Machine Learning to Predict Outcomes of Fetal Cardiac Disease: A Pilot Study.

Prediction of outcomes following a prenatal diagnosis of congenital heart disease (CHD) is challenging. Machine learning (ML) algorithms may be used to reduce clinical uncertainty and improve prognostic accuracy. We performed a pilot study to train ML algorithms to predict postnatal outcomes based on clinical data. Specific objectives were to predict (1) in utero or neonatal death, (2) high-acuity neonatal care and (3) favorable outcomes. We included all fetuses with cardiac disease at Sunnybrook Health Sciences Centre, Toronto, Canada, from 2012 to 2021. Prediction models were created using the XgBoost algorithm (tree-based) with fivefold cross-validation. Among 211 cases of fetal cardiac disease, 61 were excluded (39 terminations, 21 lost to follow-up, 1 isolated arrhythmia), leaving a cohort of 150 fetuses. Fifteen (10%) demised (10 neonates) and 65 (48%) of live births required high acuity neonatal care. Of those with clinical follow-up, 60/87 (69%) had a favorable outcome. Prediction models for fetal or neonatal death, high acuity neonatal care and favorable outcome had AUCs of 0.76, 0.84 and 0.73, respectively. The most important predictors for death were the presence of non-cardiac abnormalities combined with more severe CHD. High acuity of postnatal care was predicted by anti Ro antibody and more severe CHD. Favorable outcome was most predicted by no right heart disease combined with genetic abnormalities, and maternal medications. Prediction models using ML provide good discrimination of key prenatal and postnatal outcomes among fetuses with congenital heart disease.

Prediction of fetal death in monochorionic twin pregnancies complicated by Type-III selective fetal growth restriction.

OBJECTIVE: Monochorionic diamniotic twin pregnancies complicated by Type-III selective fetal growth restriction (sFGR) are at high risk of fetal death. The aim of this study was to identify predictors of fetal death in these pregnancies. METHODS: This was an international multicenter retrospective cohort study. Type-III sFGR was defined as fetal estimated fetal weight (EFW) of one twin below the 10th percentile and intertwin EFW discordance of ≥ 25% in combination with intermittent absent or reversed end-diastolic flow in the umbilical artery of the smaller fetus. Predictors of fetal death were recorded longitudinally throughout gestation and assessed in univariable and multivariable logistic regression models. The classification and regression trees (CART) method was used to construct a prediction model of fetal death using significant predictors derived from the univariable analysis. RESULTS: A total of 308 twin pregnancies (616 fetuses) were included in the analysis. In 273 (88.6%) pregnancies, both twins were liveborn, whereas 35 pregnancies had single (n = 19 (6.2%)) or double (n = 16 (5.2%)) fetal death. On univariable analysis, earlier gestational age at diagnosis of Type-III sFGR, oligohydramnios in the smaller twin and deterioration in umbilical artery Doppler flow were associated with an increased risk of fetal death, as was larger fetal EFW discordance, particularly between 24 and 32 weeks' gestation. None of the parameters identified on univariable analysis maintained statistical significance on multivariable analysis. The CART model allowed us to identify three risk groups: a low-risk group (6.8% risk of fetal death), in which umbilical artery Doppler did not deteriorate; an intermediate-risk group (16.3% risk of fetal death), in which umbilical artery Doppler deteriorated but the diagnosis of sFGR was made at or after 16 + 5 weeks' gestation; and a high-risk group (58.3% risk of fetal death), in which umbilical artery Doppler deteriorated and gestational age at diagnosis was < 16 + 5 weeks' gestation. CONCLUSIONS: Type-III sFGR is associated with a high risk of fetal death. A prediction algorithm can help to identify the highest-risk group, which is characterized by Doppler deterioration and early referral. Further studies should investigate the potential benefit of fetal surveillance and intervention in this cohort. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Growth patterns of monochorionic twin pregnancy complicated by Type-III selective fetal growth restriction.

