Delayed versus early delivery leads to similar outcome in selected cases of preeclampsia in the Finnish Genetics of Pre-eclampsia Consortium (FINNPEC) cohort.

OBJECTIVES: Most guidelines recommend induction of labor after 37 weeks of gestation in preeclampsia. This study assessed the effect of interval between diagnosis of preeclampsia and delivery on maternal and perinatal outcomes. STUDY DESIGN: A cohort of 1637 women with preeclampsia recruited at five university hospitals in Finland was studied. Outcomes were compared in two groups according to the time interval between diagnosis of PE and delivery: delivery in less than 10 days (the early delivery group) and delivery at 10 days or later after the diagnosis (the delayed delivery group). MAIN OUTCOME MEASURES: Maternal outcomes included significantly preterm delivery (delivery before 34 weeks of gestation), placental abruption, eclampsia and maternal intensive care or intensive monitoring for more than 24 h. Neonatal outcomes included small for gestational age, Apgar score of less than seven at the age of five minutes, umbilical artery pH < 7.05 and fetal death. RESULTS: No differences in frequency of preterm deliveries or maternal need for intensive care were observed between groups. Eclampsia and fetal death were rare, and their incidence did not differ between the groups. No maternal deaths were observed. Low Apgar score at five minutes of age was reported more commonly in the early delivery group, but there was no difference in fetal acidemia between groups. CONCLUSION: Early and delayed delivery lead to comparable outcomes in this cohort. Expectant management could be beneficial in women with an unripe cervix or preterm preeclampsia without severe features.

Uterine contractile activity and neonatal outcome - A blind analysis of a randomized controlled trial cohort.

INTRODUCTION: Sufficient contractions are necessary for a successful delivery but each contraction temporarily constricts the oxygenated blood flow to the fetus. Individual fetal or placental characteristics determine how the fetus can withstand this temporary low oxygen saturation. However, only a few studies have examined the impact of uterine activity on neonatal outcome and even less attention has been paid to parturients' individual characteristics. Our objective was therefore to find out whether fetuses compromised by maternal or intrapartum risk factors are more vulnerable to excessive uterine activity. MATERIAL AND METHODS: Uterine contractile activity was assessed by intrauterine pressure catheters. Women (n = 625) with term singleton pregnancies and fetus in cephalic presentation were included in this secondary, blind analysis of a randomized controlled trial cohort. Intrauterine pressure as Montevideo units (MVU), contraction frequency/10 min and uterine baseline tone were calculated for 4 h prior to birth or the decision to perform cesarean section. Uterine activity in relation to umbilical artery pH linearly or ≤7.10 was used as the primary outcome. Need for operative delivery (either cesarean section or vacuum-assisted delivery) due to fetal distress was analyzed as a secondary outcome. In addition, belonging to vulnerable subgroups with, for example, chorioamnionitis, hypertensive or diabetic disorders, maternal smoking or neonatal birthweight <10th percentile were investigated as additional risk factors. RESULTS: A linear decline in umbilical artery pH was seen with increasing intrauterine pressure in all deliveries (p < 0.001). Among parturients with suspected chorioamnionitis, every increasing 10 MVUs increased the likelihood of umbilical artery pH ≤7.10 (odds ratio [OR] 1.17, 95% confidence interval [CI] 1.02-1.34, p = 0.023). The need for operative delivery due to fetal distress was increased among all laboring women by every increasing 10 MVUs (OR 1.05, 95% CI 1.01-1.09, p = 0.015). This association with operative deliveries was further increased among parturients with hypertensive disorders (OR 1.23, 95% CI 1.05-1.43, p = 0.009) and among those with diabetic disorders (OR 1.13, 95% CI 1.04-1.28, p = 0.003). CONCLUSIONS: Increasing intrauterine pressure impairs umbilical artery pH especially among parturients with suspected chorioamnionitis. Fetuses in pregnancies affected by chorioamnionitis, hypertensive or diabetic disorders are more vulnerable to high intrauterine pressure.

Tafoxiparin, a novel drug candidate for cervical ripening and labor augmentation: results from 2 randomized, placebo-controlled studies.

