Introduction: Our objective was to compare the fetal growth velocity and fetal hemodynamics in pregnancies complicated and in those not complicated by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Material and methods: Prospective case-control study of consecutive pregnancies complicated by SARS-CoV-2 infection during the second half of pregnancy matched with unaffected women. The z scores of head circumference, abdominal circumference, femur length, and estimated fetal weight were compared between the two groups. Fetal growth was assessed by analyzing the growth velocity of head circumference, abdominal circumference, femur length, and estimated fetal weight between the second-and third-trimester scans. Similarly, changes in the pulsatility index of uterine, umbilical, and middle cerebral arteries, and their ratios were compared between the two study groups. Results: Forty-nine consecutive pregnancies complicated, and 98 not complicated, by SARS-CoV-2 infection were included. General baseline and pregnancy characteristics were similar between pregnant women with and those without SARS-CoV-2 infection. There was no difference in head circumference, abdominal circumference, femur length, and estimated fetal weight z scores between pregnancies complicated and those not complicated by SARS-CoV-2 infection at both the second-and thirdtrimester scans. Likewise, there was no difference in the growth velocity of all these body parameters between the two study groups. Finally, there was no difference in the pulsatility index of both maternal and fetal Doppler scans throughout gestation between the two groups. Conclusions: Pregnancies complicated by SARS-CoV-2 infection are not at higher risk of developing fetal growth restriction through impaired placental function. The findings from this study do not support a policy of increased fetal surveillance in these women.

STUDY QUESTION What evaluation and care is offered to women after unexplained recurrent pregnancy loss (RPL) or intra-uterine foetal death (IUFD) and what are the reproductive outcomes? SUMMARY ANSWER Women are assessed for thrombophilia and often treated with low-molecular weight heparin (LMWH) and/or low-dose aspirin (ASA). WHAT IS KNOWN ALREADY Randomized controlled trials (RCTs) on possible efficacy of heparins and/or aspirin have been inconclusive due to limited power to detect a difference and patient heterogeneity. STUDY DESIGN, SIZE, DURATION Prospective multicentre cohort study performed in 12 hospitals in three countries between 2012 and 2019. PARTICIPANTS/MATERIALS, SETTING, METHODS All consecutive pregnant women with recurrent PL (≥3 losses or 2 losses in the presence of at least one euploid foetal karyotype) or at least one IUFD. Eligible women may have undergone thrombophilia testing before conception, at the discretion of local providers. The possible assignment of women to treatments (such as LMWH) was not decided a priori but was determined based on the responsible provider’s current practice. Aims of the study were: (i) to evaluate factors associated with pregnancy outcome; (ii) to compare clinical management strategies in women with and without a subsequent successful pregnancy; and (iii) to evaluate characteristics of women who may benefit from antithrombotic therapy. A propensity score matching method was used to balance the differences in baseline characteristics. MAIN RESULTS AND THE ROLE OF CHANCE A matched sample of 265 pregnant women was analysed, with all undergoing thrombophilia screening; 103 out of 119 (86.6%) with and 98/146 (67.1%) without thrombophilia were prescribed with LMWH and/or ASA. Overall, live-births were recorded in 204 cases (77%), PL or IUFD in 61 (23%) pregnancies. Logistic regression showed a significant interaction between thrombophilia and treatment with LMWH (P = 0.03). Findings from sensitivity analysis showed odds ratio (OR) for pregnancy loss in women with inherited or acquired thrombophilia in absence of any treatment was 2.9 (95% CI, 1.4–6.1); the administration of LMWH (with or without ASA) was associated with higher odds of live-birth (OR, 10.6; 95% CI, 5.0–22.3). Furthermore, in women without thrombophilia, the odds of live-birth was significantly and independently associated with LMWH prophylaxis (alone or in association with ASA) (OR, 3.6; 95% CI, 1.7–7.9). LIMITATIONS, REASONS FOR CAUTION While the propensity score matching allows us to balance the differences in baseline characteristics, it does not eliminate all confounding. WIDER IMPLICATIONS OF THE FINDINGS Antithrombotic prophylaxis during pregnancy may be effective in women with otherwise unexplained PL or IUFD, and even more useful in those with thrombophilia. STUDY FUNDING/COMPETING INTEREST(S) The study was funded by Italian Ministry of Health (Ricerca Corrente 2018-2020). Dr G.P. has received research grant support from Bristol Myers Squibb/Pfizer Alliance, Janssen, Boston Scientific Corporation, Bayer, and Portola and consultant fees from Amgen and Agile Therapeutics. Dr E.G. has received consultant fees from Italfarmaco and Sanofi. All other authors declare that they have no conflict of interest. TRIAL REGISTRATION NUMBER NCT02385461.

Introduction Current models based on fetal biometry and maternal characteristics have a poor performance in predicting macrosomia. The primary aim of this study was to elucidate the diagnostic performance of fetal venous and arterial Dopplers in predicting macrosomia in the third trimester of pregnancy; the secondary aim was to build a multiparametric prediction model including pregnancy, ultrasound and Doppler characteristics able to predict macrosomia accurately. Material and methods Prospective cohort study including 2156 singleton pregnancies scheduled for routine ultrasound assessment at 36 weeks of gestation. Fetal biometry, estimated fetal weight (EFW), pulsatility index of the uterine, umbilical, and middle cerebral arteries, cerebroplacental ratio and umbilical vein blood flow (UVBF) normalized for fetal abdominal circumference (UVBF/AC) were recorded. Primary outcome was the prediction of fetal macrosomia, defined as a birthweight >90th percentile; secondary outcome was the prediction of newborns >4000 g. Logistic regression and area under the curve (AUC) analyses were used to analyze the data. Results Fetal macrosomia complicated 9.8% of pregnancies, and 7.7% of newborns had a birthweight >4000 g. At multivariate logistic regression analysis, maternal body mass index (adjusted odds ratio [aOR] 1.23), pregestational diabetes (aOR 1.83), a prior newborn with a birthweight >95th centile (aOR 1.49), EFW (aOR 2.23) and UVBF (aOR1.84) were independently associated with macrosomia, whereas gestational diabetes mellitus (P = .07) or any of the other Doppler parameters were not. EFW had an AUC of 0.750 and of 0.801 alone and in association with maternal characteristics for the prediction of macrosomia, respectively. The addition of UVBF to this model significantly improved the prediction of fetal macrosomia provided by maternal and ultrasound parameters with an AUC of 0.892 (De Long P = .044 and P = .0078, respectively). The predictive performance for birthweight >4000 g was similar and significantly improved when UVBF was included in the diagnostic algorithm. Conclusions Umbilical vein blood flow evaluation in the third trimester improves the diagnosis of fetal macrosomia. The optimal diagnostic performance for macrosomia is achieved by a multiparametric model including umbilical vein flow, maternal characteristics and EFW.