Antimicrobial exposure during infancy in a longitudinal California cohort.

BACKGROUND: To describe temporal and sociodemographic patterns of antimicrobial exposure during the first year of life in a large US cohort. METHODS: Singleton infants born 1998-2014 enrolled in Kaiser Permanente Northern California integrated health system (n = 345,550) were followed longitudinally via comprehensive electronic health records, capturing all systemic antimicrobial inpatient administrations and outpatient dispensings. Antimicrobial exposure was summarized by maternal and infant characteristics, birth year, inpatient/outpatient status, age in months, and drug class. RESULTS: Overall, 44% of infants in this cohort received at least one dose of antimicrobials during infancy. Decreases over time were driven by reduced outpatient dispensings specifically in later infancy, primarily for penicillins. Among infants receiving any antimicrobials the median number of exposure-days was 16. Inpatient dispensings peaked in the first 30 days of life and outpatient dispensings peaked at 10-11 months. Birth characteristics (i.e., NICU admission, gestational age) were strong independent predictors of antimicrobial exposure between 0- < 3 months; sociodemographic factors were modest predictors of exposure for 3-12 months. CONCLUSION: Predictors of antimicrobial exposure in early and late infancy are distinct with early infancy exposures highly correlated to birth characteristics. The cumulative proportion of infants exposed has decreased due to fewer late infancy outpatient dispensings. IMPACT: Comprehensive antimicrobial exposure histories and the maternal and infant characteristics predicting exposure have not been well described in US populations. This analysis provides estimates of cumulative antimicrobial exposures by sociodemographic factors, delivery characteristics, month of life, inpatient/outpatient status, and antibiotic class among one of the largest US HMOs. Predictors of early infancy antimicrobial exposures differ from those in late infancy, with early exposures strongly correlated to birth characteristics and late infancy exposures modestly related to sociodemographic factors. Antimicrobial exposure among infants decreased over the time period primarily due to reduced outpatient dispensings in later infancy.

Maternal obesity and childhood asthma risk: Exploring mediating pathways.

BACKGROUND: Growing evidence for the effect of maternal obesity on childhood asthma motivates investigation of mediating pathways. OBJECTIVE: To investigate if childhood body mass index (BMI), gestational weight gain (GWG) and preterm birth mediate the association of maternal obesity on childhood asthma risk. METHODS: We used electronic medical records from mother-child pairs enrolled in Kaiser Permanente Northern California integrated healthcare system. Children were followed from their birth (2005-2014) until at least age 4 (n = 95,723), age 6 (n = 59,230) or age 8 (n = 25,261). Childhood asthma diagnosis at each age was determined using ICD-9/10 codes and medication dispensings. Prepregnancy BMI (underweight [<18.5], normal [18.5-24.9], overweight [25-29.9], obese [≥30] kg/m2 ) were defined using height and weight measurements close to the last menstrual period date. Child's BMI (Centers for Disease Control and Prevention BMI-for-age percentiles: underweight [<5th], normal [5th-85th], overweight [85th-95th], obese [>95th]) were obtained using anthropometric measurements taken the year preceding each follow-up age. GWG (delivery weight-prepregnancy weight) was categorised based on Institutes of Medicine recommendations (inadequate, adequate, excessive). Implementing first causal inference test (CIT) then causal mediator models (to decompose the natural direct and indirect effects), we examined the potential mediating effect of childhood BMI, GWG, and preterm birth on the association between prepregnancy BMI (continuous and categorical) and childhood asthma. RESULTS: Overall, risk of childhood asthma increased as prepregnancy BMI increased (age 4 risk ratio: 1.07, 95% confidence interval: 1.04, 1.09, per 5 kg/m2 increase in BMI; similar for age 6 and 8). CIT identified childhood BMI and preterm birth, but not GWG as potential mediators. Causal mediation models confirmed childhood BMI, but not preterm birth, as having a partial mediating effect. Results were similar for age 6 and 8, and when continuous mediators (instead of binary) were assessed. CONCLUSIONS: Childhood overweight/obesity has a modest mediating effect on the association between prepregnancy BMI and childhood asthma.

Prepregnancy body mass index and risk of childhood asthma.

