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Objectives: Twin pregnancies are at higher risk of stillbirth compared to singletons. Fetal growth restriction (FGR) is a major cause of perinatal mortality, but its impact on twins vs singletons remains unclear. The primary objective of this study was to investigate the association of FGR and small‐for‐gestational age (SGA) with stillbirth in twin compared with singleton pregnancies. A secondary objective was to assess these associations stratified by gestational age at delivery. Furthermore, we aimed to compare the associations of FGR and SGA with stillbirth in twin pregnancies using twin‐specific vs singleton birth‐weight charts, stratified by chorionicity. Methods: This was a retrospective cross‐sectional study of pregnancies receiving obstetric care and giving birth between 1999 and 2022 at St George's Hospital, London, UK. The exclusion criteria included triplet and higher‐order pregnancies, those resulting in miscarriage or live birth at ≤ 23 + 6 weeks, termination of pregnancy and missing data regarding birth weight or gestational age at birth. Birth‐weight data were collected and FGR and SGA were defined as birth weight <5th and <10th centiles, respectively. While standard logistic regression was used for singleton pregnancies, the association of FGR and SGA with stillbirth in twin pregnancies was investigated using mixed‐effects logistic regression models. For twin pregnancies, intercepts were allowed to vary for twin pairs to account for intertwin dependency. Analyses were stratified by gestational age at delivery and chorionicity. Statistical significance was set at P ≤ 0.001. Results: The study included 95 342 singleton and 3576 twin pregnancies. There were 494 (0.52%) stillbirths in singleton and 41 (1.15%) stillbirths in twin pregnancies (17 dichorionic and 24 monochorionic). SGA and FGR were associated significantly with stillbirth in singleton pregnancies across all gestational ages at delivery: the odds ratios (ORs) for SGA and FGR were 2.36 ((95% CI, 1.78–3.13), P < 0.001) and 2.67 ((95% CI, 2.02–3.55), P < 0.001), respectively, for delivery before 32 weeks; 2.70 ((95% CI, 1.71–4.31), P < 0.001) and 2.82 ((95% CI, 1.78–4.47), P < 0.001), respectively, for delivery between 32 and 36 weeks; and 3.85 ((95% CI, 2.83–5.21), P < 0.001) and 4.43 ((95% CI, 3.16–6.12), P < 0.001), respectively, for delivery after 36 weeks. In twin pregnancies, when stratified by gestational age at delivery, both SGA and FGR determined by twin‐specific birth‐weight charts were associated with increased odds of stillbirth for those delivered before 32 weeks (SGA: OR, 3.87 (95% CI, 1.56–9.50), P = 0.003 and FGR: OR, 5.26 (95% CI, 2.11–13.01), P = 0.001), those delivered between 32 and 36 weeks (SGA: OR, 6.67 (95% CI, 2.11–20.41), P = 0.001 and FGR: OR, 9.54 (95% CI, 3.01–29.40), P < 0.001) and those delivered beyond 36 weeks (SGA: OR, 12.68 (95% CI, 2.47–58.15), P = 0.001 and FGR: OR, 23.84 (95% CI, 4.62–110.25), P < 0.001). However, the association of stillbirth with SGA and FGR in twin pregnancies was non‐significant when diagnosis was based on singleton charts (before 32 weeks: SGA, P = 0.014 and FGR, P = 0.005; 32–36 weeks: SGA, P = 0.036 and FGR, P = 0.008; after 36 weeks: SGA, P = 0.080 and FGR, P = 0.063). Conclusion: Our study demonstrates that SGA and, especially, FGR are associated significantly with an increased risk of stillbirth across all gestational ages in singleton pregnancies, and in twin pregnancies when twin‐specific birth‐weight charts are used. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. Linked article: There is a comment on this article by Nicolaides et al. Click here to view the Correspondence. [ABSTRACT FROM AUTHOR]

