Composite Adverse Perinatal Outcome Research Articles

Comparison of composite adverse perinatal outcomes in early- and late-onset intrahepatic cholestasis of pregnancy

Aim: To compare composite adverse perinatal outcomes (CAPO) in women with early- and late-onset intrahepatic cholestasis of pregnancy (ICP). Materials and Methods: This study was designed as a single-center, retrospective study in a tertiary hospital and included a total of 198 patients with ICP, including 36 patients with early-onset ICP (EO-ICP) and 162 patients with late-onset ICP (LO-ICP). ICP that developed before the 28th week of gestation was defined as EO-ICP, and ICP that occurred after the 28th week of gestation was defined as LO-ICP. The existence of at least one of the following criteria was defined as CAPO: umbilical cord arterial pH < 7.20, fifth-minute Apgar score < 5, and neonatal intensive care stay of >24 hours. Results: The rates of spontaneous preterm birth and neonatal intensive care admission were statistically significantly higher in the EO-ICP group (p0.05), however, the CAPO rate was significantly higher in the EO-ICP group (p=0.028). Receiver operator characteristic analysis revealed an optimal cut-off value of 33.5 μmol/L for the serum bile acid level, at which this parameter had 74% sensitivity and 68% specificity (area under the curve=0.759; p

Utility of the cerebro-placental-uterine ratio in predicting composite adverse perinatal outcomes in pregestational diabetes: A prospective cohort study.

To examine the cerebro-placental-uterine ratio (CPUR) in pregnant women with pregestational diabetes and determine its role in predicting adverse prenatal outcomes. This prospective, cohort study conducted at a tertiary hospital included 65 patients with pregestational diabetes (25 with type1 diabetes, 40 with type2 diabetes) and 130 low-risk patients in the control group. The cerebroplacental (CPR) ratio and the CPUR were calculated. Composite adverse perinatal outcome (CAPO) is defined as the presence of any of the following: (1) Neonatal intensive care unit (NICU) admission, (2) Apgar at 5 min <7, and (3) umbilical cord arterial pH <7.10. The relationship of CPR and CPUR with CAPO was investigated. CPR and CPUR were significantly lower in the pregestational diabetes group than in the control group. The NICU admission was higher in the case group. In receiver operating characteristic analyses, the optimal cut-off value of CPUR was 1.46 (AUC = 0.72, p = 0.003, 80% sensitivity, and 69% specificity) to predict CAPO and the optimal cut-off value of CPUR was 1.50 for NICU admission (AUC = 0.70, p = 0.013, 77% sensitivity, and 66% specificity). Low CPUR values were found to be associated with adverse perinatal outcomes in women with pregestational diabetes. With the increasing number of studies, CPUR is expected to be utilized more widely in routine obstetric practice.

Role of Ductus Venosus Doppler Sonography for the Prediction of Perinatal Outcome in Term Pregnancies Complicated by Gestational Diabetes Mellitus.

Ductus venosus (DV) Doppler velocimetry reflects fetal cardiac function. Gestational diabetes mellitus (GDM) is assumed to impair cardiac function due to fetal hyperglycemia. The purpose of this study was to assess the ability of DV Doppler to predict an adverse perinatal outcome (APO) in term pregnancies with GDM. This is a retrospective cohort study including GDM pregnancies of singleton, non-anomalous fetuses without any signs of placental dysfunction. All GDM women who primarily had a vaginal delivery attempt and in which DV Doppler was examined from 37+0 weeks on were included. Receiver operating characteristic curve (ROC) analyses were performed to assess the predictive value of DV pulsatility index (DV-PI) regarding a composite APO (CAPO). Furthermore, a subgroup analysis was performed regarding the presence of a large-for-gestational-age (LGA) newborn. A total of n=89 cases were included. Overall, CAPO occurred in 26 out of 89 cases (29.2%). All DV Doppler examinations showed a positive A wave. DV-PI was>95th percentile in 8 out of 89 cases (9%). Overall, ROC analysis showed no significant association of DV-PI with CAPO (AUC=0.523, p=0.735). However, regarding individual APO parameters, ROC analysis showed a significant association of DV-PI with 5th-min AGPAR (AUC=0.960, p=0.027), which was not confirmed after exclusion of LGA cases. In GDM pregnancies at term, DV Doppler sonography seems to have no benefit for APO prediction.