OBJECTIVES: Little is known regarding fetal growth patterns in monochorionic twin pregnancy complicated by Type-III selective fetal growth restriction (sFGR). We aimed to assess fetal growth and umbilical artery Doppler pattern in Type-III sFGR across gestation and evaluate the effect of changing Doppler flow pattern on growth and intertwin growth discordance. METHODS: This was a retrospective cohort study of all Type-III sFGR pregnancies managed at nine fetal centers over a 12-year time period. Higher-order multiple pregnancy and cases with major fetal anomaly or other monochorionicity-related complications at presentation were excluded. Estimated fetal weight (EFW) was assessed on ultrasound for each twin pair at five timepoints (16-20, 21-24, 25-28, 29-32 and > 32 weeks' gestation) and compared with singleton and uncomplicated monochorionic twin EFW. EFW and intertwin EFW discordance were compared between pregnancies with normalization of umbilical artery Doppler of the smaller twin later in pregnancy and those with persistently abnormal Doppler. RESULTS: Overall, 328 pregnancies (656 fetuses) met the study criteria. In Type-III sFGR, the smaller twin had a lower EFW than an average singleton fetus (EFW Z-score ranging from -1.52 at 16 weeks to -2.69 at 36 weeks) and an average monochorionic twin in uncomplicated pregnancy (Z-score ranging from -1.73 at 16 weeks to -1.49 at 36 weeks) throughout the entire gestation, while the larger twin had a higher EFW than an average singleton fetus until 22 weeks' gestation and was similar in EFW to an average uncomplicated monochorionic twin throughout gestation. As pregnancy advanced, growth velocity of both twins decreased, with the larger twin remaining appropriately grown and the smaller twin becoming more growth restricted. Intertwin EFW discordance remained stable throughout gestation. On multivariable longitudinal modeling, normalization of fetal umbilical artery Doppler was associated with better growth of the smaller twin (P = 0.002) but not the larger twin (P = 0.1), without affecting the intertwin growth discordance (P = 0.09). CONCLUSIONS: Abnormal fetal growth of the smaller twin in Type-III sFGR was evident early in pregnancy, while EFW of the larger twin remained normal throughout gestation. Normalization of umbilical artery Doppler was associated with improved fetal growth of the smaller twin. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Gestational weight gain in twin gestations and pregnancy outcomes: a systematic review and meta-analysis.

BACKGROUND: Data on the association of inappropriate gestational weight gain (GWG) and adverse outcomes in twin pregnancies are limited and inconsistent. OBJECTIVES: To perform a systematic review and meta-analysis on the association between GWG and adverse outcomes in twin pregnancies. SEARCH STRATEGY: Ovid, Medline, EMBASE and Cochrane Central databases from 1 January 1990 until 23 September 2020. SELECTION CRITERIA: Interventional and observational studies evaluating the association between GWG and adverse outcomes in twin pregnancies. DATA COLLECTION AND ANALYSIS: Data were extracted by two independent reviewers. Summary odds ratios (OR) were calculated using a random-effects model in a subset of studies that analysed GWG as a categorical variable in relation to the Institute of Medicine (IOM) recommendations. The primary outcome was preterm birth. MAIN RESULTS: From 277 citations, 19 studies involving 36 023 women with twin pregnancies were included in the qualitative analysis, of which 14 were included in the meta-analysis. Overall, 56.8% of women experienced inappropriate GWG: 35.4% (95% CI 30.0-41.0%) gained weight below and 21.4% (95% CI 14.2-29.5%) gained weight above IOM recommendations. Compared with GWG within IOM guidelines, GWG below IOM guidelines was associated with preterm birth before 32 weeks of gestation (OR 3.38; 95% CI 2.05-5.58), and a reduction in the risk of pre-eclampsia (OR 0.68; 95% CI 0.48-0.97). GWG above IOM guidelines was associated with an increased risk of pre-eclampsia that was consistent across all body mass index categories. CONCLUSIONS: Inappropriate GWG affects over half of twin pregnancies, so is a common and potentially modifiable risk factor for preterm birth and pre-eclampsia.

DEVELOPING twin-specific 75-g oral glucose tolerance test diagnostic thresholds for gestational diabetes based on the risk of future maternal diabetes: a population-based cohort study.

