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.

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.

Uterine electrical activity, oxytocin and labor: translating electrical into mechanical.

PURPOSE: Uterine activity plays a crucial role in labor, especially when utero-tonic materials are administered. We aimed to determine the electrical responsiveness of the uterine musculature to labor augmentation with oxytocin using electrical uterine myography (EUM) technology, and to assess whether the kinetics of the EUM device may serve as a predictor for successful vaginal delivery. METHODS: EUM prospectively measured electrical uterine activity in women with singleton gestations at term (≥ 37 + 0 weeks) undergoing labor augmentation by oxytocin administration. The results were reported as the EUM index, which represented the mean electrical activity in 10-min intervals and measured in units of microwatt per second (mW/s). Measurements were performed at least 30 min before oxytocin initiation and until at least four contractions per 10 min were recorded by standard tocodynamometry. The delta EUM index was defined as the difference between the mean EUM index before and after the initiation of oxytocin. RESULTS: The mean EUM index increased significantly during oxytocin augmentation in all the parturients (P < 0.001). Mean and minimum (but not maximum) uterine electrical activity during oxytocin infusion correlated with the baseline uterine activity. The delta EUM index was not significantly affected by demographic or obstetric parameters. There was no correlation between the delta EUM index and time to delivery or the mean EUM index during oxytocin administration and time to delivery. CONCLUSIONS: Uterine electrical activity as evaluated by EUM is significantly intensified following oxytocin administration, regardless of obstetrical characteristics, and is correlated with the baseline uterine electrical activity prior to oxytocin infusion.

Different formulas, different thresholds and different performance-the prediction of macrosomia by ultrasound.

OBJECTIVE: The sonographic prediction of fetal macrosomia affects obstetrical decision regarding the timing and mode of delivery. We aimed to compare the accuracy of various formulas for prediction of macrosomia at different thresholds. STUDY DESIGN: This was a retrospective cohort study of singleton gestations at term, with fetal biometrical measurements taken up to 7 days prior to delivery (2007 to 2014). Sonographic estimated fetal weight was calculated using 20 previously published formulas. Macrosomia prediction was evaluated for every formula utilizing: (1) measures of accuracy (sensitivity, specificity and so on); (2) comparison of the systematic and random errors (SE and RE), and the proportion of estimates within 10% of actual birth weight for macrosomic and non-macrosomic neonates. Performance measurements were evaluated for different macrosomia thresholds: 4000, 4250 and 4500 g. Best performing formula for every threshold was defined as the one with the lowest Euclidean distance (=SQRT(SE2+RE2)). RESULTS: Out of 7977 women who met the inclusion criteria, 754 (9.4%) delivered a neonate weighing ⩾4000 g, 266 (3.3%) delivered a neonate weighing⩾4250 g and 75 (0.9%) delivered a neonate weighing⩾4500 g. Considerable variability was noted between the accuracy parameters of the different formulas, with Woo's formula integrating Abdominal circumference (AC) and femur length (FL) as the most sensitive formula with the highest negative predictive value for all thresholds and Woo's formula using AC, FL and biparietal diameter (BPD) as the most specific for all thresholds. The same formula also demonstrated the best overall accuracy. Regardless of threshold chosen, 80% or more of formulas demonstrated negative systematic error, meaning lower EFW than actual birthweight. As for the Euclidean distance, Hadlock's formula (AC, FL and BPD) ranked the highest for the 4000 and 4250 g thresholds, whereas Shepard's formula (AC and BPD) ranked the highest for the 4500 g threshold. CONCLUSION: Considerable variability exist between formulas for prediction of neonatal macrosomia. Formulas by Hadlock's and Shepard's utilizing AC, BPD±FL were most accurate for macrosomia prediction at 4000, 4250 and 4500 g thresholds, respectively.

Prediction of large for gestational age by various sonographic fetal weight estimation formulas-which should we use?