Cervical pessary versus vaginal progesterone in women with a singleton pregnancy, a short cervix, and no history of spontaneous preterm birth at less than 34 weeks’ gestation: open label, multicentre, randomised, controlled trial

ObjectiveTo compare the effectiveness of cervical pessary and vaginal progesterone in the prevention of adverse perinatal outcomes and preterm birth in pregnant women of singletons with no prior spontaneous preterm...

The Association between discordant umbilical arterial resistance in growth-restricted fetuses and adverse outcomes

Assessing the umbilical artery pulsatility index (UA PI) via Doppler measurements plays a critical role in evaluating fetal growth impairment. This study aims to investigate perinatal outcomes associated with discordant PIs of umbilical arteries (UAs) in growth-restricted fetuses. In this retrospective cohort study, all singleton pregnancies were included if their estimated fetal weight (EFW) and/or abdominal circumference (AC) fell below the 10th percentile for gestational age (2017-2022). Eligible cases included singleton pregnancies with concurrent sampling of both UAs within 14 days of birth at the US evaluation closest to delivery. Exclusion criteria comprised births before 22 weeks gestation, evidence of absent/reverse end-diastolic flow in either UA and known fetal genetic/structural anomalies. The study compared cases with discordant UA pulsatility index (PI) values (defined as one UA-PI ≤ 95th percentile and the other UA-PI > 95th percentile for gestational age) to pregnancies where both UAs had normal PI values and those with both UAs displaying abnormal PI values. The primary outcome assessed was the occurrence of composite adverse neonatal outcomes. Multivariable logistic regressions were performed, adjusting for relevant covariates. The study encompassed 1,014 patients, including 194 (19.1%) with discordant UA PI values among those who had both UA sampled close to delivery, 671 (66.2%) with both UAs having normal PI values and 149 (14.7%) with both UAs exhibiting abnormal values. Pregnancies with discordant UAs PI displayed compromised sonographic parameters compared to those with both UAs showing normal PI values. Similarly, the number of the abnormal UAs PI was associated with adverse perinatal in a dose response manner. Cases with one abnormal (discordant) UA PI showed favorable sonographic parameters and perinatal outcomes compared to those with both abnormal UA PI values and cases with both UAs abnormal PI values showed worse sonographic parameters and perinatal outcomes compared to those with discordant UA PI. Multivariate analysis revealed that discordant UAs PI was significantly and independently associated with composite adverse perinatal outcomes, with an adjusted odds ratio (aOR) of 1.75 (95% confidence interval [CI] 1.24-2.47). Evaluating the resistance indices of both umbilical arteries may provide useful data and assist in assessing adverse perinatal outcomes among growth-restricted fetuses.

Vaginal misoprostol versus vaginal dinoprostone for cervical ripening and induction of labour: An individual participant data meta-analysis of randomised controlled trials.

Induction of labour (IOL) is common practice and different methods carry different effectiveness and safety profiles. To compare the effectiveness, and maternal and perinatal safety outcomes of IOL with vaginal misoprostol versus vaginal dinoprostone using individual participant data from randomised clinical trials. The following databases were searched from inception to March 2023: CINAHL Plus, ClinicalTrials.gov, Cochrane Pregnancy and Childbirth Group Trial Register, Ovid Embase, Ovid Emcare, Ovid MEDLINE, Scopus and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). Randomised controlled trials (RCTs), with viable singleton gestation, no language restrictions, and all published and unpublished data. An individual participant data meta-analysis was carried out. Ten of 52 eligible trials provided individual participant data, of which two were excluded after checking data integrity. The remaining eight trials compared low-dose vaginal misoprostol versus dinoprostone, including 4180 women undergoing IOL, which represents 32.8% of all participants in the published RCTs. Of these, 2077 were assigned to low-dose vaginal misoprostol and 2103 were assigned to vaginal dinoprostone. Compared with vaginal dinoprostone, low-dose vaginal misoprostol had a comparable rate of vaginal birth. Composite adverse perinatal outcomes did not differ between the groups. Compared with vaginal dinoprostone, composite adverse maternal outcomes were significantly lower with low-dose vaginal misoprostol (aOR 0.80, 95% CI 0.65-0.98, P = 0.03, I2  = 0%). Low-dose vaginal misoprostol and vaginal dinoprostone for IOL are comparable in terms of effectiveness and perinatal safety. However, low-dose vaginal misoprostol is likely to lead to a lower rate of composite adverse maternal outcomes than vaginal dinoprostone.

Doppler ultrasound of umbilical and middle cerebral artery in third trimester small-for-gestational age fetuses to decide on timing of delivery for suspected fetal growth restriction: A cohort with nested RCT (DRIGITAT).

