Maternal smoking during pregnancy, offspring smoking, adverse childhood events, and risk of major depression: a sibling design study.

BACKGROUND: Evidence of a biologically plausible association between maternal smoking during pregnancy (MSP) and the risk of depression is discounted by null findings from two sibling studies. However, valid causal inference from sibling studies is subject to challenges inherent to human studies of MSP and biases particular to this design. We addressed these challenges in the first sibling study of MSP and depression conducted among adults past the peak age for the onset of depression, utilizing a prospectively collected and biologically validated measure of MSP and accounting for non-shared as well as mediating factors. METHODS: We fit GEE binomial regression models to correct for dependence in the risk of depression across pregnancies of the same mother. We also fit marginal structural models (MSM) to estimate the controlled direct effect of MSP on depression that is not mediated by the offspring's smoking status. Both models allow the estimation of within- and between-sibling risk ratios. RESULTS: The adjusted within-sibling risk ratios (RRW) from both models (GEE: RRW = 1.97, CI 1.16-3.32; MSM: RRW = 2.08, CI 1.04-4.17) evinced an independent association between MSP and risk of depression. The overall effects from a standard model evinced lower associations (GEE: RRT = 1.12, CI 0.98-1.28; MSM: RRT = 1.18, CI 1.01-1.37). CONCLUSIONS: Based on within-sibling information free of unmeasured shared confounders and accounting for a range of unshared factors, we found an effect of MSP on the offspring's risk of depression. Our findings, should they be replicated in future studies, highlight the importance of considering challenges inherent to human studies of MSP and affective disorders.

Infections During Pregnancy and Risks for Adult Psychosis: Findings from the New England Family Study.

For the past 40 years, our team has conducted a unique program of research investigating the prenatal risks for schizophrenia and related adult psychiatric disorders. The New England Family Study is a long-term prospective cohort study of over 16,000 individuals followed from the prenatal period for over 50 years. This chapter summarizes several major phases and findings from this work, highlighting recent results on maternal prenatal bacterial infections and brain imaging. Implications regarding the causes and potential prevention of major psychotic disorders are discussed.

Involuntary tobacco smoke exposures from conception to 18 years increase midlife cardiometabolic disease risk: a 40-year longitudinal study.

Few population studies have sufficient follow-up period to examine early-life exposures with later life diseases. A critical question is whether involuntary exposure to tobacco smoke from conception to adulthood increases the risk of cardiometabolic diseases (CMD) in midlife. In the Collaborative Perinatal Project, serum-validated maternal smoking during pregnancy (MSP) was assessed in the 1960s. At a mean age of 39 years, 1623 offspring were followed-up for the age at first physician-diagnoses of any CMDs, including diabetes, heart disease, hypertension, or hyperlipidemia. Detailed information on their exposure to environmental tobacco smoke (ETS) in childhood and adolescence was collected with a validated questionnaire. Cox regression was used to examine associations of in utero exposure to MSP and exposure to ETS from birth to 18 years with lifetime incidence of CMD, adjusting for potential confounders. We calculated midlife cumulative incidences of hyperlipidemia (25.2%), hypertension (14.9%), diabetes (3.9%), and heart disease (1.5%). Lifetime risk of hypertension increased by the 2nd -trimester exposure to MSP (adjusted hazard ratio: 1.29, 95% confidence interval: 1.01-1.65), ETS in childhood (1.11, 0.99-1.23) and adolescence (1.22, 1.04-1.44). Lifetime risk of diabetes increased by joint exposures to MSP and ETS in childhood (1.23, 1.01-1.50) or adolescence (1.47, 1.02-2.10). These associations were stronger in males than females, in never-daily smokers than lifetime ever smokers. In conclusion, early-life involuntary exposure to tobacco smoke increases midlife risk of hypertension and diabetes in midlife.

Child and Adolescent Abuse Patterns and Incident Obesity Risk in Young Adulthood.

