Prediction of stillbirth from maternal demographic and pregnancy characteristics

Objectives: To develop a model for prediction of stillbirth based on maternal characteristics and components of medical history and evaluate the performance of screening of this model for all stillbirths and those due to impaired placentation and unexplained causes. Methods: This was a prospective screening study of 113,415 singleton pregnancies at 11+0-13+6 and 19+0-24+6 weeks’ gestation. The population included 113,019 live births and 396 (0.35%) antepartum stillbirths; 230 (58%) were secondary to impaired placentation and 166 (42%) were due to other or unexplained causes. Multivariate logistic regression analysis was used to determine the factors from maternal characteristics and medical history which provided a significant contribution to the prediction of stillbirth. Results: The risk for stillbirth increased with maternal weight (OR 1.01 per kg after 69 kg), was higher in women of Afro-Caribbean race (OR 2.01), assisted conception (OR 1.79), cigarette smokers (OR 1.71), those with a history of chronic hypertension (OR 2.62), SLE/APS (OR 3.61) or diabetes mellitus (OR 2.55) and was increased in parous women with a history of previous stillbirth (OR 4.81). The model predicted 26% of unexplained stillbirths and 31% of those due to impaired placentation at FPR of 10%; within the impaired placentation group the DR of stillbirth at 37 weeks (38% vs 28%). Conclusions: A model based on maternal characteristics and medical history recorded in early pregnancy can potentially predict one third of subsequent stillbirths. The extent to which such stillbirths could be prevented remains to be determined

Value of routine ultrasound examination at 35–37 weeks' gestation in diagnosis of non‐cephalic presentation

Background: Undiagnosed non-cephalic presentation in labor carries increased risks for both the mother and baby. Routine pregnancy care based on maternal abdominal palpation fails to detect the majority of non-cephalic presentations. Objective: To report the incidence of non-cephalic presentation at a routine scan at 35+0 - 36+6 weeks’ gestation and subsequent management of such pregnancies. Methods: This was a retrospective analysis of prospectively collected data in 45,847 singleton pregnancies that had undergone routine ultrasound examination at 35+0 - 36+6 weeks’ gestation. Patients with breech or transverse / oblique presentation were divided into two groups, first those that would have elective cesarean section for fetal or maternal indications other than the abnormal presentation, and second, those that would potentially require ECV. The latter group was reassessed in 1-2 weeks and if there was persistence of the abnormal presentation the parents were offered the options of ECV versus elective cesarean section at 38-40 weeks’ gestation. Multivariable logistic regression analysis was carried out to determine which of the factors from maternal and pregnancy characteristics provided a significant contribution in the prediction of first, non-cephalic presentation at the 35+0 - 36+6 weeks scan, second, successful ECV from non-cephalic to cephalic presentation, and third, spontaneous rotation from non-cephalic to cephalic presentation. Results: First, at 35+0 - 36+6 weeks the fetal presentation was cephalic in 43,416 (94.7%) pregnancies, breech in 1,987 (4.3%) and transverse or oblique in 444 (1.0%). Second, multivariable analysis demonstrated that the chance of non-cephalic presentation increased with increasing maternal age and weight, decreasing height, earlier gestational age at scan, and it was higher in the presence of placenta previa, oligohydramnios and polyhydramnios, in nulliparous than parous women and lower in women of South Asian and mixed racial origin than in White women. Third, 22% of cases of non-cephalic presentation were not eligible for ECV because of planned cesarean section for indications other than the malpresentation. Fourth, of those eligible for ECV only 48.5% (646/1,332) accepted the procedure and this was successful in 39.0% (252/646) of cases. Fifth, the chance of successful ECV increased with increasing maternal age and was lower in nulliparous than parous women. Sixth, in 33.9% (738/2,179) of pregnancies with non-cephalic presentation where successful ECV was not carried out there was a subsequent spontaneous rotation to cephalic presentation. Seventh, the chance of spontaneous rotation from non-cephalic to cephalic presentation increased with increasing interval between the scan and delivery and decreased with increasing birth weight, it was higher in women of Black than White racial origin, if the presentation was transverse or oblique than breech and if there was polyhydramnios and lower in nulliparous than parous women and in the presence of placenta previa. Eighth, in 109 (0.3%) of cephalic presentations there was subsequent rotation to non-cephalic presentation and in 41% of these the diagnosis was made during labor. Ninth, in the total of 2,431 cases of non-cephalic presentation at the time of the scan the presentation at birth was cephalic in 985 (40.5%); in 738 (74.9%) this was due to spontaneous rotation and in 247 (25.1%) due to successful ECV. Tenth, prediction of non-cephalic presentation at the 35+0 - 36+6 weeks scan and successful ECV from maternal and pregnancy factors was poor, but prediction of spontaneous rotation from non-cephalic to cephalic presentation was moderately good and this could be incorporated in the counselling of women prior to undertaking ECV. Conclusions: The problem of unexpected non-cephalic presentation in labor can to a great extent be overcome by a routine ultrasound examination at 35+0 - 36+6 weeks’ gestation. The incidence of non-cephalic presentation at the 35+0 - 36+6 weeks scan was about 5%, but, in about 40% of these cases the presentation at birth was cephalic, mainly due to subsequent spontaneous rotation and to a lesser extent as a consequence of successful ECV

