Outpatient vs inpatient induction of labor with oral misoprostol: A retrospective study.

INTRODUCTION: Induction of labor is one of the most common obstetrical procedures today, with a successively rising rate. With a limited number of hospital beds, the option of starting induction at home has gained increasing attention. The primary aim of this study was to compare the proportion of women achieving vaginal delivery and the duration of hospital stay before delivery in induction of labor with oral misoprostol starting at home and induction with oral misoprostol at the hospital, in a low-risk population. MATERIAL AND METHODS: Women with home induction (n = 282) were individually matched to controls induced at the hospital during the same time period regarding parity, age, body mass index, labor unit and indication for induction. RESULTS: The rates of vaginal birth were similar in outpatients and inpatients (84.8% vs 86.2%; p = 0.5). Time from hospital admission to delivery in the outpatient group was significantly shorter than in the inpatient group (12.8 vs 20.6 h; p < 0.001), as was total hospital stay (2 vs 3 days; p < 0.001). There were no significant differences between the groups in neonatal or maternal outcomes. One patient undergoing outpatient induction had an unplanned home birth. CONCLUSIONS: Starting induction at home reduced the time spent in hospital without affecting the vaginal delivery rate. Although underpowered to assess safety, this study did not show any differences in adverse maternal and perinatal outcomes between inpatients and outpatients. Further research is needed to evaluate the safety of outpatient induction of labor with misoprostol.

Sublingual misoprostol vs. oral misoprostol solution for induction of labor: A retrospective study.

Introduction: Induction of labor (IOL) is one of the most common obstetrical procedures, with an increasing rate. The prostaglandin E1 analogue misoprostol is frequently used as a primary method of labor induction. The optimal dose and route of administration is yet to be ascertained. Aim: To compare efficiacy and safety between a regimen of sublingually administered misoprostol and a regimen of orally administered misoprostol, with cesarean delivery as primary outcome. Methods: A retrospective study was conducted including women carrying a live, singleton fetus in a cephalic position with labor induced at >37 + 0 gestational weeks at Skåne University hospital, Lund, between January 1st 2013 to December 31st 2017. Data was obtained from computerized obstetrical charts. Results: Totally 2,404 women were included; 974 induced with sublingual misoprostol and 1,430 with oral solution. In primiparous women the cesarean delivery rate was lower in primiparous women induced with oral compared to sublingual misoprostol (20.5% vs. 28.6%, p < 0.001), whereas in parous women the rates did not differ significantly 4.9% vs. 7.5%; NS). The increased risk of caesarean remained after controlling for potential confounding factors (adjusted odds ratio 1.49 (1.14-1.95). Women induced with sublingual misoprostol had a shorter time to vaginal delivery when compared to oral solution (primiparous median 16.7 h vs. 21.7 h; p < 0.001, parous median 9.9 h vs. 13.3 h; p = 0.01), and a higher rate of vaginal delivery within 24 h (primiparas 77.7% vs. 63.3%, p < 0.001, parous 93.2% vs. 84.2%; p = 0.01). Conclusion: IOL with oral misoprostol solution was associated with a significantly higher vaginal delivery rate when compared to sublingual misoprostol, whereas sublingual misoprostol was associated with a significantly shorter time from induction to vaginal delivery. Oral administration is considered the most safe and efficient administration of misoprostol, although more studies are needed to find the optimal route and dosage of misoprostol for IOL.

[Postpartum hemorrhage and need of blood transfusions]. / Postpartumblödningar med blodtransfusioner har ökat.

