Antenatal betamethasone and incidence of neonatal respiratory distress
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《英国医生杂志》
1 Conwy and Denbighshire NHS Trust, Glan Clwyd Hospital, Rhyl, Denbighshire LL18 5UJ, 2 Institute of Medical and Social Care Research, University of Wales Bangor LL572PX
Correspondence to: P Stutchfield DrPeter.Stutchfield@cd-tr.wales.nhs.uk
Objective To test whether steroids reduce respiratory distress in babies born by elective caesarean section at term.
Design Multicentre pragmatic randomised trial.
Setting 10 maternity units.
Participants 998 consenting women randomised at decision to deliver by elective caesarean section; 503 randomised to treatment group.
Interventions The treatment group received two intramuscular doses of 12 mg betamethasone in the 48 hours before delivery. The control group received treatment as usual.
Outcome measures The primary outcome was admission to special care baby unit with respiratory distress. Secondary outcomes were severity of respiratory distress and level of care in response.
Results Sex, birth weight, and gestation were not different between the two groups. Of the 35 babies admitted to special baby units with respiratory distress, 24 were in the control group and 11 in the intervention group (P = 0.02). The incidence of admission with respiratory distress was 0.051 in the control group and 0.024 in the treatment group (relative risk 0.46, 95% confidence interval 0.23 to 0.93). The incidence of transient tachypnoea of the newborn was 0.040 in the control group and 0.021 in the treatment group (0.54, 0.26 to 1.12). The incidence of respiratory distress syndrome was 0.011 in the control group and 0.002 in the treatment group (0.21, 0.03 to 1.32).
Conclusions Antenatal betamethasone and delaying delivery until 39 weeks both reduce admissions to special care baby units with respiratory distress after elective caesarean section at term.
The rate of caesarean section in England rose from 9% in 1980 to 22% in 2003 as a result of changing practice in the management of previous caesarean and breech presentation as well as increased choice for women.1 2 This increase has included some women who opted for caesarean section at socially convenient times, without medical reasons.3 One survey reported that 69% of consultant obstetricians in England and Wales agree to women's requests for section in the absence of obstetric indications.4 Recent guidelines from the National Institute for Clinical Excellence (NICE, now National Institute for Health and Clinical Excellence) have recommended that a woman's request alone is not an indication for caesarean section.5
The consequences of elective caesarean section at term for the baby have received little attention. The incidence of respiratory distress is much higher than in vaginal delivery (0.036 v 0.0053).6 Other risk factors for respiratory distress include gestational age, mode of delivery, male sex, fetal asphyxia, maternal asthma and diabetes, and type of anaesthesia given during delivery (regional or general).6-9 The development of respiratory distress leads to admission to a special care baby unit or neonatal intensive care unit, often at a distance, separation from the mother, and complications from invasive procedures including artificial ventilation.
Antenatal corticosteroids reduce the incidence of respiratory distress in preterm babies.10 Guidance has long recommended their routine use when delivery is expected before 34 weeks' gestation.11 12 However, no trials have been conducted of antenatal corticosteroids in mothers delivered by elective caesarean section at term.
The antenatal steroids for term caesarean section (ASTECS) randomised trial therefore sought to evaluate whether giving the recommended two doses of betamethasone before delivery13 reduces the incidence of respiratory distress in babies delivered by elective caesarean section at term. Five studies lasting between three and 20 years, with more than 1500 patients, have shown no adverse effects of a single course of antenatal corticosteroids, neither through infection of fetus or mother nor in long term neurological or cognitive effects.10 12
Methods
In 1995 the ASTECS team submitted the protocol to the National Perinatal Trial Centre, started recruitment, and invited other obstetric units to participate. By November 1998, altogether 10 units were taking part.
Mothers were eligible for the trial if elective caesarean section was planned at 37 weeks' gestation or beyond. Exclusion criteria included severe maternal hypertension, history of peptic ulceration, severe fetal rhesus sensitisation, and evidence of intrauterine infection. We used an algorithm from the Confidential Enquiry into Sudden Death in Infancy (CESDI) to calculate gestation from last menstrual period, expected date of delivery, and estimates from first ultrasound scan and at birth. Women who were eligible received an explanation of the study and an information sheet. In the 48 hours before elective caesarean section, women received either two intramuscular doses of 12 mg of betamethasone, separated by 24 hours, or treatment as usual, without antenatal steroids.
