Comparative effectiveness of treating prenatal depression with counseling versus antidepressants in relation to preterm delivery.

BACKGROUND: Maternal depression during pregnancy is prevalent and has been associated with increased risk of preterm delivery. However, comparative effectiveness of 2 commonly used treatment options, mental health counseling and use of antidepressants, in mitigating the risk of preterm delivery associated with maternal depression remains uncertain. Although antidepressant use has been associated with increased risk of preterm delivery in many previous studies, a direct head-to-head comparison between these 2 treatment options has not been investigated. Thus, the comparative risk-benefit profiles of those 2 treatment options remain unclear. OBJECTIVE: To determine the comparative effectiveness of 2 commonly used options for treating prenatal depression in limiting the risk of preterm delivery associated with maternal depression. STUDY DESIGN: A large prospective cohort study was conducted among 82,170 pregnant women at Kaiser Permanente Northern California, an integrated health care delivery system. Clinically diagnosed depression and its treatments (use of antidepressants and mental health counseling) were identified from the Kaiser Permanente Northern California electronic health record system. Gestational age was also recorded for all deliveries and captured by electronic health records for determining preterm delivery. RESULTS: Using Cox proportional hazards regression incorporating propensity score methodology to ensure comparability between comparison cohorts, relative to those without depression, pregnant women with untreated depression had 41% increased risk of preterm delivery: adjusted hazard ratio=1.41, 95% confidence interval=1.24 to 1.60, confirming increased risk of preterm delivery associated underlying maternal depression. Relative to untreated depression, any mental health counseling was associated with an 18% of reduced risk of preterm delivery: adjusted hazard ratio=0.82 (0.71-0.96). The inverse association showed a dose-response pattern: increased number of counseling visits was associated with greater reduction in preterm delivery risk with 43% reduction in preterm delivery risk associated with 4 or more visits (adjusted hazard ratio=0.57, 95% confidence interval=0.45-0.73). In contrast, use of antidepressants during pregnancy was associated with an additional 31% increased risk of preterm delivery independent of underlying depression: adjusted hazard ratio=1.31, 95% confidence interval=1.06 to 1.61. This positive association also showed a dose-response relationship: a longer duration of use was associated with an even higher risk. CONCLUSION: This study provides much needed evidence regarding the comparative effectiveness of 2 common treatment options for prenatal depression in the context of preterm delivery risk. The results indicate that, to reduce preterm delivery risk due to maternal depression, mental health counseling is more effective. Use of antidepressants may add additional risk of preterm delivery, independent of the underlying depression. The findings provide data for clinicians and pregnant women to make informed and evidence-based treatment decisions that take into account the risks and benefits to both maternal and fetal health.

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.

Incidence Rates of Medically Attended COVID-19 in Infants Less Than 6 Months of Age.

BACKGROUND: Studies suggest infants may be at increased risk of severe coronavirus disease 2019 (COVID-19) relative to older children, but few data exist regarding the incidence of COVID-19 episodes and associated risk factors. We estimate incidence rates and describe characteristics associated with medically attended COVID-19 episodes among infants younger than 6 months of age. METHODS: We analyzed electronic medical record data from a cohort of infants born March 1, 2020-February 28, 2021. Data from 3 health care delivery systems included demographic characteristics, maternal and infant outpatient visit and hospitalization diagnoses and severe acute respiratory syndrome coronavirus syndrome 2 (SARS-CoV-2) test results. Medically attended COVID-19 episodes were defined by positive SARS-CoV-2 clinical tests and/or COVID-19 diagnosis codes during medical care visits. Unadjusted and site-adjusted incidence rates by infant month of age, low and high SARS-CoV-2 circulation periods and maternal COVID-19 diagnosis were calculated. RESULTS: Among 18,192 infants <6 months of age whose mothers received prenatal care within the 3 systems, 173 (1.0%) had medically attended COVID-19 episodes. Incidence rates were highest among infants under 1 month of age (2.0 per 1000 person-weeks) and 1 month (2.0 per 1000 person-weeks) compared with older infants. Incidence rates were also higher for infants born to women with postpartum COVID-19 compared with women without known COVID-19 and women diagnosed with COVID-19 during pregnancy. CONCLUSIONS: Infants of women with postpartum COVID-19 had a higher risk of medically attended COVID-19 than infants born to mothers who were diagnosed during pregnancy or never diagnosed underscoring the importance of COVID-19 prevention measures for their household members and caregivers to prevent infections in infants.

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.