Postpartum hemorrhage is responsible for one fourth of the maternal mortality worldwide. In high resource countries there is an increasing trend in frequency of postpartum hemorrhage and need of blood transfusions. The reason for this increase is probably multifactorial. Major bleeding requires massive blood transfusion (MT), defined as transfusion of >10 units of erythrocytes within 24 hours. In Sweden the incidence of MT due to obstetric hemorrhage is reported to be 53 per 100 000 deliveries and the majority of the cases are due to placental complications, such as placenta previa and placenta accreta. These placental complications have increased over the past years as a consequence of a higher rate of cesarean deliveries. To reduce the number of deliveries requiring blood transfusion postpartum, prophylactic measures such as identification of women at increased risk, optimizing management of hemorrhage and evaluating the effect of every transfused unit of erythrocytes is important.

A Relative Bioavailability Study of Two Misoprostol Formulations Following a Single Oral or Sublingual Administration.

INTRODUCTION: Misoprostol (Cytotec) was primarily made for treating gastric ulcers. However today it is mostly used for abortion, treating postpartum hemorrhage, and for induction of labor. The tablet contains 200 µg of misoprostol, yet the dosages used for induction of labor are much smaller (25-50 µg), leading to uncertainty of dosage in daily use. AIM: To evaluate and compare the relative bioavailability of two misoprostol products (Angusta 25 µg and Cytotec 200 µg tablets) administered orally or sublingually given in a daily clinical setting to women admitted for induction of labor at term. METHODS: Women carrying a live, singleton fetus in a cephalic position and with a gestational age between 259 and 296 days were included. Blood samples were collected at 0, 5, 10, 20, 30, 40, 50, 75, 100, 120, 180, and 240 minutes. A serum analytical assay was performed and pharmacokinetic parameters were calculated. Patients were assigned to one of three groups. RESULTS: A total of 72 patients were included. No significant differences demographic characteristics were found. The ratios for AUC, AUC (0-t), and Cmax were similar in all three groups, but CI-values were outside the required 80-125%. Sublingual administration yielded a 20-30% higher bioavailability and a 50% higher Cmax than compared to the oral route. CONCLUSION: The relative bioavailability between Angusta and Cytotec could not be confirmed as being equal at the 25 µg or 50 µg level because the 90% CI-values when comparing the ratios for AUC, AUC(0-t), and Cmax were wider than accepted. The reason for this could be the real-life, non-standardized circumstances in which the study was conducted. Sublingual administration seems to have higher bioavailability than oral administration. More studies are needed to ascertain an optimal dosage regime balancing both safety and efficacy for mother and child. CLINICAL TRIAL REGISTRATION: www.ClinicalTrials.gov, identifier NCT02516631.

PP038. Renal ETK/BMX activation decreased in preeclampsia.

INTRODUCTION: Vascular endothelial growth factors (VEGF's) are essential to angiogenesis and play a central role in the pathophysiology of preeclampsia. Specifically, antagonists of VEGFR2 cause a preeclampsia-like syndrome, in humans and rats[1]. ETK/BMX is a receptor tyrosine kinase (RTK) which induces VEGF expression and forms a complex with VEGFR2, whereby VEGF and TNF can induce a reciprocal activation of both kinases. OBJECTIVES: To determine the levels of phosphorylation, and thus activation, of VEGFR2 and ETK/BMX in renal tissue from women with preeclampsia and with healthy pregnancies. METHODS: Renal tissue was obtained with consent from six preeclamptic and six healthy pregnant women included in a previous renal needle biopsy study[2] and a RayBio® Phosphorylation Antibody Array was used according to instructions. RESULTS: Phosphorylated ETK/BMX was significantly reduced in the preeclamptic women compared to in the healthy pregnant women. There was no difference in phosphorylated VEGFR2 between groups. CONCLUSION: These data suggest that ETK/BMX could be an important mediator of VEGF function in healthy pregnancy, in the kidneys more so than VEGFR2, and that absence of the positive feedforward signalling that ETK/BMX and VEGF together accomplish, and/or a TNF induced activation of this, may play a role in the pathophysiology of preeclampsia.

Folate and vitamin B12 in idiopathic male infertility.

