Neurodevelopment of Extremely Preterm Infants who had Necrotizing Enterocolitis with or without Late Bacteremia

doi:10.1016/j.jpeds.2010.05.042

The Journal of Pediatrics

Volume 157, Issue 5, November 2010, Pages 751-756.e1

https://doi.org/10.1016/j.jpeds.2010.05.042 Get rights and content

Objective

To evaluate neurodevelopment after necrotizing enterocolitis (NEC) and late bacteremia, alone and together.

Study design

Sample included 1155 infants born at 23 to 27 weeks' gestation. NEC was classified by the modified Bell's staging criteria and grouped as medical NEC or surgical NEC. Late bacteremia was defined as a positive blood culture result after the first postnatal week. Neurodevelopment was assessed at 24 months corrected age. Multivariable models estimated the risk of developmental dysfunction and microcephaly associated with medical or surgical NEC with and without late bacteremia.

Results

Children who had surgical NEC unaccompanied by late bacteremia were at increased risk of psychomotor developmental indexes <70 (OR = 2.7 [1.2, 6.4]), and children who had both surgical NEC and late bacteremia were at increased risk of diparetic cerebral palsy (OR = 8.4 [1.9, 39]) and microcephaly (OR = 9.3 [2.2, 40]). In contrast, children who had medical NEC with or without late bacteremia were not at increased risk of any developmental dysfunction.

Conclusion

The risk of neurodevelopmental dysfunction and microcephaly is increased in children who had surgical NEC, especially if they also had late bacteremia. These observations support the hypothesis that bowel injury might initiate systemic inflammation potentially affecting the developing brain.

Section snippets

Methods

The sample for this analysis is a subset of the 1506 infants enrolled in the ELGAN Study, a prospective cohort study designed to identify characteristics and exposures that increase the risk of structural and functional neurologic disorders in preterm infants.¹² During the years 2002–2004, women delivering between 23 and 27 6/7 weeks of gestation at 1 of 14 participating institutions in 11 cities in 5 states were enrolled in the study. The enrollment and consent processes were approved by the

Results

Of the 1155 eligible children, 59 (5%) had medical NEC, 42 (4%) had surgical NEC, 70 (6%) had culture-proven early bacteremia, and 279 (24%) had culture-proven late bacteremia. The incidence of early bacteremia was not different in infants with and without NEC. In contrast, the incidence of late bacteremia was higher in infants with NEC than in those without NEC (34% vs 23%).

Table I documents the percent of infants in each diagnostic stratum (column headings) who were given the

Discussion

In this large prospective cohort of extremely preterm infants, infants who had development of medical NEC were not at statistically significantly increased risk of either any of the developmental disorders we assessed or of microcephaly. On the other hand, children who had surgical NEC without accompanying late bacteremia were at an increased risk of a PDI <70. Children who had development of surgical NEC and had culture-proven late bacteremia were at prominently increased risk of diparetic

