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DOI: 10.1055/a-2495-3600
Derivation and Validation of Prediction of Preterm Preeclampsia Using Machine Learning Algorithms
Funding nuMoM2b specimen and data collection were supported by grant funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): U10 HD063036; U10 HD063072; U10 HD063047; U10 HD063037; U10 HD063041; U10 HD063020; U10 HD063046; U10 HD063048; and U10 HD063053. In addition, support was provided by Clinical and Translational Science Institutes: UL1TR001108 and UL1TR000153.

Abstract
Objective
This study aimed to develop machine learning (ML) models for predicting preterm preeclampsia using the information available before 23 weeks gestation.
Study Design
This was a secondary analysis of the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be (nuMoM2b) cohort. We considered 131 features available before 23 weeks including maternal demographics, obstetrics and family history, social determinants of health, physical activity, nutrition, and early second-trimester ultrasound. Our primary outcome was preterm preeclampsia before 37 weeks. The dataset was randomly split into a training set (70%) and a validation set (30%). ML models using glmnet, multilayer perceptron, random forest, XGBoost (extreme gradient boosting), and LightGBM models were developed. Using the ML approach that achieved the best area under the curve (AUC), we developed the final model. Further feature selection was conducted from the top 25 important features based on SHapley Additive exPlanations (SHAP) values. The performance of the final model was assessed using the validation dataset.
Results
Of 9,467 individuals, 219 (2.3%) had preterm preeclampsia. The AUC of the XGBoost model was the highest (AUC = 0.749 [95% confidence interval (95% CI), 0.736–0.762]) compared with other models. Therefore, XGBoost was used to develop models using fewer variables. The XGBoost model with the eight features (in order of importance: mean uterine artery pulsatility index in the early second trimester, chronic hypertension, pregestational diabetes, uterine artery notch, systolic and diastolic blood pressure in the first trimester, body mass index, and maternal age) was chosen as the final model as it had an AUC of 0.741 (95% CI, 0.730–0.752) which was not inferior to the original model (p = 0.58). The final model in the validation dataset had an AUC of 0.779 (95% CI, 0.722–0.831). An online application of the final model was developed ( https://kawakita.shinyapps.io/Preterm_preeclampsia/ ).
Conclusion
ML algorithms using information available before 23 weeks can accurately predict preterm preeclampsia before 37 weeks.
Key Points
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Prediction models using uterine artery Doppler have not been adopted in the US.
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We developed a model using an ML algorithm.
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An online application of the final model was developed.
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ML algorithms using information available before 23 weeks can accurately predict preterm preeclampsia before 37 weeks.
Note
The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Publication History
Received: 20 October 2024
Accepted: 03 December 2024
Accepted Manuscript online:
04 December 2024
Article published online:
24 December 2024
© 2024. Thieme. All rights reserved.
Thieme Medical Publishers, Inc.
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References
- 1 Abalos E, Cuesta C, Grosso AL, Chou D, Say L. Global and regional estimates of preeclampsia and eclampsia: a systematic review. Eur J Obstet Gynecol Reprod Biol 2013; 170 (01) 1-7
- 2 Ananth CV, Keyes KM, Wapner RJ. Pre-eclampsia rates in the United States, 1980-2010: age-period-cohort analysis. BMJ 2013; 347: f6564
- 3 Lisonkova S, Sabr Y, Mayer C, Young C, Skoll A, Joseph KS. Maternal morbidity associated with early-onset and late-onset preeclampsia. Obstet Gynecol 2014; 124 (04) 771-781
