Ampicillin-metronidazole treatment in idiopathic preterm labour: a randomised controlled multicentre trial

Objective To determine whether treatment with ampicillin and metronidazole in women with threatened idiopathic preterm labour will prolong the gestation and reduce maternal and neonatal infectious morbidity.
Design Randomised controlled double-blind trial.
Setting Six obstetric departments in the Copenhagen area.
Population One hundred and twelve women with singleton pregnancies, with threatened idiopathic preterm labour and intact amniotic membranes at 26 to 34 weeks of gestation.
Methods Random allocation to eight days intravenous and oral treatment with ampicillin and metronidazole, or placebo.
Main outcome measures Number of days from admission to delivery, gestational age at delivery, rates of preterm delivery, low birthweight, maternal infections and neonatal infections.
Results Treatment with ampicillin and metronidazole was associated with a significant prolongation of pregnancy (admission to delivery 47.5 days versus 27 days,   P < 0.05  ), higher gestational age at delivery (37 weeks versus 34 weeks,   P < 0.05  ), decreased incidence of preterm birth (42% versus 65%,   P < 0.05  ), and lower rate of admission to neonatal intensive care unit (40% versus 63%,   P < 0.05  ), when compared with placebo treatment. Antibiotic treatment had no significant effects on infectious morbidity.
Conclusions Treatment with ampicillin and metronidazole in women with threatened idiopathic preterm labour significantly prolonged the gestation, but had no effects on maternal and neonatal infectious morbidity.     

Progesterone for maintenance tocolytic therapy after threatened preterm labour: a randomised controlled trial

BACKGROUND: Women with preterm labour that is arrested with tocolytic therapy are at increased risk of recurrent preterm labour. The efficacy of maintenance tocolytic therapy after successful arrest of preterm labour remains controversial. AIM: The purpose of this study was to determine whether supplementation of vaginal progesterone after inhibition of preterm labour is associated with an increased latency period and a decreased recurrent of preterm labour. METHODS: This trial was conducted in 70 women who presented with symptoms of threatened preterm labour, who after arrest of uterine activity were then randomised to progesterone therapy or no treatment. Treatment group received progesterone suppository (400 mg) daily until delivery and control group received no treatment. RESULTS: Longer mean latency until delivery (36/11 +/- 17/9 vs 24/52 +/- 27/2) (mean + standard deviation) days; respiratory distress syndrome 4 (10.8%) vs 12 (36.4%) P = 0.021; low birthweight 10 (27%) vs 17 (51.5%) P = 0.04; and birthweight (3101.54 +/- 587.9 g vs r 2609.39 +/- 662.9 g, P = 0.002), were significantly different between the two groups. No significant differences were found between recurrent preterm labour 13 (35.1%) vs 19 (57.6%), P = 0.092; admission to intensive care unit 9 (24.3%) vs 13 (39.4%), P= 0.205 ; and neonatal sepsis 2 (5.4%) vs 6 (18.2%) P = 0.136, for the progesterone and control groups, respectively. CONCLUSION: The use of vaginal progesterone suppository after successful parenteral tocolysis associated with a longer latency preceding delivery but failed to reduce the incidence of readmission for preterm labour.     

Effect of amoxicillin sulbactam in threatened preterm labour with intact membranes: a randomised controlled trial

OBJECTIVE: To determine whether treatment with amoxicillin-sulbactam in women with threatened idiopathic preterm labour will prolong the gestation and reduce preterm birth rates in a Latin-American population. METHODS: A double-blind, placebo-controlled, randomized trial was conducted in 96 women who were hospitalized for preterm labour between 24 and 34 weeks of gestation at the Pereira Rossell Hospital, in Montevideo, Uruguay. The primary outcome measure was prematurity. The sample size was calculated a priori based on the hospital database. Statistical analyses were performed using the t-test, chi square, weighted mean difference (WMD) and relative risk (RR) with their confidence intervals (95% CI). Analysis by intention-to-treat. RESULTS: Out of 47 patients assigned for antibiotics, 43 completed the treatment. There were no significant statistical differences between antibiotics and placebo group in prematurity (RR:1.04, 95% CI: 0.59, 1.84), prolongation of pregnancy (WMD:0.23, 95% CI: -0.96, 1.42) and other perinatal outcomes. CONCLUSION: Antibiotics did not prove to have benefits in improving perinatal outcomes in this Latin American population.     

