To evaluate whether fetal growth restriction (FGR) with or without abnormal Dopplers is associated with intracranial abnormalities and death in premature infants.
Premature infants with and without FGR born between 2016 and 2019 were included. Primary outcome was death, severe intraventricular hemorrhage (IVH) or periventricular leukomalacia (PVL). Groups were compared using standard bivariate testing and multivariable regression.
Among 168 FGR and 560 non-FGR infants, FGR infants with abnormal Dopplers had an increased incidence of death, severe IVH or PVL compared to non-FGR infants (13% (16/123) vs. 7% (41/560); p = 0.03) while FGR infants with normal Dopplers had a nonsignificant decrease. In a logistic regression model, FGR with abnormal Dopplers was associated with more than three times higher odds of death, severe IVH or PVL (OR 3.2, 95% CI 1.54,6.49; p < 0.001).
Growth-restricted infants with abnormal Dopplers had an increased risk of death, intracranial abnormalities, and prematurity-related morbidities.
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The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
Kesavan K, Devaskar SU. Intrauterine growth restriction: postnatal monitoring and outcomes. Pediatr Clin N Am. 2019;66:403–23.
Rogers EE, Piecuch RE. Neurodevelopmental outcomes of infants who experience intrauterine growth restriction. Neoreviews. 2009;10:e100–112.
Martins JG, Biggio JR, Abuhamad A, Society for Maternal-Fetal Medicine. Society for Maternal-Fetal Medicine Consult Series #52: diagnosis and management of fetal growth restriction. Am J Obstet Gynecol. 2020;223:B2–17.
Bernstein IM, Horbar JD, Badger GJ, Ohlsson A, Golan A. Morbidity and mortality among very-low-birth-weight neonates with intrauterine growth restriction. The Vermont Oxford Network. Am J Obstet Gynecol. 2000;182:198–206.
Unterscheider J, Daly S, Geary MP, Kennelly MM, McAuliffe FM, O’Donoghue K, et al. Optimizing the definition of intrauterine growth restriction: the multicenter prospective PORTO Study. Am J Obstet Gynecol. 2013;208:290.e1–6.
Kurjak A, Predojevic M, Stanojevic M, Salihagic-Kadic A, Miskovic B, Badrelden A, et al. Intrauterine growth restriction and cerebral palsy. Acta Inf Med. 2010;18:64–82.
Uquillas KR, Grubbs BH, Prosper AE, Chmait RH, Grant EG, Walker DK. Doppler US in the evaluation of fetal growth and perinatal health. Radiographics. 2017;37:1831–8.
American College of Obstetricians and Gynecologists. Fetal growth restriction. ACOG Practice Bulletin No. 134. Obstet Gynecol. 2013;121:1122–33.
Figueras F, Gardosi J. Intrauterine growth restriction: new concepts in antenatal surveillance, diagnosis, and management. Am J Obstet Gynecol. 2011;204:288–300.
Turan OM, Turan S, Berg C, Gembruch U, Nicolaides KH, Harman CR, et al. Duration of persistent abnormal ductus venosus flow and its impact on perinatal outcome in fetal growth restriction. Ultrasound Obstet Gynecol. 2011;38:295–302.
Ortigosa Rocha C, Bittar RE, Zugaib M. Neonatal outcomes of late-preterm birth associated or not with intrauterine growth restriction. Obstet Gynecol Int. 2010;2010:231842.
Bozzetti V, Paterlini G, van Bel F, Visser GHA, Tosetti L, Gazzolo D, et al. Cerebral and somatic NIRS-determined oxygenation in IUGR preterm infants during transition. J Matern Fetal Neonatal Med. 2016;29:443–6.
Cohen E, Baerts W, Caicedo Dorado A, Naulaers G, van Bel F, Lemmers PMA. Cerebrovascular autoregulation in preterm fetal growth restricted neonates. Arch Dis Child Fetal Neonatal Ed. 2019;104:F467–472.
Cohen E, Baerts W, van Bel F. Brain-sparing in intrauterine growth restriction: considerations for the neonatologist. Neonatology. 2015;108:269–76.
