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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Impact of obesity and other risk factors on labor dystocia in term primiparous women: a case control study.

BACKGROUND: Purpose of this study was to investigate differences between primiparous term pregnancies, one leading to vaginal delivery (VD) and the other to acute cesarean section (CS) due to labor dystocia in the first stage of labor. We particularly wanted to assess the influence of body mass index (BMI) on CS risk. METHODS: A retrospective case-control study in a tertiary delivery unit with 5200 deliveries annually. Cases were 296 term primiparous women whose intended vaginal labor ended in acute CS because of dystocia. Controls were primiparas with successful vaginal delivery VD (n = 302). The data were retrieved from medical records. Multiple logistic regression analyses were used to assess the associations between BMI and covariates on labor dystocia. RESULTS: In the cases ending with acute CS, women were older (OR 1.06 [1.03-1.10]), shorter (OR 0.94 [0.91-0.96]) and more often had a chronic disease (OR 1.60 [1.1-2.29]). In this group fetal malposition (OR 42.0 [19.2-91.9]) and chorioamnionitis (OR 10.9 [5.01-23.6]) were more common, labor was less often in an active phase (OR 3.37 [2.38-4.76]) and the cervix was not as well ripened (1.5 vs. 2.5 cm, OR 0.57 [0.48-0.67] on arrival at the birth unit. BMI was higher in the dystocia group (24.1 vs. 22.6 kg/m2, p < 0.001), and rising maternal pre-pregnancy BMI had a strong association with dystocia risk. If BMI increased by 1 kg/m2, the risk of CS was 10% elevated. Among obese primiparas, premature rupture of membranes, chorioamnionitis and induction of labor were more common. Their labors were less often in an active phase at hospital admission. Severely obese primiparas (BMI ≥ 35 kg/m2) had 4 hours longer labor than normal-weight parturients. CONCLUSIONS: Labor dystocia is a multifactorial phenomenon in which the possibility to ameliorate the condition via medical treatment is limited. Hospital admission at an advanced stage of labor is recommended. Pre-pregnancy weight control in the population at reproductive age is essential, as a high BMI is strongly associated with labor dystocia.

Subclinical inflammation associated with prolonged TIMP-1 upregulation and arterial stiffness after gestational diabetes mellitus: a hospital-based cohort study.

BACKGROUND: Gestational diabetes mellitus (GDM) has significant implications for the future health of the mother. Some clinical studies have suggested subclinical inflammation and vascular dysfunction after GDM. We aimed to study whether concentrations of high-sensitivity C-reactive protein (hsCRP), tissue inhibitor of metalloproteinase-1 (TIMP-1), matrix metalloproteinase-8 (MMP-8) and -9, as well as values of arterial stiffness differ between women with and without a history of GDM a few years after delivery. We also investigated possible effects of obesity on the results. METHODS: We studied two cohorts-120 women with a history of GDM and 120 controls-on average 3.7 years after delivery. Serum concentrations of hsCRP were determined by immunonephelometric and immunoturbidimetric methods, MMP-8 by immunofluorometric assay, and MMP-9 and TIMP-1 by enzyme-linked immunosorbent assays. Pulse wave velocity (PWV) was determined using the foot-to-foot velocity method from carotid and femoral waveforms by using a SphygmoCor device. Arterial compliance was measured non-invasively by an HDI/PulseWave™CR-2000 arterial tonometer. All 240 women were also included in subgroup analyses to study the effect of obesity on the results. Multiple linear regression analyses were performed with adjustment for confounding factors. RESULTS: PWV after pregnancy complicated by GDM was significantly higher than after normal pregnancy, 6.44 ± 0.83 (SD) vs. 6.17 ± 0.74 m/s (p = 0.009). Previous GDM was also one of the significant determinants of PWV in multiple linear regression analyses. On the other hand, compliance indices of both large (p = 0.092) and small (p = 0.681) arteries did not differ between the study cohorts. Serum TIMP-1 levels were significantly increased after previous GDM (p = 0.020). However, no differences were found in the serum levels of MMP-8, MMP-9 or hsCRP. In subgroup analyses, there were significantly higher concentrations of hsCRP (p = 0.015) and higher PWV (p < 0.001) among obese women compared with non-obese ones. CONCLUSIONS: PWV values were significantly higher after GDM compared with normoglycemic pregnancies and were associated with prolonged TIMP-1 upregulation. Cardiovascular risk factors were more common in participants with high BMI than in those with previous GDM.

Term twin birth - impact of mode of delivery on outcome.