Dysfunctional labour: a randomised trial

Sixty-one women making slow progress in the active phase of spontaneous labour with intact membranes were randomised to oxytocin and amniotomy, amniotomy only or expectant management. The data show that oxytocin significantly increases the rate of cervical dilatation and shortens prolonged labour, when compared with amniotomy alone and expectant management (   P = 0.144  and 0–0.06, respectively). The impact on the operative delivery rate and neonatal outcome is difficult to assess due to the small number of relevant adverse outcomes. Women reported higher satisfaction score in the two groups where intervention followed the diagnosis of dysfunctional labour.     

Subcutaneous sterile water injection for labour pain: a randomised controlled trial

BACKGROUND: About 30% of women experience severe continuous low-back pain in labour, but limited options are available to reduce this pain especially in developing countries and remote areas. AIMS: To evaluate the efficacy of subcutaneous sterile water injection in reduction of labour pain compared with placebo. METHODS: One hundred (100) consecutive patients were enrolled in a double-blind randomised controlled trial. During the first stage of labour with planned normal vaginal delivery, the intervention group (n = 50) received 0.5 mL sterile water injected subcutaneously and the control group (n = 50) received normal saline as a placebo. Pain score was measured before and 10 and 45 min after the injection, using the faces rating scale. MAIN OUTCOME MEASURE: Low-back labour pain. RESULTS: The two groups were not significantly different regarding maternal age and weight, gestational age, parity and gravidity and degree of effacement. The median pain score was equal in both groups prior to the injection. Pain severity was reduced in both groups after the injection. However, the median pain score in the sterile water group was significantly lower than the placebo group 10 min (P < 0.01), as well as 45 min, after the injection (P < 0.01). CONCLUSION: Administering one subcutaneous injection of sterile water in a painful point of the lumbosacral area is effective in reducing low-back pain during labour.     

Prostaglandin E vaginal gel to treat dystocia in spontaneous labour: a multicentre randomised placebo-controlled trial

OBJECTIVE: To test the safety and efficacy of prostaglandin E(2) (PgE(2)) as a treatment for dystocia in spontaneous labour. DESIGN: Randomised, double-blind, placebo-controlled trial. SETTING: Multicentre study in nine university-affiliated hospitals in Canada. Population Three hundred and thiry-two nulliparous women with spontaneous labour at term. METHODS: Women who had progressed < 2 cm of cervical dilation in the 4 hours following the diagnosis of labour were randomly assigned to receive a single dose of either 1 mg (n= 112) or 2 mg (n= 111) PgE(2) vaginal gel or placebo gel (n= 109). MAIN OUTCOME MEASURES: The primary outcome was resolution of dystocia, defined as a change in cervical dilatation of >0.5 cm per hour in the 6 hours following gel administration. Secondary outcomes were progress of labour, uterine hyperstimulation (more than five contractions in 10 minutes or a contraction lasting more than 2 minutes), use of oxytocin, method of delivery, maternal and neonatal morbidity. RESULTS: Dystocia resolved more often after PgE(2) 1 mg (49%), RR 1.53 (95% CI 1.1, 2.1) and PgE(2) 2 mg (49%), RR 1.5 (CI 1.1, 2.1), compared with placebo (32%). Hyperstimulation was increased after PgE(2) 2 mg treatment (15%), RR 5.6 (95% CI 1.7, 18), but not after PgE(2) 1 mg (5.4%), RR 1.9 (CI 0.50, 7.6) when compared with placebo (2.8%). There was an increase in caesarean sections performed in the second stage of labour in the PgE(2) groups versus placebo. There were no differences in measures of maternal or neonatal morbidity. CONCLUSION: A single 1-mg dose of PgE(2) vaginal gel is more effective than placebo in resolving dystocia, without increasing uterine hyperstimulation, but may be associated with an increase in the incidence of second stage caesarean section.     