Objective: To evaluate whether trigger and oocyte collection at a smaller follicle size decreases the risk of premature ovulation while maintaining the reproductive potential of oocytes in women with a severely diminished ovarian reserve undergoing modified natural‐cycle in‐vitro fertilization. Methods: This was a retrospective cohort study including women who had at least one unsuccessful cycle (due to no response) of conventional ovarian stimulation with a high dosage of gonadotropins and subsequently underwent a modified natural cycle with a solitary growing follicle (i.e. only one follicle > 10 mm at the time of trigger). The association between follicle size at trigger and various cycle outcomes was tested using regression analyses. Results: A total of 160 ovarian stimulation cycles from 110 patients were included in the analysis. Oocyte pick‐up (OPU) was performed in 153 cycles and 7 cycles were canceled due to premature ovulation. Patients who received their trigger at smaller follicle sizes (≤ 15 mm) had significantly lower rates of premature ovulation and thus higher rates of OPU (98.9% vs 90.8%; odds ratio, 9.56 (95% CI, 1.58–182.9); P = 0.039) compared with those who received their trigger at larger follicle sizes (> 15 mm). On multivariable analysis, smaller follicle sizes at trigger (> 10 to 13 mm, > 13 to 15 mm, > 15 mm to 17 mm) were not associated significantly with a lower rate of cumulus–oocyte complex (COC) retrieval, metaphase‐II (MII) oocytes or blastulation when compared to the > 17‐mm group. On sensitivity analysis including only the first cycle of each couple, the maturity rate among those with COC retrieval was highest in follicle sizes > 15 to 17 mm (92.3%) and > 13 to 15 mm (91.7%), followed by > 10 to 13 mm (85.7%) and lowest in the > 17‐mm group (58.8%). During the study period, five euploid blastocysts developed from 48 fertilized MII oocytes with follicle sizes of 12 mm (n = 3), 14 mm (n = 1) and 16 mm (n = 1) at trigger. Of those, four were transferred and resulted in two live births, both of which developed from follicles with a size at trigger of 12 mm. Conclusions: The ideal follicle size for triggering oocyte maturation may be smaller in women with a severely diminished ovarian reserve managed on a modified natural cycle when compared to conventional cut‐offs. The risk of OPU cancellation was significantly higher in women triggered at follicle size > 15 mm and the yield of mature oocytes was not adversely affected in women triggered at follicle size > 13 to 15 mm compared with > 15 to 17 mm. Waiting for follicles to reach sizes > 17mm may be detrimental to achieving optimal outcome. © 2024 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objective: Pregnancies with fetal growth restriction (FGR) are at increased risk for pre‐eclampsia. Angiogenic markers including soluble fms‐like tyrosine kinase‐1 (sFlt‐1) and placental growth factor (PlGF) are altered in pregnancies complicated by FGR, but their utility for predicting pre‐eclampsia in growth‐restricted pregnancies is uncertain. This study aimed to evaluate the prognostic value of angiogenic markers for predicting the development of pre‐eclampsia in pregnancies with FGR and suspected pre‐eclampsia. Methods: This was a retrospective study of singleton pregnancies with FGR, defined according to Delphi consensus criteria, which underwent sampling of sFlt‐1 and PlGF for suspicion of pre‐eclampsia at the Medical University of Vienna, Vienna, Austria, between 2013 and 2020. Women with an established diagnosis of pre‐eclampsia at sampling were excluded. Cox regression analysis and logistic regression analysis were performed to evaluate the association of angiogenic markers with the development of pre‐eclampsia at various timepoints. Results: In this cohort of 93 women, pre‐eclampsia was diagnosed in 14 (15.1%) women within 1 week after sampling, 21 (22.6%) within 2 weeks after sampling and 38 (40.9%) at any time after assessment. The sFlt‐1/PlGF ratio consistently showed a stronger association with the development of pre‐eclampsia compared to sFlt‐1 or PlGF alone (pre‐eclampsia within 1 week: area under the receiver‐operating‐characteristics curve, 0.87 vs 0.82 vs 0.72). Models including the sFlt‐1/PlGF ratio were associated more strongly with pre‐eclampsia hazard compared to models including sFlt‐1 or PlGF alone (concordance index, 0.790 vs 0.759 vs 0.755). The risk classification capability of the sFlt‐1/PlGF ratio decreased after the 2‐week timepoint. The established cut‐off value for the sFlt‐1/PlGF ratio of < 38 was effective for ruling out pre‐eclampsia within 2 weeks, with a negative predictive value of 0.933 and sensitivity of 0.952. Conclusions: Use of the sFlt‐1/PlGF ratio is preferrable to the use of PlGF alone for the prediction of pre‐eclampsia in pregnancies with FGR. Established cut‐offs for ruling out the development of pre‐eclampsia in the short term seem to be effective in these patients. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objectives: To use superb microvascular imaging (SMI) to evaluate longitudinally spiral artery (SA) and uterine artery (UtA) vascular adaptation in normal human pregnancy, and to develop reference ranges for use at various gestational ages throughout pregnancy. Methods: The data for this study were obtained from the National Institutes of Health (NIH)‐funded Human Placenta Project. Women aged 18–35 years, with a body mass index < 30 kg/m2, without comorbidities, with a singleton gestation conceived spontaneously, and gestational age at or less than 13 + 6 weeks were eligible for inclusion. The current analysis was restricted to uncomplicated pregnancies carried to term. Exclusion criteria included maternal or neonatal complications, fetal or umbilical cord anomalies, abnormal placental implantation or delivery < 37 weeks. Women who fulfilled the inclusion criteria formed the reference population of the Human Placenta Project study. Each participant underwent eight ultrasound examinations during pregnancy. The pulsatility index (PI) of both the left and right UtA were obtained twice for each artery and the presence or absence of a notch was noted. Using SMI technology, the total number of SA imaged was recorded in a sagittal placental section at the level of cord insertion. The PI and peak systolic velocity (PSV) were also measured in a total of six SA, including two in the central portion of the placenta, two peripherally towards the uterine fundal portion, and two peripherally towards the lower uterine segment. Results: A total of 90 women fulfilled the study criteria. Maternal UtA‐PI decreased throughout the first half of pregnancy from a mean ± SD of 1.39 ± 0.50 at 12–13 weeks' gestation to 0.88 ± 0.24 at 20–21 weeks' gestation. The mean number of SA visualized in a sagittal plane of the placenta increased from 8.83 ± 2.37 in the first trimester to 16.99 ± 3.31 in the late‐third trimester. The mean SA‐PI was 0.57 ± 0.12 in the first trimester and decreased progressively during the second trimester, reaching a nadir of 0.40 ± 0.10 at 24–25 weeks, and remaining constant until the end of pregnancy. SA‐PSV was highest in early pregnancy with a mean of 57.16 ± 14.84 cm/s at 12–13 weeks' gestation, declined to a mean of 49.38 ± 17.88 cm/s at 20–21 weeks' gestation and continued to trend downward for the remainder of pregnancy, reaching a nadir of 34.50 ± 15.08 cm/s at 36–37 weeks' gestation. A statistically significant correlation was noted between SA‐PI and UtA‐PI (r = 0.5633; P < 0.001). Multilevel regression models with natural cubic splines were used to create reference ranges of SA‐PSV and SA‐PI for given gestational ages. Conclusion: From early gestation, we have demonstrated the ability to image and quantify SA blood flow in normal pregnancy, and have developed reference ranges for use at various gestational ages throughout pregnancy. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objectives: Angiogenic marker assessment, such as the ratio of soluble fms‐like tyrosine kinase‐1 (sFlt‐1) to placental growth factor (PlGF), is known to be a useful tool in the prediction of pre‐eclampsia (PE). However, evidence from surveillance strategies in pregnancies with a PE diagnosis is lacking. Therefore, we aimed to assess the predictive performance of longitudinal maternal serum angiogenic marker assessment for both maternal and perinatal adverse outcomes when compared to standard laboratory parameters in pregnancies with confirmed PE. Methods: This was a retrospective analysis of prospectively collected data from January 2013 to December 2020 at the Medical University of Vienna. The inclusion criteria were singleton pregnancy with confirmed PE and post‐diagnosis maternal serum angiogenic marker assessment at a minimum of two timepoints. The primary outcome was the predictive performance of longitudinal sFlt‐1 and PlGF assessment for adverse maternal and perinatal outcomes compared to conventional laboratory monitoring at the same time in pregnancies with confirmed PE. Composite adverse maternal outcome included intensive care unit admission, pulmonary edema, eclampsia and/or death. Composite adverse perinatal outcome included stillbirth, neonatal death, placental abruption, neonatal intensive care unit admission, intraventricular hemorrhage, necrotizing enterocolitis, respiratory distress syndrome and/or mechanical ventilator support. Results: In total, 885 post‐diagnosis sFlt‐1/PlGF ratio measurements were obtained from 323 pregnant women with confirmed PE. For composite adverse maternal outcome, the highest standalone predictive accuracy was obtained using maternal serum sFlt‐1/PlGF ratio (area under the receiver‐operating‐characteristics curve (AUC), 0.72 (95% CI, 0.62–0.81)), creatinine (AUC, 0.71 (95% CI, 0.62–0.81)) and lactate dehydrogenase (LDH) levels (AUC, 0.73 (95% CI, 0.65–0.81)). Maternal platelet levels (AUC, 0.65 (95% CI, 0.55–0.74)), serum alanine aminotransferase (ALT) (AUC, 0.59 (95% CI, 0.49–0.69)) and aspartate aminotransferase (AST) (AUC, 0.61 (95% CI, 0.51–0.71) levels had poor standalone predictive accuracy. The best prediction model consisted of a combination of maternal serum LDH, creatinine levels and sFlt‐1/PlGF ratio, which had an AUC of 0.77 (95% CI, 0.68–0.85), significantly higher than sFlt‐1/PlGF ratio alone (P = 0.037). For composite adverse perinatal outcome, the highest standalone predictive accuracy was obtained using maternal serum sFlt‐1/PlGF ratio (AUC, 0.82 (95% CI, 0.75–0.89)) and creatinine (AUC, 0.74 (95% CI, 0.67–0.80)) levels, sFlt‐1/PlGF ratio being superior to creatinine alone (P < 0.001). Maternal serum LDH levels (AUC, 0.65 (95% CI, 0.53–0.74)), platelet count (AUC, 0.57 (95% CI, 0.44–0.67)), ALT (AUC, 0.58 (95% CI, 0.48–0.67)) and AST (AUC, 0.58 (95% CI, 0.48–0.67)) levels had poor standalone predictive accuracy. No combination of biomarkers was superior to maternal serum sFlt‐1/PlGF ratio alone for prediction of composite adverse perinatal outcome (P > 0.05 for all). Conclusions: In pregnancies with confirmed PE, longitudinal maternal serum angiogenic marker assessment is a good predictor of adverse maternal and perinatal outcomes and superior to some conventional laboratory parameters. Further studies should focus on optimal surveillance following diagnosis of PE. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objective: Ventriculomegaly can be associated with long‐term neurodevelopmental impairment. Prenatal diagnosis of ventriculomegaly is most commonly made at the routine second‐trimester anomaly scan. The value of first‐trimester ultrasound has expanded to early diagnosis and screening of fetal abnormalities. The objective of this study was to assess the predictive accuracy of first‐trimester choroid‐plexus‐to‐lateral‐ventricle‐or‐head ratios for development of ventriculomegaly at a later gestational age. Methods: This was a case–control study of fetuses with isolated ventriculomegaly diagnosed after 16 weeks' gestation and a control group of normal fetuses (without ventriculomegaly). The exclusion criteria included aneuploidy, genetic syndrome and/or other brain abnormality. Stored two‐dimensional first‐trimester ultrasound images were analyzed blindly offline and fetal biometry was performed in the axial view of the fetal head. The ratios of choroid plexus area (PA) to lateral ventricular area (VA), choroid plexus length (PL) to lateral ventricular length (VL), choroid plexus diameter (PD) to lateral ventricular diameter (VD) and PA to biparietal diameter (BPD) were measured at 11 + 0 to 13 + 6 weeks' gestation. Intra‐ and interobserver variability of measurement of these fetal head biometric parameters at 11 + 0 to 13 + 6 weeks' gestation were assessed in 20 normal fetuses using intraclass correlation coefficients with 95% CI. The accuracy of first‐trimester biometric measurements for prediction of ventriculomegaly was assessed using the area under the receiver‐operating‐characteristics curves (AUC). Results: The analysis included 683 singleton pregnancies, of which 102 fetuses were diagnosed with ventriculomegaly. Ventriculomegaly was mild in 86 (84.3%) cases and severe in the other 16 (15.7%). All first‐trimester fetal choroid‐plexus‐to‐lateral‐ventricle/head ratios were significantly lower in cases with ventriculomegaly compared with controls (P < 0.001), with good inter‐ and intraobserver agreement (≥ 0.95) for the majority of the fetal head biometric parameters assessed. On adjusting for crown–rump length, optimism‐adjusted AUC values obtained after cross‐validation showed that both PL/VL ratio (AUC, 0.87 (95% CI, 0.73–0.98)) and PA/VA ratio (AUC, 0.90 (95% CI, 0.82–0.98)) had good predictive accuracy for severe ventriculomegaly. The PA/BPD ratio (AUC, 0.73 (95% CI, 0.54–0.90)) had modest predictive ability, which was significantly lower compared with that of the PA/VA ratio and PL/VL ratio (P = 0.003 and P = 0.001, respectively). The predictive accuracy of PD/VD ratio was low with an AUC of 0.65 (95% CI, 0.47–0.84). Optimism‐adjusted AUC values obtained after cross‐validation showed that PA/VA ratio offered the highest predictive accuracy for mild ventriculomegaly with an AUC of 0.84 (95% CI, 0.79–0.89), followed by PL/VL ratio (AUC, 0.82 (95% CI, 0.76–0.88)), PA/BPD ratio (AUC, 0.76 (95% CI, 0.69–0.82)) and PD/VD ratio (AUC, 0.75 (95% CI, 0.67–0.81)). Calibration plots showed that both PA/VA and PL/VL ratios had good calibration. Conclusion: First‐trimester prediction of ventriculomegaly using ratios of fetal choroid plexus to lateral ventricle/head appears promising. Future prospective studies are needed to validate the predictive accuracy of these ultrasound markers as a screening tool for ventriculomegaly. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