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Value of routine ultrasound examination at 35-37 weeks' gestation in diagnosis of fetal abnormalities

Objective: To investigate the potential value of routine ultrasound examination at 35-37 weeks’ gestation in the diagnosis of previously unknown fetal abnormalities. Methods: This was a prospective study in 52,401 singleton pregnancies attending for a routine ultrasound examination at 35+0 - 36+6 weeks’ gestation; all pregnancies had a previous scan at 18-24 weeks and 47,215 also had a scan at 11-13 weeks. We included pregnancies resulting in livebirth or stillbirth but excluded those with known chromosomal abnormalities. The abnormalities were classified according to affected major organ system and the type and incidence of new abnormalities was determined. Results: In the study population the incidence of fetal abnormalities was 2.2% (1,168 / 52,401), including 847 (72.5%) that had been previously diagnosed during the first and / or second trimester, 247 (21.2%) that were detected for the first time at 35-37 weeks and 74 (6.3%) that were detected for the first time postnatally. The most common abnormalities that were diagnosed during the first and / or second trimester, that were also observed at 35-37 weeks, included aberrant right subclavian artery, ventricular septal defect, talipes, unilateral renal agenesis and / or pelvic kidney, hydronephrosis, duplex kidney or unilateral multicystic kidney, cystic pulmonary airway malformation, ventriculomegaly, cleft lip and palate, polydactyly,abdominal cyst or gastroschisis. The most common abnormalities seen at 35-37 weeks were hydronephrosis, mild ventriculomegaly, ventricular septal defect, duplex kidney, ovarian cyst and arachnoid cyst. The incidence of abnormalities first seen at 35-37 weeks was 0.5% and the most common were ovarian cysts, microcephaly, achondroplasia, dacryocystocele and hematocolpos. The incidence of abnormalities first seen postnatally was 0.1% and the most common were isolated cleft palate, polydactyly or syndactyly and ambiguous genitalia or hypospadias; prenatal examination of the genitalia was not a compulsory part of the protocol. Conclusions: A high proportion of fetal abnormalities are detected for the first time during a routine ultrasound examination at 35-37 weeks’ gestation. Such diagnosis and subsequent management, including selection of time and place for delivery and postnatal investigations, could potentially improve postnatal outcome

Comparison of different methods of measuring angle of progression in prediction of labor outcome

