Global report on preterm birth and stillbirth (3 of 7): evidence for effectiveness of interventions. Antibiotic treatment of preterm labor with intact membranes: a multicenter, randomized, double-blinded, placebo-controlled trial. Failure to prevent preterm labour and delivery in twin pregnancy using prophylactic oral salbutamol. Cervicovaginal microflora and pregnancy outcome: results of a double-blind, placebo-controlled trial of erythromycin treatment. Prophylactic administration of clindamycin 2% vaginal cream to reduce the incidence of spontaneous preterm birth in women with an increased recurrence risk: a randomised placebo-controlled double-blind trial. Prospective randomised controlled trial of an infection screening programme to reduce the rate of preterm delivery. A randomised, double-blind placebo-controlled trial of ascorbic acid supplementation for the prevention of preterm labour. A prospective, randomized, placebo-controlled trial of penicillin in preterm premature rupture of membranes. Prevention of preterm birth in high-risk patients: the role of education and provider contact versus home uterine monitoring.
Interventions directed toward mothers before and during pregnancy and childbirth may help reduce preterm births and stillbirths. Survival of preterm newborns may also be improved with interventions given during these times or soon after birth. This comprehensive review assesses existing interventions for low- and middle-income countries (LMICs).
                Approximately 2,000 intervention studies were systematically evaluated through December 31, 2008. They addressed preterm birth or low birth weight; stillbirth or perinatal mortality; and management of preterm newborns. Out of 82 identified interventions, 49 were relevant to LMICs and had reasonable amounts of evidence, and therefore selected for in-depth reviews. Each was classified and assessed by the quality of available evidence and its potential to treat or prevent preterm birth and stillbirth. Impacts on other maternal, fetal, newborn or child health outcomes were also considered. Assessments were based on an adaptation of the Grades of Recommendation Assessment, Development and Evaluation criteria.
                Most interventions require additional research to improve the quality of evidence. Others had little evidence of benefit and should be discontinued. The following are supported by moderate- to high-quality evidence and strongly recommended for LMICs: Two interventions prevent preterm births--smoking cessation and progesterone. Eight interventions prevent stillbirths--balanced protein energy supplementation, screening and treatment of syphilis, intermittant presumptive treatment for malaria during pregnancy, insecticide-treated mosquito nets, birth preparedness, emergency obstetric care, cesarean section for breech presentation, and elective induction for post-term delivery. Eleven interventions improve survival of preterm newborns--prophylactic steroids in preterm labor, antibiotics for PROM, vitamin K supplementation at delivery, case management of neonatal sepsis and pneumonia, delayed cord clamping, room air (vs. 100% oxygen) for resuscitation, hospital-based kangaroo mother care, early breastfeeding, thermal care, and surfactant therapy and application of continued distending pressure to the lungs for respiratory distress syndrome
                The research paradigm for discovery science and intervention development must be balanced to address prevention as well as improve morbidity and mortality in all settings. This review also reveals significant gaps in current knowledge of interventions spanning the continuum of maternal and fetal outcomes, and the critical need to generate further high-quality evidence for promising interventions. Although an association between subclinical intrauterine infection and preterm birth is well established, there is conflicting evidence regarding the benefits of antibiotic administration to women in preterm labor with intact membranes. We attempted to determine the effect of ampicillin-amoxicillin and erythromycin treatment on prolongation of pregnancy, the rate of preterm birth, and neonatal morbidity in patients with preterm labor and intact membranes.
                A multicenter, randomized, double-blinded, placebo-controlled trial was designed and implemented by the Maternal-Fetal Medicine Units Network of the National Institute of Child Health and Human Development. Two hundred seventy-seven women with singleton pregnancies and preterm labor with intact membranes (24 to 34 weeks) were randomly allocated to receive either antibiotics or placebos.
