Neurodevelopmental outcome of premature infants after antenatal phenobarbital exposure.
OBJECTIVE
We previously demonstrated that antenatal phenobarbital does not decrease the risk of intracranial hemorrhage or early death in premature infants. The objective of the present study was to evaluate the impact of antenatal phenobarbital exposure on the neurodevelopmental outcome of premature infants born to women who were participating in the randomized clinical trial of antenatal phenobarbital exposure.


METHODS
Infants were evaluated at 18 to 22 months corrected age with a standard neurologic examination and the Bayley scales of infant development measuring the mental developmental index and the psychomotor developmental index.


RESULTS
Of the 578 infants <34 weeks of gestational age who were born to women who were enrolled in the primary study, 7 infants died after discharge from the neonatal intensive care unit, and 135 infants were lost to follow-up. Infants who were lost to follow-up had a higher mean birth weight and gestational age and a lower maternal education, but the rates of intracranial hemorrhage were comparable to those infants who were evaluated. Among the infants who were evaluated (n = 436; 76%), the mean birth weight and gestational age, maternal education, and frequency and distribution of intracranial hemorrhage were similar in the antenatal phenobarbital exposed and placebo groups. Eighteen infants (8%) in the antenatal phenobarbital exposed group and 21 infants (11%) in the placebo group had cerebral palsy (P = not significant). There was no difference between the 2 groups in either the median Bayley II mental developmental index (85 in the antenatal phenobarbital and 86 in the placebo group) or the Psychomotor Developmental Index (91 in the antenatal phenobarbital and 91 in the placebo group). Infants with intracranial hemorrhage (23%) had significantly lower mental developmental index and psychomotor developmental index scores than infants with no intracranial hemorrhage, independent of antenatal phenobarbital exposure. In the total cohort of 436 infants, the presence of intracranial hemorrhage or periventricular leukomalacia was associated with lower mental developmental index and psychomotor developmental index scores; the presence of increasing birth weight, maternal education, and a complete course of antenatal steroids was associated with a higher mental developmental index score.


CONCLUSIONS
Antenatal phenobarbital exposure did not favorably or adversely affect the neurodevelopmental outcome of premature infants at 18 to 22 months of age.
Shankaran
Seetha
S
Wayne State University, Detroit, MI, USA. s_shankaran@wayne.edu
Papile
Lu-Ann
LA
Wright
Linda L
LL
Ehrenkranz
Richard A
RA
Mele
Lisa
L
Lemons
James A
JA
Korones
Sheldon B
SB
Stevenson
David K
DK
Donovan
Edward F
EF
Stoll
Barbara J
BJ
Fanaroff
Avroy A
AA
Oh
William
W
Verter
Joel
J
D000927:Anticonvulsants / Q000009:adverse effects* / Q000627:therapeutic use; D002490:Central Nervous System / Q000187:drug effects*; D002657:Child Development / Q000187:drug effects*; D005260:Female; D005333:Fetus / Q000187:drug effects; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007234:Infant, Premature; D020300:Intracranial Hemorrhages / Q000517:prevention & control; D008137:Longitudinal Studies; D008297:Male; D009483:Neuropsychological Tests; D010634:Phenobarbital / Q000009:adverse effects* / Q000627:therapeutic use; D011247:Pregnancy; D011295:Prenatal Care; D011297:Prenatal Exposure Delayed Effects; D011597:Psychomotor Performance / Q000187:drug effects*; D016032:Randomized Controlled Trials as Topic
D000927:Anticonvulsants; D010634:Phenobarbital