The trial centre in Rhyl held a list of treatment allocations derived from the random number generator in MS Excel but concealed from all participants. Midwives with signed consent from a mother phoned Rhyl and received the next allocation on the list. They informed the mother and recorded the allocation in her notes. As ASTECS was a pragmatic trial to estimate the effectiveness of betamethasone for caesarean section at term in routine clinical practice, blinding participants and professionals was neither desirable nor possible.
Outcome measures
The primary outcome was admission to a special care baby unit with respiratory distress. Secondary outcomes were severity of respiratory distress and level of care needed.14 To diagnose respiratory distress within 24 hours of birth needed tachypnoea (more than 60 breaths per minute) with grunting, recession, or nasal flaring. From reported arterial gases and oximetry measurements, we graded respiratory distress as mild if the baby received less than 30% oxygen, severe if it received more than 70% oxygen or ventilatory support, otherwise moderate. We asked for chest radiographs of babies admitted with respiratory distress. Two neonatal radiologists (David Pilling, consultant radiologist at Alder Hey Children's Hospital, and Alan Sprigg, consultant radiologist at Sheffield Children's Hospital) independently assessed these for the radiological features of transient tachypnoea of the newborn or the reticular granular pattern of respiratory distress syndrome.15
Sample size and analysis
Recruiting 1100 mothers would have yielded 80% power of detecting a reduction in the percentage of babies admitted to special baby units with respiratory distress from 8% to 4% when a 5% significance level was used. Because antenatal steroids do not reduce respiratory distress syndrome in twin pregnancy,16 we analyse only singleton deliveries. Analysis was by intention to treat, t test for normally distributed data, and 2 test for categorical data, using logistic regression to adjust for confounding variables.
Results
Recruitment began in Rhyl in February 1995 and another nine centres by November 1998. The last pregnant woman entered the trial in April 2002. Follow-up continued until December 2002, when all babies had left hospital. In all 998 women entered the study—313 from Bradford Royal Infirmary, 233 from Ipswich Hospital, 210 from Glan Clwyd Hospital, 135 from Southmead Hospital, and 107 from the remaining six centres.
Figure 1 shows the flow of participants through the trial. The trial centre received no data after randomisation on 29 women. There were 20 sets of twins, and seven mothers gave birth before 37 weeks' gestation. Hence 942 babies were available for intention to treat analysis, 467 in the treatment group and 475 in the control group. These two groups were similar in mothers' age, asthma, and smoking, and in babies' sex and birth weight (table 1). Eighty six (9.1%) were born at 37 weeks' working gestation, 434 (46.1%) at 38 weeks, 357 (37.9%) at 39 weeks, 46 (4.9%) at 40 weeks, 13 (1.4%) at 41 weeks, and 6 (0.6%) at 42 or more weeks. Ten women (four in the treatment group) had diabetes: six had gestational diabetes that was controlled by diet, three had type 1 diabetes and one type 2 diabetes. None of their babies developed respiratory distress. In all, 51 women delivered by emergency section before random allocation came into effect.
Fig 1 Flow of participants through the trial
Table 1 Mothers' and babies' characteristics by intention to treat
Primary outcome: admission to special care baby unit
Table 2 shows that 35 babies entered these units with respiratory distress, 24 in the control group and 11 in the treatment group (P = 0.021). The incidence of admission with respiratory distress was therefore 0.051 in the control group and 0.024 in the treatment group—a relative risk of 0.46 in favour of treatment (95% confidence interval 0.23 to 0.93).
