Background: A growing body of evidence suggests that SARS-COV-2 infection during pregnancy may affect maternal-fetal outcomes and possibly result in implications for the long-term development of SARS-CoV-2–exposed children. Objective: The PROUDEST (Pregnancy Outcomes and Child Development Effects of SARS-CoV-2 Infection Study) is a multicenter, prospective cohort study designed to elucidate the repercussions of COVID-19 for the global health of mothers and their children. Methods: The PROUDEST trial comprises 2 prospective, sequential substudies. The PREGNANT substudy will clinically assess the effects of SARS-CoV-2 infection on pregnancy, childbirth, and puerperium from a mechanistic standpoint to elucidate the pregnancy-related inflammatory and immunological phenomena underlying COVID-19. Pregnant women aged 18-40 years who have been exposed (proven with laboratory tests) to SARS-CoV-2 (group A; n=300) will be compared to control subjects with no laboratory evidence of in-pregnancy exposure to the virus (group B; n=300). Subjects exposed to other infections during pregnancy will be excluded. The BORN substudy is a long-term follow-up study that will assess the offspring of women who enrolled in the prior substudy. It will describe the effects of SARS-CoV-2 exposure during pregnancy on children’s growth, neurodevelopment, and metabolism from birth up to 5 years of age. It includes two comparison groups; group A (exposed; n=300) comprises children born from SARS-CoV-2–exposed pregnancies, and group B (controls; n=300) comprises children born from nonexposed mothers. Results: Recruitment began in July 2020, and as of January 2021, 260 pregnant women who were infected with SARS-CoV-2 during pregnancy and 160 newborns have been included in the study. Data analysis is scheduled to start after all data are collected. Conclusions: Upon completion of the study, we expect to have comprehensive data that will provide a better understanding of the effects of SARS-CoV-2 infection and related inflammatory and immunological processes on pregnancy, puerperium, and infancy. Our findings will inform clinical decisions regarding the care of SARS-CoV-2–exposed mothers and children and support the development of evidence-based public health policies. Trial Registration: Brazilian Register of Clinical Trials RBR65QXS2; https://ensaiosclinicos.gov.br/rg/RBR-65qxs2 International Registered Report Identifier (IRRID): DERR1-10.2196/26477

Introduction: Little is known about the effects of intrauterine exposure to SARS-CoV-2, especially on growth and neurodevelopment in children. Objective: We wished to verify the effect of intrauterine exposure to SARS-CoV-2 on neurological development in children. Methods: Infants born to mothers presenting with SARS-CoV-2 infection during pregnancy were enrolled in a prospective descriptive–analytical study involving outpatient appointments performed 6 and 12 months after birth. Their neurological development was assessed using the Bayley-III Scale, using a score of >85 as the cutoff threshold for identifying developmental delay. Differences between groups were assessed through an ANOVA, using Bonferroni correction for multiple comparisons. Regression models were employed to examine the associations between the Bayley-III scores and maternal features. Results: Two hundred and sixty-nine infants were evaluated, most of whom were born full-term and with birth weights appropriate for gestational age at delivery. Developmental delays were observed in 26% of the infants in at least one of the Bayley-III domains. The language domain was particularly affected, with impairments observed in children exposed to SARS-CoV-2 closer to the time of delivery. These findings were statistically significant (p < 0.05). Conclusions: Infants born to mothers presenting with SARS-CoV-2 infection during pregnancy presented developmental delays at 6 and 12 months, particularly in the language domain. These findings reinforce the relevance of long-term clinical follow-ups of newborns exposed to SARS-CoV-2 infection during pregnancy.