ObjectivesTo evaluate the strength of association between maternal and pregnancy characteristics and the risk of adverse perinatal outcomes in pregnancies with laboratory confirmed COVID-19.MethodsSecondary analysis of a multinational, cohort study on all consecutive pregnant women with laboratory-confirmed COVID-19 from February 1, 2020 to April 30, 2020 from 73 centers from 22 different countries. A confirmed case of COVID-19 was defined as a positive result on real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay of nasal and pharyngeal swab specimens. The primary outcome was a composite adverse fetal outcome, defined as the presence of either abortion (pregnancy loss before 22 weeks of gestations), stillbirth (intrauterine fetal death after 22 weeks of gestation), neonatal death (death of a live-born infant within the first 28 days of life), and perinatal death (either stillbirth or neonatal death). Logistic regression analysis was performed to evaluate parameters independently associated with the primary outcome. Logistic regression was reported as odds ratio (OR) with 95% confidence interval (CI).ResultsMean gestational age at diagnosis was 30.6±9.5 weeks, with 8.0% of women being diagnosed in the first, 22.2% in the second and 69.8% in the third trimester of pregnancy. There were six miscarriage (2.3%), six intrauterine device (IUD) (2.3) and 5 (2.0%) neonatal deaths, with an overall rate of perinatal death of 4.2% (11/265), thus resulting into 17 cases experiencing and 226 not experiencing composite adverse fetal outcome. Neither stillbirths nor neonatal deaths had congenital anomalies found at antenatal or postnatal evaluation. Furthermore, none of the cases experiencing IUD had signs of impending demise at arterial or venous Doppler. Neonatal deaths were all considered as prematurity-related adverse events. Of the 250 live-born neonates, one (0.4%) was found positive at RT-PCR pharyngeal swabs performed after delivery. The mother was tested positive during the third trimester of pregnancy. The newborn was asymptomatic and had negative RT-PCR test after 14 days of life. At logistic regression analysis, gestational age at diagnosis (OR: 0.85, 95% CI 0.8–0.9 per week increase; p<0.001), birthweight (OR: 1.17, 95% CI 1.09–1.12.7 per 100 g decrease; p=0.012) and maternal ventilatory support, including either need for oxygen or CPAP (OR: 4.12, 95% CI 2.3–7.9; p=0.001) were independently associated with composite adverse fetal outcome.ConclusionsEarly gestational age at infection, maternal ventilatory supports and low birthweight are the main determinants of adverse perinatal outcomes in fetuses with maternal COVID-19 infection. Conversely, the risk of vertical transmission seems negligible.

Despite the increasing number of published studies, objective evidence is still needed to draw any conclusion on the course of SARS-COV-2 infection acquired during pregnancy. What are the clinical implications of this work? The study showed that in pregnancies complicated by SARS-COV-2, the risk of maternal mortality was 0.8%, but about 11% of women required admission to ICU. Pregnancies affected by SARS-COV-2 were also complicated by 23% rate preterm birth, and 4.1% rate of perinatal death. The risk of vertical transmission was negligible.

