Clinical significance of cerebroplacental ratio.

PURPOSE OF REVIEW: Two-thirds of the pregnancies complicated by stillbirth demonstrate growth restriction. Identification of the foetus at risk of growth restriction is essential to reduce the risk of stillbirth. The aim of this review is to critically appraise the current evidence regarding clinical utility of cerebroplacental ratio (CPR) in antenatal surveillance. RECENT FINDINGS: The CPR has emerged as an assessment tool for foetuses at increased risk of growth disorders. CPR is a better predictor of adverse events compared with middle-cerebral artery or umbilical artery Doppler alone. The predictive value of CPR for adverse perinatal outcomes is better for suspected small-for-gestational age foetuses compared with appropriate-for-gestational age (AGA) foetuses. CPR could be useful for the risk stratification of small-for-gestational age foetuses to determine the timing of delivery and also to calculate the risk of intrapartum compromise or prolonged admission to the neonatal care unit. Although there are many proposed cut-offs for an abnormal CPR value, evidence is currently lacking to suggest the use of one cut-off over another. CPR appears to be associated with increased risk of intrapartum foetal compromise, abnormal growth velocity, and lower birthweight in AGA foetuses as well. Moreover, birthweight differences are better explained with CPR compared to other factors such as ethnicity. However, the role of CPR in predicting adverse perinatal outcomes such as acidosis or low Apgar scores in AGA foetuses is yet to be determined. SUMMARY: CPR appears to be a useful surrogate of suboptimal foetal growth and intrauterine hypoxia and it is associated with a variety of perinatal adverse events

Evidence for uteroplacental malperfusion in fetuses with major congenital heart defects.

AIMS: Fetuses affected by congenital heart defects (CHD) are considered to be at increased risk of fetal growth restriction and intrauterine demise. Whether these risks are a direct consequence of fetal CHD or a result of associated uteroplacental dysfunction is not evident from the data of recent studies. The aim of this study was to investigate the prevalence of uteroplacental dysfunction reflected by abnormal uterine artery Doppler indices and reduced fetal growth in CHD pregnancies. METHODS: This is a retrospective case-control study including singleton pregnancies referred for detailed fetal cardiac assessment subsequently diagnosed with or without CHD. Mid-trimester uterine artery Doppler assessment at 20-24 weeks as well as third trimester fetal biometry and arterial Doppler pulsatility indices (PI) were performed. All fetal biometry were converted into centiles and Doppler values to multiples of median (MoM) to adjust for physiological changes with gestation. RESULTS: The study included 811 pregnancies including 153 cases where the fetus was diagnosed with CHD. Mid-pregnancy uterine artery PI was significantly higher in women with fetal CHD compared to controls (0.90MoM vs 0.83MoM; p = 0.006). In the third trimester, median centiles for fetal head circumference (45.4 vs 57.07; p<0.001), abdominal circumference (51.17 vs 55.71; p = 0.014), estimated fetal weight (33.6 vs 56.7; p<0.001) and cerebroplacental ratio (CPR: 0.84MoM vs 0.95MoM; p<0.001) were significantly lower in fetuses with CHD compared to controls. The percentage of small for gestational age births <10th centile (24.0% vs 10.7%; <0.001) and low CPR <0.6MoM (11.7% vs 2.5%; p<0.001) were significantly higher in the fetal CHD cohort. CONCLUSIONS: Mid-pregnancy uterine artery resistance is increased and subsequent fetal biometry reduced in pregnancies with CHD fetuses. These findings suggest that fetal CHD are associated with uteroplacental dysfunction, secondary to impaired maternal uteroplacental perfusion resulting in relative fetal hypoxaemia and reduced fetal growth

Selective Fetal Growth Restriction in Dichorionic Twin Pregnancies: Diagnosis, Natural History, and Perinatal Outcome.