To assess the association of the umbilicocerebral ratio (UCR) with adverse perinatal outcome in late preterm small-for-gestational age (SGA) fetuses and to investigate the effect on perinatal outcomes of immediate delivery. Multicentre cohort study with nested randomised controlled trial (RCT). Nineteen secondary and tertiary care centres. Singleton SGA pregnancies (estimated fetal weight [EFW] or fetal abdominal circumference [FAC] <10th centile) from 32 to 36+6 weeks. Women were classified: (1) RCT-eligible: abnormal UCR twice consecutive and EFW below the 3rd centile at/or below35 weeks or below the 10th centile at 36 weeks; (2) abnormal UCR once or intermittent; (3) never abnormal UCR. Consenting RCT-eligible patients were randomised for immediate delivery from 34 weeks or expectant management until 37 weeks. A composite adverse perinatal outcome (CAPO), defined as perinatal death, birth asphyxia or major neonatal morbidity. The cohort consisted of 690 women. The study was halted prematurely for low RCT-inclusion rates (n = 40). In the RCT-eligible group, gestational age at delivery, birthweight and birthweight multiple of the median (MoM) (0.66, 95% confidence interval [CI] 0.59-0.72) were significantly lower and the CAPO (n = 50, 44%, p < 0.05) was more frequent. Among patients randomised for immediate delivery there was a near-significant lower birthweight (p = 0.05) and higher CAPO (p = 0.07). EFW MoM, pre-eclampsia, gestational hypertension and Doppler classification were independently associated with the CAPO (area under the curve 0.71, 95% CI 0.67-0.76). Perinatal risk was effectively identified by low EFW MoM and UCR. Early delivery of SGA fetuses with an abnormal UCR at 34-36 weeks should only be performed in the context of clinical trials.

Perinatal outcome of fetuses predicted to be large-for-gestational age on universal third-trimester ultrasound in non-diabetic pregnancy.

To describe the perinatal outcome of fetuses predicted to be large-for-gestational age (LGA) on universal third-trimester ultrasound in non-diabetic pregnancies of women attempting vaginal delivery. This was a prospective population-based cohort study of patients from a single tertiary maternity unit in the UK offering universal third-trimester ultrasound and practicing expectant management of suspected LGA until 41-42 weeks. All women with a singleton pregnancy and an estimated due date between January 2014 and September 2019 were included. Women delivering before 37 weeks, those having a planned Cesarean delivery, those with pre-existing or gestational diabetes, those with fetal abnormalities and those who did not undergo a third-trimester scan were excluded from the assessment of perinatal outcome of cases with LGA predicted on ultrasound after implementation of the universal scan period. Association of LGA on universal third-trimester ultrasound screening and perinatal adverse outcome was assessed, with the exposures of interest being estimated fetal weight (EFW) at the 90th -95th , > 95th and > 99th percentile. The reference group was composed of fetuses with EFW at the 30th -70th percentile. Analysis was performed using multivariate logistic regression. The evaluated adverse perinatal outcomes included a composite outcome of admission to neonatal intensive care unit, Apgar score < 7 at 5 min and arterial cord pH < 7.1 (CAO1) and a composite outcome of stillbirth, neonatal death and hypoxic ischemic encephalopathy (CAO2). Secondary maternal outcomes were induction of labor, mode of delivery, postpartum hemorrhage, shoulder dystocia and obstetric anal sphincter injury. Cases with EFW > 95th percentile on universal third-trimester scan were at increased risk of CAO1 (adjusted odds ratio (aOR), 2.18 (95% CI, 1.69-2.80)) and CAO2 (aOR, 2.58 (95% CI, 1.05-6.34)). Cases with EFW at the 90th -95th percentile had a less pronounced increase in the risk of CAO1 (aOR, 1.35 (95% CI, 1.02-1.78)) and were not at increased risk of CAO2. All pregnancies with a fetus predicted to be LGA were at increased risk of all of the evaluated secondary maternal outcomes except for obstetric anal sphincter injury. The risk of adverse maternal outcome was typically higher with increasing EFW. Post-hoc exploration of data suggested that shoulder dystocia had a limited contribution to composite adverse perinatal outcomes in LGA cases (population attributable fraction of 10.8% for CAO1 and 29.1% for CAO2). Cases with EFW > 95th percentile are at increased risk of severe adverse perinatal outcome, such as death and hypoxic ischemic encephalopathy. These findings should aid antenatal counseling regarding the associated risk and delivery options. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Proteinuria in predicting adverse outcomes in women with severe features of pre-eclampsia from a developing country: Aprospective cohort study.

