Preeclampsia and COVID-19: results from the INTERCOVID prospective longitudinal study.

BACKGROUND: It is unclear whether the suggested link between COVID-19 during pregnancy and preeclampsia is an independent association or if these are caused by common risk factors. OBJECTIVE: This study aimed to quantify any independent association between COVID-19 during pregnancy and preeclampsia and to determine the effect of these variables on maternal and neonatal morbidity and mortality. STUDY DESIGN: This was a large, longitudinal, prospective, unmatched diagnosed and not-diagnosed observational study assessing the effect of COVID-19 during pregnancy on mothers and neonates. Two consecutive not-diagnosed women were concomitantly enrolled immediately after each diagnosed woman was identified, at any stage during pregnancy or delivery, and at the same level of care to minimize bias. Women and neonates were followed until hospital discharge using the standardized INTERGROWTH-21st protocols and electronic data management system. A total of 43 institutions in 18 countries contributed to the study sample. The independent association between the 2 entities was quantified with the risk factors known to be associated with preeclampsia analyzed in each group. The outcomes were compared among women with COVID-19 alone, preeclampsia alone, both conditions, and those without either of the 2 conditions. RESULTS: We enrolled 2184 pregnant women; of these, 725 (33.2%) were enrolled in the COVID-19 diagnosed and 1459 (66.8%) in the COVID-19 not-diagnosed groups. Of these women, 123 had preeclampsia of which 59 of 725 (8.1%) were in the COVID-19 diagnosed group and 64 of 1459 (4.4%) were in the not-diagnosed group (risk ratio, 1.86; 95% confidence interval, 1.32-2.61). After adjustment for sociodemographic factors and conditions associated with both COVID-19 and preeclampsia, the risk ratio for preeclampsia remained significant among all women (risk ratio, 1.77; 95% confidence interval, 1.25-2.52) and nulliparous women specifically (risk ratio, 1.89; 95% confidence interval, 1.17-3.05). There was a trend but no statistical significance among parous women (risk ratio, 1.64; 95% confidence interval, 0.99-2.73). The risk ratio for preterm birth for all women diagnosed with COVID-19 and preeclampsia was 4.05 (95% confidence interval, 2.99-5.49) and 6.26 (95% confidence interval, 4.35-9.00) for nulliparous women. Compared with women with neither condition diagnosed, the composite adverse perinatal outcome showed a stepwise increase in the risk ratio for COVID-19 without preeclampsia, preeclampsia without COVID-19, and COVID-19 with preeclampsia (risk ratio, 2.16; 95% confidence interval, 1.63-2.86; risk ratio, 2.53; 95% confidence interval, 1.44-4.45; and risk ratio, 2.84; 95% confidence interval, 1.67-4.82, respectively). Similar findings were found for the composite adverse maternal outcome with risk ratios of 1.76 (95% confidence interval, 1.32-2.35), 2.07 (95% confidence interval, 1.20-3.57), and 2.77 (95% confidence interval, 1.66-4.63). The association between COVID-19 and gestational hypertension and the direction of the effects on preterm birth and adverse perinatal and maternal outcomes, were similar to preeclampsia, but confined to nulliparous women with lower risk ratios. CONCLUSION: COVID-19 during pregnancy is strongly associated with preeclampsia, especially among nulliparous women. This association is independent of any risk factors and preexisting conditions. COVID-19 severity does not seem to be a factor in this association. Both conditions are associated independently of and in an additive fashion with preterm birth, severe perinatal morbidity and mortality, and adverse maternal outcomes. Women with preeclampsia should be considered a particularly vulnerable group with regard to the risks posed by COVID-19.

Incidence de la COVID-19 sur les issues de grossesse: examen systématique et méta-analyse.

CONTEXTE: La nature exacte des répercussions de la maladie à coronavirus 2019 (COVID-19) sur la santé maternelle et néonatale reste à préciser. Nous avons cherché à évaluer l'association entre l'infection par le coronavirus du syndrome respiratoire aigu sévère 2 (SRAS-CoV-2) pendant la grossesse et les issues défavorables de la grossesse. MÉTHODES: Nous avons réalisé une revue systématique et une méta-analyse d'études observationnelles fournissant des données comparatives sur l'infection par le SRAS-CoV-2 et la gravité de la COVID-19 pendant la grossesse. Nous avons sélectionné les études admissibles à partir des bases de données MEDLINE, Embase, ClinicalTrials.gov, medRxiv et Cochrane au 29 janvier 2021, en utilisant les Medical Subject Headings (vedettes matière en médecine) et les expressions clés « severe acute respiratory syndrome coronavirus 2 OR SARS-CoV-2 OR coronavirus disease 2019 OR COVID-19 ¼ (coronavirus du syndrome respiratoire aigu sévère 2 ou SRAS-CoV-2 ou maladie à coronavirus 2019 ou COVID-19) AND « pregnancy ¼ (grossesse). Nous avons ensuite évalué la qualité méthodologique de toutes les études retenues avec l'échelle de Newcastle­Ottawa. Les issues primaires étaient la prééclampsie et la naissance prématurée. Les issues secondaires incluaient la mortinaissance et le diabète gestationnel, ainsi que d'autres issues de grossesse. Nous avons calculé des rapports de cotes (RC) sommaires ou des différences moyennes pondérées avec des intervalles de confiance (IC) à 95 % par méta-analyse à effets aléatoires. RÉSULTATS: Nous avons retenu 42 études portant sur 438 548 personnes enceintes. Comparativement à une absence d'infection par le SRAS-CoV-2 pendant la grossesse, le diagnostic de COVID-19 a été associé à la prééclampsie (RC 1,33; IC à 95 % 1,03­1,73), à la naissance prématurée (RC 1,82; IC à 95 % 1,38­2,39) et à la mortinaissance (RC 2,11; IC à 95 % 1,14­3,90). Par rapport à la COVID-19 légère, la COVID-19 grave était fortement associée à la prééclampsie (RC 4,16; IC à 95 % 1,55­11,15), à la naissance prématurée (RC 4,29; IC à 95 % 2,41­7,63), au diabète gestationnel (RC 1,99; IC à 95 % 1,09­3,64) et au faible poids à la naissance (RC 1,89; IC à 95 % 1,14­3,12). INTERPRÉTATION: La COVID-19 pourrait être associée à un risque accru de prééclampsie, de naissance prématurée et d'autres issues défavorables de la grossesse.