BACKGROUND: Slow progression of labor is a common obstetrical problem with multiple associated complications. Tafoxiparin is a depolymerized form of heparin with a molecular structure that eliminates the anticoagulant effects of heparin. We report on 2 phase II clinical studies of tafoxiparin in primiparas. Study 1 was an exploratory, first-in-pregnant-women study and study 2 was a dose-finding study. OBJECTIVE: Study 1 was performed to explore the effects on labor time of subcutaneous administration of tafoxiparin before onset of labor. Study 2 was performed to test the hypothesis that intravenous treatment with tafoxiparin reduces the risk for prolonged labor after spontaneous labor onset in situations requiring oxytocin stimulation because of dystocia. STUDY DESIGN: Both studies were randomized, double-blind, and placebo-controlled. Participants were healthy, nulliparous females aged 18 to 45 years with a normal singleton pregnancy and gestational age confirmed by ultrasound. The primary endpoints were time from onset of established labor (cervical dilation of 4 cm) until delivery (study 1) and time from start of study treatment infusion until delivery (study 2). In study 1, patients at 38 to 40 weeks of gestation received 60 mg tafoxiparin or placebo daily as 0.4 mL subcutaneous injections until labor onset (maximum 28 days). In study 2, patients experiencing slow progression of labor, a prolonged latent phase, or labor arrest received a placebo or 1 of 3 short-term tafoxiparin regimens (initial bolus 7, 21, or 35 mg followed by continuous infusion at 5, 15, or 25 mg/hour until delivery; maximum duration, 36 hours) in conjunction with oxytocin. RESULTS: The number of participants randomized in study 1 was 263, and 361 were randomized in study 2. There were no statistically significant differences in the primary endpoints between those receiving tafoxiparin and those receiving the placebo in both studies. However, in study 1, the risk for having a labor time exceeding 12 hours was significantly reduced by tafoxiparin (tafoxiparin 6/114 [5%] vs placebo 18/101 [18%]; P=.0045). Post hoc analyses showed that women who underwent labor induction had a median (range) labor time of 4.44 (1.2-8.5) hours with tafoxiparin and 7.03 (1.5-14.3) hours with the placebo (P=.0041) and that co-administration of tafoxiparin potentiates the effect of oxytocin and facilitates a shorter labor time among women with a labor time exceeding 6 to 8 hours (P=.016). Among women induced into labor, tafoxiparin had a positive effect on cervical ripening in 11 of 13 cases (85%) compared with 3 of 13 participants (23%) who received the placebo (P=.004). For women requiring oxytocin because of slow progression of labor, the corresponding results were 34 of 51 participants (66%) vs 16 of 40 participants (40%) (P=.004). In study 2, tafoxiparin had no positive effects on the secondary endpoints when compared with the placebo. Except for injection-site reactions in study 1, adverse events were no more common for tafoxiparin than for the placebo among either mothers or infants. There were few serious or treatment-related adverse events. CONCLUSION: Subcutaneous treatment with tafoxiparin before labor onset (study 1) may be effective in reducing the labor time among women undergoing labor induction and among those requiring oxytocin for slow progression of labor. Moreover, tafoxiparin may have a positive effect on cervical ripening. Short-term, intravenous treatment with tafoxiparin as an adjunct to oxytocin in patients with labor arrest (study 2) did not affect labor time or other endpoints. Both studies suggest that tafoxiparin has a favorable safety profile in mothers and their infants.

Labor induction at 41+0 gestational weeks or expectant management for the nulliparous woman: The Finnish randomized controlled multicenter trial.

INTRODUCTION: Neonatal and maternal risks increase in term pregnancy as gestational age advances and become increasingly evident post-term. Management practices of late- and post-term pregnancies vary, and the optimal time point for intervention by labor induction is yet to be determined. MATERIAL AND METHODS: This randomized controlled trial of 381 nulliparous women with unripe cervices compared labor induction at 41+0 gestational weeks (early induction) with expectant management and labor induction at 41+5 to 42+1 gestational weeks (expectant management). This multicenter study included all five university hospitals and the largest central hospital in Finland. The study period was 2018-2022. Participants were randomized to either early induction (48.8%, n = 186) or expectant management (51.2%, n = 195) with equal randomization ratios of 1:1. This was a superiority trial, and the primary outcomes were rates of cesarean section (CS) and composite of adverse neonatal outcomes. The trial was registered at the ISRCTN registry (ISRCTN83219789, https://doi.org/10.1186/ISRCTN83219789). RESULTS: The rates of CS (16.7% [n = 31] vs. 24.1% [n = 47], RR 0.7 [95% CI: 0.5-1.0], p = 0.07) and a composite of adverse neonatal outcomes (9.7% [n = 18] vs. 14.4% [n = 28], RR 0.7 [95% CI: 0.4-1.2] p = 0.16) did not significantly differ between the groups, but the operative delivery rate was lower in the early induction group than in the expectant management group (30.6% [n = 57] vs. 45.6% [n = 89], p = 0.003). The rates of hemorrhage ≥1000 mL and neonatal weight ≥4000 g were also lower in the early induction group, as was the vacuum extraction rate in women with vaginal delivery. Of the women with expectant management, 45.6% (n = 89) had spontaneous onset of labor. No perinatal deaths occurred, but one case of eclampsia appeared in the expectant management group. CONCLUSIONS: Offering labor induction to nulliparous women at 41+0 gestational weeks may decrease the probability of operative delivery, postpartum hemorrhage, and neonatal weight ≥4000 g. However, this study was underpowered to affirm the trends of rising rates of CS and adverse neonatal outcomes in the expectant management group. Thus, expectant management could remain an option for some, as one in two women with expectant management had a spontaneous onset of labor.