OBJECTIVE: To develop twin-specific outcome-based oral glucose tolerance test (OGTT) diagnostic thresholds for GDM based on the risk of future maternal type-2 diabetes. DESIGN: A population-based retrospective cohort study (2007-2017). SETTING: Ontario, Canada. METHODS: Nulliparous women with a live singleton (n = 55 361) or twin (n = 1308) birth who underwent testing for gestational diabetes mellitus (GDM) using a 75-g OGTT in Ontario, Canada (2007-2017). We identified the 75-g OGTT thresholds in twin pregnancies that were associated with similar incidence rates of future type-2 diabetes to those associated with the standard OGTT thresholds in singleton pregnancies. RESULTS: For any given 75-g OGTT value, the incidence rate of future maternal type-2 diabetes was lower for women with a twin than women with a singleton pregnancy. Using women with a negative OGTT as reference, the risk of future maternal type-2 diabetes in twin pregnancies with a positive OGTT based on the standard OGTT thresholds (9.86 per 1000 person years, adjusted hazard ratio (aHR) 4.79, 95% CI 2.69-8.51) was lower than for singleton pregnancies with a positive OGTT (18.74 per 1000 person years, aHR 8.22, 95% CI 7.38-9.16). The twin-specific OGTT fasting, 1-hour and 2-hour thresholds identified in the current study based on correlation with future maternal type-2 diabetes were 5.8 mmol/l (104 mg/dl), 11.8 mmol/l (213 mg/dl) and 10.4 mmol/l (187 mg/dl), respectively. CONCLUSIONS: We identified potential twin-specific OGTT thresholds for GDM that are associated with a similar risk of future type-2 diabetes to that observed in women diagnosed with GDM in singleton pregnancies based on standard OGTT thresholds. TWEETABLE ABSTRACT: Potential twin-specific OGTT thresholds for GDM were identified.

Neonatal outcome by planned mode of delivery in women with a body mass index of 35 or more: a retrospective cohort study.

OBJECTIVE: To compare neonatal outcomes of women with a body mass index (BMI) of ≥35 kg/m2 who underwent a trial of labour with those of women who underwent a planned primary caesarean section (CS). DESIGN: A retrospective cohort study of births between April 2012 and March 2014. SETTING: A provincial database: Better Outcomes Registry & Network (BORN) Ontario, Canada. POPULATION: A cohort of 8752 women with a BMI of ≥35 kg/m2 who had a singleton birth at 38-42 weeks of gestation. METHODS: Neonatal outcomes were compared between women who underwent a trial of labour (with either a successful vaginal birth or intrapartum CS) and those who underwent a planned CS. MAIN OUTCOME MEASURE: A composite of any of the following outcomes: intrapartum neonatal death, neonatal intensive care unit admission, 5-minute Apgar score of <7 or umbilical artery pH of <7.1. RESULTS: During the study period, 8433 (96.4%) women had a trial of labour and 319 (3.6%) had a planned CS. Intrapartum CS was performed in 1644 (19.5%) cases. There was no association between planned mode of delivery and the primary outcome (aOR 0.80, 95% CI 0.59-1.07). The primary outcome was lower among women who had a successful trial of labour (aOR 0.67, 95% CI 0.50-0.91) and was higher among women who had a failed trial of labour (aOR 1.74, 95% CI 1.21-2.48), compared with women who underwent a planned CS. CONCLUSIONS: In women with a BMI of ≥35 kg/m2 at a gestational age of 38-42 weeks, neonatal outcomes are comparable between planned vaginal delivery and planned CS, although a failed trial of labour is at risk of adverse neonatal outcome. TWEETABLE ABSTRACT: Neonatal outcomes are not affected by planned mode of delivery in women who are obese, with a BMI of ≥35 kg/m2 .

Outcome of monochorionic twin pregnancy complicated by Type-III selective intrauterine growth restriction.

