Adverse maternal, fetal, and newborn outcomes among pregnant women with SARS-CoV-2 infection: an individual participant data meta-analysis.

INTRODUCTION: Despite a growing body of research on the risks of SARS-CoV-2 infection during pregnancy, there is continued controversy given heterogeneity in the quality and design of published studies. METHODS: We screened ongoing studies in our sequential, prospective meta-analysis. We pooled individual participant data to estimate the absolute and relative risk (RR) of adverse outcomes among pregnant women with SARS-CoV-2 infection, compared with confirmed negative pregnancies. We evaluated the risk of bias using a modified Newcastle-Ottawa Scale. RESULTS: We screened 137 studies and included 12 studies in 12 countries involving 13 136 pregnant women.Pregnant women with SARS-CoV-2 infection-as compared with uninfected pregnant women-were at significantly increased risk of maternal mortality (10 studies; n=1490; RR 7.68, 95% CI 1.70 to 34.61); admission to intensive care unit (8 studies; n=6660; RR 3.81, 95% CI 2.03 to 7.17); receiving mechanical ventilation (7 studies; n=4887; RR 15.23, 95% CI 4.32 to 53.71); receiving any critical care (7 studies; n=4735; RR 5.48, 95% CI 2.57 to 11.72); and being diagnosed with pneumonia (6 studies; n=4573; RR 23.46, 95% CI 3.03 to 181.39) and thromboembolic disease (8 studies; n=5146; RR 5.50, 95% CI 1.12 to 27.12).Neonates born to women with SARS-CoV-2 infection were more likely to be admitted to a neonatal care unit after birth (7 studies; n=7637; RR 1.86, 95% CI 1.12 to 3.08); be born preterm (7 studies; n=6233; RR 1.71, 95% CI 1.28 to 2.29) or moderately preterm (7 studies; n=6071; RR 2.92, 95% CI 1.88 to 4.54); and to be born low birth weight (12 studies; n=11 930; RR 1.19, 95% CI 1.02 to 1.40). Infection was not linked to stillbirth. Studies were generally at low or moderate risk of bias. CONCLUSIONS: This analysis indicates that SARS-CoV-2 infection at any time during pregnancy increases the risk of maternal death, severe maternal morbidities and neonatal morbidity, but not stillbirth or intrauterine growth restriction. As more data become available, we will update these findings per the published protocol.

Protocol for a sequential, prospective meta-analysis to describe coronavirus disease 2019 (COVID-19) in the pregnancy and postpartum periods.

We urgently need answers to basic epidemiological questions regarding SARS-CoV-2 infection in pregnant and postpartum women and its effect on their newborns. While many national registries, health facilities, and research groups are collecting relevant data, we need a collaborative and methodologically rigorous approach to better combine these data and address knowledge gaps, especially those related to rare outcomes. We propose that using a sequential, prospective meta-analysis (PMA) is the best approach to generate data for policy- and practice-oriented guidelines. As the pandemic evolves, additional studies identified retrospectively by the steering committee or through living systematic reviews will be invited to participate in this PMA. Investigators can contribute to the PMA by either submitting individual patient data or running standardized code to generate aggregate data estimates. For the primary analysis, we will pool data using two-stage meta-analysis methods. The meta-analyses will be updated as additional data accrue in each contributing study and as additional studies meet study-specific time or data accrual thresholds for sharing. At the time of publication, investigators of 25 studies, including more than 76,000 pregnancies, in 41 countries had agreed to share data for this analysis. Among the included studies, 12 have a contemporaneous comparison group of pregnancies without COVID-19, and four studies include a comparison group of non-pregnant women of reproductive age with COVID-19. Protocols and updates will be maintained publicly. Results will be shared with key stakeholders, including the World Health Organization (WHO) Maternal, Newborn, Child, and Adolescent Health (MNCAH) Research Working Group. Data contributors will share results with local stakeholders. Scientific publications will be published in open-access journals on an ongoing basis.