INTRODUCTION: Child abuse is associated with adult obesity. Yet, it is unknown how the developmental timing and combination of abuse types affect this risk. This report examined how distinct child and adolescent abuse patterns were associated with incident obesity in young adulthood. METHODS: Data came from 7,273 participants in the Growing Up Today Study, a prospective cohort study in the U.S. with 14 waves from 1996 to 2016 (data were analyzed during 2020-2021). An abuse group variable was empirically derived using latent class analysis with indicators for child (before age 11 years) and adolescent (ages 11-17 years) physical, sexual, and emotional abuse. Risk ratios for obesity developing during ages 18-30 years were estimated using modified Poisson models. Associations of abuse groups with BMI across ages 18-30 years were then examined using mixed-effects models. All models were stratified by sex. RESULTS: Among women, groups characterized by abuse had higher BMIs entering young adulthood and greater changes in BMI per year across young adulthood. Groups characterized by multiple abuse types and abuse sustained across childhood and adolescence had approximately twice the risk of obesity as that of women in a no/low abuse group. Associations were substantially weaker among men, and only a group characterized by physical and emotional abuse in childhood and adolescence had an elevated obesity risk (risk ratio=1.38; 95% CI=1.04, 1.83). CONCLUSIONS: Obesity risk in young adulthood varied by distinct abuse groups for women and less strongly for men. Women who experience complex abuse patterns have the greatest risk of developing obesity in young adulthood.

The Family is the Patient: Promoting Early Childhood Mental Health in Pediatric Care.

Advances in developmental psychology, child psychiatry, and allied disciplines have pointed to events and experiences in the early years as the origin of many adult mental health challenges. Yet, children's mental health services still largely lack a developmental or prevention-focused orientation, with most referrals to mental health professionals occurring late, once problems are well established. An early childhood mental health system rooted in the principles of life-course health development would take a very different approach to designing, testing, and implementing prevention and intervention strategies directed toward early child mental health. Priorities for such a system include supporting healthy family environments, parent-child and family relationships, parents' emotional/behavioral health, and family routines as a means of providing the best possible neurobiological foundation for mental health across the life span. The system would include proactive, trauma-informed, multidisciplinary care, with integrated mental health and social services support embedded in pediatric primary care settings. Novel intervention approaches in need of further research include 2-generational dyadic interventions designed to improve the mental health of parents and children, mental health-oriented telemedicine, and contingency management (CM) strategies. Integral to this Life Course Health Development reformulation is a commitment by all organizations supporting children to primordial and primary prevention strategies to reduce racial and socioeconomic disparities in all settings. We contend that it is the family, not the individual child, that ought to be the identified target of these redesigned approaches, delivered through a transformed pediatric system with anticipated benefits for multiple health outcomes across the life course.

Prenatal metal mixture exposure and birth weight: A two-stage analysis in two prospective cohort studies.

The understanding of the impact of prenatal exposure to metal mixtures on birth weight is limited. We aimed to identify metal mixture components associated with birth weight and to determine additional pairwise interactions between metals showing such associations. Concentrations of 18 metals were measured using inductively coupled plasma mass spectrometry in urine samples collected in the 3rd trimester from a prenatal cohort (discovery; n = 1849) and the Healthy Baby Cohort (replication; n = 7255) in Wuhan, China. In the discovery set, we used two penalized regression models, i.e., elastic net regression for main effects and a lasso for hierarchical interactions, to identify important mixture components associated with birth weight, which were then replicated. We observed that 8 of the 18 measured metals were retained by elastic net regression, with five metals (vanadium, manganese, iron, cesium, and barium) showing negative associations with Z-scores for birth weight and three metals (cobalt, zinc, and strontium) showing positive associations. In replication set, associations remained significant for vanadium (ß = -0.035; 95% confidence interval [CI], -0.059 to -0.010), cobalt (ß = 0.073; 95% CI, 0.049 to 0.097), and zinc (ß = 0.040; 95% CI, 0.016 to 0.065) after Bonferroni correction. We additionally identified and replicated a single pairwise interaction between iron and copper exposure on birth weight (P < 0.001). Using a two-stage analysis, we identified and replicated individual metals and additional pairwise interactions-associated birth weight. The approach could be used in other studies estimating the effect of complex mixtures on human health.

Child and adolescent maltreatment patterns and risk of eating disorder behaviors developing in young adulthood.

