Infant wellbeing at 2 years of age in the Growth Restriction Intervention Trial (GRIT): multicentred randomised controlled trial. Global report on preterm birth and stillbirth (3 of 7): evidence for effectiveness of interventions. Preterm premature rupture of the membranes with fetal pulmonary maturity present: a prospective study. A randomized controlled trial of elective preterm delivery of fetuses with gastroschisis. The effect of introduction of umbilical Doppler recordings to obstetric practice. No benefit from conservative management in nulliparous women with premature rupture of the membranes (PROM) at term. A randomized study. Management of premature rupture of membranes and unfavorable cervix in term pregnancy. Delayed cord clamping in very preterm infants reduces the incidence of intraventricular hemorrhage and late-onset sepsis: a randomized, controlled trial. Intentional delivery versus expectant management with preterm ruptured membranes at 30-34 weeks' gestation.
Although delivery is widely used for preterm babies failing to thrive in utero, the effect of altering delivery timing has never been assessed in a randomised controlled trial. We aimed to compare the effect of delivering early with delaying birth for as long as possible.
                548 pregnant women were recruited by 69 hospitals in 13 European countries. Participants had fetal compromise between 24 and 36 weeks, an umbilical-artery doppler waveform recorded, and clinical uncertainty about whether immediate delivery was indicated. Before birth, 588 babies were randomly assigned to immediate delivery (n=296) or delayed delivery until the obstetrician was no longer uncertain (n=292). The main outcome was death or disability at or beyond 2 years of age. Disability was defined as a Griffiths developmental quotient of 70 or less or the presence of motor or perceptual severe disability. Analysis was by intention-to-treat. This trial has been assigned the International Standard Randomised Controlled Trial Number ISRCTN41358726.
                Primary outcomes were available on 290 (98%) immediate and 283 (97%) deferred deliveries. Overall rate of death or severe disability at 2 years was 55 (19%) of 290 immediate births, and 44 (16%) of 283 delayed births. With adjustment for gestational age and umbilical-artery doppler category, the odds ratio (95% CrI) was 1.1 (0.7-1.8). Most of the observed difference was in disability in babies younger than 31 weeks of gestation at randomisation: 14 (13%) immediate versus five (5%) delayed deliveries. No important differences in the median Griffiths developmental quotient in survivors was seen.
                The lack of difference in mortality suggests that obstetricians are delivering sick preterm babies at about the correct moment to minimise mortality. However, they could be delivering too early to minimise brain damage. These results do not lend support to the idea that obstetricians can deliver before terminal hypoxaemia to improve brain development. 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. Ninety-nine patients with premature rupture of the membranes (PROM) before 36 weeks' gestation and documented fetal pulmonary maturity were studied prospectively. Fifty-two patients in labor were allowed to deliver. The remaining 47 were randomly assigned to either prompt delivery (N = 26) or conservative management (N = 21). The overall corrected perinatal survival was excellent (96%). Only one death in the entire series clearly was due to prematurity. Expectant management prolonged gestation greater than one week in only four of 21 patients (19%), and was associated with a significantly increased risk of maternal infections. There were no failed inductions of labor, and 22 of 24 induced patients (92%) delivered vaginally. Neonatal morbidity was similar in each group. These findings in an indigent, largely black population suggest that when pulmonary maturity is present, the maternal risks of conservative management may exceed the potential benefit to the fetus and newborn. The findings of this study may be specific to the population studied, and extrapolation to dissimilar populations may not be warranted. Elective preterm delivery of the fetus with gastroschisis may help to limit injury to the extruded fetal gut and thus promote faster recovery of neonatal gut function and earlier hospital discharge. This hypothesis has not previously been tested in a prospective randomized controlled trial.
                Between May 1995 and September 1999, all women referred to a single tertiary center before 34 weeks' gestation with a sonographically diagnosed fetal gastroschisis were invited to participate in a randomized controlled trial. Eligible patients were randomized to elective delivery at 36 weeks or to await the onset of spontaneous labor. The method of delivery was not prescribed by the trial. Primary outcome measures in the neonate were the time taken to tolerate full enteral feeding (150 mL/kg per day) and duration of hospital stay.