- 4 Ghosh G, Grewal J, Männistö T. et al. Racial/ethnic differences in pregnancy-related hypertensive disease in nulliparous women. Ethn Dis 2014; 24 (03) 283-289
- 5 MacKay AP, Berg CJ, Liu X, Duran C, Hoyert DL. Changes in pregnancy mortality ascertainment: United States, 1999-2005. Obstet Gynecol 2011; 118 (01) 104-110
- 6 Chang J, Elam-Evans LD, Berg CJ. et al. Pregnancy-related mortality surveillance–United States, 1991–1999. MMWR Surveill Summ 2003; 52 (02) 1-8
- 7 Odegård RA, Vatten LJ, Nilsen ST, Salvesen KÅ, Austgulen R. Preeclampsia and fetal growth. Obstet Gynecol 2000; 96 (06) 950-955
- 8 Simpson LL. Maternal medical disease: risk of antepartum fetal death. Semin Perinatol 2002; 26 (01) 42-50
- 9 Lisonkova S, Joseph KS. Incidence of preeclampsia: risk factors and outcomes associated with early- versus late-onset disease. Am J Obstet Gynecol 2013; 209 (06) 544.e1-544.e12
- 10 Irgens HU, Reisaeter L, Irgens LM, Lie RT. Long term mortality of mothers and fathers after pre-eclampsia: population based cohort study. BMJ 2001; 323 (7323) 1213-1217
- 11 Yu CK, Khouri O, Onwudiwe N, Spiliopoulos Y, Nicolaides KH. Fetal Medicine Foundation Second-Trimester Screening Group. Prediction of pre-eclampsia by uterine artery Doppler imaging: relationship to gestational age at delivery and small-for-gestational age. Ultrasound Obstet Gynecol 2008; 31 (03) 310-313
- 12 Labarrere CA, DiCarlo HL, Bammerlin E. et al. Failure of physiologic transformation of spiral arteries, endothelial and trophoblast cell activation, and acute atherosis in the basal plate of the placenta. Am J Obstet Gynecol 2017; 216 (03) 287.e1-287.e16
- 13 Smith GC, Shah I, White IR, Pell JP, Dobbie R. Previous preeclampsia, preterm delivery, and delivery of a small for gestational age infant and the risk of unexplained stillbirth in the second pregnancy: a retrospective cohort study, Scotland, 1992-2001. Am J Epidemiol 2007; 165 (02) 194-202
- 14 Bernardes TP, Mol BW, Ravelli ACJ, van den Berg P, Boezen HM, Groen H. Early and late onset pre-eclampsia and small for gestational age risk in subsequent pregnancies. PLoS One 2020; 15 (03) e0230483
- 15 Tan MY, Syngelaki A, Poon LC. et al. Screening for pre-eclampsia by maternal factors and biomarkers at 11-13 weeks' gestation. Ultrasound Obstet Gynecol 2018; 52 (02) 186-195
- 16 Velauthar L, Plana MN, Kalidindi M. et al. First-trimester uterine artery Doppler and adverse pregnancy outcome: a meta-analysis involving 55,974 women. Ultrasound Obstet Gynecol 2014; 43 (05) 500-507
- 17 MacDonald TM, Walker SP, Hannan NJ, Tong S, Kaitu'u-Lino TJ. Clinical tools and biomarkers to predict preeclampsia. EBioMedicine 2022; 75: 103780
- 18 Litwinska M, Syngelaki A, Wright A, Wright D, Nicolaides KH. Management of pregnancies after combined screening for pre-eclampsia at 19-24 weeks' gestation. Ultrasound Obstet Gynecol 2018; 52 (03) 365-372
- 19 Panaitescu A, Ciobanu A, Syngelaki A, Wright A, Wright D, Nicolaides KH. Screening for pre-eclampsia at 35-37 weeks' gestation. Ultrasound Obstet Gynecol 2018; 52 (04) 501-506
- 20 Parry S, Carper BA, Grobman WA. et al; Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be Group. Placental protein levels in maternal serum are associated with adverse pregnancy outcomes in nulliparous patients. Am J Obstet Gynecol 2022; 227 (03) 497.e1-497.e13
- 21 Shazly SA, Trabuco EC, Ngufor CG, Famuyide AO. Introduction to machine learning in obstetrics and gynecology. Obstet Gynecol 2022; 139 (04) 669-679
- 22 Haas DM, Parker CB, Wing DA. et al; NuMoM2b study. A description of the methods of the Nulliparous Pregnancy Outcomes Study: monitoring mothers-to-be (nuMoM2b). Am J Obstet Gynecol 2015; 212 (04) 539.e1-539.e24
- 23 Hastie T, Qian J, Tay K. An introduction to glmnet. CRAN R Repository. 2021 . Accessed November 7, 2023 at: https://haoen-cui.github.io/SOA-Exam-PA-R-Package-Documentation/glmnet/articles/glmnet.html
