Induction of labour in nulliparous and multiparous women: a UK, multicentre, open-label study of intravaginal misoprostol in comparison with dinoprostone.

OBJECTIVE: To compare the efficacy and safety of a 25-microgram vaginal tablet of misoprostol (APL202) with dinoprostone (3-mg vaginal tablet) in cervical ripening and labour induction. DESIGN: A randomised, open-label, noninferiority, comparative study in two maternal populations. SETTING: Eighteen NHS study centres across the UK. POPULATION: Nulliparous or multiparous women with a singleton pregnancy eligible for induction of labour. METHODS: Women were randomised to receive either misoprostol, initially 25 micrograms (50 micrograms in nulliparous women with Bishop score < or =4) followed by 25 micrograms after 4 and 8 hours, or dinoprostone, initially 3 mg followed by 3 mg after 6 hours. Clinical noninferiority of misoprostol was defined as an absolute difference between treatments of no more than 10% for the primary outcome. MAIN OUTCOME MEASURES: The number of vaginal deliveries achieved within 24 hours of labour induction. Maternal and fetal safety outcomes. RESULTS: A total of 626 women were randomised to misoprostol (n = 318) or dinoprostone (n = 308) treatment. The rate of vaginal deliveries achieved within 24 hours of induction did not significantly differ between the misoprostol and dinoprostone (43 versus 47%; 3.74% difference, 95% CI -3.58 to 11.05, respectively) treatment groups. The treatments were generally comparable for other secondary efficacy measures. Maternal and fetal adverse events were similarly distributed across the misoprostol and dinoprostone groups. CONCLUSIONS: Low-dose misoprostol is efficacious in cervical ripening and labour induction and demonstrates a similar fetal and maternal safety profile to dinoprostone.

Insulin and insulin propeptides at birth in offspring of diabetic mothers.

Maternal diabetes during pregnancy is associated with excess fetal growth and increased fetal insulin production. We hypothesized that insulin propeptides (proinsulin and 32-33 split proinsulin) might be more robust indicators of chronic fetal overproduction of insulin. We examined insulin-like molecules in cord blood (ILM) (insulin, proinsulin, and 32-33 split proinsulin) in relation to birth weight, maternal glycemia, and cord glucose in 140 offspring of mothers with type 1 diabetes (ODM) and 49 offspring of mothers who did not have diabetes (CONTROL) as well as degradation of ILM in response to sampling conditions at birth. Insulin propeptides were abundant in cord blood, comprising 50% of ILM in CONTROL and 36% in ODM (P < 0.0001) and more resistant to degradation than insulin (P < 0.05). Concentrations of all three ILM were highly intercorrelated with median values 2- to 5-fold higher in ODM than CONTROL [e.g. median (range): insulin ODM 110 (60-217) pmol/liter; CONTROL 22 (15-37) pmol/liter; P < 0.0001]. In ODM, 32-33 split proinsulin and proinsulin were more closely related to birth weight (Spearman r for ILM: r(32-33 split)= 0.54; r(PROINSULIN): r = 0.54; r(INSULIN) = 0.40: r(32-33 split) and r(PROINSULIN) > r(INSULIN)P < 0.05) and fetal leptin (r(32-33 split)= 0.55; r(PROINSULIN); r = 0.54; r(INSULIN) = 0.22: r(32-33 split) and r(PROINSULIN) > r(INSULIN)P < 0.05) than insulin). By contrast, insulin was more closely related to cord glucose (r(32-33 split) = 0.15; r(PROINSULIN): r = 0.10; r(INSULIN) = 0.42: r(INSULIN) > r(32-33 split) and r(PROINSULIN)P < 0.05). In CONTROL, 32-33 split proinsulin was also more closely related to fetal leptin r(32-33 split)= 0.61; r(PROINSULIN): r = 0.29; r(INSULIN) = 0.33: r(32-33 split) > r(INSULIN)P < 0.05). In ODM, 32-33 split proinsulin and proinsulin have closer relationships to fetal growth and leptin concentrations at birth than insulin. Measurement of insulin propeptides may be advantageous in assessment of the influence of maternal hyperglycemia on the newborn.