Table 2 Outcomes by group
Secondary outcomes
No mother of a control baby admitted to a special care baby unit received general anaesthetic, compared with five (45%) in the treatment group (P < 0.001). Three (12%) of the control babies so admitted received neonatal resuscitation, compared with eight (73%) in the treatment group (P < 0.001). Four (36%) of these intervention babies also received ventilation through a mask, and two (18%) also received intubation, compared with none in the control group (P = 0.006 and P = 0.09, respectively). The two groups did, however, not differ significantly with regard to the sex, birth weight, or gestation of infants admitted to a special baby unit.
Table 3 shows that the severity of respiratory distress in babies admitted to special care baby unit was similar in both groups. We received radiographs relating to 22 of the 35 babies admitted with respiratory distress. The remaining 13 babies had diagnoses of transient tachypnoea of the newborn on discharge. Nineteen control babies had transient tachypnoea of the newborn and five had respiratory distress syndrome, compared with 10 treated babies with transient tachypnoea and one with respiratory distress syndrome. The incidence of respiratory distress syndrome was therefore 0.011 in the control group and 0.002 in the treatment group (relative risk 0.21, 0.03 to 1.32), and the incidence of transient tachypnoea of the newborn was 0.040 in the control group and 0.021 in the treatment group (0.54, 0.26 to 1.12).
Table 3 Reason for admission to special care baby unit by group
Only two intervention babies received intensive care—one at level 1 for one day and level 2 (high dependency) for three days, the other at level 2 for one day (fig 2). In contrast, 14 control babies received intensive care; three with respiratory distress syndrome required ventilation for between two and five days and stays of between 12 and 18 days. Antenatal betamethasone thus substantially reduced resource use in special baby units.
Fig 2 Babies admitted to a special care baby unit in descending order of intensity of care and of length of stay: intention to treat analysis
The logistic regression model in figure 3 predicts the probability of admission to special care baby unit with respiratory distress from the gestational age of the baby. The predicted probability of admission at 37 weeks was 11.4% in the control group and 5.2% in the treatment group, at 38 weeks it was 6.2% and 2.8%, respectively, and at 39 weeks it was 1.5% and 0.6%.
Fig 3 Probability of admission to special care baby unit with respiratory distress by gestation (observed and predicted by logistic model): intention to treat analysis. Logistic regression model: z=-5.034+2.139 (if baby is 37 weeks)+1.472 (if baby is 38 weeks)+0.840 (if mother was not randomised to receive betamethasone) where the default is randomised to receive betamethasone at 39 weeks. Predicted probability=exp(z)/
Adverse effects
Reports of side effects came from seven mothers in the treatment group who had received two doses of betamethasone and one who had received only one. Five reported generalised flushing, one nausea, one tenderness at the injection site, and one increased energy with difficulty in sleeping. No such reports came from the control group. No reports were made of wound infection or neonatal sepsis.
Discussion
Royal College of Obstetricians and Gynaecologists Clinical Effectiveness Unit. The national sentinel caesarean section audit report. London: RCOG Press, 2001.
Department of Health. NHS maternity statistics, England: 2002-3. London: DoH, 2004. (Bulletin 2004/10.)
Doctors told to curb "posh" caesareans. Sunday Times 2004 April 25: 14.
Cotzias CS, Paterson-Brown S, Fisk NM. Obstetricians say yes to maternal request for elective caesarean section: a survey of current opinion. Eur J Obstet Gynaecol Reprod Biol 2001;97: 15-6.
National Collaborating Centre for Women and Children's Health. Caesarean section clinical guideline. London: RCOG Press, 2004.
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.
Robert ME, Neff RK, Hubbell JP, Taeusch HW, Avery ME. Association between maternal diabetes and the respiratory distress syndrome in the newborn. N Engl J Med 1976;294: 357-60.
Schatz M, Zeiger RS, Hoffman CP, Saunders BS, Harden KM, Forsythe AB. Increased transient tachypnoea of the newborn in infants of asthmatic mothers. Am J Dis Child 1991;145: 156-8.
Demissie K, Marcella SW, Breckenridge MB, Rhoads GG. Maternal asthma and transient tachypnoea of the newborn. Pediatrics 1998;102: 84-90.
Crowley P. Prophylactic corticosteriods for preterm birth. Cochrane Database Syst Rev 2000;(2): CD000065.