Satisfaction and dissatisfaction with pain relief and birth experience among induced and spontaneous-onset labours ending in vaginal birth: A prospective cohort study.

Objective: To assess pain relief and overall birth experience in induced vs. spontaneous-onset labours and to clarify variables among induced parturients determining satisfaction and dissatisfaction. Study design: A prospective study of 2042 women. 575 women with induced and 1467 with spontaneous-onset labour answered multiple questions in a questionnaire regarding the experience of birth giving. Satisfaction was numerically assessed via a visual analogue scale (VAS 0-10). Results: Induction of labour (IOL) did not worsen the average experience of pain relief, but the proportion of women dissatisfied with pain relief was slightly higher after IOL compared with spontaneous-onset labour (SOL). IOL was associated with lower satisfaction with overall birth experience compared with SOL (VAS 8.0 vs. 8.4; p < 0.001). Among IOL parturients incorrect timing of pain relief was strongly associated with dissatisfaction with pain relief, as were deficient information and induction with misoprostol. Epidural blockade was the most important factor preventing dissatisfaction with pain relief. Unsatisfactory overall experience of birth was associated with deficient pain relief, its incorrect timing or deficient information, as well as vacuum extraction as the mode of delivery. Conclusions: Induction of labour is a risk factor of dissatisfaction regarding pain relief and overall birth experience. The strongest impact on dissatisfaction among induced parturients concerning pain relief was delayed timing of effective labour analgesia. Poor pain relief, its incorrect timing and deficient information on pain relief were strong predictive factors of dissatisfaction with the overall birth experience.

Thromboelastometry-guided treatment algorithm in postpartum haemorrhage: a randomised, controlled pilot trial.

BACKGROUND: Postpartum haemorrhage causes significant mortality among parturients. Early transfusion of blood products based on clinical judgement and conventional coagulation testing has been adapted to the treatment of postpartum haemorrhage, but rotational thromboelastometry (ROTEM) may provide clinicians means for a goal-directed therapy to control coagulation. We conducted a parallel design, randomised, controlled trial comparing these two approaches. We hypothesised that a ROTEM-guided protocol would decrease the need for red blood cell transfusion. METHODS: We randomised 60 parturients with postpartum haemorrhage of more than 1500 ml to receive either ROTEM-guided or conventional treatment, with 54 patients included in the final analysis. The primary outcome was consumption of blood products, and secondarily we assessed for possible side-effects of managing blood loss such as thromboembolic complications, infections, and transfusion reactions. RESULTS: The median (25th-75th percentile) number of RBC units transfused was 2 (1-4) in the ROTEM group and 3 (2-4) in the control group (P=0.399). The median number of OctaplasLG® units given was 0 in both groups (0-0 and 0-2) (P=0.030). The median total estimated blood loss was 2500 ml (2100-3000) in the ROTEM group and 3000 ml (2200-3100) in the control group (P=0.033). No differences were observed in secondary outcomes. CONCLUSIONS: ROTEM-guided treatment of postpartum haemorrhage could have a plasma-sparing effect but possibly only a small reduction in total blood loss. CLINICAL TRIAL REGISTRATION: NCT02461251.

Association of dietary fiber, liquid intake and lifestyle characteristics with gastrointestinal symptoms and pregnancy outcome.

Objectives: Heartburn and constipation are common gastrointestinal symptoms during pregnancy. High fiber and liquid intake have beneficial effects on these symptoms in non- pregnant population. Our aim was to evaluate the association of dietary fiber, fluid intake and lifestyle characteristics with constipation, heartburn, and pregnancy outcome. Study design: Two hundred pregnant women were enrolled in this prospective cohort study during the 1st trimester of pregnancy. Participants completed a self- administered questionnaire concerning bowel symptoms, dietary fiber, liquid intake, and lifestyle characteristics before pregnancy, during pregnancy and post-partum. After exclusions 173 pregnant women participated the study and 173, 173, 136, 109 and 91 completed pre-pregnancy, and 1st, 2nd, and 3rd trimester, and post-partum questionnaires, respectively. Data on deliveries and perinatal outcome (n = 173) were collected from hospital records. In trajectory analysis, the women were clustered in groups based on the intake of fiber and liquids. Generalized linear mixed models and logistic regression analyses were used to find associations of fiber and fluid intake with constipation, heartburn and pregnancy outcome. Results and conclusions: Heartburn increased significantly during pregnancy and the highest prevalence (33%) was during the third trimester. A combination of low fiber and low fluid intake increased the risk of constipation during pregnancy (OR 5.9, 95% CI 2.00-17.4). Low fiber intake increased the risk of combined adverse outcome (cesarean section, premature delivery and/or small for gestational age; OR 3.4, 95% CI 1.2-9.6). Sufficient fiber and liquid intake may be protective against pregnancy-associated constipation and may be associated with improved pregnancy outcome.

