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BackgroundConsidering the public health importance of stillbirth, this study quantified the trends in stillbirths over eight decades in England and Wales.MethodsThis longitudinal study utilized the publicly available aggregated data from the Office for National Statistics that captured maternity information for babies delivered in England and Wales from 1940 to 2019. We computed the trends in stillbirth with the associated incidence risk difference, incidence risk ratio, and extra lives saved per decade.ResultsFrom 1940-2019, 56 906 273 births were reported. The stillbirth rate declined (85%) drastically up to the early 1980s. In the initial five decades, the estimated number of deaths per decade further decreased by 67 765 (9.49/1000 births) in 1940-1949, 2569 (0.08/1000 births) in 1950-1959, 9121 (3.50/1000 births) in 1960-1969, 15 262 (2.31/1000 births) in 1970-1979, and 10 284 (1.57/1000 births) in 1980-1989. However, the stillbirth rate increased by an additional 3850 (0.58/1000 births) stillbirths in 1990-1999 and 693 (0.11/1000 births) stillbirths in 2000-2009. The stillbirth rate declined again during 2010-2019, with 3714 fewer stillbirths (0.54/1000 births). The incidence of maternal age 35 years) increased.ConclusionsThe stillbirth rate declined drastically, but the rate of decline slowed in the last three decades. Though teenage pregnancy (

Objectives To compare perinatal outcome and growth discordance between trichorionic triamniotic (TCTA) and dichorionic triamniotic (DCTA) or monochorionic triamniotic (MCTA) triplet pregnancies. Methods This was a multicenter cohort study using population-based data on triplet pregnancies from 11 Northern Survey of Twin and Multiple Pregnancy (NorSTAMP) maternity units and the Southwest Thames Region of London Obstetric Research Collaborative (STORK) multiple pregnancy cohort, for 2000-2013. Perinatal outcomes (from ≥ 24 weeks' gestation to 28 days of age), intertriplet fetal growth and birth-weight (BW) discordance and neonatal morbidity were analyzed in TCTA compared with DCTA/MCTA pregnancies. Results Monochorionic placentation of a pair or trio in triplet pregnancy (n = 72) was associated with a significantly increased risk of perinatal mortality (risk ratio, 2.7 (95% CI, 1.3-5.5)) compared with that in TCTA pregnancies (n = 68), due mainly to a much higher risk of stillbirth (risk ratio, 5.4 (95% CI, 1.6-18.2)), with 57% of all stillbirth cases resulting from fetofetal transfusion syndrome, while there was no significant difference in neonatal mortality (P = 0.60). The associations with perinatal mortality and stillbirth persisted when considering only pregnancies not affected by a major congenital anomaly. DCTA/MCTA triplets had lower BW and demonstrated greater BW discordance than did TCTA triplets (P = 0.049). Severe BW discordance of > 35% was 2.5-fold higher in DCTA/MCTA compared with TCTA pregnancies (26.1% vs 10.4%), but this difference did not reach statistical significance (P = 0.06), presumably due to low numbers. Triplets in both groups were delivered by Cesarean section in over 95% of cases, at a similar gestational age (median, 33 weeks' gestation). The rate of respiratory (P = 0.28) or infectious (P = 0.08) neonatal morbidity was similar between the groups. Conclusions Despite close antenatal surveillance, monochorionic placentation of a pair or trio in triamniotic triplet pregnancy was associated with a significantly increased stillbirth risk, mainly due to fetofetal transfusion syndrome, and with greater size discordance. In liveborn triplets, there was no adverse effect of monochorionicity on neonatal outcome. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

This review aims at summarizing the latest evidence on diagnosis, natural history and management of caesarean scar pregnancy (CSP).CSP can result in maternal morbidity from major haemorrhage, uterine rupture, placenta accreta spectrum disorders and hysterectomy. Classification of the CSP types, presence of fetal heart activity, gestational age and residual myometrial thickness seem to influence rates of ongoing pregnancy, subsequent development of placenta accreta with expectant management, as well as success and complication rates associated with various methods of pregnancy termination. Expectant management may be appropriate in certain good prognosis cases, such as absent fetal heart activity or when the myometrial layer at the implantation site is relatively thick. Surgical treatments are typically associated with higher success rates, but seem to result in severe haemorrhage more frequently than medical treatments, which have higher failure rates. Although other treatment modalities are available, in general, the size and quality of evidence to guide care provision in CSP is very poor.CSP can be associated with severe maternal morbidity but can also lead to a livebirth. There is currently a lack of good-quality evidence to predict the outcome of CSP and provide informed and evidence-based care.