To study the adverse maternal and perinatal outcomes in women with severe pre-eclampsia (SPE) among different ranges of proteinuria. This prospective cohort study was conducted in Jawaharlal Institute of Postgraduate Medical Education and Research, India. After obtaining informed written consent, the 202 singleton women fulfilling the criteria of severe features of pre-eclampsia were stratified based on the value of urine protein-creatinine ratio (UPCR) as mild, moderate, severe, and massive proteinuria during pregnancy. Clinical outcomes were assessed and patients were followed up until 12 weeks postpartum to identify persistent proteinuria and hypertension. Of the 202 women with SPE, adverse maternal outcomes were seen in 34.65% (n = 70) and adverse perinatal outcomes in 75.74% (n = 153). The demographic and clinical factors were similar among women with increasing severity of proteinuria, except for mean systolic blood pressure, serum creatinine and total serum protein. UPCR was found to have a significant correlation with composite adverse perinatal outcome (P < 0.001) and individual outcomes of neonatal intensive care unit admission for >48 h (P = 0.01) and neonatal sepsis (P = 0.02) but not adverse maternal outcomes (P = 0.201). The optimum UPCR cutoff for adverse perinatal outcomes was 1.6 (sensitivity, 73.2%; specificity, 52.7%). In addition, 14.85% of the women had a persistently elevated UPCR and 3.96% had hypertension at 3 months postpartum. In women with SPE, severe and massive proteinuria were related to composite adverse perinatal outcome but not composite adverse maternal outcome. Moreover, antenatal 24-h proteinuria was significantly associated with persistent proteinuria. Significant proteinuria in women with SPE poses a risk for chronic renal dysfunction, requiring follow-up.

Longitudinal assessment of angiogenic markers in prediction of adverse outcome in women with confirmed pre-eclampsia.

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. 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. 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). 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.

Umbilical artery half peak systolic velocity deceleration time: a novel Doppler parameter for prediction of neonatal outcomes in pregnant women with preeclampsia.

To assess the effectiveness of half peak systolic velocity deceleration time (hPSV-DT) in predicting neonatal outcomes in pregnant women with preeclampsia and to compare its usefulness with the conventional umbilical artery (UA) pulsatility index (PI) approach. A prospective cohort study was conducted among pregnant women with preeclampsia who were admitted to the Department of Perinatology, Ministry of Health Ankara City Hospital between 01 September 2022 and 01 January 2023 at 28-41weeks gestational age. 55 patients were divided into two groups: the study group with UA hPSV-DT value < 5th percentile (n = 22) and the control group with UA hPSV-DT value ≥ 5th percentile (n = 33). UA hPSV-DT calculates the time in milliseconds needed to halve the maximal velocity of the UA waveform using Doppler ultrasonography. Birth weight, gestational age at birth, 1st minute APGAR, 5th minute APGAR, and umbilical cord pH values were significantly lower in the anormal hPSV-DT group (p < 0.05). Additionally, the rates of admission to NICU, respiratory distress syndrome (RDS), delivery time < 34weeks, and birth weight < 2500g were significantly more frequent in the anormal hPSV-DT group compared to the normal hPSV-DT group (p < 0.05). UA-PI > 95th percentile was detected in only 2 (8%) of 23 patients whose newborns were admitted to the NICU (p = 0.149), while hPSV-DT < 5th percentile was detected in 16 (69%) of 23 patients (p < 0.001). According to ROC analysis, the area under the curve was 0.82 (95% CI 0.06-0.28) for admission to the NICU. The best balance of sensitivity/specificity in ROC curves was 221.5 (82.6% sensitivity, 69.1% specificity, p < 0.001). UA hPSV-DT was successful in predicting composite adverse perinatal outcomes in pregnant women with preeclampsia. It is a promising novel method that is accurate, quantitative, reproducible, and easily applicable. With further studies, this method may be a primary diagnostic tool in the management of high-risk pregnancies and in determining the optimal timing of delivery.

EP13.22: Doppler ultrasound indices and composite adverse perinatal outcome of early‐ and late‐onset FGR of estimated fetal weight &lt; 3rd centile

EP13.22: Doppler ultrasound indices and composite adverse perinatal outcome of early‐ and late‐onset FGR of estimated fetal weight &lt; 3rd centile

Cerebroplacental versus Umbilicocerebral Ratio-Analyzing the Predictive Value Regarding Adverse Perinatal Outcomes in Low- and High-Risk Fetuses at Term.

