Pregnant women may be at higher risk of severe complications associated with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which may lead to obstetrical complications. We performed a case control study comparing pregnant women with severe coronavirus disease 19 (cases) to pregnant women with a milder form (controls) enrolled in the COVI-Preg international registry cohort between March 24 and July 26, 2020. Risk factors for severity, obstetrical and immediate neonatal outcomes were assessed. A total of 926 pregnant women with a positive test for SARS-CoV-2 were included, among which 92 (9.9%) presented with severe COVID-19 disease. Risk factors for severe maternal outcomes were pulmonary comorbidities [aOR 4.3, 95% CI 1.9–9.5], hypertensive disorders [aOR 2.7, 95% CI 1.0–7.0] and diabetes [aOR2.2, 95% CI 1.1–4.5]. Pregnant women with severe maternal outcomes were at higher risk of caesarean section [70.7% (n = 53/75)], preterm delivery [62.7% (n = 32/51)] and newborns requiring admission to the neonatal intensive care unit [41.3% (n = 31/75)]. In this study, several risk factors for developing severe complications of SARS-CoV-2 infection among pregnant women were identified including pulmonary comorbidities, hypertensive disorders and diabetes. Obstetrical and neonatal outcomes appear to be influenced by the severity of maternal disease.

Background and Purpose Dopamine and corticotrophin‐releasing hormone (CRH; also known as corticotrophin‐releasing factor) are key neurotransmitters in the interaction between stress and addiction. Repeated treatment with cocaine potentiates glutamatergic transmission in the rat basolateral amygdala/cortex pathway through a synergistic action of D1‐like dopamine receptors and CRH type‐2α receptors (CRF2α receptors). We hypothesized that this observed synergism could be instrumented by heteromers containing the dopamine D1 receptor and CRF2α receptor. Experimental Approach D1/CRF2α receptor heteromerization was demonstrated in HEK293T cells using co‐immunoprecipitation, BRET and FRET assays, and by using the heteromer mobilization strategy. The ability of D1 receptors to signal through calcium, when singly expressed or co‐expressed with CRF2α receptors, was evaluated by the calcium mobilization assay. Key Results D1/CRF2α receptor heteromers were observed in HEK293T cells. When singly expressed, D1 receptors were mostly located at the cell surface whereas CRF2α receptors accumulated intracellularly. Interestingly, co‐expression of both receptors promoted D1 receptor intracellular and CRF2α receptor cell surface targeting. The heteromerization of D1/CRF2α receptors maintained the signalling through cAMP of both receptors but switched D1 receptor signalling properties, as the heteromeric D1 receptor was able to mobilize intracellular calcium upon stimulation with a D1 receptor agonist. Conclusions and Implications D1 and CRF2α receptors are capable of heterodimerization in living cells. D1/CRF2α receptor heteromerization might account, at least in part, for the complex physiological interactions established between dopamine and CRH in normal and pathological conditions such as addiction, representing a new potential pharmacological target.

Objectives In fetuses with isolated left‐sided congenital diaphragmatic hernia (LCDH), prenatal detection of severe pulmonary hypoplasia is important, as fetal therapy can improve survival. Cases with mild or moderate lung hypoplasia still carry a considerable risk of mortality and morbidity, but there has been less interest in the accurate prediction of outcome in these cases. In this study of fetuses with mild or moderate isolated LCDH, we aimed to investigate: (1) the association between intrapulmonary artery (IPA) Doppler findings and mortality at discharge; (2) whether adding IPA Doppler findings improves the prediction of mortality based on lung size and liver herniation; and (3) the association between IPA Doppler findings and early neonatal morbidity. Methods This was a retrospective study of all consecutive fetuses assessed at the BCNatal and UZ Leuven hospitals between 2008 and 2020 with a prenatal diagnosis of isolated, non‐severe LCDH, defined as observed‐to‐expected lung‐to‐head ratio (o/e‐LHR) > 25%, that were managed expectantly during pregnancy followed by standardized neonatal management. An additional inclusion criterion was the availability of IPA Doppler measurements. The primary outcome was the association between IPA Doppler findings and mortality at discharge. Other predictors included o/e‐LHR, liver herniation and gestational age at birth. Secondary outcomes were the association between IPA Doppler findings and the presence of pulmonary hypertension (PHT), need for supplemental oxygen at discharge and need for extracorporeal membrane oxygenation. IPA pulsatility index (PI) values were converted into Z‐scores. Logistic regression analysis was performed to investigate the associations between predictor variables and outcome, and the best model was chosen based on the Nagelkerke R2. Results Observations for 70 non‐severe LCDH cases were available. Fifty‐four (77%) fetuses survived until discharge. On logistic regression analysis, higher IPA‐PI was associated with an increased risk of mortality (odds ratio (OR), 3.96 (95% CI, 1.62–9.70)), independently of o/e‐LHR (OR, 0.87 (95% CI, 0.79–0.97)). An IPA‐PI Z‐score cut‐off of 1.8 predicted mortality with a detection rate of 69% and specificity of 93%. Adding IPA‐PI to o/e‐LHR improved significantly the model's performance (Nagelkerke R2, 46% for o/e‐LHR + IPA‐PI vs 28% for o/e‐LHR (P < 0.002)), with a detection rate of 81% at a 10% false‐positive rate. IPA‐PI was associated with PHT (OR, 2.20 (95% CI, 1.01–4.59)) and need for oxygen supplementation at discharge (OR, 1.90 (95% CI, 1.10–3.40)), independently of lung size. Conclusions In fetuses with mild or moderate LCDH, IPA‐PI was associated with mortality and morbidity, independently of lung size. A model combining o/e‐LHR with IPA‐PI identified up to four in five cases that eventually died, despite being considered to have non‐severe pulmonary hypoplasia. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

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