Crowley P, Chalmers I, Keirse MJNC. The effects of corticosteroid administration before preterm delivery: an overview of the evidence from controlled trials. Br J Obstet Gynaecol 1990;97: 11-25.
Royal College of Obstetricians and Gynaecologists Scientific Advisory Committee. RCOG guidelines No 7: antenatal corticosteroids to prevent respiratory distress syndrome. 2nd ed. London: RCOG Press, 2004: 1-9.
McCarthy M. Recommendations for antenatal corticosteroids. Lancet 1994;343: 726.
Report of working group of the British Association of Perinatal Medicine and Neonatal Nurses Association on categories of babies requiring neonatal care. Arch Dis Child 1992;67: 868-9.
Avery ME, Gatewood OB, Brumley G. Transient tachypnoea of newborn. Am J Dis Child 1966;111: 380-5.
Quist-Therson EC, Myhr TL, Ohlsson A. Antenatal steroids to prevent respiratory distress syndrome; multiple gestation as an effect modifier. Acta Obstet Gynecol Scand 1999;78: 388-92.
Hillan EM. Postoperative morbidity following caesarean delivery. J Adv Nurs 1995;22: 1035-42.
Watlers DV, Oliver RE. The role of catecholamines in lung fluid absorption at birth. Pediatr Res 1978;12: 239-42.
Rimmer S, Fawcitt J. Delayed clearance of pulmonary fluid in the neonate. Arch Dis Child 1982;57: 63-7.
O'Brodovich HM. Immature epithelial Na+ channel expression is one of the pathogenetic mechanisms leading to human neonatal respiratory distress syndrome. Proc Assoc Am Physicians 1996;108: 345-55.
Symanski ME. Maternal-infant bonding, practice issues for the 1990s. J Nurs Midwifery 1992;37: 2:67S-73S
Madar J, Richmond S, Hey E. Surfactant deficient respiratory distress after elective delivery at `term'. Acta Paediatr 1999;88: 1244-8.
Smith GC, Wood AM, White IR, Pell JP, Cameron AD, Dobbie R. Neonatal respiratory morbidity at term and the risk of childhood asthma. Arch Dis Child 2004;89: 956-60.(Peter Stutchfield, consultant paediatric)
Correspondence to: P Stutchfield DrPeter.Stutchfield@cd-tr.wales.nhs.uk
Objective To test whether steroids reduce respiratory distress in babies born by elective caesarean section at term.
Design Multicentre pragmatic randomised trial.
Setting 10 maternity units.
Participants 998 consenting women randomised at decision to deliver by elective caesarean section; 503 randomised to treatment group.
Interventions The treatment group received two intramuscular doses of 12 mg betamethasone in the 48 hours before delivery. The control group received treatment as usual.
Outcome measures The primary outcome was admission to special care baby unit with respiratory distress. Secondary outcomes were severity of respiratory distress and level of care in response.
Results Sex, birth weight, and gestation were not different between the two groups. Of the 35 babies admitted to special baby units with respiratory distress, 24 were in the control group and 11 in the intervention group (P = 0.02). The incidence of admission with respiratory distress was 0.051 in the control group and 0.024 in the treatment group (relative risk 0.46, 95% confidence interval 0.23 to 0.93). The incidence of transient tachypnoea of the newborn was 0.040 in the control group and 0.021 in the treatment group (0.54, 0.26 to 1.12). The incidence of respiratory distress syndrome was 0.011 in the control group and 0.002 in the treatment group (0.21, 0.03 to 1.32).
Conclusions Antenatal betamethasone and delaying delivery until 39 weeks both reduce admissions to special care baby units with respiratory distress after elective caesarean section at term.