BACKGROUND: Child maltreatment may be an important risk factor for eating disorder (ED) behaviors. However, most previous research has been limited to clinical, female, and cross-sectional samples, and has not adequately accounted for complex abuse patterns. OBJECTIVE: To determine whether women and men with distinct patterns of child and adolescent maltreatment have higher risks of developing ED behaviors in young adulthood than individuals with a low probability of maltreatment. PARTICIPANTS AND SETTING: Data came from 7010 U.S. women and men (95% White) in the Growing Up Today Study, a prospective, community-based cohort study (14 waves between 1996 and 2016). METHODS: We used a previously created maltreatment variable that was empirically derived using latent class analysis. Maltreatment groups were characterized as: "no/low abuse," "child physical abuse," "adolescent emotional abuse," "child and adolescent physical and emotional abuse," and "child and adolescent sexual abuse." We estimated risk ratios for ED behaviors developing in young adulthood using the modified Poisson approach with generalized estimating equations. We stratified models by sex. RESULTS: Groups characterized by maltreatment had elevated risks of incident ED behaviors compared with the "no/low abuse" group among both women and men. For women, risks tended to be strongest among the "child and adolescent sexual abuse" group. For men, risks tended to be strongest among the "child and adolescent physical and emotional abuse" group. Risks were particularly strong for purging behaviors. CONCLUSION: Risk of incident ED behaviors in young adulthood varied by distinct maltreatment groups. Detecting maltreatment early may help prevent EDs and subsequent maltreatment.

Associations of telomere length at birth with predicted atherosclerotic lesions and cardiovascular disease risk factors in midlife: A 40-year longitudinal study.

BACKGROUND AND AIMS: Adult telomere length (TL) is substantially determined by birth TL, but associations of birth TL with cardiovascular disease (CVD) are unknown. METHODS: We included 144 adult offspring born in 1959-1966 from the Collaborative Perinatal Project, a US birth cohort. Birth TL was measured from banked cord blood with quantitative polymerase chain reaction. Atherosclerotic lesions were predicted by the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) score that was based on blood pressure, lipids, hemoglobin A1c, and body weight at the midlife follow-up in 2003-2008 (average age: 42 years). Information on midlife CVD risk factors including the age at first diagnoses of hypertension, hypercholesterolemia, and diabetes was also collected. We used linear and logistic regression models to analyze associations of birth TL with the continuous PDAY score and categorical CVD risk factors, respectively, adjusting for prenatal confounders. RESULTS: At midlife follow-up, 31.2% and 18.7% of participants had ever been diagnosed with hypercholesterolemia and hypertension, respectively, and 8.3% met the criteria for metabolic syndrome. Short birth TL (Quartile 1, Q1) was associated with a higher PDAY score (adjusted ß: 1.78, 95% CI: 0.31, 3.25), increased odds of hypercholesterolemia (adjusted odds ratio [OR]: 3.23, 95% CI: 1.28, 8.18) and the presence of any cardiometabolic abnormalities (adjusted OR: 2.54, 95% CI: 1.00, 6.48) as compared to longer birth TL (Q2-Q4) after adjusting for prenatal confounders. CONCLUSIONS: People born with short TL may be at increased risk of predicted midlife atherosclerotic lesions and hypercholesterolemia. Future studies with larger sample sizes and CVD morbidities are warranted to replicate our findings.

Impact of prenatal maternal cytokine exposure on sex differences in brain circuitry regulating stress in offspring 45 years later.

Stress is associated with numerous chronic diseases, beginning in fetal development with in utero exposures (prenatal stress) impacting offspring's risk for disorders later in life. In previous studies, we demonstrated adverse maternal in utero immune activity on sex differences in offspring neurodevelopment at age seven and adult risk for major depression and psychoses. Here, we hypothesized that in utero exposure to maternal proinflammatory cytokines has sex-dependent effects on specific brain circuitry regulating stress and immune function in the offspring that are retained across the lifespan. Using a unique prenatal cohort, we tested this hypothesis in 80 adult offspring, equally divided by sex, followed from in utero development to midlife. Functional MRI results showed that exposure to proinflammatory cytokines in utero was significantly associated with sex differences in brain activity and connectivity during response to negative stressful stimuli 45 y later. Lower maternal TNF-α levels were significantly associated with higher hypothalamic activity in both sexes and higher functional connectivity between hypothalamus and anterior cingulate only in men. Higher prenatal levels of IL-6 were significantly associated with higher hippocampal activity in women alone. When examined in relation to the anti-inflammatory effects of IL-10, the ratio TNF-α:IL-10 was associated with sex-dependent effects on hippocampal activity and functional connectivity with the hypothalamus. Collectively, results suggested that adverse levels of maternal in utero proinflammatory cytokines and the balance of pro- to anti-inflammatory cytokines impact brain development of offspring in a sexually dimorphic manner that persists across the lifespan.