                Of 44 eligible women, 42 were randomized, 21 to elective delivery and 21 to await spontaneous labor. There were 20 liveborn infants in each group. Four babies in the elective group and 4 in the spontaneous group delivered before 36 weeks' gestation but were included in the analysis on an intention-to-treat basis. Mean gestational age at delivery was 35.8 weeks in the elective group and 36.7 weeks in the spontaneous group. Primary closure of the gastroschisis was achieved in a similar proportion (80%-85%) of infants in both groups. Two babies in the elective group died from short gut complications. In the survivors, there was a trend in favor of a shorter median time to achieve full enteral feeding (30.5 vs 37.5 days) and a shorter median duration of hospital stay (47.5 vs 53 days) in the elective group, but this was not statistically significant. These findings remained unaltered when the data were reanalyzed after (a) excluding infants with intestinal atresia or (b) excluding infants born before 36 weeks' gestation.
                Although limited by the small number of patients, this randomized controlled trial demonstrates no significant benefit from elective preterm delivery of fetuses with gastroschisis. To assess the effect on obstetric practice of clinician access to umbilical artery Doppler ultrasound results.
                Randomised controlled trial.
                A large teaching hospital.
                Two thousand two hundred and eighty-nine pregnancies defined as being at risk by referral for Doppler or fetal monitoring.
                Continuous wave Doppler studies of umbilical artery. Results immediately available to clinicians.
                Fetal outcome: perinatal mortality, Apgar score and admission to the neonatal unit. Obstetric intervention: admission to hospital, induction of labour and caesarean section. Use of of fetal well being: cardiotocography, biophysical profile and ultrasound biometry.
                The treatment and control groups were comparable in age, parity, gestation at point of entry and risk features. There were no overall differences in perinatal outcome, obstetric intervention or use of fetal monitoring. Examination of a subset recruited only because of hypertension or suspected intrauterine growth retardation (n = 754) similarly showed no difference attributable to group randomisation. Comparison of only those pregnancies retrospectively defined as low risk and high risk showed more use of cardiotocography in the high risk group with access to Doppler (P = 0.007) but no difference in the low risk group.
                Doppler umbilical artery recording has been shown to perform well in prediction power of antenatal fetal compromise. What has been examined in this study is the response of clinicians to the test. The results suggest that obstetricians do not use the test to modify their risk assessment, and, therefore, the need for fetal monitoring in particular pregnancies. There is a real need for accumulation of information from very large data sets, particularly in the prediction power of Doppler for antenatal fetal compromise from apparently chronic utero-placental cause to guide use of monitoring resources. If simply added to existing fetal monitoring techniques in a hospital where these are widely used, then umbilical artery Doppler recordings may at present simply involve extra resources of staff and expenses, without benefit. To compare maternal and fetal outcome in pregnancies with premature rupture of the membranes (PROM) at term with either early induction of labor or conservative management awaiting spontaneous labor.
                A prospective randomized trial.
                The University Hospital of Lund, Sweden.
                Altogether 369 women with singleton pregnancy, cephalic presentation, gestational duration 36-41 weeks, were randomized either to induction of labor (n = 139) or conservative management up to 3 days (n = 138). Those eligible but not participating in the study totalled 92. MAIN OBSTETRIC MEASURES: Obstetric intervention rate (cesarean section or instrumental delivery) and short-term neonatal morbidity.
                No difference was found in the rate of obstetric intervention between the induction of labor group and the group with conservative management (12.2 vs. 18.8%; chi 2 = 2.3, p greater than 0.05). A slightly increased rate of neonatal infections was seen in the latter group (0.7 vs. 4.3%; chi 2 = 3.2, p less than 0.05).