BACKGROUND: Growing evidence suggests that maternal obesity may affect the intrauterine environment and increase a child's risk of developing asthma. We aim to investigate the relationship between prepregnancy obesity and childhood asthma risk. METHODS: Cohorts of children enrolled in Kaiser Permanente Northern California integrated healthcare system were followed from birth (2005-2014) to age 4 (n = 104,467), 6 (n = 63,084), or 8 (n = 31,006) using electronic medical records. Child's asthma was defined using ICD codes and asthma-related prescription medication dispensing. Risk ratios (RR) and 95% confidence intervals (95% CIs) for child's asthma were estimated using Poisson regression with robust error variance for (1) prepregnancy BMI categories (underweight [<18.5], normal [18.5-24.9], overweight [25-29.9], obese 1 [30-34.9], and obese 2/3 [≥35]) and (2) continuous prepregnancy BMI modeled using cubic splines with knots at BMI category boundaries. Models were adjusted for maternal age, education, race, asthma, allergies, smoking, gestational weight gain, child's birth year, parity, infant sex, gestational age, and child's BMI. RESULTS: Relative to normal BMI, RRs (95%CIs) for asthma at ages 4, 6, and 8 were 0.91 (0.75, 1.11), 0.95 (0.78, 1.16), and 0.97 (0.75, 1.27) for underweight, 1.06 (0.99, 1.14), 1.08 (1.01, 1.16), and 1.03 (0.94, 1.14) for overweight, 1.09 (1.00, 1.19), 1.12 (1.03, 1.23), 1.03 (0.91, 1.17) for obese 1, and 1.10 (0.99, 1.21), 1.13 (1.02, 1.25), 1.14 (0.99, 1.31) for obese 2/3. When continuous prepregnancy BMI was modeled with splines, child's asthma risk generally increased linearly with increasing prepregnancy BMI. CONCLUSIONS: Higher prepregnancy BMI is associated with modestly increased childhood asthma risk.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Testing and Detection During Peripartum Hospitalizations Among a Multicenter Cohort of Pregnant Persons: March 2020-February 2021.

BACKGROUND: Identifying severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections during peripartum hospitalizations is important to guide care, implement prevention measures, and understand infection burden. METHODS: This cross-sectional analysis used electronic health record data from hospitalizations during which pregnancies ended (peripartum hospitalizations) among a cohort of pregnant persons at 3 US integrated healthcare networks (sites 1-3). Maternal demographic, medical encounter, SARS-CoV-2 testing, and pregnancy and neonatal outcome information was extracted for persons with estimated delivery and pregnancy end dates during March 2020-February 2021 and ≥1 antenatal care record. Site-stratified multivariable logistic regression was used to identify factors associated with testing and compare pregnancy and neonatal outcomes among persons tested. RESULTS: Among 17 858 pregnant persons, 10 863 (60.8%) had peripartum SARS-CoV-2 testing; 222/10 683 (2.0%) had positive results. Testing prevalence varied by site and was lower during March-May 2020. Factors associated with higher peripartum SARS-CoV-2 testing odds were Asian race (adjusted odds ratio [aOR]: 1.36; 95% confidence interval [CI]: 1.03-1.79; referent: White) (site 1), Hispanic or Latino ethnicity (aOR: 1.33; 95% CI: 1.08-1.64) (site 2), peripartum Medicaid coverage (aOR: 1.33; 95% CI: 1.06-1.66) (site 1), and preterm hospitalization (aOR: 1.69; 95% CI: 1.19-2.39 [site 1]; aOR: 1.39; 95% CI: 1.03-1.88 [site 2]). CONCLUSIONS: Findings highlight potential disparities in SARS-CoV-2 peripartum testing by demographic and pregnancy characteristics. Testing practice variations should be considered when interpreting studies relying on convenience samples of pregnant persons testing positive for SARS-CoV-2. Efforts to address testing differences between groups could improve equitable testing practices and care for pregnant persons with SARS-CoV-2 infections.

Cesarean delivery and the risk of allergic rhinitis in children.

BACKGROUND: Cesarean delivery (C-section) may influence the infant microbiome and affect immune system development and subsequent risk for allergic rhinitis (AR). OBJECTIVE: To investigate the association between C-section and AR at ages 6, 8, and 10 years. METHODS: Data were collected prospectively through Kaiser Permanente Northern Californias (KPNC) integrated healthcare system. Children were eligible if they were born in a KPNC hospital and remained in the KPNC system for minimum 6 years (n = 117,768 age 6; n = 75,115 age 8; n = 40,332 age 10). Risk ratios (RR) for C-section and AR were estimated at each follow-up age and adjusted for important covariates, including intrapartum antibiotics, pre-pregnancy body mass index, maternal allergic morbidities, and breastfeeding. Subanalyses considered information on C-section indication, labor, and membrane rupture. RESULTS: After adjusting for confounders, we did not observe an association between C-section and AR at follow-up ages 6, 8, or 10 years (RR [CI]: 6 years, 0.98 [0.91, 1.04]; 8 years, 1.00 [0.95, 1.07]; 10 years, 1.03 [0.96, 1.10]). In stratified analyses, there was limited evidence that C-section increases the risk of AR in certain subgroups (eg, children of non-atopic mothers, second or higher birth order children), but most estimated risk ratios were consistent with no association. Estimated associations were unaffected by participant attrition, missing data, or intrapartum antibiotics. CONCLUSION: C-section delivery was not associated with AR at follow-up ages of 6, 8, or 10 years in a large contemporary US cohort.

Caesarean delivery and the risk of atopic dermatitis in children.

