Clinical risk factors of adverse outcomes among women with COVID-19 in the pregnancy and postpartum period: a sequential, prospective meta-analysis.

OBJECTIVE: This sequential, prospective meta-analysis sought to identify risk factors among pregnant and postpartum women with COVID-19 for adverse outcomes related to disease severity, maternal morbidities, neonatal mortality and morbidity, and adverse birth outcomes. DATA SOURCES: We prospectively invited study investigators to join the sequential, prospective meta-analysis via professional research networks beginning in March 2020. STUDY ELIGIBILITY CRITERIA: Eligible studies included those recruiting at least 25 consecutive cases of COVID-19 in pregnancy within a defined catchment area. METHODS: We included individual patient data from 21 participating studies. Data quality was assessed, and harmonized variables for risk factors and outcomes were constructed. Duplicate cases were removed. Pooled estimates for the absolute and relative risk of adverse outcomes comparing those with and without each risk factor were generated using a 2-stage meta-analysis. RESULTS: We collected data from 33 countries and territories, including 21,977 cases of SARS-CoV-2 infection in pregnancy or postpartum. We found that women with comorbidities (preexisting diabetes mellitus, hypertension, cardiovascular disease) vs those without were at higher risk for COVID-19 severity and adverse pregnancy outcomes (fetal death, preterm birth, low birthweight). Participants with COVID-19 and HIV were 1.74 times (95% confidence interval, 1.12-2.71) more likely to be admitted to the intensive care unit. Pregnant women who were underweight before pregnancy were at higher risk of intensive care unit admission (relative risk, 5.53; 95% confidence interval, 2.27-13.44), ventilation (relative risk, 9.36; 95% confidence interval, 3.87-22.63), and pregnancy-related death (relative risk, 14.10; 95% confidence interval, 2.83-70.36). Prepregnancy obesity was also a risk factor for severe COVID-19 outcomes including intensive care unit admission (relative risk, 1.81; 95% confidence interval, 1.26-2.60), ventilation (relative risk, 2.05; 95% confidence interval, 1.20-3.51), any critical care (relative risk, 1.89; 95% confidence interval, 1.28-2.77), and pneumonia (relative risk, 1.66; 95% confidence interval, 1.18-2.33). Anemic pregnant women with COVID-19 also had increased risk of intensive care unit admission (relative risk, 1.63; 95% confidence interval, 1.25-2.11) and death (relative risk, 2.36; 95% confidence interval, 1.15-4.81). CONCLUSION: We found that pregnant women with comorbidities including diabetes mellitus, hypertension, and cardiovascular disease were at increased risk for severe COVID-19-related outcomes, maternal morbidities, and adverse birth outcomes. We also identified several less commonly known risk factors, including HIV infection, prepregnancy underweight, and anemia. Although pregnant women are already considered a high-risk population, special priority for prevention and treatment should be given to pregnant women with these additional risk factors.

Fetal magnetic resonance imaging at 36 weeks predicts neonatal macrosomia: the PREMACRO study.

BACKGROUND: Large-for-gestational-age fetuses are at increased risk of perinatal morbidity and mortality. Magnetic resonance imaging seems to be more accurate than ultrasound in the prediction of macrosomia; however, there is no well-powered study comparing magnetic resonance imaging with ultrasound in routine pregnancies. OBJECTIVE: This study aimed to prospectively compare estimates of fetal weight based on 2-dimensional ultrasound and magnetic resonance imaging with actual birthweights in routine pregnancies. STUDY DESIGN: From May 2016 to February 2019, women received counseling at the 36-week clinic. Written informed consent was obtained for this Ethics Committee-approved study. In this prospective, single-center, blinded study, pregnant women with singleton pregnancies between 36 0/7 and 36 6/7 weeks' gestation underwent both standard evaluation of estimated fetal weight with ultrasound according to Hadlock et al and magnetic resonance imaging according to the formula developed by Baker et al, based on the measurement of the fetal body volume. Participants and clinicians were aware of the results of the ultrasound but blinded to the magnetic resonance imaging estimates. Birthweight percentile was considered as the gold standard for the ultrasound and magnetic resonance imaging-derived percentiles. The primary outcome was the area under the receiver operating characteristic curve for the prediction of large-for-gestation-age neonates with birthweights of ≥95th percentile. Secondary outcomes included the comparative prediction of large-for-gestation-age neonates with birthweights of ≥90th, 97th, and 99th percentiles and small-for-gestational-age neonates with birthweights of ≤10th, 5th, and 3rd percentiles for gestational age and maternal and perinatal complications. RESULTS: Of 2914 women who were initially approached, results from 2378 were available for analysis. Total fetal body volume measurements were possible for all fetuses, and the time required to perform the planimetric measurements by magnetic resonance imaging was 3.0 minutes (range, 1.3-5.6). The area under the receiver operating characteristic curve for the prediction of a birthweight of ≥95th percentile was 0.985 using prenatal magnetic resonance imaging and 0.900 using ultrasound (difference=0.085, P<.001; standard error, 0.020). For a fixed false-positive rate of 5%, magnetic resonance imaging for the estimation of fetal weight detected 80.0% (71.1-87.2) of birthweight of ≥95th percentile, whereas ultrasound for the estimation of fetal weight detected 59.1% (49.0-68.5) of birthweight of ≥95th percentile. The positive predictive value was 42.6% (37.8-47.7) for the estimation of fetal weight using magnetic resonance imaging and 35.4% (30.1-41.1) for the estimation of fetal weight using ultrasound, and the negative predictive value was 99.0% (98.6-99.3) for the estimation of fetal weight using magnetic resonance imaging and 98.0% (97.6-98.4) for the estimation of fetal weight using ultrasound. For a fixed false-positive rate of 10%, magnetic resonance imaging for the estimation of fetal weight detected 92.4% (85.5-96.7) of birthweight of ≥95th percentile, whereas ultrasound for the estimation of fetal weight detected 76.2% (66.9-84.0) of birthweight of ≥95th percentile. The positive predictive value was 29.9% (27.2-32.8) for the estimation of fetal weight using magnetic resonance imaging and 26.2% (23.2-29.4) for the estimation of fetal weight using ultrasound, and the negative predictive value was 99.6 (99.2-99.8) for the estimation of fetal weight using magnetic resonance imaging and 98.8 (98.4-99.2) for the estimation of fetal weight using ultrasound. The area under the receiver operating characteristic curves for the prediction of large-for-gestational-age neonates with birthweights of ≥90th, 97th, and 99th percentiles and small-for-gestational-age neonates with birthweights of ≤10th, 5th, and 3rd percentiles was significantly larger in prenatal magnetic resonance imaging than in ultrasound (P<.05 for all). CONCLUSION: At 36 weeks' gestation, magnetic resonance imaging for the estimation of fetal weight performed significantly better than ultrasound for the estimation of fetal weight in the prediction of large-for-gestational-age neonates with birthweights of ≥95th percentile for gestational age and all other recognized cutoffs for large-for-gestational-age and small-for-gestational-age neonates (P<.05 for all).

