Intrauterine Growth Restriction: Obstetric and Neonatal Aspects. Intervention Strategies
Normal fetal growth can be altered by several pathological processes, including genetic diseases, infections, congenital anomalies, maternal hypoxia, and inadequate placental exchanges. The impossibility to reach the fetal genetic growth potential because of placental malfunction is defined intrauterine growth restriction (IUGR). IUGR causes slowing fetal growth, so that fetal biometry shifts from a higher to a significantly lower percentile during gestation, and it progressively leads to fetal hypoxia, acidemia, multiorgan damage, and death. Indeed, IUGR is associated with an excess of perinatal mortality and short- and long-term morbidity as well as metabolic syndrome in the adulthood. Prenatal diagnosis and appropriate timing of delivery improve neonatal outcomes.
When a fetus is found to be small for gestational age (SGA) at prenatal ultrasound, every effort has to be made to differentiate IUGR from other causes of impaired fetal growth. In case of IUGR, the clinical management is critically dependent on gestational age at onset. In early onset IUGR, the timing of delivery has to take into account the risks of prolonged intrauterine hypoxia versus the complications associated with preterm birth. In late onset IUGR, early induction of labor is probably the most cost-efficient method to prevent perinatal mortality and morbidity. In intermediate-onset IUGR there is a lack of clear evidence about the best tool to identify the fetuses that would benefit of timely delivery.
At birth, neonatal weight, length, and head circumference are indicators of the quality and quantity of intrauterine growth. SGA newborns, both preterm and term, have increased perinatal mortality risk and short-term complications such as birth asphyxia, infections, hypothermia, hypoglycemia, feeding difficulties, respiratory distress syndrome, bronchopulmonary dysplasia, retinopathy of prematurity, and necrotizing enterocolitis.
Even if most term children born SGA experience catch-up growth and achieve a normal adult height, approximately 10% of them remain shorter than peers born appropriate for gestational age. Preterm SGA infants can take four or more years to achieve heights in a normal range and the majority of them show a postnatal growth deficit at the time of hospital discharge (Extra Uterine Growth Restriction, EUGR).
Being born SGA is associated with long-term unfavorable outcomes such as learning difficulties, behavior problems, and development of metabolic syndrome.
The recognition of intrauterine malnutrition and the monitoring of early postnatal growth are of utmost importance for optimum survival and long-term outcomes of SGA infants.
List of Abbreviations
Appropriate for gestational age
Body mass index
Extra uterine growth restriction
International mormalized ratio
Intrauterine growth restriction
Large for gestational age
Respiratory distress syndrome
Retinopathy of prematurity
Small for gestational age
- Baschat AA, Cosmi E, Bilardo CM, Wolf H, Berg C, Rigano S, Germer U, Moyano D, Turan S, Hartung J, Bhide A, Müller T, Bower S, Nicolaides KH, Thilaganathan B, Gembruch U, Ferrazzi E, Hecher K, Galan HL, Harman CR (2007) Predictors of neonatal outcome in early-onset placental dysfunction. Obstet Gynecol 109:253–261PubMedCrossRefGoogle Scholar
- Boers KE, Vijgen SM, Bijlenga D, van der Post JA, Bekedam DJ, Kwee A, van der Salm PC, van Pampus MG, Spaanderman ME, de Boer K, Duvekot JJ, Bremer HA, Hasaart TH, Delemarre FM, Bloemenkamp KW, van Meir CA, Willekes C, Wijnen EJ, Rijken M, le Cessie S, Roumen FJ, Thornton JG, van Lith JM, Mol BW, Scherjon SA, DIGITAT study group (2010) Induction versus expectant monitoring for intrauterine growth restriction at term: randomized equivalence trial (DIGITAT). BMJ 341:c7087PubMedPubMedCentralCrossRefGoogle Scholar