Objective: First, to compare the manual sagittal and para-sagittal and automated para-sagittal methods of measuring the angle of progression (AOP) by transperineal ultrasound during labor, and second, to develop models for the prediction of time-to-delivery and need for cesarean section (CS) for failure to progress (FTP) in a population of patients undergoing induction of labor. Methods: This was a prospective observational study of transperineal ultrasound on a cohort of 512 women with singleton pregnancies undergiong induction of labor. A random selection of 50 stored images was assessed for inter- and intra-observer reliability between methods. In the cases of vaginal delivery univariate linear, multivariate linear and quantile regression were performed to predict time-to-delivery. Univariate and multivariate binomial logistic regression were performed to predict CS for FTP in the first stage of labor. Results: The intra correlation coefficients (ICC) for the manual para-sagittal method for a single observer was 0.97 (CI 0.95-0.98) and for two observers was 0.96 (CI 0.93-0.98) indicating good reliability. The ICC for the sagittal method for a single observer was 0.93 (0.88-0.96) and for two observers was 0.74 (0.58-0.84) indicating moderate reliabilty for a single observer and poor reliability between two observers. Bland-Altman analysis demonstrated narrower limits of agreement for the manual para-saggittal approach than for the sagittal approach for both single and two observers. The automated para-sagittal method failed to capture an image in 19% of cases. The mean difference between sagittal and para-sagittal methods was 110. In pregnancies resulting in vaginal delivery, 54% of the variation in time-to-delivery was explained in a model combining parity, epidural and syntocinon use during labour and the sonographic findings of fetal head position and AOP. In the prediction of CS for FTP in the first stage of labour a model which combined maternal factors with the sonographic measurements of AOP and estimated fetal weight was superior to one utilising maternal factors alone (area under the curve 0.80 vs 0.76). Conclusions: First, the method of measuring AOP with greatest reliability is the manual parasagittal technique and future research should focus on this technique, second, over half of the variation in time to vaginal delivery can be explained by a model that combines maternal factors, pregnancy characteristics and ultrasound findings, and third, the ability of AOP to provide clinically useful prediction CS for FTP in the first stage of labour is limited

Prediction of stillbirth from maternal factors, fetal biometry and uterine artery Doppler at 19-24 weeks

Objectives: To evaluate the performance of screening for all stillbirths and those due to impaired placentation and unexplained or other causes by a combination of maternal factors, fetal biometry and uterine artery pulsatility index (UT-PI) at 19-24 weeks’ gestation and compare this performance to that of screening by UT-PI alone. Methods: This was a prospective screening study of 70,003 singleton pregnancies including 69,735 live births and 268 (0.38%) antepartum stillbirths; 159 (59%) were secondary to impaired placentation and 109 (41%) were due to other or unexplained causes. Multivariate logistic regression analysis was used to develop a model for prediction of stillbirth based on a combination of maternal factors, fetal biometry and UT-PI. Results: Combined screening predicted 55% of all stillbirths, including 75% of those due to impaired placentation and 23% of those that were due to other causes or unexplained, at false positive rate of 10%; within the impaired placentation group the detection rate of stillbirth at 37 weeks (88% vs 46%; p<0.001). The performance of screening by the combined test was superior to that of selecting the high-risk group on the basis of UT-PI being above the 90th percentile for gestational age, which predicted 48% of all stillbirths, 70% of those due to impaired placentation and 15% of those that were due to other causes or unexplained. Conclusions: Second-trimester screening by a combination of UT-PI with maternal factors and fetal biometry can predict a high proportion of stillbirths and in particular those due to impaired placentation