OBJECTIVE: Type-III selective intrauterine growth restriction (sIUGR) is associated with a high and unpredictable risk of fetal death and fetal brain injury. The objective of this study was to describe the prospective risk of fetal death and the risk of adverse neonatal outcome in a cohort of twin pregnancies complicated by Type-III sIUGR and treated according to up-to-date guidelines. METHODS: We reviewed retrospectively all monochorionic diamniotic twin pregnancies complicated by Type-III sIUGR managed at nine fetal centers over a 12-year period. Higher-order multiple gestations and pregnancies with major fetal anomalies or other monochorionicity-related complications at initial presentation were excluded. Data on fetal and neonatal outcomes were collected and management strategies reviewed. Composite adverse neonatal outcome was defined as neonatal death, invasive ventilation beyond the resuscitation period, culture-proven sepsis, necrotizing enterocolitis requiring treatment, intraventricular hemorrhage Grade > I, retinopathy of prematurity Stage > II or cystic periventricular leukomalacia. The prospective risk of intrauterine death (IUD) and the risk of neonatal complications according to gestational age were evaluated. RESULTS: We collected data on 328 pregnancies (656 fetuses). After exclusion of pregnancies that underwent selective reduction (n = 18 (5.5%)), there were 51/620 (8.2%) non-iatrogenic IUDs in 35/310 (11.3%) pregnancies. Single IUD occurred in 19/328 (5.8%) pregnancies and double IUD in 16/328 (4.9%). The prospective risk of non-iatrogenic IUD per fetus declined from 8.1% (95% CI, 5.95-10.26%) at 16 weeks, to less than 2% (95% CI, 0.59-2.79%) after 28.4 weeks and to less than 1% (95% CI, -0.30 to 1.89%) beyond 32.6 weeks. In otherwise uncomplicated pregnancies with Type-III sIUGR, delivery was generally planned at 32 weeks, at which time the risk of composite adverse neonatal outcome was 29.0% (31/107 neonates). In twin pregnancies that continued to 34 weeks, there was a very low risk of IUD (0.7%) and a low risk of composite adverse neonatal outcome (11%). CONCLUSIONS: In this cohort of twin pregnancies complicated by Type-III sIUGR and treated at several tertiary fetal centers, the risk of fetal death was lower than that reported previously. Further efforts should be directed at identifying predictors of fetal death and optimal antenatal surveillance strategies to select a cohort of pregnancies that can continue safely beyond 33 weeks' gestation. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Customized birth-weight centiles and placenta-related fetal growth restriction.

OBJECTIVE: The value of using customized birth-weight centiles to improve the diagnostic accuracy for fetal growth restriction (FGR), in comparison with using population-based charts, remains a matter of debate. One potential explanation for the conflicting data is that most studies used measures of perinatal mortality and morbidity as proxies for placenta-mediated FGR, many of which are not specific and may be confounded by other factors such as prematurity. The aim of this study was to compare the diagnostic accuracy of small-for-gestational age (SGA) at birth, defined according to customized vs population-based charts, for associated abnormal placental pathology. METHODS: This was a secondary analysis of data from a prospective cohort study on risk factors for placenta-mediated complications and abnormal placental pathology in low-risk nulliparous women. All placentae were sent for detailed histopathological examination by two perinatal pathologists. The primary exposure was SGA, defined as birth weight < 10th centile for gestational age using either a customized (SGAcust ) or a population-based (SGApop ) birth-weight reference. The outcomes of interest were one of three types of abnormal placental pathology associated with FGR: maternal vascular malperfusion (MVM), chronic villitis and fetal vascular malperfusion (FVM). Adjusted relative risks (aRR) with 95% CIs were estimated using modified Poisson regression analysis, with adjustment for smoking, body mass index and aspirin treatment. RESULTS: A total of 857 nulliparous women met the study criteria. The proportions of infants identified as SGA based on the customized and population-based charts were 12.6% (108/857) and 11.4% (98/857), respectively. A diagnosis of SGA using either customized or population-based charts was associated with an increased risk of any placental pathology (aRR, 3.04 (95% CI, 2.29-4.04) and 1.60 (95% CI, 1.10-2.31), respectively) and MVM pathology (aRR, 12.33 (95% CI, 6.60-23.03) and 5.29 (95% CI, 2.87-9.76), respectively). SGAcust , but not SGApop , was also associated with an increased risk for chronic villitis (aRR, 1.85 (95% CI, 1.07-3.18)) and FVM pathology (aRR, 2.48 (95% CI, 1.25-4.93)). SGAcust had a higher detection rate for any placental pathology (30.3% vs 17.1%; P < 0.001), MVM pathology (63.2% vs 39.5%; P = 0.003) and chronic villitis (20.8% vs 8.3%; P = 0.007) than did SGApop , for a similar false-positive rate. This was mainly the result of a higher detection rate for abnormal pathology in the white and East-Asian subgroups and a lower false-positive rate for abnormal pathology in the South-Asian subgroup by SGAcust than by SGApop . In addition, pregnancies in the SGAcust group, but not those in the SGApop group, were more likely to be complicated by preterm birth and a low 5-min Apgar score than were the corresponding non-SGA group. CONCLUSION: These findings suggest that customized birth-weight centiles may be superior to population-based birth-weight centiles in detecting FGR that is due to underlying placental disease. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Benefit of antenatal corticosteroids by year of birth among preterm infants in Canada during 2003-2017: a population-based cohort study.

