Mechanisms of injury to white matter adjacent to a large intraventricular hemorrhage in the preterm brain

Ira Adler, Dan Batton, Bradford Betz, Steven Bezinque, Kirsten Ecklund, Joseph Junewick, Roy McCauley, Cindy Miller, Joanna Seibert, Barbara Specter, Sjirk Westra, Alan Leviton

J Clin Ultrasound 2010;38:254-258.

PubMed Link

Support was found for possibility that ventricular wall does not function as an efficient barrier, allowing ventricular contents to affect WM where it causes damage. PVHI may not be only or most frequent mechanism of WM damage adjacent to a large IVH.

SNAP-II and SNAPPE-II and the risk of structural and functional brain disorders in ELGANs

Olaf Dammann, Mary Naples, Francis Bednarek, Bhavesh Shah, Karl C K Kuban, T Michael O'Shea, Nigel Paneth, Elizabeth N Allred, Alan Leviton, ELGAN Study Investigators

The ELGAN study. Neonatology 2010;97:71-82.

PubMed Link

After adjustment for GA, high SNAP-II and SNAPPE-II scores predicted IVH, mod/sev VMeg and EL lesions in cerebral WM. Only 2 highest decile for GA and a Z score >1, predicted EL lesions. Neither SNAP-II nor SNAPPE-II predicted CP. MDI and PDI scores <55 were predicted by both high SNAP-II and SNAPPE-II High SNAP-II and SNAPPE-II inconsistently predicted positive screen for ASD and small HC at 24 mos.

Microbiologic and histologic characteristics of the extremely preterm infant’s placenta predict white matter damage and later cerebral palsy. the ELGAN study

Alan Leviton, Elizabeth N Allred, Karl C K Kuban, Jonathan L Hecht, Andrew B Onderdonk, T Michael O'shea, Nigel Paneth

Pediatr Res. 2010;67:95-101

PubMed Link

Recovery of single microorganism predicts EL, whereas polymicrobial cultures & skin flora predicted VM and EL. DP CP predicted by single or multiple organisms, and skin flora. Histologic inflammation predicted VM and DP CP. Risk of VM, but not DP CP, associated with organism recovery, heightened by presence of histologic inflammation. Organism recovery not needed for placenta inflammation to predict DP CP

Inter-institutional variation in prediction of death by SNAP-II and SNAPPE-II among extremely preterm infants

Olaf Dammann, Bhavesh Shah, Mary Naples, Francis Bednarek, John Zupancic, Elizabeth N Allred, Alan Leviton, ELGAN Study Investigators

Pediatrics. 2009;124:e1001-6

PubMed Link

The rate of death before day 28 was 13, whereas overall mortality rate was 18%. SNAP-II, SNAPPE-II, and mortality rates ↓ with increasing GA. Even within GA strata, risk of death ↓ with ↓SNAP-II and SNAPPE-II values. The PPV of most SNAP-II and SNAPPE-II cutoff levels were ~30%, especially in infants with SNAP-II >/=30.

The ELGAN study of the brain and related disorders in extremely low gestational age newborns

T M O'Shea, E N Allred, O Dammann, D Hirtz, K C K Kuban, N Paneth, A Leviton, ELGAN study Investigators

Early Hum Dev. 2009;85:719-25

PubMed Link

The following are associated with ultrasongraphically detected WMD, CP, or both: preterm labor-preterm delivery, prelabor PROM, or cervical insufficiency; microorgs in placenta, including human skin microflora; placental inflammation; lower GA; greater neonatal illness severity; severe CLD; neonatal bacteremia; and NEC.

Antenatal Complications and the Risk of Neonatal Cerebral White Matter Damage and Later Cerebral Palsy in Children Born at an Extremely Low GA

Thomas F McElrath, Elizabeth N Allred, Kim A Boggess, Karl Kuban, T Michael O'Shea, Nigel Paneth, Alan Leviton, ELGAN Study Investigators

Am J Epidemiol 2009;170:819-828.