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Neurodevelopmental outcome of infants who develop necrotizing enterocolitis: The gut-brain axis
2023, Seminars in Perinatology
Necrotizing enterocolitis (NEC) poses a significant risk for neurodevelopmental impairment in extremely preterm infants. The gut microbiota shapes the development of the gut, immune system, and the brain; and dysbiosis drive neonatal morbidities including NEC. In this chapter, we delineate a gut-brain axis linking gut microbiota to the adverse neurological outcomes in NEC patients. We propose that in NEC, immaturity of the microbiome along with aberrant gut microbiota-driven immaturity of the gut barrier and immune system can lead to effects including systemic inflammation and circulating microbial mediators. This nexus of gut microbiota-driven systemic effects further interacts with a likewise underdeveloped blood-brain barrier to regulate neuroinflammation and neurodevelopment. Targeting deviant gut-brain axis signaling presents an opportunity to improve the neurodevelopmental outcomes of NEC patients.
Growth During Infancy After Extremely Preterm Birth: Associations with Later Neurodevelopmental and Health Outcomes
2023, Journal of Pediatrics
To evaluate associations between changes in weight, length, and weight/length ratio during infancy and outcomes later in life among individuals born extremely preterm.
Among participants in the Extremely Low Gestational Age Newborn (ELGAN) study, we measured weight and length at discharge from the neonatal intensive care unit (NICU) and at age 2 years and evaluated neurocognitive, psychiatric, and health outcomes at age 10 years and 15 years. Using multivariable logistic regression, we estimated associations between gains in weight, length, and weight/length ratio z-scores between discharge and 2 years and outcomes at 10 and 15 years. High gain was defined as the top quintile of change; low gain, as the bottom quintile of change.
High gains in weight and weight/length were associated with greater odds of obesity at 10 years, but not at 15 years. These associations were found only for females. High gain in length z-score was associated with lower odds of obesity at 15 years. The only association found between high gains in growth measures and more favorable neurocognitive or psychiatric outcomes was between high gain in weight/length and lower odds of cognitive impairment at age 10 years.
During the 2 years after NICU discharge, females born extremely preterm with high gains in weight/length or weight have greater odds of obesity at 10 years, but not at 15 years. Infants with high growth gains in the 2 years after NICU discharge have neurocognitive and psychiatric outcomes in middle childhood and adolescence similar to those of infants with lower gains in weight and weight/length.
Functional status of brainstem auditory pathway in babies born below 30 week gestation with necrotizing enterocolitis
2022, Brain and Development
Recent studies showed that neonatal necrotizing enterocolitis (NEC) adversely affects the brainstem auditory pathway in babies born at 30–40 week gestation. We compared the functional status of the pathway between babies born below 30 week gestation with NEC and those without NEC for any differences to understand whether NEC also affects the pathway in babies born at a smaller gestation.
Brainstem auditory evoked response was studied at term in NEC babies born below 30 week gestation. The data obtained were compared with age-matched non-NEC babies for any abnormalities, and then compared with previously reported NEC babies born at 30–34 week gestation for any differences.
Although the latencies of waves I and III did not differ significantly between NEC and non-NEC babies, wave V latency in NEC babies was longer than in non-NEC babies at all click rates used. In particular, I–V interpeak interval, reflecting brainstem conduction time, in NEC babies was significant longer than in non-NEC babies. Wave V amplitude and the V/I amplitude ratios in NEC babies was smaller than in non-NEC babies at some click rates. The I–V interval in our NEC babies born below 30 week gestation was longer than in previously reported NEC babies born at 30–34 week gestation at all click rates.
NEC babies born below 30 week gestation are associated with delayed brainstem conduction time. Functional status of the brainstem auditory pathway in NEC babies born below 30 week gestation is less favorable than that in those with greater gestation.
Extreme prematurity: Risk and resiliency
2022, Current Problems in Pediatric and Adolescent Health Care
Citation Excerpt :
The neonatal morbidity that has most consistently been associated with adverse neurodevelopmental outcomes is ultrasound-identified cerebral white matter injury.70,114-122 Less consistently, these adverse outcomes have been associated with severe bronchopulmonary dysplasia,123,124 necrotizing enterocolitis requiring surgery,62,125 sepsis,69,126 and severe retinopathy of prematurity.127-129 These neonatal morbidities co-occur so frequently that it is challenging to identify effects of individual factors.130
Individuals born extremely preterm (before 28 weeks of gestation) comprise only about 0.7% of births in the United States and an even lower proportion in other high resource countries. However, these individuals account for a disproportionate number of children with cerebral palsy, intellectual deficit, autism spectrum disorder, attention deficit hyperactivity disorder, and epilepsy. This review describes two large multiple center cohorts comprised of individuals born extremely preterm: the EPICURE cohort, recruited 1995 in the United Kingdom and the Republic of Ireland, and the Extremely Low Gestational Age Newborn (ELGAN), recruited 2002–2004 in five states in the United States. The primary focus of these studies has been neurodevelopmental disorders, but also of interest are growth, respiratory illness, and parent- and self-reported global health and well-being. Both of these studies indicate that among individuals born extremely preterm the risks of most neurodevelopmental disorders are increased. Early life factors that contribute to this risk include perinatal brain damage, some of which can be identified using neonatal head ultrasound, bronchopulmonary dysplasia, and neonatal systemic inflammation. Prenatal factors, particularly the family's socioeconomic position, also appear to contribute to risk. For most adverse outcomes, the risk is higher in males. Young adults born extremely preterm who have neurodevelopmental impairment, as compared to those without such impairment, rate their quality of life lower. However, young adults born extremely preterm who do not have neurodevelopmental impairments rate their quality of life as being similar to that of young adults born at term. Finally, we summarize the current state of interventions designed to improve the life course of extremely premature infants, with particular focus on efforts to prevent premature birth and on postnatal efforts to prevent adverse neurodevelopmental outcomes
Association of Infection in Neonates and Long-Term Neurodevelopmental Outcome
2021, Clinics in Perinatology
Neurodevelopmental and growth outcomes of extremely preterm infants with necrotizing enterocolitis or spontaneous intestinal perforation
2021, Journal of Pediatric Surgery
To evaluate neurodevelopment and growth in extremely preterm infants with or without necrotizing enterocolitis or spontaneous intestinal perforation.
We conducted a retrospective cohort study of infants admitted to Canadian neonatal intensive care units in 2010 to 2011. We assessed outcomes at 18 to 24 months’ corrected ages for preterm infants < 29 weeks of gestational age at birth with spontaneous intestinal perforation or non-perforated or perforated necrotizing enterocolitis, and for preterm infants with none of these gastrointestinal complications. The primary outcome was a composite of death or significant neurodevelopmental impairment at 18 to 24 months’ corrected age. We used multivariable logistic regression models to adjust for gestational age, small for gestational age, prenatal steroids, cesarean section, multiple gestations, and SNAP-II score.
Of 2,019 infants total, 39 (1.9%) had spontaneous intestinal perforation, 61 (3%) had perforated necrotizing enterocolitis, and 115 (5.7%) had non-perforated necrotizing enterocolitis. Infants with spontaneous intestinal perforation (aOR 2.11; 95% CI 1.01–4.42), necrotizing enterocolitis (aOR 2.58; 95% CI 1.81–3.68), or any bowel perforation (aOR 3.97; CI 2.43–6.48) had higher odds of death or significant neurodevelopmental impairment compared to infants with none of these bowel diseases.
Spontaneous intestinal perforation, necrotizing enterocolitis, or any bowel perforation are risk factors for death or significant neurodevelopmental impairment in extremely preterm infants.
Study type: prognosis study (cohort study: retrospective)
II

