武功密笈

小黃藏書

¹ ACS: antenatal corticosteroids

¹ Single-course ACS:

­ Betamethasone 12mg IM q12h ´ 2 doses, or

­ Dexamethasone 6mg IM q6h ´ 6 doses

ø Safety of a single-course ACS:

not associated with any adverse neonatal outcomes, such as reduced lung

volume, abnormal neurologic status, decreased growth, neonatal sepsis,

or clinically significant adrenal suppression

ø Efficacy of a single-course ACS:

Fetuses exposed to ACS required less surfactant therapy and had lower

oxygen requirements and decreased need for prolonged mechanical

ventilation in the neonatal period. In addition, the infants had imiproved

circulatory stability, less intraventricular hemorrhage, and ultimately,

decreased mortality rates.

¹ Multiple-course ACS (weekly ACS):

­ Repeat ACS therapy weekly until 34 weeks’ gestation

ø Hypothesis of repetitive-dosing ACS:

Beneficial effects of ACS were present between 24 hours and 7 days after

treatment.

ø Safety of multiple-course ACS: not established

ø Efficacy of multiple-course ACS: not established

　

¹ ACS accelerate lung maturation in humans and many other species through

two mechanisms:

j Cytoarchitectural change:

­ Speeding up the normal thinning of the double capillary loops

¢ Forming the thin gas-exchanging walls of the air sacs or alveoli

¢ Rapid alveolization (permanently and irreversibly)

­ Suppressing the formation of secondary septa (a necessary step in alveoli formation)

¢ Reduction in alveoli number

k Biochemical stimulation of surfactant synthesis:

­ Enhancing maturation of the surfactant-producing type II pneumocyte

¢ Stimulation of surfactant production

­ Stimulating various pathways for synthesizing surfactant (reversibly)

¢ Stimulation of surfactant production

¹ Single-dose vs. multiple-dose ACS:

­ Single-dose ACS: not adversely affecting pulmonary function

­ Multiple-dose ACS: not evaulated

¹ Effect of ACS on surfactant production:

? ACS increases surfactant synthesis in a dose-dependent fashion and may

also be gestational-age dependent.

‚ ACS helps choline become incorporated into dipalmitoylphosphatidylcholine

and lamellar bodies in type II pheumocytes.

ƒ Serial doses may possibly downregulate steroid receptors, resulting in

decreased or disordered surfactant production.

¹ No data are available on the effects of prolonged ACS stimulation of the type II

pneumocytes in humans.

¹ Corticosteroids exert pleotropic effects on CNS:

Ranging from regulation of cellular growth and differentiation, alterations in

electrophysiologic activity, to important influences on mood, motivation, and

learned behavior patterns

¹ ACS exposure can negatively affect brain growth and cell proliferation, which

may also be dependent on the gestational age and duration of exposure.

­ The most general effect is a long-lasting decrease in tissue weight of the

cerebellum and cerebrum or rats and mice, accompanied by significant

reduction in DNA content, suggesting fewer brain cell development.

­ The dose at which dexamethasone impairs brain-cell development is lower

than the threshold for inducing general growth restriction.

¹ A study of Hagan and French: (Limited by low power and the lack of an adequate control group)

­ Serial courses of ACS were not associated with reduced mortality or

improved respiratory outcomes.

­ At age of 3 years, the effect of multiple courses of ACS on growth was no

longer apparent and there was no obvious detrimental effect on neurologic

development (cerebral palsy, blindness, deafness, or OQ scores). However,

more behavior problems were associated with more ACS exposure.

­ At age of 6 years, repeated ACS courses were associated with persistent

hyperactive behaviors on Child Behavior Check List.

　

¹ Data from rats, mice, sheep, and monkey studies all suggest that ACS have a

profound negative effect on pre- and postnatal growth.

¹ Data from human studies: limited.

¹ Increased risks of opportunistic infections or infectious morbidity:

­ Published data were conflicting and limited in both single and multiple

courses of ACS.

　

¹ There is no evidence that a single course of ACS shortens the latency interval

(time from ACS to delivery).

¹ Serial courses of ACS may enhance the risk of preterm delivery:

j Glucocorticoids stimulate expression of CRH (corticotropin-releasing hormone)

’ Increased prostanoids production by amnion, chorion, and decidual cells

’ Increased uterine activity

k Chronic glucocorticoid therapy is

associated with shorter latency periods and increased PTD rates in

PPROM settings.

l Repeated glucocorticoid therapy has been associated with an increased risk

of premature contractions in patients with multifetal pregnancies.

　

¹ Neither the efficacy nor safety of serial courses of glucocorticoids has been

established.

¹ Marginal benefit from fetal lung maturation conveyed by repeated doses of ACS

may not outweigh the potential risks of adverse fetal CNS development, increased

infectious morbidity, prenatal or postnatal growth restriction, and the potential for

promoting preterm deliveries.

¹ Until randomized, controlled trials yield results about the efficacy and safety of

multiple ACS exposures, we obstetricians should exercise caution when

prescribing repetitive courses. At a minimum, review with a patient the potential

benefits and risks of multiple courses and document your discussion in the

medical record. Avoid prophylactic treatment with oral corticosteroids and reserve

ACS for those women at highest risk for PTD, rather than giving them

indiscriminately to all patients with minor potential risk factors.