BACKGROUND:Prenatal cannabis use may be underreported due to social stigma and fear of legal repercussions. The study assesses the validity of self-reported prenatal cannabis use versus urine toxicology measures and determines correlates of non-disclosure. METHODS:Data are from a statewide population-based pregnancy cohort (MARCH- Michigan Archive for Research on Child Health). Participants were recruited at first prenatal visit from 22 clinics in 2017-2023. We calculated sensitivity, specificity, positive predictive values (PPV), negative predictive values (NPV) of self-reported cannabis use using urine toxicology as the criterion standard. RESULTS:606 participants who self-reported cannabis use data within 30 days of urine collection were considered for analysis. Self-reports identified a prevalence of 14.2% for prenatal cannabis use, whereas urinalysis prevalence was 19.1%. Sensitivity, specificity, PPV, and NPV of self-report were 57.8%, 96.1%, 77.9% and 90.6%, respectively. No significant differences were observed between participants who disclosed and those who did not, except for race and ethnicity. The sensitivity of self-reports among Non-Hispanic Blacks was 45.5% compared to 73.0% for their non-Hispanic White counterparts. CONCLUSIONS:Self-reports can underestimate prenatal cannabis use especially among disadvantaged populations. The use of biospecimens to assess cannabis exposure is warranted for reducing misclassification and improving validity in research studies.

Acetaminophen is among the most common over-the-counter medications used during pregnancy. Given inconsistent findings from both experimental and epidemiological studies on associations between use and adverse health outcomes, further research is warranted. To address this, our objective was to assess the relationship between prenatal acetaminophen use and birth outcomes. We studied 8957 mother-infant pairs from 36 pediatric study sites participating in the Environmental influences on Child Health Outcomes (ECHO) program. After imputation and inverse probability weighting, we used regression models to examine the relationship between acetaminophen during pregnancy and the following outcomes: (1) preterm birth, (2) birthweight, (3) small-for-gestational age (SGA), and (4) large-for-gestational-age (LGA). Approximately 59% of mothers reported using acetaminophen at any point during their pregnancy (n = 5257). After adjustment for relevant covariates, prenatal acetaminophen use was associated with lower odds of LGA (adjusted odds ratio [aOR]: 0.87; 95% CI: 0.79, 0.96). Prenatal acetaminophen use was not associated with preterm birth (aOR: 0.99; 95% CI: 0.86, 1.14), birthweight (aβ: -7.52 g; 95% CI: -27.80, 12.77) or SGA (aOR: 1.02; 95% CI: 0.88, 1.18). Based on these findings, future research should test for dose-response, trimester-specific exposures, and factors affecting individual responses.

Firearms are the leading cause of death among children in the United States (US). As of 2023, half of US states had enacted laws allowing permitless concealed carry of firearms. Our cross-sectional study evaluated the association between permitless concealed carry laws and child general health using data from the nationwide Environmental influences on Child Health Outcomes (ECHO) Cohort collected between 2003 and 2023. Children aged 1-21 years with caregiver- or self-reported general health status were included. Secondary outcomes included child internalizing and externalizing behaviors and child stress. Regression models estimated the association of exposure to state-level permitless concealed carry laws six months prior to each outcome, adjusted for individual- and area-level covariates. One-fifth (20.9%) of the sample (n = 11,325) lived in states allowing permitless concealed carry of a handgun. Children living in these states were 25% less likely (OR: 0.75, 95% CI: 0.60, 0.95) to report excellent/very good general health and had psychological stress scores 0.21 standard deviations higher (β = 0.21, 95% CI: 0.10, 0.31) than children in other states. There was no statistically significant association with internalizing or externalizing behavior scores. Our study found that children living in states that allow permitless concealed carry of firearms had worse general health and higher stress, suggesting the need for policy changes to address gun violence as a public health and human rights crisis.

Better understanding racial disparities observed during the COVID-19 pandemic can be aided by SARS-CoV-2 serology testing. However, racial minorities may be underrepresented in serosurveillance efforts not only due to lack of testing accessibility, but also due to hesitancy towards participating in antibody testing programs stemming from medical mistrust. We designed a randomized control trial to evaluate how non-invasive salivary antibody testing and culturally targeted communication might be used to promote racial equity in uptake of SARS-CoV-2 serology testing during the COVID-19 pandemic. To evaluate these approaches, we recruited African American and White American participants from Flint, Michigan. Participants viewed a novel, animated didactic video about SARS-CoV-2 antibody testing, with half of African Americans viewing a culturally targeted version. We measured cognitive and affective responses that indicated receptivity to SARS-CoV-2 serology testing. We also provided a non-invasive salivary antibody screening opportunity, and we measured screening uptake as a behavioral outcome. Finally, we measured baseline sociodemographic, psychological, and health factors that could affect these responses. In addition to evaluating health communication approaches, multiplex SARS-CoV-2 antibody profiles can be subsequently linked to prescreen measures, and to inflammatory markers that were concomitantly measured in whole saliva. Ultimately, we aim to reduce COVID-19 racial disparities and bolster future pandemic preparedness through promoting equity in understanding and uptake of serology testing.