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: All authors are members of the ELGAN Study Group.

: Supported by a cooperative agreement with the National Institute of Neurological Diseases and Stroke (5U01NS040069-05) and a program project grant from the National Institute of Child Health and Human Development (NIH-P30-HD-18655). The authors declare no conflicts of interest.

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Original ArticleNeurodevelopment of Extremely Preterm Infants who had Necrotizing Enterocolitis with or without Late Bacteremia

Objective

Study design

Results

Conclusion

Section snippets

Methods

Results

Discussion

Clin Perinatol

Clin Perinatol

Early Hum Dev

Early Hum Dev

J Pediatr Surg

J Pediatr

J Pediatr

Early Hum Dev

Semin Fetal Neonatal Med

Neurodevelopmental and growth outcomes of extremely low birth weight infants after necrotizing enterocolitis

Pediatrics

Very low birth weight outcomes of the National Institute of Child health and human development neonatal research network, January 1995 through December 1996. NICHD Neonatal Research Network

Pediatrics

Necrotizing enterocolitis and neurodevelopmental outcome in extremely low birth weight infants <1000 g

J Perinatol

Growth and neurodevelopmental outcome of very low birth weight infants with necrotizing enterocolitis

Acta Paediatr

Severity of necrotizing enterocolitis: influence on outcome at 2 years of age

Pediatrics

Necrotizing enterocolitis in infants: clinical outcome and influence on growth and neurodevelopment

J Formos Med Assoc

Neurodevelopmental outcome in very low birthweight infants with necrotizing enterocolitis requiring surgery

J Paediatr Child Health

Original Article
Neurodevelopment of Extremely Preterm Infants who had Necrotizing Enterocolitis with or without Late Bacteremia