This systematic review and meta-analysis investigated whether the use of low-dose aspirin during pregnancy by women with chronic hypertension reduces the odds of superimposed preeclampsia and poor perinatal outcomes.In September 2021, the following sources were searched: Embase, MEDLINE, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform, and EU Clinical Trials Register. Only human studies were included, with no time or language restrictions.Cohort, case-control, and randomized controlled studies reporting women with chronic hypertension pregnant with a singleton were included. Eligible studies compared low-dose aspirin use during pregnancy with a control arm.Risk of bias was assessed using the RoB 2 and ROBINS-I tools. A meta-analysis was performed using a random-effects model, estimating odds ratios and 95% confidence and prediction intervals, and the quality of data was assessed with the GRADE approach. Heterogeneity was investigated in regard to study methodology, timing of commencement of aspirin, and the outcome of preterm preeclampsia.Nine studies (3 retrospective cohort studies and 6 randomized trials) including 2150 women with chronic hypertension were included. Low-dose aspirin prophylaxis did not significantly reduce the odds of superimposed preeclampsia in the randomized controlled trials (odds ratio, 0.83; 95% confidence interval, 0.55-1.25; prediction interval, 0.27-2.56; low-quality evidence) or observational studies (odds ratio, 1.21; 95% confidence interval, 0.78-1.87; prediction interval, 0.07-20.80; very low-quality evidence). Low-dose aspirin also did not reduce the odds of preterm preeclampsia (odds ratio, 1.17; 95% confidence interval, 0.74-1.86), and early aspirin initiation had no significant impact. There was no significant effect on small-for-gestational-age neonates or perinatal mortality; however, there was a significant reduction in preterm birth (odds ratio, 0.63; 95% confidence interval, 0.45-0.89; moderate-quality evidence). The quality of the evidence is limited by heterogeneity and risk of bias.This meta-analysis was unable to demonstrate a significant change in the odds of superimposed preeclampsia, small-for-gestational-age infants, or perinatal mortality with the use of low-dose aspirin in women with chronic hypertension. However, significant reduction in preterm birth justifies the continued use of aspirin prophylaxis. This work was prospectively registered on the International Prospective Register of Systematic Reviews (registration number CRD42021285921).

Chronic hypertension (CHT) is the main risk factor for cardiovascular diseases in women with a history of hypertensive disorders of pregnancy (HDP).This study sought to assess the effectiveness of peripartum screening in predicting CHT after HDP.In this longitudinal prospective study, women with HDP underwent peripartum transthoracic echocardiography and were evaluated for CHT (blood pressure ≥140/90 mm Hg or on antihypertensive medication) at least 3 months postpartum. Univariable and multivariable analyses assessed the association between clinical and transthoracic echocardiography data and a postpartum diagnosis of CHT.At a median postpartum follow-up of 124 days (IQR: 103-145 days), 70 (33.2%) of 211 women remained hypertensive. Compared with normotensive women, women with CHT were older (35.5 ± 5.0 years vs 32.9 ± 5.6 years; P = 0.001), were more likely to be Afro-Caribbean (27.1% vs 7.8%; P 0.0001), had higher body mass index (33.4 ± 5.9 kg/mThis peripartum screening approach might be used to identify women at risk of CHT who would benefit from intensive blood pressure monitoring and pharmacological strategies from the early postpartum period to prevent cardiovascular disease.

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) 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.

