1. Steroid in pregnancy
제일병원 주산기분과
전임의 안계형

2. Steroid의 분류
• Corticosteroid
- glucocorticoid: regulate many aspects of
metabolism and immune function (cortisol)
- mineralcorticoid: maintain blood volume and
control
renal excretion of electrolytes (aldosterone)
Most medical “steroid” drugs are cortocosteroid
• Anabolic steroid: interact with androgen receptors
to increase muscle and bone synthesis
• Sex hormone: produce sex difference or support
reproduction (androgens,
estrogens,progesterones)

3. Steroid in pregnancy
• Systemic corticosteroids:
autoimmune and inflammatory
conditions
• Inhaled steroids:
first-line treatment for asthma
• Topical corticosteroids:
allergic and inflammatory dermatologic
diseases(atopic dermatitis and
psoriasis)

4. Steroid in pregnancy
Molecular weight
• Prednisolone: 360g/mol C21H28O5
• Prednisone: 358g/mol C21H26O5
• Cortisone: 376g/mol C21H28O5
• Dexamethasone: 392g/mol C22H9FO5
=>Cross human placenta

5. Half life of corticosteroid

6. www.motherisk.org

7. Motherisk update 2004
Systemic corticosteroid
• Prednisone, cortisone, prednisolone,
dexamethasone
• Association with oral clefts
• one case-control and several prospective
cohort studies:
failed to show such an association.
• A metaanalysis conducted by the Motherisk
program of 123175 women who received oral
corticosteroids during the first trimester :
showed a slightly increased risk of oral clefts.

8. Motherisk update 2004
Systemic corticosteroid
• Odd ratios (ORs) in case control studies:
threefold increase in oral clefts among off
spring of women who received oral
corticosteroids during pregnancy.
• six cohort studies : no significant increase in
oral clefts.

9. Motherisk update 2004
Systemic corticosteroid
• Increase incidence of low birth weight and
stillbirths(often associated with the
condotion for which the mothers were given
the drugs)

10. Motherisk update 2004
Inhaled corticosteroids
• asthma or other respiratory symptoms
• beclomethasone,budesonide,flunisolide,flutic
asone,mometasone, and triamcinoloneIt
• up to 4% of all pregnancies : complicated by
maternal asthma.
• Poor control of chronic asthma and
exacerbation of acute asthma during
pregnancy -> hypoxia, low birth weight, and
intrauterine growth restriction

11. Motherisk update 2004
Inhaled corticosteroids
A randomized controlled study
• long-term use of low-dose budesonide
decreases the risk of severe exacerbations
• improves asthma control in patients with
mild, persistent asthma of recent onset.
• reduce risk of hospitalization due to asthma.

12. Motherisk update 2004
Topical corticosteroids
• The systemic effects of topical corticosteroids
-> generally limited
-> only about 3% of the medication in topical
preparations is absorbed systemically
following 8 hours of contact

13. Motherisk update 2004
Topical corticosteroids
• When corticosteroids are used long term
or on large areas of skin
-> systemic effects
• Epidemiologic fetal safety data on topical
corticosteroids -> sparse.
• Two population-based studies
: treatment with topical corticosteroids
during pregnancy did not increase risk of
congenital abnormalities in humans.

14. Motherisk update
discussion
• oral clefts : occur at about one per thousand
births
• minimal absolute effect on the overall
malformation rate of 3%.
• palate formation : completed by 12 weeks’
gestation
-> no risk of oral clefts exists thereafter.

15. Motherisk update
discussion
• When exposure has already occurred
-> a level II ultrasound scan
(to detect clefting)
• More studies are needed to determine which
cleft phenotype is associated with
corticosteroids and whether it is cleft lip
(with or without palate) or cleft palate alone,
or both

17. Corticosteroids During Pregnancy and Oral
Clefts: A Case-Control Study
• Case subjects: 1,184 liveborn infants with
nonsyndromic oral clefts.
• results (logistic regression analysis):
show a relationship between exposure to
corticosteroids during the first trimester of
pregnancy and an increased risk of cleft
lip (with or without cleft palate) in the
newborn infants
(OR: 6.55; CI: 1.44–29.76; P: 0.015)

18. Corticosteroids During Pregnancy and Oral
Clefts: A Case-Control Study

19. Corticosteroids During Pregnancy and Oral
Clefts: A Case-Control Study
• Use of corticosteroids during the first
trimester of pregnancy, should be
restricted to the following situations:
life-threatening situations
diseases without any other safe
therapeutic alternative
cases with replacement therapy.

21. Birth Defects After Maternal Exposure to
Corticosteroids: Prospective Cohort Study
and Meta-Analysis of Epidemiological Studies
• 184 women exposed to prednisone in
pregnancy
• 188 pregnant women who were counseled
by Motherisk for nonteratogenic
exposure.
• primary outcome:
rate of major birth defects.
• A meta-analysis of all epidemiological
studies was conducted.