Impact of metronidazole therapy on preterm birth in women with bacterial vaginosis flora (Gardnerella vaginalis): a randomised, placebo controlled trial

Objective To ascertain whether metronidazole treatment of women with a heavy growth of Gardnerella vaginalis during mid-pregnancy would reduce the risk of spontaneous preterm birth.
Design A multicentre, randomised, placebo-controlled trial
Setting Four metropolitan hospitals.
Participants Eight hundred and seventy-nine singleton women with a heavy growth of G. vaginalis or Gram stain indicative of bacterial vaginosis at 19 weeks of gestation.
Interventions Oral metronidazole (400 mg) or placebo twice daily for two days at 24 weeks of gestation, and at 29 weeks if G. vaginalis found in test-of-cure swab four weeks after treatment.
Main outcome measures Spontaneous preterm birth less than 37 weeks.
Results Intention-to-treat analysis showed no difference between metronidazole and placebo groups in overall preterm birth (31/429 [7.2%] vs 32/428 [7.5%]) or spontaneous preterm birth (20/429 [4.7%] vs 24/428 [5.6%]). Among the 480 women with bacterial vaginosis, treatment had no effect on spontaneous preterm birth (11/242 [4.5%] vs 15/238 [6.3%]). In the subset of 46 women with a previous preterm birth, women in the metronidazole group showed a significant reduction in spontaneous preterm birth (2/22 [9.1%] vs 10/24 [41.7%], OR 0.14, 95%CI 0.01–0.84). A treatment effect was also found in compliant women with a previous preterm birth and bacterial vaginosis (0/14 [0%] vs 6/17 [35.3%], OR 0.0,95%CI 0.0–0.94).
Conclusion Metronidazole treatment of women with a heavy growth of G. vaginalis or bacterial vaginosis did not reduce the preterm birth rate. Among women with a previous preterm birth, treatment reduced the risk of spontaneous preterm birth. Further studies are required to confirm these findings.     

Transabdominal amnioinfusion in preterm premature rupture of membranes: a randomised controlled trial

OBJECTIVE: To evaluate the role of transabdominal amnioinfusion in improving the perinatal outcomes of pregnancies complicated by preterm premature rupture of membranes (pPROM). DESIGN: A randomised controlled trial. SETTING: A teaching hospital in Italy, obstetric unit. Population Women with singleton pregnancies complicated by pPROM, between 24 + 0 and 32 + 6 weeks of gestation. METHODS: Patients were randomised 24 hours after admission to our referral hospital, to expectant management with transabdominal amnioinfusion or expectant management only. MAIN OUTCOME MEASURES: The effects of transabdominal amnioinfusion on pPROM-delivery interval and on perinatal outcomes. RESULTS: Of the 65 women with pPROM 34 met the inclusion criteria. Seventeen women were assigned to amnioinfusion (the amnioinfusion group) and the other 17 to expectant management. Compared with the control group (median: 8 days; range: 3-14), the pPROM-delivery period was significantly longer in women who underwent amnioinfusion (median: 21 days; range: 15-29) (P < 0.05). Women with amnioinfusion were less likely to deliver within seven days since pPROM (RR: 0.18; range: 0.04-0.69 95% CI) or within two weeks (RR: 0.46; range: 0.21-1.02 95% CI). In the amnioinfusion group the neonatal survival was significantly higher at each gestational age (P < 0.01, Yates's correction for Log Rank Test) with a reduction in pulmonary hypoplasia. CONCLUSIONS: We demonstrated that compared with standard expectant management the treatment with transabdominal amnioinfusion after pPROM resulted in significant prolongation of pregnancy and better neonatal outcomes.     