Fetal Medicine Foundation fetal and neonatal population weight charts

Objective: To develop fetal and neonatal population weight charts. The rationale for this objective is that while reference ranges of estimated fetal weight (EFW) are representative of the whole population, the traditional approach of deriving birth-weight (BW) charts is misleading because a high proportion of babies born preterm arises from pathological pregnancies. We propose that the reference population for BW charts, as in the case of EFW charts, should be all babies at a given gestational age including those still in utero. Patients: Two sources of data were used for this study and in both the inclusion criteria were singleton pregnancy, dating by fetal crown-rump length at 11+0 to 13+6 weeks’ gestation, ultrasonographic measurements of fetal head circumference (HC), abdominal circumference (AC) and femur length (FL), and livebirth of phenotypically normal neonate. Dataset 1, comprised a sample of 5,163 paired measurements of EFW and BW; the ultrasound scans were carried out at 22-43 weeks’ gestation and birth occurred within 2 days of the ultrasound examination. The EFW was derived from the measurements of HC, AC and FL using the formula reported by Hadlock et al. in 1985. Dataset 2, comprised a sample of 95,579 pregnancies with EFW obtained by routine ultrasonographic fetal biometry at 20+0 to 23+6 weeks’ gestation (n=45,034), or at 31+0 to 33+6 weeks (n=19,224) or at 35+0 to 36+6 weeks (n=31,321); for the purpose of this study we included data for only one of the three visits. Methods: In the development of reference ranges of EFW and BW with gestational age the following assumptions were made: first, the EFW and BW have a common median, dependent on gestational age and second, deviations from the median occur in both EFW and BW and these deviations are correlated with different levels of spread for EFW and BW, dependent on gestational age. We adopted a Bayesian approach to inference combining information from the two datasets using Markov Chain Monte–Carlo sampling (MCMC). The fitted model assumed that the mean log transformed measurements of EFW and BW are related to gestational age according to a cubic equation and that deviations about the mean follow a bivariate Gaussian distribution. Results: In the case of EFW in dataset 2 there was a good distribution of values 90th, >95th and >97th percentiles of the reference range of EFW with gestational age throughout the gestational age range of 20+0- 36+6 weeks. In the case of BW there was a good distribution of values only for the cases born at >39 weeks’ gestation. For preterm births, particularly at 27-36 weeks, the BW was below the 3rd, 5th and 10th percentiles in a very high proportion of cases and this was particularly marked for cases of iatrogenic birth. The incidence of SGA fetuses and neonates in the respective EFW and BW charts was higher in women of Black than White racial origin. Conclusion: We established a BW chart for the population of all babies at a given gestational age, including those still in utero, which overcomes the problem of underestimation of growth restriction in preterm births. The BW and EFW charts have a common median but they differ in the levels of spread from the median

Diagnosis of fetal defects in twin pregnancies at routine 11-13-week ultrasound examination

Objective: To examine the performance of the routine 11-13 weeks scan in detecting fetal defects in twin pregnancies and to examine if in pregnancies with fetal defects, compared to those with normal fetuses, there is increased incidence of nuchal translucency (NT) thickness ≥95th and ≥99th percentiles or intertwin discordance in crown-rump length (CRL) ≥10% and ≥15%. Methods: This was a retrospective analysis of prospectively collected data in twin pregnancies undergoing routine ultrasound examination for fetal anatomy, according to standardized protocols, at 11-13 weeks’ gestation between 2002 and 2019. Pregnancies with known chromosomal abnormalities were excluded. The final diagnosis of fetal defects was based on the results of postnatal examination in the case of livebirths and on the findings of the last ultrasound examination in the cases of pregnancy termination, miscarriage or stillbirth. The performance of the 11-13 weeks scan in the detection of fetal defects was determined. Results: The study population of 6,366 twin pregnancies with two live fetuses at 11-13 weeks’ gestation, included 4,979 (78.2%) dichorionic (DC) and 1,387 (21.8%) monochorionic (MC) twin pregnancies. The main findings were: first, the overall incidence of fetal defects was higher in MC than DC twins (2.8% vs. 1.3%); second, the proportion of defects diagnosed in the first-trimester was higher in MC than in DC twins (52.6% vs. 27.1%); third, the pattern of defects in relation to detectability at the 11-13 weeks scan, always detectable, sometimes detectable and never detectable, was similar to that previously reported in singleton pregnancies; fourth, always detectable defects included acrania, alobar holoprosencephaly, encephalocele, pentalogy of Cantrell, exomphalos, body stalk anomaly, TRAP sequence and conjoined twins; fifth, the incidence of fetal NT ≥95th percentile was higher in those with than without defects (16.5% vs. 4.5% in DC twins and 19.2% vs. 5.9% in MC twins) and this was also true for NT >99th percentile (8.3% vs. 1.0% in DC twins and 15.4% vs. 2.0% in MC twins); and sixth, the incidence of CRL discordance ≥10% was higher in those with than without defects (20.2% vs. 7.9% in DC twins and 33.8% vs. 9.3% in MC twins) and this was also true for CRL discordance ≥15% (10.1% vs. 1.9% in DC twins and 28.2% vs. 2.8% in MC twins). Conclusions: First, fetal defects are more common in MC than in DC twin pregnancies, second, first-trimester detection of fetal defects in DC twin pregnancies is similar to that in singleton pregnancies, third, detectability of defects in MC twins is higher than in DC twins, fourth, in twin pregnancies with fetal defects there is a higher intertwin discordance in CRL and incidence of high NT, but the predictive performance of screening by these markers is poor