The sFlt-1 (soluble fms-like tyrosine kinase-1), PlGF (placental growth factor), and their ratio are useful for predicting delivery because of preeclampsia in singleton pregnancies. Evidence on the utility of sFlt-1/PlGF ratio in twin pregnancies is lacking. We aimed to evaluate the predictive value of sFlt-1/PlGF ratio for delivery because of preeclampsia in twins. A retrospective data analysis of 164 twin pregnancies with suspected preeclampsia was performed. The sFlt-1/PlGF ratio, which was known to clinicians, was significantly higher in women who delivered within 1 and 2 weeks compared with those who did not (median: 98.9 and 84.2 versus 23.5 pg/mL, respectively; P P >0.100 for interaction). The area under the curve values of sFlt-1/PlGF were significantly higher than for PlGF alone (mean 0.88 and 0.88 versus 0.81 and 0.80) for predicting delivery because of preeclampsia within 1 and 2 weeks of blood sampling ( P =0.055 and 0.001, respectively). sFlt-1/PlGF ratio lower than 38 was able to rule-out delivery within 1 and 2 weeks with a negative predictive value of 98.8% and 96.4% for delivery because of preeclampsia within 1 and 2 weeks, respectively. A cutoff of 38 is applicable for ruling out delivery because of preeclampsia in twin pregnancies.

OBJECTIVE Pregnancies complicated by pre-eclampsia with a small-for-gestational-age (SGA) neonate have poorer maternal hemodynamic function compared to those with hypertensive disorders of pregnancy (HDP) and an appropriately grown neonate. Arterial stiffness is a recognized prognostic marker of cardiovascular disease in the general population. The aim of this study was to compare maternal arterial stiffness between hypertensive pregnancies with, and those without, a SGA neonate and normotensive control pregnancies. METHODS This was a prospective cohort study of pregnancies complicated by pre-eclampsia or gestational hypertension and healthy normotensive control pregnancies, presenting to a tertiary referral hospital between January 2012 and May 2018. Maternal arterial stiffness was assessed by aortic pulse-wave velocity (PWV) and aortic augmentation index (AIx), which were recorded using a non-invasive device (Arteriograph®). Maternal and hemodynamic factors were adjusted for using linear regression analysis. Pregnancies with HDP were divided into those that delivered a SGA (birth weight

IntroductionFetal heart rate (FHR) monitoring is a vital aspect of fetal well-being assessment, and the current method of computerised cardiotocography (cCTG) is limited to the hospital setting. Non-invasive fetal ECG (NIFECG) has the ability to produce FHR patterns through R wave detection while eliminating confusion with maternal heart rate, but is presently limited to research use. Femom is a novel wireless NIFECG device that is designed to be placed without professional assistance, while connecting to mobile applications. It has the ability to achieve home FHR monitoring thereby allowing more frequent monitoring, earlier detection of deterioration, while reducing hospital attendances. This study aims to assess the feasibility, reliability, and accuracy of femom (NIFECG) by comparing its outputs to cCTG monitoring.Methods and analysisThis is a single-centred, prospective pilot study, taking place in a tertiary maternity unit. Women with a singleton pregnancy over 28+0weeks’ gestation who require antenatal cCTG monitoring for any clinical indication are eligible for recruitment. Concurrent NIFECG and cCTG monitoring will take place for up to 60 min. NIFECG signals will be postprocessed to produce FHR outputs such as baseline FHR and short-term variation (STV). Signal acceptance criteria is set as Ethics and disseminationApproval has been obtained from South-East Scotland Research Ethics Committee 02 and MHRA. The results of this study will be published in peer-reviewed journals, and presented at international conferences.Trial registration numberNCT04941534.