Background and Objectives: The aim of this study was to investigate the prediction of adverse perinatal outcomes using the cerebroplacental (CPR) and umbilicocerebral (UCR) ratios in different cohorts of singleton pregnancies. Materials and Methods: In this retrospective cohort study, we established our own Multiple of Median (MoM) for CPR and UCR. The predictive value for both ratios was studied in the following outcome parameters: emergency cesarean delivery, operative intervention (OI), OI due to fetal distress, 5-min Apgar < 7, admission to neonatal intensive care unit, and composite adverse perinatal outcome. The performance of the ratios was assessed in the following cohorts: total cohort (delivery ≥ 37 + 0 weeks gestation, all birth weight centiles), low-risk cohort (delivery ≥ 37 + 0 weeks gestation, birth weight ≥ 10. centile), prolonged pregnancy cohort (delivery ≥ 41 + 0 weeks gestation, birth weight ≥ 10. centile) and small-for-gestational-age fetuses (delivery ≥ 37 + 0 weeks gestation, birth weight < 10. centile). The underlying reference values for MoM were estimated using quantile regression depending on gestational age. Prediction performance was evaluated using logistic regression models assessing the corresponding Brier score, combining discriminatory power and calibration. Results: Overall, 3326 cases were included. Across all cohorts, in the case of a significant association between a studied outcome parameter and CPR, there was an association with UCR, respectively. The Brier score showed only minimal differences for both ratios. Conclusions: Our study provides further evidence regarding predictive values of CPR and UCR. The results of our study suggest that reversal of CPR to UCR does not improve the prediction of adverse perinatal outcomes.

Clinical implications of crown-rump length discordance at 11 to 14 weeks in dichorionic twins

Crown-rump length discordance, defined as ≥10% discordance, has been investigated as an early sonographic marker of subsequent growth abnormalities and is associated with an increased risk of fetal loss in twin pregnancies. Previous studies have not investigated the prevalence of fetal aneuploidy or structural anomalies in twins with discordance or the independent association of crown-rump length discordance with adverse perinatal outcomes. Moreover, data are limited on cell-free DNA screening for aneuploidy in dichorionic twins with discordance. This study aimed to evaluate whether crown-rump length discordance in dichorionic twins between 11 and 14 weeks of gestation is associated with a higher risk of aneuploidy, structural anomalies, or adverse perinatal outcomes and to assess the performance of cell-free DNA screening in dichorionic twin pregnancies with crown-rump length discordance. This was a secondary analysis of a multicenter retrospective cohort study that evaluated the performance of cell-free DNA screening for the common trisomies in twin pregnancies from December 2011 to February 2020. For this secondary analysis, we included live dichorionic pregnancies with crown-rump length measurements between 11 and 14 weeks of gestation. First, we compared twin pregnancies with discordant crown-rump lengths with twin pregnancies with concordant crown-rump lengths and analyzed the prevalence of aneuploidy and fetal structural anomalies in either twin. Second, we compared the prevalence of a composite adverse perinatal outcome, which included preterm birth at <34 weeks of gestation, hypertensive disorders of pregnancy, stillbirth or miscarriage, small-for-gestational-age birthweight, and birthweight discordance. Moreover, we assessed the performance of cell-free DNA screening in pregnancies with and without crown-rump length discordance. Outcomes were compared with multivariable regression to adjust for confounders. Of 987 dichorionic twins, 142 (14%) had crown-rump length discordance. The prevalence of aneuploidy was higher in twins with crown-rump length discordance than in twins with concordance (9.9% vs 3.9%, respectively; adjusted relative risk, 2.7; 95% confidence interval, 1.4-4.9). Similarly, structural anomalies (adjusted relative risk, 2.5; 95% confidence interval, 1.4-4.4]) and composite adverse perinatal outcomes (adjusted relative risk, 1.2; 95% confidence interval, 1.04-1.3) were significantly higher in twins with discordance. A stratified analysis demonstrated that even without other ultrasound markers, there were increased risks of aneuploidy (adjusted relative risk, 3.5; 95% confidence interval, 1.5-8.4) and structural anomalies (adjusted relative risk, 2.7; 95% confidence interval, 1.5-4.8) in twins with CRL discordance. Cell-free DNA screening had high negative predictive values for trisomy 21, trisomy 18, and trisomy 13, regardless of crown-rump length discordance, with 1 false-negative for trisomy 21 in a twin pregnancy with discordance. Crown-rump length discordance in dichorionic twins is associated with an increased risk of aneuploidy, structural anomalies, and adverse perinatal outcomes, even without other sonographic abnormalities. Cell-free DNA screening demonstrated high sensitivity and negative predictive values irrespective of crown-rump length discordance; however, 1 false-negative result illustrated that there is a role for diagnostic testing. These data may prove useful in identifying twin pregnancies that may benefit from increased screening and surveillance and are not ascertained by other early sonographic markers.