Application of a new protocol for providing obstetric care in an outpatient service during the COVID-19 pandemic in a public hospital in Madrid, Spain

Objective To evaluate the clinical implementation of a preventive COVID-19 protocol regarding re-organization of appointments and documented infections among health workers in an obstetric outpatient service. Methods Descriptive analysis of the antenatal care at our obstetric outpatient service and infection rates among health care providers from March 19th to May 22nd, 2020. Appointments were divided into telephone calls or face-to-face examinations. A pre-consultation triage was implemented to identify suspected SARS-CoV2 infected women to reschedule them 14 days later or, if the consultation was non-delayable, to use complete Personal Protective Equipment (PPE). Firstly, the number of face-to-face appointments, telephone appointments, and COVID-19 diagnoses in pregnant women were analyzed. Secondly, the number of obstetricians and nurses diagnosed with SARS-CoV2 infection and their serologic status during universal screening in May 2020 were recorded. Results One thousand eight hundred forty-two obstetric appointments were scheduled during this period, including 432 (23.5%) telephone appointments (96.53% according to clinical protocol, 1.62% symptomatic patients advised to stay at home, and 1.85% COVID-19 confirmed cases), and 1,410 (76.5%) face-to-face appointments (9.7% did not attend due to fear of getting the infection, 3.1% were lost-to-follow-up, 0.5% were rescheduled due to COVID-19 symptoms and 86.7% who did attend). Of the 1,223 women attending their hospital appointment, 3.6% screened positive at the triage (72.7% rescheduled and 27.3% seen with PPE). 43 rRT-PCR-SARS-CoV2 tests were performed, and two tested positive. No COVID-19 symptoms were reported among health workers at the outpatient obstetric service, and only one nurse presented immunoglobulin (Ig)G anti-SARS-CoV2. Conclusion A prompt implementation of a preventive protocol in a hospital obstetric outpatient service, including triage, hygienic and preventive measurements, and rescheduling pregnancy appointments, reduces the percentage of health workers affected by SARS-CoV2.

Congenital infection of SARS-CoV-2 in live-born neonates: a population-based descriptive study.

OBJECTIVE: To evaluate the evidence of mother-to-child transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: This is a descriptive, multicentre, observational study in nine tertiary care hospitals throughout Spain. The study population was women with coronavirus disease 2019 during pregnancy. Mother-to-child transmission was defined as positive real-time RT-PCR of SARS-CoV-2 in amniotic fluid, cord blood, placenta or neonatal nasopharyngeal swabs taken immediately after birth. RESULTS: We included 43 women with singleton pregnancies and one with a twin pregnancy, as a result we obtained 45 samples of placenta, amniotic fluid and umbilical cord blood. The median gestational age at diagnosis was 34.7 weeks (range 14-41.3 weeks). The median interval between positive RT-PCR and delivery was 21.5 days (range 0-141 days). Fourteen women (31.8%, 95% CI 18.6%-47.6%) were positive at the time of delivery. There was one singleton pregnancy with SARS-CoV-2 RT-PCR positive in the placenta, amniotic fluid and umbilical cord blood (2.2%, 95% CI 0.1%-11.8%). Nasopharyngeal aspiration was performed on 38 neonates at birth, all of which were negative (0%, 95% CI 0%-9.3%). In 11 neonates the nasopharyngeal aspiration was repeated at 24-48 hours, and one returned positive (9.1%, 95% CI 0.2%-41.3%). CONCLUSIONS: The presence of SARS-CoV-2 in placenta, amniotic fluid and cord blood shows that mother-to-child transmission is possible but uncommon.

Pregnancy Outcomes and SARS-CoV-2 Infection: The Spanish Obstetric Emergency Group Study.

Pregnant women who are infected with SARS-CoV-2 are at an increased risk of adverse perinatal outcomes. With this study, we aimed to better understand the relationship between maternal infection and perinatal outcomes, especially preterm births, and the underlying medical and interventionist factors. This was a prospective observational study carried out in 78 centers (Spanish Obstetric Emergency Group) with a cohort of 1347 SARS-CoV-2 PCR-positive pregnant women registered consecutively between 26 February and 5 November 2020, and a concurrent sample of PCR-negative mothers. The patients' information was collected from their medical records, and the association of SARS-CoV-2 and perinatal outcomes was evaluated by univariable and multivariate analyses. The data from 1347 SARS-CoV-2-positive pregnancies were compared with those from 1607 SARS-CoV-2-negative pregnancies. Differences were observed between both groups in premature rupture of membranes (15.5% vs. 11.1%, p < 0.001); venous thrombotic events (1.5% vs. 0.2%, p < 0.001); and severe pre-eclampsia incidence (40.6 vs. 15.6%, p = 0.001), which could have been overestimated in the infected cohort due to the shared analytical signs between this hypertensive disorder and COVID-19. In addition, more preterm deliveries were observed in infected patients (11.1% vs. 5.8%, p < 0.001) mainly due to an increase in iatrogenic preterm births. The prematurity in SARS-CoV-2-affected pregnancies results from a predisposition to end the pregnancy because of maternal disease (pneumonia and pre-eclampsia, with or without COVID-19 symptoms).