Perinatal Outcomes of Fetuses with Early Growth Restriction, Late Growth Restriction, Small for Gestational Age, and Adequate for Gestational Age

Abstract

Objective To evaluate the association between early-onset fetal growth restriction (FGR), late-onset FGR, small for gestational age (SGA) and adequate for gestational age (AGA) fetuses and adverse perinatal outcomes.

Methods This was a retrospective longitudinal study in which 4 groups were evaluated: 1 — early-onset FGR (before 32 weeks) (n = 20), 2 — late-onset FGR (at or after 32 weeks) (n = 113), 3 — SGA (n = 59), 4 — AGA (n = 476). The Kaplan-Meier curve was used to compare the time from the diagnosis of FGR to birth. Logistic regression was used to determine the best predictors of adverse perinatal outcomes in fetuses with FGR and SGA.

Results A longer time between the diagnosis and birth was observed for AGA than for late FGR fetuses (p < 0.001). The model including the type of FGR and the gestational age at birth was significant in predicting the risk of hospitalization in the neonatal intensive care unit (ICU) (p < 0.001). The model including only the type of FGR predicted the risk of needing neonatal resuscitation (p < 0.001), of respiratory distress (p < 0.001), and of birth at < 32, 34, and 37 weeks of gestation, respectively (p < 0.001).

Conclusion Fetal growth restriction and SGA were associated with adverse perinatal outcomes. The type of FGR at the moment of diagnosis was an independent variable to predict respiratory distress and the need for neonatal resuscitation. The model including both the type of FGR and the gestational age at birth predicted the risk of needing neonatal ICU hospitalization.

Resumo

Objetivo Avaliar o efeito da restrição de crescimento fetal (RCF) precoce, RCF tardio, fetos pequenos constitucionais para idade gestacional (PIG) e fetos adequados para idade gestacional (AIG) sobre resultados adversos perinatais.

Métodos Estudo longitudinal e retrospectivo, no qual foram avaliados quatro grupos: 1 — RCF precoce (< 32 semanas) (n = 20), 2 — RCF tardio (≥ 32 semanas) (n = 113), 3 — PIG (n = 59), 4 — AIG (n = 476). A curva de Kaplan-Meier foi utilizada para comparar o tempo entre o diagnóstico da RCF e o parto. Regressão logística foi utilizada para determinação dos melhores previsores de resultados perinatais adversos entre os fetos com RCF e PIG.

Resultados Os fetos AIGs apresentaram maior tempo entre o diagnóstico e parto, enquanto fetos RCF tardio apresentaram menor tempo (p < 0,001). O modelo contendo tanto os tipos de RCF quanto a idade gestacional no momento do parto foi significativo em predizer o risco de internação na unidade de terapia intensiva (UTI) neonatal (p < 0,001). O modelo incluindo apenas o tipo de FGR prediz o risco de ressuscitação neonatal (p < 0,001), de desconforto respiratório (p < 0,001) e de nascimento < 32, 34 e 37 semanas de gestação, respectivamente (p < 0,001).

Conclusão Os desvios do crescimento, RCF e PIG, foram associados a resultados perinatais adversos. O tipo de RCF no momento do diagnóstico foi variável independente para predizer necessidade de reanimação neonatal e desconforto respiratório. O modelo que incluiu o tipo de FGR e idade gestacional no nascimento prediz o risco de necessitar de internação em UTI neonatal.

Keywords

fetal growth restriction - small for gestational age - adverse perinatal outcomes

Palavras-chave

restrição do crescimento fetal - pequeno para a idade gestacional - resultados perinatais adversos

Contributors

All of the authors contributed with the project and data interpretation, the writing of the article, the critical review of the intellectual content, and with the final approval of the version to be published.