Type 1 diabetes-related antibodies in the fetal circulation: prevalence and influence on cord insulin and birth weight in offspring of mothers with type 1 diabetes.

During pregnancy, maternal type 1 diabetes-associated autoantibodies may cross the placenta. It is proposed that insulin antibodies (IA) allow transfer of insulin across the placenta, contributing to fetal hyperinsulinemia and macrosomia. We assessed the prevalence of IA, the tyrosine phosphatase IA-2, and glutamic acid decarboxylase (GADA) in cord blood from offspring of mothers with type 1 diabetes (ODM, n = 138) and control mothers (control, n = 47) and further assessed cross-sectional relationships of antibody titers to birth weight and fetal insulin. In ODM, antibodies were frequently present in cord blood; 124 ODM (95%) were positive for IA, 82 (59%) were positive for GADA antibodies, and 61 (44%) were positive for IA-2 antibodies. In controls, GADA and IA-2 antibodies were absent, whereas seven controls (15%) were positive for IA at low titers (P < 0.0001 ODM vs. controls for all).ODM with IA (IA positive) or without IA (IA negative) had similar birth weights (mean +/- sd: IA positive, 3.8 +/- 0.7 kg; IA negative, 4.0 +/- 0.6 kg; P = 0.31) and cord insulin concentrations (IA positive: median, 112 pmol/liter; interquartile range, 62-219 pmol/liter; IA negative: median, 114 pmol/liter; interquartile range, 59-194 pmol/liter; P = 0.96). Similarly, the presence of GADA and/or IA-2 autoantibodies (n = 103) was not associated with differences in birth weight or insulin concentrations. Antibody titers were not associated with birth weight or insulin as continuous variables in either controls or ODM. Islet autoantibodies and IA are a common finding in cord blood of ODM, but we found no evidence that they influence offspring insulin concentrations or weight at birth.

A comparative study of the effects of adrenoceptor antagonists on platelet aggregation and thromboxane generation.

Platelet aggregation and thromboxane A2 have been implicated in the pathogenesis of several forms of vascular disease. The aim of this study was to determine the effect of a wide range of adrenoceptor antagonists on platelet aggregation, and thromboxane A2 production, from normal human platelet rich plasma in vitro. Labetalol, pindolol and propranolol inhibited platelet aggregation to collagen in a dose dependent manner. Increasing the concentration of collagen "shifted" the dose response curve to the right. These 3 drugs also significantly inhibited thromboxane A2 generation in response to collagen but not to arachidonic acid. This effect was independent of any inhibitory effect of these drugs on platelet aggregation, and occurred at a drug concentration close to that obtained in vivo. Atenolol, metoprolol, prazosin and timolol were similarly assessed but had no effect on either platelet aggregation or thromboxane A2 generation. This ability of labetalol, pindolol, and propranolol to inhibit platelet aggregation and thromboxane generation, may be of clinical benefit in view of the increasing evidence implicating thromboxane A2 in the pathogenesis of vascular disease.

Secretion of tissue inhibitors of matrix metalloproteinases by human fetal membranes, decidua and placenta at parturition.

At parturition, breakdown of extracellular matrix in the fetal membranes may play a part in the rupture of the membranes and in the aetiology of premature rupture, in addition to having a regulatory role in the cell-cell interactions and signalling at the feto-maternal interface to stimulate myometrial contractility. The matrix metalloproteinases (MMPs) are important enzymes for the breakdown of extracellular matrix and their activity is regulated by a family of endogenous inhibitors, the tissue inhibitors of matrix metalloproteinases (TIMPs). At parturition, alteration in the balance between MMPs and TIMPs may mediate this extracellular matrix breakdown during rupture of fetal membranes. The aims of this study were to determine if the intrauterine secretion of TIMPs changes at labour, and to characterise their cellular sources. A broad range of TIMP activities (27-30 kDa, 24 kDa and 21 kDa) were detected by reverse zymography in term amniotic fluid. There was a significant (P<0.05) decrease in the amount of TIMPs in amniotic fluid and their release with the onset of labour. The TIMPs were characterised by immunoblot as TIMPs-1, -2, -3 and -4. High levels of TIMPs were secreted by explants of chorio-decidua, decidua parietalis and placenta, with less being released by amnion. Immunolocalisation studies revealed a specific distribution pattern for each of the TIMP isoforms. Trophoblast cells of chorion laeve, decidua parietalis and placental syncytiotrophoblast demonstrated specific immunoreactivity for all four isoforms. TIMPs were also found bound to selective regions of extracellular matrix. The decrease in TIMPs during labour may permit increased breakdown of extracellular matrix in the fetal membranes and decidua at parturition, thus altering cell signalling at the feto-maternal interface and facilitating membrane rupture.