A study investigated the immune response of pregnant women vaccinated with mRNA and inactivated SARS-CoV-2 vaccines against the Omicron variant. The results showed that pregnant women who received the mRNA vaccine had higher neutralizing antibody levels against both the Wuhan and Omicron variants compared to those who received the inactivated vaccine. However, neutralizing antibody activity against the Omicron variant was lower compared to the Wuhan variant for both vaccine types. The study suggests the importance of booster shots and new-generation vaccines targeted against variants of concern. The choice of vaccine type for booster shots may be based on regional availability rather than efficacy data in pregnant women. [Extracted from the article]

Objective: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in pregnancy is associated with increased risk of adverse maternal and perinatal outcomes. Vaccines are highly effective at preventing severe coronavirus disease 2019 (COVID-19), but there are limited data on COVID-19 vaccines in pregnancy. This study aimed to investigate the reactogenicity and immunogenicity of COVID-19 vaccines in pregnant women when administered according to the 12-week-interval dosing schedule recommended in the UK.Methods: This was a cohort study of pregnant women receiving COVID-19 vaccination between April and September 2021. The outcomes were immunogenicity and reactogenicity after COVID-19 vaccination. Pregnant women were recruited by phone, e-mail and/or text and were vaccinated according to vaccine availability at their local vaccination center. For immunogenicity assessment, blood samples were taken at specific timepoints after each dose to evaluate nucleocapsid protein (N) and spike protein (S) antibody titers. The comparator group comprised non-pregnant female healthcare workers in the same age group who were vaccinated as part of the national immunization program in a contemporaneous longitudinal cohort study. Longitudinal changes in serum antibody titers and association with pregnancy status were assessed using a two-step regression approach. Reactogenicity assessment in pregnant women was undertaken using an online questionnaire. The comparator group comprised non-pregnant women aged 18-49 years who had received two vaccine doses in primary care. The association of pregnancy status with reactogenicity was assessed using logistic regression analysis.Results: Overall, 67 pregnant women, of whom 66 had received a mRNA vaccine, and 79 non-pregnant women, of whom 50 had received a mRNA vaccine, were included in the immunogenicity study. Most (61.2%) pregnant women received their first vaccine dose in the third trimester, while 3.0% received it in the first trimester and 35.8% in the second trimester. SARS-CoV-2 S-antibody geometric mean concentrations after mRNA vaccination were not significantly different at 2-6 weeks after the first dose but were significantly lower at 2-6 weeks after the second dose in infection-naïve pregnant compared with non-pregnant women. In pregnant women, prior infection was associated with higher antibody levels at 2-6 weeks after the second vaccine dose. Reactogenicity analysis included 108 pregnant women and 116 non-pregnant women. After the first dose, tiredness and chills were reported less commonly in pregnant compared with non-pregnant women (P = 0.043 and P = 0.029, respectively). After the second dose, feeling generally unwell was reported less commonly (P = 0.046) in pregnant compared with non-pregnant women.Conclusions: Using an extended 12-week interval between vaccine doses, antibody responses after two doses of mRNA COVID-19 vaccine were found to be lower in pregnant compared with non-pregnant women. Strong antibody responses were achieved after one dose in previously infected women, regardless of pregnancy status. Pregnant women reported fewer adverse events after both the first and second dose of vaccine. These findings should now be addressed in larger controlled studies. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

This article examines the effects of antihypertensive therapy on cardiovascular parameters in women with hypertensive disorders of pregnancy (HDP) and in a pre-eclamptic rat model. The study found that women with HDP experienced significant impairment of cardiac output, augmentation index, and systemic vascular resistance compared to healthy controls. Antihypertensive therapy improved cardiovascular parameters in women with gestational hypertension but did not have a significant impact on those with pre-eclampsia. The study suggests that current standard therapy for pre-eclampsia may not be sufficient to improve cardiovascular impairment. [Extracted from the article]