AIMS:To estimate the prevalence of prenatal cannabis use in Michigan, USA, using self-reports and urine toxicology and to examine factors associated with use. DESIGN:Observational study using data from the Michigan Archive for Research on Child Health (MARCH) cohort, part of the National Institutes of Health's Environmental influences on Child Health Outcomes (ECHO) program. It is a prospective statewide pregnancy cohort recruited in 2017-2023 using births as a sampling frame. SETTING:A three-stage stratified cluster sample design that randomly selected hospitals, prenatal clinics and mothers across the lower peninsula of Michigan, where 97% of Michigan hospital births take place. PARTICIPANTS:Pregnant individuals recruited at their first prenatal visit primarily from 20 clinics serving 11 hospitals. Of 1105 eligible pregnant participants, 1092 (98.8%) had information on cannabis use either from self-reports (n = 999), urine toxicology (n = 1028) or both (n = 945). Study participants had a median age of 29.3 years (interquartile range = 7.6). MEASUREMENTS:Cannabis use was self-reported by interviewer-administered phone surveys twice during pregnancy and further ascertained by measuring tetrahydrocannabinol (THC) metabolites in up to two urine samples collected during pregnancy. The prevalence of cannabis use was estimated using sampling weights and clustering by sampled hospital to account for the complex survey design. FINDINGS:The weighted prevalence of prenatal cannabis use was 16.8% [95% confidence interval (CI) = 8.0%-25.7%] based on either self-report or urinalysis. Prevalence based on self-report alone was 12.3% (95% CI = 6.1%-18.6%) and from urinalysis alone was 13.3% (95% CI = 5.1%-21.6%). Adjusted for creatinine concentrations, levels of 11-nor-9-carboxy-tetrahydrocannabinol (THC-COOH) in positive samples ranged from 5.43 to 4694.89 ng/mg with a median of 122.00 ng/mg. Multivariate analysis revealed that participants who were single [adjusted prevalence rate ratio (aPRR) = 2.08, 95% CI = 1.15-3.78], had lower educational attainment (aPRR = 3.76, 95% CI = 1.23-11.53 for some college education and aPRR = 3.15, 95% CI = 0.97-10.25 for high school education as compared with undergraduate education or above), reported symptoms of depression (aPRR = 1.72, 95% CI = 1.19-2.48) and had a history of adverse childhood events (ACEs; aPRR = 2.04, 95% CI = 1.21-3.45 for ACEs ≥ 3 and aPRR = 1.64, 95% CI = 1.07-2.52 for 1-2 ACEs as compared to 0 ACEs) were more likely to use cannabis prenatally. CONCLUSIONS:Cannabis use is estimated to have occurred in one of six pregnancies in a population-based sample in Michigan, USA.

In contrast to therapy in oncology and immune-related diseases, where dozens of monoclonal antibodies (mAbs) have been introduced, often in transformative fashion, the use of mAbs for infectious diseases is generally underdeveloped, with fewer than a dozen mAbs currently licensed for the treatment of microbial diseases. This situation is paradoxical given that antibodies are major products of the immune system for protecting against infectious diseases. The underdevelopment of mAbs for infectious diseases has several causes including the availability of effective therapy against many microbial diseases, the fact that many pathogenic microbes are antigenically diverse and thus all strains are not covered by a single mAb, and the high expense of mAb therapies. Despite these hurdles the number of mAbs licensed for infectious disease indications is slowly increasing and there are numerous opportunities for the development of mAbs in the prevention and treatment of microbial diseases.

