Building a growing genomic data repository for maternal and fetal health through the PING Consortium.

Background: Prenatally transmitted viruses can cause severe damage to the developing brain. There is unexplained variability in prenatal brain injury and postnatal neurodevelopmental outcomes, suggesting disease modifiers. Discordant outcomes among dizygotic twins could be explained by genetic susceptibly or protection. Among several well-recognized threats to the developing brain, Zika is a mosquito-borne, positive-stranded RNA virus that was originally isolated in Uganda and spread to cause epidemics in Africa, Asia, and the Americas. In the Americas, the virus caused congenital Zika syndrome and a multitude of neurodevelopmental disorders. As of now, there is no preventative treatment or cure for the adverse outcomes caused by prenatal Zika infection. The Prenatal Infection and Neurodevelopmental Genetics (PING) Consortium was initiated in 2016 to identify factors modulating prenatal brain injury and postnatal neurodevelopmental outcomes for Zika and other prenatal viral infections. Methods: The Consortium has pooled information from eight multi-site studies conducted at 23 research centers in six countries to build a growing clinical and genomic data repository. This repository is being mined to search for modifiers of virally induced brain injury and developmental outcomes. Multilateral partnerships include commitments with Children's National Hospital (USA), Instituto Nacional de Salud (Colombia), the Natural History of Zika Virus Infection in Gestation program (Brazil), and Zika Instituto Fernandes Figueira (Brazil), in addition to the Centers for Disease Control and Prevention and the National Institutes of Health. Discussion: Our goal in bringing together these sets of patient data was to test the hypothesis that personal and populational genetic differences affect the severity of brain injury after a prenatal viral infection and modify neurodevelopmental outcomes. We have enrolled 4,102 mothers and 3,877 infants with 3,063 biological samples and clinical data covering over 80 phenotypic fields and 5,000 variables. There were several notable challenges in bringing together cohorts enrolled in different studies, including variability in the timepoints evaluated and the collected clinical data and biospecimens. Thus far, we have performed whole exome sequencing on 1,226 participants. Here, we present the Consortium's formation and the overarching study design. We began our investigation with prenatal Zika infection with the goal of applying this knowledge to other prenatal infections and exposures that can affect brain development.

Zika virus prevention behaviors and knowledge among male partners of pregnant people and lack of condom use as a prevention behavior from the Zika en Embarazadas y Niños (ZEN) prospective cohort study, Colombia.

OBJECTIVE: Zika virus (ZIKV) infection in pregnancy can cause brain and eye abnormalities and neurodevelopmental sequelae. In the absence of medical countermeasures, behavioral interventions were recommended to prevent mosquito bites and sexual transmission of ZIKV. This report uses data from the Zika en Embarazadas y Niños (ZEN) prospective cohort study in Colombia to describe the knowledge, attitudes, and behaviors (KAB) related to ZIKV prevention in male partners compared to those of their pregnant partners at study enrollment during February 2017-2018. RESULTS: Most male partners reported wearing protective clothing such as long pants (97.6%) and long sleeves (72.8%), as well as covering ankles and feet (89.1%) to prevent ZIKV infection. When comparing the preventive behavior of condom use between male and pregnant partners, 26 pairs (10.0%) both responded that they performed the behavior. Overall, 25.1% of male partners and 18.9% of pregnant people reported any condom use during the three months before enrolling in ZEN. When comparing other preventive behaviors between male and pregnant partners, the behavior which was most frequently reported by both partners was wearing long pants (85.4%), and the least frequently reported by both partners was using condoms after finding out about a partner's pregnancy (3.4%).

Severity of illness by pregnancy status among laboratory-confirmed SARS-CoV-2 infections occurring in reproductive-aged women in Colombia.

BACKGROUND: Multiple studies have described increased risk of severe coronavirus disease (COVID-19) among pregnant women compared to nonpregnant women. The risk in middle-income countries where the distributions of age groups and preexisting conditions may differ is less known. OBJECTIVES: To determine whether pregnant women with SARS-CoV-2 infection are at increased risk for severe COVID-19 compared to nonpregnant women in Colombia. METHODS: We analysed national surveillance data from Colombia, of women aged 15-44 years with laboratory-confirmed infection with SARS-CoV-2 by molecular or antigen testing, from 6 March 2020 to 12 December 2020. An enhanced follow-up of pregnant women with COVID-19 was established to monitor pregnancy and birth outcomes. RESULTS: Of 371,363 women aged 15-44 years with laboratory-confirmed SARS-CoV-2 infection, 1.5% (n = 5614) were reported as pregnant; among those, 2610 (46.5%) were considered a complete pregnancy for reporting purposes at the time of analysis. Hospitalisation (23.9%) and death (1.3%) occurred more frequently among pregnant symptomatic women compared to nonpregnant symptomatic women (2.9% and 0.3%, respectively). Compared to nonpregnant symptomatic women, pregnant symptomatic women were at increased risk of hospitalisation (adjusted risk ratio [RR] 2.19, 95% confidence interval [CI] 2.07, 2.32) and death (RR 1.82, 95% CI 1.60, 2.07), after adjusting for age, type of health insurance and presence of certain underlying medical conditions. Among complete pregnancies, 55 (2.1%) were pregnancy losses, 72 (2.8%) resulted in term low birthweight infants and 375 (14.4%) were preterm deliveries. CONCLUSIONS: Although pregnant women were infrequently reported with laboratory-confirmed SARS-CoV-2 infection, pregnant symptomatic women with COVID-19 were at increased risk for hospitalisation and death compared to nonpregnant symptomatic women. Almost all infections we reported on were third-trimester infections; ongoing follow-up is needed to determine pregnancy outcomes among women infected earlier in pregnancy. Healthcare providers should counsel pregnant women about preventive measures to protect from SARS-CoV-2 infection and when to seek care.

