PLAIN LANGUAGE SUMMARY Corticosteroids given to women in early labour help the babies' lungs to mature and so reduce the number of babies who die or suffer Babies born very early are at risk of breathing difficulties(respiratory distress syndrome)and other complications at birth. Some babies have developmental delay and some do not survive the initial complications. In animal studies, corticosteroids are shown to help the lungs to mature and so it was suggested these drugs may help babies in preterm labour too. This review of 21 trials shows that a singl course of corticosteroid, given to the mother in preterm labour and before the baby is born, helps to develop the baby's lungs and reduces complications like respiratory distress syndrome. Furthermore, this treatment results in fewer babies dying and fewer commo serious neurological and abdominal problems, e.g. cerebroventricular haemorrhage and necrotising enterocolitis, that affect babies born very early. There does not to be any negative effects of the corticosteroid on the mother. Long-term outcomes on both baby and BACKGR。UND Mature lungs contain more than 40 different cell types derived from this early tissue. From 8 to 16 weeks' gestation, the major Respiratory distress syndrome(RDS) is a serious complication of bronchial airways and associated respiratory units of the lung are preterm birth and the primary cause of early neonatal death and progressively formed. At this time the lung blood vessels also be- disability. It affects up to one fifth of low birthweight babies(less gin to grow in parallel. From 17 to 25 weeks gestation, the air- than 2500 g) and two thirds of extremely low birthweight babies ways grow, widen and lengthen( canalisation). Terminal bronchi- oles with enlargements that subsequently give rise to terminal sacs (the primitive alveoli)are formed. These are the functional Respiratory failure in these infants occurs as a result of surfactant of the lung (respiratory lobules). It is at this stage that the increas- deficiency, poor lung ar other organs. Neonatal survival after preterm birth improves with ing proximity of blood capillaries begins the air-blood interface gestation(Doyle 2001a), reflecting improved maturity of organ required for effective air exchange. This can only take place at the terminal bronchioles. At the end of the canalicular stage, type systems. However, those who survive early neonatal care are at and Il pneumocytes can be seen in the alveoli. From 28 to 35 ncreased risk of long-term neurological disability(Doyle 2001b). weeks'gestation, the alveoli can be counted and with increasing age they become more mature. Lung volume increases four-fold While researching the effects of the steroid dexamethasone on pre- between 29 weeks and term Alveolar number shows a curvilinear mature parturition in fetal sheep in 1969, Liggins found that there increase with age but a linear relationship with bodyweight. At as some inflation of the lungs oflambs born at gestations at which birth there are an average of 150 million alveoli(half the expected the lungs would be expected to be airless(Liggins 1969). He the- adult number). The alveoli produce surfactant. The alveolar stage orised, from these observations, that dexamethasone might have continues for one to two years after birth. In the preterm infant, accelerated the appearance of pulmonary surfactant. The hypoth- low alveolar numbers probably contribute to respiratory dysfunc esis is that corticosteroids act to trigger the synthesis of ribonucleic tion of phospholipids or in the breakdown of glycogen. Subsequent tation. Lamellar bodis, which store surfactant, appear at 22 to a number of organ systems(Padbury 1996; Vyas 1997). Liggins 24 weeks. Surfactant is a complex mixture of lipids and apopro. and Howie performed the first randomised controlled trial in hu. choline, phosphatidylglycerol and apoproteins A, B, C and D tion of RDS in 1972(Lig. Surfactant is needed to maintain stability when breathing prevent collapse of the alveoli. Premature infants have a qualita- Fetal lung development rIve ative deficiency of surfactant, which predisposes to Some understanding of fetal lung development may be useful in RDS. Ar the low lung volume associated with expiration, surface understanding why RDS occurs and why corticosteroids work. tension becomes very high, leading to atelectasis with subsequent Fetal lung development can be divided into five stages: embryonic, intrapulmonary shunting, ventilation perfusion inequalities and pseudoglandular, canalicular, terminal sac and alveolar. The lung ultimately respiratory failure. Capillary leakage allows inhibitors first appears as an outgrowth of the foregut at 22 to 26 from plasma to reach alveoli and inactivate any surfactant that may days after conception. By 34 days, the outgrowth has divided into be present. Hypoxia, acidosis and hypothermia(common prob- ft and right sides and further to form the major units of the lung. lems in the very preterm infant) can reduce surfactant synthesis Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth( Review) Copyright @2006 The Cochrane Collaboration. Published by John wiley& Sons, LtdP L A I N L A N G U A G E S U M M A R Y Corticosteroids given to women in early labour help the babies’ lungs to mature and so reduce the number of babies who die or suffer breathing problems at birth Babies born very early are at risk of breathing