- 24 Rojas R. Neural networks: a systematic introduction. 1st ed.. Berlin, Heidelberg: Springer; 2013
- 25 Breiman L. Random forests. Mach Learn 2001; 45: 5-32 . Accessed November 7, 2023 at: https://www.stat.berkeley.edu/~breiman/randomforest2001.pdf
- 26 Chen T, Guestrin C. Xgboost: A scalable tree boosting system. Paper presented at: Proceedings of the 22nd ACM SIGKDD International Conference on Knowledge Discovery and Data Mining. San Francisco, CA; August 13-17, 2016
- 27 Zeng H, Yang C, Zhang H. et al. A lightGBM-based EEG analysis method for driver mental states classification. Comput Intell Neurosci 2019; 2019: 3761203
- 28 Ke G, Meng Q, Finley T. et al. Lightgbm: A highly efficient gradient boosting decision tree. Adv Neural Inf Process Syst 2017; 30: 3146-3154
- 29 Steyerberg EW. Clinical Prediction Models: A Practical Approach to Development, Validation, and Updating. Springer International Publishing; 2019
- 30 Rodríguez JD, Pérez A, Lozano JA. Sensitivity analysis of kappa-fold cross validation in prediction error estimation. IEEE Trans Pattern Anal Mach Intell 2010; 32 (03) 569-575
- 31 Sundararajan M, Najmi A. The many Shapley values for model explanation. Paper presented at: Proceedings of the 37th International Conference on Machine Learning. 13-18 July 2020
- 32 Lundberg SM, Lee S. A unified approach to interpreting model predictions. Advances in neural information processing systems. 2017: 30 . Accessed December 12, 2024 at: https://proceedings.neurips.cc/paper_files/paper/2017/file/8a20a8621978632d76c43dfd28b67767-Paper.pdf
- 33 Vyas DA, Eisenstein LG, Jones DS. Hidden in plain sight—reconsidering the use of race correction in clinical algorithms. N Engl J Med 2020; 383 (09) 874-882
- 34 American College of Obstetricians and Gynecologists. ACOG Committee Opinion No. 743: Low-dose aspirin use during pregnancy. Obstet Gynecol 2018; 132 (01) e44-e52
- 35 DeLong ER, DeLong DM, Clarke-Pearson DL. Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics 1988; 44 (03) 837-845
- 36 Nahm FS. Receiver operating characteristic curve: overview and practical use for clinicians. Korean J Anesthesiol 2022; 75 (01) 25-36
- 37 Vickers AJ, Elkin EB. Decision curve analysis: a novel method for evaluating prediction models. Med Decis Making 2006; 26 (06) 565-574
- 38 Schisterman EF, Perkins NJ, Liu A, Bondell H. Optimal cut-point and its corresponding Youden Index to discriminate individuals using pooled blood samples. Epidemiology 2005; 16 (01) 73-81
- 39 Rolnik DL, Selvaratnam RJ, Wertaschnigg D. et al. Routine first trimester combined screening for preterm preeclampsia in Australia: a multicenter clinical implementation cohort study. Int J Gynaecol Obstet 2022; 158 (03) 634-642
- 40 Hu J, Gao J, Liu J. et al. Prospective evaluation of first-trimester screening strategy for preterm pre-eclampsia and its clinical applicability in China. Ultrasound Obstet Gynecol 2021; 58 (04) 529-539
- 41 Osterman MJK, Martin JA. Timing and adequacy of prenatal care in the United States, 2016. Natl Vital Stat Rep 2018; 67 (03) 1-14
- 42 Buekens P, Kotelchuck M, Blondel B, Kristensen FB, Chen JH, Masuy-Stroobant G. A comparison of prenatal care use in the United States and Europe. Am J Public Health 1993; 83 (01) 31-36
- 43 Parry S, Sciscione A, Haas DM. et al; Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-be. Role of early second-trimester uterine artery Doppler screening to predict small-for-gestational-age babies in nulliparous women. Am J Obstet Gynecol 2017; 217 (05) 594.e1-594.e10
- 44 Esplin MS, Elovitz MA, Iams JD. et al; nuMoM2b Network. Predictive accuracy of serial transvaginal cervical lengths and quantitative vaginal fetal fibronectin levels for spontaneous preterm birth among nulliparous women. JAMA 2017; 317 (10) 1047-1056
- 45 Lambert-Messerlian G, Palomaki GE. Fewer women aged 35 and older choose serum screening for Down's syndrome: impact and implications. J Med Screen 2019; 26 (02) 59-66