Twin birth: The maternal experience.

OBJECTIVE: Twin birth is a special setting for women giving birth, and the experience of childbirth can be different from singleton birth. The objective of this study was to evaluate and compare the childbirth experiences of twin mothers and singleton mothers. We also aimed to identify the risk factors of a negative childbirth experience in the whole study population. METHODS: All live diamniotic twin deliveries in the study hospital of at least 35+0 weeks of gestation with a plan of vaginal birth were included in this matched groups study from August 2015 to August 2019. For every twin birth, two singleton birth controls were selected and matched with parity, the actual mode of birth, and gestational weeks at birth. Six weeks after birth, a Childbirth Experience Questionnaire (CEQ) was sent to mothers, and 72 twin mothers and 126 singleton mothers returned the questionnaire. RESULTS: The twin mothers' overall childbirth experience was positive. They reported a significantly lower opportunity to choose the birthing position (p < 0.001). Otherwise, there were no differences in the CEQ mean total scores between the study groups. Intrapartum cesarean section raised the risk of a negative childbirth experience and there was a high level of satisfaction with midwifery care among the whole study population. CONCLUSION: The overall maternal experience in planned vaginal twin birth was positive. Twin mothers felt less often able to choose their birthing position, otherwise the childbirth experience did not differ from that of singleton mothers.

Dietary fibre intake and lifestyle characteristics in relation to nausea or vomiting during pregnancy-a questionnaire-based cohort study.

Nausea or vomiting in pregnancy (NVP) are among the commonest symptoms experienced in early pregnancy. We wanted to evaluate the association of dietary fibre intake, lifestyle characteristics and bowel function with NVP. One hundred and eighty-eight participants completed a self-administered questionnaire concerning bowel function, dietary fibre intake and lifestyle characteristics. Women suffering from NVP (n = 91) consumed significantly more fibre derived from cereal products (p=.026) and total fibre (p=.043) during pre-pregnancy period was compared to women without NVP (n = 97). In both groups, intake of total fibre and fibre derived from fruit and vegetables increased significantly during the first trimester. Dietary fibre intake did not protect from NVP. However, women suffering from NVP were able to maintain their fibre intake. Dietary fibre is tolerated well during NVP, and this finding can be used when giving diet counselling to women suffering from NVP.Impact statementWhat is already known on this subject? Nausea or vomiting in pregnancy (NVP) are among the commonest symptoms experienced in early pregnancy. The pathophysiology of NVP remains unknown, but it has been suggested to be multifactorial. Diet during pregnancy may have an impact on NVP. It is generally advised to avoid meat, poultry, fish, eggs and spicy and fatty foods during periods of NVP, but there is limited data on the effects of diet of NVP.What do the results of this study add? Women suffering from NVP have been shown to eat less meat (and thus protein) compared to women without NVP. Dietary fibre reduces constipation and heartburn and it also keeps blood glucose levels stable. Because of various beneficial effects of fibre on the digestive system, we hypothesised that a high fibre intake may alleviate the symptoms of NVP.What are the implications of these findings for clinical practice and/or further research? The aim of the present study was to investigate whether the amount or source of dietary fibre are associated with NVP. We wanted to investigate intake of fibre derived from cereal products (mostly representing insoluble fibre) and fibre derived from fruit and vegetables (containing mostly soluble fibre) separately in relationship to NVP, as the mechanisms of action of these fibre groups are different. There are no observational studies including also pre-pregnancy consumption of fibre when focussing on the association between fibre and NVP. The results of this study can be used when giving diet counselling to women suffering from NVP.

Angiogenic Effect of Pravastatin Alone and with Sera from Healthy and Complicated Pregnancies Studied by in vitro Vasculogenesis/Angiogenesis Assay.