PURPOSE:The vaginal microbiome is dynamic, typically shifting during pregnancy toward enrichment of Lactobacillus. However, proliferation of Lactobacillus may be absent among women with preterm births (PTBs). We sought to identify robust vaginal microbiota signatures along with host factors that predicted PTB across diverse U.S. cohorts. METHODS:We meta-analyzed 16S rRNA gene amplicon sequence data from the Environmental influences on Child Health Outcomes Cohort. We classified community state types (CSTs) and employed penalized logistic regression models to assess the association between vaginal CST and PTB. We generated supervised random forest models and validated them using a train-and-test approach to identify the most predictive vaginal taxa and host factors. RESULTS:Of 683 births, 12 % were preterm. Overall, 26 % had a non- L. iners Lactobacillus-dominant CST (I, II, V), 43 % had a L. iners-dominant CST (III), and 30 % had a diverse, non-Lactobacillus-dominant (IV-B, IV-C) CST. Vaginal CST was strongly associated with PTB (adjusted odds ratio [aOR], 3.86, 95 % confidence interval [CI], 1.57-11.3 for diverse, non-Lactobacillus-dominant communities and aOR, 3.03, 95 % CI, 1.25-8.78 for L. iners-dominant compared to L. crispatus-dominant communities). The model with the highest area under the curve (AUC=.77) included Gardnerella vaginalis, age, Prevotella timonensis, and L. crispatus. CONCLUSIONS:Along with host factors, vaginal microbiota could be used for predictive risk scoring for PTB across different U.S. cohorts.

BACKGROUND:Maternal thyroid dysfunction and maternal depression during pregnancy may increase the risk of child behavioral and emotional problems. We sought to investigate the independent and interactive associations of these two risk factors with child behavior problems. METHODS:We combined data from four cohorts in the Environmental influences on Child Health Outcomes (ECHO) program (N = 949). Maternal thyroid function (thyroid-stimulating hormone [TSH], free thyroxine [fT4], thyroid peroxidase autoantibodies [TPO-Ab], fT4/TSH ratio) was measured predominantly during the first half of pregnancy. We harmonized maternal depression into a continuous measure of antepartum depressive symptomatology and a dichotomous measure reflecting (history of) clinical depression. Child internalizing and externalizing problems were harmonized to the T-score metric of the Child Behavior Checklist. We used multiple linear regression and random effects meta-analysis to assess the average relationship between each predictor and outcome, and the variability in these relationships across cohorts. RESULTS:Across cohorts, antepartum depressive symptomatology was positively associated with both internalizing (meta B = 2.879, 95 % CI 1.87-3.89, p < .001) and externalizing problems (meta B = 1.683, 95 % CI 0.67-2.69, p = .001). None of the indicators of maternal thyroid function was associated with child behavior problems across cohorts. TPO-Ab concentrations were positively associated with child externalizing problems only in offspring of depressed mothers (meta B = 3.063, 95 % CI 0.73-5.40, p = .010). CONCLUSIONS:This study supports the importance of maternal antepartum mental health for child behavior across diverse populations. However, we found little empirical evidence for an association between maternal thyroid function within the normal range during pregnancy and child behavioral problems.

The twenty-first century has witnessed seven human viral pandemics. Approximately once every three to four years over the past quarter-century, the world has experienced a new viral epidemic that expanded well beyond its original national borders to become a pandemic. The probability that another pandemic caused by a previously unknown agent will occur in the near future is thus very high and public health agencies must prioritize mechanisms for detecting their first signals. At the onset of these recent pandemics, no specific therapeutic agent was available for any of the newly emergent pathogens. However, convalescent plasma therapy can be available as soon as there are survivors and is likely to be effective if used early and in sufficient strength. But for the three forms of passive antibody-convalescent plasma, monoclonal antibodies, and hyperimmune globulins-to be available and effective in a pandemic situation, careful strategic planning will be necessary. In the pre-pandemic period, we must reinforce the capacities of blood banks and plasma fractionating companies in the production and storage of their products; ensure that outpatient settings can provide intravenous products; educate providers in the proper use of plasma; and create a research infrastructure to examine the effectiveness of passive antibody products. Once a pandemic is underway, regulatory bodies should simplify the approval of research and emergency use protocols and develop treatment registries. Incentives for the rapid production of monoclonal antibodies and hyperimmune globulins will likely be required. A national resource to link providers with passive antibody products and national databases to monitor pandemic progress and pandemic treatment will permit the most effective allocation of pandemic-fighting resources. We cannot afford to wait until the next pandemic is upon us to respond. The time to strengthen clinical, research, and manufacturing infrastructure to permit us to be ready to confront the next new virulent pathogen is now.