Severe Acute Respiratory Syndrome Coronavirus 2 and Pregnancy Outcomes According to Gestational Age at Time of Infection.

We conducted an international multicenter retrospective cohort study, PregOuTCOV, to examine the effect of gestational age at time of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on obstetric and neonatal outcomes. We included all singleton pregnancies with a live fetus at 10 weeks' gestation in which pregnancy outcomes were known. The exposed group consisted of patients infected with SARS-CoV-2, whereas the unexposed group consisted of all remaining patients during the same period. Primary outcomes were defined as composite adverse obstetric outcomes and composite adverse neonatal outcomes. Of 10,925 pregnant women, 393 (3.60%) were infected with SARS-CoV-2 (exposed group). After matching for possible confounders, we identified statistically significant increases in the exposed group of composite adverse obstetric outcomes at >20 weeks' gestation and of composite adverse neonatal outcomes at >26 weeks' gestation (p<0.001). Vaccination programs should target women early in pregnancy or before conception, if possible.

Spontaneous twin anemia polycythemia sequence: diagnosis, management, and outcome in an international cohort of 249 cases.

BACKGROUND: Twin anemia polycythemia sequence is a chronic form of unbalanced fetofetal transfusion through minuscule placental anastomoses in monochorionic twins, leading to anemia in the donor and polycythemia in the recipient. Owing to the low incidence of twin anemia polycythemia sequence, data on diagnosis, management, and outcome are limited. OBJECTIVE: This study aimed to investigate the diagnosis, management, and outcome in a large international cohort of spontaneous twin anemia polycythemia sequence. STUDY DESIGN: Data from the international twin anemia polycythemia sequence registry, retrospectively collected between 2014 and 2019, were used for this study. A total of 17 fetal therapy centers contributed to the data collection. The primary outcomes were perinatal mortality and severe neonatal morbidity. Secondary outcomes included a risk factor analysis for perinatal mortality and severe neonatal morbidity. RESULTS: A total of 249 cases of spontaneous twin anemia polycythemia sequence were included in this study, 219 (88%) of which were diagnosed antenatally and 30 (12%) postnatally. Twin anemia polycythemia sequence was diagnosed antenatally at a median gestational age of 23.7 weeks (interquartile range, 9.7-28.8; range, 15.1-35.3). Antenatal management included laser surgery in 39% (86 of 219), expectant management in 23% (51 of 219), delivery in 16% (34 of 219), intrauterine transfusion (with partial exchange transfusion) in 12% (26 of 219), selective feticide in 8% (18 of 219), and termination of pregnancy in 1% (3 of 219) of cases. Perinatal mortality rate was 15% (72 of 493) for the total group, 22% (54 of 243) for donors, and 7% (18 of 242) for recipients (P<.001). Severe neonatal morbidity occurred in 33% (141 of 432) of twins with twin anemia polycythemia sequence and was similar for donors (32%; 63 of 196) and recipients (33%; 75 of 228) (P=.628). Independent risk factors for spontaneous perinatal mortality were donor status (odds ratio, 3.8; 95% confidence interval, 1.9-7.5; P<.001), antenatal twin anemia polycythemia sequence stage (odds ratio, 6.3; 95% confidence interval, 1.4-27.8; P=.016 [stage 2]; odds ratio, 9.6; 95% confidence interval, 2.1-45.5; P=.005 [stage 3]; odds ratio, 20.9; 95% confidence interval, 3.0-146.4; P=.002 [stage 4]), and gestational age at birth (odds ratio, 0.8; 95% confidence interval, 0.7-0.9; P=.001). Independent risk factors for severe neonatal morbidity were antenatal twin anemia polycythemia sequence stage 4 (odds ratio, 7.9; 95% confidence interval, 1.4-43.3; P=.018) and gestational age at birth (odds ratio, 1.7; 95% confidence interval, 1.5-2.1, P<.001). CONCLUSION: Spontaneous twin anemia polycythemia sequence can develop at any time in pregnancy from the beginning of the second trimester to the end of the third trimester. Management for twin anemia polycythemia sequence varies considerably, with laser surgery being the most frequent intervention. Perinatal mortality and severe neonatal morbidity were high, the former especially so in the donor twins.

