Effect of SARS-CoV-2 infection on fetal umbilical vein flow and cardiac function: a prospective study.

OBJECTIVES: To explore whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can affect umbilical vein blood flow (UVBF) and fetal cardiac function. METHODS: Prospective case-control study of consecutive pregnancies complicated by SARS-CoV-2 infection during the second half of pregnancy matched with unaffected women. Measurements of UVBF normalized for fetal abdominal circumference (UVBF/AC), atrial area (AA) and ventricular sphericity indices (SI) were compared between the two study groups. Chi-square and Mann-Whitney U tests were sued to analyze the data. RESULTS: Fifty-four consecutive pregnancies complicated and 108 not complicated by SARS-CoV-2 infection were included. The median gestational age at infection was 30.2 (interquartile range [IQR] 26.2 34.1). General baseline and pregnancy characteristics were similar between pregnant women with compared to those without SARS-CoV-2 infection. There was no difference in UVBF/AC (study groups z value -0.11 vs. 0.14 control p 0.751) values between pregnancies complicated compared to those not complicated by SARS-CoV-2 infection. Likewise, there was no difference in the left and right AA (left 1.30 vs. 1.28 p=0.221 and right 1.33 vs. 1.31 p=0.324) and SI (left 1.75 vs. 1.77 p=0.208 and right 1.51 vs. 1.54 p=0.121) between the two groups. CONCLUSIONS: SARS-CoV-2 infection does not affect UVBF and fetal cardiac function in uncomplicated pregnancies.

Preparing an obstetric unit in the heart of the epidemic strike of COVID-19: quick reorganization tips.

COVID-19 is placing considerable strain on healthcare systems. Disaster and military medicine specialists were involved in the outbreak in Italy, after many units were overwhelmed. Health providers were caught off guard and personnel was unprepared to face this unprecedented threat. Local decisions accelerated the rate of the spread. Many countries declared a state of emergency and lockdown to contain the exponential transmission of the disease. The purpose of this review is to suggest quick key points of strategies to implement in obstetric units without delay to respond to the oncoming wave, based on experience and feedback from the field. It is essential in an emergency situation to understand what is at stake and prepare maternity wards in the best possible way.

Modeling gestational age centiles for fetal umbilicocerebral ratio by quantile regression analysis: a secondary analysis of a prospective cross-sectional study.

OBJECTIVE: There is a lack of evidence on whether to favor cerebroplacental ratio (CPR) or umbilicocerebral ratio (UCR) when assessing pregnancies at risk of fetal growth restriction. The Recent evidences highlight a significant heterogeneity in the methodology of previously published studies reporting reference ranges for Doppler indices, which may affect the clinical applicability of these charts. The aim of this study was to develop charts of UCR based upon a recently proposed standardized methodology and using quantile regression. METHODS: This was a secondary analysis of a prospective cross-sectional study including low-risk singleton pregnancies between 24 and 40 weeks of gestation undergoing Doppler recordings. The UCR centile values were established by quantile regression at different gestational age intervals. Quantile regression analysis was used to build the UCR chart. RESULT: 2516 low- risk singleton pregnancies were included in the analysis. UCR decreased with advancing gestational age. The 3rd, 5th 10th, 50th, 90th, 95th, and 97th centiles according to gestational age are provided, as well as equations to allow calculation of any other percentile. CONCLUSIONS: We have established gestational age-specific normative centiles reference limits for UCR.

Findings from a multicentre, observational study on reproductive outcomes in women with unexplained recurrent pregnancy loss: the OTTILIA registry.

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.

Cardiac function in fetal growth restriction.

Fetal growth restriction (FGR) is defined as the inability of the fetus to reach its growth potential. According to the onset of the disease is defined early (<32 weeks) or late (≥32 weeks). FGR is associated with an increased risk of adverse short- and long-term outcomes, including hypoxemic events and neurodevelopmental delay compared to normally grown fetuses and increased risk of complications in the infanthood and adulthood. The underlying cause of FGR is placental insufficiency leading to chronic fetal hypoxia that affects cardiac hemodynamic with different mechanism in early and late onset growth restriction. In early onset FGR adaptive mechanisms involve the diversion of the cardiac output preferentially in favor of the brain and the heart, while abnormal arterial and venous flow manifest in the case of further worsening of fetal hypoxia. In late FGR the fetal heart shows a remodeling of its shape and function mainly related to a reduction of umbilical vein flow. In this review we discuss the modifications occurring at the level of the fetal cardiac hemodynamic in fetuses with early and late FGR.