This volume takes a broad overview of antibody-based therapies prior to and during the COVID pandemic and examines their potential use in future pandemics. Passive antibody therapy was the first effective antimicrobial treatment and its development in the early twentieth century helped catalyze immunological and microbiological research. During the era of serum therapy (1890-1940) antibody-based therapies were developed against both viral and bacterial diseases. Effective treatment required an understanding of how to quantify antibodies, how to develop serotype-specific sera and recognition of the need to treat early in disease. Thus, although the era of serum therapy essentially ended with the development of small molecule antimicrobial therapy in the 1940s, antibody-based therapies led to important new scientific understanding, while remaining in use for some toxin and venom-caused diseases and in the prevention of outbreaks of viral hepatitis. A renewed interest in antibody-based therapies was seen in the widespread deployment of convalescent plasma and monoclonal antibodies during the COVID-19 pandemic. Convalescent plasma will likely be the first specific therapy during outbreaks with new pathogens for which there is no other therapy. For all forms of antibody-based therapies, effectiveness relies on the key principles of antibody therapy, namely, treatment early in disease with preparations containing sufficient antibody specific to the microbe in question.

The Michigan Archive for Research on Child Health study produced a probability sample of Michigan births between 2017 and 2023, with data collection beginning at first prenatal visit and continuing up to age 4. Birth certificate data were used to create a sampling frame of hospitals and associated obstetric clinics, from which a probability-proportional-size sample of 10 hospitals was drawn. Close to 100 pregnancies were then recruited in clinics serving each sampled hospital, yielding a probability sample of 1021 births. This sample was supplemented with 109 births from a certainty selection of a Flint, MI hospital, for a total sample of 1130. The resulting response rate was high, with 100% of sampled hospitals and 65% of sampled clinics participating. Comparing the resulting sample with all 2017-2023 Michigan births showed close correspondence with respect to birth outcomes (birthweight, gestational age, Apgar scores, gestational diabetes) and mothers' demographics (age, race, education, marital status), with underrepresentation of Hispanic ethnicity and overrepresentation of reported smoking. Given the recent failures of two major prospective birth cohorts (the US National Childrens' Study and the UK Life Study), our work shows a way forward for representative pre- and post-natal studies of births.

This commentary is on the original article by Reid et al. on pages 1582–1589 of this issue.

The use of the serum or plasma of patients or animals who have recovered from an infectious disease, or had been immunized with a relevant antigen, to treat or prevent the same infection in others began in the late 1880s when French and German scientists uncovered, one step at a time, several of the elements of the immune system's response to infection. A key finding was that the damage caused by some bacteria depends upon their secreted toxins which can be neutralized by biologic agents. Antitoxins to diphtheria and tetanus began to be manufactured in large animals in France, Germany, and the US in the 1890s and were soon being used worldwide. The impact of diphtheria antitoxin on childhood mortality was profound. Shortly after the development of antitoxins, convalescent serum began to be used for its anti-bactericidal properties thus addressing serious infections caused by non-toxin-producing organisms. The effectiveness of antitoxins and antisera was demonstrated by examining mortality rates in hospitals before and after the introduction of antitoxins, by comparisons of treated and untreated patients, by comparing early and late treatment and dosage, by examining vital data mortality trends, and by several randomized and alternate assignment trials. Antitoxins continue to have a role in the rare cases of diphtheria and other conditions largely eradicated by immunization, but serum therapy nearly disappeared from the medical armamentarium with the development of antibiotics in the 1940s. Inasmuch as new human pathogens are now emerging with unprecedented regularity as seen in the recent COVID-19 pandemic, and because specific therapies are unlikely to be available for them, plasma-based antibody therapies are likely to again carve out a niche in infectious disease control.

OBJECTIVES Breastfeeding practices may protect against offspring obesity, but this relationship is understudied among women with obesity. We describe the associations between breastfeeding practices and child BMI for age z-score (BMIz), stratified by maternal BMI. METHODS We analyzed 8134 dyads from 21 cohorts in the Environmental Influences on Child Health Outcomes Program. Dyads with data for maternal pre-pregnancy BMI, infant feeding practices, and ≥1 child BMI assessment between the ages of 2 and 6 years were included. The associations between breastfeeding practices and continuous child BMIz were assessed by using multivariable linear mixed models. RESULTS Maternal pre-pregnancy BMI category prevalence was underweight: 2.5%, healthy weight: 45.8%, overweight: 26.0%, and obese: 25.6%. Median child ages at the cessation of any breastfeeding and exclusive breastfeeding across the 4 BMI categories were 19, 26, 24, and 17 weeks and 12, 20, 17, and 12 weeks, respectively. Results were in the hypothesized directions for BMI categories. Three months of any breastfeeding was associated with a lower BMIz among children whose mothers were a healthy weight (−0.02 [−0.04 to 0.001], P = .06), overweight (−0.04 [−0.07 to −0.004], P = .03), or obese (−0.04 [−0.07 to −0.006], P = .02). Three months of exclusive breastfeeding was associated with a lower BMIz among children whose mothers were a healthy weight (−0.06 [−0.10 to −0.02], P = .002), overweight (−0.05 [−0.10 to 0.005], P = .07), or obese (−0.08 [−0.12 to −0.03], P = .001). CONCLUSIONS Human milk exposure, regardless of maternal BMI category, was associated with a lower child BMIz in the Environmental Influences on Child Health Outcomes cohorts, supporting breastfeeding recommendations as a potential strategy for decreasing the risk of offspring obesity.