- Boers KE, van Wyk L, van der Post JA, Kwee A, van Pampus MG, Spaanderdam ME, Duvekot JJ, Bremer HA, Delemarre FM, Bloemenkamp KW, de Groot CJ, Willekes C, Rijken M, Roumen FJ, Thornton JG, van Lith JM, Mol BW, le Cessie S, Scherjon SA, DIGITAT Study Group (2012) Neonatal morbidity after induction vs expectant monitoring in intrauterine growth restriction at term: a subanalysis of the DIGITAT RCT. Am J Obstet Gynecol 206:344 e1–344 e7CrossRefGoogle Scholar
- Bora R, Mukhopadhyay K, Saxena AK, Jain V, Narang A (2009) Prediction of feed intolerance and necrotizing enterocolitis in neonates with absent end diastolic flow in umbilical artery and the correlation of feed intolerance with postnatal superior mesenteric artery flow. J Matern Fetal Neonatal Med 22:1092–1096PubMedCrossRefGoogle Scholar
- Cameron N (2004) Measuring techniques and instruments. In: Nicoletti I, Benso L, Gilli G (eds) Physiological and pathological auxology. Edizioni Centro Studi Auxologici, Firenze, pp 117–159Google Scholar
- Clayton PE, Cianfarani S, Czernichow P, Johannsson G, Rapaport R, Rogol A (2007) Management of the child born small for gestational age through to adulthood: a consensus statement of the International Societies of Pediatric ndocrinology and the Growth Hormone Research Society. J Clin Endocrinol Metab 92:804–810PubMedCrossRefGoogle Scholar
- Cruz-Martinez R, Savchev S, Cruz-Lemini M, Mendez A, Gratacos E, Figueras F (2015) Clinical utility of third-trimester uterine artery Doppler in the prediction of brain hemodynamic deterioration and adverse perinatal outcome in small-for-gestational-age fetuses. Ultrasound Obstet Gynecol 45:273–278PubMedCrossRefGoogle Scholar
- Eixarch E, Meler E, Iraola A, Illa M, Crispi F, Hernandez-Andrade E, Gratacos E, Figueras F (2008) Neurodevelopmental outcome in 2-year-old infants who were small-for-gestational-age term fetuses with cerebral blood flow redistribution. Ultrasound Obstet Gynecol 32:894–899PubMedCrossRefGoogle Scholar
- Griffin IJ, Tancredi DJ, Bertino E, Lee HC, Profit J (2015) Postnatal growth failure in very low birthweight infants born between 2005 and 2012. Arch Dis Child Fetal Neonatal Ed 101:F1–F6Google Scholar
- Jarvis S, Glinianaia SV, Torrioli MG, Platt MJ, Miceli M, Jouk PS, Johnson A, Hutton J, Hemming K, Hagberg G, Dolk H, Chalmers J, Surveillance of Cerebral Palsy in Europe (SCPE) collaboration of European Cerebral Palsy Registers (2003) Cerebral palsy and intrauterine growth in single births: European collaborative study. Lancet 362:1106–1111PubMedCrossRefGoogle Scholar
- Lees C, Marlow N, Arabin B, Bilardo CM, Brezinka C, Derks JB, Duvekot J, Frusca T, Diemert A, Ferrazzi E, Ganzevoort W, Hecher K, Martinelli P, Ostermayer E, Papageorghiou AT, Schlembach D, Schneider KT, Thilaganathan B, Todros T, van Wassenaer-Leemhuis A, Valcamonico A, Visser GH, Wolf H, TRUFFLE Group (2013) 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 Gynecol 42:400–408PubMedCrossRefGoogle Scholar
- Lees C, Marlow N, van Wassenaer-Leemhuis A, Arabin B, Bilardo CM, Brezinka C, Calvert S, Derks JB, Diemert A, Duvekot JJ, Ferrazzi E, Frusca T, Ganzevoort W, Hecher K, Martinelli P, Ostermayer E, Papageorghiou AT, Schlembach D, Schneider KTM, Thilaganathan B, Todros T, Valcamonico A, Visser GHA, Wolf H, on behalf of the TRUFFLE Group (2015) The Trial of Randomized Umbilical and Fetal Flow in Europe (TRUFFLE) study: two year neurodevelopmental and intermediate perinatal outcomes. Lancet 385:2162–2172PubMedCrossRefGoogle Scholar