OBJECTIVE: To evaluate the changes in the associations of antenatal corticosteroids (ACS) with neonatal mortality and severe neurological injury over time (2003-17). DESIGN: National, population-representative, retrospective cohort study. SETTING: Level III neonatal intensive care units participating in the Canadian Neonatal Network. POPULATION: All infants born at 230/7 -336/7 weeks of gestation (n = 43 456). METHODS: We estimated the associations between exposure to ACS and neonatal outcomes by year of birth. Year of birth was considered both continuously and categorically as three consecutive epochs. MAIN OUTCOME MEASURE: Neonatal mortality and severe neurological injury. RESULTS: The absolute rates of neonatal mortality and severe neurological injury decreased during the study period in both the ACS and No ACS groups. For infants born at 230/7 -306/7 weeks of gestation, ACS was associated with similar reductions in neonatal mortality across the three epochs (9.0% versus 18.1%, adjusted relative risk [aRR] 0.54, 95% CI 0.47-0.61 in 2003-09; 7.6% versus 19.6%, aRR 0.51, 95% CI 0.44-0.59 in 2010-13; and 7.3% versus 14.5%, aRR 0.56, 95% CI 0.46-0.68 in 2014-17) and in severe neurological injury (13.2% versus 25.8%, aRR 0.57, 95% CI 0.50-0.64 in 2003-09; 7.4% versus 17.4%, aRR 0.53, 95% CI 0.43-0.66 in 2010-14; and 7.2% versus 14.8%, aRR 0.59, 95% CI 0.48-0.74 in 2014-17). CONCLUSION: Despite the ongoing improvements in neonatal care of preterm infants, as reflected by the gradual decrease in the absolute rates of neonatal mortality and severe neurological injury, the association of ACS treatment with neonatal mortality and severe neurological injury among extremely preterm infants born at 23-30 weeks of gestation has remained stable throughout the study period of 15 years. TWEETABLE ABSTRACT: Despite the gradual decrease in the rates of neonatal mortality and severe neurological injury, antenatal corticosteroids remain an important intervention in the current era of neonatal care.

Cesarean delivery or induction of labor in pre-labor twin gestations: a secondary analysis of the twin birth study.

BACKGROUND: In the Twin Birth Study, women at 320/7-386/7 weeks of gestation, in whom the first twin was in cephalic presentation, were randomized to planned vaginal delivery or cesarean section. The study found no significant differences in neonatal or maternal outcomes in the two planned mode of delivery groups. We aimed to compare neonatal and maternal outcomes of twin gestations without spontaneous onset of labor, who underwent induction of labor or pre-labor cesarean section as the intervention of induction may affect outcomes. METHODS: In this secondary analysis of the Twin Birth Study we compared those who had an induction of labor with those who had a pre-labor cesarean section. The primary outcome was a composite of fetal or neonatal death or serious neonatal morbidity. Secondary outcome was a composite of maternal morbidity and mortality. TRIAL REGISTRATION: NCT00187369. RESULTS: Of the 2804 women included in the Twin Birth Study, a total of 1347 (48%) women required a delivery before a spontaneous onset of labor occurred: 568 (42%) in the planned vaginal delivery arm and 779 (58%) in the planned cesarean arm. Induction of labor was attempted in 409 (30%), and 938 (70%) had a pre-labor cesarean section. The rate of intrapartum cesarean section in the induction of labor group was 41.3%. The rate of the primary outcome was comparable between the pre-labor cesarean section group and induction of labor group (1.65% vs. 1.97%; p = 0.61; OR 0.83; 95% CI 0.43-1.62). The maternal composite outcome was found to be lower with pre-labor cesarean section compared to induction of labor (7.25% vs. 11.25%; p = 0.01; OR 0.61; 95% CI 0.41-0.91). CONCLUSION: In women with twin gestation between 320/7-386/7 weeks of gestation, induction of labor and pre-labor cesarean section have similar neonatal outcomes. Pre-labor cesarean section is associated with favorable maternal outcomes which differs from the overall Twin Birth Study results. These data may be used to better counsel women with twin gestation who are faced with the decision of interventional delivery.