The rate of caesarean section in England rose from 9% in 1980 to 22% in 2003 as a result of changing practice in the management of previous caesarean and breech presentation as well as increased choice for women.1 2 This increase has included some women who opted for caesarean section at socially convenient times, without medical reasons.3 One survey reported that 69% of consultant obstetricians in England and Wales agree to women's requests for section in the absence of obstetric indications.4 Recent guidelines from the National Institute for Clinical Excellence (NICE, now National Institute for Health and Clinical Excellence) have recommended that a woman's request alone is not an indication for caesarean section.5
The consequences of elective caesarean section at term for the baby have received little attention. The incidence of respiratory distress is much higher than in vaginal delivery (0.036 v 0.0053).6 Other risk factors for respiratory distress include gestational age, mode of delivery, male sex, fetal asphyxia, maternal asthma and diabetes, and type of anaesthesia given during delivery (regional or general).6-9 The development of respiratory distress leads to admission to a special care baby unit or neonatal intensive care unit, often at a distance, separation from the mother, and complications from invasive procedures including artificial ventilation.
Antenatal corticosteroids reduce the incidence of respiratory distress in preterm babies.10 Guidance has long recommended their routine use when delivery is expected before 34 weeks' gestation.11 12 However, no trials have been conducted of antenatal corticosteroids in mothers delivered by elective caesarean section at term.
The antenatal steroids for term caesarean section (ASTECS) randomised trial therefore sought to evaluate whether giving the recommended two doses of betamethasone before delivery13 reduces the incidence of respiratory distress in babies delivered by elective caesarean section at term. Five studies lasting between three and 20 years, with more than 1500 patients, have shown no adverse effects of a single course of antenatal corticosteroids, neither through infection of fetus or mother nor in long term neurological or cognitive effects.10 12
Methods
In 1995 the ASTECS team submitted the protocol to the National Perinatal Trial Centre, started recruitment, and invited other obstetric units to participate. By November 1998, altogether 10 units were taking part.
Mothers were eligible for the trial if elective caesarean section was planned at 37 weeks' gestation or beyond. Exclusion criteria included severe maternal hypertension, history of peptic ulceration, severe fetal rhesus sensitisation, and evidence of intrauterine infection. We used an algorithm from the Confidential Enquiry into Sudden Death in Infancy (CESDI) to calculate gestation from last menstrual period, expected date of delivery, and estimates from first ultrasound scan and at birth. Women who were eligible received an explanation of the study and an information sheet. In the 48 hours before elective caesarean section, women received either two intramuscular doses of 12 mg of betamethasone, separated by 24 hours, or treatment as usual, without antenatal steroids.
The trial centre in Rhyl held a list of treatment allocations derived from the random number generator in MS Excel but concealed from all participants. Midwives with signed consent from a mother phoned Rhyl and received the next allocation on the list. They informed the mother and recorded the allocation in her notes. As ASTECS was a pragmatic trial to estimate the effectiveness of betamethasone for caesarean section at term in routine clinical practice, blinding participants and professionals was neither desirable nor possible.
Outcome measures
The primary outcome was admission to a special care baby unit with respiratory distress. Secondary outcomes were severity of respiratory distress and level of care needed.14 To diagnose respiratory distress within 24 hours of birth needed tachypnoea (more than 60 breaths per minute) with grunting, recession, or nasal flaring. From reported arterial gases and oximetry measurements, we graded respiratory distress as mild if the baby received less than 30% oxygen, severe if it received more than 70% oxygen or ventilatory support, otherwise moderate. We asked for chest radiographs of babies admitted with respiratory distress. Two neonatal radiologists (David Pilling, consultant radiologist at Alder Hey Children's Hospital, and Alan Sprigg, consultant radiologist at Sheffield Children's Hospital) independently assessed these for the radiological features of transient tachypnoea of the newborn or the reticular granular pattern of respiratory distress syndrome.15
Sample size and analysis
Recruiting 1100 mothers would have yielded 80% power of detecting a reduction in the percentage of babies admitted to special baby units with respiratory distress from 8% to 4% when a 5% significance level was used. Because antenatal steroids do not reduce respiratory distress syndrome in twin pregnancy,16 we analyse only singleton deliveries. Analysis was by intention to treat, t test for normally distributed data, and 2 test for categorical data, using logistic regression to adjust for confounding variables.
