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Longitudinal twin growth discordance patterns and adverse perinatal outcomes - 18/06/25

Doi : 10.1016/j.ajog.2024.12.029 
Smriti Prasad, MRCOG a, Işıl Ayhan, MD a, Doaa Mohammed, MBBS a, Erkan Kalafat, MD b, Asma Khalil, MD, FRCOG a, c, d, e,
a Fetal Medicine Unit, St George's University Hospitals NHS Foundation Trust, London, United Kingdom 
b Department of Obstetrics and Gynecology, Koc University Hospital, Istanbul, Turkey 
c Vascular Biology Research Centre, Molecular and Clinical Sciences Research Institute, St George's University of London, London, United Kingdom 
d Twin and Multiple Pregnancy Centre for Research and Clinical Excellence, St George's University Hospital, St George's University of London, London, United Kingdom 
e Fetal Medicine Unit, Liverpool Women's Hospital, Liverpool, United Kingdom 

Corresponding author: Asma Khalil, MD, FRCOG.

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 cerebroplacental ratio 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 cerebroplacental ratio 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 cerebroplacental ratio 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.

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Key words : adverse, artificial intelligence, discordance, fetal death, fetal growth restriction, intrauterine demise, longitudinal, perinatal, neonatal, machine learning, morbidity, mortality, multiple pregnancy, neonatal unit, outcomes, small for gestational age, singleton pregnancy, stillbirth, twin


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 S.P. and I.A. contributed equally to the work.
 The authors report no conflicts of interest.
 Cite this article as: Prasad P, Ayhan I, Mohammed D, et al. Longitudinal twin growth discordance patterns and adverse perinatal outcomes. Am J Obstet Gynecol 2025;233:73.e1-14.


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Vol 233 - N° 1

P. 73.e1-73.e14 - juillet 2025 Retour au numéro
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