Am J Perinatol 2024; 41(11): 1544-1553
DOI: 10.1055/a-2183-5155
Original Article

Impact of Size for Gestational Age on Multivariate Analysis of Factors Associated with Necrotizing Enterocolitis in Preterm Infants: Retrospective Cohort Study

Mariela Sánchez-Rosado
1   Division of Neonatal-Perinatal Medicine, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas
2   Division of Neonatology, Joe DiMaggio Children's Hospital, Hollywood, Florida
,
Jordan D. Reis
1   Division of Neonatal-Perinatal Medicine, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas
3   Department of Pediatrics, Baylor Scott and White, Dallas, Texas
,
Mambarambath A. Jaleel
1   Division of Neonatal-Perinatal Medicine, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas
,
Kimberly Clipp
4   Department of Pediatrics, Parkland Health and Hospital System, Dallas, Texas
,
Kate L.M. Mangona
5   Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Texas
,
L Steven Brown
4   Department of Pediatrics, Parkland Health and Hospital System, Dallas, Texas
,
David B. Nelson
6   Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, and Parkland Health, Dallas, Texas
,
Myra H. Wyckoff
1   Division of Neonatal-Perinatal Medicine, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas
,
Diksha Verma
7   University of Texas Southwestern Medical Center, Dallas, Texas
8   Department of Anesthesiology, University of Texas Southwestern Medical Center, Dallas, Texas
,
Isabelle Kiefaber
7   University of Texas Southwestern Medical Center, Dallas, Texas
,
Cheryl S. Lair
4   Department of Pediatrics, Parkland Health and Hospital System, Dallas, Texas
,
Sujir P. Nayak
1   Division of Neonatal-Perinatal Medicine, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas
,
Patti J. Burchfield
1   Division of Neonatal-Perinatal Medicine, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas
,
Anita Thomas
1   Division of Neonatal-Perinatal Medicine, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas
,
1   Division of Neonatal-Perinatal Medicine, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas
› Author Affiliations
Funding None.

Abstract

Objective Necrotizing enterocolitis (NEC) primarily affects preterm, especially small for gestational age (SGA), infants. This study was designed to (1) describe frequency and timing of NEC in SGA versus non-SGA infants and (2) assess whether NEC is independently associated with the severity of intrauterine growth failure.

Study Design Retrospective cohort study of infants without severe congenital malformations born <33 weeks' gestational age (GA) carried out from 2009 to 2021. The frequency and time of NEC were compared between SGA and non-SGA infants. Multivariate logistic regression was used to assess whether NEC was independently associated with intrauterine growth restriction. Severe growth restriction was defined as birth weight Z-score <  −2.

Results Among 2,940 infants, the frequency of NEC was higher in SGA than in non-SGA infants (25/268 [9.3%] vs. 110/2,672 [4.1%], respectively, p < 0.001). NEC developed 2 weeks later in SGA than non-SGA infants. In multivariate analysis, the adjusted odds of NEC increased with extreme prematurity (<28 weeks' GA) and with severe but not moderate growth restriction. The adjusted odds of NEC increased with urinary tract infection or sepsis within a week prior to NEC, were lower in infants fed their mother's own milk until discharge, and did not change over five epochs. NEC was independently associated with antenatal steroid (ANS) exposure in infants with birth weight (BW) Z-score < 0.

Conclusion NEC was more frequent in SGA than in non-SGA infants and developed 2 weeks later in SGA infants. NEC was independently associated with severe intrauterine growth failure and with ANS exposure in infants with BW Z-score < 0.

Key Points

  • We studied 2,940 infants <33 weeks' GA.

  • We assessed NEC.

  • NEC was more frequent in SGA infants.

  • NEC occurred 2 weeks later in SGA infants.

  • NEC was associated with severe growth restriction.

Data Availability

The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.


Note

M.S-R., J.D.R., D.V., I.K., P.B., L.S.B, L.P.B.: necrotizing enterocolitis in small for SGA versus appropriate for GA (AGA) infants. Poster presentation, PAS, Denver, CO; April 25, 2022.


Authors' Contributions

M.S-R. conceptualized and designed the study, collected and reviewed data from the medical records, and wrote the first draft of the manuscript. L.P.B. conceptualized and designed the study, collected and reviewed data from the medical records. L.P.B. and L.S.B. conducted the statistical analyses. P.B., A.T., I.K., and D.V. extracted data from the EHR. M.S-R., J.D.R., M.A.J., L.P.B., K.C., and C.L. were part of the QI on NEC. All authors participated in the interpretation of the data, critically reviewed the revisions, and approved the final manuscript as submitted.