Maternal Immune activity during pregnancy and socioeconomic disparities in children's self-regulation.

Maternal immune activity during pregnancy has been associated with risk for psychiatric disorders in offspring, but less is known about its implications for children's emotional and behavioral development. This study examined whether concentrations of five cytokines assayed from prenatal serum were associated with socioeconomic status (SES) and racial disparities in their offspring's self-regulation abilities. Participants included 1628 women in the Collaborative Perinatal Project (CPP). Seven behavioral items conceptually related to self-regulation were rated by CPP psychologists when children were 4 years old. Concentrations of interleukin (IL)-1ß, IL-6, IL-8, tumor necrosis factor (TNF)-α, and IL-10 were assessed. Covariates included child sex and mother's age, psychiatric disorders, and medical conditions during pregnancy. There were significant SES differences in child self-regulation, with higher SES children scoring higher on self-regulation (ß = 0.18, 95% CI [0.11, 0.25]), but no racial differences. The concentration of IL-8 in maternal serum was associated with higher child self-regulation, ß = 0.09, 95% CI [0.02, 0.16]. In mediation analyses, variation in maternal IL-8 contributed to the association between family SES and child self-regulation (ß = 0.02, 95% CI [0.003, 0.030]), explaining about one-tenth of the SES disparities. This study suggests pregnancy as an early sensitive period and maternal immune activity as an important context for child development.

Gestational Cytokines and the Developmental Expression of Obesity in Childhood.

OBJECTIVE: This study examined the extent to which maternal immune activity during pregnancy is associated with childhood adiposity, and if so, whether associations at birth differ from those in infancy and childhood. Sex-specific associations were also examined. METHODS: Participants were 1,366 singleton pregnancies from the Collaborative Perinatal Project (1959-1966). Interleukin-1ß (IL-1ß), IL-6, TNF-α, IL-8, and IL-10 in maternal sera were assayed repeatedly during pregnancy. Children's BMI was calculated repeatedly from birth through age 8 and derived age- and sex-normalized BMI z scores (BMIz). Linear mixed models were used to estimate the cumulative concentration of each cytokine in the second and third trimesters and then related this concentration to child BMIz. RESULTS: Children exposed to higher IL-1ß, IL-6, IL-8, and IL-10 concentrations had lower BMIz at birth but higher BMIz during childhood. Higher concentrations of IL-8 and IL-1ß were also associated with higher BMIz during infancy (B per log increase in IL-8 = 0.04; 95% CI: 0.02 to 0.07; B per log increase in IL-1ß = 0.03; 95% CI: 0.001 to 0.06). The associations between TNF-α and BMIz were in opposing directions in boys (B = -0.13; 95% CI: -0.31 to 0.04) and girls (B = 0.14; 95% CI: 0.02 to 0.26) during childhood. CONCLUSIONS: Maternal prenatal inflammation contributes to the age- and sex-specific programming of obesity risk in childhood.

Using latent class analysis to empirically classify maltreatment according to the developmental timing, duration, and co-occurrence of abuse types.

