376 Phenobarbital
the phenobarbital group grew older, they had shorter attention spans and
more trouble with spelling and math.
Worse deformities have been seen when phenobarbital is used in combi-
nation with some other drugs than when used alone. A review of epilepsy
medicines published in 1997 said malformations from phenobarbital are no
more likely than from carbamazepine, phenytoin, or valproic acid—yet those
latter three substances have been found to cause birth defects. A 1994 analysis
of outcomes in several hundred pregnancies concluded that birth defects were
more likely from phenobarbital than from carbamazepine or phenytoin.
Phenobarbital and other epilepsy drugs may reduce vitamin K levels in a
fetus, a reduction that can promote bleeding and cause disfiguring birth de-
fects. Some researchers think that pregnant women using such drugs should
ingest extra vitamin K.
Researchers believe that pregnant rats receiving phenobarbital seem to pro-
duce male offspring with “feminized behavior” and female offspring with
masculine behavior. A group of humans who were prenatally exposed to
phenobarbital showed higher rates of homosexual, cross-gender, and trans-
sexual behavior when compared to a matched group that had no prenatal
exposure to phenobarbital.
After phenobarbital is given to pregnant rats, their mature progeny act more
nervous and uneasy than mature progeny from rats not exposed to the drug
during pregnancy and also exhibit defects in reproductive ability. Mice ex-
posed to the drug during fetal development and soon after birth show im-
proper functioning of the hippocampus (a part of the brain affecting memory),
and their brains weigh less than normal. Tests of thinking ability in adult
humans whose mothers used phenobarbital and phenytoin while pregnant
reveal deficiency in perceiving differences among geometrical figures. Other
research has found that such adults generally have normal intelligence but
are far likelier to have learning difficulties than adults who did not have pre-
natal exposure to the phenobarbital-phenytoin combination. Two studies have
found verbal intelligence scores to be below expectations in men whose moth-
ers took phenobarbital while pregnant, and another study found psychological
maturation to be slowed in about 20% of children whose mothers received
phenobarbital while pregnant. The director of a National Institutes of Health
research center reported contrary findings in which offspring performed better
if their mothers had used phenobarbital while pregnant, but analysts have
noted methodological aspects in that study that weaken its findings.
The drug is sometimes given to pregnant women having premature labor,
to reduce the hazard of infants developing bleeding inside the skull. One
follow-through study found that infants born to pregnant women receiving
such therapy had better nervous system development than children from
mothers who did not receive such therapy, measured both in organic and
cognitive factors. Another study measuring two such populations found the
phenobarbital children to have lower mental development.
If a pregnant woman uses phenobarbital her infant can be born dependent
on the drug; neonatal withdrawal is characterized by peevishness, vomiting,
and poor muscle tone. Typically a nursing woman’s milk will contain about
45% of the phenobarbital level found in her blood. Breast-feeding by mothers