Longitudinal twin growth discordance patterns and adverse perinatal outcomes

Abstract

Background: Growth discordance in twin pregnancies is associated with increased perinatal morbidity and mortality, yet the patterns of discordance progression and the utility of Doppler assessments remain underinvestigated. Objective: The objective of this study was to conduct a longitudinal assessment of intertwin growth and Doppler discordance to identify possible distinct patterns and to investigate the predictive value of longitudinal discordance patterns for adverse perinatal outcomes in twin pregnancies. Study design: This retrospective cohort study included twin pregnancies followed and delivered at a tertiary hospital in London (United Kingdom) between 2010 and 2023. We included pregnancies with at least 3 ultrasound assessments after 18 weeks and delivery beyond 34 weeks’ gestation. Monoamniotic twin pregnancies, pregnancies with twin-to-twin transfusion syndrome, genetic or structural abnormalities, or incomplete data were excluded. Data on chorionicity, biometry, Doppler indices, maternal characteristics and obstetrics, and neonatal outcomes were extracted from electronic records. Doppler assessment included velocimetry of the umbilical artery, middle cerebral artery, and cerebroplacental ratio. Intertwin growth discordance was calculated for each scan. The primary outcome was a composite of perinatal mortality and neonatal morbidity. Statistical analysis involved multilevel mixed effects regression models and unsupervised machine learning algorithms, specifically k-means clustering, to identify distinct patterns of intertwin discordance and their predictive value. Predictive models were compared using the area under the receiver operating characteristic curve, calibration intercept, and slope, validated with repeated cross-validation. Analyses were performed using R, with significance set at P<.05. Results: Data from 823 twin pregnancies (647 dichorionic, 176 monochorionic) were analyzed. Five distinct patterns of intertwin growth discordance were identified using an unsupervised learning algorithm that clustered twin pairs based on the progression and patterns of discordance over gestation: low-stable (n=204, 24.8%), mild-decreasing (n=171, 20.8%), low-increasing (n=173, 21.0%), mild-increasing (n=189, 23.0%), and high-stable (n=86, 10.4%). In the high-stable cluster, the rates of perinatal morbidity (46.5%, 40/86) and mortality (9.3%, 8/86) were significantly higher compared to the low-stable (reference) cluster (P<.001). High-stable growth pattern was also associated with a significantly higher risk of composite adverse perinatal outcomes (odds ratio: 70.19, 95% confidence interval: 24.18–299.03, P<.001; adjusted odds ratio: 76.44, 95% confidence interval: 25.39–333.02, P<.001). The model integrating discordance pattern with cerebroplacental ratio discordance at the last ultrasound before delivery demonstrated superior predictive accuracy, evidenced by the highest area under the receiver operating characteristic curve of 0.802 (95% confidence interval: 0.712–0.892, P<.001), compared to only discordance patterns (area under the receiver operating characteristic curve: 0.785, 95% confidence interval: 0.697–0.873), intertwin weight discordance at the last ultrasound prior to delivery (area under the receiver operating characteristic curve: 0.677, 95% confidence interval: 0.545–0.809), combination of single measurements of estimated fetal weight and cardiopulmonary resuscitation discordance at the last ultrasound prior to delivery (area under the receiver operating characteristic curve: 0.702, 95% confidence interval: 0.586–0.818), and single measurement of cardiopulmonary resuscitation discordance only at the last ultrasound (area under the receiver operating characteristic curve: 0.633, 95% confidence interval: 0.515–0.751). Conclusion: Using an unsupervised machine learning algorithm, we identified 5 distinct trajectories of intertwin fetal growth discordance. Consistent high discordance is associated with increased rates of adverse perinatal outcomes, with a dose—response relationship. Moreover, a predictive model integrating discordance trajectory and cardiopulmonary resuscitation discordance at the last visit demonstrated superior predictive accuracy for the prediction of composite adverse perinatal outcomes, compared to either of these measurements alone or a single value of estimated fetal weight discordance at the last ultrasound prior to delivery.