INTRODUCTION: The main aims of this study were to compare maternal and neonatal outcomes in term twin birth according to the planned mode of delivery and to study the effects of chorionicity and inter-twin delivery time on neonatal outcome. MATERIAL AND METHODS: A single-center cohort study of 495 women with twin deliveries at ≥37+0 weeks of gestation. Term twin deliveries were divided into a trial of labor group (TOL, 69.3%) and a planned cesarean section (CS) group (30.7%). The primary outcomes were maternal and neonatal morbidity. RESULTS: 80.8% of women attempting TOL achieved vaginal birth. In the TOL group, mothers had less bleeding [median 500 mL (range 150-2700 mL) vs. 950 mL (range 150-3500 mL), p < 0.001) and fewer surgical complications (3.2% vs. 8.6%, p = 0.011), whereas second twins more often had five-minute Apgar scores of <7 (5.0% vs. 0%, p = 0.002) or umbilical artery pH < 7.05 (5.7% vs. 0%, p = 0.003), compared with the planned CS group. There was a slight, non-significant tendency for more NICU admissions in the TOL group, yet the need for NICU treatment was infrequent in the whole study material. Outcomes among dichorionic (DC) second twins were similar to those in the whole material, but among monochorionic (MC) second twins there were no differences between the TOL and planned CS groups. In secondary analysis, a five-minute Apgar score <7 occurred significantly more often in the DC group among second twins if the inter-twin delivery time exceeded 30 min. CONCLUSIONS: TOL is a good option for women with twin pregnancy at term, regardless of chorionicity. Active management of labor for the second twin is important, also in DC births. Maternal outcomes were more favorable with TOL and although low Apgar scores and low umbilical blood pH may be more frequent after TOL - especially with the second twin - serious neonatal morbidity is rare and does not differ from that after planned CS.

Women treated for epilepsy during pregnancy: outcomes from a nationwide population-based cohort study.

INTRODUCTION: Women with epilepsy (WWE) are generally treated as a risk group during pregnancy, but over 90% of pregnant WWE have favorable pregnancies. However, the risk of some pregnancy and delivery complications may be increased among WWE, especially those on antiepileptic drugs. MATERIAL AND METHODS: This nationwide, retrospective population-based cohort study includes WWE who gave birth in Finland during 1987-2008 (n = 1737) and the reference cohort of a random sample of women without epilepsy (n = 4357). Identification of the cohorts, and information on hospitalizations and deliveries were obtained from the Finnish Health Registers and population statistics. Multivariate analyses were conducted by binomial regression. RESULTS: WWE were more often hospitalized during pregnancy for accidents or other external causes [adjusted risk ratio (aRR) 1.74, 95% confidence interval (CI) 0.98-3.09], premature rupture of membranes (aRR 1.75, 95% CI 1.14-2.69) and premature contractions (aRR 1.75, 95% CI 1.36-2.23). Hospitalizations for infections were more frequent in WWE (1.4% vs. 0.4%, aRR 3.15, 95% CI 1.72-5.76). The risk for induction of delivery or a cesarean section was increased in WWE. There was no difference in premature deliveries between the groups, but the risk of being small for gestational age (aRR 1.57, 95% CI 1.23-2.01), admission to neonatal intensive care unit (aRR 1.66, 95% CI 1.39-1.97), and need for respiratory care (aRR 2.37, 95% CI 1.57-3.60) was clearly increased in the offspring of WWE. CONCLUSIONS: WWE are at an increased risk of complications and hospitalizations during pregnancy and delivery. However, the majority of WWE have a normal pregnancy and delivery.

Cardiotocography in breech versus vertex delivery: an examiner-blinded, cross-sectional nested case-control study.