OBJECTIVE: To determine the direct effect of pravastatin on angiogenesis and to study the interaction between pravastatin and maternal sera from women with early- or late-onset pre-eclampsia (PE), intrauterine growth restriction, or healthy pregnancy. METHODS: We collected 5 maternal serum samples from each group. The effect of pravastatin on angiogenesis was assessed with and without maternal sera by quantifying tubule formation in a human-based in vitro assay. Pravastatin was added at 20, 1,000, and 8,000 ng/mL concentrations. Concentrations of angiogenic and inflammatory biomarkers in serum and in test medium after supplementation of serum alone and with pravastatin (1,000 ng/mL) were measured. RESULTS: Therapeutic concentration of pravastatin (20 ng/mL) did not have significant direct effect on angiogenesis, but the highest concentrations inhibited angiogenesis. Pravastatin did not change the levels of biomarkers in the test media. There were no changes in angiogenesis when therapeutic dose of pravastatin was added with maternal sera, but there was a trend to wide individual variation towards enhanced angiogenesis, particularly in the early-onset PE group. CONCLUSIONS: At therapeutic concentration, pravastatin alone or with maternal sera has no significant effect on angiogenesis, but at high concentrations the effect seems to be anti-angiogenic estimated by in vitro assay.

Impact of mode of delivery on perinatal outcome in moderately and late preterm twin birth.

OBJECTIVE: To examine the impact of the mode of delivery on neonatal and maternal outcomes in moderately and late preterm twin birth. METHODS: This single-center cohort study included 275 live diamniotic moderately and late preterm twin deliveries at 32+0 -36+6  weeks of gestation. These twin deliveries were divided into two groups according to the planned mode of delivery: trial of labor (TOL) (N=199, 72.4%) and planned cesarean section (CS) (N=76, 27.6%). The primary outcome was neonatal morbidity. Maternal outcome and the effects of gestational age and chorionicity on neonatal outcome were also studied. RESULTS: Of the women in the TOL group, 170 (85.4%) delivered vaginally. Both for the first and second twin, and for dichorionic or monochorionic deliveries, there were no differences between the TOL and CS groups in composite neonatal morbidity or in other neonatal outcomes. No significant differences were found between the TOL and CS groups when the moderately and late preterm gestational age cohorts were studied separately. Mothers in the planned CS group more often had puerperal infection and surgical complications in comparison with mothers in the TOL group. CONCLUSION: Among 275 moderately and late preterm twin deliveries, planned mode of delivery did not affect neonatal outcome.

Therapeutic doses of metformin do not have impact on angiogenesis in presence of sera from pre-eclamptic, IUGR and healthy pregnancies.

Recent evidence suggests that metformin may prevent pre-eclampsia by reverting the angiogenic imbalance in maternal sera. In this study, we investigated effect of metformin on angiogenesis by quantifying tubule formation in a human-based in vitro test with co-culture of human adipose stromal cell (hASC) and human umbilical vein endothelial cell (HUVEC). A total of 20 pregnant women were recruited in the study. Serum samples were obtained from women with early- and late-onset pre-eclampsia and from women with pregnancies complicated by intrauterine growth restriction (IUGR) without pre-eclampsia (N = 5 in each of the three groups). Serum samples from women with healthy pregnancies served as controls (N = 5). The direct effect of metformin on angiogenesis was first assessed without maternal sera. Secondly, we investigated the impact of metformin on angiogenesis in the present of maternal sera. Metformin was used at 5, 50 and 600 µg/ml concentrations. Angiogenic and inflammatory biomarkers in maternal sera were analyzed by immunoassays. When the direct effect of metformin was studied, the two lowest concentrations of metformin did not affect tubule formation (angiogenesis), but the highest concentration inhibited angiogenesis. When metformin was supplemented at therapeutic concentrations of 5 and 50 µg/ml along with serum samples, there was no change in tubule formation in comparison to maternal sera alone. However, strong inhibitory effect on tubule formation was observed in all groups with the highest, non-therapeutic (600 µg/ml), concentration of metformin.

Risk factors of unsuccessful vaginal twin delivery.

INTRODUCTION: Twin trial of labor presents a challenge to obstetricians, as it is associated with a greater number of adverse birth outcomes compared with singleton deliveries. The risk of poor outcome has shown to be highest with unsuccessful vaginal twin delivery. The purpose of this study was to identify the clinical risk factors associated with intrapartum cesarean section in late preterm and term twin births. MATERIAL AND METHODS: All live diamniotic twin deliveries of at least 35+0 weeks of gestation with planned vaginal delivery were included in this retrospective single-center cohort study. Maternal and newborn characteristics were compared between a vaginal delivery group and an intrapartum cesarean section group. Logistic regression analysis was carried out to determine independent risk factors of intrapartum cesarean section. Further, maternal and neonatal outcomes were compared between groups of vaginal delivery and cesarean section for both twins and also between groups of vaginal delivery and cesarean section for the second twin only (combined delivery). The impact of presentation of the second twin on the mode of twin delivery and on neonatal outcome was also examined. RESULTS: Among 821 twin pregnancies, 581 mothers (70.8%) attempted trial of labor and were eligible for the study. With a cephalic-presenting first twin, the trial of labor rate was 89.3% and vaginal delivery was successful in 82.8%. Nulliparity (odds ratio [OR] 3.2, 95% confidence interval [CI] 2.0-5.1) and non-cephalic presentation of the second twin (OR 3.0, 95% CI 1.9-4.8) were found to be independent risk factors of cesarean section. However, 76.1% of mothers with non-cephalic second twins achieved vaginal delivery and perinatal outcomes were comparable with cases of cephalic-presenting second twins. When comparing delivery modes, maternal outcomes were more favorable with vaginal delivery, whereas combined delivery increased the second twin's risk of adverse neonatal outcome. CONCLUSIONS: This study, with high rates of trial of labor and successful vaginal twin delivery, found nulliparity and non-cephalic presentation of the second twin to be risk factors of intrapartum cesarean section in twin pregnancies.

