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.

Women's subjective perceptions and background factors associated with poor maternal childbirth experience among induced and spontaneous onset of labour: a two-year tertiary hospital cohort study.

BACKGROUND: Women undergoing induction of labour (IOL) more often have poor childbirth experience compared to women with spontaneous onset of labour (SOL). For understanding and optimizing childbirth experience in IOL, we investigated the subjective maternal reasons and perceptions leading to poor childbirth experience in IOL compared to SOL, as well as the background factors and delivery outcomes associated with the poor experience. METHODS: Two-year retrospective cohort study included 836/19442 deliveries (4.3%) with poor childbirth experience in induced or spontaneous onset at term in Helsinki University Hospital. Poor childbirth experience occurred in 389/5290 (7.4%) cases of IOL and in 447/14152 (3.2%) of SOL. Childbirth experience was measured after delivery using Visual Analog Scale (VAS) score, with poor experience defined as VAS < 5. The primary outcome of the study were the maternal reasons for poor childbirth experience. The parameters were collected in the hospital database and statistical analyses were performed by using Mann-Whitney U-test and t-test. RESULTS: The subjective maternal reasons for poor childbirth experience were pain (n = 529, 63.3%), long labour (n = 209, 25.0%), lack of support by care givers (n = 108, 12.9%), and unplanned caesarean section (CS) (n = 104, 12.4%). The methods of labour analgesia were similar among the women who expressed pain as the main reason compared with those who didn't. When comparing the reasons according to the onset of labour, IOL group more often reported unplanned CS (17.2% vs. 8.3%; p < 0.001) and lack of support by the care givers (15.4% vs. 10.7%; p = 0.04), while SOL group more often named pain (68.7% vs. 57.1%; p = 0.001) and rapid labour (6.9% vs. 2.8%; p = 0.007). In multivariable logistic regression model, IOL was associated with lower risk for pain compared to SOL (adjusted OR 0.6, 95%CI 0.5-0.8; p < 0.01). Primiparas more often reported long labour (29.3% vs. 14.3%; p < 0.001) and concern over own or baby's wellbeing (5.7% vs. 2.1%; p = 0.03) compared to multiparas. Women who feared childbirth more often reported lack of support compared to women with no fear (22.6% vs. 10.7%; p < 0.001). CONCLUSION: The main reasons for poor childbirth experience were pain, long labour, unplanned CS and the lack of support by care givers. The childbirth experience is complex and could be optimized by information, support and presence of care givers especially in induced labour.

Endogenous erythropoietin at birth is associated with neurodevelopmental morbidity in early childhood.

BACKGROUND: New biomarkers that predict later neurodevelopmental morbidity are needed. This study evaluated the associations between umbilical cord serum erythropoietin (us-EPO) and neurodevelopmental morbidity by the age of 2-6.5 years in a Finnish cohort. METHODS: This study included 878 non-anomalous children born alive in 2012 to 2016 in Helsinki University Hospitals and whose us-EPO concentration was determined at birth. Data of these children were linked to data from the Finnish Medical Birth Register and the Finnish Hospital Discharge Register. Neurodevelopmental morbidity included cerebral palsy, epilepsy, intellectual disability, autism spectrum disorder, sensorineural defects, and minor neurodevelopmental disorders. RESULTS: In the cohort including both term and preterm children, us-EPO levels correlated with gestational age (r = 0.526) and were lower in premature children. High us-EPO levels (>100 IU/l) were associated with an increased risk of severe neurodevelopmental morbidity (OR: 4.87; 95% CI: 1.05-22.58) when adjusted for the gestational age. The distribution of us-EPO levels did not differ in children with or without the later neurodevelopmental diagnosis. CONCLUSIONS: Although high us-EPO concentration at birth was associated with an increased risk of neurodevelopmental morbidity in early childhood, the role of us-EPO determination in clinical use appears to be minor. IMPACT: We determined whether endogenous umbilical cord serum erythropoietin would be a new useful biomarker to predict the risk of neurodevelopmental morbidity. This study evaluated the role of endogenous erythropoietin at birth in neurodevelopmental morbidity with a study population of good size and specific diagnoses based on data from high-quality registers. Although high umbilical cord serum erythropoietin concentration at birth was associated with an increased risk of neurodevelopmental morbidity in early childhood, the clinical value of erythropoietin determination appears to be minor.

Planned vaginal and planned cesarean delivery outcomes in pregnancies complicated with pregestational type 1 diabetes - A three-year academic tertiary hospital cohort study.