                Of the 2373 patients screened for participation in this study in six medical centers, 277 women were enrolled (n = 133 for antibiotics group vs n = 144 for placebo group). In each study group, 60% of patients completed all the study medications. The overall prevalence of microbial invasion of the amniotic cavity was 5.8% (14/239). No significant difference between the antibiotic group and the placebo group was found in maternal outcomes, including duration of randomization-to-delivery interval, frequency of preterm delivery (< 37 weeks), frequency of preterm premature rupture of membranes, clinical chorioamnionitis, endometritis, and number of subsequent admissions for preterm labor. Similarly, no significant difference in neonatal outcomes could be detected between the two groups including respiratory distress syndrome, bronchopulmonary dysplasia, intraventricular hemorrhage, sepsis, and admission and duration of newborn intensive special care unit hospitalization.
                The results of this study do not support the routine use of antibiotic administration to women in preterm labor with intact membranes. A double blind, controlled study was performed to see whether the use of prophylactic oral salbutamol would reduce the incidence of preterm labour in twin pregnancy. Of the 144 women studied, 74 took salbutamol and 70 placebo. No difference was found in the length of gestation, birthweight or fetal outcome, although fewer babies suffered from respiratory distress syndrome in the salbutamol group. Women did not experience troublesome side-effects from salbutamol. Available information suggests that some instances of preterm birth or premature rupture of membranes are associated with clinically unrecognized infection and inflammation of the lower uterine segment, decidua, and fetal membranes. Various cervicovaginal microorganisms have been recovered from these sites. Many of these microorganisms produce factors that may lead to weakening of the fetal membranes, release of prostaglandins, or both. This study evaluated the presence of various lower genital tract microflora and bacterial conditions in 229 women enrolled in a double-blind, placebo-controlled trial of short-course erythromycin treatment at 26 to 30 weeks' gestation to prevent preterm birth. Demographic, obstetric, and microbiologic parameters were prospectively evaluated. Premature rupture of membranes occurred less frequently (p less than 0.01) among women who received erythromycin (6%) versus placebo (16%). Preterm premature rupture of membranes also occurred less frequently, although not significantly (p = 0.3) in patients who received erythromycin (2%) versus placebo (5%). Erythromycin treatment significantly decreased the occurrence of premature rupture of membranes among women who were initially positive for Chlamydia trachomatis infection. Logistic regression analysis demonstrated that C. trachomatis (p = 0.05; odds ratio, 9), vaginal wash phospholipase C (p = 0.08; odds ratio, 6) and prior preterm birth (p = 0.007; odds ratio 17) were associated with increased risk of preterm birth. Bacterial vaginosis, Mycoplasma hominis, Ureaplasma urealyticum were not significantly associated with increased risk of preterm birth or preterm rupture of membranes. These findings support a role for selected lower genital tract microflora in preterm birth and premature rupture. Large controlled treatment trials of specific infections or conditions associated with preterm birth and premature rupture of membranes are required to confirm the value of antimicrobial treatments in prevention of microbial-associated preterm birth. To test the hypothesis that prophylactic administration of clindamycin 2% vaginal cream can reduce the incidence of preterm birth in a high risk population.
                A multi-centre, randomised, double-blind, placebo-controlled trial.
                Twelve city hospitals in The Netherlands.
                One hundred and sixty-eight women with a singleton pregnancy and a history of a spontaneous preterm delivery in the preceding pregnancy.
                Clindamycin 2% vaginal cream, or placebo cream, administered daily for seven days at 26 and 32 weeks of gestation.
                Spontaneous preterm birth at < 37 weeks, admission for threatened preterm labour, neonatal infectious morbidity.
                In the intention-to-treat analysis no difference was found in overall preterm birth between clindamycin and placebo (23% vs 18%, respectively). In the subgroup who completed the trial and administered all medication, more women delivered before 34 weeks in the clindamycin group (1.4% in the placebo vs 9.0% in the clindamycin group; P < 0.05). The length of admissions for threatened preterm labour did not differ. More infectious neonatal morbidity was seen in the clindamycin group (5/83 vs 0/85; P < 0.05).