Secretory leukocyte protease inhibitor concentration increases in amniotic fluid with the onset of labour in women: characterization of sites of release within the uterus.

Secretory leukocyte protease inhibitor is a potent inhibitor of neutrophil function, a mediator of mucosal immunity and an inhibitor of NF|gkB regulated inflammatory responses. However, its source, function and regulation within the uterus during pregnancy and at parturition are not well defined. In amniotic fluid, the concentration of secretory leukocyte protease inhibitor increased significantly from 2nd trimester (24+/-3 ng/ml; mean+/-s.e.m.; n=20) to term (751+/-53 ng/ml; P<0.05; n=15) with a further profound increase (P<0.005) with the onset of labour (3929+/-1076 ng/ml; n=15). To establish the intra-uterine sites of secretion, explants (n=6 different patients per tissue) were collected at term after elective caesarean section. High levels of secretory leukocyte protease inhibitor were released by decidua (135.2+/-12.4 pg/mg; mean+/-s.e.m.) and chorio-decidua (325.1+/-26.4 pg/mg) with less by amnion (55.6+/-6.0 pg/mg) and placenta (9.2+/-1.9 pg/mg). Intense immunoreactivity for secretory leukocyte protease inhibitor was detected predominantly in decidua parietalis cells adherent to the chorion laeve and myometrium, and also in decidua basalis. We propose that, within the pregnant uterus, secretory leukocyte protease inhibitor is released by decidua, fetal membranes and potentially the fetal lung. The increase in secretory leukocyte protease inhibitor may act to modulate pro-inflammatory paracrine interactions for the maintenance of pregnancy and limit those occurring at parturition within the uterus.

Production of prostaglandins E and Falpha by corpora lutea, corpora albicantes and stroma from the human ovary.

This study has shown that corpora lutea, stromal tissue and corpora albicantes from human ovaries contain prostaglandin E (PGE) and PGFalpha, and that the two former tissues can synthesize these prostaglandins during incubation. Enhanced syntheses, especially of PGE, occurred on adding arachidonic acid to the incubation medium, and the presence of prostaglandin synthetase activity was conclusively demonstrated. In corpora lutea obtained during the early and mid-luteal phase, the mean concentrations of PGE and PGFalpha were 34.3 and 9l9 ng/g respectively (mean ratio PGE:PGFalpha = 3.7); similar values were found in three corpora lutea from women at 10-12 weeks of pregnancy. All these corpora lutea contained appreciable amounts of progesterone and oestradiol-17beta. Prostaglandin levels were generally lower in corpora lutea obtained during the late luteal phase, although the PGE:PGFalpha ratio had increased to a mean value of 8.4. In corpora albicantes, the concentrations of both PGE and PGFalpha were significantly higher than the levels found in corpora lutea (P less than 0.01), whilst the mean ratio of PGE:PGFalpha had fallen significantly to 1.8 (P less than 0.01). Prostaglandin levels in stromal tissue varied considerably between individuals. The mean values were significantly lower than those of the corpora albicantes (P less than 0.01) but not significantly different to corpora lutea at any stage. These findings are discussed in relation to the possible role of prostaglandins in ovarian steroidogenesis and corpus luteum regression in man.

Chorionic prostaglandin catabolism is decreased in the lower uterine segment with term labour.