BACKGROUND: Finland has the world's highest incidence of 62.5/100000 of diabetes mellitus type 1 (DM1) with approximately 400 (1%) DM1 pregnancies annually. Pregnancies complicated by DM1 are accompanied with increased risk for perinatal morbidity and mortality. Timing and mode of delivery are based on the risk of complications, yet the data on labor induction is limited. The aim of this study was to compare delivery outcomes in planned vaginal (VD) and planned cesarean deliveries (CD) in late preterm and term DM1 pregnancies, and to evaluate the feasibility of labor induction. MATERIALS AND METHODS: Pregnant women with DM1, live singleton fetus in cephalic presentation ≥34 gestational weeks delivering in Helsinki University Hospital between January 1st 2017 and December 31st 2019 were included. The primary outcome were the rates of adverse maternal and perinatal outcome. The study population was classified according to the 1980-revised White's classification. Statistical analyses were performed by IBM SPSS Statistics for Windows. RESULTS: Two hundred four women were included, 59.8% (n = 122) had planned VD. The rate of adverse maternal outcome was 27.5% (n = 56), similar between the planned modes of delivery and White classes. The rate of perinatal adverse outcome was 38.7% (n = 79), higher in planned CD (52.4% vs. 29.5%;p = 0.001). The most common adverse perinatal event was respiratory distress (48.8% vs. 23.0%;p <  0.001). The rate of adverse perinatal outcome was higher in White class D + Vascular compared to B + C (45.0% vs. 25.0%, OR after adjustment by gestational age 2.34 [95% CI 1.20-4.50];p = 0.01). The total rate of CD was 63.7% (n = 130), and 39.3% (n = 48) in planned VD. Women with White class D + Vascular more often had emergency CD compared to White Class B + C (48.6% vs. 25.0%;p = 0.009). The rate of labor induction was 51%, being 85.2% in planned VD. The rate of VD in induced labor was 58.7% (n = 61) and the rate of failed induction was 14.1% (n = 15). CONCLUSION: Planned VD was associated with lower rate of adverse perinatal outcome compared to planned CS, with no difference in the rates of adverse maternal outcome. Induction of labor may be feasible option but should be carefully considered in this high-risk population.

Comparison of primiparous women's childbirth experience in labor induction with cervical ripening by balloon catheter or oral misoprostol - a prospective study using a validated childbirth experience questionnaire (CEQ) and visual analogue scale (VAS).

INTRODUCTION: Primiparity and labor induction, especially when cervical ripening is required, are risk factors for a negative childbirth experience. Our aim was to compare childbirth experience in primiparous women with cervical ripening by balloon catheter or oral misoprostol using the validated Childbirth Experience Questionnaire (CEQ). We also wanted to compare assessment of a negative childbirth experience by visual analogue scale (VAS) and CEQ. MATERIAL AND METHODS: This is a prospective study of 362 primiparous women undergoing cervical ripening and labor induction by balloon catheter (67.4%) or oral misoprostol (32.6%) at Helsinki University Hospital, Finland, between January 1, 2019 and January 31, 2020. After delivery, the women assessed their childbirth experience using the CEQ, and patient records provided the patient characteristics, delivery outcomes and VAS ratings. We analyzed the results using IBM SPSS Statistics. RESULTS: Overall, the women experienced their labor and delivery rather positively, with a mean CEQ score of 2.9 (SD 0.6) (scale 1-4), and no differences were detectable when comparing women with cervical ripening by balloon catheter or misoprostol. However, women with balloon catheter were more often satisfied with the method chosen for them and would choose the same method in a future pregnancy. Compared with CEQ, VAS seems mainly to reflect the women's perception of their own capacity to give birth and the safety of the hospital setting, not the level of professional support or participation in decision-making. According to our results, CEQ and VAS are comparable, but the usability of the CEQ is limited by its inability to distinguish the most negative and the most positive experiences, and the VAS is limited by its simplicity. CONCLUSIONS: Women with cervical ripening by balloon catheter or oral misoprostol experienced their childbirth rather positively, results being similar in both groups. However, women with cervical ripening by balloon catheter were more content with their labor induction. The CEQ and VAS can both be used to assess the childbirth experience of primiparous women undergoing labor induction, but both methods have limitations.

Vaginal streptococcus B colonization is not associated with increased infectious morbidity in labor induction.