Oral versus patient-controlled intravenous administration of oxycodone for pain relief after cesarean section.

PURPOSE: The optimal postoperative analgesia after cesarean section (CS) remains to be determined. The primary objective of this study was to assess whether oral oxycodone provides the same or better pain control and satisfaction with pain relief as oxycodone given intravenously using a patient-controlled analgesia (PCA) infusion device. The secondary objectives were to compare the gastrointestinal symptoms and postsurgical recovery of the two groups. METHODS: This prospective randomized trial was conducted at a University Hospital between February 2015 and June 2017. Altogether 270 CS patients were randomly assigned to receive postoperative oxycodone pain relief by IV PCA (n = 133) or orally (n = 137). Pain control and satisfaction with pain treatment were assessed by a numeric rating scale (NRS) at 2, 4, 8, and 24 h postoperatively. RESULTS: No differences were found in NRS pain scores or satisfaction between the groups except at 24 h pain when coughing; there was a statistically significant difference favoring the IV PCA group (p = 0.006). In the IV PCA group, the patients experienced more nausea at 4 h (p = 0.001) and more vomiting at 8 h (p = 0.010). Otherwise, postoperative recovery was similar in both groups. The equianalgesic dose of oxycodone was significantly smaller in the oral group (p = 0.003). CONCLUSIONS: This study indicates that oral oxycodone provides pain control and satisfaction with pain relief equal to IV oxycodone PCA for postoperative analgesia after cesarean section. Satisfaction with pain treatment was high in both groups, and both methods were well tolerated. Early nausea was less common with oral medication.

Pregnancy outcome in women after total hip replacement: A population-based study.

OBJECTIVE: Only a few small studies have been published on pregnancies after total hip replacement (THR), and they have reported no adverse pregnancy outcomes after THR. The aim of our study was to evaluate whether maternal THR affects pregnancy outcomes on a population-based level. STUDY DESIGN: Data for this nationwide register-based cohort study have been collected from four national registries in Finland from 1980 to 2007. All females who had undergone THR during that period formed the patient group, and three controls for each patient without THR were selected. Patient group comprised 2429 women, 719 (29.6%) of whom had 1190 pregnancies ending in singleton deliveries. Of those births, 986 were before THR and 204 after THR. The control group comprised 7276 women, 2805 (38.6%) of whom had 5112 pregnancies ending in singleton deliveries, 3695 occurred before the index date (time point when THR took place within the patient group) and 1417 after. Logistic regression model was used to analyze univariable and adjusted odds ratios (aOR) for adverse neonatal outcomes after maternal THR compared with controls. Data were adjusted using the following variables: maternal age, smoking, rheumatoid arthritis. RESULTS: Stillbirth was more common in the patient group compared with control group 4 (2.0%) vs 8 (0.6%) p = 0.02. Moreover, neonates in the patient group were more likely to be born preterm (aOR 3.58, p=<0.001), small for gestational age (aOR 2.83, p = 0.006) and low birthweight (aOR 4.79, p=<0.001), compared to control group. Trial of labor more likely ended in emergency cesarean section in the patient group than in the control group 39 (28.9%) vs 150 (11.6%), p=<0.001. Adverse pregnancy outcome was more common after THR also when compared to pregnancies before THR. CONCLUSIONS: Neonates born after maternal total hip replacement have an increased risk of stillbirth, small for gestational age, low birthweight and preterm birth. Trial of labor is more likely to end in emergency cesarean section.

The efficacy of misoprostol vaginal insert compared with oral misoprostol in the induction of labor of nulliparous women: A randomized national multicenter trial.

