Attention-deficit hyperactivity disorder (ADHD) is one of
the most common conditions of childhood and approximately 30% of patients are
estimated to continue pharmacologic treatment into adulthood (approximately 4%
of the adult population suffers from ADHD). First line medications most often
used to treat ADHD in adults are Dextroamphetamine (Dexedrine, Adderall) and
Methylphenidate (Concerta, Ritalin, Metadate).
Similarly to what applies to most drugs, the use of
stimulants in pregnancy should be individually and carefully assessed, weighing
their pros and cons, risks and benefits for each woman and her needs. In several cases of mild to moderate ADHD, the
soon-to-be mother can function reasonably well without stimulants, with some
behavioral modifications and/or non-stimulant medications. In more severe
cases, however, they must continue on pharmacologic treatment in order to
function.
We talked about the use of caffeine in pregnancy on a
previous blog post.
Alternative pharmacologic treatment options include tricyclic antidepressants, bupropion
and clonidine, which have more evidence to support their safety in pregnancy
than stimulants. However, large population studies have shown that the number of women who take stimulants during pregnancy has
been getting progressively higher within the last decade, exposing a troubling lack of information
regarding potential fetal risks in humans and urging for more post-marketing research.
A group from
Boston University reviewed data from the Slone Epidemiology Center’s
Birth Defects Study (BDS), an ongoing case-control surveillance effort focused
on birth defects in relation to antenatal medication use in 29,540 women (19,811
cases and 9,729 controls) who were interviewed between 1998 and 2014. They noted
that “In animal studies, methylphenidate has not produced teratogenic effects
in mice or rats; in rabbits, only doses that were about 40 times the maximum
recommended human dose resulted in an increased risk of spina bifida.
Amphetamines given orally in doses approximately 1.5 and 8 times the normal
human dose to both pregnant mice and rabbits had no apparent effects on fetal
development, although parenteral doses at approximately 6 times the human dose
resulted in fetal malformations in mice. However, it is important to note
that animal studies are not predictive of human effects; teratogenicity in
animals does not imply the same effect in humans, and lack of teratogenicity in
animals does not ensure no effect in humans”, they conclude, adding that “The
few human studies that have explored possible effects of these drugs on the
fetus included only small numbers of subjects or were primarily focused on
methylphenidate, while our experience indicates that amphetamine mixed salts is
by far the most common (and most rapidly increasing) ADHD medication used by
pregnant women in the United States”, says Louik and colleagues.
Most of the data we currently have derives from large Danish
population studies. In one of them,
Pottegård and colleagues evaluated data of 222 exposed and 2,220 unexposed pregnancies
from 2005 to 2012 and found no statistically significant difference between the
two groups in terms of risk for major congenital malformations. The same group also studied a total of 180
children exposed to methylphenidate in utero during first trimester (among whom
four children with major malformations were observed) and concluded that methylphenidate
exposure during pregnancy does not appear to be associated with a substantially
(i.e. more than twofold) increased risk of congenital malformations.
A large cohort study monitoring 50,282 women with medication
exposure during pregnancy with 367 women taking Dextroamphetamine and 215
unspecified Amphetamines in the first trimester demonstrated no increase in the
risk of malformation in exposed infants.
Based on these studies, the available data for
methylphenidate suggest no increase in the risk of malformation when used at
therapeutic doses.
However, there is some evidence that these infants may be at
increased risk for low birth weight, preterm birth, growth retardation and
neonatal withdrawal symptoms, but those findings are based on very small
studies with several confounding limitations.
Good 2010 did a chart review including 267 women who had positive urine tests for methamphetamine compared
to a control group of women with negative urine tests, and found a higher risk
of preterm delivery (52% vs. 17%), low Apgar scores (6% vs. 1–2%), and
neonatal mortality (4% vs. 1%).
A study by Bro et al, published on the Journal of Clinical
Epidemiology in 2015 on the adverse pregnancy outcomes
after exposure to methylphenidate or atomoxetine during pregnancy looked at 989,932 pregnancies,
in which 186 (0.02%) women used MPH/ATX and 275 (0.03%) women had been
diagnosed with ADHD but who did not take MPH/ATX. They found that exposure to
MPH/ATX was associated with an increased risk of spontaneous abortion but also found that women with ADHD who did
not take MPH/ATX also carried an increased risk. MPH/ATX was however associated
with low Apgar scores <10, an association not found among women with
ADHD who did not use MPH/ATX.