Medically Attended Influenza During Pregnancy in the 2019-2020 and 2020-2021 Influenza Seasons.

Influenza testing and case-confirmation rates in pregnant populations have not been reported during the coronavirus disease 2019 (COVID-19) pandemic. Using electronic medical record data from a cohort of nearly 20,000 pregnancies in the United States, this retrospective cohort study examines the frequency of acute respiratory or febrile illness encounters, influenza testing, and influenza positivity during the 2020-2021 influenza season, which occurred during the COVID-19 pandemic, compared with the 2019-2020 influenza season, which largely did not. The ratios of influenza tests to acute respiratory or febrile illness visits were similar in the 2019-2020 and 2020-2021 influenza seasons (approximately 1:8 and 1:9, respectively) but were low and varied by study site. Although influenza testing in pregnant patients continued in the 2020-2021 season, when severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) circulation was widespread in the United States, no cases of influenza were identified in our study cohort.

The clinical burden of extremely preterm birth in a large medical records database in the United States: complications, medication use, and healthcare resource utilization.

INTRODUCTION: Approximately 5% of global preterm births are extremely premature (EP), defined as occurring at less than 28 weeks gestational age. Advances in care have led to an increase in the survival of EP infants during the neonatal period. However, EP infants have a higher risk of developing complications such as bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH), and retinopathy of prematurity (ROP). BPD and other respiratory morbidities are particularly prevalent among this population. To understand the healthcare resource utilization (HRU) of EP infants in the United States, the clinical and economic burden of extreme prematurity was examined in this retrospective study of data extracted from electronic medical records in the Kaiser Permanente Northern California (KPNC) health system. METHODS: The analysis included data from EP infants live-born between January 1997 and December 2016, and focused on complications and HRU up to 3 years corrected age (CA), covering the period up to December 2018. Stillbirths, infants born at <22 weeks gestational age, and infants with major congenital malformations were excluded. Complications of interest (BPD, IVH, and ROP) and medication use were compared by age group (≤1 year, >1 year and ≤2 years, and >2 years and ≤3 years CA). Analysis of HRU included hospital readmissions, ambulatory visits, and emergency room (ER) visits. RESULTS: A total of 2154 EP births (0.32% of total live births and 4.0% of preterm births that met the inclusion/exclusion criteria) were analyzed. The prevalence of EP birth showed a declining trend over time. ROP was the most commonly recorded complication during the birth hospitalization (37.1% any stage; 2.9% Stages 3 and 4). BPD was recorded in 34.3% of EP infants. IVH (any grade) was recorded in 22.7% of EP infants (6.4% Grades III and IV). A majority (78.7%) of EP infants were diagnosed with at least one respiratory condition during the first year CA, the most common being pneumonia (68.9%); the prevalence of respiratory conditions decreased over the second and third years CA. During the first 3 years CA, the most common medications prescribed to children born EP were inhaled bronchodilators (approximately 30% of children); at least 15% of children received systemic corticosteroids and inhaled steroids during this period. During the first 3 years CA, at least one hospital readmission was recorded for 16.4% of children born EP; 57.1% of these readmissions were related to respiratory conditions. At least one ER visit was recorded for 33.8% of children born EP, for which 53.1% were due to a respiratory condition. Ambulatory visits were recorded for 54.2% of EP children, for which 82.9% were due to a respiratory condition. CONCLUSIONS: The short- and long-term clinical burden of EP birth was high. The onset of BPD, IVH, and ROP was common during the birth hospitalization for EP infants. Medication use, hospital readmission, and clinic visits (ER and ambulatory) occurred frequently in these children during the first 3 years CA, and were commonly due to respiratory conditions. Strategies prioritizing the reduction of risk and severity of respiratory conditions may alleviate the clinical burden of EP birth over the long term.

Respiratory Viral Infections and Infection Prevention Practices Among Women With Acute Respiratory Illness During Delivery Hospitalizations During the 2019-2020 Influenza Season.

BACKGROUND: We conducted a cross-sectional study of pregnant women with acute respiratory illness during delivery hospitalizations during influenza season to describe clinical testing for respiratory viruses and infection prevention practices. METHODS: Women had nasal swabs tested for influenza and other respiratory viruses. Among 91 enrolled women, 22 (24%) had clinical testing for influenza. RESULTS: Based on clinical and study testing combined, 41 of 91 (45%) women had samples positive for respiratory viruses. The most common virus was influenza (17 of 91, 19%); 53% (9 of 17) of influenza virus infections were identified through study testing alone. Only 16% of women were on droplet precautions. CONCLUSIONS: Peripartum respiratory infections may be underrecognized.