BACKGROUND: Individuals can have vastly different maltreatment experiences depending on the types, developmental timing, and duration of abuse. Women and men may be differentially affected by distinct abuse patterns. OBJECTIVE: To examine whether maltreatment subgroups could be identified based on the types, developmental timing, and duration of abuse, and to determine their prevalence among a large, community-based sample. We also examined sex differences in associations of maltreatment subgroups with adverse health outcomes. PARTICIPANTS AND SETTING: Data came from 9310 women and men (95 % White) in the United States who responded to the Growing Up Today Study questionnaire in 2007 (aged 19-27 years). METHODS: Participants reported on physical, sexual, and emotional abuse occurring in childhood (before age 11 years) and adolescence (ages 11-17 years). We conducted latent class (LC) analyses using indicators for child and adolescent abuse. We examined associations of LCs with health outcomes using sex-stratified log-binomial models with generalized estimated equations. RESULTS: We identified five LCs characterized by: 1) no/low abuse (59 %), 2) child physical abuse (16 %), 3) adolescent emotional abuse (9%), 4) child and adolescent physical and emotional abuse (16 %), and 5) child and adolescent sexual abuse (1%). LCs were uniquely associated adult health outcomes among both women and men. Associations of LCs with eating disorder behaviors appeared stronger for men than women. CONCLUSIONS: Individuals experience distinct patterns of maltreatment based on the types, developmental timing, and duration of abuse. These patterns are uniquely associated with adverse health outcomes in adulthood, and can be identified using LCA.

Assessing the relationship between psychosocial stressors and psychiatric resilience among Chilean disaster survivors.

BACKGROUND: According to the stress inoculation hypothesis, successfully navigating life stressors may improve one's ability to cope with subsequent stressors, thereby increasing psychiatric resilience. AIMS: Among individuals with no baseline history of post-traumatic stress disorder (PTSD) and/or major depressive disorder (MDD), to determine whether a history of a stressful life event protected participants against the development of PTSD and/or MDD after a natural disaster. METHOD: Analyses utilised data from a multiwave, prospective cohort study of adult Chilean primary care attendees (years 2003-2011; n = 1160). At baseline, participants completed the Composite International Diagnostic Interview (CIDI), a comprehensive psychiatric diagnostic instrument, and the List of Threatening Experiences, a 12-item questionnaire that measures major stressful life events. During the study (2010), the sixth most powerful earthquake on record struck Chile. One year later (2011), the CIDI was re-administered to assess post-disaster PTSD and/or MDD. RESULTS: Marginal structural logistic regressions indicated that for every one-unit increase in the number of pre-disaster stressors, the odds of developing post-disaster PTSD or MDD increased (OR = 1.21, 95% CI 1.08-1.37, and OR = 1.16, 95% CI 1.06-1.27 respectively). When categorising pre-disaster stressors, individuals with four or more stressors (compared with no stressors) had higher odds of developing post-disaster PTSD (OR = 2.77, 95% CI 1.52-5.04), and a dose-response relationship between pre-disaster stressors and post-disaster MDD was found. CONCLUSIONS: In contrast to the stress inoculation hypothesis, results indicated that experiencing multiple stressors increased the vulnerability to developing PTSD and/or MDD after a natural disaster. Increased knowledge regarding the individual variations of these disorders is essential to inform targeted mental health interventions after a natural disaster, especially in under-studied populations.

Cytokine concentrations throughout pregnancy and risk for psychosis in adult offspring: a longitudinal case-control study.

BACKGROUND: Schizophrenia has been associated with pregnancy and birth complications and fetal exposure to inflammation is thought to be a common underlying mechanism. However, whether the risk is specific to particular phases of pregnancy is unclear. The aim of this study was to characterise and compare longitudinal patterns of maternal serum concentrations of cytokines across pregnancy between offspring who were later ascertained to have a psychotic disorder, non-psychotic siblings of these cases, and unrelated, non-psychotic individuals who served as controls. METHODS: The National Collaborative Perinatal Project was a large-scale prospective longitudinal study that assessed the effects of perinatal factors on infant and child development. At sites across the USA, over 50 000 pregnant women were enrolled during prenatal clinical visits between 1959 and 1965. The present study draws from the Philadelphia cohort, which includes 9236 surviving offspring of 6753 pregnant women. Psychotic disorder diagnoses in adulthood were assessed with review of medical records and were confirmed with a validation study. Concentrations of TNFα, IL-1ß, IL-5, IL-6, IL-8, IL-10, and IL-17a were assessed using a multiplex bead assay in archived maternal serum samples collected across prenatal visits and birth. We characterized cytokine patterns with linear mixed models. FINDINGS: Our final sample comprised 90 cases, 79 siblings (of 40 cases), and 273 matched controls. Concentrations of proinflammatory cytokines TNFα, IL-1ß, and IL-6 were significantly higher in maternal serum of offspring who later developed psychosis compared with maternal serum of matched controls. These differences were greatest in the first half of pregnancy (7-20 weeks), with no difference observed during the second half of pregnancy. INTERPRETATION: Our results suggest that exposure to high maternal proinflammatory cytokine concentrations in early pregnancy might play a part in psychosis. These findings place the timing of risk associated with maternal inflammation much earlier in prenatal development than previously documented in humans and provide insight into a potential developmental pathway to the disorder. FUNDING: National Institute of Mental Health (P50) Silvio O Conte Center at Johns Hopkins, Stanley Foundation, March of Dimes, Yale University, National Science Foundation, and National Institute of Child Health and Human Development/Division of Intramural Population Health Research.