Antenatal management and neonatal outcomes of monochorionic twin pregnancies in a tertiary teaching hospital: a 10-year review.

Monochorionic (MC) pregnancy is a high risk pregnancy with well-defined specific complications, such as twin-to-twin transfusion syndrome (TTTS) and twin anaemia-polycythaemia sequence (TAPS). Laser photocoagulation (LPC) is an effective treatment for both complications. In the current retrospective study, we determined the incidence of MC pregnancy complications in a tertiary care centre during a 10-year period. Single foetal death (FD) beyond 14 weeks' gestation was significantly higher when complicated by either TTTS, TAPS or selective foetal growth restriction (21.4%, 16.7% and 9.1% versus 1.6%, p<.001, p=.02 and p=.04, respectively). We also demonstrated that twins' weight discordance >20% is an independent risk factor for single or double FD after LPC. Consequently, prior to LPC, patients should be counselled that early diagnosis of TTTS, advanced Quintero stages and weight discordances >20% are potential risk factors for FD. Further studies are needed to identify additional risk factors for TTTS and TAPS outcome after LPC.Impact StatementWhat is already known on this subject? Monochorionic (MC) pregnancy is a high risk pregnancy with well-defined specific complications, such as twin-twin transfusion syndrome (TTTS) and twin anaemia-polycythaemia sequence (TAPS). Laser photocoagulation (LPC) is an effective treatment for both complications.What the results of this study add? The results of the current study determined the incidence of MC pregnancy complications in a tertiary care centre in Brussels, and identified that twins' weight discordance >20% is an independent risk factor for single or double foetal death after LPC.What the implications are of these findings for clinical practice and/or further research? Prior to laser coagulation, patients should be counselled that early diagnosis of TTTS, Quintero stages 3 or 4 and weight discordances >20% are potential risk factors for foetal demise. Further studies are needed to identify additional risk factors for TTTS and TAPS outcome after LPC.

An ACVRL1 gene mutation presenting as vein of Galen malformation at prenatal diagnosis.

Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal dominant disease. The diagnostic criteria of HHT, or Curaçao criteria, include the following: recurrent epistaxis or nighttime nose bleeding, mucocutaneous telangiectases, visceral arteriovenous malformation, or an appropriate family history. The diagnosis is classified as definite if three criteria are present, possible if two criteria are present, and unlikely if only one is present. Nowadays, the confirmation of HHT diagnosis is based on molecular genetic studies. It has been showed that only mutations of genes encoding proteins within the transforming growth factor beta signaling pathway were responsible for the manifestation of the disease. The vein of Galen malformation (VOGM) as a presenting sign of HHT is rare. The prenatal diagnosis of HHT is even rarer. Herein, we present a case of prenatally diagnosed case of HHT based on the presence of VOGM in the fetus. To our knowledge, it is the first time that the gene mutation discovered in this case manifested as VOGM in the fetal life.

Cell-Free DNA Analysis in Maternal Blood: Differences in Estimates between Laboratories with Different Methodologies Using a Propensity Score Approach.

OBJECTIVES: To evaluate the failure rate and performance of cell-free DNA (cfDNA) testing, mainly in terms of detection rates for trisomy 21, performed by 2 laboratories using different analytical methods. METHODS: cfDNA testing was performed on 2,870 pregnancies with the HarmonyTM Prenatal Test using the targeted digital analysis of selected regions (DANSR) method, and on 2,635 pregnancies with the "Cerba test" using the genome-wide massively parallel sequencing (GW-MPS) method, with available outcomes. Propensity score analysis was used to match patients between the 2 groups. A comparison of the detection rates for trisomy 21 between the 2 laboratories was made. RESULTS: In all, 2,811 patients in the Harmony group and 2,530 patients in the Cerba group had no trisomy 21, 18, or 13. Postmatched comparisons of the patient characteristics indicated a higher no-result rate in the Harmony group (1.30%) than in the Cerba group (0.75%; p = 0.039). All 41 cases of trisomy 21 in the Harmony group and 93 cases in the Cerba group were detected. CONCLUSIONS: Both methods of cfDNA testing showed low no-result rates and a comparable performance in detecting trisomy 21; yet GW-MPS had a slightly lower no-result rate than the DANSR method.

Comparison of conventional 2D ultrasound to magnetic resonance imaging for prenatal estimation of birthweight in twin pregnancy.

