No abstract

Objective To assess the clinical and financial impact, and identify the problems, of providing routine antenatal RhD immunoglobulin prophylaxis for Rhesus D negative nulliparae.Design A retrospective (198G1986) and prospective (1987)(1988)(1989)(1990)(1991)(1992)(1993)(1994)(1995)(1996) comparison between two similar populations, one population with nulliparae offered routine RhD immunoglobulin 500 IU prophylaxis at 28 and 34 weeks of gestation part way through the study period, and the other population not offered prophylaxis at any time.Setting Obstetric units in two counties (three health districts) with similar annual numbers of matemities and the Regional Blood Transfusion Service antenatal serology laboratory.Participants Non-sentisitised Rhesus D negative pregnant nulliparae.Interventions Intramuscular RhD immunoglobulin 500 IU at 28 and 34 weeks of gestation to eligible women booked for confinement in one county; the intervention not offered in the other county.Main outcome measures 1. Rhesus D sensitised second pregnancy rate; 2. success in providing prophylaxis to eligible women; 3. serology laboratory activity changes; 4. potential savings from the prophylaxis programme.Prophylaxis significantly reduced iso-immunisation in the next pregnancy when compared with historical (OR 0.28, CI 0,14453; P < 0.0001) and contemporary controls (OR 0.43, CI 0.22486; P = 0.02). However, success at achieving comprehensive prophylaxis was disappointing, with only 89% of eligible women receiving the first injection, 74% both injections, and for only 29% were both at the correct gestation. Fifty-two percent of women delivered after 40 weeks of gestation, beyond the period of adequate prophylaxis protection. The savings in antenatal interventions, neonatal care and possible long term ill-health that result from very preterm birth should be considerable.Routine prophylaxis for nulliparae significantly reduces the incidence of sensitised next pregnancies with consequent savings, and its adoption nationwide should be encouraged. A programme offering antenatal prophylaxis for all Rhesus D negative women is unlikely to be economic. Improvement in uptake of prophylaxis is needed; alternative administration strategies should be explored.

Phosphoinositide hydrolysis is important in mediating the actions of oxytocin and prostaglandin (PG) F2 alpha on uterine contractions during labour. We have measured the effect of oxytocin, PGF2 alpha and other agents on the formation of inositol phosphates (IPs) in cultured human myometrial cells labelled with [3H]inositol and on changes in intracellular free Ca2+ concentration ([Ca2+]i) in cells loaded with Fura-2. Oxytocin induced the formation of [3H]IPs in a concentration-dependent manner with an EC50 (concentration of agonist producing 50% of the maximal response) of 1.4 +/- 0.5 nmol/l (mean +/- S.E.M.). The maximal response was obtained with 1 mumol oxytocin/l and represented a stimulation of 670% over basal. PGF2 alpha also stimulated the formation of [3H]IPs and the response at 1 mumol/l was a 204% stimulation over basal. The effects of PGF2 alpha were independent of extracellular Ca2+ but the effect of oxytocin was reduced with low extracellular Ca2+. Cyclic AMP formation, induced by forskolin or PGE2, had no effect on the stimulated levels of [3H]IPs. Pertussis toxin (PT) reduced the oxytocin-stimulated formation of [3H]IPs in a concentration-dependent manner. The maximal effect of PT resulted in an 80% reduction in the formation of [3H]IPs. However, PGF2 alpha stimulation was not affected by PT treatment. To analyse the action of PT further, we studied its effect on oxytocin-induced changes in [Ca2+]i. The basal [Ca2+]i was 112 +/- 4 nmol/l (n = 225 cells) and was not affected by PT treatment (109 +/- 3 nmol/l; n = 200 cells). In the absence of PT, 1 mumol oxytocin/l increased [Ca2+]i to a peak of 522 +/- 26 nmol/l, and in PT-treated cells, the [Ca2+]i peak was reduced to 348 +/- 16 nmol/l. Similar inhibitory effects of PT were obtained at oxytocin concentrations ranging from 1 to 100 nmol/l. Our data suggest that in human myometrial cells, the oxytocin-induced production of [3H]IPs and increase in [Ca2+]i are mediated by a PT-sensitive G-protein. However, a significant fraction of the oxytocin response appears to be mediated by a PT-insensitive G-protein, possibly a member of the Gq family.

Oxytocin is used widely for the induction and augmentation of labour, but there is little information about the dynamics of oxytocin receptors in human myometrium during parturition, and the possible effect of oxytocin infusion. This information is important because G protein-coupled receptors, such as the oxytocin receptor, undergo desensitization after prolonged or repeated stimulation. The concentration of myometrial oxytocin receptors and the steady state of its mRNA were measured in patients undergoing Caesarean sections before or during spontaneous or induced labour. The concentration of receptors before labour was 477 (175-641) fmol mg(-1) protein (median, quartile range), and decreased to 140 (72-206; P < 0.05) and 118 (69-75; P < 0.01) fmol mg(-1) protein during prolonged oxytocin-augmented and oxytocin-induced labour, respectively. The corresponding oxytocin receptor mRNA concentrations decreased by 60- and 300-fold, respectively. The decrease in receptor binding and mRNA in women receiving oxytocin infusion indicates that homologous receptor desensitization occurs in vivo.