Optimism and Social Support Predict Healthier Adult Behaviors Despite Socially Disadvantaged Childhoods.

BACKGROUND: Studies have shown adverse effects of a disadvantaged childhood on adult health-promoting behaviors and related outcomes. Optimism and social support have been linked to greater likelihood of engaging in healthy behavior, but it is unclear whether these positive psychosocial factors may buffer harmful effects of early adversity. This study aims to determine if optimism and social support in adulthood can modify effects of childhood disadvantage on health behavior-related outcomes. METHODS: Longitudinal data were analyzed from a subset of participants in a US birth cohort established in 1959-1966 (ns of 681-840, per outcome). An index of childhood social disadvantage was derived from adverse socioeconomic and family stability factors reported by mothers at child's birth and age 7 years. Health behavior-related outcomes were self-reported when participants were of mean age 47 years. Multivariable adjusted robust Poisson regressions were performed. RESULTS: Regardless of level of childhood social disadvantage, we found higher levels of optimism and social support were both associated with higher probabilities of being a non-smoker (relative risk [RR]optimism = 1.17, 95% confidence interval [CI] = 1.09-1.26; RRsocial support = 1.24, 95%CI = 1.11-1.39), having a healthy diet (RRoptimism = 1.25, 95%CI = 1.10-1.43; RRsocial support = 1.27, 95%CI = 1.04-1.56), and a healthy body mass index (RRoptimism = 1.18, 95%CI = 1.00-1.40; RRsocial support = 1.29, 95%CI = 1.00-1.66). Interactions link higher optimism or social support with lower risk of smoking among those with moderate childhood disadvantage. CONCLUSIONS: Overall, these findings are consistent with the possibility that positive psychosocial resources contribute to maintaining a healthy lifestyle in mid-adulthood and may buffer effects of childhood social disadvantage.

Feasibility of Using a Nationally Representative Telephone Survey to Monitor Multiple Sclerosis Prevalence in the United States.

BACKGROUND: Multiple sclerosis (MS) is the most common chronic neurologic disease of young adults, placing a heavy burden on patients, families, and the healthcare system. Ongoing surveillance of the incidence and prevalence of MS is critical for health policy and research, but feasible options are limited in the United States and many other countries. We investigated the feasibility of monitoring the prevalence of MS using a large national telephone survey of the adult US population. METHODS: We developed questions to estimate the lifetime prevalence and age of onset of MS using the US-based Behavioral Risk Factor Surveillance System (BRFSS) and piloted these questions in 4 states (MN, RI, MD, and TX). There was a total of 45,198 respondents aged 18 years and above. Analyses investigated individual state and combined prevalence estimates along with health-related comorbidities and limitations. MS prevalence estimates from the BRFSS were compared to estimates from multi-source administrative claims and traditional population-based methods. RESULTS: The estimated lifetime prevalence of self-reported MS (per 100,000 adults) was 682 (95% CI 528-836); 384 (95% CI 239-529) among males and 957 (95% CI 694-1,220) among females. Estimates were consistent across the 4 states but much higher than recently published estimates using population-based administrative claims data. This was observed for both national results and for MS prevalence estimates from other studies within specific states (MN, RI, and TX). Prevalence estimates for Caucasian, African American, and Hispanic respondents were 824, 741, and 349 per 100,000 respectively. Age and sex distributions were consistent with prior epidemiologic reports. Comorbidity and functional limitations were more pronounced among female than male respondents. CONCLUSIONS: While yielding higher overall MS prevalence estimates compared to recent studies, this large-scale self-report telephone method yielded relative prevalence estimates (e.g., prevalence patterns of MS by sex, age, and race-ethnicity) that were generally comparable to other surveillance approaches. With certain caveats, population-based telephone surveys may eventually offer the ability to investigate novel disease correlates and are relatively feasible, and affordable. Further work is needed to create a valid question set and methodology for case ascertainment before this approach could be adopted to accurately estimate MS prevalence.