A major challenge in epidemiology is knowing when an exposure effect is large enough to be clinically important, in particular how to interpret a difference in mean outcome in unexposed/exposed groups. Where it can be calculated, the proportion/percentage beyond a suitable cut-point is useful in defining individuals at high risk to give a more meaningful outcome. In this simulation study we compute differences in outcome means and proportions that arise from hypothetical small effects in vulnerable sub-populations. Data from over 28,000 mother/child pairs belonging to the Environmental influences on Child Health Outcomes Program were used to examine the impact of hypothetical environmental exposures on mean birthweight, and low birthweight (LBW) (birthweight < 2500g). We computed mean birthweight in unexposed/exposed groups by sociodemographic categories (maternal education, health insurance, race, ethnicity) using a range of hypothetical exposure effect sizes. We compared the difference in mean birthweight and the percentage LBW, calculated using a distributional approach. When the hypothetical mean exposure effect was fixed (at 50, 125, 167 or 250g), the absolute difference in

Background: Physical activity and sedentary behavior may differentially impact health-related quality of life in adults with cerebral palsy. Objective: The present investigation assessed the independent relationships between aspects of physical activity and sedentary behavior related to health related quality of life in adults with cerebral palsy. Methods: Through a cross-sectional online survey of 118 adults with cerebral palsy, participants self-reported the extent of their functional impairments using the Gross Motor Function Classification System, Manual Ability Classification System, and Communication Function Classification System; while mental and physical health-related quality of life were assessed using the RAND-36. Physical activity and sedentary behavior were quantified using the Physical Activity and Disability Survey-Revised and Sedentary Behavior Questionnaire, respectively. Results: Accounting for potential confounding influences of impairments, neither exercise-related physical activity, leisure time- related physical activity, occupational physical activity, nor sedentary behavior was associated with any characterization of health-related quality of life. However, greater engagement in general lifestyle physical activity was related to superior mental health-related quality of life. Conclusion: These findings provide initial evidence to suggest that focusing public health and therapeutic recommendations for individuals with cerebral palsy on general physical activity engagement throughout the day might incur potential benefits for enhancing mental health- related quality of life in this population.

In the Spring of 2020, the United States of America (USA) deployed COVID-19 convalescent plasma (CCP) to treat hospitalized patients. Over 500,000 patients were treated with CCP during the first year of the pandemic. In this study, we estimated the number of actual inpatient lives saved by CCP treatment in the United States of America based on CCP weekly use, weekly national mortality data, and CCP mortality reduction data from meta-analyses of randomized controlled trials and real-world data. We also estimate the potential number of lives saved if CCP had been deployed for 100% of hospitalized patients or used in 15 to 75% of outpatients. Depending on the assumptions modeled in stratified analyses, we estimated that CCP saved between 16,476 and 66,296 lives. The CCP ideal use might have saved as many as 234,869 lives and prevented 1,136,133 hospitalizations. CCP deployment was a successful strategy for ameliorating the impact of the COVID-19 pandemic in the USA. This experience has important implications for convalescent plasma use in future infectious disease emergencies.

Population-level study of pregnancy and infancy, including the monitoring of its several key mortality rates (maternal, infant, perinatal) is an important contributor to the ongoing success of perinatal medical care. Sharp declines in US infant mortality began in the 1960's and persisted into the 1990's, with a slower rate of decline since then. While mortality has declined, there has been little improvement in the key drivers of infant mortality over this period – preterm birth and congenital malformations – attesting to the impact of newborn intensive care in reducing mortality in high risk newborns. A high prevalence of disability is found in survivors of newborn intensive care, although recently developed interventions in labor and the newborn period may ameliorate this risk in some situations. Two notable preventive interventions developed in recent decades have been the encouragement of back and side sleeping to reduce the risk of sudden infant death syndrome, and periconceptional folate supplementation to reduce the risk of neural tube defects.