Sublingual compared with oral misoprostol in term labour induction: a randomised controlled trial

Objective To compare the efficacy and patient acceptability of 50 μg of sublingual misoprostol with 100 μg of oral misoprostol in the induction of labour at term.
Design Non-blinded randomised comparative trial.
Setting Tertiary level UK Hospital.
Sample Two hundred and fifty women at term with indications for labour induction.
Methods Fifty micrograms of sublingual misoprostol or 100 μg of oral misoprostol was administered every four hours after random allocation, to a maximum of five doses.
Main outcome measures Number of patients delivering vaginally within 24 hours of the induction, mode of delivery, neonatal outcomes and patient acceptability.
Results There was no significant difference in the number of women delivering vaginally within 24 hours of the induction in the sublingual group as compared with the oral group (62.8% vs 59%, RR 1.1, 95% CI 0.6–2.1), or in the mean induction to delivery time (21.8 vs 24.1 h, mean difference 2.3 h 95% CI −2.2 to +6.7). There was no difference in the uterine hyperstimulation rates (1.6% in both groups), operative delivery rates or neonatal outcomes. In the sublingual group, 92.6% found the induction acceptable with 15.8% finding the tablets with an unpleasant taste, while in the oral group it was 96.9% and 4%, respectively. More patients in the oral group thought that they would consider the same method of induction again as compared with the sublingual group (58.6% vs 40%, RR 1.4, 95% CI 1.04–1.9).
Conclusion Fifty micrograms of sublingual misoprostol every four hours has the same efficacy and safety profile as compared with 100 μg orally, but the oral route might be preferred by women.     

Routine oxytocin in the third stage of labour: a placebo controlled randomised trial

Objective To compare intravenous oxytocin administration (Partocon® 10 IU) with saline solution in the management of postpartum haemorrhage in the third stage of labour.
Design A double-blind, randomised controlled trial involving 1000 parturients with singleton fetuses in cephalic presentation and undergoing vaginal delivery, randomly allocated to treatment with oxytocin ( n =513) or 0.9% saline solution ( n =487).
Setting Labour ward at a central county hospital.
Main outcome measures Mean blood loss (total, and before and after placenta delivery); frequencies of blood loss > 800 mL, need of additional oxytocic treatment, postpartum haemoglobin < 10 g/dL; and duration of postpartum hospitalisation.
Results As compared with saline solution, oxytocin administration was associated with significant reduction in mean total blood loss (407 versus 527 mL), and in frequencies of postpartum haemorrhage > 800 mL (8.8% versus 15.2%), additional treatment with metylergometrine (7.8% versus 13.8%), and postpartum Hb < 10 g/dL (9.7% versus 15.2%), and a nonsignificant increase in the frequency of manual placenta removal (3.5% versus 2.3%). There was no group difference in the mean duration of postpartum hospitalisation (4.6 versus 4.5 days, respectively).
Conclusions Administration of intravenous oxytocin in the third stage of labour is associated with an approximately 22% reduction in mean blood loss, and approximately 40% reductions in frequencies of postpartum haemorrhage (> 500 mL or >800 mL) and of postpartum haemoglobin < 10 g/dL. Identification of risk groups for oxytocin treatment does not seem worthwhile. Oxytocin is a cheap atoxic drug and should be given routinely after vaginal delivery.     

Treatment with a gonadotrophin releasing hormone agonist before endometrial resection: a multicentre, randomised controlled trial