BACKGROUND: During prenatal follow-up of twin pregnancies, accurate identification of birthweight and birthweight discordance is important to identify the high-risk group and plan perinatal care. Unfortunately, prenatal evaluation of birthweight discordance by 2-dimensional ultrasound has been far from optimal. OBJECTIVE: The objective of the study was to prospectively compare estimates of fetal weight based on 2-dimensional ultrasound (ultrasound-estimated fetal weight) and magnetic resonance imaging (magnetic resonance-estimated fetal weight) with actual birthweight in women carrying twin pregnancies. STUDY DESIGN: Written informed consent was obtained for this ethics committee-approved study. Between September 2011 and December 2015 and within 48 hours before delivery, ultrasound-estimated fetal weight and magnetic resonance-estimated fetal weight were conducted in 66 fetuses deriving from twin pregnancies at 34.3-39.0 weeks; gestation. Magnetic resonance-estimated fetal weight derived from manual measurement of fetal body volume. Comparison of magnetic resonance-estimated fetal weight and ultrasound-estimated fetal weight measurements vs birthweight was performed by calculating parameters as described by Bland and Altman. Receiver-operating characteristic curves were constructed for the prediction of small-for-gestational-age neonates using magnetic resonance-estimated fetal weight and ultrasound-estimated fetal weight. For twins 1 and 2 separately, the relative error or percentage error was calculated as follows: (birthweight - ultrasound-estimated fetal weight (or magnetic resonance-estimated fetal weight)/birthweight) × 100 (percentage). Furthermore, ultrasound-estimated fetal weight, magnetic resonance-estimated fetal weight, and birthweight discordance were calculated as 100 × (larger estimated fetal weight-smaller estimated fetal weight)/larger estimated fetal weight. The ultrasound-estimated fetal weight discordance and the birthweight discordance were correlated using linear regression analysis and Pearson's correlation coefficient. The same was done between the magnetic resonance-estimated fetal weight and birthweight discordance. To compare data, the χ2, McNemar test, Student t test, and Wilcoxon signed rank test were used as appropriate. We used the Fisher r-to-z transformation to compare correlation coefficients. RESULTS: The bias and the 95% limits of agreement of ultrasound-estimated fetal weight are 2.99 (-19.17% to 25.15%) and magnetic resonance-estimated fetal weight 0.63 (-9.41% to 10.67%). Limits of agreement were better between magnetic resonance-estimated fetal weight and actual birthweight as compared with the ultrasound-estimated fetal weight. Of the 66 newborns, 27 (40.9%) were of weight of the 10th centile or less and 21 (31.8%) of the fifth centile or less. The area under the receiver-operating characteristic curve for prediction of birthweight the 10th centile or less by prenatal ultrasound was 0.895 (P < .001; SE, 0.049), and by magnetic resonance imaging it was 0.946 (P < .001; SE, 0.024). Pairwise comparison of receiver-operating characteristic curves showed a significant difference between the areas under the receiver-operating characteristic curves (difference, 0.087, P = .049; SE, 0.044). The relative error for ultrasound-estimated fetal weight was 6.8% and by magnetic resonance-estimated fetal weight, 3.2% (P < .001). When using ultrasound-estimated fetal weight, 37.9% of fetuses (25 of 66) were estimated outside the range of ±10% of the actual birthweight, whereas this dropped to 6.1% (4 of 66) with magnetic resonance-estimated fetal weight (P < .001). The ultrasound-estimated fetal weight discordance and the birthweight discordance correlated significantly following the linear equation: ultrasound-estimated fetal weight discordance = 0.03 + 0.91 × birthweight (r = 0.75; P < .001); however, the correlation was better with magnetic resonance imaging: magnetic resonance-estimated fetal weight discordance = 0.02 + 0.81 × birthweight (r = 0.87; P < .001). CONCLUSION: In twin pregnancies, magnetic resonance-estimated fetal weight performed immediately prior to delivery is more accurate and predicts small-for-gestational-age neonates significantly better than ultrasound-estimated fetal weight. Prediction of birthweight discordance is better with magnetic resonance imaging as compared with ultrasound.

Screening for Sex Chromosome Aneuploidy by Cell-Free DNA Testing: Patient Choice and Performance.

OBJECTIVE: To study patient choice regarding testing for sex chromosome aneuploidy (SCA) and the performance of cell-free DNA (cfDNA) screening for SCA. METHODS: Patient choice regarding screening for SCA and factors influencing this choice were evaluated in a single center. In a subsequent two-center study, cases that screened positive for SCA were analyzed to determine the positive predictive value (PPV) for each SCA. RESULTS: In all, 1,957 (61.9%) of the 3,162 patients undergoing cfDNA testing opted for SCA screening. Regression analysis demonstrated that independent predictors of a patient's decision for SCA were earlier gestational age, spontaneous conception, and cfDNA chosen as a primary method of screening. A total of 161 cases screened positive for SCA and follow-up data were available for 118 (73.3%). Forty-six of the 61 cases of 45,X were false-positive results and 15 were concordant with the fetal karyotype (PPV = 24.6%). Seventeen of the 22 cases of 47,XXX were false positive and 5 concordant (PPV = 22.7%). Eleven of the 30 cases of 47,XXY were false positive and 19 concordant (PPV = 63.3%). All 5 cases of 47,XYY were correctly identified, thus yielding a PPV of 100%. CONCLUSION: More than half of the patients undergoing cfDNA aneuploidy screening also opted for SCA testing, but they were less likely to do so in the presence of an increased risk of trisomy. SCAs involving the X chromosome had a lower PPV than those involving the Y chromosome.