OBJECTIVE Pregnancies complicated by fetal growth restriction (FGR) have a worse outcome than those with a small-for-gestational-age (SGA) fetus. There is increasing evidence of a maternal cardiovascular role in the pathophysiology of FGR. We aimed to compare maternal hemodynamic indices between pregnancies complicated by FGR and those delivering a SGA neonate, using a non-invasive device. METHODS This was a prospective study of normotensive pregnancies complicated by FGR (defined as estimated fetal weight (EFW)

Recent evidence suggests that home blood pressure monitoring (HBPM) is an effective way of managing women with hypertensive disorders of pregnancy (HDP) without increasing adverse outcomes. The aim of this systematic review and meta-analysis was to investigate the safety and efficacy of HBPM during pregnancy. Medline, EMBASE and the Cochrane library databases were searched electronically in November 2018. Studies were included from which data could be extracted on the pregnancy outcomes and included pregnancies with HDP or at increased risk of developing HDP. Data from nine studies were included in the meta-analysis. The use of HBPM during the antenatal period was associated with reduced risk of induction of labor (OR: 0.55, 95% CI: 0.36–0.82, 444 women, I2 = 0%), prenatal hospital admissions (OR: 0.31, 95% CI: 0.19–0.49, 416 women, I2 = 0%) and diagnosis of preeclampsia (OR: 0.50, 95% CI: 0.31–0.81, 725 women, I2 = 37%). The number of antenatal visits was significantly less in the HBPM group (standard mean difference: −0.49, 95% CI: −0.82 to −0.16, 738 women, I2 = 75%). There were no significant differences between HBPM and conventional care regarding composite maternal, fetal or neonatal outcomes when used during the antenatal period. There were no significant differences between the groups who had HBPM compared to those who had conventional care regarding postpartum readmissions and obtaining a blood pressure measurement within 10 days of delivery after discharge. The significant clinical heterogeneity and low quality of evidence are the main limitations, and therefore, more high quality studies are needed.

Purpose of review This review examines the variation in clinical practice with regards to ultrasound estimation of fetal weight, as well as calculation of fetal weight centiles. Recent findings Placental dysfunction is associated with fetal smallness from intrauterine malnutrition as well as fetal disability and even stillbirth from hypoxemia. Although estimating fetal weight can be done accurately, the issue of which fetal weight centile chart should be used continues to be a contentious topic. The arguments against local fetal growth charts based on national borders and customization for variables known to be associated with disease are substantial. As for other human diseases such as hypertension and diabetes, there is a rationale for the use of an international fetal growth reference standard. Irrespective of the choice of fetal growth reference standard, a significant limitation of small for gestational age (SGA) detection programs to prevent stillbirth is that the majority of stillborn infants at term were not SGA at the time of demise. Summary Placental dysfunction can present with SGA from malnutrition and/or stillbirth from hypoxemia depending on the gestational age of onset. Emerging data show that at term, fetal Doppler arterial redistribution is associated more strongly with perinatal death than fetal size. Properly conducted trials of the role for maternal characteristics, fetal size, placental biomarkers, and Doppler assessing fetal well-being are required urgently.