Objective To ascertain whether treatment with a gonadotrophin releasing hormone agonist before endometrial resection reduces absorption of distension fluid and operating time and facilitates the procedure.
Design A multicentre, prospective, randomised controlled study.
Participants Seventy-one premenopausal women with established menorrhagia.
Interventions Eight weeks of goserelin depot treatment before endometrial resection of immediate surgery in the early proliferative phase of the cycle.
Main outcome measures Irrigation fluid deficit, operating time and degree or difficulty of the procedure.
Results After randomisation eight women withdrew from the study, leaving 33 women in the goserelin arm and 30 in the immediate surgery arm. Mean (SD) operating time was 15.1 (9.0) min in the goserelin group versus 16.9 (9.5) min in the controls; mean difference † 1.8 min, 95% CI, −2.9 to + 64. Mean (SD) distension medium deficit was, respectively, 422 (287) ml versus 564 (291 ml); mean difference + 142 ml, 95 % CI-4 to + 288. The goserelin effect was restricted to the 29 women with adenomyosis as the mean (SD) fluid deficit was considerably less in the 19 treated women than in the 10 controls (299 (206) ml versus 597 (135) ml; mean difference + 298 ml, 95YO CI +149 to + 447). The surgeons classified the intraoperative difficulties as none in 6, minimal in 20, moderate in 7, and severe in no cases in the goserelin group; corresponding figures in the group without pretreatment were 2, 14, 13, and 1.
Conclusions Goserelin administration before endometrial resection may reduce absorption of fluid at surgery in women with adenomyosis and may facilitate intrauterine operating conditions.     

The effect of indomethacin tocolysis in preterm labour on perinatal outcome: a randomised placebo-controlled trial

Objective To determine whether indomethacin tocolysis in preterm labour is associated with a better perinatal outcome than placebo.
Design A randomised placebo-controlled trial.
Setting Two university teaching hospitals with level three neonatal intensive care units.
Population Women in preterm labour with intact membranes between 23 and 30 weeks of gestation.
Methods Random allocation to tocolysis with indomethacin (50 mg followed by 25 mg 6 hourly for 48 hours) or placebo in a double-blind fashion.
Main outcome measures The primary outcome, perinatal mortality or severe neonatal morbidity, was defined as perinatal death, necrotising enterocolitis, bronchopulmonary dysplasia, intraventricular haemorrhage or pen-ventricular leucomalacia. Data were analysed using odds ratios (OR) and 95% confidence intervals (95% CI).
Results Between March 1995 and February 1996, 34 women (39 babies) were recruited. The baseline characteristics of the two groups were similar. No patient was lost to follow up. In the indomethacin group, gestation was prolonged by > 48 hours in 13/16 (81%) of women vs 10/18 (56%) in the placebo group. The incidence of perinatal mortality or severe neonatal morbidity was not significantly different between the groups, but occurred in twice as many babies in the indomethacin group as in the placebo group d/l9 (32%) vs 3/20 (15%) OR (95% CI) 2.62 (0.44–18.8). There was one perinatal death, of a baby delivered at 24 weeks of gestation. This occurred in the indomethacin group.
Conclusion There is no evidence that indomethacin tocolysis is beneficial, and further trials are needed to assess the impact of indomethacin tocolysis in preterm labour.     

Preventing postnatal depression in mothers of very preterm infants: a randomised controlled trial

OBJECTIVE: To test whether a cognitive-behaviour therapy intervention program reduces the prevalence of depression during the first postnatal year in mothers of very preterm babies. DESIGN: Prospective, single blind, randomised, controlled study. SETTING: Perinatal centre in Western Australia. PARTICIPANTS: One hundred and ninety-nine out of 673 English-speaking mothers of infants admitted to the neonatal unit. INTERVENTION: A six-session cognitive-behaviour therapy intervention program provided by a research midwife between weeks two and six after birth. Women in the control group received standard care. MAIN OUTCOME MEASURES: Depression and anxiety disorders occurring in the first year assessed by a clinical psychologist at structured interview using the Schedule for Affective Disorders and Schizophrenia (SADS) at 2 weeks, 2, 6 and 12 months. RESULTS: One hundred and one women were randomised to the intervention group and 98 to the control group. Fifty-four mothers (27%) in the trial were diagnosed with minor or major depression in the 12 months following very preterm delivery, 29 (29%) in the intervention group and 25 (26%) in the control group (relative risk 1.1 [95% CI 0.80-1.5]). There were no differences in the time of onset or the duration of the episodes of depression between the groups. Overall, 74 mothers (37%) of the 199 met criteria for a diagnosis of psychological morbidity during the first year. CONCLUSIONS: Our intervention program did not alter the prevalence of depression in these mothers. Rates of depression and stress reactions are high in these mothers.     