INTRODUCTION: Our objective was to compare the efficacy of a 200-µg misoprostol vaginal insert vs oral misoprostol regarding the cesarean section rate and the time interval to vaginal delivery in nulliparous women with unfavorable cervix. MATERIAL AND METHODS: In this prospective multicenter trial, 283 nulliparous women at term with Bishop score <6 were randomized to induction of labor with either a misoprostol vaginal insert (n = 140) or oral misoprostol (n = 143). In the oral misoprostol group, a 50-µg dose of oral misoprostol was administered every 4 hours up to three times during the first day; during the second day, the dose was increased to 100-µg every 4 hours up to three times during the first day, if necessary. Primary outcome was the cesarean section rate. Secondary outcomes were the time from induction of labor to vaginal delivery, the rate of other induction methods needed, labor augmentation with oxytocin and/or amniotomy, use of tocolytics and adverse neonatal and maternal events. RESULTS: In the misoprostol vaginal insert group, median time to vaginal delivery was shorter (24.5 hours vs 44.2 hours, P < 0.001), whereas no difference was found in the cesarean section rate (33.8% vs 29.6%, odds ratio [OR] 1.21, 95% confidence interval [CI] 0.66-1.91, P = 0.67). Other induction methods and labor augmentation with oxytocin and/or amniotomy were less frequent in the misoprostol vaginal insert group (OR 0.32, 95% CI 0.18-0.59 and OR 0.56, 95% CI 0.32-0.99, respectively). Need for tocolysis and meconium-stained amniotic fluid were more common in the misoprostol vaginal insert group (OR 3.63, 95% CI 1.12-11.79 and OR 2.38, 95% CI 1.32-4.29, respectively). Maternal and neonatal adverse events did not differ between groups. CONCLUSIONS: Misoprostol vaginal insert proved to shorten the time to vaginal delivery and to reduce the use of other methods of labor induction and augmentation, but it did not reduce the cesarean section rate compared with oral misoprostol. The benefit of more rapid delivery associated with misoprostol vaginal insert should be weighed against the greater risks for uterine hyperstimulation and meconium-stained amniotic fluid.

Obstetric patients' health-related quality of life before and after intensive care.

BACKGROUND: Intensive care admissions during pregnancy, childbirth, and postpartum period are relatively well investigated. However, very little is known about these obstetric patients' health-related quality of life (HRQoL) before and after critical care. OBJECTIVE: The objective of this study was to assess obstetric patients' HRQoL before intensive care admission (baseline) and at 6 months after discharge (follow-up) DESIGN: This was a retrospective database study. In a 5-year period, the data of all women admitted to the intensive care unit (ICU) during pregnancy, delivery, or up to 42 days postpartum were analysed. METHODS: Four multidisciplinary ICUs of Finnish University hospitals participated. The HRQoL was assessed using the EuroQol-5D (EQ-5D) instrument with utility score (EQsum) and visual analogue scale (EQ-VAS). RESULTS: A total of 283 obstetric patients were identified from the clinical information system. Of these, 99 (35%) completed the EQ-5D questionnaires both at baseline and follow-up, and 65 of them (23%) completed EQ-VAS. The comparison of patients' EQsum scores before intensive care admission and after discharge showed that patients' HRQoL remained good (0.970 vs 0.972) (max 1.0) or increased (0.788 vs 0.982) in 80.8% of the patients. Patients reported improved overall health on the EQ-VAS at 6 months follow-up (EQ-VAS mean, 71.86 vs 88.20; p ≤ 0.001) (max 100). However, 19.2% of the patients had lower HRQoL (EQsum mean 0.987 vs 0.798) at follow-up. Following intensive care, 15% of the patients had more pain/discomfort, and 11% expressed more depression/anxiety. Multiparous patients were more likely to suffer from worsened depression/anxiety (p = 0.024). CONCLUSION: In the majority of the obstetric patients, HRQoL at 6 months follow-up remained good or had increased from baseline. However, nearly one-fifth of the patients had impaired HRQoL after discharge. Thus, intensive care management should take in to consideration follow-up program after intensive care of ICU-admitted obstetric patients.

Angiogenic capacity in pre-eclampsia and uncomplicated pregnancy estimated by assay of angiogenic proteins and an in vitro vasculogenesis/angiogenesis test.

OBJECTIVE: The purpose of the study was to determine the angiogenic capacity of sera in early and late pregnancy and in umbilical blood serum after childbirth, and to define how angiogenic properties assessed in a functional in vitro test are related to individual angiogenic proteins in six women with pre-eclampsia and in six healthy pregnant controls. METHODS: Maternal first and third trimester serum samples, and umbilical blood samples after childbirth, were tested in an in vitro human adipose stromal cell-human umbilical vein endothelial cell (hASC-HUVEC) vasculogenesis/angiogenesis assay. The angiogenic properties of the samples were measured by quantifying tubule formation. Concentrations of total placental growth factor (PlGF), total vascular endothelial growth factor (VEGF), soluble fms-like tyrosine kinase 1 (sFlt-1) and soluble endoglin (sEng) were determined by immunoassay. RESULTS: First-trimester maternal sera of both groups had a stimulatory effect on angiogenesis in vitro and levels of angiogenic proteins did not differ between the groups. Third-trimester maternal sera in the pre-eclampsia group had an inhibitory effect on tubule formation, while those from normal pregnancies remained stimulatory. Compared with the first trimester there was a significant change in the concentrations of angiogenic proteins toward an anti-angiogenic state in pre-eclampsia. Umbilical blood serum exhibited strong anti-angiogenic effects without a significant difference between groups. CONCLUSIONS: Third-trimester serum of pre-eclamptic patients is anti-angiogenic. This phenomenon is not yet present in the first trimester. Umbilical blood serum shows inhibitory effects on angiogenesis after normal as well as pre-eclamptic pregnancy.