22. Birth Defects After Maternal Exposure to
Corticosteroids: Prospective Cohort Study
and Meta-Analysis of Epidemiological Studies
• Results: no statistical difference in the rate of
major anomalies between the corticosteroid-
exposed and control groups.
• In the meta-analysis
odds ratio for major malformations with all cohort
studies:1.45 and 3.03
• odds ratio for case-control studies examining oral
clefts was significant (3.35 [95% CI 1.97, 5.69]).

23. Birth Defects After Maternal Exposure to
Corticosteroids: Prospective Cohort Study
and Meta-Analysis of Epidemiological Studies
• Conclusions: Although prednisone does
not represent a major teratogenic risk
in humans at therapeutic doses, it does
increase by an order of 3.4-fold the
risk of oral cleft, which is consistent
with the existing animal
studies.

24. Birth Defects After Maternal Exposure to
Corticosteroids: Prospective Cohort Study
and Meta-Analysis of Epidemiological Studies

25. Birth Defects After Maternal Exposure to
Corticosteroids: Prospective Cohort Study
and Meta-Analysis of Epidemiological Studies

26. Birth Defects After Maternal Exposure to
Corticosteroids: Prospective Cohort Study
and Meta-Analysis of Epidemiological Studies

35. Guideline on Steroids in Pregnancy
Major possible adverse effects
• orofacial clefts when used preconception and in the
first trimester of pregnancy, and foetal growth
restriction and preterm delivery
• especially potent/very potent topical corticosteroids
(evidence from a Cochrane Review an d data
mining of the World Health Organisation
International Database of Adverse Drug Reactions)

36. Guideline on Steroids in Pregnancy
A large population-based cohort studies
(84,133 pregnant women from the UK
General Practice Research Database)
• significant association of foetal growth
restriction with maternal exposure to
potent/very potent topical corticosteroids
• but not with mild/moderate topical
steroids

37. Guideline on Steroids in Pregnancy
• No associations of any potency with orofacial
cleft, preterm delivery, and foetal death
• antibiotic-containing topical corticosteroid:
associated with an increased risk for foetal
growth restriction and foetal death
• current evidence is sufficient for doctors and
pregnant women to a well-informed decision as
to whether to use topical corticosteroids in
pregnancy.

38. Guideline on Steroids in Pregnancy
• The evidence suggests that mild/moderate
topical corticosteroids are preferred to
potent/very potent ones in pregnancy,
because of the risk of foetal growth
restriction.

39. Guideline on Steroids in Pregnancy

40. Guideline on Steroids in Pregnancy

41. Guideline on Steroids in Pregnancy

42. Guideline on Steroids in Pregnancy

43. Guideline on Steroids in Pregnancy

44. Guideline on Steroids in Pregnancy

45. Recommendations
1. Mild/moderate topical corticosteroids should be
used in preference to more potent corticosteroids in
pregnancy (Grade of recommendation: B).
2.Potent/very potent topical corticosteroids should be
used as second-line therapy for as short a time as
possible, and appropriate obstetric care should be
provided as they increase the risk of foetal growth
restriction (Grade of recommendation: B).

46. Recommendations
3.systemic corticosteroids have a greater
bioavailability than that of topical
corticosteroids, and have a higher potential for
foetotoxicity than topical corticosteroids
(systemic corticosteroids are associated with a
reduction in fetal birth weight and an increase in
preterm delivery and should not be used in
preference (Grade of recommendation: B).

47. Recommendations
4.the danger of adverse events is increased
when areas with high absorption (e.g.genitals,
eyelids, flexures) are treated
(Grade of recommendation: B)
5.The data are not available to determine if newer
more lipophilic topical corticosteroids (mometasone,
fluticasone and methylprednisolone aceponate,) with
a good therapeutic index are associated with less
foetal growth restriction despite theoretical grounds
to suggest this and the practical advantage of
once daily application (Grade of recommendation:C).

48. Recommendations
6. Antibiotic-containing topical corticosteroid
preparations should be avoided in pregnancy
(until more robust evidence is available)
because of concern for increased risk for
foetal growth restriction and foetal death.
(Grade of recommendation: C).

49. Advice to women about using topical
corticosteroids in pregnancy
1. Women can be reassured
• no significantly increased risk for orofacial cleft,
preterm delivery and foetal death when using
topical corticosteroids in pregnancy.
• no increased risk for foetal growth restriction
when using mild/moderate topical
corticosteroids in pregnancy.

50. Advice to women about using topical
corticosteroids in pregnancy
2. Women should be informed
• small risk for foetal growth restriction when using
potent/very potent topical corticosteroids
• but this risk is less than that of systemic
corticosteroids
• additional risk for preterm delivery has been
found in women using systemic corticosteroids.
3. Depending on the severity of their skin
conditions, women should use topical
corticosteroids of the least potency required and
limit the amount of use

51. Williams OBSTETRICS 24th
• systemic corticosteroids are category
D if used in the first trimester,
however, they are not considered to
represent a major teratogenic risk.

52. ?
“should be used during pregnancy
only if the potential benefit justifies
the potential risk to the foetus”

53. 감사합니다.