Results
Recruitment began in Rhyl in February 1995 and another nine centres by November 1998. The last pregnant woman entered the trial in April 2002. Follow-up continued until December 2002, when all babies had left hospital. In all 998 women entered the study—313 from Bradford Royal Infirmary, 233 from Ipswich Hospital, 210 from Glan Clwyd Hospital, 135 from Southmead Hospital, and 107 from the remaining six centres.
Figure 1 shows the flow of participants through the trial. The trial centre received no data after randomisation on 29 women. There were 20 sets of twins, and seven mothers gave birth before 37 weeks' gestation. Hence 942 babies were available for intention to treat analysis, 467 in the treatment group and 475 in the control group. These two groups were similar in mothers' age, asthma, and smoking, and in babies' sex and birth weight (table 1). Eighty six (9.1%) were born at 37 weeks' working gestation, 434 (46.1%) at 38 weeks, 357 (37.9%) at 39 weeks, 46 (4.9%) at 40 weeks, 13 (1.4%) at 41 weeks, and 6 (0.6%) at 42 or more weeks. Ten women (four in the treatment group) had diabetes: six had gestational diabetes that was controlled by diet, three had type 1 diabetes and one type 2 diabetes. None of their babies developed respiratory distress. In all, 51 women delivered by emergency section before random allocation came into effect.
Fig 1 Flow of participants through the trial
Table 1 Mothers' and babies' characteristics by intention to treat
Primary outcome: admission to special care baby unit
Table 2 shows that 35 babies entered these units with respiratory distress, 24 in the control group and 11 in the treatment group (P = 0.021). The incidence of admission with respiratory distress was therefore 0.051 in the control group and 0.024 in the treatment group—a relative risk of 0.46 in favour of treatment (95% confidence interval 0.23 to 0.93).
Table 2 Outcomes by group
Secondary outcomes
No mother of a control baby admitted to a special care baby unit received general anaesthetic, compared with five (45%) in the treatment group (P < 0.001). Three (12%) of the control babies so admitted received neonatal resuscitation, compared with eight (73%) in the treatment group (P < 0.001). Four (36%) of these intervention babies also received ventilation through a mask, and two (18%) also received intubation, compared with none in the control group (P = 0.006 and P = 0.09, respectively). The two groups did, however, not differ significantly with regard to the sex, birth weight, or gestation of infants admitted to a special baby unit.
Table 3 shows that the severity of respiratory distress in babies admitted to special care baby unit was similar in both groups. We received radiographs relating to 22 of the 35 babies admitted with respiratory distress. The remaining 13 babies had diagnoses of transient tachypnoea of the newborn on discharge. Nineteen control babies had transient tachypnoea of the newborn and five had respiratory distress syndrome, compared with 10 treated babies with transient tachypnoea and one with respiratory distress syndrome. The incidence of respiratory distress syndrome was therefore 0.011 in the control group and 0.002 in the treatment group (relative risk 0.21, 0.03 to 1.32), and the incidence of transient tachypnoea of the newborn was 0.040 in the control group and 0.021 in the treatment group (0.54, 0.26 to 1.12).
Table 3 Reason for admission to special care baby unit by group
Only two intervention babies received intensive care—one at level 1 for one day and level 2 (high dependency) for three days, the other at level 2 for one day (fig 2). In contrast, 14 control babies received intensive care; three with respiratory distress syndrome required ventilation for between two and five days and stays of between 12 and 18 days. Antenatal betamethasone thus substantially reduced resource use in special baby units.
Fig 2 Babies admitted to a special care baby unit in descending order of intensity of care and of length of stay: intention to treat analysis
The logistic regression model in figure 3 predicts the probability of admission to special care baby unit with respiratory distress from the gestational age of the baby. The predicted probability of admission at 37 weeks was 11.4% in the control group and 5.2% in the treatment group, at 38 weeks it was 6.2% and 2.8%, respectively, and at 39 weeks it was 1.5% and 0.6%.