PubMed Link

Infants w/ACS had lower risks of VMeg & EL (10% vs. 23%, P < 0.001 & 7% vs. 11%, P = 0.06). Risk of VMeg ↑ w/preterm labor: OR = 2.3, 95% CI: 1.1, 4.9), PROM (OR = 3.6, 95% CI: 1.5, 8.7), and cervical insuff (OR = 2.8, 95% CI: 1.4, 5.5) compared w/ infants delivered for PE. Risk of EL lesion was ↑ w/ preterm labor (OR = 2.7, 95% CI: 1.2, 5.7) and IUGR (OR = 3.3, 95% CI: 1.2, 9.4). Doubling of DP risk w/preterm labor & PROM not sign, nor was doubling of QP and tripling of DP risk ass’ed w/ cervical insuff

Maternal antenatal complications and the risk of neonatal cerebral WMD and later CP in ELGANs

Thomas F McElrath, Elizabeth N Allred, Kim A Boggess, Karl Kuban, T Michael O'Shea, Nigel Paneth, Alan Leviton, ELGAN Study Investigators

Am J Epidemiol. 2009;170:819-28

PubMed Link

Mothers that received antenatal steroids tended to have lower risks of VM and EL (10% vs. 23%, P < 0.001 and 7% vs. 11%, P = 0.06). Risk of VM was ↑ for infants delivered because of PL (OR = 2.3, 95% CI: 1.1, 4.9), PPROM (OR = 3.6, 95% CI: 1.5, 8.7), and cervical insufficiency (OR = 2.8, 95% CI: 1.4, 5.5) compared to infants delivered because of PE. Risk of an EL was ↑ for infants with PL (OR = 2.7, 95% CI: 1.2, 5.7) and IUGR (OR = 3.3, 95% CI: 1.2, 9.4).

Fetal Growth Restriction and Chronic Lung Disease among infants born before the 28th week of gestation

Carl Bose, Linda J Van Marter, Matthew Laughon, T Michael O'Shea, Elizabeth N Allred, Padmani Karna, Richard A Ehrenkranz, Kim Boggess, Alan Leviton, Extremely Low Gestational Age Newborn Study Investigators

Pediatrics 2009;124;e450-e458

PubMed Link

Among the prenatal factors, B. Wt z scores, used as a marker of FGR, provided most information about CLD risk. Indicators of placental inflammation and infection not associated with ↑risk of CLD. W/i ~all strata of prenatal, placental, and neonatal variables, FGRs infants were at ↑CLD risk. FGR was the only maternal or prenatal characteristic that was highly predictive of CLD after adjustment for other risks.

Developmental correlates of head circumference at birth and at two years in a cohort of ELGANs

Karl C K Kuban, Elizabeth N Allred, T Michael O'Shea, Nigel Paneth, Sjirk Westra, Cindy Miller, N Paul Rosman, Alan Leviton

J Pediatr 2009;155:344-9.e1-3

PubMed Link

A total of 11% of infants in our sample had MC at 2 years. MC at 2 years, but not at birth, predicts severe motor and cognitive impairments at 2 years. A total of 71% of children with congenital MC had a normal HC at 2 years and had neurodevelopmental outcomes ~ those with nl HC at birth and 2 years. Among children with MC at 2 years, more than half had a MDI <70, and nearly a third had CP. The risks were increased if child also had cerebral WM damage on neonatal HUS.Among ELGANs, MC at 2 yrs, but not at birth, is associated with motor and cognitive impairment at age 2.

Nutritional practices and growth velocity in the first month of life in extremely premature infants

Camilia R Martin, Yolanda F Brown, Richard A Ehrenkranz, T Michael O'Shea, Elizabeth N Allred, Mandy B Belfort, Marie C McCormick, Alan Leviton, Extremely Low Gestational Age Newborns Study Investigators

Pediatrics 2009;124:649-57

PubMed Link

Protein and fat delivery ~current nutritional recommendations, whereas CBH & total energy intake delivery did not. Yet, GV of infants > current guideline of 15 g/kg per/d. Yet, we found growth restriction (ie, weight for GA < 10th centile) in 75% of infants at 28 d. Early nutrients is important determinant of postnatal growth. Extrauterine growth restriction remains high in ELGANs even when w/GV rate within current guidelines.