Objective: There is little evidence related to the effects of the Omicron severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant on pregnancy outcomes, particularly in unvaccinated women. This study aimed to compare pregnancy outcomes of unvaccinated women infected with SARS-CoV-2 during the pre-Delta, Delta and Omicron waves.Methods: This was a retrospective cohort study conducted at two tertiary care facilities: Sancaktepe Training and Research Hospital, Istanbul, Turkey, and St George's University Hospitals NHS Foundation Trust, London, UK. Included were women who tested positive for SARS-CoV-2 by real-time reverse-transcription polymerase chain reaction (RT-PCR) during pregnancy, between 1 April 2020 and 14 February 2022. The cohort was divided into three periods according to the date of their positive RT-PCR test: (i) pre-Delta (1 April 2020 to 8 June 2021 in Turkey, and 1 April 2020 to 31 July 2021 in the UK), (ii) Delta (9 June 2021 to 27 December 2021 in Turkey, and 1 August 2021 to 27 December 2021 in the UK) and (iii) Omicron (after 27 December 2021 in both Turkey and the UK). Baseline data collected included maternal age, parity, body mass index, gestational age at diagnosis and comorbidities. The primary outcome was the need for oxygen supplementation, classified as oxygen support via nasal cannula or breather mask, non-invasive mechanical ventilation with continuous positive airway pressure (CPAP) or high-flow oxygen, mechanical ventilation with intubation, or extracorporeal membrane oxygenation (ECMO). Inferences were made after balancing of confounders, using an evolutionary search algorithm. Selected confounders were maternal age, body mass index and gestational age at diagnosis of infection.Results: During the study period, 1286 unvaccinated pregnant women with RT-PCR-proven SARS-CoV-2 infection were identified, comprising 870 cases during the pre-Delta period, 339 during the Delta wave and 77 during the Omicron wave. In the confounder-balanced cohort, infection during the Delta wave vs during the pre-Delta period was associated with increased need for nasal oxygen support (risk ratio (RR), 2.53 (95% CI, 1.75-3.65); P < 0.001), CPAP or high-flow oxygen (RR, 2.50 (95% CI, 1.37-4.56); P = 0.002), mechanical ventilation (RR, 4.20 (95% CI, 1.60-11.0); P = 0.003) and ECMO (RR, 11.0 (95% CI, 1.43-84.7); P = 0.021). The maternal mortality rate was 3.6-fold higher during the Delta wave compared to the pre-Delta period (5.3% vs 1.5%, P = 0.010). Infection during the Omicron wave was associated with a similar need for nasal oxygen support (RR, 0.62 (95% CI, 0.25-1.55); P = 0.251), CPAP or high-flow oxygen (RR, 1.07 (95% CI, 0.36-3.12); P = 0.906) and mechanical ventilation (RR, 0.44 (95% CI, 0.06-3.45); P = 0.438) with that in the pre-Delta period. The maternal mortality rate was similar during the Omicron wave and the pre-Delta period (1.3% vs 1.3%, P = 0.999). The need for nasal oxygen support during the Omicron wave was significantly lower compared to the Delta wave (RR, 0.26 (95% CI, 0.11-0.64); P = 0.003). Perinatal outcomes were available for a subset of the confounder-balanced cohort. Preterm birth before 34 weeks' gestation was significantly increased during the Delta wave compared with the pre-Delta period (15.4% vs 4.9%, P < 0.001).Conclusions: Among unvaccinated pregnant women, SARS-CoV-2 infection during the Delta wave, in comparison to the pre-Delta period, was associated with increased requirement for oxygen support (including ECMO) and higher maternal mortality. Disease severity and pregnancy complications were similar between the Omicron wave and pre-Delta period. SARS-CoV-2 infection of unvaccinated pregnant women carries considerable risks of morbidity and mortality regardless of variant, and vaccination remains key. Miscommunication of the risks of Omicron infection may impact adversely vaccination uptake among pregnant women, who are at increased risk of complications related to SARS-CoV-2. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objective: The use of twin-specific vs singleton growth charts in the assessment of twin pregnancy has been controversial. The aim of this study was to assess whether a diagnosis of small-for-gestational age (SGA) made using twin-specific estimated-fetal-weight (EFW) and birth-weight (BW) charts is associated more strongly with adverse neonatal outcomes in twin pregnancies, compared with when the diagnosis is made using singleton charts.Methods: This was a cohort study of twin pregnancies delivered at St George's Hospital, London, between January 2007 and May 2020. Twin pregnancies complicated by intrauterine death of one or both twins, fetal aneuploidy or major abnormality, twin-twin transfusion syndrome or twin anemia-polycythemia sequence and those delivered before 32 weeks' gestation, were excluded. SGA was defined as EFW or BW below the 10th centile, and was assessed using both twin-specific and singleton EFW and BW charts. The main study outcome was composite adverse neonatal outcome. Mixed-effects logistic regression analysis with random pregnancy-level intercepts was used to test the association between SGA classified using the different charts and adverse neonatal outcome.Results: A total of 1329 twin pregnancies were identified, of which 913 (1826 infants) were included in the analysis. Of these pregnancies, 723 (79.2%) were dichorionic and 190 (20.8%) were monochorionic. Using the singleton charts, 33.3% and 35.7% of pregnancies were classified as SGA based on EFW and BW, respectively. The corresponding values were 5.9% and 5.6% when using the twin-specific charts. Classification as SGA based on EFW using the twin charts was associated significantly with composite adverse neonatal outcome (odds ratio (OR), 4.78 (95% CI, 1.47-14.7); P = 0.007), as compared with classification as appropriate-for-gestational age (AGA). However, classification as SGA based on EFW using the singleton standard was not associated significantly with composite adverse neonatal outcome (OR, 1.36 (95% CI, 0.63-2.88); P = 0.424). Classification as SGA based on EFW using twin-specific standards provided a significantly better model fit than did using the singleton standard (likelihood ratio test, P < 0.001). When twin-specific charts were used, classification as SGA based on BW was associated significantly with a 9.3 times increased odds of composite adverse neonatal outcome (OR, 9.27 (95% CI, 2.86-30.0); P < 0.001). Neonates classified as SGA according to the singleton BW standard but not according to the twin-specific BW standards had a significantly lower rate of composite adverse neonatal outcome than did AGA twins (OR, 0.24 (95% CI, 0.07-0.66); P = 0.009).Conclusions: The singleton charts classified one-third of twins as SGA, both prenatally and postnatally. Infants classified as SGA according to the twin-specific charts, but not those classified as SGA according to the singleton charts, had a significantly increased risk of adverse neonatal outcome compared with infants classified as AGA. This study provides further evidence that twin-specific charts perform better than do singleton charts in the prediction of adverse neonatal outcome in twin pregnancies. The use of these charts may reduce misclassification of twins as SGA and improve identification of those that are truly growth restricted. © 2021 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objective: Although the most recent guidance from the International Society for the Study of Hypertension in Pregnancy (ISSHP) has highlighted the role of angiogenic marker assessment in the diagnosis of pre-eclampsia (PE) in women with chronic hypertension, the ISSHP has withheld recommending its implementation due to the limited available evidence in this group of women. Therefore, we aimed to investigate the value of soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) assessment in women with chronic hypertension and suspected superimposed PE.Methods: This was a retrospective analysis of prospectively collected data recorded in an electronic database between January 2013 and October 2019. Women with chronic hypertension and singleton pregnancy who had suspected superimposed PE were included. Superimposed PE was suspected in women presenting with worsening hypertension, epigastric pain, new-onset edema, dyspnea or neurological symptoms. The exclusion criteria were delivery within 1 week after assessment for reasons other than PE, chronic kidney disease, history of cardiac disease, fetal aneuploidy, genetic syndrome or major structural anomaly and missing pregnancy outcome. Maternal serum angiogenic markers (sFlt-1, PlGF and sFlt-1/PlGF ratio) were measured. The primary outcome was the utility of angiogenic markers in the prediction of superimposed PE. Predictive accuracy was assessed for superimposed PE diagnosed at different timepoints, including within 1 week after assessment and any time before birth. The secondary outcome was comparison of adverse maternal and perinatal outcomes between women with superimposed PE diagnosed according to the traditional ISSHP criteria and those diagnosed according to extended criteria including angiogenic markers. The predictive accuracy of each angiogenic marker was assessed using receiver-operating-characteristics-curve analysis. Area under the curve (AUC) values were compared using De Long's test. A sensitivity analysis was planned for gestational age at assessment. The association of various variables with composite adverse maternal and perinatal outcomes was assessed using binomial regression.Results: The study included 142 pregnant women with chronic hypertension and suspected superimposed PE, of whom 25 (17.6%) developed PE within 1 week after assessment, 52 (36.6%) developed PE at any timepoint before birth and 90 (63.4%) delivered without PE. Maternal serum angiogenic imbalance was associated significantly with superimposed PE diagnosed according to the ISSHP criteria within 1 week or at any time after assessment (P < 0.001 for both). The predictive accuracy of maternal serum sFlt-1/PlGF ratio for superimposed PE diagnosed within 1 week after assessment was superior to that of maternal serum PlGF level (AUC, 0.91 vs 0.86; P = 0.032). The addition of angiogenic imbalance to the traditional ISSHP diagnostic criteria was associated with an increase in the detection rate (35.1% increase; 95% credible interval (CrI), 16.6-53.6%) and positive (9.6% increase; 95% CrI, 0.0-20.6%) and negative (3.1% increase; 95% CrI, 1.3-4.9%) predictive values for composite adverse maternal outcome, with high posterior probabilities of an increase in each predictive accuracy parameter (> 99.9%, 95.6% and > 99.9%, respectively), without a meaningful decrease in specificity. The addition of angiogenic imbalance improved the detection rate for composite adverse perinatal outcome (20.6% increase; 95% CrI, 0.0-42.2%), with a high posterior probability (96.9%). There was a corresponding drop in specificity (5.7% decrease; 95% CrI, -2.3% to 13.6%), with a posterior probability of 91.8%.Conclusions: In women with chronic hypertension and suspected superimposed PE, addition of maternal serum angiogenic markers to the traditional diagnostic criteria for superimposed PE improved significantly the sensitivity for the prediction of both maternal and perinatal adverse outcomes. Implementation of angiogenic marker assessment in the evaluation of pregnant women with chronic hypertension should therefore be considered. © 2021 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Historically, pregnant women have been excluded from the majority of drug and vaccine trials, a practice that has been criticized widely by the scientific community1-3. The principles of this vaccination technology should also apply to COVID-19 vaccines and provides generic reassurance around the use of mRNA vaccines in pregnancy. Available SARS-CoV-2 vaccines and their safety profiles Four different types of COVID-19 vaccine are currently available (Table 3): mRNA, viral vector, inactivated virus and recombinant antigen. As with the mRNA vaccines, there are limited data on the safety of adenovirus vector-based vaccines in pregnancy, though adenovirus vector-based Zika virus vaccines have been tested in pregnant mice without safety concerns35. [Extracted from the article]

Background: Women with a history of hypertensive disorders of pregnancy (HDP) are at increased long‐term risk of cardiovascular disease. However, there has been increasing evidence on the same risks in the months following birth. Objectives: This review aims to estimate the incidence of hypertension in the first 2 years after HDP. Search strategy: MEDLINE, Embase and Cochrane databases were systematically searched in October 2019. Selection criteria: Observational studies comparing hypertension rate following HDP and normotensive pregnancies up to 2 years. Data collection and analysis: A meta‐analysis to calculate the odds ratio (OR) with a 95% confidence interval (CI) and a sub‐group analysis excluding women with chronic hypertension were performed. Main results: Hypertension was diagnosed within the first 2 years following pregnancy in 468/1646 (28.4%) and 584/6395 (9.1%) of the HDP and control groups, respectively (OR 6.28; 95% CI 4.18–9.43; I2 = 56%). The risk of hypertension in HDP group was significantly higher in the first 6 months following delivery (OR 18.33; 95% CI 1.35–249.48; I2 = 84%) than at 6–12 months (OR 4.36; 95% CI 2.81–6.76; I2 = 56%) or between 1–2 years postpartum (OR 7.24; 95% CI 4.44–11.80; I2 = 9%). A sub‐group analysis demonstrated a similar increase in the risk of developing postpartum hypertension after HDP (OR 5.75; 95% CI 3.92–8.44; I2 = 49%) and pre‐eclampsia (OR 6.83; 95% CI 4.25–10.96; I2 = 53%). Conclusions: The augmented risk of hypertension after HDP is highest in the early postpartum period, suggesting that diagnosis and targeted interventions to improve maternal cardiovascular health may need to be commenced in the immediate postpartum period. The risk of hypertension within 2 years of birth is six‐fold higher in women who experienced pre‐eclampsia. The risk of hypertension within 2 years of birth is six‐fold higher in women who experienced pre‐eclampsia. This article includes Author Insights, a video abstract available at https://vimeo.com/rcog/authorinsights16545 [ABSTRACT FROM AUTHOR]