BACKGROUND: Caesarean delivery (C-section) may disrupt maternal-infant microbial transfer and alter immune system development and subsequent risk for atopic dermatitis. OBJECTIVE: Investigate the association between C-section and atopic dermatitis by age four and examine potential sources of bias in the relationship in a large cohort study. METHODS: Maternal and child information was collected through Kaiser Permanente Northern California's (KPNC) integrated healthcare system. Data sources included electronic medical records, pharmacy databases, state birth records, and prospectively collected breastfeeding surveys. Children were eligible if they were born in a KPNC or contracting hospital between 2005 and 2014 and had continuous enrolment in the KPNC system for at least four years (n = 173 105). Modified Poisson regression with robust variance estimation was used to estimate the association between C-section and atopic dermatitis overall and when stratified by demographic and labour and delivery characteristics. RESULTS: Although unadjusted analyses showed a positive association between C-section and atopic dermatitis [RR(95%CI): 1.06(1.03, 1.10)], this effect was attenuated towards the null after adjustment [aRR(95%CI): 1.02(0.99, 1.05)]. In stratified analyses, there was evidence that C-section increased atopic dermatitis risk among certain subgroups (eg firstborns, overweight/obese pre-pregnancy BMI), but associations were weak. C-section delivery conditions indicative of the least exposure to maternal microbiome (ie no labour, short interval between membrane rupture and delivery) showed no evidence of association with atopic dermatitis. Estimated associations were not strongly influenced by intrapartum antibiotics, breastfeeding, missing data, or familial factors. CONCLUSION: Caesarean delivery was not associated with atopic dermatitis by age four in this large US cohort. This association did not appear to be biased by intrapartum antibiotics, breastfeeding behaviour, C-section indication, missing covariates, or familial factors.

Use of nonsteroidal antiinflammatory drugs during pregnancy and the risk of miscarriage.

BACKGROUND: Nonsteroidal antiinflammatory drugs are among the medications most widely used by pregnant women, and previous studies have reported an increased risk of miscarriage that is associated with nonsteroidal antiinflammatory drug use during pregnancy. Although the findings have not always been consistent, there is a well-established mechanism for the association: nonsteroidal antiinflammatory drugs inhibit the production of prostaglandin, which is essential for successful embryonic implantation. Abnormal implantation increases the risk of miscarriage. OBJECTIVE: The purpose of this study was to examine the impact of nonsteroidal antiinflammatory drug use in early pregnancy on the risk of miscarriage, especially regarding the timing and duration of use. STUDY DESIGN: We conducted a cohort study among pregnant members of Kaiser Permanente Northern California, an integrated healthcare delivery system. Pregnant Kaiser Permanente Northern California members (N=1097) were recruited very early in pregnancy (median gestational age at enrollment, 39 days) to achieve optimal ascertainment of miscarriage, including early miscarriages, which are often missed in studies of miscarriages. Based on the use of nonsteroidal antiinflammatory drugs and acetaminophen, which has similar indication as nonsteroidal antiinflammatory drugs, 3 cohorts were formed: (1) women who used nonsteroidal antiinflammatory drugs only, (2) women who used acetaminophen only (to control for indication), and (3) women who used neither nonsteroidal antiinflammatory drugs nor acetaminophen (unexposed control subjects). Among all eligible women contacted, 63% participated in the study. Miscarriages were ascertained from both electronic medical record data and directly from interviews with participants. The Cox proportional hazards model with accommodation for left truncation was used to examine the risk of miscarriage associated with the use of nonsteroidal antiinflammatory drugs and acetaminophen during pregnancy; we controlled for potential confounders. RESULTS: After an adjustment for multiple confounders that included maternal age, previous miscarriage, multivitamin use, caffeine drinking, and smoking during pregnancy, we found that nonsteroidal antiinflammatory drug use during pregnancy was associated with a statistically significant increased risk of miscarriage compared with both unexposed control subjects (adjusted hazard ratio, 1.59; 95% confidence interval, 1.13-2.24) and acetaminophen users (indication control subjects; adjusted hazard ratio, 1.45; 95% confidence interval, 1.01-2.08). The risk was largely due to nonsteroidal antiinflammatory drug use around conception (adjusted hazard ratio, 1.89; 95% confidence interval, 1.31-2.71) with a statistically significant dose-response relationship: adjusted hazard ratio, 1.37 (95% confidence interval, 0.70-2.71) for nonsteroidal antiinflammatory drug use of ≤14 days; adjusted hazard ratio, 1.85 (95% confidence interval, 1.24-2.78) for nonsteroidal antiinflammatory drug use of ≥15 days. The association was stronger for early miscarriage (<8 weeks gestational age): adjusted hazard ratio, 4.08 (95% confidence interval, 2.25-7.41). Women with lower body mass index (<25 kg/m2) appeared to be more susceptible to the effect of nonsteroidal antiinflammatory drug use around conception (adjusted hazard ratio, 3.78; 95% confidence interval, 2.04-6.99) than women with high body mass index (≥25 kg/m2; adjusted hazard ratio, 1.03; 95% confidence interval, 0.61-1.72). CONCLUSION: After we controlled for confounding by indication, nonsteroidal antiinflammatory drug use around conception was associated with an increased risk of miscarriage with a dose-response relationship. In addition, women with lower body mass index could be especially vulnerable to the effects of nonsteroidal antiinflammatory drug use around the time of embryonic implantation, although this new observation must be confirmed in future studies.