Risk and Causes of Early Mortality among Extremely Preterm Infants Born Small for Gestational Age

Abstract

Objective

Extreme preterm (EPT) delivery, occurring before 28 weeks of gestation, carries high morbidity and mortality risks. Small for gestational age (SGA) infants, approximately 8 to 20% of EPT neonates, face increased risks. Mortality risk varies with gestational age and birth weight, with mixed reports on specific morbidities. This study aims to determine mortality rates and common causes of death among EPT SGA infants.

Study Design

The study used data from the CDC National Vital Statistics System, covering births and deaths from 2016 to 2021, with follow-up through 2022. It included infants born between 22 and 27 weeks gestation who were admitted to the neonatal intensive care unit. The outcome was all-cause in-hospital mortality within 30 days of birth, with causes of mortality classified based on the International Classification of Diseases, 10th revision codes. SGA was the primary independent variable.

Results

Based on a sample of n = 96,134 infants, we estimated 13% were born SGA and 30-day mortality rates were higher among SGA compared with non-SGA infants (31 vs. 13%). On multivariable analysis, SGA infants had higher 30-day mortality than non-SGA (odds ratio: 3.82; confidence interval 95% [CI]: 3.64, 4.01; p < 0.001), and were more likely to have death ascribed to complications of short gestation rather than other causes of death (relative risk ratio: 1.42; 95% CI: 1.27, 1.59; p < 0.001).

Conclusion

SGA infants receiving intensive care have a high mortality risk, especially due to complications of short gestation and low birth weight complications.

Key Points

• EPT infants face high mortality risk.

• Mortality risk is increased for infants born SGA.

• Mortality in SGA EPT infants is frequently attributed to complications of prematurity and small size.

Keywords

extreme prematurity - small for gestational age - causes of death - National Vital Statistics system

Publication History

Received: 09 September 2024

Accepted: 04 February 2025

Accepted Manuscript online:
05 February 2025

Article published online:
06 March 2025

• References

• 1 Taylor GL, O'Shea TM. Extreme prematurity: risk and resiliency. Curr Probl Pediatr Adolesc Health Care 2022; 52 (02) 101132
• 2 Stoll BJ, Hansen NI, Bell EF. et al. Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Trends in care practices, morbidity, and mortality of extremely preterm neonates, 1993-2012. JAMA 2015; 314 (10) 1039-1051
• 3 Katz J, Lee AC, Kozuki N, Black RE. Mortality risk among term and preterm small for gestational age infants. Nestle Nutr Inst Workshop Ser 2015; 81: 29-35
• 4 Baer RJ, Rogers EE, Partridge JC. et al. Population-based risks of mortality and preterm morbidity by gestational age and birth weight. J Perinatol 2016; 36 (11) 1008-1013
• 5 Boghossian NS, Geraci M, Edwards EM, Horbar JD. Morbidity and mortality in small for gestational age infants at 22 to 29 weeks' gestation. Pediatrics 2018; 141 (02) e20172533
• 6 Giapros V, Drougia A, Krallis N, Theocharis P, Andronikou S. Morbidity and mortality patterns in small-for-gestational age infants born preterm. J Matern Fetal Neonatal Med 2012; 25 (02) 153-157
• 7 Grisaru-Granovsky S, Reichman B, Lerner-Geva L. et al. Israel Neonatal Network. Mortality and morbidity in preterm small-for-gestational-age infants: a population-based study. Am J Obstet Gynecol 2012; 206 (02) 150.e1-150.e7
• 8 Westby Wold SH, Sommerfelt K, Reigstad H. et al. Neonatal mortality and morbidity in extremely preterm small for gestational age infants: a population based study. Arch Dis Child Fetal Neonatal Ed 2009; 94 (05) F363-F367
• 9 Ray JG, Park AL, Fell DB. Mortality in infants affected by preterm birth and severe small-for-gestational age birth weight. Pediatrics 2017; 140 (06) e20171881
• 10 Mendez-Figueroa H, Truong VT, Pedroza C, Chauhan SP. Morbidity and mortality in small-for-gestational-age infants: a secondary analysis of nine MFMU network studies. Am J Perinatol 2017; 34 (04) 323-332
• 11 Tsai LY, Chen YL, Tsou KI, Mu SC. Taiwan Premature Infant Developmental Collaborative Study Group. The impact of small-for-gestational-age on neonatal outcome among very-low-birth-weight infants. Pediatr Neonatol 2015; 56 (02) 101-107
• 12 Suenaga H, Nakanishi H, Uchiyama A, Kusuda S. Neonatal research network of Japan. Small for gestational age affects outcomes on singletons and inborn births in extremely preterm infants: a Japanese cohort study. Am J Perinatol 2024; 41 (01) 780-787
• 13 Charles E, Hunt KA, Harris C, Hickey A, Greenough A. Small for gestational age and extremely low birth weight infant outcomes. J Perinat Med 2019; 47 (02) 247-251
• 14 National Center for Health Statistics. National Vital Statistics System. Accessed December 17, 2024 at: https://www.cdc.gov/nchs/nvss/index.htm
• 15 Fenton TR, Kim JH. A systematic review and meta-analysis to revise the Fenton growth chart for preterm infants. BMC Pediatr 2013; 13: 59
• 16 Palatnik A, De Cicco S, Zhang L, Simpson P, Hibbard J, Egede LE. The association between advanced maternal age and diagnosis of small for gestational age. Am J Perinatol 2020; 37 (01) 37-43
• 17 Venkatesan T, Rees P, Gardiner J. et al. National trends in preterm infant mortality in the United States by race and socioeconomic status, 1995-2020. JAMA Pediatr 2023; 177 (10) 1085-1095
• 18 Jensen EA, Foglia EE, Dysart KC. et al. Adverse effects of small for gestational age differ by gestational week among very preterm infants. Arch Dis Child Fetal Neonatal Ed 2019; 104 (02) F192-F198
• 19 McGoldrick E, Stewart F, Parker R, Dalziel SR. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev 2020; 12 (12) CD004454
• 20 Crane J, Armson A, Brunner M. et al. Antenatal corticosteroid therapy for fetal maturation. Journal of obstetrics and gynaecology. JOGC 2003; 25 (01) 45-52
• 21 Arias E, Heron M, Hakes J. National Center for Health Statistics, US Census Bureau. The validity of race and hispanic-origin reporting on death certificates in the United States: an update. Vital Health Stat 2 2016; 1 (172) 1-21
• 22 Catalano A, Davis NL, Petersen EE. et al. Pregnant? Validity of the pregnancy checkbox on death certificates in four states, and characteristics associated with pregnancy checkbox errors. Am J Obstet Gynecol 2020; 222 (03) 269.e1-269.e8
• 23 Edwards EM, Ehret DEY, Soll RF, Horbar JD. Survival of infants born at 22 to 25 weeks' gestation receiving care in the NICU: 2020-2022. Pediatrics 2024; 154 (04) e2024065963