BACKGROUND: The safety of vaginal breech delivery has been debated for decades. Although it has been shown to predispose infants to immediate depression, several observational studies have also shown that attempting vaginal breech delivery does not increase perinatal morbidity or low Apgar score at the age of five minutes. Cardiotocography monitoring is recommended during vaginal breech delivery, but comparative data describing differences between cardiotocography tracings in breech and vertex deliveries is scarce. This study aims to evaluate differences in intrapartum cardiotocography tracings between breech and vertex deliveries in the final 60 min of delivery. A secondary goal is to identify risk factors for suboptimal neonatal outcome in the study population. METHODS: One hundred eight breech and 108 vertex singleton, intended vaginal deliveries at term from a tertiary hospital with 5000 annual deliveries were included. Two experienced obstetricians, blinded to fetal presentation, neonatal outcome and actual mode of delivery, evaluated traces recorded 60 min before delivery. They provided a three-tier classification and evaluated different trace features according to FIGO (1987) guidelines. Factors associated with acidemia and low Apgar scores were identified by univariate and multivariable analyses performed with binary logistic regression. Student's T-test and chi-square test were used, as appropriate. RESULTS: Late decelerations were seen in 13.9 % of breech and 2.8 % of vertex deliveries (p = 0.003) and decreased variability in 26.9 % of breech and 8.3 % of vertex deliveries (p < 0.001). In multivariable analysis complicated variable decelerations and breech presentation were identified as risk factors for neonatal acidemia and low Apgar score at the age of five minutes. Pathological trace and breech presentation were independent risk factors for low Apgar score at the age of one minute. CONCLUSIONS: Decreased variability and late decelerations were more prevalent in breech compared to vertex deliveries. Pathological trace predicts immediate neonatal depression and especially complicated variable decelerations may signal more severe distress. Further research is needed to create guidelines for safe management of vaginal breech delivery.

Oxidized LDL, insulin resistance and central blood pressure after gestational diabetes mellitus.

INTRODUCTION: Gestational diabetes mellitus (GDM) is an indicator of future cardiovascular disease. We investigated whether sensitive biomarkers of increased cardiovascular risk differ between women with and without a history of GDM few years after pregnancy, and whether obesity affects the results. MATERIAL AND METHODS: We studied two cohorts - 120 women with a history of GDM and 120 controls, on average 3.7 years after delivery. Circulating concentrations of oxidized low-density lipoprotein (oxLDL) were determined by ELISA. The homeostasis model assessment of insulin resistance (HOMA-IR) index was used to estimate insulin resistance. Central blood pressure (cBP) was measured noninvasively from a radial artery pulse wave. The primary outcomes were possible differences in oxLDL, HOMA-IR or cBP between the groups. Secondly, we investigated the influence of obesity on the results, also using adjusted multiple linear regression analyses. RESULTS: OxLDL concentrations or cBP did not differ between the two cohorts, but HOMA-IR was significantly higher in women with previous GDM than in controls, 1.3 ± 0.9 (SD) and 1.1 ± 0.9, respectively (p = 0.022). In subgroup analyses, HOMA-IR (p < 0.001), systolic (p < 0.001) and diastolic (p < 0.001) cBP were significantly higher in obese subgroups compared with non-obese ones. Body mass index was an important determinant of HOMA-IR and cBP in multiple linear regression analyses. CONCLUSIONS: Over 3 years after delivery, women with GDM were still more insulin-resistant than controls. Obesity turned out to be a more important determinant of insulin resistance and cBP compared with GDM.

Diagnosis and treatment of severe hemolytic disease of the fetus and newborn: a 10-year nationwide retrospective study.

OBJECTIVE: Outcome after intrauterine transfusions due to severe hemolytic disease of the fetus and newborn. DESIGN: Nationwide population-based retrospective cohort study. SETTING: All women treated with intrauterine transfusions for hemolytic disease of the fetus and newborn in Finland in 2003-2012. POPULATION: 339 intrauterine transfusions, performed in 104 pregnancies of 84 women. METHODS: Information on antenatal screening of red cell antibodies and red cell units issued for intrauterine transfusion was obtained from the Finnish Red Cross Blood Service database, and obstetric and neonatal data from hospital records. MAIN OUTCOME MEASURES: Procedure-related complications, perinatal mortality, neonatal morbidity. RESULTS: Overall survival was 94.2% (95% confidence interval 89.7-98.7). There were four fetal and two neonatal deaths. Procedure-related fetal loss rate was 1.2% (95% confidence interval 0.04-2.4) per procedure and 3.8% (95% confidence interval 0.1-7.5) per pregnancy. Of the four procedure-related losses, three were due to technically difficult intrauterine transfusions causing infection and preterm birth. Of the live born infants, 19% (95% confidence interval 11.3-26.7) were born before 32 weeks' gestation. The incidence of severe neonatal morbidity (respiratory distress syndrome, severe cerebral injury, sepsis) was 22.2% (95% confidence interval 13.4-30.2). Poor outcome (death, severe neonatal morbidity) was negatively associated with gestational age at first transfusion (p = 0.001) and at birth (p = 0.00006). Follow-up of the infants was too incomplete to assess the neurodevelopmental outcome. CONCLUSIONS: Although overall survival is comparable with previous studies, our concern is procedure-related infections and preterm births. Close collaboration between the university hospitals is needed to ensure timely treatment, operator skills and systematic follow-up of the children.