Effect of SARS-CoV-2 infection during the second half of pregnancy on fetal growth and hemodynamics: A prospective study.

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 third-trimester 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.

Women's compliance with ultrasound in labor: a prospective observational study.

OBJECTIVE: To explore women's compliance with ultrasound evaluation (UE) during labor compared with standard vaginal examination (VE). METHODS: This is a prospective observational cohort study including uncomplicated singleton pregnancies with the fetus in vertex presentation from 37 weeks of gestation. Labor progress was assessed by both VE and UE. Women acceptability was assessed using a modified Wijma Delivery experience questionnaire (W-DEQ) based on six different items and resulting in a score ranging from 6 (not tolerated) to 36 (well tolerated). The primary outcome of the study was to compute the differences in the overall modified W-DEQ questionnaire between UE and VE. Secondary outcomes were to assess the differences between UE and VE in each individual item of modified W-DEQ questionnaire and to elucidate whether such differences persist in pregnancies experiencing compared to those not experiencing prolonged labor or unplanned emergency operative delivery. RESULTS: One hundred and twenty-four women were included in the study and 109 completed the full questionnaire. The overall global acceptability score was significantly higher for UE compared to VE (27 IQR 25-29 versus 18 IQR 16-22; p ≤ .001). When stratifying the analysis to each individual item of the W-DEQ questionnaire separately, significant differences for intrusiveness (p = .04); painful (p = .01) and privacy ensured (p = .01) were found between UE and VE. In pregnancies experiencing prolonged labor, the global W-DEQ acceptability score for UE resulted significantly higher (30 versus 23; p = .005) than in those delivering within 12 hours. Likewise, UE acceptability score was significantly higher (28 IQR 24-30 versus 22 IQR 20-25; p = .01) in women having spontaneous vaginal birth compared to those undergoing operative delivery. Finally, there was no difference in the acceptability score between women with spontaneous onset of labor compared to those undergoing elective induction. CONCLUSIONS: UE is better tolerated VE for assessment of labor progress; women's compliance with UE prior to delivery increased in the presence of prolonged labor or unplanned operative delivery.

The added value of umbilical vein flow in predicting fetal macrosomia at 36 weeks of gestation: A prospective cohort study.

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.

Hemodynamic factors associated with fetal cardiac remodeling in late fetal growth restriction: a prospective study.

Background Altered cardiac geometry affects a proportion of fetuses with growth restriction (FGR). The aim of this study was to explore the hemodynamic factors associated with cardiac remodeling in late FGR. Methods This was a prospective study of singleton pregnancies complicated by late-onset FGR undergoing assessment of left (LV) and right (RV) ventricular sphericity-index (SI). The study population was divided in two groups according to the presence of cardiac remodelling, defined as LVSI <5th centile. The following outcomes were explored: gestational age at birth, birthweight, caesarean section (CS) for fetal distress, umbilical artery (UA) pH and neonatal admission to special care unit. The differences between the 2 groups in UA pulsatility index (PI), middle cerebral artery (MCA) PI, uterine artery PI, cerebroplacental ratio (CPR) and umbilical vein (UV) flow corrected for fetal abdominal circumference (UVBF/AC) were tested. Results In total, 212 pregnancies with late FGR were enrolled in the study. An abnormal LV SI was detected in 119 fetuses (56.1%). Late FGR fetuses with cardiac remodeling had a lower birthweight (2390 g vs. 2490; P = 0.04) and umbilical artery pH (7.21 vs. 7.24; P = 0.04) and were more likely to have emergency CS (42.8% vs. 26.9%; P = 0.023) and admission to special care unit (13.4% vs. 4.3%; P = 0.03) compared to those with normal LVSI. No difference in either UA PI (p = 0.904), MCA PI (P = 0.575), CPR (P = 0.607) and mean uterine artery PI (P = 0.756) were present between fetuses with or without an abnormal LV SI. Conversely, UVBF/AC z-score was lower (-1.84 vs. -0.99; P ≤ 0.001) in fetuses with cardiac remodeling and correlated with LV (P ≤ 0.01) and RV SI (P ≤ 0.02). Conclusion Fetal cardiac remodelling occurs in a significant proportion of pregnancies complicated by late FGR and is affected by a high burden of short-term perinatal compromise. The occurrence of LV SI is independent from fetal arterial Dopplers while it is positively associated with umbilical vein blood flow.