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Importance: In utero exposure to maternal infections has been associated with abnormal neurodevelopment among offspring. The emergence of a new, now endemic infection (SARS-CoV-2) warrants investigating developmental implications for exposed offspring., Objective: To assess whether in utero exposure to maternal COVID-19 is associated with abnormal neurodevelopmental scores among children ages 12, 18, and 24 months., Design, Setting, and Participants: Data were ascertained from the ASPIRE (Assessing the Safety of Pregnancy in the Coronavirus Pandemic) trial, a prospective cohort of pregnant individuals aged 18 years or older who were enrolled before 10 weeks' gestation and their children. Individuals were recruited online from May 14, 2020, to August 23, 2021, using the Society for Assisted Reproductive Technology and BabyCenter, an online media platform. Participants from all 50 states and Puerto Rico completed activities remotely., Exposure: In utero exposure to COVID-19., Main Outcomes and Measures: Birth mothers completed the Ages & Stages Questionnaires, Third Edition, a validated screening tool for developmental delays, at 12, 18, and 24 months' post partum. A score below the cutoff in any domain (communication, gross motor, fine motor, problem-solving, and social skills) was considered an abnormal developmental screen (scores range from 0 to 60 in each domain, with higher scores indicating less risk for neurodevelopmental delay)., Results: The cohort included 2003 pregnant individuals (mean [SD] age, 33.3 [4.2] years) enrolled before 10 weeks' gestation and who completed study activities; 1750 (87.4%) had earned a college degree. Neurodevelopmental outcomes were available for 1757 children at age 12 months, 1522 at age 18 months, and 1523 at age 24 months. The prevalence of abnormal screens for exposed vs unexposed offspring at age 12 months was 64 of 198 (32.3%) vs 458 of 1559 (29.4%); at age 18 months, 36 of 161 (22.4%) vs 279 of 1361 (20.5%); and at age 24 months, 29 of 151 (19.2%) vs 230 of 1372 (16.8%). In an adjusted mixed-effects logistics regression model, no difference in risk of abnormal neurodevelopmental screens was observed at age 12 months (adjusted risk ratio [ARR], 1.07 [95% CI, 0.85-1.34]), age 18 months (ARR, 1.15 [95% CI, 0.84-1.57]), or age 24 months (ARR, 1.01 [95% CI, 0.69-1.48]). Supplemental analyses did not identify differential risk based on trimester of infection, presence vs absence of fever, or breakthrough infection following vaccination vs primary infection., Conclusions and Relevance: In this cohort study of pregnant individuals and offspring, exposure to maternal COVID-19 was not associated with abnormal neurodevelopmental screening results through 24 months' post partum. Continued study of diverse groups of children is needed because, among other factors, evidence suggests sensitivity of the developing fetal brain to maternal immune activation.

Objective: To evaluate the safety and pharmacokinetics of MIV-150 and zinc acetate in a carrageenan gel (PC-1005). Acceptability, adherence, and pharmacodynamics were also explored., Design: A 3-day open-label safety run-in (n = 5) preceded a placebo-controlled, double-blind trial in healthy, HIV-negative, abstinent women randomized (4:1) to vaginally apply 4 mL of PC-1005 or placebo once daily for 14 days., Methods: Assessments included physical examinations, safety labs, colposcopy, biopsies, cervicovaginal lavages (CVLs), and behavioral questionnaires. MIV-150 (plasma, CVL, tissue), zinc (plasma, CVL), and carrageenan (CVL) concentrations were determined with LC-MS/MS, ICP-MS, and ELISA, respectively. CVL antiviral activity was measured using cell-based assays. Safety, acceptability, and adherence were analyzed descriptively. Pharmacokinetic parameters were calculated using noncompartmental techniques and actual sampling times. CVL antiviral EC50 values were calculated using a dose-response inhibition analysis., Results: Participants (n = 20) ranged from 19-44 years old; 52% were black or African American. Among those completing the trial (13/17, PC-1005; 3/3, placebo), 11/17 reported liking the gel overall; 7 recommended reducing the volume. Adverse events, which were primarily mild and/or unrelated, were comparable between groups. Low systemic MIV-150 levels were observed, without accumulation. Plasma zinc levels were unchanged from baseline. Seven of seven CVLs collected 4-hour postdose demonstrated antiviral (HIV, human papillomavirus) activity. High baseline CVL anti-herpes-simplex virus type-2 (HSV-2) activity precluded assessment of postdose activity., Conclusions: PC-1005 used vaginally for 14 days was well tolerated. Low systemic levels of MIV-150 were observed. Plasma zinc levels were unchanged. Postdose CVLs had anti-HIV and anti-human papillomavirus activity. These data warrant further development of PC-1005 for HIV and sexually transmitted infection prevention., Competing Interests: The authors have no conflicts of interest to disclose.

Textbooks are an expression of the state of development of a discipline at a given moment in time. By reviewing eight epidemiology textbooks published over the course of a century, we have attempted to trace the evolution of five epidemiologic concepts and methods: study design (cohort studies and case-control studies), confounding, bias, interaction and causal inference. Overall, these eight textbooks can be grouped into three generations. Greenwood (1935) and Hill (first edition 1937; version reviewed 1961)'s textbooks belong to the first generation, "early epidemiology", which comprise early definitions of bias and confounding. The second generation, "classic epidemiology", represented by the textbooks of Morris (first edition 1957; version reviewed 1964), MacMahon & Pugh (first edition 1960; version reviewed 1970), Susser (1973), and Lilienfeld & Lilienfeld (first edition 1976; version reviewed 1980), clarifies the properties of cohort and case-control study designs and the theory of disease causation. Miettinen (1985) and Rothman (1986)'s textbooks belong to a third generation, "modern epidemiology", presenting an integrated perspective on study designs and their measures of outcome, as well as distinguishing and formalizing the concepts of confounding and interaction. Our review demonstrates that epidemiology, as a scientific discipline, is in constant evolution and transformation. It is likely that new methodological tools, able to assess the complexity of the causes of human health, will be proposed in future generations of textbooks.