Publication History

Received: 10 March 2023

Accepted: 27 September 2023

Accepted Manuscript online:
28 September 2023

Article published online:
27 October 2023

© 2023. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 
  • References

  • 1 Neu J, Walker WA. Necrotizing enterocolitis. N Engl J Med 2011; 364 (03) 255-264
  • 2 Andrews RE, Coe KL. Clinical presentation and multifactorial pathogenesis of necrotizing enterocolitis in the preterm infant. Adv Neonatal Care 2021; 21 (05) 349-355
  • 3 Cho H, Lee EH, Lee KS, Heo JS. Machine learning-based risk factor analysis of necrotizing enterocolitis in very low birth weight infants. Sci Rep 2022; 12 (01) 21407
  • 4 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
  • 5 Lamireau N, Greiner E, Hascoët JM. Risk factors associated with necrotizing enterocolitis in preterm infants: a case-control study. Arch Pediatr 2023; 30 (07) 477-482
  • 6 Gitau K, Ochieng R, Limbe M, Kathomi C, Orwa J. The incidence and modifiable risk factors for necrotizing enterocolitis in preterm infants: a retrospective cohort study. J Matern Fetal Neonatal Med 2023; 36 (02) 2253351
  • 7 Gephart SM, Fleiner M, Msowoya A, Rothers J. Prediction of GutCheckNEC and its relation to severity of illness and measures of deterioration in necrotizing enterocolitis. Adv Neonatal Care 2023; 23 (04) 377-386
  • 8 Ree IM, Smits-Wintjens VE, Rijntjes-Jacobs EG. et al. Necrotizing enterocolitis in small-for-gestational-age neonates: a matched case-control study. Neonatology 2014; 105 (01) 74-78
  • 9 Huang Y, Zhang L, Sun H. et al. Neonatal outcome of small for gestational age infants born at 26–33 weeks' gestation in Chinese neonatal intensive care units. Transl Pediatr 2021; 10 (04) 754-764
  • 10 Anne RP, Vardhelli V, Oleti TP. et al. Propensity-matched comparison of very preterm small- and appropriate-for-gestational-age neonates. Indian J Pediatr 2022; 89 (01) 59-66
  • 11 Motta C, Scott W, Mahony L. et al. The association of congenital heart disease with necrotizing enterocolitis in preterm infants: a birth cohort study. J Perinatol 2015; 35 (11) 949-953
  • 12 Riskin A, Riskin-Mashiah S, Itzchaki O. et al; Israel Neonatal Network. Mode of delivery and necrotizing enterocolitis in very preterm very-low-birth-weight infants. J Matern Fetal Neonatal Med 2021; 34 (23) 3933-3939
  • 13 Dogra S, Mukhopadhyay K, Narang A. Feed intolerance and necrotizing enterocolitis in preterm small-for-gestational age neonates with normal umbilical artery Doppler flow. J Trop Pediatr 2012; 58 (06) 513-516
  • 14 Kliegman RM, Walsh MC. Neonatal necrotizing enterocolitis: pathogenesis, classification, and spectrum of illness. Curr Probl Pediatr 1987; 17 (04) 213-288
  • 15 Brion LP, Rosenfeld CR, Heyne R. et al. Adjustable feedings plus accurate serial length measurements decrease weight-length disproportion in very preterm infants. J Perinatol 2019; 39 (12) 1694 (Correction: J Perinatol 2019 39(8):1131–1139)
  • 16 Brion LP, Rosenfeld CR, Heyne R. et al. Optimizing individual nutrition in preterm very low birth weight infants: double-blinded randomized controlled trial. J Perinatol 2020; 40 (04) 655-665
  • 17 Sanchez-Rosado M, Lair CS, Edwards A. et al. Growth after implementing a donor breast milk program in neonates <33 weeks gestational age or birthweight <1500 grams: Retrospective cohort study. J Perinatol 2023; 43 (05) 608-615
  • 18 Sanchez AM, Jimenez JM, Manroe BL, Rosenfeld CR, Tyson TE. Systems approach to the evaluation of maternal and neonatal care. Paper presented at: Proceedings of 12th Hawaii International Conference on System Sciences. Selected Papers in Medical Information Processing. January 4–5 1979 III. 140-151