difficulties (respiratory distress syndrome) and other complications at birth. Some babies have developmental delay and some do not survive the initial complications. In animal studies, corticosteroids are shown to help the lungs to mature and so it was suggested these drugs may help babies in preterm labour too. This review of 21 trials shows that a single course of corticosteroid, given to the mother in preterm labour and before the baby is born, helps to develop the baby’s lungs and reduces complications like respiratory distress syndrome. Furthermore, this treatment results in fewer babies dying and fewer common serious neurological and abdominal problems,e.g. cerebroventricular haemorrhageand necrotising enterocolitis, that affect babies born very early. There does not appear to be any negative effects of the corticosteroid on the mother. Long-term outcomes on both baby and mother are also good. B A C K G R O U N D Respiratory distress syndrome (RDS) is a serious complication of preterm birth and the primary cause of early neonatal death and disability. It affects up to one fifth of low birthweight babies (less than 2500 g) and two thirds of extremely low birthweight babies (less than 1500 g). Respiratory failure in these infants occurs as a result of surfactant deficiency, poor lung anatomical development and immaturity in other organs. Neonatal survival after preterm birth improves with gestation (Doyle 2001a), reflecting improved maturity of organ systems. However, those who survive early neonatal care are at increased risk of long-term neurological disability (Doyle 2001b). History Whileresearching theeffects of thesteroid dexamethasone on pre￾mature parturition in fetal sheep in 1969, Liggins found that there wassomeinflation of thelungs of lambs born at gestationsatwhich the lungs would be expected to be airless (Liggins 1969). He the￾orised, from these observations, that dexamethasone might have accelerated the appearance of pulmonary surfactant. The hypoth￾esis is thatcorticosteroidsact to trigger thesynthesis of ribonucleic acid that codes for particular proteins involved in the biosynthesis of phospholipids or in the breakdown of glycogen. Subsequent work has suggested that, in animal models,corticosteroids mature a number of organ systems (Padbury 1996; Vyas 1997). Liggins and Howie performed the first randomised controlled trial in hu￾mans of betamethasone for the prevention of RDS in 1972 (Lig￾gins 1972b). Fetal lung development Some understanding of fetal lung development may be useful in understanding why RDS occurs and why corticosteroids work. Fetal lung developmentcan be divided into fivestages:embryonic, pseudoglandular, canalicular, terminal sac and alveolar. The lung first appears as an outgrowth of the primitive foregut at 22 to 26 days after conception. By 34 days, the outgrowth has divided into leftand right sides and further to form the major units of thelung. Mature lungs contain more than 40 different cell types derived from this early tissue. From 8 to 16 weeks’ gestation, the major bronchial airways and associated respiratory units of the lung are progressively formed. At this time the lung blood vessels also be￾gin to grow in parallel. From 17 to 25 weeks’ gestation, the air￾ways grow, widen and lengthen (canalisation). Terminal bronchi￾oles with enlargements that subsequently give rise to terminal sacs (the primitive alveoli) are formed. These are the functional units of the lung (respiratory lobules). It is at this stage that the increas￾ing proximity of blood capillaries begins the air-blood interface, required for effective air exchange. This can only take place at the terminal bronchioles. At the end of the canalicular stage, type I and II pneumocytes can be seen in the alveoli. From 28 to 35 weeks’ gestation, the alveoli can be counted and with increasing age they become more mature. Lung volume increases four-fold between 29 weeks and term. Alveolar number shows a curvilinear increase with age but a linear relationship with bodyweight. At birth there are an average of 150 million alveoli (half the expected adult number). The alveoli produce surfactant. The alveolar stage continues for one to two years after birth. In the preterm infant, low alveolar numbers probably contribute to respiratory dysfunc￾tion. The fetal lung also matures biochemically with increasing ges￾tation. Lamellar bodies, which store surfactant, appear at 22 to 24 weeks. Surfactant is a complex mixture of lipids and apopro￾teins, the main constituents of which are dipalmitoylphosphatidyl choline, phosphatidylglycerol and apoproteins A, B, C and D. Surfactant is needed to maintain stability when breathing out, to prevent collapse of the alveoli. Premature infants have a qualita￾tiveand quantitative deficiency of surfactant, which predisposes to RDS. At the low lung volume associated with expiration, surface tension becomes very high, leading to atelectasis with subsequent intrapulmonary shunting, ventilation perfusion inequalities and ultimately respiratory failure. Capillary leakage allows inhibitors from plasmato reach alveoliand inactivateany surfactant that may be present. Hypoxia, acidosis and hypothermia (common prob￾lems in the very preterm infant) can reduce surfactant synthesis Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth (Review) 2 Copyright © 2006 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd 第 96 页