The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly contagious and has significant alterations to its spike protein structure, providing it with significant ability to evade immune response elicited by coronavirus disease 2019 (COVID-19) vaccines1. However, these reports are based on data derived mostly from countries with a high vaccination rate, and there are no data on the outcome of Omicron variant infection in vaccinated and unvaccinated pregnant women. Our findings emphasize the importance of full SARS-CoV-2 vaccination to protect pregnant women during the Omicron wave despite its apparently lower effectiveness against PCR-confirmed infection with the Omicron variant11. [Extracted from the article]

Objective: Identification of the fetus at risk of intrapartum compromise has many benefits. Impaired maternal cardiovascular function is associated with placental hypoperfusion predisposing to intrapartum fetal distress. The aim of this study was to assess the predictive accuracy of maternal hemodynamics for the risk of operative delivery due to presumed fetal compromise in women undergoing induction of labor (IOL).Methods: In this prospective cohort study, patients were recruited between November 2018 and January 2019. Women undergoing IOL were invited to participate in the study. A non-invasive ultrasonic cardiac output monitor (USCOM-1A®) was used for cardiovascular assessment. The study outcome was operative delivery due to presumed fetal compromise, which included Cesarean or instrumental delivery for abnormal fetal heart monitoring. Regression analysis was used to test the association between cardiovascular markers, as well as the maternal characteristics, and the risk of operative delivery due to presumed fetal compromise. Receiver-operating-characteristics-curve analysis was used to assess the predictive accuracy of the cardiovascular markers for the risk of operative delivery for presumed fetal compromise.Results: A total of 99 women were recruited, however four women were later excluded from the analysis due to semi-elective Cesarean section (n = 2) and failed IOL (n = 2). The rate of operative delivery due to presumed fetal compromise was 28.4% (27/95). Women who delivered without suspected fetal compromise (controls) were more likely to be parous, compared to those who had operative delivery due to fetal compromise (52.9% vs 18.5%; P = 0.002). Women who underwent operative delivery due to presumed fetal compromise had a significantly lower cardiac index (median, 2.50 vs 2.60 L/min/m2 ; P = 0.039) and a higher systemic vascular resistance (SVR) (median, 1480 vs 1325 dynes × s/cm5 , P = 0.044) compared to controls. The baseline model (being parous only) showed poor predictive accuracy, with an area under the curve of 0.67 (95% CI, 0.58-0.77). The addition of stroke volume index (SVI) < 36 mL/m2 , SVR > 7.2 logs or SVR index (SVRI) > 7.7 logs improved significantly the predictive accuracy of the baseline model (P = 0.012, P = 0.026 and P = 0.012, respectively).Conclusion: In this pilot study, we demonstrated that prelabor maternal cardiovascular assessment in women undergoing IOL could be useful for assessing the risk of intrapartum fetal compromise necessitating operative delivery. The addition of SVI, SVR or SVRI improved significantly the predictive accuracy of the baseline antenatal model. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether assessment of longitudinal change in Doppler variables in small-for-gestational-age (SGA) fetuses improves the prediction of those at risk of stillbirth.Methods: This was a longitudinal study of two cohorts of singleton pregnancies, which included SGA and appropriate-for-gestational-age (AGA) fetuses, respectively. The inclusion criteria for the SGA cohort were singleton pregnancy at ≥ 20 weeks' gestation, classified as SGA (estimated fetal weight < 10th centile). The AGA cohort consisted of singleton pregnancies deemed at high risk of being SGA, which were followed up longitudinally but remained AGA. Fetal middle cerebral artery (MCA) pulsatility index (PI) and umbilical artery (UA)-PI were measured longitudinally and cerebroplacental ratio (CPR) was calculated, and values were converted to multiples of the median. The last two measurements prior to delivery were included in the analysis. Longitudinal models for Doppler variables were developed using linear-mixed models and their accuracy in the prediction of stillbirth was tested using generalized linear models. A Bayesian framework was employed to compare the accuracy of longitudinal and standard (last-scan measurement) models.Results: In total, 1549 AGA and 941 SGA pregnancies were included in the analysis. There were 30 (3.2%) and no stillbirth cases in the SGA and AGA groups, respectively. Change in MCA-PI, UA-PI and CPR with advancing gestation was significantly different between liveborn AGA and SGA fetuses, with a less pronounced difference with advancing gestation. Using the last measurement, the best models for the prediction of stillbirth in SGA pregnancies were those based on CPR (accuracy, 75.0%; 95% CI, 72.6-77.2%) and UA-PI (accuracy, 71.0%; 95% CI, 68.6-73.4%). The posterior probability of the standard CPR model having a higher accuracy compared with the UA-PI model was 97.2% (magnitude of change (MC), 3.9%; 95% credible interval (CrI), 0.5-7.3%). The accuracies of the standard, compared with the longitudinal, models for UA-PI (71.0% vs 72.8%), MCA-PI (64.6% vs 63.8%) and CPR (75.0% vs 74.9%) in the prediction of stillbirth were not significantly different. The posterior probabilities for improvement in accuracy using longitudinal, compared with standard, assessment were 50.1% (MC, < 0.1%; 95% CrI, -3.3 to 3.3%), 35.2% (MC, -0.1%; 95% CrI, -4.5 to 2.8%) and 82.2% (MC, 1.9%; 95% CrI, -1.5 to 5.3%) for CPR, MCA-PI and UA-PI models, respectively. Therefore, change in Doppler parameters did not improve the accuracy of the prediction of stillbirth, compared with that of the last-scan measurement.Conclusion: Longitudinal assessment of Doppler parameters was not useful in improving the detection of stillbirth in SGA pregnancies, as compared with a single-point assessment. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: To identify key factors associated with adverse perinatal outcome in monochorionic diamniotic twin pregnancy complicated by selective fetal growth restriction (sFGR).Methods: This was a retrospective cohort study of all monochorionic diamniotic twin pregnancies diagnosed with sFGR at ≥ 16 weeks' gestation, in a single tertiary referral center between March 2000 and May 2015. The presence of coexisting twin-twin transfusion syndrome (TTTS) was noted. Fetal biometry and Doppler indices, including those of the umbilical artery (UA) and ductus venosus (DV), were recorded at the time of diagnosis. The type of sFGR was diagnosed according to the pattern of end-diastolic flow in the UA of the smaller twin. DV pulsatility indices for veins (DV-PIV) were converted to Z-scores and estimated fetal weight values to centiles, to correct for gestational age (GA). Cox proportional hazards model was used to examine for independent predictors of adverse perinatal outcome, which was defined according to survival and included both intrauterine fetal demise and neonatal death of the FGR twin.Results: We analyzed 104 pregnancies, of which 66 (63.5%) were diagnosed with Type-I and 38 (36.5%) with Type-II sFGR at initial presentation. In pregnancies complicated by Type-II sFGR, the diagnosis of sFGR was made earlier than in those complicated by Type-I sFGR (mediam GA, 19.6 vs 21.5 weeks; P = 0.012), and Type-II sFGR was associated with increased risk of adverse perinatal outcome (intrauterine demise of the smaller twin, 34.2% vs 10.6%; P = 0.004). Twin pregnancies complicated by sFGR resulting in perinatal demise had a significantly earlier diagnosis (P = 0.002) and lower birth-weight centile of the smaller twin (P < 0.01), those with Type-I sFGR had earlier GA at delivery (P = 0.007) and those with Type-II sFGR had higher DV-PIV Z-score of the smaller twin (P = 0.003), when compared with pregnancies resulting in live birth. Coexisting TTTS had no significant impact on the perinatal outcome of pregnancies diagnosed with either Type-I or Type-II sFGR (P > 0.05 for both). Earlier GA at diagnosis (hazard ratio (HR), 0.70 (95% CI, 0.56-0.88); P = 0.002), Type-II sFGR (HR, 3.53 (95% CI, 1.37-9.07); P = 0.008) and higher DV-PIV Z-score (HR, 1.36 (95% CI, 1.12-1.65); P = 0.001) were significantly associated with increased risk of adverse perinatal outcome of the smaller twin.Conclusions: Pregnancies complicated by Type-II sFGR are diagnosed significantly earlier and are associated with increased risk of adverse perinatal outcome compared with those with Type-I sFGR. Coexisting TTTS has no significant impact on the perinatal outcome of pregnancies diagnosed with either Type-I or Type-II sFGR. Earlier GA at diagnosis, Type-II sFGR and higher DV-PIV Z-score are associated significantly with increased risk of adverse perinatal outcome of the smaller twin. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: Twin pregnancy is associated with a 2-3-fold increased risk of stillbirth compared with singleton pregnancy. Despite the fact that the growth pattern in twins has been shown to be different from that in singletons, it is controversial whether twin-specific growth charts should be used routinely. A major goal of prenatal ultrasound is to identify fetuses with growth restriction at risk of stillbirth. The main aim of this study was to compare the performance of chorionicity-specific twin charts with singleton charts, both customized and non-customized, in the antenatal prediction of small-for-gestational-age (SGA) stillborn and liveborn fetuses.Methods: This was a multicenter cohort study analyzing data from the Southwest Thames Obstetric Research Collaborative (STORK) multiple pregnancy cohort (2000-2009) and a second cohort of twin pregnancies at St George's University Hospital (SGH) (2011-2016). The STORK cohort was used to compare the performance of the twin charts and non-customized singleton charts of Poon et al. and the SGH cohort was used to validate the twin-specific charts and compare their performance against customized (Gestation Related Optimal Weight (GROW)) and non-customized (Poon) singleton charts. The primary outcome was the prediction of SGA cases that were stillborn and those that were liveborn in twin pregnancies. Estimated fetal weight (EFW) available from the last examination (24 weeks' gestation and onwards) before delivery or demise was used to classify the fetuses as SGA (EFW < 10th centile or < 3rd centile) or appropriate for gestational age. The proportions of predicted SGA stillbirths and SGA live births were calculated using the three different charts.Results: The STORK cohort consisted of 1850 dichorionic (DC) and 300 monochorionic (MC) twin pregnancies. The SGH cohort consisted of 579 DC and 180 MC twin pregnancies. The stillbirth rates in the STORK and SGH cohorts were 1.1% and 1.3%, respectively. In those liveborn in the STORK cohort, using a 10th -centile cut-off to define SGA, the non-customized singleton chart classified a significantly greater proportion as SGA than did the twin chart, regardless of chorionicity (P < 0.001). However, there was no significant difference between the twin and the non-customized singleton charts with regard to the proportion of stillbirth cases that were classified as SGA (P = 0.479). In the SGH cohort, the non-customized singleton chart classified 8.5% of all liveborn fetuses as SGA (EFW < 10th centile) compared with 12.8% using the customized singleton chart and 7.1% using the twin chart (P < 0.001 and P = 0.005, respectively). However, there was no significant difference among the three charts in the proportion of stillbirths classified as SGA, regardless of chorionicity (P = 0.999). Similar results were obtained when the third centile cut-off was used to define SGA.Conclusions: Compared with the STORK chorionicity-specific twin charts, the customized and non-customized singleton charts classified prenatally as SGA more liveborn fetuses. However, the three charts classified as SGA a similar proportion of stillborn cases. Our preliminary results suggest that these twin charts could safely reduce unnecessary medical intervention in twin pregnancies. Further research on the topic is needed before clinical recommendations can be made. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: Metformin has been reported to reduce the risk of pre-eclampsia. It is also known to influence soluble fms-like tyrosine kinase-1 level, which correlates significantly with the gestational age at onset and severity of pre-eclampsia. The main aim of this systematic review and meta-analysis of randomized trials was to determine whether metformin use is associated with the incidence of hypertensive disorders of pregnancy (HDP).Methods: MEDLINE (1947 to September 2017), Scopus (1970 to September 2017) and the Cochrane Library (inception to September 2017) were searched for relevant citations in the English language. Only randomized controlled trials on metformin use, reporting the incidence of pre-eclampsia or pregnancy-induced hypertension, were included. Studies on populations with a high probability of metformin use prior to randomization (those with type II diabetes or polycystic ovary syndrome) were excluded. Random-effects models with the Mantel-Haenszel method were used for subgroup analyses. Bayesian random-effects meta-regression was used to summarize the evidence.Results: In total, 3337 citations matched the search criteria. After evaluating 2536 abstracts and performing full-text review of 52 studies, 15 were included in the review. In women with gestational diabetes, metformin use was associated with a reduced risk of pregnancy-induced hypertension when compared with insulin (relative risk (RR), 0.56; 95% CI, 0.37-0.85; I2  = 0%; 1260 women) and a non-significantly reduced risk of pre-eclampsia (RR, 0.83; 95% CI, 0.60-1.14; I2  = 0%; 1724 women). In obese women, when compared with placebo, metformin use was associated with a non-significant reduction in risk of pre-eclampsia (RR, 0.74; 95% CI, 0.09-6.28; I2  = 86%; 840 women). In women with gestational diabetes, metformin use was also associated with a non-significant reduction in risk of any HDP (RR, 0.71; 95% CI, 0.41-1.25; I2  = 0%; 556 women) when compared with glyburide. When studies were combined using Bayesian random-effects meta-regression, with treatment type as a covariate, the posterior probabilities of metformin having a beneficial effect on the prevention of pre-eclampsia, pregnancy-induced hypertension and any HDP were 92.7%, 92.8% and 99.2%, respectively, when compared with any other treatment or placebo.Conclusions: There is a high probability that metformin use is associated with reduced HDP incidence when compared with other treatments or placebo. The small number of studies included in the analysis, the low quality of evidence and the clinical heterogeneity preclude generalization of these results to broader populations. Given the clinical importance of this topic and the magnitude of effect observed in this meta-analysis, further prospective trials are urgently needed. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Imaging modalities play a crucial role in the management of suspected COVID-19 patients. Before reverse transcription polymerase chain reaction (RT-PCR) test results are positive, 60-93% of patients have positive chest computed tomographic (CT) findings consistent with COVID-19. We report a case of positive lung ultrasound findings consistent with COVID-19 in a woman with an initially negative RT-PCR result. The lung ultrasound-imaging findings were present between the negative and subsequent positive RT-PCR tests and correlated with CT findings. The point-of-care lung-ultrasound examination was easy to perform and, as such, could play an important role in the triage of women with suspected COVID-19. The neonatal swabs, cord blood and placental swab RT-PCR tests were negative for SARS-CoV-2, a finding consistent with the published literature suggesting no vertical transmission of this virus in pregnant women. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: To assess the agreement between home blood-pressure monitoring (HBPM) and blood-pressure measurements in a clinic setting, in a cohort of pregnant women with hypertensive disorders of pregnancy (HDP).Methods: This was a cohort study of 147 pregnant women with HDP conducted at St George's Hospital, University of London, London, UK, between 2016 and 2017. Inclusion criteria were chronic hypertension, gestational hypertension or high risk of developing pre-eclampsia, no significant proteinuria and no hematological or biochemical abnormalities. Each included patient was prescribed a personalized schedule of hospital visits and blood-pressure measurements, according to their individual risk as per UK National Institute for Health and Care Excellence guidelines. The blood-pressure measurement at the clinic and the HBPM reading obtained closest to that hospital visit were paired for analysis. Only one pair of measurements was used per patient. Differences between home and clinic blood-pressure measurements were tested using the Wilcoxon signed rank test or paired t-test, and were also assessed visually using Bland-Altman plots. Comparison of the binary outcomes was performed using McNemar's chi-square test. Subgroup analysis was performed in the following gestational-age windows: < 14 weeks, 15-22 weeks, 23-32 weeks and 33-42 weeks' gestation.Results: A total of 294 blood-pressure measurements from 147 women were included in the analysis. Median systolic HBPM measurements were significantly lower than clinic measurements (132.0 (interquartile range (IQR), 123.0-140.0) mmHg vs 138.0 (IQR, 132.0-146.5) mmHg; P < 0.001). When stratified according to gestational age, systolic blood-pressure measurements obtained at home were significantly lower than those at clinic in all gestational-age periods except 23-32 weeks' gestation (P = 0.057). Median diastolic blood-pressure measurements at home were also significantly lower than those at clinic (85.0 (IQR, 77.0-90.0) mmHg vs 89.0 (IQR, 82.0-94.0) mmHg; P < 0.001). When stratified according to gestational age, diastolic HBPM measurements were significantly lower in the periods 5-14 weeks (P < 0.001), 15-22 weeks (P = 0.008) and 33-42 weeks (P < 0.001), compared with clinic measurements. The incidence of clinically significant systolic and diastolic hypertension based on clinic blood-pressure measurements was four to five times higher than that based on HBPM measurements (P < 0.001 and P = 0.005, respectively).Conclusions: Our study shows that, in women with HDP, blood pressure measured at home is lower than that measured in a clinic setting. This is consistent with observations in non-pregnant adults, in whom home and ambulatory monitoring of hypertensive patients is recommended. As such, HBPM has the potential to reduce the number of false-positive diagnoses of severe hypertension and unnecessary medical interventions in women with HDP. This must be carefully weighed against the risk of missing true-positive diagnoses. Prospective studies investigating the use of HBPM in pregnant women are urgently needed to determine the relevant blood-pressure thresholds for HBPM, and interval and frequency of monitoring. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: To investigate the association between abnormal cord insertion and the development of twin-specific complications, including birth-weight discordance, selective fetal growth restriction (sFGR) and twin-to-twin transfusion syndrome (TTTS).Methods: This was a single center retrospective cohort study of twin pregnancies. Abnormal cord insertion was defined as either marginal (umbilical cord attachment site less than 2 cm to the nearest margin of the placental disc) or velamentous (cord attached to the membrane before reaching the placental disc with clear evidence of vessels traversing the membranes to connect with the placental disc), as described in placental pathology reports. Twins with major structural or chromosomal abnormalities and monochorionic monoamniotic twins were not included in the study. Information on the pregnancies, ultrasound findings, prenatal investigations and interventions was obtained from the electronic ultrasound database, while data on placental histopathological findings, pregnancy outcome, mode of delivery, birth weight, gestational age at delivery and admission to the neonatal intensive care unit were obtained from maternity records. Categorical variables were compared using the chi-square or Fisher's exact test, while continuous variables were compared using the Student's t-test, ANOVA for multiple comparisons and the Kruskal-Wallis test.Results: Of the 497 twin pregnancies included in the analysis, 351 (70.6%) were dichorionic and 146 (29.4%) were monochorionic. The incidence of birth-weight discordance of 25% or more was significantly higher in pregnancies with velamentous and those with marginal cord insertions compared to those with normal cord insertion (24.0%, 15.3% vs 7.6%, P < 0.001 and P = 0.020, respectively). In pregnancies with birth-weight discordance of 25% or more, the smaller twins had significantly higher prevalence of velamentous (13.8%) and marginal (34.2%) cord insertions compared with the larger twins (1.8% and 18.5%, respectively, P < 0.001). The smaller twins of the monochorionic diamniotic pregnancies showed an even higher prevalence of velamentous (29.5%) and marginal (40.9%) cord insertions compared with the larger twins (2.3% and 31.5%, respectively, P < 0.001). Compared with the normal cord insertion group, only velamentous insertion was associated significantly with the risk of sFGR (odds ratio (OR), 9.24 (95% CI, 2.05-58.84), P < 0.001) and birth-weight discordance of 20% or more (OR, 4.34 (95% CI, 1.36-14.61), P = 0.007) and 25% or more (OR, 6.81 (95% CI, 1.67-34.12), P = 0.003) in monochorionic twin pregnancies. There was no significant association between velamentous cord insertion and TTTS (P = 0.591), or between marginal cord insertion and the development of sFGR (P = 0.233), birth-weight discordance of 25% or more (P = 0.114) or TTTS (P = 0.487). Subgroup analysis of dichorionic twins showed that abnormal cord insertion was not associated with the risk of birth-weight discordance (P = 0.999), sFGR (P = 0.308), composite neonatal adverse outcome (P = 0.637) or intrauterine death (P = 0.349).Conclusion: Monochorionic twins with velamentous cord insertion are at increased risk of birth-weight discordance and sFGR. Sonographic delineation of placental cord insertion could be of value in the antenatal stratification of twin pregnancies. Prospective studies are required to assess the value and predictive accuracy of this potential screening marker. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: To determine the accuracy of ophthalmic artery Doppler in pregnancy for the prediction of pre‐eclampsia (PE). Methods: MEDLINE, EMBASE, CINAHL and The Cochrane Library were searched for relevant citations without language restrictions. Two reviewers independently selected studies that evaluated the accuracy of ophthalmic artery Doppler to predict the development of PE and extracted data to construct 2 × 2 tables. Individual patient data were obtained from the authors if available. A bivariate random‐effects model was used for the quantitative synthesis of data. Logistic regression analysis was employed to generate receiver–operating characteristics (ROC) curves and obtain optimal cut‐offs for each investigated parameter, and a bivariate analysis was employed using predetermined cut‐offs to obtain sensitivity and specificity values and generate summary ROC curves. Results: A total of 87 citations matched the search criteria of which three studies, involving 1119 pregnancies, were included in the analysis. All included studies had clear description of the index and reference tests, avoidance of verification bias and adequate follow‐up. Individual patient data were obtained for all three included studies. First diastolic peak velocity of ophthalmic artery Doppler at a cut‐off of 23.3 cm/s showed modest sensitivity (61.0%; 95% CI, 44.2–76.1%) and specificity (73.2%; 95% CI, 66.9–78.7%) for the prediction of early‐onset PE (area under the ROC curve (AUC), 0.68; 95% CI, 0.61–0.76). The first diastolic peak velocity had a much lower sensitivity (39.0%; 95% CI, 20.6–61.0%), a similar specificity (73.2%; 95% CI, 66.9–78.7%) and a lower AUC (0.58; CI, 0.52–0.65) for the prediction of late‐onset PE. The pulsatility index of the ophthalmic artery did not show a clinically useful sensitivity or specificity at any cut‐off for early‐ or late‐onset PE. Peak ratio above 0.65 showed a similar diagnostic accuracy to that of the first diastolic peak velocity with an AUC of 0.67 (95% CI, 0.58–0.77) for early‐onset PE and 0.57 (95% CI, 0.51–0.63) for late‐onset disease. Conclusions: Ophthalmic artery Doppler is a simple, accurate and objective technique with a standalone predictive value for the development of early‐onset PE equivalent to that of uterine artery Doppler evaluation. The relationship between ophthalmic Doppler indices and PE cannot be a consequence of trophoblast invasion and may be related to maternal hemodynamic adaptation to pregnancy. The findings of this review justify efforts to elucidate the effectiveness and underlying mechanism whereby two seemingly unrelated maternal vessels can be used for the prediction of a disease considered a 'placental disorder'. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