We have examined the hypothesis that regional differences in 15-hydroxyprostaglandin dehydrogenase (PGDH) activities occur within the human fetal membranes. Further, we reasoned that a specific reduction in PGDH in the fetal membranes at the lower uterine segment might occur with labour, providing a potential mechanism for local generation of primary prostaglandins (PG) that could contribute to cervical ripening. Full-thickness membranes were obtained from patients at caesarean section in the presence or absence of labour. Membranes were sampled from three regions: close to the site of placental attachment, in the region of the internal cervical os, and from a 'middle' area between these two. PGDH activities (sum of PGF2 alpha to 15-keto PGF2 alpha and 13, 14-dihydro 15-keto PGF2 alpha conversion) and immunoreactivity varied appreciably between the three regions. PGDH activity was highest in chorion in the cervical region of patients not in labour, but was significantly lower in the chorion from membranes taken closest to the internal os of patients in labour. Loss of PGDH activity was not attributable to a diminution in the number of trophoblast cells in this area. We conclude that regional loss of PGDH in the fetal membranes (chorion) at the lower uterine segment occurs with labour. Reduced PG catabolism could facilitate local generation of bioactive PG at this site for cervical effacement.

Changes in prostaglandin synthesis and metabolism associated with labour, and the influence of dexamethasone, RU 486 and progesterone.

The objective was to compare the changes in prostaglandin synthesis and metabolism occurring within the fetal membranes that are associated with the onset of parturition and to study the effect of steroid hormones on prostaglandin metabolism. A tissue explant study was made of discs of amnion and chorion obtained from 24 pregnant women at 37-42 weeks' gestation following spontaneous labour and delivery (12 women) and elective caesarean section (12 women). Significantly more prostaglandin E2 (PGE2) and PGF2 alpha were synthesized by amnion obtained following spontaneous labour than elective caesarean section. Arachidonic acid stimulated both PGE2 and PGF2 alpha synthesis by amnion in both groups. Phorbol myristoyl acetate stimulated PGE2 synthesis in both groups. There was no difference between the groups in the capacity of the chorion to metabolize prostaglandins. Mifepristone (RU 486) reduced the metabolism of added PGE2 following spontaneous labour, while dexamethasone and progesterone had no effect on prostaglandin metabolism. In conclusion, the increase in concentration of PGE2 and PGF2 alpha associated with the onset of spontaneous labour is the result of an increase in synthesis rather than a reduction in metabolism. There was no decrease in metabolism to account for the increase in prostaglandin concentrations and, with the exception of mifepristone, metabolism was not altered by the addition of steroid hormones.

Differential secretion of chemokines from peripheral blood in pregnant compared with non-pregnant women.

The maintenance of a normal pregnancy is dependent on the delicate interaction between the endocrine and the immune systems. Cytokines are thought to play a key role in pregnancy by way of local modulation of the immune system at the level of peripheral leukocytes. This study examined the potential of peripheral venous blood cultures from pregnant women throughout gestation and from non-pregnant women to produce the chemokines monocyte chemotactic protein-1 (MCP-1), interleukin-8 (IL-8) and RANTES. Significantly (P = < 0.001), higher levels of MCP-1 were released from peripheral blood cultures from pregnant women at term than during the first trimester or from women who were not pregnant. This could not be accounted for by differences in differential blood counts. Significantly higher levels (P = < 0.05) of MCP-1 were released from PBMC preparations from pregnant compared with non-pregnant women. No 'rebound' increase in MCP-1 was observed on withdrawing progesterone support to the PBMC preparations. MCP-1 was secreted predominately from CD14+ cells with those from pregnant women producing more than those from non-pregnant women. There was no statistical difference in release of IL-8 or RANTES from either peripheral blood or PBMC preparations from pregnant or non-pregnant women. IL-8 and RANTES were secreted from CD14+ and CD14- cells, respectively. The hypothesis proposed is that the monocytes are fundamentally different in pregnancy and that measurement of MCP-1 has the potential to act as a marker of pregnancy status.

Effect of intravenous prostaglandin E 2 on platelet function, coagulation, and fibrinolysis.