Pregnancy, Birth, Infant, and Early Childhood Neurodevelopmental Outcomes among a Cohort of Women with Symptoms of Zika Virus Disease during Pregnancy in Three Surveillance Sites, Project Vigilancia de Embarazadas con Zika (VEZ), Colombia, 2016-2018.

Project Vigilancia de Embarazadas con Zika (VEZ), an intensified surveillance of pregnant women with symptoms of the Zika virus disease (ZVD) in Colombia, aimed to evaluate the relationship between symptoms of ZVD during pregnancy and adverse pregnancy, birth, and infant outcomes and early childhood neurodevelopmental outcomes. During May-November 2016, pregnant women in three Colombian cities who were reported with symptoms of ZVD to the national surveillance system, or with symptoms of ZVD visiting participating clinics, were enrolled in Project VEZ. Data from maternal and pediatric (up to two years of age) medical records were abstracted. Available maternal specimens were tested for the presence of the Zika virus ribonucleic acid and/or anti-Zika virus immunoglobulin antibodies. Of 1213 enrolled pregnant women with symptoms of ZVD, 1180 had a known pregnancy outcome. Results of the Zika virus laboratory testing were available for 569 (48.2%) pregnancies with a known pregnancy outcome though testing timing varied and was often distal to the timing of symptoms; 254 (21.5% of the whole cohort; 44.6% of those with testing results) were confirmed or presumptive positive for the Zika virus infection. Of pregnancies with a known outcome, 50 (4.2%) fetuses/infants had Zika-associated brain or eye defects, which included microcephaly at birth. Early childhood adverse neurodevelopmental outcomes were more common among those with Zika-associated birth defects than among those without and more common among those with laboratory evidence of a Zika virus infection compared with the full cohort. The proportion of fetuses/infants with any Zika-associated brain or eye defect was consistent with the proportion seen in other studies. Enhancements to Colombia's existing national surveillance enabled the assessment of adverse outcomes associated with ZVD in pregnancy.

Risk Factors for Illness Severity Among Pregnant Women With Confirmed Severe Acute Respiratory Syndrome Coronavirus 2 Infection-Surveillance for Emerging Threats to Mothers and Babies Network, 22 State, Local, and Territorial Health Departments, 29 March 2020-5 March 2021.

BACKGROUND: Pregnant women with coronavirus disease 2019 (COVID-19) are at increased risk for severe illness compared with nonpregnant women. Data to assess risk factors for illness severity among pregnant women with COVID-19 are limited. This study aimed to determine risk factors associated with COVID-19 illness severity among pregnant women with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: Pregnant women with SARS-CoV-2 infection confirmed by molecular testing were reported during 29 March 2020-5 March 2021 through the Surveillance for Emerging Threats to Mothers and Babies Network (SET-NET). Criteria for illness severity (asymptomatic, mild, moderate-to-severe, or critical) were adapted from National Institutes of Health and World Health Organization criteria. Crude and adjusted risk ratios for moderate-to-severe or critical COVID-19 illness were calculated for selected demographic and clinical characteristics. RESULTS: Among 7950 pregnant women with SARS-CoV-2 infection, moderate-to-severe or critical COVID-19 illness was associated with age 25 years and older, healthcare occupation, prepregnancy obesity, chronic lung disease, chronic hypertension, and pregestational diabetes mellitus. Risk of moderate-to-severe or critical illness increased with the number of underlying medical or pregnancy-related conditions. CONCLUSIONS: Older age and having underlying medical conditions were associated with increased risk of moderate-to-severe or critical COVID-19 illness among pregnant women. This information might help pregnant women understand their risk for moderate-to-severe or critical COVID-19 illness and can inform targeted public health messaging.

Documentation of acute change in mental status in nursing homes highlights opportunity to augment infection surveillance criteria.

Acute change in mental status (ACMS), defined by the Confusion Assessment Method, is used to identify infections in nursing home residents. A medical record review revealed that none of 15,276 residents had an ACMS documented. Using the revised McGeer criteria with a possible ACMS definition, we identified 296 residents and 21 additional infections. The use of a possible ACMS definition should be considered for retrospective nursing home infection surveillance.

Preliminary Report of Microcephaly Potentially Associated with Zika Virus Infection During Pregnancy - Colombia, January-November 2016.

In Colombia, approximately 105,000 suspected cases of Zika virus disease (diagnosed based on clinical symptoms, regardless of laboratory confirmation) were reported during August 9, 2015-November 12, 2016, including nearly 20,000 in pregnant women (1,2). Zika virus infection during pregnancy is a known cause of microcephaly and serious congenital brain abnormalities and has been associated with other birth defects related to central nervous system damage (3). Colombia's Instituto Nacional de Salud (INS) maintains national surveillance for birth defects, including microcephaly and other central nervous system defects. This report provides preliminary information on cases of congenital microcephaly identified in Colombia during epidemiologic weeks 5-45 (January 31-November 12) in 2016. During this period, 476 cases of microcephaly were reported, compared with 110 cases reported during the same period in 2015. The temporal association between reported Zika virus infections and the occurrence of microcephaly, with the peak number of reported microcephaly cases occurring approximately 24 weeks after the peak of the Zika virus disease outbreak, provides evidence suggesting that the period of highest risk is during the first trimester of pregnancy and early in the second trimester of pregnancy. Microcephaly prevalence increased more than fourfold overall during the study period, from 2.1 per 10,000 live births in 2015 to 9.6 in 2016. Ongoing population-based birth defects surveillance is essential for monitoring the impact of Zika virus infection during pregnancy on birth defects prevalence and measuring the success in preventing Zika virus infection and its consequences, including microcephaly.