Utility of ultrasound assessment in management of pregnancies with preterm prelabor rupture of membranes.

OBJECTIVES: To evaluate the utility of ultrasound markers in the management of pregnancies complicated by preterm prelabor rupture of membranes (PPROM) between 23 + 0 and 33 + 6 weeks' gestation, and to assess the ability of ultrasound markers to predict adverse neonatal outcomes. METHODS: This was a retrospective cohort study of all patients with PPROM between 23 + 0 and 33 + 6 weeks' gestation and latency period (PPROM to delivery) > 48 h, who delivered before 34 weeks' gestation at a tertiary referral center between 2005 and 2017. All patients underwent a non-stress test daily and an ultrasound scan twice a week for assessment of amniotic fluid volume, biophysical profile (BPP) and umbilical artery (UA) pulsatility index (PI). In patients with suspected fetal growth restriction, fetal middle cerebral artery (MCA)-PI was also assessed and the cerebroplacental ratio (CPR) calculated. The last ultrasound examination performed prior to delivery was analyzed. We compared the characteristics and outcomes between women who were delivered owing to clinical suspicion of chorioamnionitis and those who were not delivered for this indication. The primary objective was to evaluate the utility of ultrasound in the management of patients with PPROM. The secondary objective was to assess the diagnostic performance of ultrasound markers (BPP score < 6, oligohydramnios, UA-PI > 95th percentile, MCA-PI < 5th percentile, CPR < 5th percentile) for the prediction of composite adverse neonatal outcome, which was defined as the presence of one or more of: perinatal death, respiratory distress syndrome, periventricular leukomalacia, intraventricular hemorrhage Grade 3 or 4, necrotizing enterocolitis, hypoxic ischemic encephalopathy, neonatal sepsis or neonatal seizures. RESULTS: A total of 504 women were included in the study, comprising 120 with suspected chorioamnionitis and 384 without. Women with suspected chorioamnionitis, compared with those without, were less likely to be nulliparous (34.2% vs 45.3%; P = 0.03) and more likely to have fever (50.8% vs 2.6%; P < 0.001) and be delivered by Cesarean section (69.2% vs 42.4%; P < 0.001), mainly owing to a history of previous Cesarean section (18.3% vs 9.1%; P = 0.005) and to having non-reassuring fetal heart rate tracings (32.5% vs 14.6%; P < 0.001). No significant differences were found between the two groups with regard to the median amniotic fluid volume, overall BPP score, BPP score < 6, MCA-PI or CPR. Median UA-PI was slightly higher in the suspected-chorioamnionitis group, yet the incidence of UA-PI > 95th percentile was similar between the two groups. There was a higher incidence of composite adverse neonatal outcome in the group with suspected chorioamnionitis than in the group without (78.3% vs 64.3%, respectively; P = 0.004). However, on logistic regression analysis, none of the ultrasound markers evaluated was found to be associated with chorioamnionitis or composite adverse neonatal outcome, and they all had a poor diagnostic performance for the prediction of chorioamnionitis and composite adverse neonatal outcome. CONCLUSIONS: Commonly used ultrasound markers in pregnancies complicated by PPROM were similar between women delivered for suspected chorioamnionitis and those delivered for other indications, and performed poorly in predicting composite adverse neonatal outcome. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Amniotic fluid volume at presentation with early preterm prelabor rupture of membranes and association with severe neonatal respiratory morbidity.

