Multiple courses of antenatal corticosteroids for preterm birth (MACS): a randomised controlled trial.

BACKGROUND: One course of antenatal corticosteroids reduces the risk of respiratory distress syndrome and neonatal death. Weekly doses given to women who remain undelivered after a single course may have benefits (less respiratory morbidity) or cause harm (reduced growth in utero). We aimed to find out whether multiple courses of antenatal corticosteroids would reduce neonatal morbidity and mortality without adversely affecting fetal growth. METHODS: 1858 women at 25-32 weeks' gestation who remained undelivered 14-21 days after an initial course of antenatal corticosteroids and continued to be at high risk of preterm birth were randomly assigned to multiple courses of antenatal corticosteroids (n=937) or placebo (n=921), every 14 days until week 33 or delivery, whichever came first. The primary outcome was a composite of perinatal or neonatal mortality, severe respiratory distress syndrome, intraventricular haemorrhage (grade III or IV), periventricular leucomalacia, bronchopulmonary dysplasia, or necrotising enterocolitis. Analysis was by intention to treat. All patients and caregivers were unaware of the treatment given. This trial is registered as number ISRCTN2654148. FINDINGS: Infants exposed to multiple courses of antenatal corticosteroids had similar morbidity and mortality to those exposed to placebo (150 [12.9%] vs 143 [12.5%]). Those receiving multiple doses of corticosteroids also weighed less at birth than those exposed to placebo (2216 g vs 2330 g, p=0.0026), were shorter (44.5 cm vs 45.4 cm, p<0.001), and had a smaller head circumference (31.1 cm vs 31.7 cm, p<0.001). INTERPRETATION: Multiple courses of antenatal corticosteroids, every 14 days, do not improve preterm-birth outcomes, and are associated with a decreased weight, length, and head circumference at birth. Therefore, this treatment schedule is not recommended. FUNDING: Canadian Institutes of Health Research.

Factors associated with maternal morbidity in the Term Breech Trial.

OBJECTIVE: In the Term Breech Trial, the risk of maternal morbidity in women who delivered after planning for a caesarean section (CS) was not significantly different from those who delivered after planning for a vaginal birth. We undertook secondary analyses to determine factors associated with maternal morbidity among 2078 women. METHODS: By using multiple logistic regression analyses, we determined the effect of prelabour CS, CS during early labour, CS during active labour, vaginal birth, and other factors on maternal morbidity. For 1536 women delivered after labour, we determined the effect of variables associated with labour on maternal morbidity. RESULTS: The risk of maternal morbidity was lowest following vaginal birth (odds ratio [OR] 1.0) and highest following CS during active labour (OR 3.33; 95% confidence intervals [CI] 1.75-6.33, P < 0.001). For those delivered after labour, a short active phase of the second stage of labour (< 30 minutes) was associated with the lowest risk of maternal morbidity (OR 0.25; 95% CI 0.11-0.57, P < 0.001). CONCLUSION: For women with a singleton fetus in breech resentation at term, maternal morbidity is lowest following vaginal birth and highest following CS during active labour.

Preterm labour and birth: a survey of clinical practice regarding use of tocolytics, antenatal corticosteroids, and progesterone.

