ABSTRACT
This study tests the hypothesis that histologic placental lesions were significantly
related to incidence of early or late germinal matrix/intraventricular hemorrhage
(GM/IVH) in infants of less than 32 weeks' gestation independent of maternal or neonatal
factors. Maternal and neonatal charts of 406 singleton liveborn nonanomalous infants
born at less than 32 weeks'gestation were studied retrospectively for principal indication
for delivery, delivery mode, timing of antenatal steroid treatment, diagnosis of labor
and augmentation, tocolysis, fetal presentation, and umbilical arterial and venous
blood gas values. Extracted from neonatal charts were gestational age, growth measurements,
initial hematocrit and white blood cell count, administration of surfactant, and in
the first 3 days of life, the use of pressor agents and volume expansion, lowest blood
pressure, and data pertinent to respiratory function. Placental histologic examination
was reviewed for various lesions, including histologic acute inflammation (graded
on a scale of 0 to 4). GM/IVH (grades 1 to 4) diagnosed ultrasonographically less
than 72 hours after birth was “early.” GM/IVH diagnosed after 72 hours of life was
defined as “late.” Of the 406 patients, 44 (10.8%) had early GM/IVH; 21 (4.9%) had
late GM/IVH. Stepwise logistic regression selected five factors independently related
to increased early GM/IVH risk: Histologic acute inflammation (p <0.002); gestational
age in days (p = 0.053); antenatal steroid treatment less than 48 hours before birth
(p <0.035); volume expansion in the neonate (p <0.030), and magnesium sulfate tocolysis
(p <0.025). Stepwise regression analysis considering the grade of GM/IVH changed the
order of variables, with gestational age and use of pressor therapy being more strongly
related to higher grade of GM/IVH than amnion inflammation. Delivery mode, presentation,
principal indication for delivery, presence/augmentation of labor, mean biophysical
profile scores, mean umbilical arterial and venous blood gas values, and surfactant
therapy were not related to early GM/IVH in univariate or multivariate analyses. Neonatal
factors associated (p <0.05) with amnion inflammation were volume expansion at delivery
and in the first 3 days of life, low mean systolic pressure, low mean oxygen pressure,
low initial hematocrit and cord pH, and increased initial WBC and toxic granulations
of neutrophils. Only gestational age, and no maternal or placental factors, was significantly
related to late GM/IVH. Infants who have placentas with acute amnion inflammation
and receive volume expansion, born to mothers who receive less than 48 hour's exposure
to antenatal steroids and are selected to receive magnesium sulfate tocolysis, have
increased incidence of early but not late GM/IVH. Amnion inflammation is significantly
related to early GM/IVH and with early neonatal abnormalities in oxygenation, perfusion,
and effective blood volume. Intra-amniotic infection leads to advanced preterm labor,
which is unresponsive to tocolysis because of the inflammation. Intra-amniotic inflammation
may sensitize the fetus to postpartum stresses or initiate early GM/IVH in utero via
cytokine effects on cardiovascular instability.
Keywords
Intraventricular hemorrhage - prematurity - chorioamnionitis - placental pathology
- tocolysis - antenatal steroids