This study aims to evaluate the natural history, disease progression, and outcomes in dichorionic twins with selective fetal growth restriction (sFGR) according to different diagnostic criteria and time of onset. Dichorionic twins seen from the first trimester were included. sFGR was classified according to the Delphi consensus, and was compared to the outcomes of those classified by the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) diagnostic criteria. Early sFGR occurred before 32-weeks, and late sFGR after 32-weeks. Disease progression, neonatal outcomes such as gestation at delivery, birthweight, neonatal unit (NNU) admission, and morbidities were compared. One-hundred twenty-three of 1053 dichorionic twins had sFGR, where 8.4% were classified as early sFGR, and 3.3% were late sFGR. Disease progression was seen in 36%, with a longer progression time (5 vs. 1 week) and higher progression rate (40% vs. 26%) in early sFGR. Perinatal death was significantly higher in the sFGR than the non-sFGR group (24 vs. 16 per 1000 births, p = 0.018), and those with early sFGR had more NNU admissions than late sFGR (p = 0.005). The ISUOG diagnostic criteria yielded a higher number of sFGR than the Delphi criteria, but similar outcomes. sFGR have worse perinatal outcomes, with early onset being more prevalent. Use of the Delphi diagnostic criteria can reduce over-diagnosis of sFGR and avoid unnecessary intervention

Risk of operative delivery for intrapartum fetal compromise in small-for-gestational-age fetuses at term: external validation of the IRIS algorithm.

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 three antenatal (gestational age at delivery, parity, cerebroplacental ratio) and three intrapartum (epidural use, labor induction and augmentation using oxytocin) variables for the prediction of operative delivery due to presumed fetal compromise in SGA fetuses - the Individual RIsk aSsessment (IRIS) prediction model. The aim of this study was to test the predictive accuracy of the IRIS prediction model in an external cohort of singleton pregnancies complicated by SGA. METHODS: This was an external validation study using a cohort of pregnancies from two tertiary referral centers in Spain and England. The inclusion criteria were singleton pregnancies diagnosed with an SGA fetus, defined as estimated fetal weight (EFW) below the 10th centile for gestational age at 36 weeks or beyond, which had fetal Doppler assessment and available data on their intrapartum care and pregnancy outcomes. The main outcome in this study was the operative delivery for presumed fetal compromise. External validation was performed using the coefficients obtained in the original development cohort. The predictive accuracies of models were investigated with receiver operating characteristics (ROC) curves. The Hosmer-Lemeshow test was used to test the goodness-of-fit of models and calibration plots were also obtained for visual assessment. A mobile application using the combined model algorithm was developed to facilitate clinical use. RESULTS: Four hundred twelve singleton pregnancies with an antenatal diagnosis of SGA were included in the study. The operative delivery rate was 22.8% (n = 94). The group which required operative delivery for presumed fetal compromise had significantly fewer multiparous women (19.1 versus 47.8%, p < 0.001 in the total study population; 19.0 versus 43.5 and 19.2 versus 49.6%, UK and Spain cohort, respectively), lower cerebroplacental ratio (CPR) multiples of median (MoM) (median: 0.77 versus 0.92, p < 0.001 in the total study population; 0.77 versus 0.92 and 0.77 versus 0.92, UK and Spain cohort, respectively), more inductions of labor (74.5 versus 60.1%, p = 0.010 in the total study population; 85.7 versus 77.2 and 71.2% and 53.1, UK and Spain cohort, respectively) and more use of oxytocin augmentation (57.4 versus 39.3%, p = 0.002 in the total study population; 19.0 versus 12.0 and 68.5 and 50.4%, UK and Spain cohort, respectively) compared to those who did not require operative delivery due to presumed fetal compromise. When the original antenatal model was applied to the present cohort, we observed moderate predictive accuracy (AUC: 0.70, 95% CI: 0.64-0.76), and no signs of poor fit (p = 0.464). The original combined model, when applied to the external cohort, had moderate predictive accuracy (AUC: 0.72, 95% CI: 0.67-0.77) and also no signs of poor fit (p = 0.268) without the need for refitting. A statistically significant increase in the predictive accuracy was not achieved via refitting of the combined model (AUC 0.76 versus 0.72, p = 0.060). CONCLUSIONS: Using our recently published model, the predictive accuracy for fetal compromise requiring operative delivery in term fetuses thought to be SGA was modest and showed no signs of poor fit in an external cohort. The IRIS tool for mobile devices has been developed to facilitate wide clinical use of this prediction model

Metformin for prevention of hypertensive disorders of pregnancy in women with gestational diabetes or obesity: systematic review and meta‐analysis of randomized trials

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

The Association Between Hypertension in Pregnancy and Preterm Birth with Fetal Growth Restriction in Singleton and Twin Pregnancy: Use of Twin Versus Singleton Charts.

