chronic diseases, we have only limited knowledge of the magnitude of these associations in young adults. A multiethnic cohort of young adults was established to close current knowledge gaps; cohort demographics, cohort retention, and the potential influence of migration bias were investigated. METHODS: For this population-based cross-sectional study, demographics, and measured weight and height were extracted from electronic medical records of 1,929,470 patients aged 20 to 39 years enrolled in two integrated health plans in California from 2007 to 2009. RESULTS: The cohort included about 84.4% of Kaiser Permanente California members in this age group who had a medical encounter during the study period and represented about 18.2% of the underlying population in the same age group in California. The age distribution of the cohort was relatively comparable to the underlying population in California Census 2010 population, but the proportion of women and ethnic/racial minorities was slightly higher. The three-year retention rate was 68.4%. CONCLUSION: These data suggest the feasibility of our study for medium-term follow-up based on sufficient membership retention rates. While nationwide 6% of young adults are extremely obese, we know little to adequately quantify the health burden attributable to obesity, especially extreme obesity, in this age group. This cohort of young adults provides a unique opportunity to investigate associations of obesity-related factors and risk of cancer in a large multiethnic population.

The prevalence of obesity and obesity-related health conditions in a large, multiethnic cohort of young adults in California.

PURPOSE: To identify population groups that are most susceptible to obesity-related health conditions at young age. METHODS: For this population-based cross-sectional study, measured weight and height, diagnosis, laboratory, and drug prescription information were extracted from electronic medical records of 1,819,205 patients aged 20 to 39 years enrolled in two integrated health plans in California in 2007 through 2009. RESULTS: Overall, 29.9% of young adults were obese. Extreme obesity (body mass index [BMI] ≥ 40 kg/m(2)) was observed in 6.1% of women and 4.5% of men. The adjusted relative risk (RR) for diabetes, hypertension, dyslipidemia, and the metabolic syndrome increased sharply for those individuals with a BMI of 40 or greater, with the sharpest increase in the adjusted RR for hypertension and the metabolic syndrome. The association between weight class and dyslipidemia, hypertension, and the metabolic syndrome but not diabetes was stronger among 20.0- to 29.9-year-olds compared with 30.0- to 39.9-year-olds (P for interaction < .05). For example, compared with their normal weight counterparts of the same age group, young adults with a BMI of 40.0 to 49.9, 50.0 to 59.9, and 60 or greater kg/m(2) had a RR for hypertension of 11.73, 19.88, and 30.47 (95% confidence interval [CI], 26.39-35.17) at 20 to 29 years old, and 9.31, 12.41, and 15.43 (95% CI, 14.32-16.63) at 30 to 39 years old. CONCLUSIONS: Although older individuals were more likely to be extremely obese, the association between obesity-related health conditions was stronger in younger individuals. Hispanics and Blacks are also more likely to be obese, including extremely obese, putting them at an elevated risk for premature cardiovascular disease and some cancers relative to non-Hispanic Whites.