                Clindamycin 2% vaginal cream given prophylactically to women with a spontaneous preterm birth in the preceding pregnancy did not prevent preterm delivery or reduce the number of admissions for threatened preterm labour. The neonatal infectious morbidity in the group treated with clindamycin was significantly higher and a major concern. To evaluate whether a screening strategy in pregnancy lowers the rate of preterm delivery in a general population of pregnant women.
                Multicentre, prospective, randomised controlled trial.
                Non-hospital based antenatal clinics.
                4429 pregnant women presenting for their routine prenatal visits early in the second trimester were screened by Gram stain for asymptomatic vaginal infection. In the intervention group, the women's obstetricians received the test results and women received standard treatment and follow up for any detected infection. In the control group, the results of the vaginal smears were not revealed to the caregivers.
                The primary outcome variable was preterm delivery at less than 37 weeks. Secondary outcome variables were preterm delivery at less than 37 weeks combined with different birth weight categories equal to or below 2500 g and the rate of late miscarriage.
                Outcome data were available for 2058 women in the intervention group and 2097 women in the control group. In the intervention group, the number of preterm births was significantly lower than in the control group (3.0% v 5.3%, 95% confidence interval 1.2 to 3.6; P = 0.0001). Preterm births were also significantly reduced in lower weight categories at less than 37 weeks and <or= 2500 g. Eight late miscarriages occurred in the intervention group and 15 in the control group.
                Integrating a simple infection screening programme into routine antenatal care leads to a significant reduction in preterm births and reduces the rate of late miscarriage in a general population of pregnant women. In a previous study from this institution, patients at high risk for preterm labour were screened for the presence of bacterial vaginosis (BV). When BV was present, they were randomised to receive either treatment (metronidazole) or placebo (vitamin C). There were significantly more patients with preterm labour in the metronidazole group. The aim of this double-blind randomised placebo-controlled trial study was to determine whether vitamin C could indeed reduce the recurrence risk of preterm labour. Patients with a history of preterm labour in a preceding pregnancy were randomised to receive 250 mg vitamin C or a matching placebo twice daily until 34 weeks' gestation. They attended a dedicated premature labour clinic. Significantly more women delivered before term in the group that received vitamin C, but there was no difference in the outcome of the babies between the two groups. Supplementation with vitamin C did not prevent premature labour. Preterm premature rupture of the fetal membranes is common and frequently results in infectious complications. A prospective, randomized, controlled trial of penicillin versus placebo in preterm premature rupture of membranes is reported. The aim of the study was to determine if prophylactic antibiotics after preterm premature rupture of membranes would reduce infectious complications in the mother or neonate.
                Patients with preterm premature rupture of membranes between 21 and 37 weeks' gestation were randomized into a penicillin group that received 1 million units of benzylpenicillin intravenously every 4 hours followed by 250 mg of potassium phenoxymethyl penicillin (Pen-Vee K, Wyeth-Ayerst) orally twice daily or a placebo group before delivery. Latency period, infectious complications, and neonatal outcomes were studied.
                Patients with preterm premature rupture of membranes who received prophylactic penicillin had fewer infectious complications, including intraamniotic infection and postpartum endometritis (4 vs 11, p < 0.03), without adverse effects on the mother or fetus.
                Prophylactic penicillin in patients with preterm premature rupture of membranes reduces maternal infectious complications without adversely affecting the mother or newborn. A total of 394 patients were enrolled in a study to assess the effectiveness of an educational preterm delivery prevention program and to determine whether the addition of home uterine monitoring to the program improved results in patients at high risk of preterm labor. Both the educational program and home uterine monitoring were found to increase the percentage of women with preterm labor who sought care while still favorable for long-term suppression, resulting in a decreased incidence of preterm births and improved outcome when compared with similar high-risk patients who did not participate in these programs. In a randomized, prospective study, addition of home uterine monitoring to the educational program was found to significantly improve outcome in twin gestations but not in singleton gestations. However, the number of singleton pregnancies was too small to rule out possible benefit from home uterine monitoring in that group.
There is insufficient evidence to support or refute the use of prophylactic oral betamimetics for preventing preterm birth in women at high risk of preterm labour with a singleton pregnancy.