OBJECTIVES: We wished to determine prescribing practices of obstetricians in Canada regarding tocolytics, antenatal corticosteroids, and progesterone for women at increased risk of preterm labour and birth, and to determine whether these practices changed between 1997-98 and 2004. METHODS: Two cross-sectional surveys of Canadian obstetricians were conducted. The initial survey was in 1997-98 (N = 1313); the follow-up survey was in 2004 (N = 1508). RESULTS: Response rates were 46.4% in 1997-98 and 43.3% in 2004. Most respondents reported that they prescribed tocolytics to women with signs and symptoms of preterm labour (97.4% in 1997-98; 92.2% in 2004; P < 0.001) but use had decreased. In 1997-98, 20.0% of respondents used tocolytics for > 48 hours during one course of treatment, whereas in 2004, only 9.6% did this (P = 0.06). The tocolytic prescribed most frequently was magnesium sulphate in 1997-98 (40.6% of respondents), whereas in 2004, it was indomethacin (47.5% of respondents). The use of repeat courses of antenatal corticosteroids decreased from 72.9% in 1997-98 to 18.7% in 2004 (P < 0.001). In 2004, only a few respondents (7.0%) prescribed progesterone for women at increased risk of preterm birth. CONCLUSIONS: Most Canadian obstetricians continue to use tocolytics for women in preterm labour, although use has decreased over time, and the most frequently prescribed tocolytic has changed from magnesium sulphate to indomethacin. The use of repeat courses of antenatal corticosteroids decreased substantially during this time, and in 2004, progesterone was not in frequent use.

External cephalic version beginning at 34 weeks' gestation versus 37 weeks' gestation: a randomized multicenter trial.

OBJECTIVE: In about 3% to 4% of all pregnancies at term, the fetal presentation will be noncephalic. External cephalic version (ECV) at term has been shown to decrease the rate of noncephalic presentation at birth and to decrease the rate of cesarean section associated with breech presentation. However, success rates for ECV are low. We did a randomized trial to compare a policy of beginning ECV early, at between 34 and 36 weeks' gestation, and beginning ECV at 37 to 38 weeks' gestation. STUDY DESIGN: At 25 centers in seven countries, 233 women with a singleton breech fetus were randomly assigned to having an ECV procedure done early (at between 34 weeks 0 days and 36 weeks 0 days), or delayed (at between 37 weeks 0 days and 38 weeks 0 days). An experienced practitioner undertook the ECV procedure, and repeat ECV procedures were allowed. Tocolytics and use of epidural analgesia were included as part of the protocol. The primary outcome was the rate of noncephalic presentation at birth. An intention-to-treat analysis was used. RESULTS: Data were received for 232 women, with 116 women in each of the early and delayed ECV groups. Of these, 86.2% in the early ECV group and 67.2% in the delayed ECV group had at least one ECV performed. The rate of noncephalic presentation at birth in the early ECV group was 66 of 116 (56.9%) and 77 of 116 (66.4%) in the delayed ECV group (relative risk [RR] [95% CI] 0.86 [0.70-1.05], P =.09). The rate of serious fetal complications and the rate of preterm birth at <37 weeks were not significantly increased in the early ECV group compared with the delayed ECV group (6.9% vs 7.8%, RR [95% CI] 0.89 [0.36-2.22], P =.69 and 8.6% vs 6.1%, RR [95% CI] 1.42 [0.56-3.59], P =.31, respectively). The rate of cesarean section in the early ECV group was 75 of 116 (64.7%) and 83 of 116 (71.6%) in the delayed ECV group (RR [95% CI] 0.90 [0.76-1.08], P =.32). Neonatal outcomes were comparable in the two groups. The rate of reversion to noncephalic was low in both groups. The majority of women in both groups indicated that they would consider having an ECV in another pregnancy. CONCLUSION: Early ECV performed at 34 to 36 weeks compared with 37 to 38 weeks may reduce the risk of noncephalic presentation at delivery. A large pragmatic trial of early ECV is now required to assess this approach further in terms of cesarean section rates and neonatal outcomes before changes in clinical practice.

Crossing international boundaries: implications for the Term Breech Trial Data Coordinating Centre.

The Term Breech Trial (TBT) is a multicenter, international randomized trial that compared a policy of planned cesarean section with a policy of planned vaginal birth for selected pregnancies with a fetus in breech presentation at term. The TBT involved 121 centers in 26 countries that recruited 2088 women between January 9, 1997 and April 21, 2000. This paper briefly describes the impact of broad international collaboration on data coordinating center activities, including center selection, obtaining ethics approvals, data management, center funding, and recruitment.