OBJECTIVE: Amniotic fluid volume (AFV) plays an important role in early fetal lung development, and oligohydramnios in early pregnancy is associated with pulmonary hypoplasia. The aim of this study was to evaluate the association between AFV at the time of presentation with early preterm prelabor rupture of membranes (PPROM) and severe neonatal respiratory morbidity and other adverse pregnancy outcomes. METHODS: This was a retrospective study of all women with a singleton pregnancy, admitted to a single tertiary referral center between 2004 and 2014, for expectant management of PPROM at 20 + 0 to 28 + 6 weeks' gestation. The primary exposure was AFV at presentation, classified according to sonographic maximum vertical pocket (MVP) as: normal AFV (> 2 cm), oligohydramnios (≤ 2 cm and > 1 cm) or severe oligohydramnios (≤ 1 cm). The primary outcome was a composite variable of severe respiratory morbidity, defined as either of the following: (1) need for respiratory support in the form of mechanical ventilation using an endotracheal tube for ≥ 72 h and need for surfactant; or (2) bronchopulmonary dysplasia, defined as requirement for oxygen at postmenstrual age of 36 weeks or at the time of transfer to a Level-II facility. Adjusted odds ratios (aOR) and 95% CI for the primary and secondary outcomes were calculated for each AFV-at-presentation group (using normal AFV as the reference), adjusting for gestational age (GA) at PPROM, latency period, birth weight, mode of delivery and chorioamnionitis. RESULTS: In total, 580 women were included, of whom 304 (52.4%) had normal AFV, 161 (27.8%) had oligohydramnios and 115 (19.8%) had severe oligohydramnios at presentation. The rates of severe respiratory morbidity were 16.1%, 26.7% and 45.2%, respectively. Compared with normal AFV at presentation, oligohydramnios (aOR, 3.27; 95% CI, 1.84-5.84) and severe oligohydramnios (aOR, 4.11; 95% CI, 2.26-7.56) at presentation were associated independently with severe respiratory morbidity. Other variables that were associated independently with the primary outcome were GA at PPROM (aOR, 0.54; 95% CI, 0.43-0.69), latency period (aOR, 0.94; 95% CI, 0.91-0.98) and Cesarean delivery (aOR, 2.01; 95% CI, 1.21-3.32). CONCLUSIONS: In women with early PPROM, AFV at presentation, as assessed by the MVP on ultrasound examination, is associated independently with severe neonatal respiratory morbidity. This information may be taken into consideration when counseling women with early PPROM regarding neonatal outcome and management options. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Crystallographic orientation errors in mechanical exfoliation.

We evaluate the effect of mechanical exfoliation of van der Waals materials on crystallographic orientations of the resulting flakes. Flakes originating from a single crystal of graphite, whose orientation is confirmed using STM, are studied using facet orientations and electron back-scatter diffraction (EBSD). While facets exhibit a wide distribution of angles after a single round of exfoliation ([Formula: see text]), EBSD shows that the true crystallographic orientations are more narrowly distributed ([Formula: see text]), and facets have an approximately [Formula: see text] error from the true orientation. Furthermore, we find that the majority of graphite fractures are along armchair lines, and that the cleavage process results in an increase of the zigzag lines portion. Our results place values on the rotation caused by a single round of the exfoliation process, and suggest that when a 1-2 degree precision is necessary, the orientation of a flake can be gauged by the orientation of the macroscopic single crystal from which it was exfoliated.

Predictive value of cervical length in women with twin pregnancy presenting with threatened preterm labor.

OBJECTIVE: To assess the accuracy and determine the optimal threshold of sonographic cervical length (CL) for the prediction of preterm delivery (PTD) in women with twin pregnancies presenting with threatened preterm labor (PTL). METHODS: This was a retrospective study of women with twin pregnancies who presented with threatened PTL and underwent sonographic measurement of CL in a tertiary center. The accuracy of CL in predicting PTD in women with twin pregnancies was compared with that in a control group of women with singleton pregnancies. RESULTS: Overall, 218 women with a twin pregnancy and 1077 women with a singleton pregnancy, who presented with PTL, were included in the study. The performance of CL as a predictive test for PTD was similar in twins and singletons, as reflected by the similar correlation between CL and the examination-to-delivery interval (r, 0.30 vs 0.29; P = 0.9), the similar association of CL with risk of PTD, and the similar areas under the receiver-operating characteristics curves for differing delivery outcomes (range, 0.653-0.724 vs 0.620-0.682, respectively; P = 0.3). The optimal threshold of CL for any given target sensitivity or specificity was lower in twin than in singleton pregnancies. However, in order to achieve a negative predictive value of 95%, a higher threshold (28-30 mm) should be used in twin pregnancies. Using this twin-specific CL threshold, women with twins who present with PTL are more likely to have a positive CL test, and therefore to require subsequent interventions, than are women with singleton pregnancies with PTL (55% vs 4.2%, respectively). CONCLUSION: In women with PTL, the performance of CL as a test for the prediction of PTD is similar in twin and singleton pregnancies. However, the optimal threshold of CL for the prediction of PTD appears to be higher in twin pregnancies, mainly owing to the higher baseline risk for PTD in these pregnancies.

