Machine learning demonstrates normal fetal Doppler velocimetry associated with reduced risk of necrotizing enterocolitis among preterm infants with growth restriction
Restricted accessResearch articleFirst published online May, 2026
Machine learning demonstrates normal fetal Doppler velocimetry associated with reduced risk of necrotizing enterocolitis among preterm infants with growth restriction
Necrotizing enterocolitis (NEC) is an intestinal ischemic disease that affects preterm infants with fetal growth restriction (FGR). The role of fetal Dopplers in stratifying risk for developing NEC is unclear but the innovative use of machine learning technology may aid in identifying their contribution.
Methods
This is a single center retrospective cohort of 164 infants born before 33 weeks’ gestation with FGR from 2016 to 2019. We used machine learning to classify NEC and to evaluate the predictive values of gestational age (GA), birth weight (BW), and the presence of abnormal umbilical artery (UA) Dopplers before delivery.
Results
Early GA and lower BW strongly predicted NEC. The presence of normal fetal UA Dopplers was heavily weighted in classifying infants unlikely to develop NEC. Fetal UA Dopplers had a 95% specificity (15% sensitivity) for NEC.
Conclusions
If validated, normal fetal UA Doppler studies may identify infants with FGR at low risk for NEC who may avoid conservative NEC-prevention strategies.
UnterscheiderJDalySGearyMP, et al.Optimizing the definition of intrauterine growth restriction: the multicenter prospective PORTO Study. Am J Obstet Gynecol2013; 208: 290.e1–290.e6.
2.
NeuJWalkerWA. Necrotizing enterocolitis. N Eng J Med2011; 364: 255–264.
3.
YeeWHSoraishamASShahVS, et al.Incidence and timing of presentation of necrotizing enterocolitis in preterm infants. Pediatrics2012; 129: e298–e304.
4.
ZozayaCGarcía GonzálezIAvila-AlvarezA, et al.Incidence, treatment, and outcome trends of necrotizing enterocolitis in preterm infants: a multicenter cohort study. Front Pediatr2020; 8: 188.
5.
MalhotraAAllisonBJCastillo-MelendezM, et al.Neonatal morbidities of fetal growth restriction: pathophysiology and impact. Front Endocrinol2019; 10: 55.
6.
GariteTJClarkRThorpJA. Intrauterine growth restriction increases morbidity and mortality among premature neonates. Am J Obstet Gynecol2004; 191: 481–487.
ReeIMCSmits-WintjensVEHJRijntjes-JacobsEGJ, et al.Necrotizing enterocolitis in small-for-gestational-age neonates: a matched case-control study. Neonatology2013; 105: 74–78.
9.
HackettGACampbellSGamsuH, et al.Doppler studies in the growth retarded fetus and prediction of neonatal necrotising enterocolitis, haemorrhage, and neonatal morbidity. Br Med J (Clin Res Ed)1987; 294: 13–16.
10.
KimFBatemanDAGoldshtromN, et al.Intracranial ultrasound abnormalities and mortality in preterm infants with and without fetal growth restriction stratified by fetal Doppler study results. J Perinatol2023; 43: 560–567.
11.
KempleySGuptaNLinsellL, et al.Feeding infants below 29 weeks’ gestation with abnormal antenatal Doppler: analysis from a randomised trial. Arch Dis Child Fetal Neonatal Ed2014; 99: F6–F11.
12.
BernsteinIMHorbarJDBadgerGJ, et al.Morbidity and mortality among very-low-birth-weight neonates with intrauterine growth restriction. Am J Obstet Gynecol2000; 182: 198–206.
13.
LeafADorlingJKempleyS, et al.Early or delayed enteral feeding for preterm growth-restricted infants: a randomized trial. Pediatrics2012; 129: e1260–e1268.
14.
CheLThymannTBeringSB, et al.IUGR does not predispose to necrotizing enterocolitis or compromise postnatal intestinal adaptation in preterm pigs. Pediatr Res2010; 67: 54–59.
15.
AradhyaASMukhopadhyayKSainiSS, et al.Feed intolerance in preterm neonates with antenatal reverse end diastolic flow (REDF) in umbilical artery: a retrospective cohort study. J Matern Fetal Neonatal Med2020; 33: 1846–1852.
16.
DuciMCosmiEZorzatoP, et al.Fetal Doppler evaluation to predict NEC development. J Pers Med2022; 12: 1042.
17.
ManoguraACTuranOKushML, et al.Predictors of necrotizing enterocolitis in preterm growth-restricted neonates. Am J Obstet Gynecol2008; 198: 638.e1–638.e5.
18.
NeuJ. Necrotizing enterocolitis: the future. Neonatology2020; 117: 240–244.
19.
IrlesCGonzález-PérezGMuiñosSC, et al.Estimation of neonatal intestinal perforation associated with necrotizing enterocolitis by machine learning reveals new key factors. Int J Environ Res Public Health2018; 15: 2509.
20.