Although methylenetetrahydrofolate reductase, a folate enzyme gene, has been associated with idiopathic male infertility, few studies have examined other folate-related metabolites and genes. We investigated whether idiopathic male infertility is associated with variants in folate, vitamin B(12) (B12) and total homocysteine (tHcy)-related genes and measured these metabolites in blood. We conducted a case-control study that included 153 men with idiopathic infertility and 184 fertile male controls recruited at the Fertility Center and Antenatal Care Center, University Hospital, Malmö and Lund, Sweden. Serum folate, red cell folate (RCF), serum B12, plasma tHcy and semen quality were measured. Subjects were genotyped for 20 common variants in 12 genes related to folate/B12/homocysteine metabolism. Metabolite concentrations and genotype distributions were compared between cases and controls using linear and logistic regression with adjustment for covariates. The phosphatidylethanolamine N-methyltransferase (PEMT) M175V and TCblR rs173665 polymorphisms were significantly associated with infertility (P=0.01 and P=0.009, respectively), but not with semen quality. Among non-users of supplements, infertile men had lower serum folate concentrations than fertile men (12.89 vs. 14.73 nmol l(-1); P=0.02), but there were no significant differences in RCF, B12 or tHcy. Folate, B12 and tHcy concentrations were not correlated with any semen parameters. This study provides little support for low folate or B12 status in the pathogenesis of idiopathic male infertility. Although additional data are needed to confirm these initial findings, our results suggest that PEMT and TCblR, genes involved in choline and B12 metabolism, merit further investigation in idiopathic male infertility.

Novel blocker of NFAT activation inhibits IL-6 production in human myometrial arteries and reduces vascular smooth muscle cell proliferation.

The calcineurin/nuclear factor of activated T cells (NFAT) signaling pathway has been found to play a role in regulating growth and differentiation in several cell types. However, the functional significance of NFAT in the vasculature is largely unclear. Here we show that NFATc1, NFATc3, and NFATc4 are expressed in human myometrial arteries. Confocal immunofluorescence and Western blot analysis revealed that endothelin-1 efficiently increases NFATc3 nuclear accumulation in native arteries. Endothelin-1 also stimulates NFAT-dependent transcriptional activity, as shown by a luciferase reporter assay. Both the agonist-induced NFAT nuclear accumulation and transcriptional activity were prevented by the calcineurin inhibitor CsA and by the novel NFAT blocker A-285222. Chronic inhibition of NFAT significantly reduced IL-6 production in intact myometrial arteries and inhibited cell proliferation in vascular smooth muscle cells cultured from explants from the same arteries. Furthermore, by using small interfering RNA-mediated reduction of NFATc3, we show that this isoform is involved in the regulation of cell proliferation. Protein synthesis in intact arteries was investigated using autoradiography of [(35)S]methionine incorporation in serum-free culture. Inhibition of NFAT signaling did not affect overall protein synthesis or specifically the synthesis rates of major proteins associated with the contractile/cytoskeletal system. An intact contractile phenotype under these conditions was also shown by unchanged force response to depolarization or agonist stimulation. Our results demonstrate NFAT expression and activation in native human vessels and point out A-285222 as a powerful pharmacological blocker of NFAT signaling in the vasculature.

Serum cystatin C reflects glomerular endotheliosis in normal, hypertensive and pre-eclamptic pregnancies.

