Giving steroids before elective caesarean section
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《英国医生杂志》
Neonatal respiratory morbidity is halved, but they may be harmful in the long term
In recent years the caesarean section rate in developed countries has been rising. This may be because improved techniques to control haemorrhage, infection, and thromboembolism have increased the safety of the procedure. As a result obstetricians and pregnant women have a reduced threshold for choosing it. However, although maternal risks have decreased, the effects on the baby of surgical delivery before the due date continue to be debated.'
In this issue (p 662), Stutchfield et al confirm previous reports that elective caesarean section before 40 weeks' gestation increases neonatal admissions to the special care unit for respiratory distress (mainly for transient tachypnoea of the newborn).12 In the control group of the randomised controlled trial, 11.4% were admitted at 37 weeks, 6.2% at 38 weeks, and 1.5% at 39 weeks. If women were given two intramuscular injections of 12 mg of betamethasone in the 48 hours before delivery the rates of admission were 5.2% at 37 weeks, 2.8% at 38 weeks, and 0.6% at 39 weeks. Although none of the babies in the control group died, admission will have increased parental anxiety and the cost to the NHS and may have long term sequelae. Giving mothers betamethasone before elective casesarean section halved neonatal respiratory morbidity, so should we give steroids to all mothers before delivery?
We need to know what the potential harms for the fetus are. Lawson has summarised the growing number of reports of adverse long term effects associated with antenatal steroids.3 Animal studies show that maternal corticosteroid administration delays myelination in the fetal brain (which in humans normally continues up to the age of 2 years) and reduces the growth of all fetal brain areas, particularly the hippocampus.4 There may be long term effects on the setting of the hypothalamo-pituitary axis and glucose homeostasis.5 In preterm infants, antenatal corticosteroids have been associated with higher systolic and diastolic blood pressures in adolescence, possibly leading to clinical hypertension.6 Other studies suggest that repeated courses of antenatal steroids reduce neonatal head circumference and birth weight.7 8 Multivariate analyses of the behaviour of children in the Western Australian preterm infant follow-up study have shown that increasing the number of antenatal exposures to glucocorticoids is associated with reduced birth weight and an increase in behavioural disorders at age 3.5
In 2000, the National Institutes for Heath reported that the current benefit and risk data are insufficient to support routine use of repeat or rescue courses of antenatal corticosteroids in clinical practice.9 Clinical trials are in progress to assess potential benefits and risks of various regimens of repeat courses. Until data establish a favourable ratio of benefit to risk, repeat courses of antenatal corticosteroids, including rescue therapy, should be reserved for patients enrolled in clinical trials.9 This conclusion is supported by the American College of Obstetricians and Gynecologists and a Cochrane review.10 11
Currently, the evidence for harmful effects is strongest for repeated courses of steroids. The effect of a single course on cognitive function, however, is more reassuring, as shown by Dalziel et al in this issue (p 665).12 However, in their companion paper in the Lancet they report small but significant increases in insulin resistance which "could signify a raised risk of diabetes and cardiovascular disease as this cohort ages."w1 We should not forget that more than 2 million children were born with abnormalities of the genital tract before it was realised that these were caused by diethylstilbestrol given to their mothers as an (ineffective) treatment for threatened miscarriage,w2 and more than 10 000 babies were born with phocomelia before we realised that this was caused by the use of thalidomide in pregnancy.w3
The data presented by Stutchfield et al show that delaying non-urgent elective caesarean section until 39 weeks is much more effective in avoiding neonatal admission than giving steroids.1 For the 15% or so of such women who will go into labour between 37 and 39 weeks, the inconvenience of having their caesarean "out of hours" is likely to be less than that of having their baby admitted to special care. Most will only be in early labour, avoiding the complications of an acute intrapartum emergency.
A single course of steroids reduces neonatal mortality in babies born before 34 weeks and this perhaps justifies the small risk of long term side effects. However, no such substantial benefit has been shown after this gestation. Delaying delivery until 39 weeks, unless necessary, would seem a more prudent option than giving steroids whose long term safety, even as a single course, remains questionable.
Philip J Steer, professor of obstetrics
Imperial College, Chelsea and Westminster Hospital, London SW10 9NH (p.steer@imperial.ac.uk)
References w1-w3 are on bmj.com
Papers pp 662, 665
Competing interests: None declared.