Fig 3 Probability of admission to special care baby unit with respiratory distress by gestation (observed and predicted by logistic model): intention to treat analysis. Logistic regression model: z=-5.034+2.139 (if baby is 37 weeks)+1.472 (if baby is 38 weeks)+0.840 (if mother was not randomised to receive betamethasone) where the default is randomised to receive betamethasone at 39 weeks. Predicted probability=exp(z)/
Adverse effects
Reports of side effects came from seven mothers in the treatment group who had received two doses of betamethasone and one who had received only one. Five reported generalised flushing, one nausea, one tenderness at the injection site, and one increased energy with difficulty in sleeping. No such reports came from the control group. No reports were made of wound infection or neonatal sepsis.
Discussion
Royal College of Obstetricians and Gynaecologists Clinical Effectiveness Unit. The national sentinel caesarean section audit report. London: RCOG Press, 2001.
Department of Health. NHS maternity statistics, England: 2002-3. London: DoH, 2004. (Bulletin 2004/10.)
Doctors told to curb "posh" caesareans. Sunday Times 2004 April 25: 14.
Cotzias CS, Paterson-Brown S, Fisk NM. Obstetricians say yes to maternal request for elective caesarean section: a survey of current opinion. Eur J Obstet Gynaecol Reprod Biol 2001;97: 15-6.
National Collaborating Centre for Women and Children's Health. Caesarean section clinical guideline. London: RCOG Press, 2004.
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.
Robert ME, Neff RK, Hubbell JP, Taeusch HW, Avery ME. Association between maternal diabetes and the respiratory distress syndrome in the newborn. N Engl J Med 1976;294: 357-60.
Schatz M, Zeiger RS, Hoffman CP, Saunders BS, Harden KM, Forsythe AB. Increased transient tachypnoea of the newborn in infants of asthmatic mothers. Am J Dis Child 1991;145: 156-8.
Demissie K, Marcella SW, Breckenridge MB, Rhoads GG. Maternal asthma and transient tachypnoea of the newborn. Pediatrics 1998;102: 84-90.
Crowley P. Prophylactic corticosteriods for preterm birth. Cochrane Database Syst Rev 2000;(2): CD000065.
Crowley P, Chalmers I, Keirse MJNC. The effects of corticosteroid administration before preterm delivery: an overview of the evidence from controlled trials. Br J Obstet Gynaecol 1990;97: 11-25.
Royal College of Obstetricians and Gynaecologists Scientific Advisory Committee. RCOG guidelines No 7: antenatal corticosteroids to prevent respiratory distress syndrome. 2nd ed. London: RCOG Press, 2004: 1-9.
McCarthy M. Recommendations for antenatal corticosteroids. Lancet 1994;343: 726.
Report of working group of the British Association of Perinatal Medicine and Neonatal Nurses Association on categories of babies requiring neonatal care. Arch Dis Child 1992;67: 868-9.
Avery ME, Gatewood OB, Brumley G. Transient tachypnoea of newborn. Am J Dis Child 1966;111: 380-5.
Quist-Therson EC, Myhr TL, Ohlsson A. Antenatal steroids to prevent respiratory distress syndrome; multiple gestation as an effect modifier. Acta Obstet Gynecol Scand 1999;78: 388-92.
Hillan EM. Postoperative morbidity following caesarean delivery. J Adv Nurs 1995;22: 1035-42.
Watlers DV, Oliver RE. The role of catecholamines in lung fluid absorption at birth. Pediatr Res 1978;12: 239-42.
Rimmer S, Fawcitt J. Delayed clearance of pulmonary fluid in the neonate. Arch Dis Child 1982;57: 63-7.
O'Brodovich HM. Immature epithelial Na+ channel expression is one of the pathogenetic mechanisms leading to human neonatal respiratory distress syndrome. Proc Assoc Am Physicians 1996;108: 345-55.
Symanski ME. Maternal-infant bonding, practice issues for the 1990s. J Nurs Midwifery 1992;37: 2:67S-73S
Madar J, Richmond S, Hey E. Surfactant deficient respiratory distress after elective delivery at `term'. Acta Paediatr 1999;88: 1244-8.
Smith GC, Wood AM, White IR, Pell JP, Cameron AD, Dobbie R. Neonatal respiratory morbidity at term and the risk of childhood asthma. Arch Dis Child 2004;89: 956-60.(Peter Stutchfield, consultant paediatric)