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.

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.

Association Between Maternal Exposure to Magnetic Field Nonionizing Radiation During Pregnancy and Risk of Attention-Deficit/Hyperactivity Disorder in Offspring in a Longitudinal Birth Cohort.

Importance: An association between maternal exposure to magnetic field (MF) nonionizing radiation during pregnancy and the risk of attention-deficit/hyperactivity disorder (ADHD) has been reported in both animal and human studies. Objectives: To determine whether maternal exposure to high levels of MF nonionizing radiation is associated with an increased risk of ADHD in offspring by using more accurate measurements of MF nonionizing radiation levels and physician-diagnosed ADHD, rather than self-reports, and to determine whether the association differs for the subtypes of ADHD with or without immune-related comorbidities. Design, Setting, and Participants: A longitudinal birth cohort study was conducted at Kaiser Permanente Northern California among 1482 mother-child pairs whose mothers were participants of an existing birth cohort and whose level of exposure to MF nonionizing radiation was captured during pregnancy in 2 studies conducted from October 1, 1996, to October 31, 1998, and from May 1, 2006, to February 29, 2012. The offspring were followed up from May 1, 1997, to December 31, 2017. Exposure: All participating women wore a monitoring meter for 24 hours during pregnancy to capture the level of exposure to MF nonionizing radiation from any sources. Main Outcomes and Measures: Physician-diagnosed ADHD and immune-related comorbidities of asthma or atopic dermatitis up to 20 years of age in offspring captured in the Kaiser Permanente Northern California electronic medical record from May 1, 1997, to December 31, 2017. Confounders were ascertained during in-person interviews during pregnancy. Results: Among the 1454 mother-child pairs (548 white [37.7%], 110 African American [7.6%], 325 Hispanic [22.4%], 376 Asian or Pacific Islander [25.9%], and 95 other or unknown [6.5%]; mean [SD] maternal age, 31.4 [5.4] years]), 61 children (4.2%) had physician-diagnosed ADHD. Using Cox proportional hazards regression to account for follow-up time and confounders, compared with children whose mothers had a low level of exposure to MF nonionizing radiation during pregnancy, children whose mothers were exposed to higher levels of MF nonionizing radiation had more than twice the risk of ADHD (adjusted hazard ratio [aHR], 2.01; 95% CI, 1.06-3.81). The association was stronger for ADHD that persisted into adolescence (≥12 years of age), with an aHR of 3.38 (95% CI, 1.43-8.02). When the subtypes of ADHD were examined, the association existed primarily for ADHD with immune-related comorbidities (asthma or atopic dermatitis), with an aHR of 4.57 (95% CI, 1.61-12.99) for all ADHD cases and an aHR of 8.27 (95% CI, 1.96-34.79) for persistent cases of ADHD. Conclusions and Relevance: Consistent with the emerging literature, this study suggests that in utero exposure to high levels of MF nonionizing radiation was associated with an increased risk of ADHD, especially ADHD with immune-related comorbidity. The findings should spur more research to examine the biological association of in utero MF exposure with risk of ADHD in offspring, given that almost everyone is exposed to it.

Trivalent inactivated influenza vaccine (IIV3) during pregnancy and six-month infant development.

OBJECTIVE: Despite recommendations by professional organizations that all pregnant women receive inactivated influenza vaccine, safety concerns remain a barrier. Our objective was to assess the effect of trivalent influenza vaccines (IIV3) during pregnancy on parent report 6-month infant development. METHODS: We conducted a multi-site prospective birth cohort study during the 2010-2011 influenza season and followed pregnant women and their newborns through 6 months of age. Information on IIV3 during pregnancy was ascertained from the EHR and self-report. The Ages and Stages Questionnaire-3 (ASQ-3) was completed by the mother to assess 6-month infant neurodevelopment in five domains (communication, gross motor, fine motor, problem-solving, and personal adaptive skills). Scores for each domain above the cut-off point indicating typical development were categorized as "on schedule" while scores in the zones indicating the need for either monitoring or further assessment were categorized as "not on schedule". Multivariable logistic regression was conducted. RESULTS: Of the 1225 infant-mother pairs, 65% received IIV3 during pregnancy. In bivariate analysis, infants of women who received IIV3 during pregnancy were moderately-less likely to need monitoring or further assessment in the personal social domain compared with infants of unvaccinated women (10.0% vs. 14.1%, p = 0.033; crude OR (cOR): 0.68(95%CI:0.48,0.97)). However, after controlling for potential confounders, the findings were no longer statistically significant (aOR:0.72,95%CI: 0.49,1.06,p = 0.46). No significant unadjusted or adjusted associations emerged in any other ASQ-3 domain. CONCLUSION: There was no significant association between IIV3 exposure during pregnancy and 6-month infant development. Studies of IIV3 during pregnancy to assess longer-term developmental outcomes are indicated.