Prenatal Screening for 22q11.2 Deletion Using a Targeted Microarray-Based Cell-Free DNA Test.

OBJECTIVE: To determine the performance of a targeted microarray-based cell-free DNA (cfDNA) test (Harmony Prenatal Test®) for the identification of pregnancies at increased risk for 22q11.2 deletion. METHODS: Test performance was determined in 2 steps including a total of 1,953 plasma samples. Analytical validation was performed in 1,736 plasma samples. Clinical verification of performance was performed in an additional 217 prospectively ascertained samples from pregnancies with fetal deletion status determined by diagnostic testing. RESULTS: Analytical sensitivity was 75.4% (95% CI: 67.1-82.2%) based on 122 samples with deletions ranging from 1.96 to 3.25 Mb. In 1,614 presumed unaffected samples, specificity was determined to be at least 99.5% (95% CI: 99.0-99.7%). In the clinical cohort, 5 of 7 samples from pregnancies affected with 22q11.2 deletion were determined to have a high probability of deletion. There were no false positive results in the 210 unaffected samples in this cohort. These clinical data are consistent with the performance demonstrated in the analytical validation. CONCLUSIONS: cfDNA testing using a targeted microarray-based technology is able to identify pregnancies at increased risk for 22q11.2 deletions of 3.0 Mb and smaller while maintaining a low false positive rate.

Post-mortem whole-body magnetic resonance imaging of human fetuses: a comparison of 3-T vs. 1.5-T MR imaging with classical autopsy.

OBJECTIVE: To prospectively compare diagnostic accuracy of fetal post-mortem whole-body MRI at 3-T vs. 1.5-T. METHODS: Between 2012 and 2015, post-mortem MRI at 1.5-T and 3-T was performed in fetuses after miscarriage/stillbirth or termination. Clinical MRI diagnoses were assessed using a confidence diagnostic score and compared with classical autopsy to derive a diagnostic error score. The relation of diagnostic error for each organ group with gestational age was calculated and 1.5-T with 3-T was compared with accuracy analysis. RESULTS: 135 fetuses at 12-41 weeks underwent post-mortem MRI (followed by conventional autopsy in 92 fetuses). For all organ groups except the brain, and for both modalities, the diagnostic error decreased with gestation (P < 0.0001). 3-T MRI diagnostic error was significantly lower than that of 1.5-T for all anatomic structures and organ groups, except the orbits and brain. This difference was maintained for fetuses <20 weeks gestation. Moreover, 3-T was associated with fewer non-diagnostic scans and greater concordance with classical autopsy than 1.5-T MRI, especially for the thorax, heart and abdomen in fetuses <20 weeks. CONCLUSION: Post-mortem fetal 3-T MRI improves confidence scores and overall accuracy compared with 1.5-T, mainly for the thorax, heart and abdomen of fetuses <20 weeks of gestation. KEY POINTS: • In PM-MRI, diagnostic error using 3-T is lower than that with 1.5-T. • In PM-MRI, diagnostic scan rate is higher using 3-T than 1.5-T. • In PM-MRI, concordance with classical autopsy increases with 3-T. • PM-MRI using 3-T is particularly interesting for thoracic and abdominal organs. • PM-MRI using 3-T is particularly interesting for fetuses < 20 weeks' gestation.

A Longitudinal Study on Fetal Weight Estimation at Third Trimester of Pregnancy: Comparison of Magnetic Resonance Imaging and 2-D Ultrasound Predictions.

OBJECTIVE: To prospectively compare magnetic resonance (MR) estimation of fetal weight (MR-EFW) performed at third trimester with ultrasound (US) estimation of fetal weight (US-EFW) and actual birth weight, and to evaluate factors influencing fetal growth rate near term. METHODS: US-EFW and MR-EFW were calculated at a median of 33.0 and 37.7 weeks of gestation in 37 fetuses and plotted on curve centiles to predict birth weights at 39.3 weeks of gestation. The median absolute relative errors for predicted US-EFW and MR-EFW were calculated. Regression analysis was used to investigate the effect of different variables on fetal growth rate at 35.2 weeks of gestation. RESULTS: The relative error of actual birth weight as predicted by US at 33.0 weeks was significantly higher compared with MR (7.33 vs. 4.11%; p = 0.001). This was also the case for fetal weight predicted by US at 37.7 weeks as compared with MR (6.63 vs. 2.60%; p < 0.01). Fetal growth rate was significantly and independently positively associated with the mother's weight and with gestational age at estimation (p < 0.05 for both variables). CONCLUSION: Fetal weight estimates predicted using MR at third trimester are better than those given by prenatal US. Fetal growth rate depends on fetal and maternal characteristics.

Effects of SARS-Cov-2 mRNA vaccine on placental histopathology: Comparison of a population of uncomplicated COVID-19 positive pregnant women.