Toft PB, Leth H, Ring PB, Peitersen B, Lou HC, Henriksen O. Volumetric analysis of the normal infant brain and in intrauterine growth retardation. Early Hum Dev. 1995;43:15–29.
American College of Obstetricians and Gynecologists. Fetal growth restriction. ACOG Practice Bulletin No. 204. Obstet Gynecol 2019;133:e97–109.
Kofinas AD, Espeland MA, Penry M, Swain M, Hatjis CG. Uteroplacental Doppler flow velocity waveform indices in normal pregnancy: a statistical exercise and the development of appropriate reference values. Am J Perinatol. 1992;9:94–101.
Chou JH, Roumiantsev S, Singh R. PediTools electronic growth chart calculators: applications in clinical care, research, and quality improvement. J Med Internet Res. 2020;22. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7058170/.
Papile LA, Burstein J, Burstein R, Koffler H. Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weights less than 1,500 gm. J Pediatr. 1978;92:529–34.
Bell MJ, Ternberg JL, Feigin RD, Keating JP, Marshall R, Barton L, et al. Therapeutic decisions based upon clinical staging. Ann Surg. 1978;187:1–7.
Higgins RD, Jobe AH, Koso-Thomas M, Bancalari E, Viscardi RM, Hartert TV, et al. Bronchopulmonary dysplasia: executive summary of a workshop. J Pediatr. 2018;197:300–8.
R Core Team (2013). R: a language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing; 2013. https://www.r-project.org/.
R Studio Team (2022). RStudio: integrated development environment for R. http://www.rstudio.com/.
Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap) – a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inf. 2009;42:377–81.
Harris PA, Taylor R, Minor BL, et al. REDCap Consortium, The REDCap consortium: building an international community of software platform partners. J Biomed Inf. 2019. https://doi.org/10.1016/j.jbi.2019.103208.
Unterscheider J, O’Donoghue K, Daly S, Geary MP, Kennelly MM, McAuliffe FM, et al. Fetal growth restriction and the risk of perinatal mortality-case studies from the multicentre PORTO study. BMC Pregnancy Childbirth. 2014;14:63.
Luke B, Minogue J, Witter F. The role of fetal growth restriction and gestational age on length of hospital stay in twin infants. Obstet Gynecol. 1993;81:949–53.
Marzouk A, Filipovic-Pierucci A, Baud O, Tsatsaris V, Ego A, Charles M, et al. Prenatal and post-natal cost of small for gestational age infants: a national study. BMC Health Serv Res. 2017;17:1–8.
Aucott A, Donohue P, Northington F. Increased morbidity in severe early intrauterine growth restriction. J Perinatol. 2004;24:435–40.
Khalil A, Morales-Rosello J, Khan N, Nath M, Agarwal P, Bhide A, et al. Is cerebroplacental ratio a marker of impaired fetal growth velocity and adverse pregnancy outcome? Am J Obstet Gynecol. 2017;216:606.e1–10.
Alfirevic Z, Stampalija T, Dowswell T. Fetal and umbilical Doppler ultrasound in high-risk pregnancies. Cochrane Pregnancy and Childbirth Group, editor. Cochrane Database Syst Rev. 2017;2013:CD007529.
Carreno CA, Costantine MM, Holland MG, Ramin SM, Saade GR, Blackwell SC. Approximately one-third of medically indicated late preterm births are complicated by fetal growth restriction. Am J Obstet Gynecol. 2011;204:263.e1–4.
Khalil A, Morales-Rosello J, Khan N, Nath M, Agarwal P, Bhide A, et al. Is cerebroplacental ratio a marker of impaired fetal growth velocity and adverse pregnancy outcome? Am J Obstet Gynecol. 2017;216:606.e1–606e10.
Regan J, Masters H, Warshak CR. Estimation of the growth rate in fetuses with an abnormal cerebroplacental ratio compared to those with suspected growth restriction without evidence of centralization of blood flow. J Ultrasound Med. 2015;43:837–42.
van Bel F, van de Bor M, Stijnen T, Ruys JH. Decreased cerebrovascular resistance in small for gestational age infants. Eur J Obstet Gynecol Reprod Biol. 1986;23:137–44.