Interpretable machine learning to predict adverse perinatal outcomes: examining marginal predictive value of risk factors during pregnancy

The timely identification of nulliparas at high risk of adverse fetal and neonatal outcomes during pregnancy is crucial for initiating clinical interventions to prevent perinatal complications. Although machine learning methods have been applied to predict preterm birth and other pregnancy complications, many models do not provide explanations of their predictions, limiting the clinical use of the model. This study aimed to develop interpretable prediction models for a composite adverse perinatal outcome (stillbirth, neonatal death, estimated Combined Apgar score of <10, or preterm birth) at different points in time during the pregnancy and to evaluate the marginal predictive value of individual predictors in the context of a machine learning model. This was a secondary analysis of the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-be data, a prospective cohort study in which 10,038 nulliparous pregnant individuals with singleton pregnancies were enrolled. Here, interpretable prediction models were developed using L1-regularized logistic regression for adverse perinatal outcomes using data available at 3 study visits during the pregnancy (visit 1: 6 0/7 to 13 6/7 weeks of gestation; visit 2: 16 0/7 to 21 6/7 weeks of gestation; visit 3: 22 0/7 to 29 6/7 weeks of gestation). We identified the important predictors for each model using SHapley Additive exPlanations, a model-agnostic method of computing explanations of model predictions, and evaluated the marginal predictive value of each predictor using the DeLong test. Our interpretable machine learning model had an area under the receiver operating characteristic curves of 0.617 (95% confidence interval, 0.595-0.639; all predictor variables at visit 1), 0.652 (95% confidence interval, 0.631-0.673; all predictor variables at visit 2), and 0.673 (95% confidence interval, 0.651-0.694; all predictor variables at visit 3). For all visits, the placental biomarker inhibin A was a valuable predictor, as including inhibin A resulted in better performance in predicting adverse perinatal outcomes (P<.001, all visits). At visit 1, endoglin was also a valuable predictor (P<.001). At visit 2, free beta human chorionic gonadotropin (P=.001) and uterine artery pulsatility index (P=.023) were also valuable predictors. At visit 3, cervical length was also a valuable predictor (P<.001). Despite various advances in predictive modeling in obstetrics, the accurate prediction of adverse perinatal outcomes remains difficult. Interpretable machine learning can help clinicians understand how predictions are made, but barriers exist to the widespread clinical adoption of machine learning models for adverse perinatal outcomes. A better understanding of the evolution of risk factors for adverse perinatal outcomes throughout pregnancy is necessary for the development of effective interventions.

Evaluating the Association between Prenatal Care Visits and Adverse Perinatal Outcome in Pregnancies Complicated by Opioid Use Disorder.

This study aimed to evaluate the association between number of prenatal care visits and adverse perinatal outcome among pregnant individuals with opioid use disorder (OUD). This is a retrospective cohort of singleton, nonanomalous pregnancies complicated by OUD that delivered from January 2015 to July 2020 at our academic medical center. Primary outcome was the presence of composite adverse perinatal outcome, defined as one or more of the following: stillbirth, placental abruption, perinatal death, neonatal respiratory distress syndrome, need for morphine treatment, and hyperbilirubinemia. Logistic and linear regression estimated the association between the number of prenatal care visits and the presence of adverse perinatal outcome. A Mann-Whitney U test evaluated the association between number of prenatal care visits and length of hospital stay for the neonate. A total of 185 patients were identified, of which 35 neonates required morphine treatment for neonatal opioid withdrawal syndrome. During pregnancy, most individuals were treated with buprenorphine 107 (57.8%), whereas 64 (34.6%) received methadone, 13 (7.0%) received no treatment, and 1 (0.5%) received naltrexone. The median number of prenatal care visits was 8 (interquartile range: 4-10). With each additional visit per 10 weeks of gestational age, the risk of adverse perinatal outcome decreased by 38% (95% confidence interval [CI]: 0.451-0.854). The need for neonatal intensive care and hyperbilirubinemia also significantly decreased with additional prenatal visits. Neonatal hospital stay decreased by a median of 2 days (95% CI: 1-4) for individuals who received more than the median of eight prenatal care visits. Pregnant individuals with OUD who attend fewer prenatal care visits experience more adverse perinatal outcome. Future research should focus on barriers to prenatal care and interventions to improve access in this high-risk population. · Use of prenatal care affects newborn outcomes.. · More prenatal care shortens neonatal hospital stay.. · Prenatal care reduces certain adverse outcomes..

