出生前接受倍他米松治疗后心血管病危险因素的变化:一项随机化对照试验的30年随访调查研究

Background: Antenatal betamethasone treatment is widely used for the prevention of neonatal respiratory distress syndrome in preterm infants and substantially reduces neonatal mortality and morbidity. Fetal exposure to excess glucocorticoids has been proposed as one of the core mechanisms of the fetal origins of adult disease hypothesis. We assessed whether antenatal exposure to betamethasone for the prevention of neonatal respiratory distress syndrome affects cardiovascular risk factors at 30 years of age. Methods: We followed up at age 30 years 534 individuals whose mothers participated in a doubleblind, placebo-controlled, randomised trial of antenatal betamethasone for the prevention of neonatal respiratory distress syndrome. Mothers received two doses of betamethasone or placebo given by intramuscular injection 24 h apart. Follow-up assessments included anthropometry; measurement of blood pressure, blood lipids (after overnight fasting), and early morning cortisol levels; and a 75 g oral glucose tolerance test. Findings: There were no differences between those exposed to betamethasone and to placebo in body size, blood lipids, blood pressure, plasma cortisol, prevalence of diabetes, or history of cardiovascular disease. After a 75 g oral glucose tolerance test, participants exposed to betamethasone had higher plasma insulin concentrations at 30 min (60.5 vs 52.0 mIU/L; ratio of geometric means 1.16 95%CI 1.03 to 1.31 , p=0.02) and lower glucose concentrations at 120 min (4.8 vs 5.1 mmol/L; difference -0.26 mmol/L -0.53 to 0.00 , p=0.05) than did those exposed to placebo. Interpretation: Antenatal exposure to betamethasone might result in insulin resistance in adult offspring, but has no clinical effect on cardiovascular risk factors at 30 years of age. Thus, obstetricians should continue to use a single course of antenatal betamethasone for the prevention of neonatal respiratory distress syndrome.

出生前使用倍他米松:纳入随机对照试验31年后的心理功能和健康相关生活质量

Objectives: To determine if antenatal exposure to betamethasone for the prevention of neonatal respiratory distress syndrome alters psychological functioning and health related quality of life in adulthood. Design: Followup of the first and largest double blind, placebo controlled, randomised trial of a single course of antenatal betamethasone for the prevention of neonatal respiratory distress syndrome. Setting: Tertiary obstetric hospital in Auckland, New Zealand. Participants: 192 adult offspring, mean age 31 years, of mothers who took part in a randomised controlled trial of antenatal betamethasone for the prevention of neonatal respiratory distress syndrome (87 exposed to betamethasone and 105 exposed to placebo). Interventions: Mothers received two doses of betamethasone or placebo 24 hours apart. Main outcome measures: Cognitive functioning assessed with Wechsler abbreviated scale of intelligence; working memory and attention assessed with Benton visual retention test, paced auditory serial addition test, and Brown attention deficit disorder scale; psychiatric morbidity assessed with Beck depression inventory II, statetrait anxiety inventory, and schizotypy traits questionnaire; handedness assessed with Edinburgh handedness inventory; health related quality of life assessed with short form 36 health survey. Results: No differ ences were found between groups exposed to betamethasone and placebo in cognitiv e functioning, working memory and attention, psychiatric morbidity, handedness, or health related quality of life. Conclusions: Prenatal exposure to a single course of betamethasone does not alter cognitive functioning, working memory and attention, psychiatric morbidity, handedness, or health related quality of life in adulthood. Obstetricians should continue to use a single course of antenatal betamethasone for the prevention of neonatal respiratory distress syndrome.

出生前母亲暴露于重复剂量的糖皮质激素与出生后新生儿心血管状态的改变有关

Objective: To determine if exposure to more than one course of antenatal gluco cortlcoids is associated with changes in infant blood pressure and myocardial wa ll thickness in the first month after birth. Design: Prospective cohort study. S etting: Tertiary neonatal intensive care unit. Participants: Mothers who were el igible for but declined to enter a randomised trial of repeated doses of antenat al glucocorticoids (ACTORDS)-that is, who had a singleton, twin, or triplet pre gnancy at < 32 weeks gestation, had received an initial course of glucocorticoid s seven or more days previously, and were considered to be at continued risk of preterm birth. Main outcome measures: Blood pressure daily for the first week th en weekly until 4 weeks of age. End diastolic interventricular septal and left v entricular posterior wall (EDIVS and EDLVPW) thickness at 48-72 hours after bir th. Results: Thirty seven women were enrolled and delivered 50 infants. Thirty m others (39 infants) were exposed to one course of glucocorticoids, and seven mot hers (11 infants) to more than one course. Blood pressures were higher in the fi rst week after birth in infants exposed to multiple courses of glucocorticoids, and in infants with a latency between last exposure and delivery of less than se ven days. Systolic blood pressure on day 1 was > 2SD above published normal rang es in 67%of babies exposed to multiple courses and 24%of babies exposed to a s ingle course of glucocorticoids (p = 0.04). There was no difference between grou ps in thickness of the EDIVS or EDLVPW. However, 44/50 (88%) babies had EDIVS a nd 49/50 (98%) babies had EDLVPW thickness > 2 SD above the expected mean for b irth weight and gestation. EDIVS but not EDLVPW thickness increased with increas ing latency (mean 0.02 mm/day, P=0.03). Conclusion: Future randomised trials sho uld assess the long term effects of exposure to antenatal glucocorticoids, particularly multiple courses, on the cardiovascular status of the infant.

出生前暴露于倍他米松是否对成年后的心理功能和健康相关生活质量产生不良影响

Objectives: To determine if antenatal exposure to betamethasone for the prevention of neonatal respiratory distress syndrome alters psychological functioning and health related quality of life in adulthood. Design: Follow-up of the first and largest double blind, placebo controlled, randomised trial of a single course of antenatal betamethasone for the prevention of neonatal respiratory distress syndrome. Setting: Tertiary obstetric hospital in Auckland, New Zealand. Participants: 192 adult offspring, mean age 31 years, of mothers who took part in a randomised controlled trial of antenatal betamethasone for the prevention of neonatal respiratory distress syndrome (87 exposed to betamethasone and 105 exposed to placebo). Interventions: Mothers received two doses of betamethasone or placebo 24 hours apart. Main outcome measures: Cognitive functioning assessed with Wechsler abbreviated scale of intelligence; working memory and attention assessed with Benton visual retention test, paced auditory serial addition test, and Brown attention deficit disorder scale; psychiatric morbidity assessed with Beck depression inventory II, state-trait anxiety inventory, and schizotypy traits questionnaire; handedness assessed with Edinburgh handedness inventory; health related quality of life assessed with short form 36 health survey. Results: No differences were found between groups exposed to betamethasone and placebo in cognitive functioning, working memory and attention, psychiatric morbidity, handedness, or health related quality of life. Conclusions: Prenatal exposure to a single course of betamethasone does not alter cognitive functioning, working memory and attention, psychiatric morbidity, handedness, or health related quality of life in adulthood. Obstetricians should continue to use a single course of antenatal betamethasone for the prevention of neonatal respiratory distress syndrome.