Objective To compare the effect of induction of labour with a policy of expectant monitoring for intrauterine growth restriction near term.Design Multicentre randomised equivalence trial (the Disproportionate Intrauterine Growth Intervention Trial At Term (DIGITAT)).Setting Eight academic and 44 non-academic hospitals in the Netherlands between November 2004 and November 2008.Participants Pregnant women who had a singleton pregnancy beyond 36+0 weeks’ gestation with suspected intrauterine growth restriction.Interventions Induction of labour or expectant monitoring.Main outcome measures The primary outcome was a composite measure of adverse neonatal outcome, defined as death before hospital discharge, five minute Apgar score of less than 7, umbilical artery pH of less than 7.05, or admission to the intensive care unit. Operative delivery (vaginal instrumental delivery or caesarean section) was a secondary outcome. Analysis was by intention to treat, with confidence intervals calculated for the differences in percentages or means.Results 321 pregnant women were randomly allocated to induction and 329 to expectant monitoring. Induction group infants were delivered 10 days earlier (mean difference −9.9 days, 95% CI −11.3 to −8.6) and weighed 130 g less (mean difference −130 g, 95% CI −188 g to −71 g) than babies in the expectant monitoring group. A total of 17 (5.3%) infants in the induction group experienced the composite adverse neonatal outcome, compared with 20 (6.1%) in the expectant monitoring group (difference −0.8%, 95% CI −4.3% to 3.2%). Caesarean sections were performed on 45 (14.0%) mothers in the induction group and 45 (13.7%) in the expectant monitoring group (difference 0.3%, 95% CI −5.0% to 5.6%).Conclusions In women with suspected intrauterine growth restriction at term, we found no important differences in adverse outcomes between induction of labour and expectant monitoring. Patients who are keen on non-intervention can safely choose expectant management with intensive maternal and fetal monitoring; however, it is rational to choose induction to prevent possible neonatal morbidity and stillbirth.Trial registration International Standard Randomised Controlled Trial number ISRCTN10363217.

BackgroundHypoxic-ischaemic encephalopathy is associated with development of cerebral palsy and cognitive disability later in life and is therefore one of the fundamental problems in perinatal medicine. The xanthine-oxidase inhibitor allopurinol reduces the formation of free radicals, thereby limiting the amount of hypoxia-reperfusion damage. In case of suspected intra-uterine hypoxia, both animal and human studies suggest that maternal administration of allopurinol immediately prior to delivery reduces hypoxic-ischaemic encephalopathy.Methods/DesignThe proposed trial is a randomized double blind placebo controlled multicenter study in pregnant women at term in whom the foetus is suspected of intra-uterine hypoxia.Allopurinol 500 mg IV or placebo will be administered antenatally to the pregnant woman when foetal hypoxia is suspected. Foetal distress is being diagnosed by the clinician as an abnormal or non-reassuring foetal heart rate trace, preferably accompanied by either significant ST-wave abnormalities (as detected by the STAN-monitor) or an abnormal foetal blood scalp sampling (pH < 7.20).Primary outcome measures are the amount of S100B (a marker for brain tissue damage) and the severity of oxidative stress (measured by isoprostane, neuroprostane, non protein bound iron and hypoxanthine), both measured in umbilical cord blood. Secondary outcome measures are neonatal mortality, serious composite neonatal morbidity and long-term neurological outcome. Furthermore pharmacokinetics and pharmacodynamics will be investigated.We expect an inclusion of 220 patients (110 per group) to be feasible in an inclusion period of two years. Given a suspected mean value of S100B of 1.05 ug/L (SD 0.37 ug/L) in the placebo group this trial has a power of 90% (alpha 0.05) to detect a mean value of S100B of 0.89 ug/L (SD 0.37 ug/L) in the 'allopurinol-treated' group (z-test2-sided). Analysis will be by intention to treat and it allows for one interim analysis.DiscussionIn this trial we aim to answer the question whether antenatal allopurinol administration reduces hypoxic-ischaemic encephalopathy in neonates exposed to foetal hypoxia.Trial registration numberClinical Trials, protocol registration system: NCT00189007

There is evidence that intrauterine infection, which stimulates PG synthesis may play a role in the pathogenesis of some preterm labor. Local tissue concentrations of PGs are controlled not only by the rate of synthesis, but also by catabolism, which is regulated by 15-hydroxyprostaglandin dehydrogenase (PGDH). We hypothesized that a decrease of PGDH activity could contribute to an increase in PG output at the time of preterm labor (PTL) especially in association with infection. We measured PGDH activity with a zero order kinetic enzymatic assay, PGDH messenger ribonucleic acid by in situ hybridization and PGDH distribution and localization with immunohistochemistry in human placenta and fetal membranes from women at term before (n = 10) or after (n = 16) labor compared to preterm labor at less than 36 weeks without (n = 16) and with (n = 11) chorioamnionitis. PGDH activity in chorion was significantly lower in PTL than at term and was further reduced when PTL was associated with inflammation. Immunoreactive PGDH and PGDH messenger ribonucleic acid localized predominantly to chorionic trophoblasts at term and were reduced in PTL women with or without infection. These effects were not observed in the placenta. Loss of PGDH with infection was associated with infiltration of chorion by polymorphonuclear leukocytes, resulting in a compromised structural integrity, although the amniotic epithelium was generally intact. We conclude that a reduction in PGDH in the human fetal membranes may occur in some cases of preterm labor and may contribute to an increase in net PG accumulation and drive to myometrial contractility.

NCT00189007, Dutch Trial Register NTR1383.

Objective To evaluate if immediate catheter removal ( ICR ) after laparoscopic hysterectomy is associated with similar retention outcomes compared with delayed removal ( DCR ). Study design Non‐inferiority randomised controlled trial. Population Women undergoing laparoscopic hysterectomy in six hospitals in the Netherlands. Methods Women were randomised to ICR or DCR (between 18 and 24 hours after surgery). Primary outcome The inability to void within 6 hours after catheter removal. Results One hundred and fifty‐five women were randomised to ICR ( n = 74) and DCR ( n = 81). The intention‐to‐treat and per‐protocol analysis could not demonstrate the non‐inferiority of ICR : ten women with ICR could not urinate spontaneously within 6 hours compared with none in the delayed group (risk difference 13.5%, 5.6–24.8, P = 0.88). However, seven of these women could void spontaneously within 9 hours without additional intervention. Regarding the secondary outcomes, eight women from the delayed group requested earlier catheter removal because of complaints (9.9%). Three women with ICR (4.1%) had a urinary tract infection postoperatively versus eight with DCR (9.9%, risk difference −5.8%, −15.1 to 3.5, P = 0.215). Women with ICR mobilised significantly earlier (5.7 hours, 0.8–23.3 versus 21.0 hours, 1.4–29.9; P ≤ 0.001). Conclusion The non‐inferiority of ICR could not be demonstrated in terms of urinary retention 6 hours after procedure. However, 70% of the women with voiding difficulties could void spontaneously within 9 hours after laparoscopic hysterectomy. It is therefore questionable if all observed urinary retention cases were clinically relevant. As a result, the clinical advantages of ICR may still outweigh the risk of bladder retention and it should therefore be considered after uncomplicated laparoscopic hysterectomy. Tweetable abstract The advantages of immediate catheter removal after laparoscopic hysterectomy seem to outweigh the risk of bladder retention.