OBJECTIVE: As sonographic estimation of fetal weight (EFW) carries substantial impact, especially in large-for-gestational-age (LGA) neonates, we aimed to compare the accuracy of various formulas for prediction of LGA neonates. STUDY DESIGN: Retrospective cohort study of singleton gestations at term, with EFW up to 7 days before delivery (2007 to 2014). Small-for-gestational-age neonates were excluded. LGA prediction for various formulas was evaluated by: (i) measures of performance (sensitivity, specificity, etc.); (ii) systematic and random errors (SE and RE) and the proportion of estimates (POEs) exceeding 10% of actual birth weight. Best performing formula was defined as the one with the lowest Euclidean distance [=square root of (SE2+RE2)]. RESULTS: Out of 62 102 deliveries, 7996 met inclusion criteria, of which 1618 neonates were LGA (22%). There was a considerable variation in sensitivity (74.6±16.3%, 23.5% to 99%), specificity (86.3±10.6%, 51.7% to 99.6%), positive predictive value (64.9±12.4%, 35.6% to 93.8%), positive likelihood ratio (LR; 9.3±10.9, 2.1 to 54.2) and negative LR (0.3±0.16, 0.02 to 0.8), a mild variation in the negative predictive value (92.9±3.7%, 82.3% to 99.5%) and a minimal variation in the area under the curve (94.3%, 93.0 to 95.1; mean±s.d., range for all). Absolute SE was higher for the LGA group in 11/20 formulas (55%). The RE and POE were lower in 19/20 (95%) and 14/20 (70%) for the LGA neonates, respectively. CONCLUSION: There is a wide variation in EFW formulas performance for detecting LGA. Hadlock's formula (1985) combining abdominal circumference, femur length and biparietal diameter ranked highest.

Association of fetal biparietal diameter with mode of delivery and perinatal outcome.

OBJECTIVE: To determine the association between sonographic assessment of fetal biparietal diameter (BPD) and pregnancy outcome. METHODS: This was a retrospective cohort study of pregnancies at 37-42 weeks of gestation which had antepartum sonographic measurement of BPD within 7 days before delivery. Eligibility was limited to singleton pregnancies with neither known structural or chromosomal abnormalities nor prelabor Cesarean delivery (CD). The association of BPD with outcome was analyzed using multivariate logistic regression, receiver-operating characteristics curves and stratification according to BPD quartiles. RESULTS: In total, 3229 women were eligible for analysis, of whom 2483 (76.9%) had a spontaneous vaginal delivery (SVD), 418 (12.9%) underwent operative vaginal delivery (OVD) and 328 (10.2%) underwent CD. The mean BPD in the obstetric intervention groups (OVD and CD) was significantly higher than that in the SVD group (P < 0.001). After adjusting for confounders, increased BPD was an independent risk factor such that higher values of BPD were associated with progressively higher risk of obstetric intervention (adjusted odds ratio, 1.05 for each 1-mm increase in BPD (95% CI, 1.02-1.09)), but no clear cut-off value for obstetric intervention was found. The fourth quartile group (BPD ≥ 97 mm) was associated with a significantly lower SVD rate (P < 0.001) and higher OVD rate (P = 0.04), relative to the first (BPD 88-90 mm) and second (BPD 91-93 mm) quartile groups, with no apparent adverse impact on immediate neonatal outcome. CONCLUSIONS: Increased BPD within the week prior to delivery is an independent risk factor such that higher values of BPD are associated with progressively higher risk of obstetric intervention; however, in our experience, no adverse neonatal outcome resulted from such intervention. Thus, increased BPD should not discourage a trial of vaginal delivery.

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.

Is measurement of cervical length an accurate predictive tool in women with a history of preterm delivery who present with threatened preterm labor?

OBJECTIVE: To determine whether sonographically measured cervical length is an effective predictive tool in women with threatened preterm labor and a history of past spontaneous preterm delivery. METHODS: This was a retrospective cohort study of all women with singleton pregnancies who presented with preterm labor at less than 34 + 0 weeks' gestation and underwent sonographic measurement of cervical length in a tertiary medical center between 2007 and 2012. The accuracy of cervical length in predicting preterm delivery was compared between women with and those without a history of spontaneous preterm delivery. Women with risk factors for preterm delivery other than a history of preterm delivery were excluded from both groups. RESULTS: Overall, 1023 women who presented with preterm labor met the study criteria, of whom 136 (13.3%) had a history of preterm delivery (past-PTD group) and 887 (86.7%) had no risk factors for preterm delivery (low-risk group). The rate of preterm delivery was significantly higher for women with a history of preterm delivery (36.8% vs 22.5%; P < 0.001). Cervical length was significantly correlated with the examination-to-delivery interval in low-risk women (r = 0.32, P < 0.001) but not in women who had had a previous preterm delivery (r = 0.07, P = 0.4). On multivariable analysis, cervical length was independently associated with the risk of preterm delivery for women in the low-risk group but not for women with a history of previous preterm delivery. For women with previous preterm delivery who presented with threatened preterm labor, cervical length failed to distinguish between those who did and those who did not deliver prematurely (area under the receiver-operating characteristics curve range, 0.475-0.506). When using standardized thresholds, the sensitivity and specificity of cervical length for the prediction of preterm delivery were significantly lower in women with previous preterm delivery than in women with no risk factors for preterm delivery. CONCLUSION: Cervical length appears to be of limited value in the prediction of preterm delivery among women with threatened preterm labor who are at high risk for preterm delivery owing to a history of spontaneous preterm delivery in a previous pregnancy.