Hospitalisation for bed rest for women with a triplet pregnancy: an abandoned randomised controlled trial and meta-analysis

BACKGROUND: This abandoned randomised controlled trial assessed the effects of hospitalisation from 24 to 30 weeks gestation for women with a triplet pregnancy on the risk of preterm birth. METHODS: Women with a triplet pregnancy and no other condition necessitating hospital admission were approached for participation in the study, and randomised to either antenatal hospitalisation (hospitalised group), or to routine antenatal care (control group). The randomisation schedule used variable blocks with stratification by parity, and a researcher not involved with clinical care contacted by telephone to determine treatment allocation by opening the next in a series of consecutively numbered, opaque, sealed envelopes. Primary study outcomes were preterm birth (defined as birth less than 37 weeks gestation) and very preterm birth (defined as birth less than 34 weeks gestation), and the development of maternal pregnancy induced hypertension. The trial was ceased prior to achieving the calculated sample size due to difficulties in recruitment. The results of this randomised controlled trial were then combined with the results of another comparing bed rest in women with a triplet pregnancy. RESULTS: Seven women with a triplet pregnancy were recruited to the trial, with three randomised to the hospitalisation group, and four to the control group. There were no statistically significant differences between the two groups for the primary outcomes birth before 37 weeks (3/3 hospitalisation group versus 4/4 control group; relative risk (RR) not estimable), birth before 34 weeks (3/3 hospitalisation group versus 2/4 control group; RR 2.00 95% Confidence Intervals (CI) 0.75–5.33) and pregnancy induced hypertension (1/3 hospitalisation group versus 1/4 control group; RR 1.33 95%CI 0.13–13.74). When the results of this trial were incorporated into a meta-analysis with the previous randomised controlled trial assessing hospitalisation and bed rest for women with a triplet pregnancy, (total sample size 26 women and 78 infants), there were no statistically significant differences identified between the two groups. CONCLUSION: The results of this trial and meta-analysis suggest no benefit of routine hospitalisation and bed rest for women with a triplet pregnancy to reduce the risk of preterm birth. The adoption or continuation of a policy of routine hospitalisation and bed rest for women with an uncomplicated triplet pregnancy cannot be recommended

XRCC1 stimulates polynucleotide kinase by enhancing its damage discrimination and displacement from DNA repair intermediates

Human polynucleotide kinase (hPNK) is required for processing and rejoining DNA strand break termini. The 5'-DNA kinase and 3'-phosphatase activities of hPNK can be stimulated by the ¿scaffold¿ protein XRCC1, but the mechanism remains to be fully elucidated. Using a variety of fluorescence techniques, we examined the interaction of hPNK with XRCC1 and substrates that model DNA single-strand breaks. hPNK binding to substrates with 5'-OH termini was only ~5-fold tighter than that to identical DNA molecules with 5'-phosphate termini, suggesting that hPNK remains bound to the product of its enzymatic activity. The presence of XRCC1 did not influence the binding of hPNK to substrates with 5'-OH termini, but sharply reduced the interaction of hPNK with DNA bearing a 5'-phosphate terminus. These data, together with kinetic data obtained at limiting enzyme concentration, indicate a dual function for the interaction of XRCC1 with hPNK. First, XRCC1 enhances the capacity of hPNK to discriminate between strand breaks with 5'-OH termini and those with 5'-phosphate termini; and second, XRCC1 stimulates hPNK activity by displacing hPNK from the phosphorylated DNA product