Prediction of spontaneous preterm delivery in women presenting with premature labor: a comparison of placenta alpha microglobulin-1, phosphorylated insulin-like growth factor binding protein-1, and cervical length.

BACKGROUND: Placental alpha microglobulin-1 and phosphorylated insulin-like growth factor-binding protein-1 have been studied in patients at risk for preterm birth with signs and symptoms of preterm labor. However, a direct comparison between these 2 biomarkers, alone or in combination with cervical length measurement with an adequate sample size, has been lacking to date. OBJECTIVE: The purpose of this study was to compare the placental alpha microglobulin-1 test and the phosphorylated insulin-like growth factor-binding protein-1 test alone and in combination with cervical length measurement for the prediction of imminent spontaneous preterm birth of testing in pregnant women with symptoms of preterm labor in a tertiary care setting. STUDY DESIGN: Four hundred three patients with intact amniotic membranes and cervical dilation ≤3 cm, without recent intercourse or cerclage, between gestational weeks of 20+0 and 36+6 were recruited prospectively from 3 international centers. Placental alpha microglobulin-1 and phosphorylated insulin-like growth factor-binding protein-1 tests were conducted before cervical length measurement via transvaginal ultrasound scanning. Caregivers were blinded to the biomarker test results. Medically indicated deliveries within 14 days of testing were excluded. Standard performance statistics with 95% confidence intervals were calculated and compared based on pairwise estimates from a generalized model. RESULTS: Of 403 subjects who were enrolled in the study cohort, 94% (383/403 women) met the inclusion criteria. Median gestational age and cervical length at presentation were 30+5 weeks and 27 mm, respectively; 6.8% women (26/383 women) had spontaneous birth ≤7 days from testing. The placental alpha microglobulin-1 test was positive in 7.8% of the women (30/383 women); the phosphorylated insulin-like growth factor-binding protein-1 test was positive in 29.5% women (113/383 women). Positive predictive value for placental alpha microglobulin-1, phosphorylated insulin-like growth factor-binding protein-1, and cervical length <25 mm for the prediction of spontaneous preterm birth in the overall cohort was 60.0% (18/30 women), 18.6% (21/113 women), 11.8% (18/152 women), respectively. The negative predictive value was 97.7% (345/353 women), 98.2% (265/270 women), 96.5% (223/231 women), respectively. The prevalence of spontaneous preterm birth in this group was 6.8% (26/383 women). The positive likelihood ratios were 20.6, 3.1, and 1.8, respectively. The negative likelihood ratio were 0.3, 0.3, and 0.5, respectively. Positive predictive values for placental alpha microglobulin-1 and phosphorylated insulin-like growth factor-binding protein-1 tests in patients with cervical length shortening of 15-30 mm for the prediction of spontaneous preterm birth were 60.9% (14/23 women) and 28.1% (16/57 women), respectively. The negative predictive values were 97.1% (168/173 women) and 97.8% (136/139 women), respectively. The prevalence of spontaneous preterm birth in the 15-30 mm cohort was 9.7% (19/196 women). The positive likelihood ratios were 14.5 and 3.6, respectively. The negative likelihood ratios were 0.3 and 0.2, respectively. CONCLUSION: Placental alpha microglobulin-1 is significantly more specific than phosphorylated insulin-like growth factor-binding protein-1 for the prediction of spontaneous preterm birth ≤7 days (P<.0001), whereas both tests have comparable sensitivity. In patients with cervical length 15-30 mm, although placental alpha microglobulin-1 has a significantly higher positive predictive value and specificity compared with phosphorylated insulin-like growth factor-binding protein-1 for the prediction of spontaneous preterm birth at ≤7 days (P<.01), both tests have a comparable sensitivity and negative predictive value. In conclusion, placental alpha microglobulin-1 is a better predictor of imminent spontaneous preterm birth when compared with phosphorylated insulin-like growth factor-binding protein-1 alone or in combination with cervical length measurement. In patients with shortening of cervical length of 15-30 mm, the placental alpha microglobulin-1 test is a significantly better predictor of imminent spontaneous preterm birth within 7 days of testing than is phosphorylated insulin-like growth factor-binding protein-1.