Major trauma in pregnancy: prediction of maternal and perinatal adverse outcomes

Trauma, largely the consequence of motor vehicle crashes, is the leading cause of pregnancy-associated maternal mortality. Prediction of adverse outcomes has been difficult in pregnancy given the infrequent occurrence of traumatic events and anatomic considerations unique to pregnancy. The injury severity score, an anatomic scoring system with weighting dependent on severity and anatomic region of injury, is used in the prediction of adverse outcomes in the nonpregnant population but has yet to be validated in pregnancy. This study aimed to estimate the associations between risk factors and adverse pregnancy outcomes after major trauma in pregnancy and to develop a clinical prediction model for adverse maternal and perinatal outcomes. This was a retrospective analysis of a cohort of pregnant patients who sustained major trauma and who were admitted to 1 of 2 level 1 trauma centers. Three composite adverse pregnancy outcomes were evaluated, namely adverse maternal outcomes and short- and long-term adverse perinatal outcomes, defined as outcomes occurring within the first 72 hours of the traumatic event or encompassing the entire pregnancy. Bivariate analyses were performed to estimate the associations between clinical or trauma-related variables and adverse pregnancy outcomes. Multivariable logistic regression analyses were performed to predict each adverse pregnancy outcome. The predictive performance of each model was estimated using receiver operating characteristic curve analyses. A total of 119 pregnant trauma patients were included, 26.1% of whom met the severe adverse maternal pregnancy outcome criteria, 29.4% of whom met the severe short-term adverse perinatal pregnancy outcome definition, and 51.3% of whom met the severe long-term adverse perinatal pregnancy outcome definition. Injury severity score and gestational age were associated with the composite short-term adverse perinatal pregnancy outcome with an adjusted odds ratio of 1.20 (95% confidence interval, 1.11-1.30). The injury severity score was solely predictive of the adverse maternal and long-term adverse perinatal pregnancy outcomes with odds ratios of 1.65 (95% confidence interval, 1.31-2.09) and 1.14 (95% confidence interval, 1.07-1.23), respectively. An injury severity score ≥8 was the best cutoff for predicting adverse maternal outcomes with 96.8% sensitivity and 92.0% specificity (area under the receiver operating characteristic curve, 0.990±0.006). An injury severity score ≥3 was the best cutoff for the short-term adverse perinatal outcomes, which correlates with a 68.6% sensitivity and 65.1% specificity (area under the receiver operating characteristic curve, 0.755±0.055). An injury severity score ≥2 was the best cutoff for the long-term adverse perinatal outcomes, yielding a 68.3% sensitivity and 72.4% specificity (area under the receiver operating characteristic curve, 0.763±0.042). For pregnant trauma patients, an injury severity score of ≥8 was predictive of severe adverse maternal outcomes. Minor trauma in pregnancy, defined in this study as an injury severity score <2, was not associated with maternal or perinatal morbidity or mortality. These data can guide management decisions for pregnant patients who present after trauma.

Risk factors associated with stillbirth and adverse perinatal outcomes in dichorionic twin pregnancies complicated by selective fetal growth restriction: a cohort study.

The main aim of this study was to investigate the perinatal outcomes of dichorionic twin pregnancies complicated by selective fetal growth restriction (sFGR). Retrospective cohort study. Tertiary reference centre. Dichorionic twin pregnancies complicated by sFGR between 2000 and 2019 in St George's University Hospital. Regression analyses were performed using generalised linear models and mixed-effects generalised linear models where appropriate to account for pregnancy level dependency in variables. Time to event analyses were performed with mixed-effects Cox regression models. Stillbirth, neonatal death or neonatal unit admission with morbidity in one or both twins. A total of 102 (of 2431 dichorionic twin pregnancies) pregnancies complicated by sFGR were included in the study. The Cochrane-Armitage test revealed a significant trend for increased adverse perinatal outcome rates with more severe forms of umbilical artery flow impedance, i.e. reversed, absent, positive with resistant flow and positive flow without resistance. A multivariable model including maternal and conception characteristics had poor predictive accuracy for stillbirth (area under the curve: 0.68, 95% confidence interval [CI] 0.55-0.81) and composite adverse perinatal outcomes (area under the curve: 0.58, 95% CI 0.47-0.70). When umbilical artery Doppler parameters were added to the models, the area under the curve values improved to 0.95 (95% CI 0.89-0.99) and 0.83 (95% CI 0.73-0.92) for stillbirth and composite adverse perinatal outcomes, respectively. In dichorionic twin pregnancies complicated by sFGR, the umbilical artery Z-scores were associated with both intrauterine death and adverse perinatal outcomes.