Effects of prenatal bacterial infection on cognitive performance in early childhood.

BACKGROUND: Previous epidemiologic studies have reported adverse neurodevelopmental sequelae following prenatal infectious exposure, yet long-term effects estimated from these observational studies are often subject to biases due to confounding and loss to follow-up. OBJECTIVES: We demonstrate the joint use of inverse probability (IP) treatment and censoring weights when evaluating neurotoxic effects of prenatal bacterial infection. METHODS: We applied IP weighting for both treatment and censoring to estimate the effects of maternal bacterial infection during pregnancy on mean intelligence quotient (IQ) scores measured at age 7 using the Wechsler Intelligence Scale for Children. Participants were members of a population-based pregnancy cohort recruited in the Boston and Providence sites of the Collaborative Perinatal Project between 1959 and 1966 (n = 11 984). We calculated average treatment effects (ATE) and average treatment effects on the treated (ATT) using IP weights estimated via generalized boosted models. RESULTS: ATE- and ATT-weighted mean IQ scores were lowest among offspring exposed to multi-systemic bacterial infection during pregnancy and highest for those unexposed. The effects of prenatal bacterial infection were greater among male offspring, particularly on performance IQ scores. Offspring who were exposed to multi-systemic bacterial infection in the third trimester displayed the largest reduction in mean full-scale, verbal, and performance IQ scores at age 7 compared to those unexposed or exposed in earlier trimesters. CONCLUSIONS: We find that prenatal bacterial infection is associated with cognitive impairments at age 7. Associations are strongest for more severe infections, that occur in the third trimester, and among males. Public health intervention targeting bacterial infection in pregnant women may help enhance the cognitive development of offspring.

Maternal Bacterial Infection During Pregnancy and Offspring Risk of Psychotic Disorders: Variation by Severity of Infection and Offspring Sex.

OBJECTIVE: Previous studies suggest that prenatal immune challenges may elevate the risk of schizophrenia and related psychoses in offspring, yet there has been limited research focused on maternal bacterial infection. The authors hypothesized that maternal bacterial infection during pregnancy increases offspring risk of psychotic disorders in adulthood, and that the magnitude of this association varies as a function of severity of infectious exposure and offspring sex. METHODS: The authors analyzed prospectively collected data from 15,421 pregnancies among women enrolled between 1959 and 1966 at two study sites through the Collaborative Perinatal Project. The sample included 116 offspring with confirmed psychotic disorders. The authors estimated associations between maternal bacterial infection during pregnancy and psychosis risk over the subsequent 40 years, stratified by offspring sex and presence of reported parental mental illness, with adjustment for covariates. RESULTS: Maternal bacterial infection during pregnancy was strongly associated with psychosis in offspring (adjusted odds ratio=1.8, 95% CI=1.2-2.7) and varied by severity of infection and offspring sex. The effect of multisystemic bacterial infection (adjusted odds ratio=2.9, 95% CI=1.3-5.9) was nearly twice that of less severe localized bacterial infection (adjusted odds ratio=1.6, 95% CI=1.1-2.3). Males were significantly more likely than females to develop psychosis after maternal exposure to any bacterial infection during pregnancy. CONCLUSIONS: The study findings suggest that maternal bacterial infection during pregnancy is associated with an elevated risk for psychotic disorders in offspring and that the association varies by infection severity and offspring sex. These findings call for additional investigation and, if the findings are replicated, public health and clinical efforts that focus on preventing and managing bacterial infection in pregnant women.

