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Published on: November 20, 2015
Risk factors for periventricular white matter injury in very low birthweight neonates
Michael E Tsimis1, Clark T Johnson1, Radhika S Raghunathan2
1Department of Gynecology and Obstetrics, Division of Maternal-Fetal Medicine, Johns Hopkins University School of Medicine, Baltimore, MD.
Insights
Neonatal cerebrospinal fluid (CSF) infection is a stronger risk factor for periventricular white matter injury (PWMI) than fetal metabolic acidosis. Preventing CSF infections may significantly reduce PWMI, a precursor to cerebral palsy.
Area of Science:
- Neonatal neurology
- Perinatal medicine
- Neurodevelopmental disorders
Background:
- Periventricular white matter injury (PWMI) is a common cause of neurologic impairment and cerebral palsy in preterm neonates.
- PWMI pathogenesis involves damage to premyelinating oligodendrocytes due to free radicals, cytokine toxicity, and excitatory neurotransmitters.
- The immature cerebral vasculature of preterm infants is susceptible to ischemia, particularly in border zones and during hypotensive events.
Purpose of the Study:
- To determine the relative risk (RR) of fetal metabolic acidosis and perinatal infection in the development of PWMI.
- To investigate these risks specifically in very low birthweight (VLBW) neonates (<1500 g).
Main Methods:
- A cohort study included 374 VLBW neonates admitted between April 2009 and December 2014.
- Neonates were compared based on the presence or absence of PWMI identified by head ultrasound at 6 weeks.
- Generalized linear modeling was used to adjust for significant variables identified in bivariate analysis.
Main Results:
- Of 374 VLBW neonates, 35 (9.4%) developed PWMI.
- Neonates with PWMI had significantly lower gestational age and birthweight compared to those without.
- Fetal metabolic acidosis showed an RR of 2.59 (P = .02) and neonatal cerebrospinal fluid (CSF) infection showed an RR of 4.94 (P < .001) for association with PWMI.
Conclusions:
- Neonatal CSF infection is a more significant risk factor for PWMI than metabolic acidosis at birth.
- Reducing the incidence of CSF infections could have a greater impact on preventing PWMI.
- Preventing PWMI is crucial as it is a precursor to cerebral palsy.
Background:
The development of periventricular white matter injury (PWMI) in the preterm neonate is the most common insult portending neurologic impairment and is linked with the later development of cerebral palsy. The pathogenesis of PWMI targets premyelinating oligodendrocytes of the periventricular region secondary to free radicals, cytokine toxicity, and excitatory neurotransmitters. The primitive nature of the vasculature in the developing fetal cortex lends to its predilection to PWMI and cerebral ischemia with less arterial anastomoses at arterial border zones and failure to compensate for global hypotension, termed the "pressure-passive" circulation.
Objective:
Our objective is to determine the relative risk (RR) of fetal metabolic acidosis and perinatal infection in the development of PWMI in very low birthweight (VLBW) (<1500 g) neonates.
Study Design:
This is a cohort study of all VLBW neonates admitted to our neonatal intensive care unit from April 2009 through December 2014, comparing those who developed PWMI on neonatal head ultrasound at 6 weeks of life to those who did not. Neonates with chromosomal or major congenital abnormalities were excluded. Generalized linear modeling, adjusting for variables significantly different on bivariate analysis, was conducted.
Results:
During this 5-year and 8-month period there were 374 VLBW neonates admitted; 35 (9.4%) had PWMI. VLBW neonates without PWMI were significantly more likely to have intrauterine growth restriction (2.9% PWMI, 21.5% no PWMI; P = .006), while those neonates with PWMI had a significantly lower gestational age (26.3 ± 2.2 vs 28.0 ± 2.5 weeks; P < .001) and birthweight (868 ± 237 vs 993 ± 276 g; P = .009). There was no significant difference in umbilical arterial pH (7.25 ± 0.15 vs 7.27 ± 0.09; P = .34), base deficit (4.6 ± 6.0 vs 3.4 ± 3.3 mmol/L; P = .11), or pH <7.0 or base deficit >12 mmol/L at birth (10.7% vs 3.2%; P = .09). On bivariate analysis neonates with PWMI had a significant increase in positive cerebrospinal fluid (CSF) cultures (22.9% vs 1.5%; P < .001). The initial lumbar puncture was performed at a similar day of life, and neonates with PWMI had significantly elevated CSF white blood cell counts (5%, 50%, and 95%; 16, 175, and 709/mm(3); 1, 3, and 27/mm(3); P = .008). Generalized linear modeling, adjusted for gestational age and the presence of intrauterine growth restriction, showed that fetal metabolic acidosis had RR 2.59 (95% confidence interval, 1.14-5.92; P = .02) and neonatal CSF infection had RR 4.94 (95% confidence interval, 2.4-10.3; P < .001) for association with PWMI.
Conclusion:
The RR of neonatal CSF infection being associated with PWMI was 2-fold greater than metabolic acidosis at the time of birth. Decreasing the incidence of CSF infections would have a greater impact on preventing PWMI, a precursor of cerebral palsy.