The primary objective was to study the utility of point-of-care ultrasound (POCUS) in reducing the incidence of undiagnosed breech presentation in labour. Undiagnosed breech presentation was defined as: a) women who presented in labour or with ruptured membranes at term and were subsequently discovered to have a baby in a breech presentation, and b) women who attended for induction of labour at term and were found to have a breech presentation before commencing induction of labour. Approximately 271 POCUS would be required to prevent one undiagnosed breech presentation in labour. [Extracted from the article]

Objective: To evaluate whether routine vaginal examination during labor is associated with increased levels of anxiety and pain compared with transperineal ultrasound assessment.Methods: This was a single-blinded, parallel, randomized controlled trial conducted in a tertiary care facility. Parous pregnant women without a known psychiatric condition who were seen at the care facility between November 2015 and March 2016 were included in the trial. Participants had an uneventful pregnancy and were assigned randomly to routine digital vaginal examination or transperineal ultrasound assessment during labor. Psychological distress levels, measured by the Symptom Checklist-90-Revised, and anxiety levels, measured by State-Trait Anxiety Inventory (STAI), were recorded before admission, and pain, measured using a visual analog scale, and anxiety were recorded during the latent phase of labor, the beginning of active labor and the postpartum period. A sample size of 45 women per group (n = 90) was planned to compare methods of assessment.Results: Ninety women were randomized (1:1 allocation) to one or other of the interventions. Preadmission psychological distress and anxiety levels were similar between the two groups (P = 0.93 and 0.65, respectively). Most of the studied characteristics were similar in each group including duration of labor, number of examinations, analgesic administration during labor, episiotomy rate and interval between deliveries. Visual analog scale scores revealed that pain perception was reduced during latent (mean difference, -1.5 (95% CI, -2.51 to -0.57); P < 0.01) and active (mean difference, -1.2 (95% CI, -2.45 to -0.09); P = 0.03) stages of labor and during the postpartum period (mean difference, -0.5 (95% CI, -1.02 to -0.06); P = 0.02) in participants who had a transperineal ultrasound assessment compared with participants who had a digital vaginal examination. STAI scores revealed that anxiety levels were similar between the two groups during the latent and active phases of labor and during the postpartum period (P = 0.07, P = 0.38 and P = 0.13, respectively).Conclusions: The perception of pain was significantly reduced with the use of a transperineal ultrasound assessment compared with routine digital vaginal examination. However, only during the latent stage of labor was the magnitude of the observed effect sufficiently great to be considered clinically significant. Our results indicate that transperineal ultrasound assessment could be preferred to digital examination for the evaluation of progression of labor during this phase. Digital examination has no clinically relevant effects on state anxiety levels, as measured by the STAI. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Conclusions COVID-19 mRNA vaccination in pregnancy appears to be effective in preventing proven SARS-CoV-2 infection in pregnancy. To synthesise evidence on vaccine effectiveness and perinatal outcomes after COVID-19 vaccination in pregnancy. Studies reporting perinatal outcomes or vaccine effectiveness after COVID-19 vaccination in pregnancy were included. [Extracted from the article]