Associations of Trimester-Specific Exposure to Bisphenols with Size at Birth: A Chinese Prenatal Cohort Study.

BACKGROUND: Bisphenol A (BPA) is an endocrine disruptor that affects fetal growth in experimental studies. Bisphenol F (BPF) and bisphenol S (BPS), which have been substituted for BPA in some consumer products, have also shown endocrine-disrupting effects in experimental models. However, the effects of BPF and BPS on fetal growth in humans are unknown. OBJECTIVES: Our goal was to investigate trimester-specific associations of urinary concentrations of BPA, BPF, and BPS with size at birth. METHODS: The present study included 845 pregnant women from Wuhan, China (2013-2015), who provided one urine sample in each of the first, second, and third trimesters. Linear regressions with generalized estimating equations were applied to estimate trimester-specific associations of urinary bisphenol concentrations with birth weight, birth length, and ponderal index. Linear mixed-effects models were used to identify potential critical windows of susceptibility to bisphenols by comparing the exposure patterns of newborns in the 10th percentile of each birth anthropometric measurement to that of those in the 90th percentile. RESULTS: Medians (25th-75th percentiles) of urinary concentrations of BPA, BPF, and BPS were 1.40 (0.19-3.85), 0.65 (0.34-1.39), and 0.38 (0.13-1.11) ng/mL, respectively. Urinary BPA concentrations in different trimesters were inversely, but not significantly, associated with birth weight and ponderal index. Urinary concentrations of BPF and BPS during some trimesters were associated with significantly lower birth weight, birth length, or ponderal index, with significant trend p-values (ptrend<0.05) across quartiles of BPF and BPS concentrations. The observed associations were unchanged after additionally adjusting for other bisphenols. In addition, newborns in the 10th percentile of each birth anthropometry measure had higher BPF and BPS exposures during pregnancy than newborns in the 90th percentile of each outcome. CONCLUSIONS: Prenatal exposure to BPF and BPS was inversely associated with size at birth in this cohort. Replication in other populations is needed. https://doi.org/10.1289/EHP4664.

Impact of the 2017 ACC/AHA Guideline for High Blood Pressure on Evaluating Gestational Hypertension-Associated Risks for Newborns and Mothers.

RATIONALE: In 2017, the American College of Cardiology (ACC)/American Heart Association (AHA) released a new hypertension guideline for nonpregnant adults, using lower blood pressure values to identify hypertension. However, the impact of this new guideline on the diagnosis of gestational hypertension and the associated maternal and neonatal risks are unknown. OBJECTIVE: To estimate the impact of adopting the 2017 ACC/AHA guideline on detecting gestational blood pressure elevations and the relationship with maternal and neonatal risk in the perinatal period using a retrospective cohort design. METHODS AND RESULTS: This study included 16 345 women from China. Systolic and diastolic blood pressures of each woman were measured at up to 22 prenatal care visits across different stages of pregnancy. Logistic and linear regressions were used to estimate associations of blood pressure categories with the risk of preterm delivery, early-term delivery, and small for gestational age, and indicators of maternal liver, renal, and coagulation functions during pregnancy. We identified 4100 (25.1%) women with gestational hypertension using the 2017 ACC/AHA guideline, compared with 4.2% using the former definition. Gestational hypertension, but not elevated blood pressure (subclinical blood pressure elevation), was significantly associated with altered indicators of liver, renal, and coagulation functions during pregnancy for mothers and increased risk of adverse birth outcomes for newborns; adjusted odds ratios (95% CIs) for gestational hypertension stage 2 were 2.23 (1.18-4.24) for preterm delivery, 2.05 (1.67-2.53) for early-term delivery, and 1.43 (1.13-1.81) for small for gestational age. CONCLUSIONS: Adopting the 2017 ACC/AHA guideline would result in a substantial increase in the prevalence of gestational hypertension; subclinical blood pressure elevations during late pregnancy were not associated with increased maternal and neonatal risk in this cohort. Therefore, the 2017 ACC/AHA guideline may improve the detection of high blood pressure during pregnancy and the efforts to reduce maternal and neonatal risk. Replications in other populations are required.