• References

• 1 Frøen JF, Gardosi JO, Thurmann A, Francis A, Stray-Pedersen B. Restricted fetal growth in sudden intrauterine unexplained death. Acta Obstet Gynecol Scand 2004; 83 (09) 801-807 . Doi: 10.1111/j.0001-6349.2004.00602.x
• 2 Manning FA. Intrauterine growth retardation. In: Manning FA. , ed. Fetal Medicine: Principle and Practice. Norwalk, CT: Appleton & Lange; 1995: 317
• 3 ACOG Practice Bulletin No. 204: fetal growth restriction. Obstet Gynecol 2019; 133 (02) e97-e109 . Doi: 10.1097/AOG.0000000000003070
• 4 Nardozza LM, Caetano AC, Zamarian AC. , et al. Fetal growth restriction: current knowledge. Arch Gynecol Obstet 2017; 295 (05) 1061-1077 . Doi: 10.1007/s00404-017-4341-9
• 5 Mäkikallio K, Shah J, Slorach C. , et al. Fetal growth restriction and cardiovascular outcome in early human infancy: a prospective longitudinal study. Heart Vessels 2016; 31 (09) 1504-1513 . Doi: 10.1007/s00380-015-0742-5
• 6 Szostak-Węgierek D, Szamotulska K. Fetal development and risk of cardiovascular diseases and diabetes type 2 in adult life. Med Wieku Rozwoj 2011; 15 (03) 203-215
• 7 Karlsen HO, Johnsen SL, Rasmussen S, Kiserud T. Prediction of adverse perinatal outcome of small-for-gestational-age pregnancy using size centiles and conditional growth centiles. Ultrasound Obstet Gynecol 2016; 48 (02) 217-223 . Doi: 10.1002/uog.15835
• 8 Caradeux J, Eixarch E, Mazarico E, Basuki TR, Gratacos E, Figueras F. Longitudinal growth assessment for prediction of adverse perinatal outcome in fetuses suspected to be small-for-gestational age. Ultrasound Obstet Gynecol 2018; 52 (03) 325-331 . Doi: 10.1002/uog.18824
• 9 Salomon LJ, Alfirevic Z, Berghella V. , et al; ISUOG Clinical Standards Committee. Practice guidelines for performance of the routine mid-trimester fetal ultrasound scan. Ultrasound Obstet Gynecol 2011; 37 (01) 116-126 . Doi: 10.1002/uog.8831
• 10 Hadlock FP, Harrist RB, Carpenter RJ, Deter RL, Park SK. Sonographic estimation of fetal weight. The value of femur length in addition to head and abdomen measurements. Radiology 1984; 150 (02) 535-540 . Doi: 10.1148/radiology.150.2.6691115
• 11 Gramellini D, Chiaie D, Piantelli G, Sansebastiano L, Fieni S, Vadora E. Sonographic assessment of amniotic fluid volume between 11 and 24 weeks of gestation: construction of reference intervals related to gestational age. Ultrasound Obstet Gynecol 2001; 17 (05) 410-415 . Doi: 10.1046/j.1469-0705.2001.00264.x
• 12 Gómez O, Figueras F, Fernández S. , et al. Reference ranges for uterine artery mean pulsatility index at 11-41 weeks of gestation. Ultrasound Obstet Gynecol 2008; 32 (02) 128-132 . Doi: 10.1002/uog.5315
• 13 Acharya G, Wilsgaard T, Berntsen GK, Maltau JM, Kiserud T. Reference ranges for serial measurements of blood velocity and pulsatility index at the intra-abdominal portion, and fetal and placental ends of the umbilical artery. Ultrasound Obstet Gynecol 2005; 26 (02) 162-169 . Doi: 10.1002/uog.1902
• 14 Parra-Cordero M, Lees C, Missfelder-Lobos H, Seed P, Harris C. Fetal arterial and venous Doppler pulsatility index and time averaged velocity ranges. Prenat Diagn 2007; 27 (13) 1251-1257 . Doi: 10.1002/pd.1868