Methods This was a single centre cohort study including dichorionic twin pregnancies complicated by selective fetal growth restriction. The main aim of this study was to investigate the perinatal outcomes of dichorionic twin pregnancies complicated by selective fetal growth restriction. [Extracted from the article]

Antihypertensive therapy had no significant effect on AIx (P = 0.242) or PWV (P = 0.179). The aim of this study was to assess the effects of antihypertensive therapy on maternal hemodynamics in pregnant women with hypertensive disorders of pregnancy (HDP). [Extracted from the article]

The ratio of choroid plexus to lateral ventricle area (PAVAR), choroid plexus to lateral ventricle length (PLVLR), choroid plexus to lateral ventricle diameter (PDVDR), choroid plexus area to biparietal diameter (PA/BPD) and choroid plexus area to head circumference (PA/HC) were measured at 11-13 + 6 weeks. Conclusions First trimester prediction of ventriculomegaly using fetal choroid plexus to ventricle ratios appears promising. PA/BPD ratio (AUC 0.76, 95% CI 0.63-0.89) and PA/HC ratio (AUC 0.75, 95% CI 0.63-0.87) had modest predictive capabilities, which were significantly lower compared to PAVAR (P = 0.003 and P = 0.001, respectively). [Extracted from the article]

Angiogenic markers are a useful tool for post diagnosis surveillance and prediction of severe maternal outcomes in women with pre-eclampsia. Methods We included women with a diagnosis of pre-eclampsia and post-diagnosis angiogenic marker assessment. Angiogenic marker assessment is a useful tool for the prediction and diagnosis of pre-eclampsia. [Extracted from the article]

Conclusions Routine third trimester scan or POCUS reduces the rate of undiagnosed breech in labour. The primary objective was to compare point-of-care ultrasound (POCUS) and routine third trimester ultrasound versus routine antenatal care in reducing the incidence of undiagnosed breech presentation in labour. The rates of undiagnosed breech in labour were 1.0 (95% CI: 0.2-1.7) and 4.9 (95% CI: 3.8-6.0) per 1,000 births with and without routine third trimester scan. [Extracted from the article]

Covid 19-infection is associated with pre-eclampsia. Conclusions Pregnant women who had mild COVID-19 do not demonstrate changes in maternal hemodynamic function or increased levels of serum angiogenic markers compared to heathy controls. Maternal serum angiogenic marker assessment included soluble fms like tyrosine kinase- 1 (sFlt-1) and placental growth factor (PlGF). [Extracted from the article]

The highest stand-alone predictive performance was obtained with sFlt-1/PlGF ratio (AUROC: 0.82, 95% CI: 0.75 - 0.89) and creatinine (AUROC: 0.74, 95% CI: 0.67 - 0.80), while sFlt-1/PlGF ratio was superior to creatinine alone (P < 0.001). The aim of this study was to evaluate the prognostic value of repeat maternal serum angiogenic markers for the prediction of perinatal adverse outcomes in pregnancies with pre-eclampsia. OC06.02: Prognostic value of repeat maternal serum angiogenic markers for prediction of perinatal adverse outcomes in pregnancies with pre-eclampsia. [Extracted from the article]

An abstract of the article "Premature rupture of membranes assessment via transperineal ultrasonography as an alternative to speculum examinations" by E. Kalafat and others is presented.

Although there are no robust data from UK national bodies on the incidence of influenza in pregnant women, Google trend searches in the UK during the annual influenza season indicate a possible decline in cases. UK vaccination data from the last two seasons suggest that the public health message to pregnant women that flu vaccination was particularly important this year has had no impact. As a result, in anticipation of the approaching 2020-2021 winter influenza season in the UK, testing capacity was increased and flu vaccination programs reinforced, particularly for vulnerable populations. [Extracted from the article]

There is limited research on the first-trimester outcomes of women with coronavirus disease 2019 (COVID-19). Serological data to document previous SARS-CoV-2 infection would be useful to demonstrate a causal link between miscarriage and SARS-CoV-2 infection. However, the rate of positive SARS-CoV-2 test results did not have a significant effect on the miscarriage rate ( I P i = 0.810). [Extracted from the article]

To evaluate whether transperineal ultrasound assessment could improve the prediction of labour arrest at term when combined with clinical characteristics. The addition of AoP to the baseline model showed the angle of progression is independently associated with Caesarean due to labour arrest (OR: 0.89, 95% CI: 0.84 - 0.93, P < .0001) and significantly improved the predictive accuracy with an AUC value of 0.90 (95% CI: 0.85 - 0.96) (P < 0.001). Conclusions The measurement of the AoP within two hours of labour arrest diagnosis was significantly associated with labour arrest and improved the prediction of Caesarean delivery over clinical characteristics alone. [Extracted from the article]

Recent evidence suggests that home blood pressure monitoring (HBPM) is an effective way of managing pregnant women with hypertensive disorders without increasing adverse outcomes. There were no significant differences between HBPM and conventional care regarding NICU admissions (p = 0.075), preterm delivery (p = 0.680), intrauterine growth restriction (p = 0.624), composite maternal (p = 0.676), fetal (p = 0.811) or neonatal (p = 0.718) outcomes when used during antenatal period. HBPM was not associated with increased risk of adverse maternal or perinatal outcomes compared to conventional care. [Extracted from the article]

To assess the safety and efficacy of home blood pressure monitoring (HBPM) and office (traditional) blood pressure measurements in a cohort of pregnant women with gestational hypertension (GH). Each patient followed an individualised schedule of hospital visits and BP measurements based on the HBPM pathway or standard hospital protocol. [Extracted from the article]

To assess ultrasonographic presence of adenomyosis as a possible etiologic factor in women with recurrent miscarriage (RM) in comparison to a healthy population. Among women with RM, we could diagnose at least one possible risk factor in 42 women (63.6%) including the diagnosis of adenomyosis. [Extracted from the article]

Univariate cox model showed cardiac output (p = .003), systemic vascular resistance (p < .001), systemic vascular resistance index (p < .001) and aortic augmentation index (p = .004) were significantly associated with survival time without developing pre-eclampsia. Moreover, univariate cox models showed cardiac output (p = .013), cardiac index (p = .014), systemic vascular resistance (p < .001), systemic vascular resistance index (p < .001) and aortic augmentation index (p < .001) were significantly associated with survival time without developing composite adverse outcome. Systemic vascular resistance index and cardiac output were significantly associated with composite adverse outcome and the development of pre-eclampsia. [Extracted from the article]

Cardiac output (CO), cardiac index (CI), stroke volume (SV), stroke volume index (SVI), systemic vascular resistance (SVR) were assessed. The addition of SVI < 36 ml/m2, SVR>7.2 logs and SVRI>7.7 logs significantly improved the baseline model (p = 0.012, p = 0.026 and p = 0.012, respectively). The addition of SV, SVR and SVRI significantly improved the predictive accuracy of the baseline antenatal model in women undergoing IOL. [Extracted from the article]

Biparietal diameter and abdominal circumference variables were associated with the odds of ECS due to obstructed labour in both univariate and multivariate analyses (p < 0.05 for all). However, the predictive capabilities of biparietal diameter percentile (AUC:0.55,95%CI:0.46-0.63) and abdominal circumference percentile (AUC:0.56, 95% CI:0.48-0.64) without adjunct variables were poor. [Extracted from the article]

EP01.20: The utility of pregnancy-associated plasma protein-A (PAPP-A) MoM values in prediction of term respiratory distress syndrome This study aims to investigate if the PAPP-A multiples of median (MoM) levels could be used as a marker in early prediction of respiratory distress syndrome (RDS). First-trimester PAPP-A MoM values and postnatal RDS occurrences in these pregnancies were retrospectively analysed. [Extracted from the article]