Objective:The incidence of perinatal mortality and morbidity in triplet pregnancies according to chorionicity is yet to be established. The aim of this systematic review was to quantify perinatal mortality and morbidity in trichorionic triamniotic (TCTA), dichorionic triamniotic (DCTA) and monochorionic triamniotic (MCTA) triplets. Methods:MEDLINE, EMBASE and CINAHL databases were searched in December 2017 for literature published in English describing outcomes of DCTA, TCTA and/or MCTA triplet pregnancies. Primary outcomes were intrauterine death (IUD), neonatal death, perinatal death (PND) and gestational age at birth. Secondary outcomes comprised respiratory, neurological and infectious morbidity, as well as a composite score of neonatal morbidity. Data regarding outcomes were extracted from the included studies. Random‐effects meta‐analysis was used to estimate the risk of mortality and morbidity and to compute the difference in gestational age at birth between TCTA and DCTA triplet pregnancies. Results:Nine studies (1373 triplet pregnancies, of which 1062 were TCTA, 261 DCTA and 50 MCTA) were included in the analysis. The risk of PND was higher in DCTA than in TCTA triplet pregnancies (odds ratio (OR), 3.3 (95% CI, 1.3–8.0)), mainly owing to the higher risk of IUD in DCTA triplet pregnancies (OR, 4.6 (95% CI, 1.8–11.7)). There was no difference in gestational age at birth between TCTA and DCTA triplets (mean difference, 1.1 weeks (95% CI, –0.3 to 2.5 weeks);I2 = 85%;P = 0.12). Neurological morbidity occurred in 2.0% (95% CI, 1.1–3.3%) of TCTA and in 11.6% (95% CI, 1.1–40.0%) of DCTA triplets. Respiratory and infectious morbidity affected 28.3% (95% CI, 20.7–36.8%) and 4.2% (95% CI, 2.8–5.9%) of TCTA and 34.0% (95% CI, 21.5–47.7%) and 7.1% (95% CI, 2.7–13.3%) of DCTA triplets, respectively. The incidence of composite morbidity in TCTA and DCTA triplets was 29.6% (95% CI, 21.1–38.9%) and 34.0% (95% CI, 21.5–47.7%), respectively. When translating these figures into a risk analysis, the risk of neurological morbidity (OR, 5.4 (95% CI, 1.6–18.3)) was significantly higher in DCTA than in TCTA triplets, while there was no significant difference in the other morbidities explored. Only one study reported on outcomes of MCTA pregnancies, hence, no formal comparison with the other groups was performed. Conclusion:DCTA triplets are at higher risk of perinatal mortality and morbidity than are TCTA triplets. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Pre-eclampsia (PE) is a severe disorder that affects up to 8% of all pregnancies and represents an important cause of maternal and perinatal morbidity and mortality. The screening of the disease is a subject of studies, but the complexity and uncertainties regarding its etiology make this objective a difficult task. In addition, the costs related to screening protocols, the heterogeneity of the most affected populations and the lack of highly effective prevention methods reduce the potential of current available algorithms for screening. Thus, the National Specialized Commission of Hypertension in Pregnancy of the Brazilian Association of Gynecology and Obstetrics Federation (Febrasgo, in the Portuguese acronym) (NSC Hypertension in Pregnancy of the Febrasgo) considers that there are no screening algorithms to be implemented in the country to date and advocates that Aspirin and calcium should be widely used.

This study aimed to assess the prognostic value of cardiovascular assessment in women with gestational hypertension or chronic hypertension for the risk of preeclampsia and need for closer antenatal surveillance. This was a prospective study of pregnancies complicated by gestational hypertension or chronic hypertension presenting to St George’s Hospital, between January 2015 and May 2018. A noninvasive ultrasonic cardiac output monitor was used to obtain cardiovascular variables of cardiac output (CO) and systemic vascular resistance (SVR) and weight-adjusted indices. The primary outcome was the time to development of preeclampsia in women with gestational hypertension or chronic hypertension. In women with gestational hypertension or chronic hypertension (n=149), cox-proportional hazards analysis showed that mean arterial pressure ( P =0.006), Afro-Caribbean ethnicity ( P =0.045), and gestational age at the time of diagnosis above 34 weeks ( P P =0.035) and high SVR and low CO (adjusted hazard ratio, 7.79 [95% CI, 1.94–31.24]; P =0.003) cardiovascular profiles had significantly higher risk of earlier preeclampsia compared with women with normal SVR and normal CO. The findings of this study demonstrate that hypertensive women with increased SVR and low CO had a higher risk of developing preeclampsia sooner.

Objectives: Small-for-gestational-age fetuses (SGA) are at high risk of intrapartum fetal compromise requiring operative delivery. In a recent study, we developed a model using a combination of thr...