• 15 Mari G, Deter RL, Carpenter RL. , et al; Collaborative Group for Doppler Assessment of the Blood Velocity in Anemic Fetuses. Noninvasive diagnosis by Doppler ultrasonography of fetal anemia due to maternal red-cell alloimmunization. N Engl J Med 2000; 342 (01) 9-14 . Doi: 10.1056/NEJM200001063420102
• 16 Baschat AA, Gembruch U. The cerebroplacental Doppler ratio revisited. Ultrasound Obstet Gynecol 2003; 21 (02) 124-127 . Doi: 10.1002/uog.20
• 17 Gordijn SJ, Beune IM, Thilaganathan B. , et al. Consensus definition of fetal growth restriction: a Delphi procedure. Ultrasound Obstet Gynecol 2016; 48 (03) 333-339 . Doi: 10.1002/uog.15884
• 18 Alexander GR, Himes JH, Kaufman RB, Mor J, Kogan M. A United States national reference for fetal growth. Obstet Gynecol 1996; 87 (02) 163-168 . Doi: 10.1016/0029-7844(95)00386-X
• 19 Temming LA, Dicke JM, Stout MJ. , et al. Early second-trimester fetal growth restriction and adverse perinatal outcomes. Obstet Gynecol 2017; 130 (04) 865-869 . Doi: 10.1097/AOG.0000000000002209
• 20 Unterscheider J, O'Donoghue K, Daly S. , et al. Fetal growth restriction and the risk of perinatal mortality-case studies from the multicentre PORTO study. BMC Pregnancy Childbirth 2014; 14: 63 . Doi: 10.1186/1471-2393-14-63
• 21 Lees C, Marlow N, Arabin B. , et al; TRUFFLE Group. 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 2013; 42 (04) 400-408 . Doi: 10.1002/uog.13190
• 22 Kabiri D, Romero R, Gudicha DW. , et al. Prediction of adverse perinatal outcomes by fetal biometry: a comparison of customized and population-based standards. Ultrasound Obstet Gynecol 2019; ••• DOI: 10.1002/uog.20299.
• 23 Figueras F, Savchev S, Triunfo S, Crovetto F, Gratacos E. An integrated model with classification criteria to predict small-for-gestational-age fetuses at risk of adverse perinatal outcome. Ultrasound Obstet Gynecol 2015; 45 (03) 279-285 . Doi: 10.1002/uog.14714
• 24 Figueras F, Gratacós E. Update on the diagnosis and classification of fetal growth restriction and proposal of a stage-based management protocol. Fetal Diagn Ther 2014; 36 (02) 86-98 . Doi: 10.1159/000357592
• 25 Fernandez-Rodriguez B, de Alba C, Villalain C, Pallás CR, Galindo A, Herraiz I. Obstetric and pediatric growth charts for the detection of fetal growth restriction and neonatal adverse outcomes in preterm newborns before 34 weeks of gestation. J Matern Fetal Neonatal Med 2019; •••: 1-8 . Doi: 10.1080/14767058.2019.1626368
• 26 Eixarch E, Meler E, Iraola A. , et al. Neurodevelopmental outcome in 2-year-old infants who were small-for-gestational age term fetuses with cerebral blood flow redistribution. Ultrasound Obstet Gynecol 2008; 32 (07) 894-899 . Doi: 10.1002/uog.6249
• 27 Hershkovitz R, Kingdom JC, Geary M, Rodeck CH. Fetal cerebral blood flow redistribution in late gestation: identification of compromise in small fetuses with normal umbilical artery Doppler. Ultrasound Obstet Gynecol 2000; 15 (03) 209-212 . Doi: 10.1046/j.1469-0705.2000.00079.x
• 28 Marsál K. Obstetric management of intrauterine growth restriction. Best Pract Res Clin Obstet Gynaecol 2009; 23 (06) 857-870 . Doi: 10.1016/j.bpobgyn.2009.08.011