References
Stutchfield P, Whitaker R, Russell I. Antenatal betamethasone and incidence of neonatal respiratory distress after elective caesarean section: pragmatic randomised trial. BMJ 2005;331: 662-4.
Morrison JJ, Rennie JM, Milton PJ. Neonatal respiratory morbidity and mode of delivery at term: influence of timing of elective caesarean section. Br J Obstet Gynaecol 1995;102: 101-6.
Lawson EE. Antenatal corticosteroids—too much of a good thing? JAMA 2001;286: 1628-30.
Whitelaw A, Thoresen M. Antenatal steroids and the developing brain. Arch Dis Child Fetal Neonatal Ed 2000;83: F154-F157.
Newnham JP, Moss TJ, Nitsos I, Sloboda DM. Antenatal corticosteroids: the good, the bad and the unknown. Curr Opin Obstet Gynecol 2002;14: 607-12.
Doyle LW, Ford GW, Davis NM, Callanan C. Antenatal corticosteroid therapy and blood pressure at 14 years of age in preterm children. Clin Sci (Lond) 2000;98: 137-42.
Walfisch A, Hallak M, Mazor M. Multiple courses of antenatal steroids: risks and benefits. Obstet Gynecol 2001;98: 491-7.
Bloom SL, Sheffield JS, McIntire DD, Leveno KJ. Antenatal dexamethasone and decreased birth weight. Obstet Gynecol 2001;97: 485-90.
National Institutes of Health. Antenatal corticosteroids revisited: repeat courses. NIH Consensus Statement 2000;17:1-10. http://odp.od.nih.gov/consensus/cons/112/112_intro.htm (accessed 2 September 2005).
Committee on Obstetric Practice. ACOG committee opinion: antenatal corticosteroid therapy for fetal maturation. Obstet Gynecol 2002;99: 871-3.
Crowther CA, Harding J. Repeat doses of prenatal corticosteroids for women at risk of preterm birth for preventing neonatal respiratory disease. Cochrane Database Syst Rev 2003; CD003935.
Dalziel SR, Lim VK, Lambert A, McCarthy D, Parag V, Rodgers A, et al. Antenatal exposure to betamethasone: psychological functioning and health related quality of life 31 years after inclusion in randomised controlled trial. BMJ 2005;331: 665-8.
In recent years the caesarean section rate in developed countries has been rising. This may be because improved techniques to control haemorrhage, infection, and thromboembolism have increased the safety of the procedure. As a result obstetricians and pregnant women have a reduced threshold for choosing it. However, although maternal risks have decreased, the effects on the baby of surgical delivery before the due date continue to be debated.'
In this issue (p 662), Stutchfield et al confirm previous reports that elective caesarean section before 40 weeks' gestation increases neonatal admissions to the special care unit for respiratory distress (mainly for transient tachypnoea of the newborn).12 In the control group of the randomised controlled trial, 11.4% were admitted at 37 weeks, 6.2% at 38 weeks, and 1.5% at 39 weeks. If women were given two intramuscular injections of 12 mg of betamethasone in the 48 hours before delivery the rates of admission were 5.2% at 37 weeks, 2.8% at 38 weeks, and 0.6% at 39 weeks. Although none of the babies in the control group died, admission will have increased parental anxiety and the cost to the NHS and may have long term sequelae. Giving mothers betamethasone before elective casesarean section halved neonatal respiratory morbidity, so should we give steroids to all mothers before delivery?