Objective The aspirin use in twin pregnancies for prevention of preeclampsia is a controversial topic and the evidence on the required dose of aspirin is scarce. We aimed to assess the efficacy of 75mg/day versus 150mg/day aspirin for prevention of preeclampsia in twin pregnancies. Study Design This is a retrospective cohort study of twin pregnancies managed at St. George’s University Hospital between 2012 and 2019. The National Institute for Health and Care Excellence (NICE) guideline published in 2010 has recommended low-dose aspirin to women at high risk of preeclampsia.1 Monochorionic and dichorionic twin pregnancies were included in the cohort. Pregnancies between 2010 and 2012 were excluded to ensure thorough implementation of national guideline. High-order multi-fetal gestations and pregnancies complicated by fetal anomalies were also excluded. Twin pregnancies with any of these risk factors (hypertension in a previous pregnancy, chronic hypertension, renal disease, autoimmune disorder, diabetes, nulliparity, maternal age >40 years, pregnancy interval >10years, body mass index >35kg/m2 or family history of preeclampsia) as per NICE guideline were started on aspirin1. The aspirin dose was changed from 75mg/day to 150mg/day after 2017, following reports of effective prevention of preeclampsia using aspirin 150mg/day.2-4 The main outcome was preeclampsia diagnosed according to International Society for the Study of Hypertension in Pregnancy guideline.5 Hypertensive disorders of pregnancy (HDP) included preeclampsia or gestational hypertension. Results There were 630 pregnancies in the cohort; 404 received aspirin (108 received 150mg/day and 296 received 75mg/day), while 226 did not. There were 28 (4.4%) cases of preeclampsia and 47 (7.5%) cases of HDP in the cohort. No significant differences in maternal age (P=0.510), nulliparity (P = 0.945), chorionicity (P=0.700) were observed between 75mg/day and 150mg/day aspirin groups. The incidence of preeclampsia was similar between aspirin 150mg/day and no aspirin groups (1.8% vs. 3.1%, P=0.510). However, there was a trend towards a significant decrease in preeclampsia in those receiving aspirin 150mg/day compared to 75mg/day (1.8% vs 6.4%, P=0.067). There were no statistically significant differences between aspirin 150mg/day and no aspirin groups regarding the incidence of HDP (1.8% vs 5.3%, P =0.140), but the incidence of HDP was significantly lower in aspirin 150mg/day group compared to 75mg/day (1.8% vs 11.1%, P =0.003) (Figure 1). The incidence of HDP was significantly higher in aspirin 75mg/day group compared to no aspirin (11.1%% vs 5.3%, P=0.018). We investigated the association of aspirin dose with HDP in a multivariable logistic regression model after adjusting for maternal age in years, chorionicity, and smoking during pregnancy. The reference group was the low-risk twin pregnancies who did not receive aspirin. The direction of the association changed from a significant increase in HDP (odds ratio: 2.01, 95% confidence interval: 1.03-4.18, P=0.048) to a non-significant decrease (odds ratio: 0.31, 95% confidence interval: 0.05-1.16, P =0.127) when the aspirin dose was increased from 75mg/day to 150mg/day. Conclusion The incidence of hypertensive disorders in twin pregnancies with additional risk factors for preeclampsia was significantly lower in those receiving aspirin 150mg/day compared to 75mg/day.

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.

INTRODUCTION: Ultrasound signs of abnormal placental invasion are subjective in nature. We tested the hypothesis that placental thickness in the lower uterine segment is increased when there is abnormally invasive placenta (AIP) in women with a low-lying placenta. MATERIAL AND METHODS: Retrospective analysis of data of placental thickness in women with ultrasound evidence of major placenta previa or a low-lying anterior placenta was done. The diagnosis of AIP was confirmed both intraoperatively and on histopathology for those managed by partial myometrial excision with uterine conservation or by hysterectomy. RESULTS: In all, 131 records were available for analysis after exclusion of 33 cases due to unsuitable images and eight cases without pregnancy outcomes. The diagnosis of AIP was confirmed in 28 (21.4%) of the 131 cases. The lower segment placental thickness was significantly higher in women with AIP (median = 50.3 mm, IQR: 42.7-64.3) than in those with normal placentation (median = 30.9 mm, IQR: 22.9-42.2, P CONCLUSIONS: Lower uterine segment placental thickness is increased in women with AIP compared with those with noninvasive placentation. This association constitutes a pragmatic objective sign and may be of clinical value in improving prenatal detection of AIP in women with placental implantation in the lower uterine segment. Prospective studies are necessary to ascertain lower segment placental thickness as a predictor for AIP.