Maternal infection and antibiotic use in pregnancy and the risk of childhood obesity in offspring: a birth cohort study.

BACKGROUND/OBJECTIVES: The reported association between maternal antibiotic use and childhood obesity, if true, could change obstetric practice. However, it is unclear whether the reported association was due to antibiotics, or underlying infection or both. To examine the independent contributions of maternal infection and antibiotic use separately, we conducted a birth cohort study among Kaiser Permanente Northern California (KPNC) members. SUBJECTS/METHODS: The study consisted of 145,393 mother-child dyads. The KPNC electronic medical records provided data on maternal infections, antibiotic use during pregnancy, and longitudinal anthropometric measurements throughout childhood. Obesity was defined by BMI using CDC criteria. Mixed effects logistic regression for repeated measurements was used to analyze multiple BMI measurements per child (five measurements per child on average). RESULTS: After controlling for confounders using propensity score methodology, there was no increased risk associated with maternal antibiotic use during pregnancy once underlying infection was controlled for: OR = 0.97 (95% CI: 0.92-1.01). There was also no association with timing of use or use of broad-spectrum antibiotics, nor a dose-response relationship. In contrast, maternal untreated infection (without antibiotic use) during pregnancy was associated with a statistically significant risk of childhood obesity compared with mothers without infection: odds ratio (OR) = 1.09 (95% confidence interval (CI): 1.03-1.16). The association was stronger for GBS positive infection (OR = 1.16) than GBS negative infections (OR = 1.08). These results were further confirmed by a discordant sibling study. This discordant sibling study allowed additional control of unmeasured confounders including genetic, maternal intrauterine, and familiar factors. The consistent findings from this sibling study enhances the reproducibility of our findings. CONCLUSIONS: It is maternal infection, NOT antibiotic use, during pregnancy that is associated with increased risk of childhood obesity. While use of antibiotics should always be judicious, in the context of preventing childhood obesity, the focus should be on reducing maternal infections during pregnancy.

Factors associated with recruitment, surveillance participation, and retention in an observational study of pregnant women and influenza.

BACKGROUND: This report describes the results of recruitment efforts and the subsequent participation of pregnant women in study activities in a 2010-2012 observational study focused on influenza illness and vaccination in California and Oregon, USA. METHODS: Socio-demographic and health characteristics extracted from electronic medical records were compared among pregnant women who enrolled in the study, refused to participate, or were never reached for study invitation. These characteristics plus additional self-reported information were compared between women who enrolled in two study tracks: a prospective cohort vs. women enrolled following an acute respiratory illness (ARI) medical encounter. The characteristics of women who participated in weekly ARI surveillance (cohort enrollees, year one) and a 6-month follow-up interview (all enrollees) were also examined. RESULTS: In year one, we reached 51% (6938/13,655) of the potential participants we tried to contact by telephone, and 20% (1374/6938) of the women we invited agreed to join the prospective cohort. Women with chronic medical conditions, pregnancy complications, and medical encounters for ARI (prior to pregnancy or during the study period) were more likely to be reached for recruitment and more likely to enroll in the cohort. Twenty percent of cohort enrollees never started weekly surveillance reports; among those who did, reports were completed for 55% of the surveillance weeks. Receipt of the influenza vaccine was higher among women who joined the cohort (76%) than those who refused (56%) or were never reached (54%). In contrast, vaccine uptake among medical enrollees in year one (54%; 53/98) and two (52%; 79/151) was similar to other pregnant women in those years. Study site, white race, non-Hispanic ethnicity, and not having a child aged < 13 years at home were most consistently associated with joining as a cohort or medical enrollee and completing study activities after joining. CONCLUSIONS: We observed systematic differences in socio-demographic and health characteristics across different levels of participant engagement and between cohort and medical enrollees. More methodological research and innovation in conducting prospective observational studies in this population are needed, especially when extended participant engagement and ongoing surveillance are required.

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.

Exposure to Magnetic Field Non-Ionizing Radiation and the Risk of Miscarriage: A Prospective Cohort Study.

