Researching COVID to enhance recovery (RECOVER) pregnancy study: Rationale, objectives and design.

IMPORTANCE: Pregnancy induces unique physiologic changes to the immune response and hormonal changes leading to plausible differences in the risk of developing post-acute sequelae of SARS-CoV-2 (PASC), or Long COVID. Exposure to SARS-CoV-2 during pregnancy may also have long-term ramifications for exposed offspring, and it is critical to evaluate the health outcomes of exposed children. The National Institutes of Health (NIH) Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC aims to evaluate the long-term sequelae of SARS-CoV-2 infection in various populations. RECOVER-Pregnancy was designed specifically to address long-term outcomes in maternal-child dyads. METHODS: RECOVER-Pregnancy cohort is a combined prospective and retrospective cohort that proposes to enroll 2,300 individuals with a pregnancy during the COVID-19 pandemic and their offspring exposed and unexposed in utero, including single and multiple gestations. Enrollment will occur both in person at 27 sites through the Eunice Kennedy Shriver National Institutes of Health Maternal-Fetal Medicine Units Network and remotely through national recruitment by the study team at the University of California San Francisco (UCSF). Adults with and without SARS-CoV-2 infection during pregnancy are eligible for enrollment in the pregnancy cohort and will follow the protocol for RECOVER-Adult including validated screening tools, laboratory analyses and symptom questionnaires followed by more in-depth phenotyping of PASC on a subset of the overall cohort. Offspring exposed and unexposed in utero to SARS-CoV-2 maternal infection will undergo screening tests for neurodevelopment and other health outcomes at 12, 18, 24, 36 and 48 months of age. Blood specimens will be collected at 24 months of age for SARS-CoV-2 antibody testing, storage and anticipated later analyses proposed by RECOVER and other investigators. DISCUSSION: RECOVER-Pregnancy will address whether having SARS-CoV-2 during pregnancy modifies the risk factors, prevalence, and phenotype of PASC. The pregnancy cohort will also establish whether there are increased risks of adverse long-term outcomes among children exposed in utero. CLINICAL TRIALS.GOV IDENTIFIER: Clinical Trial Registration: http://www.clinicaltrials.gov. Unique identifier: NCT05172011.

Researching COVID to enhance recovery (RECOVER) pregnancy study: Rationale, objectives and design.

Importance: Pregnancy induces unique physiologic changes to the immune response and hormonal changes leading to plausible differences in the risk of developing post-acute sequelae of SARS-CoV-2 (PASC), or Long COVID. Exposure to SARS-CoV-2 during pregnancy may also have long-term ramifications for exposed offspring, and it is critical to evaluate the health outcomes of exposed children. The National Institutes of Health (NIH) Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC aims to evaluate the long-term sequelae of SARS-CoV-2 infection in various populations. RECOVER- Pregnancy was designed specifically to address long-term outcomes in maternal-child dyads. Methods: RECOVER-Pregnancy cohort is a combined prospective and retrospective cohort that proposes to enroll 2,300 individuals with a pregnancy during the COVID-19 pandemic and their offspring exposed and unexposed in utero, including single and multiple gestations. Enrollment will occur both in person at 27 sites through the Eunice Kennedy Shriver National Institutes of Health Maternal-Fetal Medicine Units Network and remotely through national recruitment by the study team at the University of California San Francisco (UCSF). Adults with and without SARS-CoV-2 infection during pregnancy are eligible for enrollment in the pregnancy cohort and will follow the protocol for RECOVER-Adult including validated screening tools, laboratory analyses and symptom questionnaires followed by more in-depth phenotyping of PASC on a subset of the overall cohort. Offspring exposed and unexposed in utero to SARS-CoV-2 maternal infection will undergo screening tests for neurodevelopment and other health outcomes at 12, 18, 24, 36 and 48 months of age. Blood specimens will be collected at 24 months of age for SARS-CoV-2 antibody testing, storage and anticipated later analyses proposed by RECOVER and other investigators. Discussion: RECOVER-Pregnancy will address whether having SARS-CoV-2 during pregnancy modifies the risk factors, prevalence, and phenotype of PASC. The pregnancy cohort will also establish whether there are increased risks of adverse long-term outcomes among children exposed in utero. Registration: NCT05172024.

Idiopathic Polyhydramnios: Severity and Perinatal Morbidity.