OBJECTIVE: To study the correlation between serum cystatin C levels and renal structural changes in normal, hypertensive and pre-eclamptic pregnancy to evaluate it as a marker of the degree of renal involvement in pre-eclampsia. DESIGN: An observational prospective study. SETTING: University Hospital of Lund, Sweden. SAMPLE: Thirty-six women with hypertensive disease in pregnancy and 12 healthy pregnant women in the third trimester recruited from maternal health care centres in the catchment area of the hospital. METHODS: Renal biopsy samples were obtained from all participants and the degree of endotheliosis as well as the mean glomerular volume was evaluated by light microscopy in silver methenamin-stained sections. Serum cystatin C levels were measured and correlated to the structural changes. MAIN OUTCOME MEASURES: Correlation among degree of glomerular endotheliosis, glomerular volume and serum cystatin C. RESULTS: Serum cystatin C levels differed between the different degrees of endotheliosis, showing a highly significant increasing linear trend. They also correlated significantly with glomerular volume (r = 0.60, P < 0.001). Mean serum urate and creatinine levels also increased with the degree of endotheliosis, but not above the reference interval for normal term pregnancy, even in pre-eclamptic women. CONCLUSION: Serum cystatin C may be used as a marker, not only for impaired renal function, but also for the degree of glomerular endotheliosis and increase in glomerular volume in pregnancy. It may be of value in the monitoring of pregnancies complicated by pre-eclampsia.

Glomerular endotheliosis in normal pregnancy and pre-eclampsia.

OBJECTIVE: To investigate the proportion of women with findings characteristic for pre-eclampsia, as opposed to renal disease, in a controlled study of hypertensive pregnant women undergoing antepartum renal biopsy. DESIGN: An observational prospective controlled study. SETTING: University Hospital of Lund, Sweden. SAMPLE: Thirty-six previously healthy women with hypertensive disease in pregnancy, consecutively admitted to the antenatal ward at onset of disease during a 20 month period and giving informed consent, as well as 12 voluntary healthy pregnant controls. METHODS: Renal biopsy samples were obtained from all participants and evaluated by light microscopy, electron microscopy and immunofluorescence techniques. MAIN OUTCOME MEASURES: Presence and degree of glomerular endotheliosis. RESULTS: Glomerular endotheliosis was present in all women with pre-eclampsia and gestational hypertension, and in 5 of the 12 controls, although significant differences in the degree of endotheliosis were found between the groups. Clinically undetected renal disease was not diagnosed in any of the women. CONCLUSION: Glomerular endotheliosis was found in women with normal pregnancy as well as in both non-proteinuric and proteinuric hypertension and is consequently not, as earlier believed, pathognomonic for pre-eclampsia. The transition between normal term pregnancy, gestational hypertension and pre-eclampsia appears to be a continuous process, perhaps of increasing adaptation to pregnancy. Pre-eclampsia may be the extreme of the adaptational process, rather than a separate abnormal condition. Clinically undetected renal disease could be a rare cause of hypertension in pregnancy.

Significant delay of birth in advanced preterm labour at 23 gestational weeks with an oxytocin antagonist.

CASE: A 27-year-old primigravid woman with advanced preterm labour at 23 weeks and 5 days gestation received tocolytic therapy with a continuous infusion of the oxytocin antagonist, atosiban, during 154 h. The delivery was postponed for 12 days. The baby was discharged after 3 months of neonatal care and at 6 months of age is healthy. The prolonged treatment was not associated with maternal or fetal side effects.

Blood pressure patterns through consecutive pregnancies are influenced by body mass index.

OBJECTIVE: The purpose of this study was to analyze the impact of parity and baseline body mass index on blood pressure levels in pregnancy. STUDY DESIGN: We studied a longitudinal historic cohort of 166 healthy pregnant women who gave birth in 2000 to a third child at the University Hospital of Lund; blood pressure measurements were obtained at each antenatal visit during the three consecutive pregnancies. RESULTS: The mean systolic and diastolic blood pressure levels were consistently higher during the first pregnancy at comparable weeks of gestation, significantly so during the third trimester. The body mass index correlated with diastolic blood pressure levels only in the first pregnancy, and the impact of parity on third trimester blood pressure levels was greatest in the women with a high body mass index. Age, smoking, change of paternity, or a short time interval between pregnancies did not influence blood pressure levels. CONCLUSION: The interrelationship among blood pressure levels, parity, and body mass index in normal pregnancy resembles the situation in hypertensive pregnancies, which implies common adaptive mechanisms.