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.

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.

Objective To determine the association between Doppler changes in the fetal vertebral (VA), middle cerebral (MCA), and umbilical arteries (UA) and severity of growth restriction (FGR) in fetuses delivered after 34 weeks. Method Five hundred seventy‐one Doppler examinations of the VA, MCA, and UA were performed between 26 and 41 weeks of gestation. Values were converted into multiples of the median and divided into birth weight (BW) categories: BW>P10th, BW

Objectives To evaluate whether the interval to delivery modifies the predictive accuracy of the cerebroplacental ratio (CPR) for the prediction of cesarean section for intrapartum fetal compromise (CS-IFC), either as a single marker or combined with estimated fetal weight centile (EFWc), type of labor onset (TLO) and other clinical variables. Material and methods This was a multicenter retrospective study of 5193 women with singleton pregnancies who underwent an ultrasound scan at 35+0- 41+0 weeks and gave birth within one month of examination, at any of the participating hospitals in Spain, UK, and Italy. CS-IFC was diagnosed in case of abnormal intrapartum fetal heart rate or intrapartum fetal scalp pH<7.20, requiring urgent cesarean section. The diagnostic ability of CPR in multiples of the median (CPR MoM) was evaluated at different intervals to delivery, alone and combined with EFWc, TLO, and other pregnancy data such as maternal age, maternal body mass index, parity, and fetal sex, for the prediction of CS-IFC by means of ROC curves and logistic regression analysis. Results The predictive ability of CPR MoM for CS-IFC worsened with the interval to delivery. In general, the best prediction was obtained prior to labor, and adding information related with EFWc and TLO [AUC 0.71 (95% CI 0.64-0.79), 0.73 (95% CI 0.66-0.80) and 0.75 (95% CI 0.69-0.81); P<0.0001]. Addition of more clinical data did not improve prediction. In addition, results did not vary when only cases with spontaneous onset of labor were studied. Conclusion CPR MoM prediction of CS-IFC at the end of pregnancy worsens with the interval to delivery. Accordingly, it should be done in the short term and considering EFWc and TLO.

Objectives: To establish Doppler reference values for the fetal vertebral artery resistance index (VA RI), pulsatility index (VA PI) and peak systolic velocity (VA PSV), and describe their normal ratios to the umbilical artery (UA) throughout the second and third trimester of pregnancy. Methods: Between 19 and 41 weeks of gestation, 484 ultrasound examinations of the fetal VA and UA were performed on singleton pregnant women with uncomplicated pregnancies. The VA was examined at the anatomical point where the artery surrounds the lateral masses of the atlas between the first cervical vertebra and the occipital bone, and values were obtained for the VA RI, VA PI and VA PSV. The 10th, 50th and 90th percentiles were subsequently generated for these parameters and their ratios to the UA. Results: The VA RI and VA PI reached their maximum values at the end of the second trimester. Both indexes subsequently decreased due to an increase in the diastolic flow. Conversely, the VA PSV values increased progressively until the end of gestation. As for the VA/UA ratios, the RI and PI were higher in the middle of the third trimester and decreased slightly afterwards. On the other hand, the PSV increased progressively until the end of pregnancy. Conclusions: The fetal VA can be visualized with Doppler ultrasound as early as 19 weeks’ gestation. In this study, reference values of the VA RI, PI and PSV and their ratios to the UA during the second half of pregnancy have been provided for fetal research. However, future work is necessary to further explore the possible applications of VA Doppler examination in fetal medicine.

Objective To assess the performance of fetal magnetic resonance imaging (MRI) in detecting associated anomalies in fetuses diagnosed with isolated corpus callosal (CC) anomaly on multiplanar ultrasound evaluation of the fetal brain (neurosonography). Methods This was a multicenter, retrospective cohort study involving 14 fetal medicine centers in Italy, UK, Portugal, Canada, Austria and Spain. Inclusion criteria were fetuses with an apparently isolated CC anomaly, defined as an anomaly of the CC and no other additional central nervous system (CNS) or extra‐CNS abnormality detected on expert ultrasound, including multiplanar neurosonography; normal karyotype; maternal age ≥ 18 years; and gestational age at diagnosis ≥ 18 weeks. The primary outcome was the rate of additional CNS abnormalities detected exclusively on fetal MRI within 2 weeks following neurosonography. The secondary outcomes were the rate of additional abnormalities according to the type of CC abnormality (complete (cACC) or partial (pACC) agenesis of the CC) and the rate of additional anomalies detected only on postnatal imaging or at postmortem examination. Results A total of 269 fetuses with a sonographic prenatal diagnosis of apparently isolated CC anomalies (207 with cACC and 62 with pACC) were included in the analysis. Additional structural anomalies of the CNS were detected exclusively on prenatal MRI in 11.2% (30/269) of cases, with malformations of cortical development representing the most common type of anomaly. When stratifying the analysis according to the type of CC anomaly, the rate of associated anomalies detected exclusively on MRI was 11.6% (24/207) in cACC cases and 9.7% (6/62) in pACC cases. On multivariate logistic regression analysis, only maternal body mass index was associated independently with the likelihood of detecting associated anomalies on MRI (odds ratio, 1.07 (95% CI, 1.01–1.14); P = 0.03). Associated anomalies were detected exclusively after delivery and were missed on both types of prenatal imaging in 3.9% (8/205) of fetuses with prenatal diagnosis of isolated anomaly of the CC. Conclusion In fetuses with isolated anomaly of the CC diagnosed on antenatal neurosonography, MRI can identify a small proportion of additional anomalies, mainly malformations of cortical development, which are not detected on ultrasound. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.