  • 19 Kaiser JR, Tilford JM, Simpson PM, Salhab WA, Rosenfeld CR. Hospital survival of very-low-birth-weight neonates from 1977 to 2000. J Perinatol 2004; 24 (06) 343-350
  • 20 Nelson DB, McIntire DD, Leveno KJ. Reply. Am J Obstet Gynecol 2018; 218 (03) 360-362
  • 21 Leveno KJ, McIntire DD, Bloom SL, Sibley MR, Anderson RJ. Decreased preterm births in an inner-city public hospital. Obstet Gynecol 2009; 113 (03) 578-584
  • 22 Olsen IE, Groveman SA, Lawson ML, Clark RH, Zemel BS. New intrauterine growth curves based on United States data. Pediatrics 2010; 125 (02) e214-e224
  • 23 Olsen IE, Lawson ML, Ferguson AN. et al. BMI curves for preterm infants. Pediatrics 2015; 135 (03) e572-e581
  • 24 Jobe AH, Bancalari E. Bronchopulmonary dysplasia. Am J Respir Crit Care Med 2001; 163 (07) 1723-1729
  • 25 Peduzzi P, Concato J, Kemper E, Holford TR, Feinstein AR. A simulation study of the number of events per variable in logistic regression analysis. J Clin Epidemiol 1996; 49 (12) 1373-1379
  • 26 Rocha de Moura MD, Margotto PR, Nascimento Costa K, Carvalho Garbi Novaes MR. Hypertension induced by pregnancy and neonatal outcome: Results from a retrospective cohort study in preterm under 34 weeks. PLoS ONE 2021; 16 (08) e0255783
  • 27 Avorgbedor F, Gondwe KW, Zou B, Conklin JL, Yeo S. A systematic review on outcomes of preterm small for gestational infants born to women with hypertensive disorders in pregnancy. J Perinat Neonatal Nurs 2021; 35 (04) E58-E68
  • 28 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
  • 29 Churchill D, Duley L, Thornton JG, Moussa M, Ali HS, Walker KF. Interventionist versus expectant care for severe pre-eclampsia between 24 and 34 weeks' gestation. Cochrane Database Syst Rev 2018; 10 (10) CD003106
  • 30 Blankenship SA, Brown KE, Simon LE, Stout MJ, Tuuli MG. Antenatal corticosteroids in preterm small-for-gestational age infants: a systematic review and meta-analysis. Am J Obstet Gynecol MFM 2020; 2 (04) 100215
  • 31 Riskin-Mashiah S, Riskin A, Bader D. et al; Israel Neonatal Network. Antenatal corticosteroid treatment in singleton, small-for-gestational-age infants born at 24-31 weeks' gestation: a population-based study. BJOG 2016; 123 (11) 1779-1786
  • 32 Weydig HM, Rosenfeld CR, Jaleel MA, Burchfield PJ, Frost MS, Brion LP. Association of antenatal steroids with neonatal mortality and morbidity in preterm infants born to mothers with diabetes mellitus and hypertension. J Perinatol 2021; 41 (07) 1660-1668
  • 33 Yum SK, Lee JH. Dose completion of antenatal corticosteroids and neonatal outcomes in non-small-for-gestational age or small-for-gestational age very-low-birthweight infants: a Korean population-based cohort study. Pediatr Neonatol 2022; 63 (02) 165-171
  • 34 Ražem K, Tul N, Blickstein I, Trojner Bregar A. The effect of antenatal corticosteroids on small-for-gestational age preterm neonates. J Matern Fetal Neonatal Med 2022; 35 (02) 362-365
  • 35 Pineda LC, Hornik CP, Seed PC. et al. Association between positive urine cultures and necrotizing enterocolitis in a large cohort of hospitalized infants. Early Hum Dev 2015; 91 (10) 583-586
  • 36 Boquien CY. Human milk: an ideal food for nutrition of preterm newborn. Front Pediatr 2018; 6: 295
  • 37 Parker MG, Stellwagen LM, Noble L, Kim JH, Poindexter BB, Puopolo KM. SECTION ON BREASTFEEDING, COMMITTEE ON NUTRITION, COMMITTEE ON FETUS AND NEWBORN. Promoting human milk and breastfeeding for the very low birth weight infant. Pediatrics 2021; 148 (05) e2021054272
  • 38 Leviton A, Dammann O, Engelke S. et al; ELGAN study investigators. The clustering of disorders in infants born before the 28th week of gestation. Acta Paediatr 2010; 99 (12) 1795-1800