Objectives: To evaluate the strength of association between maternal and pregnancy characteristics and the risk of adverse perinatal outcomes in pregnancies with laboratory confirmed COVID-19. Methods: Secondary analysis of a multinational, cohort study on all consecutive pregnant women with laboratoryconfirmed COVID-19 from February 1, 2020 to April 30, 2020 from 73 centers from 22 different countries. A confirmed case of COVID-19 was defined as a positive result on real-time reverse-transcriptase-polymerasechain-reaction (RT-PCR) assay of nasal and pharyngeal swab specimens. The primary outcome was a composite adverse fetal outcome, defined as the presence of either abortion (pregnancy loss before 22 weeks of gestations), stillbirth (intrauterine fetal death after 22 weeks of gestation), neonatal death (death of a live-born infant within the first 28 days of life), and perinatal death (either stillbirth or neonatal death). Logistic regression analysis was performed to evaluate parameters independently associated with the primary outcome. Logistic regression was reported as odds ratio (OR) with 95% confidence interval (CI). Results: Mean gestational age at diagnosis was 30.6±9.5 weeks, with 8.0% of women being diagnosed in the first, 22.2% in the second and 69.8% in the third trimester of pregnancy. There were six miscarriage (2.3%), six intrauterine device (IUD) (2.3) and 5 (2.0%) neonatal deaths, with an overall rate of perinatal death of 4.2% (11/ 265), thus resulting into 17 cases experiencing and 226 not experiencing composite adverse fetal outcome. Neither stillbirths nor neonatal deaths had congenital anomalies found at antenatal or postnatal evaluation. Furthermore, none of the cases experiencing IUD had signs of impending demise at arterial or venous Doppler. Neonatal deaths were all considered as prematurity-related adverse events. Of the 250 live-born neonates, one (0.4%) was found positive at RT-PCR pharyngeal swabs performed after delivery. The mother was tested positive during the third trimester of pregnancy. The newborn was asymptomatic and had negative RT-PCR test after 14 days of life. At logistic regression analysis, gestational age at diagnosis (OR: 0.85, 95% CI 0.8-0.9 per week increase; p<0.001), birthweight (OR: 1.17, 95% CI 1.09-1.12.7 per 100 g decrease; p=0.012) and maternal ventilatory support, including either need for oxygen or CPAP (OR: 4.12, 95% CI 2.3-7.9; p=0.001) were independently associated with composite adverse fetal outcome. Conclusions: Early gestational age at infection, maternal ventilatory supports and low birthweight are the main determinants of adverse perinatal outcomes in fetuses with maternal COVID-19 infection. Conversely, the risk of vertical transmission seems negligible.

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Objectives To evaluate maternal and perinatal outcomes in high compared to low-risk pregnancies complicated by SARS-COV-2 infection. Methods This was a multinational retrospective cohort study including women with laboratory-confirmed SARS-COV-2 from 76 centers from 25 different countries in Europe, United States, South America, Asia and Australia from 04 April 2020 till 28 October 2020. The primary outcome was a composite measure of maternal mortality and morbidity including admission to intensive care unit (ICU), use of mechanical ventilation, or death. Secondary outcome was a composite measure of adverse perinatal outcome, including miscarriage, fetal loss, neonatal (NND) and perinatal (PND) death, and admission to neonatal intensive care unit. All these outcomes were assessed in high-risk compared to low-risk pregnancies. Pregnancies were considered as high risk in case of either pre-existing chronic medical conditions pre-existing pregnancy or obstetric disorders occurring in pregnancy. Fisher-test and logistic regression analysis were used to analyze the data. Results 887 singleton pregnancies tested positive to SARS-COV-2 at RT-PCR nasal and pharyngeal swab were included in the study. The risk of composite adverse maternal outcome was higher in high compared to low risk-pregnancies with an OR of 1.52 (95% CU 1.03-2.24; p= 0.035). Likewise, women carrying a high risk-pregnancies were also at higher risk of hospital admission (OR: 1.48, 95% CI 1.07-2.04; p= 0.002), presence of severe respiratory symptoms (OR: 2.13, 95% CI .41-3.21; p= 0.001), admission to ICU (OR: 2.63, 95% CI 1.42-4.88) and invasive mechanical ventilation (OR: 2.65, 95% CI 1.19- 5.94; p= .002). When exploring perinatal outcomes, high-risk pregnancies were also at high risk of adverse perinatal outcome with an OR 0f 1.78 (95% CI .15-2.72; p= 0.009). However, such association was mainly due to the higher incidence of miscarriage in high risk compared to low risk pregnancies (5.3% vs 1.6%, p= 0.008), while there was no difference as regard as the other explored outcomes between the two study groups. At logistic regression analysis, maternal age (OR: 1.12, 95% CI 1.02-1.22, p= 0.023) and the presence of a high-risk pregnancies (OR: 4.21, 95% CI 3.90-5.11, p<0.001) were independently associated with adverse maternal outcome. Conclusions High-risk pregnancies complicated by SARS-COV-2 infection are at higher risk of adverse maternal outcome compared to low-risk gestations.