Prostaglandin E(2) (PGE(2)) was infused intravenously to eight women for the termination of pregnancy and tests of platelet function: coagulation and fibrinolysis were studied before and during the infusion.Platelet adhesiveness, as measured by a cellophane membrane test-cell system, was significantly diminished by PGE(2), a change which was not noted by the glass-bead column technique. The administration of PGE(2) caused more rapid platelet disaggregation following ADP-induced aggregation but had no effect on the platelet count, collagen-induced aggregation, or platelet factor 3 activity. An increase in plasma antithrombin concentration and euglobulin lysis activity was also noted. These results support the concept that prostaglandin E(2) might have a role in the prevention of thrombosis.

Neutrophil activation is confined to the maternal circulation in pregnancy-induced hypertension.

The aim of this study was to determine whether neutrophil activation occurs in the fetal circulation in pregnancy-induced hypertension and to correlate this with evidence of neutrophil activation in the maternal circulation. Twenty-one normal pregnancies and 23 complicated by pregnancy-induced hypertension were studied in the third trimester. The mean length of gestation at delivery was significantly shorter (P less than .01) and the mean birth weight percentile was significantly lower (P less than .05) in the hypertensive group; otherwise the groups were comparable. Blood was obtained before cesarean delivery or established labor in the mothers and immediately after delivery from the umbilical vein. Plasma neutrophil elastase, which is released after neutrophil activation, was measured by radioimmunoassay as a marker for neutrophil activation. The mean (+/- standard error) concentration of neutrophil elastase in maternal plasma in the hypertensive group (35.9 +/- 4.7 ng/mL) was significantly higher than in the normal group (20.8 +/- 0.87 ng/mL) (P less than .005). The concentration of neutrophil elastase in umbilical venous plasma was not significantly different between the normal and hypertensive groups. However, significantly higher concentrations of neutrophil elastase were found in the umbilical venous plasma of pregnancies delivered vaginally compared with those delivered by cesarean (P less than .05) regardless of diagnosis. There was no correlation between maternal venous and umbilical venous plasma neutrophil elastase concentrations, birth weight percentile, plasma urate, or platelet count. These data suggest that neutrophil activation is confined to the maternal circulation in pregnancy-induced hypertension where it may contribute to vascular damage and dysfunction in areas such as the placental bed.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of mifepristone on cervical ripening and labor induction in primigravidae.

OBJECTIVE: To compare the effects of 50 mg or 200 mg of oral mifepristone with placebo on cervical ripening and induction of labor in primigravid women at term with unfavorable cervices. METHODS: This was a double-blind study in which 80 primigravidae at term with a modified Bishop score of 4 or less were randomly assigned to one of three treatment groups. They were assessed at 24-hour intervals for 72 hours, after which labor was induced if it had not occurred spontaneously. RESULTS: Two hundred milligrams of mifepristone resulted in a favorable cervix (with a Bishop score greater than 6 or in spontaneous labor) in significantly more women than placebo (P = .01). An improvement in cervical ripening was seen in the group given 50 mg of mifepristone, but this was not statistically significant. There were more cesarean deliveries performed for fetal distress in the group treated with 200 mg of mifepristone than placebo, but this was not statistically significant and was not associated with any differences between groups in terms of neonatal outcome. CONCLUSION: Mifepristone, a progesterone antagonist, is known to cause softening and dilation of the human early pregnant cervix and an increase in uterine activity. It is theoretically attractive for use as an adjunct in cervical priming and labor induction. In this study, 200 mg of mifepristone was significantly more likely to result in a favorable cervix than placebo.

Mechanisms involved in the stimulatory effect of amniotic fluid on prostaglandin production by human fetal membranes.

This study aims to investigate potential mechanisms involved in the stimulatory effect of amniotic fluid on prostaglandin production by fetal membranes. A cell culture study of amnion and chorion was obtained following elective caesarean section, incubated with amniotic fluid collected at term (37-42 weeks' gestation) following either spontaneous labour (n = 6) or elective caesarean section (n = 6). The effect of addition of cycloheximide and actinomycin D (inhibitors of translation and transcription respectively), and staurosporine and genistein (inhibitors of protein kinase C and tyrosine kinase respectively) to these cultures was investigated. ANOVA was employed for statistical analysis. Cycloheximide and staurosporine significantly inhibited the stimulatory effect of spontaneous labour and elective section amniotic fluid on PGE2 production by amnion, and PGEM production by chorion. Genistein significantly inhibited the stimulatory effect of spontaneous labour amniotic fluid on PGE2 and PGEM production by amnion and chorion respectively. The stimulatory effect of amniotic fluid on prostaglandin production is dependent on new protein synthesis, presumably cyclooxygenase (COX), and stimulation of cell signal transduction pathways involving protein kinase C and tyrosine kinase.

