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British Guideline on the MAnAGeMent of AsthMA
7.6.2 INHALED STEROIDS
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No significant association has been demonstrated between major congenital malformations or
adverse perinatal outcome and exposure to inhaled steroids. 530,534-537, 822, 825, 828 A meta-analysis
of four studies of inhaled corticosteroid use in pregnancy showed no increase in the rate of
major malformations, pre-term delivery, low birth weight or pregnancy-induced hypertension. 829
The UK case control study included 1,429 infants exposed to inhaled steroids and found no
increased risk of major congenital malformations. 822
Inhaled anti-inflammatory treatment has been shown to decrease the risk of an acute attack
of asthma in pregnancy 519 and the risk of readmission following asthma exacerbation. 517 A
randomised placebo controlled trial of inhaled beclometasone versus oral theophylline in
moderate asthma in pregnancy showed no difference in the primary outcome of one or more
asthma exacerbations resulting in medical intervention, but inhaled beclometasone was better
tolerated. 807
B use inhaled steroids as normal during pregnancy.
7.6.3 THEOPHyLLINES
No significant association has been demonstrated between major congenital malformations or
adverse perinatal outcome and exposure to methylxanthines. 530,538
For women requiring theophylline to maintain asthma control, measurement of theophylline
levels is recommended. Since protein binding decreases in pregnancy, resulting in increased
free drug levels, a lower therapeutic range is probably appropriate. 539
C use oral and intravenous theophyllines as normal during pregnancy.
d Check blood levels of theophylline in acute severe asthma and in those critically
dependent on therapeutic theophylline levels.
7.6.4 STEROID TABLETS
There is much published literature showing that steroid tablets are not teratogenic522, 530, 540 but
a slight concern that they may be associated with oral clefts. Data from several studies have
failed to demonstrate this association with first trimester exposure to steroid tablets540, 830 but
one case control study found a significant association, although this increase is not significant
if only paired controls are considered. 542 Although one meta-analysis reported an increased
risk, 541 a prospective study by the same group found no difference in the rate of major birth
defects in prednisolone-exposed and control babies. 541 A more recent population based case
control study revealed a crude odds ratio of corticosteroid exposure from four weeks before
through to 12 weeks after conception of 1.7 (95% CI, 1.1-2.6) for cleft lip. 831 Another case
control study822 including 262 exposed infants found no such association, although this was
not limited to first trimester exposure.
The association is therefore not definite and even if it is real, the benefit to the mother and the
fetus of steroids for treating a life threatening disease justify the use of steroids in pregnancy. 524,
815 Moreover, the various studies of steroid exposure include many patients with conditions
other than asthma, and the pattern of steroid use was generally as a regular daily dose rather
than as short courses, which is how asthma patients would typically receive oral steroids.
Prednisolone is extensively metabolized by placental enzymes so only 10% reaches the fetus,
making this the oral steroid of choice to treat maternal asthma in pregnancy. Pregnant women
with acute asthma exacerbation are less likely to be treated with steroid tablets than non-pregnant
women. 527 Failure to administer steroid tablets when indicated increases the risk of ongoing
exacerbation and therefore the risk to the mother and her fetus.
Some studies have found an association between steroid tablet use and pregnancy-induced
hypertension or pre-eclampsia, pre-term labour 520 and fetal growth but severe asthma may be
a confounding variable. 832
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