The effect of gestational age on neonatal outcome in low-risk singleton term deliveries.

OBJECTIVE: To assess the association between gestational age at delivery and adverse neonatal outcome among term low-risk singleton neonates. METHODS: A retrospective cohort study design was used. The study group included all low-risk singleton term (37 + 0 to 41 + 6 weeks) newborns delivered in a single tertiary university-affiliated medical center over a 5-year period. Outcome of neonates delivered at 37 + 0 to 37 + 6 weeks of gestation (early term) and 41 + 0 to 41 + 6 weeks of gestation (late term) was compared to that of neonates delivered at 39 + 0-39 + 6 weeks of gestation (control). RESULTS: Overall, the outcome of 30 229 neonates was analyzed. The incidence of neonatal mortality was 1.0 per 1000 live-born neonates, with no significant difference between the various gestational age groups. Early term newborns were at higher risk for respiratory morbidity, hypoglycemia, hypocalcemia, thrombocytopenia and unexplained jaundice, and had higher rates of prolonged hospital stay, NICU admission, sepsis workup and antibiotic treatment. On multivariate analysis, early term delivery was an independent predictor for composite respiratory morbidity (OR=2.4, 95% CI 1.6-3.8, p < 0.001), unexplained jaundice (OR=2.1, 95% CI 1.7-2.5, p < 0.001), hypoglycemia (OR=2.5, 95% CI 1.5-4.3, p < 0.001) and NICU admission (OR=1.9, 95% CI 1.5-2.5, p < 0.001). Late term neonates had a significantly higher rate of large for gestational date, but did not differ from controls with respect to the rate of composite neurologic or respiratory complications, NICU admission, birth trauma or infectious morbidity. CONCLUSION: Even in low-risk singleton deliveries, early term is associated with an increased risk of neonatal morbidity.

Macrosomic newborns of non-diabetic mothers: anthropometric measurements and neonatal complications.

OBJECTIVE: To assess the association of anthropometric measurements with neonatal complications in macrosomic newborns of non-diabetic mothers. DESIGN: Retrospective cohort study. PATIENTS: All liveborn, singleton, full term newborns with birth weight ≥4000 g born to non-diabetic mothers at a tertiary medical centre in 1995-2005 (n=2766, study group) were matched to the next born, healthy, full term infant with a birth weight of 3000-4000 g (control group). Exclusion criteria were multiple birth, congenital infection, major malformations and pregnancy complications. INTERVENTION: Data collection by file review. OUTCOME MEASURES: Complication rates were compared between study and control groups and between symmetric and asymmetric macrosomic newborns, defined by weight/length ratio (WLR), Body Mass Index and Ponderal Index. RESULTS: The 2766 non-diabetic macrosomic infants identified were matched to 2766 control infants. The macrosomic group had higher rates of hypoglycaemia (1.2% vs 0.5%, p=0.008), transient tachypnoea of the newborn (1.5% vs 0.5%, p<0.001), hyperthermia (0.6% vs 0.1%, p=0.012), and birth trauma (2% vs 0.7%, p<0.001), with no cases of symptomatic polycythaemia, and only one case of hypoglycaemia. Hypoglycaemia was positively associated with birth weight. It was significantly higher in the asymmetric than the symmetric macrosomic newborns, defined by WLR (1.7% vs 0.3%, p<0.001). CONCLUSIONS: Macrosomic infants of non-diabetic mothers are at increased risk of neonatal complications. However, routine measurements of haematocrit and calcium may not be necessary. Symmetric macrosomic infants (by WLR) have a similar rate of hypoglycaemia as normal-weight infants. Thus, repeat glucose measurements in symmetric macrosomic infants are not justified.