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The prediction of birth weight may be improved by the measurement of hormones or growth factors in the mother. We measured body weight (BW) and plasma levels of placental GH (PGH), IGF-I, IGF-binding protein-1 (IGFBP-1), and leptin at the time of the glucose challenge test (GCT) in 289 women, who were pregnant with a single fetus, between 24 and 29 wk gestational age (GA). Delivery occurred 12 ؎ 2 (mean ؎ SD) wk later.First, we examined which variables regulate these hormonal factors. Multiple regression showed that PGH concentrations were determined by GA at sampling and were negatively related to BW. IGF-I levels were mainly determined by PGH, and also by insulin, BW, and (negatively) age. IGFBP-1 concentrations were negatively determined by BW, insulin, and IGF-I. BW was also a powerful determinant of leptin levels, with insulin as a less robust determinant.Second, we examined the relation to glucose levels. PGH, IGF-I, and IGFBP-1 concentrations were not correlated with post-GCT glucose levels and were comparable in women with a normal or disturbed GCT (glucose >7.8 mmol/liter; n ‫؍‬ 72).Finally, we examined the relation with birth weight and placental weight. Birth weight, corrected for GA and stratified into percentile groups, and the ponderal index at birth were strongly related to maternal BW, but not to maternal PGH, IGF-I, or IGFBP-1 levels. Neither was maternal leptin related to birth weight, but leptin concentrations were slightly higher in women who delivered obese babies. Placental weight was not related to any of the hormonal factors.This prospective study indicates that the variation in circulating PGH, IGF-I, IGFBP-1, and leptin between 24 and 29 wk of pregnancy is strongly dependent on maternal BW, but is unrelated to glucose tolerance. In addition, the measurement of PGH, IGF-I, IGFBP-1, or leptin at the time of the GCT is not useful clinically to predict birth weight. (J Clin Endocrinol Metab 87: 2875-2882, 2002)

Context Polycystic ovary syndrome (PCOS), a highly prevalent endocrine disorder characterized by hyperandrogenism, is the leading cause of anovulatory infertility. Objective This proof-of-concept study evaluated clinical efficacy and safety of the neurokinin 3 (NK3) receptor antagonist fezolinetant in PCOS. Design This was a phase 2a, randomized, double-blind, placebo-controlled, multicenter study (EudraCT 2014-004409-34). Setting The study was conducted at 5 European clinical centers. Patients Women with PCOS participated in the study. Intervention Interventions included fezolinetant 60 or 180 mg/d or placebo for 12 weeks. Main Outcome Measure The primary efficacy endpoint was change in total testosterone. Gonadotropins, ovarian hormones, and safety/tolerability were also assessed. Results Seventy-three women were randomized, and 64 participants completed the study. Adjusted mean (SE) changes in total testosterone from baseline to week 12 for fezolinetant 180 and 60 mg/d were −0.80 (0.13) and −0.39 (0.12) nmol/L versus −0.05 (0.10) nmol/L with placebo (P&lt;0.0001 and P&lt;0.05, respectively). Adjusted mean (SE) changes from baseline in luteinizing hormone (LH) for fezolinetant 180 and 60 mg/d were −10.17 (1.28) and −8.21 (1.18) versus −3.16 (1.04) IU/L with placebo (P&lt;0.0001 and P=0.0022); corresponding changes in follicle-stimulating hormone (FSH) were −1.46 (0.32) and −0.92 (0.30) versus −0.57 (0.26) IU/L (P=0.0336 and P=0.3770), underpinning a dose-dependent decrease in the LH-to-FSH ratio versus placebo (P&lt;0.001). Circulating levels of progesterone and estradiol did not change significantly versus placebo (P&gt;0.1). Fezolinetant was well tolerated. Conclusions Fezolinetant had a sustained effect to suppress hyperandrogenism and reduce the LH-to-FSH ra