Objective Pre-eclampsia (PE) is associated with impaired trophoblastic invasion and typical villous and vascular placental lesions. The primary aim of this study was to quantify the prevalence of placental histopathological lesions in pregnancies complicated by PE. Methods MEDLINE, EMBASE and CINAHL were searched electronically, and relevant articles reporting on placental histopathological lesions were assessed according to the following criteria: study design, number of pregnancies included, severity of PE and whether the pathologist was blinded to the clinical information. Prospective and retrospective case–control studies including ≥ 100 pregnancies were included in the systematic review. The incidence of each type of histological lesion according to the Perinatal Section of the Society for Pediatric Pathology classification in pre-eclamptic and normal pregnancies was identified, and lesions were categorized into two main groups: villous lesions and vascular lesions. Random-effects meta-analysis of proportions was used for analysis. Between-study heterogeneity was assessed using the I2 statistic. Results The search yielded 717 citations, and a total of eight studies (four blinded and four non-blinded) were included in the review. In unblinded studies, the pooled prevalence of villous lesions was 11.6% and 48.2% in normal and pre-eclamptic pregnancies, respectively, giving a pooled odds ratio (OR) of 7.59. In blinded studies, the pooled prevalence of villous lesions was 18.5% and 42.0% in normal and pre-eclamptic pregnancies, respectively, giving a pooled OR of 4.28. In unblinded studies, the pooled prevalence of vascular lesions was 8.1% and 37.3% in normal and pre-eclamptic pregnancies, respectively, giving a pooled OR of 20.34. In blinded studies, the pooled prevalence of vascular lesions was 9.8% and 38.9%, in normal and pre-eclamptic pregnancies, respectively, giving a pooled OR of 7.08. Conclusions In blinded studies, the incidence of both placental villous and vascular histopathological lesions is four- to seven-fold higher in pre-eclamptic than in normal pregnancies. Greater differences are reported in unblinded studies. Despite the higher probability (point prevalence) of finding abnormal placental pathology in pregnancies with PE, placental lesions are not specific to the diagnosis of PE. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Prenatal diagnosis is a rapidly evolving speciality. Screening for aneuploidy begins with non-sonographic features of background risk of maternal age and past and family history. It is possible to diagnose major structural defects in the foetus using second trimester scans. Serum biochemistry markers in the early second trimester were added to increase the detection rate of aneuploidy. However, as some of these abnormalities were amenable to detection earlier in the first trimester, newer modalities were introduced. Nuchal translucency (NT) measurement was one of the main advances with regard to first trimester screening. Additional markers such as the presence of nasal bone, tricuspid regurgitation, ductus venosus and megacystis; together with first trimester serum biochemistry, further enhanced the detection rate of chromosomal abnormalities. Advances in research and technology have resulted in the availability of non-invasive prenatal testing from 10 weeks of gestation. This has facilitated the detection of the three major chromosomal aneuploidies at very early gestation. However, there are a wide range of genetic syndromes that are not confined to the main trisomies. There are specific markers on ultrasound that can be linked to specific syndromes. Hence, a structured and stepwise approach is needed to identify and reach a possible diagnosis. As anomalies are classified into malformations, deformations and disruptions, it is important to note that not all markers detected are due to genetic syndromes and not all genetic syndromes can be detected on ultrasound scan. In this chapter, we outline common structural markers and their association with main genetic syndromes.

Angiogenic markers such as PlGF (placental growth factor) and sFlt-1 (soluble Fms-like tyrosine kinase-1) have been shown to be useful for predicting adverse outcome in women suspected of having preeclampsia. The aim of the current study was to evaluate the prognostic value of angiogenic markers and maternal risk factors in pregnant women with hypertension. This was a prospective study of pregnancies complicated by preeclampsia, gestational hypertension, or chronic hypertension presenting to 1 of 2 tertiary referral hospitals between May 2013 and May 2018. Maternal characteristics along with blood samples for angiogenic marker analysis were obtained from participants. The primary outcome was delivery related to preeclampsia within 1 and 2 weeks. In total, 302 women with hypertension were included in the study cohort. The baseline model included maternal body mass index, mean arterial pressure, and clinical diagnosis at the time of assessment. The use of sFlt-1/PIGF ratio combined with the baseline model significantly improved the area under the curve values for predicting delivery within a week (0.83 versus 0.88; P =0.025) or in 2 weeks (0.86 versus 0.93; P =0.001) due to preeclampsia-related events in gestational ages