Perinatal outcome of oligohydramnios in academic hospitals in a low resource setting.

Oligohydramnios has been a topical issue in obstetrics. The prevalence of oligohydramnios ranges from 1 to 5%. Conflicting data exists concerning its effects on adverse perinatal outcome. This study aims to assess perinatal outcomes of oligohydramnios at the Mekelle Public Hospitals from April 1, 2018 - March 31, 2019. This was a cross-sectional study and a total population purposive sampling method was employed to collect data prospectively. During the study period, there were a total of 10,451 deliveries in both hospitals. Oligohydramnios complicated 332 pregnancies (3.2%, 95%CI: 2.9%, 3.5%) across all gestations and 273 pregnancies (2.6%, 95% CI: 2.3%, 2.9%) at term. The composite adverse perinatal outcome rate was 29.7% (95% CI, 24.5, 35.4). Primigravidity and presenting at post-term gestation were associated with adverse perinatal outcome. Nearly 70% of mothers gave birth via Cesarean delivery. Oligohydramnios was found to be associated with a significant increase in adverse newborn and maternal outcomes in the study setting. Although a significant proportion of mothers underwent Cesarean delivery for a perceived increased complications associated with vaginal delivery in this population of patients, Cesarean delivery was found to not improve perinatal outcome. Primigravids and postdated pregnancies must receive increased surveillance to detect oligohydramnios early and to institute appropriate and timely interventions. Indications for Cesarean delivery in patients complicated by oligohydramnios must be carefully examined to balance the benefit on the perinatal outcome on the one hand and to avoid unnecessary major surgery with potential fatal maternal complications on the other.

Cost-effectiveness analysis of induction of labour at 41 weeks and expectant management until 42 weeks in low risk women (INDEX trial).

To assess the cost-effectiveness of elective induction of labour (IOL) at 41 weeks and expectant management (EM) until 42 weeks. Cost-effectiveness analysis from a healthcare perspective alongside a randomised controlled trial (INDEX). 123 primary care midwifery practices and 45 obstetric departments of hospitals in the Netherlands. We studied 1801 low-risk women with late-term pregnancy, randomised to IOL at 41 weeks (N=900) or EM until 42 weeks (N=901). The incremental cost-effectiveness ratio (ICER) was expressed as the ratio of the difference in costs and the difference in main perinatal outcomes. A Cost-Effectiveness Acceptability Curve (CEAC) was constructed to assess whether induction is cost-effective for a range of monetary values as thresholds. We performed subgroup analysis for parity. Direct medical costs, composite adverse perinatal outcome (CAPO) (perinatal mortality, NICU admission, Apgar 5min < 7, plexus brachialis injury and/or meconium aspiration syndrome) and composite severe adverse perinatal outcome (SAPO) (including Apgar 5min < 4 instead of < 7). The average costs were €3858 in the induction group and €3723 in the expectant group (mean difference €135; 95 % CI -235 to 493). The ICERs of IOL compared to EM to prevent one additional CAPO and SAPO was €9436 and €14,994, respectively. The CEAC showed a 80 % chance of IOL being cost-effective with a willingness-to-pay of €22,000 for prevention of one CAPO and €50,000 for one SAPO. Subgroup analysis showed a willingness-to-pay to prevent one CAPO for nulliparous of €47,000 and for multiparous €190,000. To prevent one SAPO the willingness-to-pay is €62,000 for nulliparous and €970,000 for multiparous women. Induction at 41 weeks has an 80 % chance of being cost-effective at a willingness-to-pay of €22,000 for prevention of one CAPO and €50,000 for prevention of one SAPO. Subgroup analysis suggests that induction could be cost-effective for nulliparous women while it is unlikely cost-effective for multiparous women.Cost-effectiveness in other settings will depend on baseline characteristics of the population and health system organisation and funding.