Valproate: A New Cause of Birth Defects -- Report from
Italy and Follow-Up from France
Studies by the Indagine Policentrica Italiana sulle
Malformazioni
Congenite (IPIMC) in 1980-1982 found a significant association
between
valproic-acid exposure during the first trimester of pregnancy and
spina bifida (Table 2). Among 118 infants with spina bifida, two
(1.7%) were exposed to valproic acid; in the group with other
malformations, three (0.1%) of 4,489 were exposed.
Further data from France on the association between spina
bifida
aperta among infants with birth defects and valproic-acid use
during
the first trimester update the preliminary report from Lyon (Tables
3
and 4) (1). An infant with spina bifida, who had intrauterine
exposure to valproic acid, has been added, and an infant with spina
bifida, whose mother had not been recognized as having epilepsy,
has
been properly classified. These data represent the cumulative
experience during 1976 and from 1978 to December 1982.
Reported by Bolletino Epidemiologica Nazionale (November 25, 1982);
E
Robert, MD, Institut Europeen des Genomutations, Lyon, France;
Birth
Defects Br, Chronic Diseases Div, Center for Environmental Health,
CDC.
Editorial Note
Editorial Note: In addition to these new data from Italy and
France,
a United Kingdom researcher has reported that, of infants born to
196
pregnant women treated with valproic acid, 157 (80%) were normal
and
nine (5%) had spina bifida (2). The remaining 30 infants had other
structural defects, including cardiovascular defects, orofacial
clefts, and digital abnormalities. Since most of the pregnancies
were
reported either to the U.K. researcher or to a drug company and
since
normal pregnancies would tend not to be reported, there is probably
some bias in the direction of reporting abnormal pregnancies.
Given
that these data were collected before the report from France and
that
spina bifida accounted for 23% (9/39) of the reported
abnormalities,
the 10-fold excess reported from the United Kingdom is probably not
due entirely to reporting bias.
With these new data, valproic acid and sodium valproate should
be
considered human teratogens. CDC has estimated that a pregnant
woman
in the United States treated with these drugs would have a 1%-2%
risk
of having a child with spina bifida.* Since this risk is similar
to
the risk of spina bifida recurrence in subsequent pregnancies,
women
exposed in the first trimester should consult their physicians
about
further prenatal counseling. A pregnant woman undergoing treatment
for epilepsy should not change her drug therapy without first
consulting her physician.
Little is known about the relationship between valproic acid
and
other birth defects. To better define the risk of such therapy,
CDC
is assembling a registry of women taking valproic acid during
pregnancy. Physicians caring for such women are urged to report
these
pregnancies to the CDC registry as soon as possible by calling
(404)
452-4035 on weekdays between 8 a.m. and 4:30 p.m., Eastern time, or
by
writing the Birth Defects Branch, Chronic Diseases Division, Center
for Environmental Health, Centers for Disease Control, Atlanta,
Georgia 30333.
References
CDC. Valproic acid and spina bifida: a preliminary
report--France. MMWR 1982;31:565-6.
Jeavons PM. Sodium valproate and neural-tube defects (letter).
Lancet 1982;2:1282-3.
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