Inhibition of platelet aggregation in whole blood by adrenoceptor antagonists.

It has recently become possible to study platelet aggregation in whole blood which may more closely resemble the in-vivo situation as the platelets are left in their natural milieu with red and white cells present which themselves can influence aggregation. The effects of 4 adrenoceptor antagonists on platelet aggregation in whole blood were studied in-vitro using the Clay-Adams Ultra Flo 100 whole blood platelet counter. Labetalol, pindolol and propranolol inhibited aggregation to 0.5 microgram/ml collagen in a dose dependent manner, and were synergistic with prostacyclin in inhibiting collagen induced aggregation. These 3 drugs also promoted reversal of aggregation induced by 10 microM ADP, but only inhibited 0.5 mM arachidonic acid induced aggregation at high drug concentrations. Atenolol had no effect on either collagen, ADP or arachidonic acid induced aggregation. The anti-platelet effect of these drugs may be of value in the treatment of vascular disease.

Inhibition of whole blood platelet aggregation by nicardipine, and synergism with prostacyclin in-vitro.

Platelets are involved in the pathogenesis of vascular disease, and calcium channel blocking agents (CCB) such as nicardipine, are being used in the treatment of such disorders. CCB's are known to have minor anti-platelet actions from studies performed in platelet rich plasma (PRP). Recently it has become possible to study platelet aggregation in whole blood. The effects of nicardipine on whole blood platelet aggregation were studied in-vitro using the Clay-Adams Ultra Flo 100 whole blood platelet counter. Nicardipine inhibited aggregation to 0.5 micrograms/ml collagen, and 0.5 mM arachidonic acid in a dose dependent manner, but had minimal effects on aggregation to 10 microM ADP. Nicardipine also acted synergistically with prostacyclin to inhibit aggregation. The effect of nicardipine on generation of PGI2 and TxA2 from whole blood was studied. Nicardipine did not affect TxA2 production, but significantly increased PGI2 production at high concentration. The effect of nicardipine on vascular PGI2 production was also assessed using umbilical artery rings, but nicardipine had no effect on PGI2 production. This study confirms that CCBs have inhibitory actions on platelet aggregation, and this may be of value in the treatment of vascular disease.

Pharmacological modulation of cervical compliance in the first and second trimesters of pregnancy.

PIP: Health practitioners use many methods and agents to bring on cervical ripening in early pregnancy, such as intracervical tents and pharmacological techniques, to induce a therapeutic abortion. Prostaglandins alter myometrial and cervical tissue and are the most often used pharmacological technique. Reduced collagen concentration, an increase in water volume, an increase in prostaglandins (PGE2, PGI2, and PGF2 alpha), and a change in the glycosaminoglycan (GAG) content coincide with cervical ripening, yet the mechanism responsible for these changes is obscure. Prostaglandins appear to cause the breakdown of collagen or change the GAG/proteoglycan content. Research shows that prostaglandins can initiate cervical ripening at any stage of pregnancy. Estradiol stimulates prostaglandin production thereby al so inducing cervical dilation. Relaxin also demonstrates an ability to ripen the cervix. In addition, mifepristone (RU-486) is gaining acceptance as a cervical ripening agent. In fact, RU-486 and gemeprost have at least 95% success rate compared to 92% for gemeprost alone or 85% with RU-486 alone. The only effective and acceptable prostaglandins to use at gestation of 0-8 weeks are sulprostone, gemeprost, and 9-methylene-PGE2. At t his gestational age, pharmacological modulation is all that is needed. Even though they are effective (abortion rate 90%), side effects are expected to occur (pain, nausea, and vomiting). Similarly, prostaglandin analogues are preferable for cervical ripening in women at 8-12 weeks gestation. Suction curettage or other surgical techniques then are used to remove the conceptus. At 12-16 weeks gestation, many physicians prefer the same protocol as that of 8-12 weeks gestation. Other choose to infuse PGE2 and saline into the amniotic fluid to stimulate uterine contractions. Another procedure at 12-16 weeks involves 1mg vaginal pessaries of gemeprost every 3 hours to ripen the cervix and stimulate contractions. After 16 weeks, the methods for 12-16 weeks still apply.^ieng

Prostaglandins as therapy for labour induction or therapeutic abortion.