The effects of acupuncture during labour on nulliparous women: a randomised controlled trial

BACKGROUND: Acupuncture is as an ancient system of diagnosis and treatment. It is regarded as a complementary tool for pain management. AIMS: To assess the effects of acupuncture on nulliparous women during labour with respect to pain, labour duration and maternal acceptability. METHODS: One hundred and forty-four healthy nulliparous women in active phase were randomised into the study and control group, receiving real and minimal acupuncture, respectively. Visual analogue scale was used to assess pain. Objectives were to evaluate acupuncture effect on pain and labour duration and patients' willingness to receive acupuncture for subsequent pregnancies. RESULTS: Visual analogue scale pain score in the study group was lower after two hours. Active phase duration and the oxytocin units administered were lower in the study group. Study group patients had greater willingness to receive acupuncture again. No adverse effects were detected. CONCLUSIONS: Acupuncture could reduce pain experience, active phase duration and oxytocin units. Patients were satisfied and no adverse effects were noted.     

A multicentre randomised controlled trial comparing elective and selective caesarean section for the delivery of the preterm breech infant

Objective To determine the optimum mode of delivery for women in preterm breech labour at a gestational age of 26 to 32 weeks.
Design A multicentre randomised controlled trial. Setting Twenty-six hospitals in England, UK.
Participants Women with a singleton breech fetus in spontaneous preterm labour between 26 and 32 completed weeks of gestation, with no clear indication for a caesarean section or vaginal breech delivery.
Intervention Random allocation to either 'intention to delivery vaginally' or 'intention to deliver by caesarean section'.
Main outcome measures Perinatal mortality, neonatal morbidity, maternal morbidity and gestation at delivery.
Results The trial was closed after 17 months because of low recruitment, by which time substantial numbers of women had been in the eligible gestation period. Thirteen women from six hospitals were recruited. One infant, randomised to and delivered vaginally, was stillborn. Three fetal presentations were cephalic at delivery despite a diagnosis of breech presentation at trial entry. No formal statistical analysis was performed due to the small numbers.
Conclusions No conclusions about the optimum mode of delivery for women in preterm labour with a fetus presenting by the breech can be drawn from this trial. The low accrual rate was due to clinicians' reluctance to randomise eligible women, reflecting the circumstances and nature of the trial.     

The effect of indomethacin tocolysis in preterm labour on perinatal outcome: a randomised placebo-controlled trial.

OBJECTIVE: To determine whether indomethacin tocolysis in preterm labour is associated with a better perinatal outcome than placebo. DESIGN: A randomised placebo-controlled trial. SETTING: Two university teaching hospitals with level three neonatal intensive care units. POPULATION: Women in preterm labour with intact membranes between 23 and 30 weeks of gestation. METHODS: Random allocation to tocolysis with indomethacin (50 mg followed by 25 mg 6 hourly for 48 hours) or placebo in a double-blind fashion. MAIN OUTCOME MEASURES: The primary outcome, perinatal mortality or severe neonatal morbidity, was defined as perinatal death, necrotising enterocolitis, bronchopulmonary dysplasia, intraventricular haemorrhage or peri-ventricular leucomalacia. Data were analysed using odds ratios (OR) and 95% confidence intervals (95% CI). RESULTS: Between March 1995 and February 1996, 34 women (39 babies) were recruited. The baseline characteristics of the two groups were similar. No patient was lost to follow up. In the indomethacin group, gestation was prolonged by > 48 hours in 13/16 (81%) of women vs 10/18 (56%) in the placebo group. The incidence of perinatal mortality or severe neonatal morbidity was not significantly different between the groups, but occurred in twice as many babies in the indomethacin group as in the placebo group--6/19 (32%) vs 3/20 (15%) OR (95% CI) 2.62 (0.44-18.8). There was one perinatal death, of a baby delivered at 24 weeks of gestation. This occurred in the indomethacin group. CONCLUSION: There is no evidence that indomethacin tocolysis is beneficial, and further trials are needed to assess the impact of indomethacin tocolysis in preterm labour.