We need to know what the potential harms for the fetus are. Lawson has summarised the growing number of reports of adverse long term effects associated with antenatal steroids.3 Animal studies show that maternal corticosteroid administration delays myelination in the fetal brain (which in humans normally continues up to the age of 2 years) and reduces the growth of all fetal brain areas, particularly the hippocampus.4 There may be long term effects on the setting of the hypothalamo-pituitary axis and glucose homeostasis.5 In preterm infants, antenatal corticosteroids have been associated with higher systolic and diastolic blood pressures in adolescence, possibly leading to clinical hypertension.6 Other studies suggest that repeated courses of antenatal steroids reduce neonatal head circumference and birth weight.7 8 Multivariate analyses of the behaviour of children in the Western Australian preterm infant follow-up study have shown that increasing the number of antenatal exposures to glucocorticoids is associated with reduced birth weight and an increase in behavioural disorders at age 3.5
In 2000, the National Institutes for Heath reported that the current benefit and risk data are insufficient to support routine use of repeat or rescue courses of antenatal corticosteroids in clinical practice.9 Clinical trials are in progress to assess potential benefits and risks of various regimens of repeat courses. Until data establish a favourable ratio of benefit to risk, repeat courses of antenatal corticosteroids, including rescue therapy, should be reserved for patients enrolled in clinical trials.9 This conclusion is supported by the American College of Obstetricians and Gynecologists and a Cochrane review.10 11
Currently, the evidence for harmful effects is strongest for repeated courses of steroids. The effect of a single course on cognitive function, however, is more reassuring, as shown by Dalziel et al in this issue (p 665).12 However, in their companion paper in the Lancet they report small but significant increases in insulin resistance which "could signify a raised risk of diabetes and cardiovascular disease as this cohort ages."w1 We should not forget that more than 2 million children were born with abnormalities of the genital tract before it was realised that these were caused by diethylstilbestrol given to their mothers as an (ineffective) treatment for threatened miscarriage,w2 and more than 10 000 babies were born with phocomelia before we realised that this was caused by the use of thalidomide in pregnancy.w3
The data presented by Stutchfield et al show that delaying non-urgent elective caesarean section until 39 weeks is much more effective in avoiding neonatal admission than giving steroids.1 For the 15% or so of such women who will go into labour between 37 and 39 weeks, the inconvenience of having their caesarean "out of hours" is likely to be less than that of having their baby admitted to special care. Most will only be in early labour, avoiding the complications of an acute intrapartum emergency.
A single course of steroids reduces neonatal mortality in babies born before 34 weeks and this perhaps justifies the small risk of long term side effects. However, no such substantial benefit has been shown after this gestation. Delaying delivery until 39 weeks, unless necessary, would seem a more prudent option than giving steroids whose long term safety, even as a single course, remains questionable.
Philip J Steer, professor of obstetrics
Imperial College, Chelsea and Westminster Hospital, London SW10 9NH (p.steer@imperial.ac.uk)
References w1-w3 are on bmj.com
Papers pp 662, 665
Competing interests: None declared.
References
Stutchfield P, Whitaker R, Russell I. Antenatal betamethasone and incidence of neonatal respiratory distress after elective caesarean section: pragmatic randomised trial. BMJ 2005;331: 662-4.
Morrison JJ, Rennie JM, Milton PJ. Neonatal respiratory morbidity and mode of delivery at term: influence of timing of elective caesarean section. Br J Obstet Gynaecol 1995;102: 101-6.
Lawson EE. Antenatal corticosteroids—too much of a good thing? JAMA 2001;286: 1628-30.
Whitelaw A, Thoresen M. Antenatal steroids and the developing brain. Arch Dis Child Fetal Neonatal Ed 2000;83: F154-F157.
Newnham JP, Moss TJ, Nitsos I, Sloboda DM. Antenatal corticosteroids: the good, the bad and the unknown. Curr Opin Obstet Gynecol 2002;14: 607-12.
Doyle LW, Ford GW, Davis NM, Callanan C. Antenatal corticosteroid therapy and blood pressure at 14 years of age in preterm children. Clin Sci (Lond) 2000;98: 137-42.
Walfisch A, Hallak M, Mazor M. Multiple courses of antenatal steroids: risks and benefits. Obstet Gynecol 2001;98: 491-7.
Bloom SL, Sheffield JS, McIntire DD, Leveno KJ. Antenatal dexamethasone and decreased birth weight. Obstet Gynecol 2001;97: 485-90.
National Institutes of Health. Antenatal corticosteroids revisited: repeat courses. NIH Consensus Statement 2000;17:1-10. http://odp.od.nih.gov/consensus/cons/112/112_intro.htm (accessed 2 September 2005).
Committee on Obstetric Practice. ACOG committee opinion: antenatal corticosteroid therapy for fetal maturation. Obstet Gynecol 2002;99: 871-3.
Crowther CA, Harding J. Repeat doses of prenatal corticosteroids for women at risk of preterm birth for preventing neonatal respiratory disease. Cochrane Database Syst Rev 2003; CD003935.
Dalziel SR, Lim VK, Lambert A, McCarthy D, Parag V, Rodgers A, et al. Antenatal exposure to betamethasone: psychological functioning and health related quality of life 31 years after inclusion in randomised controlled trial. BMJ 2005;331: 665-8.