                We found no benefit from conservative management for up to 3 days in women with PROM at term, compared with immediate induction of labor. There was no difference in the number of obstetric interventions during labor. The neonatal infectious morbidity was slightly higher in conservatively managed cases. One hundred thirty-four indigent patients at term who had premature rupture of membranes and a cervix unfavorable for induction of labor (80% effacement or less, 2 cm dilation or less) were randomized to compare expectant with intervention management. Women with any medical or obstetric condition warranting immediate intervention were excluded from the study. Patients treated expectantly were placed at bed rest and observed for labor or infection. Patients managed by intervention were given oxytocin if labor did not ensue within 12 hours of rupture of the membranes. Patients in the intervention protocol had longer labor (P less than .02) and a higher incidence of both cesarean delivery (P less than .05) and intraamniotic infection (P less than .05). There was only one case of proven neonatal sepsis, and this occurred in a patient managed by induction of labor. There was no statistically significant difference between groups in mean length of maternal hospitalization. This study compared the effects of immediate (ICC) and delayed (DCC) cord clamping on very low birth weight (VLBW) infants on 2 primary variables: bronchopulmonary dysplasia (BPD) and suspected necrotizing enterocolitis (SNEC). Other outcome variables were late-onset sepsis (LOS) and intraventricular hemorrhage (IVH).
                This was a randomized, controlled unmasked trial in which women in labor with singleton fetuses <32 weeks' gestation were randomly assigned to ICC (cord clamped at 5-10 seconds) or DCC (30-45 seconds) groups. Women were excluded for the following reasons: their obstetrician refused to participate, major congenital anomalies, multiple gestations, intent to withhold care, severe maternal illnesses, placenta abruption or previa, or rapid delivery after admission.
                Seventy-two mother/infant pairs were randomized. Infants in the ICC and DCC groups weighed 1151 and 1175 g, and mean gestational ages were 28.2 and 28.3 weeks, respectively. Analyses revealed no difference in maternal and infant demographic, clinical, and safety variables. There were no differences in the incidence of our primary outcomes (BPD and suspected NEC). However, significant differences were found between the ICC and DCC groups in the rates of IVH and LOS. Two of the 23 male infants in the DCC group had IVH versus 8 of the 19 in the ICC group. No cases of sepsis occurred in the 23 boys in the DCC group, whereas 6 of the 19 boys in the ICC group had confirmed sepsis. There was a trend toward higher initial hematocrit in the infants in the DCC group.
                Delayed cord clamping seems to protect VLBW infants from IVH and LOS, especially for male infants. To determine maternal and neonatal outcomes in pregnancies complicated by preterm rupture of membranes (PROM) at 30-34 weeks' gestation.
                A randomized controlled trial was conducted to study the benefits of expectant management in women hospitalized for PROM at 30-34 weeks' gestation. During this investigation, no tocolytics, corticosteroids, or prophylactic antibiotics were used.
                Sixty-eight women with PROM were managed expectantly and 61 were delivered intentionally. The mean gestational age at study entry was 31.7 weeks in both the expectant management and intentional delivery groups (P > .05). The mean gestational ages at delivery were similar (32.0 and 31.7 weeks, respectively). Other indices of pregnancy outcome (ie, birth weight, intraventricular hemorrhage, necrotizing enterocolitis, sepsis, respiratory distress syndrome, and perinatal death) were not significantly improved by expectant management. However, there was a significant increase in the incidence of chorioamnionitis and antepartum hospitalization in the women managed expectantly.
                There were no clinically significant neonatal advantages to expectant management of ruptured membranes at 30-34 weeks. Antepartum hospitalization was decreased by 2.5 days in those women randomized to intentional delivery.
Currently there is insufficient evidence on the benefits and harms of immediate delivery compared with deferred delivery in cases of suspected fetal compromise at preterm gestations to make firm recommendations to guide clinical practice. Where there is uncertainty whether or not to deliver a preterm fetus with suspected fetal compromise, there seems to be no benefit to immediate delivery. Deferring delivery until test results worsen or increasing gestation favours delivery may improve the outcomes for mother and baby. More research is needed to guide clinical practice.