Machine Learning Models for the Prediction of Preterm Birth at Mid-Gestation Using Individual Characteristics and...

Preterm birth (PTB), defined as birth before 37 completed weeks of gestation, is a major global health challenge and a leading cause of neonatal mortality. PTB is broadly classified into spontaneous and medically indicated (iatrogenic), which have distinct etiologies. While prediction is key to improving outcomes, there is a lack of models that specifically differentiate between spontaneous and iatrogenic PTB subtypes. This study aimed to develop and validate predictive models for the prediction of spontaneous and iatrogenic PTB at <32, <34, and <37 weeks' gestation using medical history and readily available second-trimester data.

This was a retrospective cohort study on singleton pregnancies from a single tertiary institution (2012-2025). Predictor variables included maternal characteristics, obstetric history, and second-trimester ultrasound markers. Four algorithms, including multivariable Logistic Regression and three machine learning methods (Random Forest, XGBoost, and a Neural Network), were trained and evaluated on a held-out test set (20% of the data). Model performance was primarily assessed by the Area Under the Curve (AUC).

In total, 9805 singleton pregnancies were included. The models performed significantly better for iatrogenic PTB than for spontaneous PTB. For delivery <37 weeks, the highest AUC for iatrogenic PTB was 0.764 (Random Forest), while for spontaneous PTB it was 0.609 (Neural Network). Predictive accuracy improved for earlier gestations; for delivery <32 weeks, the best model for iatrogenic PTB achieved an AUC of 0.862 (Neural Network), and the best model for spontaneous PTB achieved an AUC of 0.749 (Random Forest). Model interpretation revealed that iatrogenic PTB was primarily driven by markers of placental dysfunction, such as estimated fetal weight by ultrasound scan and uterine artery pulsatility index, while spontaneous PTB was most associated with a history of PTB and a short cervical length.

Models using routine mid-gestation data demonstrate effective prediction for iatrogenic PTB, with accuracy improving for earlier, more severe cases. In contrast, performance for spontaneous PTB was modest. Traditional Logistic Regression performed comparably to complex machine learning algorithms, highlighting that the clinical value is rooted in the subtype-specific modeling approach rather than in algorithmic complexity.