Castillo-Melendez M, Yawno T, Allison BJ, Jenkin G, Wallace EM, Miller SL. Cerebrovascular adaptations to chronic hypoxia in the growth restricted lamb. Int J Dev Neurosci. 2015;45:55–65.
Gowland P. Placental MRI. Semin Fetal Neonatal Med. 2005;10:485–90.
Andescavage N, duPlessis A, Metzler M, Bulas D, Vezina G, Jacobs M, et al. In vivo assessment of placental and brain volumes in growth restricted fetuses with and without fetal Doppler changes using quantitative 3D MRI. J Perinatol. 2017;37:1278–84.
Andescavage N, You W, Jacobs M, Kapse K, Quistorff J, Bulas D, et al. Exploring in vivo placental microstructure in healthy and growth-restricted pregnancies through diffusion-weighted magnetic resonance imaging. Placenta. 2020;93:113–8.
Gilbert WM, Danielsen B. Pregnancy outcomes associated with intrauterine growth restriction. Am J Obstet Gynecol. 2003;188:1596–601.
Hackett GA, Campbell S, Gamsu H, Cohen-Overbeek T, Pearce JM. Doppler studies in the growth retarded fetus and prediction of neonatal necrotising enterocolitis, haemorrhage, and neonatal morbidity. BMJ. 1987;294:13–6.
Cruz-Martinez R, Tenorio V, Padilla N, Crispi F, Figueras F, Gratacos E. Risk of ultrasound-detected neonatal brain abnormalities in intrauterine growth-restricted fetuses born between 28 and 34 weeks’ gestation: relationship with gestational age at birth and fetal Doppler parameters: abnormal Doppler in IUGR fetuses and neonatal brain abnormality. Ultrasound Obstet Gynecol. 2015;46:452–9.
Hout BM, Eken P, Linden D, Wittebol-Post D, Aleman S, Jennekens-Schinkel A, et al. Visual, cognitive, and neurodevelopmental outcome at 5½ years in children with perinatal haemorrhagic-ischaemic brain lesions. Dev Med Child Neurol. 1998;40:820–8.
Wu YW, Croen LA, Shah SJ, Newman TB, Najjar DV. Cerebral palsy in a term population: risk factors and neuroimaging findings. Pediatrics. 2006;118:690–7.
Padilla N, Perapoch J, Carrascosa A, Acosta-Rojas R, Botet F, Gratacós E. Twelve-month neurodevelopmental outcome in preterm infants with and without intrauterine growth restriction: outcome in intrauterine growth restricted infants. Acta Paediatr. 2010;99:1498–503.
Strauss RS, Dietz WH. Growth and development of term children born with low birth weight: effects of genetic and environmental factors. J Pediatr. 1998;133:67–72.
Thornton JG, Hornbuckle J, Vail A, Spiegelhalter DJ, Levene M, GRIT study group. Infant wellbeing at 2 years of age in the Growth Restriction Intervention Trial (GRIT): multicentred randomised controlled trial. Lancet. 2004;364:513–20.
Walker D-M, Marlow N, Upstone L, Gross H, Hornbuckle J, Vail A, et al. The Growth Restriction Intervention Trial: long-term outcomes in a randomized trial of timing of delivery in fetal growth restriction. Am J Obstet Gynecol. 2011;204:34.e1–9.
Bolisetty S, Dhawan A, Abdel-Latif M, Bajuk B, Stack J, Oei J-L, et al. Intraventricular hemorrhage and neurodevelopmental outcomes in extreme preterm infants. Pediatrics. 2014;133:55–62.
We would like to thank Kiyoko Ohira-Kist for her time and effort in collecting and inputting our institution’s data into the Vermont Oxford Network Database. We would like to thank Cynthia Masson for managing the REDCap maternal and neonatal database as part of the Obstetrics and Gynecology Department at Columbia University Irving Medical Center.
The authors declare no competing interests.
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Kim, F., Bateman, D.A., Goldshtrom, N. et al. Intracranial ultrasound abnormalities and mortality in preterm infants with and without fetal growth restriction stratified by fetal Doppler study results. J Perinatol (2023). https://doi.org/10.1038/s41372-023-01621-8