Objective To estimate the association between the severity of idiopathic polyhydramnios and adverse outcomes. Study Design Retrospective cohort study of deliveries at one hospital from 2000 to 2012 with an amniotic fluid index (AFI) measurement ≥24 + 0 weeks' gestation. Pregnancies complicated by diabetes, multiples, or fetal anomalies were excluded. Exposure was the degree of polyhydramnios: normal (AFI 5-24 cm), mild (≥ 24-30 cm), and moderate-severe (> 30 cm). Primary outcomes were perinatal mortality, neonatal intensive care unit (NICU) admission, and postpartum hemorrhage. Results There were 10,536 pregnancies: 10,188 with a normal AFI, 274 mild (78.74%), and 74 moderate-severe polyhydramnios (21.26%). Adverse outcomes were increased with idiopathic polyhydramnios: NICU admission (adjusted odds ratio [AOR] 3.71, 95% confidence interval [CI] 2.77-4.99), postpartum hemorrhage (AOR 15.81, 95% CI 7.82-31.96), macrosomia (AOR 3.41, 95% CI 2.61-4.47), low 5-minute Apgar score (AOR 2.60, 95% CI 1.57-4.30), and cesarean (AOR 2.16, 95% CI 1.74-2.69). There were increasing odds of macrosomia (mild: AOR 3.19, 95% CI 2.36-4.32; moderate-severe: AOR 4.44, 95% CI 2.53-7.79) and low 5-minute Apgar score (mild: AOR 2.24, 95% CI 1.23-4.08; moderate-severe: AOR 3.93, 95% CI 1.62-9.55) with increasing severity of polyhydramnios. Conclusion Idiopathic polyhydramnios is independently associated with increased risks of morbidity. There appears to be a dose-response relationship for neonatal macrosomia and low 5-minute Apgar score risks.

A single center's experience with noninvasive prenatal testing.

PURPOSE: Massively parallel sequencing to detect fetal aneuploidy has high sensitivity and specificity for the detection of trisomies 21, 18, and 13 in high-risk populations. The purpose of our study was to review our institution's experience with the use of noninvasive prenatal testing for aneuploidy screening. METHODS: This was a descriptive study of patients who had undergone noninvasive prenatal testing between January and September 2012 at the UNC Prenatal Diagnosis unit. RESULTS: Two hundred and eight women had undergone noninvasive prenatal testing during the study period. The majority of patients were white (62.9%) and of advanced maternal age (71.2%). The fetal fraction was below the threshold in three obese patients (1.4%). An abnormal noninvasive prenatal test (aneuploidy detected or "unclassified" result) was reported in 6.3% (13/208) of the patients. Noninvasive prenatal testing had a combined sensitivity of 87.5% and specificity of 99.5% for detection of trisomies 21, 18, and 13. There were "unclassified" results in 11.1% (5/45) of the patients. Over the study period, the number of patients requesting noninvasive prenatal testing increased monthly. The rate of amniocenteses significantly declined (8.1% before vs. 5.3% after noninvasive prenatal testing, P < 0.01). CONCLUSION: An increase in uptake of noninvasive prenatal testing and a significant decline in amniocentesis procedures were observed. The rates of "unclassified," false-positive, and false-negative results were higher than anticipated based on published preclinical trials.

Factors influencing visualization of the intracranial translucency during first-trimester screening for aneuploidy.

OBJECTIVE: Neural tube defects occur in 1/2000 live births. Imaging of the intracranial translucency (IT) during first-trimester screening has been proposed as an early screen for open neural tube defects (ONTD). This study evaluates visualization of the IT and factors influencing its visualization during first-trimester ultrasound screening for aneuploidy. METHODS: Ultrasound images for patients undergoing first-trimester screening for aneuploidy from January 1, 2009, through July 31, 2009, were reviewed for IT visualization, defined as an intracranial translucency parallel to the nuchal translucency. Second-trimester ultrasounds and delivery records were reviewed for the presence of fetal ONTD. RESULTS: The IT was visualized in 74.8% of 759 gestations studied at a mean gestational age of 12 weeks, 5 days. Among gestations where the IT was visualized, we found a larger crown-rump length, lower maternal weight, and more fetuses in the supine position (p < 0.0001). Predictive models for visualization of the IT were formulated based on these factors. CONCLUSION: The IT can be visualized in the majority of patients in the standard midsagittal plane used for measurement of the nuchal translucency. Visualization is significantly associated with crown-rump length, gestational age, maternal weight, and fetal position. Visualization of the IT is feasible.