1. INTRODUCTION: This study investigates the impact of SARS-CoV-2 infection on placental histopathology in pregnant women, comparing outcomes between vaccinated and non-vaccinated individuals. Despite known adverse pregnancy outcomes linked to SARS-CoV-2 infection, the specific effects on the placenta remain unclear. Although vaccination has demonstrated a substantial reduction in infection severity, its impact on placental health requires more insight. 2. METHODS: Between March 2021 and July 2022, 387 COVID-19-positive women were admitted for delivery. Of these, 98 with non-severe symptoms were analyzed: 35 vaccinated during pregnancy, and 63 non-vaccinated. Two independent pathologists evaluated all placental specimens. 3. RESULTS: The only differing obstetrical characteristic between groups was the mode of delivery (p 0.047), lacking clinical implications. Over 85% of placentas exhibited microscopic abnormalities, predominantly maternal vascular supply disorders (vaccinated 89.1%; unvaccinated 85.5%). Comparing vaccinated and unvaccinated groups revealed statistically significant differences, notably in increased focal perivillous fibrin deposits (IFPFD) [17.1% vs. 33.3% (p 0.04)] and avascular fibrotic villi (AFV) [0% vs. 11.1% (p 0.04)]. Binomial logistic regression confirmed the vaccine's protective role against IFPFD (aOR 0.36; 95%CI 013-0.99) and AVF (aOR 0.06, 95% CI 0.003-0.98). A sub-analysis in vaccinated women showed a positive correlation between the timing of the first dose and IFPFD presence (p 0.018). 4. DISCUSSION: The lower incidence of maternal and fetal vascular malperfusion placental features in vaccinated women, coupled with the timing correlation, supports the vaccine's protective effect on placental tissue in COVID-19-infected pregnant patients. Notably, no side effects were reported post-vaccination, emphasizing the vaccine's safety and advocating for its secure administration in pregnant populations.

Is the mental health of couples with twins more at risk? Results from an Italian cohort study.

Introduction: Our retrospective study aimed to investigate whether parents of twins encounter heightened psychological and emotional distress one year after childbirth, in comparison to parents of singletons within an Italian cohort. Methods: Exclusion criteria included multiparity, preterm birth, congenital anomalies, stillbirth, >2 fetus pregnancies, and pre-existing maternal mental health disorders. Out of the 300 couples (600 parents) invited to participate, 286 parents (158 mothers, 128 fathers) successfully completed a self-administered survey. We analyzed three scores separately for mothers and fathers, differentiating between singleton and twin pregnancies: the Edinburgh Postnatal Depression Scale (EPDS) score, the State and Trait Anxiety Inventory (STAI)-Y1 score, and the STAI-Y2 score. Results: Logistic models were used to assess the influence of age, BMI, marital status, education, and employment on the three binary scores (EPDS, STAI-Y1, and STAI-Y2), revealing no significant differences in absolute scores between parents of singletons and twins. Paired analysis revealed significantly higher EPDS (mean increase: 3.8, SD: 6.5), STAI-Y1 (mean increase: 5.4, SD: 12.5), and STAI-Y2 (mean increase: 4.5, SD: 12.4) scores for mothers (p < 0.0001). Approximately 10% of women and 8% of men reported suicidal thoughts. Discussion: Contrary to expectations, no substantial psychological differences emerged between parents of twins and singletons. Adjusting for confounders through univariate analysis maintained nonsignificant trends. Nevertheless, caution in interpretation is warranted due to strict inclusion criteria favoring twin pregnancies with better outcomes. Unintended bias could have resulted from routine psychological support offered to mothers of twins in our clinic. This presents an important framework for future research, including randomized controlled trials comparing parents of multiples with psychological support to those without.Finally, the elevated prevalence of depression symptoms and suicidal thoughts in our cohort underscores the importance of mental health during pregnancy and early parenting. We advocate for the screening of parents for postpartum depression and various psychological conditions, encompassing a spectrum of anxiety disorders. Those at elevated risk of mental distress should be proactively offered appropriate support.

Maternal and fetal outcomes after planned cesarean or vaginal delivery in twin pregnancy: a comparison between 2 third level birth centers.

BACKGROUND: Twin pregnancy is associated with higher risks of adverse perinatal outcomes for both the mother and the babies. Among the many challenges in the follow-up of twin pregnancies, the mode of delivery is the last but not the least decision to be made, with the main influencing factors being amnionicity and fetal presentation. The aim of the study was to compare perinatal outcomes in two European centers using different protocols for twin birth in case of non-cephalic second twin; the Italian patients being delivered mainly by cesarean section with those in Belgium being routinely offered the choice of vaginal delivery (VD). METHODS: This was a dual center international retrospective observational study. The population included 843 women with a twin pregnancy ≥ 32 weeks (dichorionic or monochorionic diamniotic pregnancies) and a known pregnancy outcome. The population was stratified according to chorionicity. Demographic and pregnancy data were reported per pregnancy, whereas neonatal outcomes were reported per fetus. We used multiple logistic regression models to adjust for possible confounding variables and to compute the adjusted odds ratio (adjOR) for each maternal or neonatal outcome. RESULTS: The observed rate of cesarean delivery was significantly higher in the Italian cohort: 85% for dichorionic pregnancies and 94.4% for the monochorionic vs 45.2% and 54.4% respectively in the Belgian center (p-value < 0.001). We found that Belgian cohort showed significantly higher rates of NICU admission, respiratory distress at birth and Apgar score of < 7 after 5 min. Despite these differences, the composite severe adverse outcome was similar between the two groups. CONCLUSION: In this study, neither the presentation of the second twin nor the chorionicity affected maternal and severe neonatal outcomes, regardless of the mode of delivery in two tertiary care centers, but VD was associated to a poorer short-term neonatal outcome.