(a) Prostaglandins (especially PGE2) are highly effective for ripening the cervix and inducing labour. If the cervix is already ripe, a small dose of PGE2 may be all that is required to initiate a labour which resembles spontaneous labour as closely as possible. (b) Amniotomy is the central event. Although it is possible for an infant to be born in the caul, i.e. in intact membranes, it is the general rule for the membranes to rupture or to be ruptured during labour. Such rupture leads to heightened activity of endogenous prostaglandins. The timing of amniotomy is crucial. Performed too early, before the cervix is ripe, it may lead to complications. Delayed too late, we may lose the advantage of its uterine sensitizing. (c) Oxytocin is a potent myometrial stimulant if the uterus is primed to respond to it by prostaglandins, either endogenous or exogenous. It must be given intravenously and many mothers find this disagreeable. In most instances of labour induction, a proper combination of prostaglandin therapy and amniotomy may allow the use of oxytocin to be avoided, but it remains the therapy of final resort to carry labour through to delivery if required.

Induction of labour by different methods in primiparous women. I Some perinatal and postnatal problems.

A personal prospective study was made of some perinatal and postnatal problems associated with induction of labour by three different methods in primiparous women with unripe cervices. The methods of induction were: (A) amniotomy followed by intravenous oxytocin [49], (B) amniotomy followed by intravenous prostaglandin E2 [39], (C) prostaglandin E2 by the extra-amniotic route [42]. A spontaneous group (D) comprising 54 mother--infant pairs was also studied. Length of gestation was between 37 and 42 wk in all but 2 cases. There was no perinatal mortality, and no infant had hyaline membrane disease. A close association was found between method of delivery and method (or absence) or induction. The caesarean section rate was highest in group C and lowest in group D. The spontaneous vaginal delivery rate was lowest in group C and highest in group D. More infants in the three induction groups were admitted to the Special Care Baby Unit (SCBU) than in the spontaneous group. No significant associations were found between the severity of the conditions leading to induction and caesarean section rates, low Apgar scores, admissions to SCBU, or the favourability of the cervix before induction. Among those who intended to breast feed fewer infants in the spontaneous group changed from breast to bottle while in hospital and after discharge from hospital than in the combined induction groups. Success in breast-feeding was not significantly associated with method of delivery or whether the infant was admitted to SCBU or not.

Labetalol therapy in pregnancy induced hypertension: the effects on fetoplacental circulation and fetal outcome.

We prospectively studied the effects of oral labetalol therapy in patients with moderate to severe pregnancy induced hypertension (PIH). The outcome variables were blood pressure control, effect on umbilical artery flow velocity waveforms (UAFVW) and fetal outcome. Forty-two patients were recruited, all had moderate to severe PIH. The mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) on entry were 154 +/- 7 mmHg and 104 +/- 5 mmHg, respectively. All had significant proteinuria. After 1 week on labetalol therapy, 85% of patients had their blood pressure controlled. The reduction in both SBP and DBP was statistically significant. There were no significant changes in UAFVW, Resistance Index (RI), uric acid or platelets. The mean fetal age on entry was 246 +/- 10 days while gestation at delivery was 258 +/- 17 days. The mean birth weight was 2712 +/- 609 g. No perinatal mortality occurred in this study. Labetalol is an effective drug in controlling blood pressure and does not adversely affect the UAFVW. No neonatal problems were attributed directly to the drug. Fetal outcome was satisfactory despite the 12 fetuses that were growth-retarded. Labetalol allows safe prolongation of pregnancies complicated by PIH.