Magnetic field (MF) non-ionizing radiation is widespread and everyone is exposed to some degree. This prospective cohort study of 913 pregnant women examined the association between high MF exposure and miscarriage risk. Cox (proportional hazards) regression was used to examine the association. After controlling for multiple other factors, women who were exposed to higher MF levels had 2.72 times the risk of miscarriage (hazard ratio = 2.72, 95% CI: 1.42-5.19) than those with lower MF exposure. The increased risk of miscarriage associated with high MF was consistently observed regardless of the sources of high MF. The association was much stronger if MF was measured on a typical day of participants' pregnancies. The finding also demonstrated that accurate measurement of MF exposure is vital for examining MF health effects. This study provides fresh evidence, directly from a human population, that MF non-ionizing radiation could have adverse biological impacts on human health.

Infection and antibiotic use in infancy and risk of childhood obesity: a longitudinal birth cohort study.

BACKGROUND: Data from previous studies have suggested a possible association between antibiotic use in infancy and risk of childhood obesity, with implications for health-care delivery and obesity prevention strategies. However, whether the observed association was due to antibiotic use or underlying infection, or both, is unclear. We aimed to disentangle the effect of antibiotic use in infancy from that of underlying infection on the risk of childhood obesity. METHODS: In this longitudinal birth cohort study, we included infants in the Kaiser Permanente Northern California population born between Jan 1, 1997, and March 31, 2013. We used electronic medical records to ascertain data for antibiotic use, infection diagnosis, and anthropometric measurements (and thus BMI and obesity status) from birth up to age 18 years. We used standard mixed-effects logistic regression for repeated measurements to analyse multiple BMI measurements per child (median five measurements) and to obtain odds ratios (ORs) and 95% CIs for obesity risk. We also did a substudy in 547 same-sex twin pairs with discordant exposure status to substantiate our findings. FINDINGS: 260 556 individuals were included in our analysis. After controlling for maternal age, race or ethnic origin, pre-pregnancy BMI, preterm delivery, low birthweight, maternal antibiotic use, and infection during pregnancy, infection without antibiotic use in infancy was associated with an increased risk of childhood obesity compared with controls without infection (OR 1·25, 95% CI 1·20-1·29). A clear dose-response relation was seen between infection episodes and risk of childhood obesity (ptrend <0·0001). By contrast, compared with infants with untreated infection, antibiotic use during infancy was not associated with risk of childhood obesity (1·01, 0·98-1·04). Neither broad-spectrum nor narrow-spectrum antibiotics were associated with risk of childhood obesity. These findings were supported by the results of the twin set analysis. INTERPRETATION: Infection, but not antibiotic use, during infancy is associated with risk of childhood obesity. This finding will need to be replicated in future studies. Although our results do not rule out a potential effect of antibiotics on microbiome composition and the use of antibiotics should always be judicious, they suggest that treatment of common infections with antibiotics in infancy is unlikely to be a main contributor to childhood obesity. FUNDING: Kaiser Permanente Center for Effectiveness & Safety Research.

Results of a pilot study using self-collected mid-turbinate nasal swabs for detection of influenza virus infection among pregnant women.

BACKGROUND: We evaluated the feasibility of asking pregnant women to self-collect and ship respiratory specimens. METHODS: In a preliminary laboratory study, we compared the RT-PCR cycle threshold (CT) values of influenza A and B viruses incubated at 4 storage temperatures (from 4 to 35°C) for 6 time periods (8, 24, 48, 72, and 168 hours and 30 days), resulting in 24 conditions that were compared to an aliquot tested after standard freezing (-20°C) (baseline condition). In a subsequent pilot study, during January-February, 2014, we delivered respiratory specimen collection kits to 53 pregnant women with a medically attended acute respiratory illness using three delivery methods. RESULTS: CT values were stable after storage at temperatures <27°C for up to 72 hours for influenza A viruses and 48 hours for influenza B viruses. Of 53 women who received kits during the pilot, 89% collected and shipped nasal swabs as requested. However, 30% (14/47) of the women took over 2 days to collect and ship their specimen. The human control gene, ribonuclease P (RNase P), was detected in 100% of nasal swab specimens. However, the mean CT values for RNase P (26.5, 95% confidence interval [CI] = 26.0-27.1) and for the 8 influenza A virus positives in our pilot (32.2, 95% CI = 28.9-35.5) were significantly higher than the CTs observed in our 2010-2012 study using staff-collected nasal pharyngeal swabs (P-values < 0.01). DISCUSSION: Self-collection of respiratory specimens is a promising research method, but further research is needed to quantify the sensitivity and specificity of the approach.