COVID-19 and preeclampsia with severe features at 34-weeks gestation.

The evolving coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to a rapid expansion of knowledge on the disease's clinical manifestations, laboratory and radiographic abnormalities, and patient trajectories. One area of particular focus is the effect that this illness may have on pregnancy and maternal-fetal disease. As of April 24, 2020, we identified 55 English language reports in the scientific literature summarizing data for 339 women and 258 fetuses and neonates. The majority of these data have focused on maternal-fetal transmission and neonatal outcomes. One systematic review and meta-analysis including the spectrum of coronaviruses [Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), and COVID-19] in pregnancy noted increased rates of adverse outcomes associated with this group of infections. Here, we report the case of a COVID-19 positive woman presenting to our emergency department (ED) at 34 weeks gestation with preeclampsia. This case highlights the unique diagnostic and therapeutic challenges associated with treating patients with these concomitant diseases.

Maternal COVID-19 infection, clinical characteristics, pregnancy, and neonatal outcome: A prospective cohort study.

OBJECTIVE: To study the effect of COVID-19 on pregnancy and neonatal outcomes. STUDY DESIGN: Prospective cohort study in a large tertiary maternity unit within a university hospital with an average annual birth of over 10,000 births. We prospectively collected and analysed data for a cohort of 23 pregnant patients including singleton and multiple pregnancies tested positive for COVID-19 between February 2020 and April 2020 inclusive to assess the effect of COVID-19 on pregnancy, and neonatal outcomes. RESULTS: Twenty-three pregnant patients tested positive for COVID-19, delivering 20 babies including a set of twins, with four ongoing pregnancies at the time of manuscript submission. 16/23 (70 %) whom tested positive were patients from Asian (Indian sub-continent) background. The severity of the symptoms ranged from mild in 13/23 (65.2 %) of the patients, moderate in 2/23 (8.7 %), and severe in 8/23 (34.8 %). Four out of total 23 COVID-19 pregnant patients (17.4 %) developed severe adult respiratory distress syndrome complications requiring ICU support, one of whom led to maternal death 1/23 (4.3 %). 11/23 (48 %) of the patients had pre-existing co-morbidities, with morbid obesity 5/23 (21.7 %) and diabetes 4/23 (17.4 %) being the more commonly represented. Of the 23 pregnant patients 19 were in their third trimester of pregnancy and delivered; 7/19 (36.8 %) had preterm birth, 3/19 (15.8 %) developed adult respiratory distress syndrome before delivery, and 2/19 (10.5 %) had pre-eclampsia. 16/19 (84 %) of patients delivered by C-section. Out of the 20 new-borns, 18 were singletons with a set of twin. CONCLUSION: COVID-19 is associated with high prevalence of preterm birth, preeclampsia, and caesarean section compared to non-COVID pregnancies. COVID-19 infection was not found in the newborns and none developed severe neonatal complications.

SARS-CoV-2 infection of the placenta.

BACKGROUNDThe effects of the novel coronavirus disease 2019 (COVID-19) in pregnancy remain relatively unknown. We present a case of second trimester pregnancy with symptomatic COVID-19 complicated by severe preeclampsia and placental abruption.METHODSWe analyzed the placenta for the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through molecular and immunohistochemical assays and by and electron microscopy and measured the maternal antibody response in the blood to this infection.RESULTSSARS-CoV-2 localized predominantly to syncytiotrophoblast cells at the materno-fetal interface of the placenta. Histological examination of the placenta revealed a dense macrophage infiltrate, but no evidence for the vasculopathy typically associated with preeclampsia.CONCLUSIONThis case demonstrates SARS-CoV-2 invasion of the placenta, highlighting the potential for severe morbidity among pregnant women with COVID-19.FUNDINGBeatrice Kleinberg Neuwirth Fund and Fast Grant Emergent Ventures funding from the Mercatus Center at George Mason University. The funding bodies did not have roles in the design of the study or data collection, analysis, and interpretation and played no role in writing the manuscript.