Placental dysfunction has a deleterious influence on fetal size and is associated with higher rates of perinatal morbidity and mortality. This association underpins the strategy of fetal size evaluation as a mechanism to identify placental dysfunction and prevent stillbirth. The optimal method of routine detection of small for gestational age (SGA) remains to be clarified with choices between estimation of symphyseal-fundal height versus routine third-trimester ultrasound, various formulae for fetal weight estimation by ultrasound, and the variable use of national, customized, or international fetal growth references. In addition to these controversies, the strategy for detecting SGA is further undermined by data demonstrating that the relationship between fetal size and adverse outcome weakens significantly with advancing gestation such that near term, the majority of stillbirths and adverse perinatal outcomes occur in normally sized fetuses. The use of maternal serum biochemical and Doppler parameters near term appears to be superior to fetal size in the identification of fetuses compromised by placental dysfunction and at increased risk of damage or demise. Multiparameter models and predictive algorithms using maternal risk factors, and biochemical and Doppler parameters have been developed, but need to be prospectively validated to demonstrate their effectiveness.

Additional file 1: Supplementary methods: Additional details for handling missing data and evaluating predictive performance of models. Table S1: Search strategy for pre-eclampsia prediction models. Table S2: Predictors evaluated in the models externally validated in the IPPIC-UK cohorts. Table S3: Prediction models and equations identified from the literature search. Table S4: Study level characteristics of IPPIC-UK cohorts. Table S5: Patient characteristics of IPPIC-UK cohorts. Table S6: Number and proportion missing for each predictor in each cohort used for external validation. Table S7: Risk of bias assessment of the IPPIC-UK cohorts using the PROBAST tool. Table S8: Summary of linear predictor values and predicted probabilities for each model in each cohort. Table S9: Predictive performance statistics for models in the individual IPPIC-UK cohorts. Table S10: Predictive performance statistics for models in nulliparous women in all cohorts and in the POP cohort. Fig. S1: Decision curves for early pre-eclampsia models in SCOPE, UPBEAT and POP. Fig. S2: Decision curves for late pre-eclampsia models in SCOPE, Allen 2017, UPBEAT and POP.

Fetal therapy is defined as any prenatal treatment administered to the mother or fetus with the primary indication to improve perinatal or long-term outcomes for the fetus or newborn. The practice of fetal therapy is a relatively new concept in the field of obstetrics. It originated over 55 years ago when Liley et al. first performed intraperitoneal transfusion for the treatment of fetal anaemia. Since then, the practice has evolved from open fetal surgery to minimally invasive techniques used to manage an array of complex conditions. The domain of fetal therapy is an ever-evolving specialty. This chapter discusses key principles and techniques of current fetal therapy. As well as providing background information on how these techniques have evolved, it also focuses on determining what information future developments may bring.

Preeclampsia is associated with increased cardiovascular long-term risk; however, the underlying functional and structural mechanisms are unknown. We investigated maternal cardiac alterations after preeclampsia. Female rats harboring the human angiotensinogen gene [TGR(hAogen)L1623] develop a preeclamptic phenotype with hypertension and albuminuria during pregnancy when mated with male rats bearing the human renin gene [TGR(hRen)L10J] but behave physiologically normal before and after pregnancy. Furthermore, rats were treated with pravastatin. We tested the hypothesis that statins are a potential therapeutic intervention to reduce cardiovascular alterations due to simulated preeclamptic pregnancy. Although hypertension persists for only 8 days in pregnancy, former preeclampsia rats exhibit significant cardiac hypertrophy 28 days after pregnancy observed in both speckle tracking echocardiography and histological staining. In addition, fibrosis and capillary rarefaction was evident. Pravastatin treatment ameliorated the remodeling and improved cardiac output postpartum. Preeclamptic pregnancy induces irreversible structural changes of cardiac hypertrophy and fibrosis, which can be moderated by pravastatin treatment. This pathological cardiac remodeling might be involved in increased cardiovascular risk in later life.