Prediction of large-for-gestational-age neonate by routine third-trimester ultrasound

Objectives: First, to evaluate and compare the performance of routine ultrasonographic estimated fetal weight (EFW) and fetal abdominal circumference (AC) at 31+0 - 33+6 and 35+0 - 36+6 weeks’ gestation in the prediction of large for gestational age (LGA) neonates born at ≥37 weeks’ gestation. Second, to assess the additive value of fetal growth velocity between 32 and 36 weeks’ gestation on the performance of EFW at 35+0 - 36+6 weeks’ gestation for prediction of LGA neonates. Third, to define the predictive performance for LGA neonates of different EFW cut-offs at routine ultrasound examination at 35+0 - 36+6 weeks’ gestation. Fourth, to propose a two-stage strategy for identifying pregnancies with LGA fetuses that may benefit from iatrogenic delivery during the 38th gestational week. Methods: First, data from 21,989 singleton pregnancies that had undergone routine ultrasound examination at 31+0 - 33+6 weeks’ gestation and 45,847 that had undergone routine ultrasound examination at 35+0 - 36+6 weeks were used to compare the predictive performance of EFW and AC for LGA neonates with birthweight >90th and >97th percentiles born at ≥37 weeks’ gestation. Second, data from 14,497 singleton pregnancies that had undergone routine ultrasound examination at 35+0 - 36+6 weeks’ gestation and had a previous scan at 30+0 – 34+6 weeks were used to determine, through multivariable logistic regression analysis, whether addition of growth velocity, defined by a difference in EFW and AC Z-scores between the early and late third trimester scans divided by the time interval between them, improved the performance of EFW at 35+0 - 36+6 weeks in the prediction of delivery of LGA neonates born at ≥37 weeks’ gestation. Third, in the database of the 45,847 pregnancies that had undergone routine ultrasound examination at 35+0 - 36+6 weeks’ gestation the screen positive and detection rate of LGA neonates born at ≥37 weeks’ gestation and at ≤10 days from the initial scan were calculated for different EFW percentile cut-offs between the 50th and 90th percentile. Results: First, the areas under the receiver operating characteristic curves (AUROC) of screening for LGA neonates were significantly higher with EFW Z-score than AC Z-score and at 35+0 - 36+6 than at 31+0 - 33+6 weeks’ gestation (p90th percentile at 35+0 - 36+6 weeks’ gestation the predictive performance for LGA neonates born at ≥37 weeks’ gestation was modest (65% and 46% for neonates with birthweight >97th and >90th percentiles, respectively, at screen positive rate of 10%), but the performance was better for prediction of LGA neonates born at ≤10 days from the scan (84% and 71% for neonates with birthweight >97th and >90th percentiles, respectively, at screen positive rate of 11%). Fourth, screening by EFW >70th percentile at 35+0 - 36+6 weeks’ gestation predicted 91% and 82% of LGA neonates with birthweight >97th and >90th percentiles born at ≥37 weeks’ gestation, at screen positive rate of 32%, and the respective values of screening by EFW >85th percentile for prediction of LGA neonates born at ≤10 days from the scan were 88%, 81% and 15%. On the basis of these results it was proposed that routine fetal biometry at 36 weeks’ gestation is a screening rather than diagnostic test for fetal macrosomia and that EFW >70th percentile should be used to identify pregnancies in need for another scan at 38 weeks and in the latter those with EFW >85th percentile should be considered for iatrogenic delivery during the 38th week. Conclusions: First, the predictive performance for LGA neonates by routine ultrasonographic examination during the third trimester is higher if the scan is carried out at 36 than at 32 weeks, the method of screening is EFW than fetal AC, the outcome measure is birthweight >97th than >90th percentile and if delivery occurs within 10 days than at any stage after assessment. Second, prediction of LGA neonates by EFW >90th percentile is modest and the study presents a two-stage strategy for maximizing the prenatal prediction of LGA neonates