Menopausal symptoms after the discontinuation of long-term hormone replacement therapy in women under 60: a 3-year follow-up.

BACKGROUND: Prescriptions for hormone replacement therapy (HRT) declined following the publication of the Women's Health Initiative study. The number of women who experience recurrence of menopausal symptoms after discontinuation of long-term HRT (LT-HRT), the length of time these symptoms last and the preferred alternative treatments remain unknown. METHODS: This prospective 3-year follow-up study analyses the prevalence and intensity of menopausal symptoms that occur in young postmenopausal women who discontinued LT-HRT. Symptoms were evaluated using the Menopause Rating Scale. RESULTS: Women (254) who discontinued LT-HRT (mean use: 6.9 ± 2.3 years) were recruited. Mean age at menopause was 48.1 ± 3.4 years. Mean age at discontinuation was 56.8 ± 3.7 years. 23% of the women were lost to follow-up. Of the remaining 196 women, 93% experienced a recurrence of menopausal symptoms within the first year, 25% resumed low-dose HRT, 62% used vaginal estrogens, 54% used phytoestrogens, and 2% used alternative therapies. A decrease in symptom prevalence and intensity was observed during the 3-year follow-up. CONCLUSIONS: Symptoms re-appeared in a significant proportion of patients within the first year after discontinuation of LT-HRT. However, after 3 years, the majority of these women were asymptomatic. Patients who discontinue LT-HRT may require a more detailed follow-up immediately after the discontinuation of treatment.

Dysregulation of diurnal salivary cortisol production is associated with spontaneous preterm delivery: a pilot study.

OBJECTIVES: The purpose of this study was to evaluate whether the diurnal fluctuation of salivary cortisol and its overall diurnal secretion are associated with the length of gestation in patients who were admitted to the hospital with an assigned diagnosis of possible preterm labor (PL) at a gestational age of 28-33 weeks. METHODS: In 22 patients, maternal saliva samples were collected for a cortisol assay 4 times per day (8 AM, 12 AM, 4 PM and 8 PM) on day 4 and day 6 after antenatal corticosteroid prophylaxis to prevent neonatal respiratory distress syndrome. RESULTS: Eight patients who ultimately delivered before term (32.6 ± 1.7 gestation weeks) showed an inverted fluctuation of salivary cortisol on both days 4 and 6, morning cortisol levels being significantly lower than evening levels. In contrast, in 14 patients who delivered at term (39.5 ± 0.6 gestation weeks), the physiological diurnal fluctuation of salivary cortisol was maintained. In addition, a distinctive feature of women delivering before term was a significantly hampered salivary cortisol diurnal production measured on day 6. CONCLUSIONS: Corticoadrenal activity is dysregulated and anticipates very preterm delivery in women with an assigned diagnosis of possible PL.

Multiple Pregnancy and the Risk of Postpartum Hemorrhage: Retrospective Analysis in a Tertiary Level Center of Care.

The aim of our study was to identify characteristics associated with postpartum hemorrhage (PPH defined as blood loss >1000 mL) in twin pregnancies in order to select patients at higher risk to be treated. This retrospective study includes multiple pregnancies between 2015 and 2020. The possible association between pregnancy characteristics and the primary endpoint (occurrence of PPH) was conducted using chi-square or Fisher exact test and Wilcoxon test. Then, univariate logistic models were performed considering as outcome the PPH, and the odds ratios with 95% CI were estimated. Finally, a multivariate logistic model was implemented, including all significant covariates. Seven hundred seven twin pregnancies giving birth beyond 32 weeks were included and of those, 120 (16.97%) had a PPH. The univariate analysis showed that factors significantly associated with PPH were: Preterm delivery, episiotomy, neonatal weight, and mode of delivery. The multivariate analysis showed that the most important factors were episiotomy and neonatal weight. The results show that the performance of episiotomy and the neonatal weight are the factors that most impact the risk of PPH in twin pregnancies. The correct identification of factors associated with PPH in twins could ideally allow to modify the clinical management and positively affect the rate of complications.

Risk factors associated with severe perineal lacerations during vaginal delivery: a 10-year propensity score-matched observational study.