- Morley R, Fewtrell MS, Abbott RA, Stephenson T, MacFadyen U, Lucas A (2004) Neurodevelopment in children born small for gestational age: a randomized trial of nutrient-enriched versus standard formula and comparison with a reference breastfed group. Pediatrics 113:515–521PubMedCrossRefGoogle Scholar
- Pallotto EK, Woelnerhanssen B, Putt M (2004) Incidence and risk factors for prolonged hypoglycemia in small for gestational age infants. Abstract, Society for Pediatric and Perinatal EpidemiologyGoogle Scholar
- Papageorghiou AT, Ohuma EO, Altman DG, Todros T, Cheikh Ismail L, Lambert A, Jaffer YA, Bertino E, Gravett MG, Purwar M, Noble JA, Pang R, Victora CG, Barros FC, Carvalho M, Salomon LJ, Bhutta ZA, Kennedy SH, Villar J, International Fetal and Newborn Growth Consortium for the 21st Century (INTERGROWTH-21st) (2014) International standards for fetal growth based on serial ultrasound measurements: the Fetal Growth Longitudinal Study of the INTERGROWTH-21st Project. Lancet 384:869–879PubMedCrossRefGoogle Scholar
- Rizzo G, Prefumo F, Ferrazzi E, Zanardini C, Di Martino D, Boito S, Aiello E, Ghi T, SIEOG working group on fetal biometric charts (2016) The effect of fetal sex on customized fetal growth charts. J Matern Fetal Neonatal Med 3:1–8Google Scholar
- Singer DB, Sung CJ, Wigglesworth JS (1991) Fetal growth and maturation with standards for body and organ development. In: Wigglesworth JS, Singer DB (eds) Textbook of fetal and perinatal pathology. Blackwell, London, pp 11–47Google Scholar
- Sovio U, White IR, Dacey A, Pasupathy D, Smith GC (2015) Screening for fetal growth restriction with universal third trimester ultrasonography in nulliparous women in the Pregnancy Outcome Prediction (POP) study: a prospective cohort study. Lancet 386:2089–2097PubMedPubMedCentralCrossRefGoogle Scholar
- Tajik P, van Wyk L, Boers KE, le Cessie S, Zafarmand MH, Roumen F, van der Post JA, Porath M, van Pampus MG, Spaanderdam ME, Kwee A, Duvekot JJ, Bremer HA, Delemarre FM, Bloemenkamp KW, de Groot CJ, Willekes C, van Lith JM, Bossuyt PM, Mol BW, Scherjon SA, DIGITAT Study Group (2014) Which intrauterine growth restricted fetuses at term benefit from early labour induction? A secondary analysis of the DIGITAT randomised trial. Eur J Obstet Gynecol Reprod Biol 172:20–25PubMedCrossRefGoogle Scholar
- Tanner JM (1989) Foetus into man, 2nd edn. Castlemead Publication, Welwyn Garden CityGoogle Scholar
- The American Academy of Pediatrics and the American College of Obstetricians and Gynecologist (2007) Standard terminology for reporting of reproductive health statistics in the United States. In: Guideline for prenatal care. American Academy of Pediatrics, Elk Grove VillageGoogle Scholar
- van Wyk L, Boers KE, van der Post JA, van Pampus MG, van Wassenaer AG, van Baar AL, Spaanderdam ME, Becker JH, Kwee A, Duvekot JJ, Bremer HA, Delemarre FM, Bloemenkamp KW, de Groot CJ, Willekes C, Roumen FJ, van Lith JM, Mol BW, le Cessie S, Scherjon SA, DIGITAT Study Group (2012) Effects on (neuro developmental and behavioral outcome at 2 years of age of induced labor compared with expectant management in intrauterine growth-restricted infants: long-term outcomes of the DIGITAT trial. Am J Obstet Gynecol 206:406 e1–406 e7CrossRefGoogle Scholar
- Varda NM, Gregoric A (2009) Metabolic syndrome in the pediatric population: a short overview. Pediatric Rev 1:e1Google Scholar
- Wit JM, Finken MJ, Rijken M, de Zegher F (2006) Preterm growth restraint: a paradigm that unifies intrauterine growth retardation and preterm extrauterine growth retardation and has implications for the small-for-gestational-age indication in growth hormone therapy. Pediatrics 117:e793–e795PubMedCrossRefGoogle Scholar