OBJECTIVE: To compare the rates of fetal growth restriction (FGR) in singleton and twin pregnancies using singleton and twin-specific birthweight standards. METHODS: The study included liveborn twin and singleton pregnancies between January 2000 and January 2019. Hypertensive disorders of pregnancy (HDP) included gestational hypertension and pre-eclampsia. The study outcomes were FGR or small-for-gestational-age (SGA) at birth as assessed using singleton and twin reference charts. RESULTS: The analysis included 1473 twin and 62,432 singleton pregnancies. In singleton pregnancies the risk of PTB <34 weeks without HDP (OR 2.82, p < 0.001), delivery ≥34 weeks with HDP (OR 2.38, p < 0.001), and PTB <34 weeks with HDP (OR 13.65, p < 0.001) were significantly higher in the pregnancies complicated by FGR compared to those without. When selective fetal growth restriction (sFGR) was assessed using the singleton standard, the risk of PTB <34 weeks without HDP (OR 1.03, p = 0.872), delivery ≥34 weeks with HDP (OR 1.36, p = 0.160) were similar in the pregnancies complicated by sFGR compared to those without, while the risk of PTB <34 weeks with HDP (OR 2.41, p = 0.025) was significantly higher in the pregnancies complicated by sFGR compared to those without. When sFGR was assessed using the twin-specific chart, the risk of PTB <34 weeks without HDP (OR 3.55, p < 0.001), delivery ≥34 weeks with HDP (OR 3.17, p = 0.004), and PTB <34 weeks with HDP (OR 5.69, p < 0.001) were significantly higher in the pregnancies complicated by sFGR compared to those without. The stronger and more consistent association persisted in the subgroup analyses according to chorionicity. The strength of association in dichorionic twin pregnancies resembles that of the singletons more closely and consistently when the FGR was diagnosed using the twin-specific charts. CONCLUSION: FGR in twin pregnancies has a stronger and more consistent association with HDP and PTB when using twin-specific rather than singleton charts. This study provides further evidence supporting the use of twin-specific charts when assessing fetal growth in twin pregnancies

Incidence of postpartum hypertension within 2 years of a pregnancy complicated by pre-eclampsia: a systematic review and meta-analysis.

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. TWEETABLE ABSTRACT: The risk of hypertension within 2 years of birth is six-fold higher in women who experienced pre-eclampsia

Performance of Antenatal Diagnostic Criteria of Twin-Anemia-Polycythemia Sequence.

This study aims to elicit the validation performance of different diagnostic criteria and to evaluate the disease course and perinatal outcomes of pregnancies complicated by twin anemia polycythemia sequence (TAPS). Monochorionic diamniotic (MCDA) twin pregnancies who received serial middle cerebral artery (MCA) peak systolic velocity (PSV) measurements without non-TAPS-related demise or major anomalies were included. Course of disease, antenatal intervention, additional ultrasound features, and perinatal outcomes were compared between each criteria and onset. Forty-nine cases of TAPS and 203 non-TAPS controls were identified. The incidence of TAPS was 19.2%, 15.7%, 7.8%, and 6.3% for ΔPSV MoM > 0.373, ΔPSV MoM > 0.5, traditional, and Delphi consensus criteria, respectively (p 0.373 (87.0 vs. 59.0%, p = 0.037). TAPS had a significantly higher birth weight discordance than uncomplicated MCDA twins (25.3 vs. 7.3%, p 0.373 criteria identified milder cases, without a significant impact on neonatal outcomes