BACKGROUND: Severe perineal lacerations are rare obstetrical complications in high-income countries. However, the prevention of obstetric anal sphincter injuries is crucial because of their long-term consequences on a woman's digestive function, sexual-mental health, and well-being. The probability of obstetric anal sphincter injuries can be predicted by assessing antenatal and intrapartum risk factors. OBJECTIVE: This study aimed to assess the incidence of obstetric anal sphincter injuries at a single institution for 10 years and to identify women more at risk by evaluating the relationship between antenatal and intrapartum risk factors and severe perineal tears. The main outcome measured in this study was the occurrence of obstetric anal sphincter injuries during vaginal delivery. STUDY DESIGN: This was an observational retrospective cohort study conducted at a University Teaching Hospital in Italy. The study was conducted from 2009 to 2019 using a prospectively maintained database. The study cohort included all women with singleton pregnancy at term who delivered via vaginal delivery in cephalic presentation. Of note, data analysis was performed in 2 stages: a propensity score matching to balance possible differences between patients with obstetric anal sphincter injuries and those without and a stepwise univariate and multivariate logistic regression. A secondary analysis was performed to further evaluate the effect of parity, epidural anesthesia, and duration of the second stage of labor by adjusting for potential confounders. RESULTS: Of 41,440 patients screened for eligibility, 22,156 met the inclusion criteria, and 15,992 were balanced after propensity score matching. Obstetric anal sphincter injuries occurred in 81 cases (0.4%), 67 (0.3%) after spontaneous delivery and 14 (0.8%) after vacuum delivery(P=.002). There was an increased odds of severe lacerations of nearly 2-fold for nulliparous women delivering by vacuum delivery (adjusted odds ratio, 2.85; 95% confidence interval, 1.19-6.81; P=.019), with a reciprocal reduction in women with spontaneous vaginal delivery (adjusted odds ratio, 0.35; 95% confidence interval, 0.15-0.84; P=.019) and at least 1 previous delivery (adjusted odds ratio, 0.51; 95% confidence interval, 0.31-0.85; P=.005). Epidural anesthesia was associated with a lower incidence of obstetric anal sphincter injuries (adjusted odds ratio, 0.54; 95% confidence interval, 0.33-0.86; P=.011). The risk of severe lacerations was independent of the duration of the second stage of labor (adjusted odds ratio, 1.00; 95% confidence interval, 0.99-1.00; P=.3), whereas the risk was reduced when mediolateral episiotomy was performed (adjusted odds ratio, 0.20; 95% confidence interval, 0.11-0.36; P<.001). Neonatal risk factors include head circumference (odds ratio, 1.50; 95% confidence interval, 1.18-1.90; P=.001) and vertex malpresentation (adjusted odds ratio, 2.71; 95% confidence interval, 1.08-6.78; P=.033). Induction of labor (adjusted odds ratio, 1.13; 95% confidence interval, 0.72-1.92; P=.6), frequent obstetrical examinations (adjusted odds ratio, 1.17; 95% confidence interval, 0.72-1.90), and women's supine position at birth (adjusted odds ratio, 1.25; 95% confidence interval, 0.61-2.55; P=.5) were further evaluated. Among severe obstetrical complications, shoulder dystocia increased the risk of obstetric anal sphincter injuries by nearly 4 times (adjusted odds ratio, 3.92; 95% confidence interval, 0.50-30.74; P=.2), whereas postpartum hemorrhage occurred 3 times more often in cases of delivery complicated by severe lacerations (adjusted odds ratio, 3.35; 95% confidence interval, 1.76-6.40; P<.001). The relationship among obstetric anal sphincter injuries, parity, and the use of epidural anesthesia was further confirmed in a secondary analysis. We found that primiparas who delivered without epidural anesthesia had the highest risk of obstetric anal sphincter injuries (adjusted odds ratio, 2.53; 95% confidence interval, 1.46-4.39; P=.001). CONCLUSION: Severe perineal lacerations were found to be a rare complication of vaginal delivery. By using a robust statistical model, such as propensity score matching, we were able to investigate a broad range of antenatal and intrapartum risk factors, including use of epidural anesthesia, number of obstetrics examinations, and patient position at birth, which are usually underreported. Moreover, we found that women who delivered for the first time without epidural anesthesia had the highest risk of obstetric anal sphincter injuries.

The impact of placental anastomoses and umbilical cord insertions' sites on monochorionic twin pregnancy outcomes: Evidence from color-dye injection studies.

INTRODUCTION: Our knowledge of monochorionic pregnancies' complications is largely based on the extensive ongoing research on monochorionic placental structure. Previous studies on the concordance of umbilical cord insertions are limited. This study aimed to evaluate placental anastomoses and cord insertions as independent risk factors for neonatal adverse outcomes. METHODS: This was a prospective study conducted at Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy from April 2021 to December 2022. Seventy-six women with a monochorionic pregnancy were enrolled at their first-trimester scan. After delivery, all placentas that were confirmed to be monochorionic were analyzed according to standard protocols, including those of complicated monochorionic twin pregnancies. The primary outcomes were a Composite Monochorionic Pregnancy Outcome (CMPO) and a Composite Neonatal Adverse Outcome (CNAO). The secondary outcome was the birth weight discordance between the neonates. RESULTS: The CMPO occurred in 15.8 % pregnancies, and the CNAO occurred in 67.1 % pregnancies. The analysis confirmed a significant association between velamentous cord insertions and neonatal adverse events (p = 0.003). Also, a significant positive association (p = 0.0326) between twin birth weight discordance and discordance in twins umbilical cord insertions' sites was found. No significant association between the number and type of the anastomoses and both the CMPO or CNAO was detected. DISCUSSION: Our data suggest that the routine sonographic assessment of umbilical cords' insertion sites during the first trimester could be helpful in predicting fetal and neonatal adverse events. We believe that this sonographic assessment should start to be implemented in our routine care of monochorionic pregnancies.