마더리스크라운드 - Steroid in pregnancy

Steroid in pregnancy

제일병원 주산기분과

전임의 안계형

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)


• Systemic corticosteroids:

autoimmune and inflammatory conditions

• Inhaled steroids:

first-line treatment for asthma

• Topical corticosteroids:

allergic and inflammatory dermatologic

diseases(atopic dermatitis and psoriasis)


Molecular weight

• Prednisolone: 360g/mol C21H28O5

• Prednisone: 358g/mol C21H26O5

• Cortisone: 376g/mol C21H28O5

• Dexamethasone: 392g/mol C22H9FO5

=>Cross human placenta

Half life of corticosteroid

www.motherisk.org

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.

• 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.



• Increase incidence of low birth weight and stillbirths(often associated with the condotion for which the mothers were given the drugs)




Inhaled corticosteroids

• asthma or other respiratory symptoms

• beclomethasone,budesonide,flunisolide,fluticasone,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

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.


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

• 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.


Topical corticosteroids

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.

• 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

Motherisk update discussion

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)



• 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.

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.



• 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]).



• 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.







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)


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


• 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.


• 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.







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).

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).

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).

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).

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.

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

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.

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

?

감사합니다.

Health & Medicine

마더리스크라운드 - Steroid in pregnancy