COVID-19 is associated with early emergence of preeclampsia: results from a large regional collaborative.

Objective: To investigate the relationship between preeclampsia and SARS-CoV-2 infection during pregnancy. Methods: This was a retrospective cohort study of pregnant women between March and October 2020. Pregnant patients admitted to 14 obstetrical centers in Michigan, USA formed the study population. Of the N = 1458 participants, 369 had SARS-CoV-2 infection (cases). Controls were uninfected pregnancies that were delivered in the same obstetric unit within 30 days of the index case. Robust Poisson regression was used to estimate relative risk (RR) of preterm and term preeclampsia and preeclampsia involving placental lesions. The analysis included adjustment for relevant clinical and demographic risk factors.Results: SARS-CoV-2 infection during pregnancy increased the risk of preeclampsia [adjusted aRR = 1.69 (1.26-2.26)], preeclampsia involving placental lesions [aRR = 1.97(1.14-3.4)] and preterm preeclampsia 2.48(1.48-4.17). Although the highest rate of preeclampsia was observed in patients infected with SARS-CoV-2 who were symptomatic (18.4%), there was increased risk even in asymptomatic SARS-CoV-2 infected patients (14.2%) relative to non-infected controls (8.7%) (p < 0.05). This association with symptomatology was also noted with preterm preeclampsia for which the rate doubled from 2.7% in controls to 5.2% in asymptomatic cases and reached 11.8% among symptomatic cases (p < 0.05). The rate of preterm preeclampsia among cases of pregnant people self-identified as Black reached 10.1% and was almost double the rate of the reminder of the group of infected pregnancies (5.3%), although the rate among uninfected was almost the same (2.7%) for both Black and non-Black groups (interaction p = 0.05).Conclusions: Infection with SARS-CoV-2 increases the risk of preeclampsia even in the absence of symptoms, although symptomatic persons are at even higher risk. Racial disparities in the development of preterm preeclampsia after SARS-CoV-2 infection may explain discrepancies in prematurity between different populations.

Maternal SARS-COV-2 infection and prematurity: the Southern Michigan COVID-19 collaborative.

OBJECTIVE: COVID-19 has been reported to increase the risk of prematurity, however, due to the frequent absence of unaffected controls as well as inadequate accounting for confounders in many studies, the question requires further investigation. We sought to determine the impact of COVID-19 disease on preterm birth (PTB) overall, as well as related subcategories such as early prematurity, spontaneous, medically indicated preterm birth, and preterm labor (PTL). We assessed the impact of confounders such as COVID-19 risk factors, a-priori risk factors for PTB, symptomatology, and disease severity on rates of prematurity. METHODS: This was a retrospective cohort study of pregnant women from March 2020 till October 1st, 2020. The study included patients from 14 obstetric centers in Michigan, USA. Cases were defined as women diagnosed with COVID-19 at any point during their pregnancy. Cases were matched with uninfected women who delivered in the same unit, within 30 d of the delivery of the index case. Outcomes of interest were frequencies of prematurity overall and subcategories of preterm birth (early, spontaneous/medically indicated, preterm labor, and premature preterm rupture of membranes) in cases compared to controls. The impact of modifiers of these outcomes was documented with extensive control for potential confounders. A p value <.05 was used to infer significance. RESULTS: The rate of prematurity was 8.9% in controls, 9.4% in asymptomatic cases, 26.5% in symptomatic COVID-19 cases, and 58.8% among cases admitted to the ICU. Gestational age at delivery was noted to decrease with disease severity. Cases were at an increased risk of prematurity overall [adjusted relative risk (aRR) = 1.62 (1.2-2.18)] and of early prematurity (<34 weeks) [aRR = 1.8 (1.02-3.16)] when compared to controls. Medically indicated prematurity related to preeclampsia [aRR = 2.46 (1.47-4.12)] or other indications [aRR = 2.32 (1.12-4.79)], were the primary drivers of overall prematurity risk. Symptomatic cases were at an increased risk of preterm labor [aRR = 1.74 (1.04-2.8)] and spontaneous preterm birth due to premature preterm rupture of membranes [aRR = 2.2(1.05-4.55)] when compared to controls and asymptomatic cases combined. The gestational age at delivery followed a dose-response relation with disease severity, as more severe cases tended to deliver earlier (Wilcoxon p < .05). CONCLUSIONS: COVID-19 is an independent risk factor for preterm birth. The increased preterm birth rate in COVID-19 was primarily driven by medically indicated delivery, with preeclampsia as the principal risk factor. Symptomatic status and disease severity were significant drivers of preterm birth.

Characterization of amniotic fluid sludge in preterm and term gestations.

OBJECTIVE: To describe the characteristics of amniotic fluid sludge obtained from patients in term and preterm gestations. METHODS: This cross-sectional study included patients with dense aggregates of particulate matter detected in amniotic fluid, observed with transvaginal sonography. All patients were in labor and had an impending delivery, either preterm or at term. Echogenic material contained within amniotic fluid was retrieved transvaginally by needle amniotomy under direct visualization. The amniotic fluid analysis consisted of a Gram stain, cultures for aerobic/anaerobic bacteria and genital mycoplasmas, and a white blood cell count. RESULTS: Twenty-five patients ranging from 18 to 41 weeks of gestation were included in the study. We observed the following: (1) the appearance of amniotic fluid was consistent with pus-like material, vernix, or meconium by naked eye examination; (2) samples collected before 33 weeks of gestation (n = 13) had a pus-like appearance; however, after this gestational age, most of the samples [83% (10/12)] appeared to be consistent with vernix; (3) amniotic fluid cultures were positive for microorganisms in 13 patients, of which 10 were preterm gestations before 33 weeks; (4) the most frequent microorganisms retrieved by culture were genital mycoplasmas (Ureaplasma urealyticum [46% (6/13)]), followed by Mycoplasma hominis [31% (4/13)] and Candida albicans [15% (2/13)]; and (5) patients with sonographic particulate matter in preterm gestations frequently presented acute histologic chorioamnionitis and funisitis, but these conditions were rare in patients at term. CONCLUSION: The nature of amniotic fluid particulate material varies as a function of gestational age. The material obtained in preterm gestations is frequently related to an inflammatory process, while that obtained at term is often consistent with vernix and appears to represent a maturational process.

The dilemma of inherited dysfibrinogenemia during pregnancy.

Inherited dysfibrinogenemia is a rare disorder caused by mutations in the fibrinogen gene, described in approximately 400 families to date. We present the case of a 20-year-old woman at 7 weeks of pregnancy with a history of two first-trimester spontaneous abortions and a family history of thrombotic events. Her testing revealed evidence of dysfibrinogenemia, necessitating multidisciplinary management planning including Hematology, OB-GYN, Maternal-Fetal Medicine, Blood Bank Services and Anesthesia. Antenatal care included a combination of intravenous fibrinogen infusions to maintain fibrinogen levels above 100 mg/dl and anticoagulation with low molecular weight heparin. She had an uneventful full-term delivery and continued fibrinogen infusions and thromboprophylaxis for 6 weeks postpartum. The combination of fibrinogen infusions and anticoagulation maintained the balance between bleeding and clotting in our patient during pregnancy. We recommend a multidisciplinary team approach for the management of dysfibrinogenemia during pregnancy to provide successful pregnancy outcomes.