ChoHLeeEHLeeK-S, et al.Machine learning-based risk factor analysis of necrotizing enterocolitis in very low birth weight infants. Sci Rep2022; 12: 21407.
21.
HoovenTALinASalleb-AouissiA. Multiple instance learning for predicting necrotizing enterocolitis in premature infants using microbiome data. Proc ACM Conf Health Inference Learn2020; 2020: 99–109.
22.
SongYYLuY. Decision tree methods: applications for classification and prediction. Shanghai Arch Psychiatry2015; 27: 130–135.
23.
FentonTRKimJH. A systematic review and meta-analysis to revise the Fenton growth chart for preterm infants. BMC Pediatr2013; 13: 59.
24.
MartinsJGBiggioJRAbuhamadA, et al.Society for Maternal-Fetal Medicine consult series #52: diagnosis and management of fetal growth restriction: (replaces clinical guideline number 3, April 2012). Am J Obstet Gynecol2020; 223: B2–B17.
25.
Fetal growth restriction: ACOG practice bulletin, number 227. Obstet Gynecol2021; 137:E16–E28.
26.
KofinasADEspelandMAPenryM, et al.Uteroplacental Doppler flow velocity waveform indices in normal pregnancy: a statistical exercise and the development of appropriate reference values. Am J Perinatol1992; 9: 94–101.
27.
WalshMCKliegmanRM. Necrotizing enterocolitis: treatment based on staging criteria. Pediatr Clin North Am1986; 33: 179–201.
28.
ChenTGuestrinC. XGBoost: a scalable tree boosting system. In: Proceedings of the 22nd ACM SIGKDD international conference on knowledge discovery and data mining, San Francisco, California, USA, 13–17 August 2016, Association for Computing Machinery, 2016, pp. 785–794.
29.
TeamRDCR. A language and environment for statistical computing. R Foundation for Statistical Computing, 2013.
BozzettiVTagliabuePEVisserGHA, et al.Feeding issues in IUGR preterm infants. Early Hum Dev2013; 89: S21–S23.
32.
BattersbyCSanthalingamTCosteloeK, et al.Incidence of neonatal necrotising enterocolitis in high-income countries: a systematic review. Arch Dis Child Fetal Neonatal Ed2018; 103: F182–F189.
33.
FloodKUnterscheiderJDalyS, et al.The role of brain sparing in the prediction of adverse outcomes in intrauterine growth restriction: results of the multicenter PORTO Study. Am J Obstet Gynecol2014; 211: 288.e1–288.e5.
34.
Rial-CresteloMLubuskyMParra-CorderoM, et al.Term planned delivery based on fetal growth assessment with or without the cerebroplacental ratio in low-risk pregnancies (RATIO37): an international, multicentre, open-label, randomised controlled trial. Lancet2024; 403: 545–553.
35.
OddieSJYoungLMcGuireW. Slow advancement of enteral feed volumes to prevent necrotising enterocolitis in very low birth weight infants. Cochrane Database Syst Rev2021; 8: CD001241.
36.
DorlingJAbbottJBerringtonJ, et al.Controlled trial of two incremental milk-feeding rates in preterm infants. N Engl J Med2019; 381: 1434–1443.
37.
ShahPNathanEDohertyD, et al.Optimising enteral nutrition in growth restricted extremely preterm neonates – a difficult proposition. J Matern Fetal Neonatal Med2015; 28: 1981–1984.
38.
WalshVBrownJVECopperthwaiteBR, et al.Early full enteral feeding for preterm or low birth weight infants. Cochrane Database Syst Rev2020; 12: CD013542.
39.
MorganJYoungLMcGuireW. Delayed introduction of progressive enteral feeds to prevent necrotising enterocolitis in very low birth weight infants. Cochrane Database Syst Rev2014; 2014: CD001970.
40.
YoonSALeeMHChangYS. Impact of time to full enteral feeding on long-term neurodevelopment without mediating by postnatal growth failure in very-low-birth-weight-infants. Sci Rep2023; 13: 2990.
41.
McElroySJLueschowSR. State of the art review on machine learning and artificial intelligence in the study of neonatal necrotizing enterocolitis. Front Pediatr2023; 11: 1182597.
42.
LureACDuXBlackEW, et al.Using machine learning analysis to assist in differentiating between necrotizing enterocolitis and spontaneous intestinal perforation: a novel predictive analytic tool. J Pediatr Surg2021; 56: 1703–1710.
43.
LeesCMarlowNArabinB, et al.Perinatal morbidity and mortality in early-onset fetal growth restriction: cohort outcomes of the trial of randomized umbilical and fetal flow in Europe (TRUFFLE). Ultrasound Obstet Gynecol2013; 42: 400–408.
44.
DamodaramMStoryLKulinskayaE, et al.Early adverse perinatal complications in preterm growth-restricted fetuses. Aust N Z J Obstet Gynaecol2011; 51: 204–209.
45.
UnterscheiderJDalySGearyMP, et al.Predictable progressive Doppler deterioration in IUGR: does it really exist?Am J Obstet Gynecol2013; 209: 539.e1–539.e7.
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