INTRODUCTION: Labor induction rates are increasing and, in Finland today, one of three labors is induced. Group B streptococcus (GBS) is a bacterium found in 10%-30% of pregnant women and it can be transmitted to the neonate during vaginal delivery. Although GBS is rarely harmful in the general population, it is the leading cause of severe neonatal infections such as sepsis, pneumonia, and meningitis. In addition, GBS can cause maternal morbidity. Labor induction in GBS-positive women has not yet been investigated but concerns of infectious morbidity associated with balloon catheters have been raised. MATERIAL AND METHODS: A historical cohort study of 1959 women undergoing labor induction by balloon catheter in Helsinki University Hospital, Finland, between January 1, 2014 and December 31, 2017. Women with viable singleton term pregnancy in cephalic presentation, unfavorable cervix (Bishop score <6), and intact amniotic membranes were included. GBS was screened by rapid qualitative in vitro test (XPert® GBS) from vaginal and perineal culture upon admission for labor induction. All women testing positive received prophylactic antibiotics. RESULTS: Of the women, 469 (23.9%) were GBS-positive. The rate of maternal intrapartum infection was 7.4%, being lower in the GBS-positive group compared with the GBS-negative group (4.7% vs 8.3%; p = 0.01). The rate of maternal postpartum infection was 3.9%, and the rate of neonatal infection was 3.3%, both being similar between the groups. Also, no difference in the rates of other adverse neonatal outcomes was seen. No GBS sepses occurred in the study. In multivariable logistic regression, rupture of membranes to delivery interval ≥12 hours was associated with maternal intrapartum and postpartum infection, as well as neonatal infection. Other risk factors for maternal intrapartum infection were GBS-negativity, nulliparity, prolonged pregnancy (≥41 weeks), and Bishop score <3 at the start of induction. Cesarean section was associated with postpartum endometritis, while nulliparity, gestational diabetes, and maternal intrapartum infection were associated with neonatal infection. CONCLUSIONS: Regarding maternal and neonatal infectious morbidity, labor induction with balloon catheter appears safe in women colonized with GBS when prophylactic antibiotics are administered at the onset of labor or at membrane rupture.

Maternal childbirth experience in induced and spontaneous labour measured in a visual analog scale and the factors influencing it; a two-year cohort study.

BACKGROUND: Poor maternal childbirth experience plays a role in family planning and subsequent pregnancies. The aim of this study was to compare childbirth experiences in induced and spontaneous labor and to investigate the factors influencing the childbirth experience. METHODS: This two-year cohort study included all women with term singleton pregnancies in cephalic presentation aiming for vaginal delivery at Helsinki University Hospital between January 2017 and December 2018. Maternal satisfaction in the childbirth experience was measured after delivery using a Visual Analog Scale (VAS) score. A low childbirth experience score was defined as VAS < 5. The characteristics and delivery outcomes of the study population were collected in the hospital database and analyzed by SPSS. RESULTS: A total of 18,396 deliveries were included in the study, of which 28.9% (n = 5322) were induced and 71.1% (n = 13 074) were of spontaneous onset. The total caesarean delivery rate was 9.3% (n = 1727). Overall, 4.5% (n = 819) of the women had a low childbirth experience VAS score. The women who underwent labor induction were less satisfied with their birth experience compared to women with spontaneous onset of labor [7.5% (n = 399) vs. 3.2% (n = 420); p < 0.001]. Poor childbirth experience was associated with primiparity [OR 2.0 (95% CI 1.6-2.4)], labor induction [OR 1.6 (95% CI 1.4-1.9)], caesarean delivery [OR 4.5 (95% CI 3.7-5.5)], operative vaginal delivery [OR 3.3 (95% CI 2.7-4.0)], post-partum hemorrhage [OR 1.3 (95% CI 1.1-1.6)], and maternal infections [OR 1.7 (95% CI 1.3-2.4)]. CONCLUSIONS: Poor childbirth experience was associated with labor induction, primiparity, operative delivery, and labor complications, such as post-partum hemorrhage and maternal infections. These results highlight the aspects of care for which patient experience may be improved by additional support and counselling.

Balloon catheter use for cervical ripening in women with term pre-labor rupture of membranes: A 5-year cohort study.

INTRODUCTION: To investigate the safety of balloon catheter for cervical ripening in women with term pre-labor rupture of membranes (PROM) and to compare the incidence of maternal and neonatal infections in women with PROM and women with intact membranes undergoing cervical ripening with a balloon catheter. MATERIAL AND METHODS: This retrospective cohort study of 1923 women with term singleton pregnancy and an unfavorable cervix undergoing cervical ripening with a balloon catheter was conducted in Helsinki University Hospital between January 2014 and December 2018. For each case of PROM, two controls were assigned. The main outcome measures were the rates of maternal and neonatal infections. Statistical analyses were performed by SPSS. RESULTS: In all, 641 (33.3%) women following PROM and 1282 (66.6%) women with intact amniotic membranes underwent labor induction. The rates of intrapartum infection (3.7% vs 7.7%; P = .001) and neonatal infection (1.7% vs 3.8%; P = .01) were not increased in women induced by balloon catheter following PROM. Intrapartum infections were associated with nulliparity (odds ratio [OR] 3.3, 95% confidence interval [CI] 1.6-6.5), history of previous cesarean section (OR 2.8, 95% CI 1.2-6.4), extended gestational age ≥41 weeks (OR 1.9, 95% CI 1.2-3.0) and an induction to delivery interval of 48 hours or more (OR 2.0, 95% CI 1.2-3.3). The risk of neonatal infection was associated with nulliparity (OR 3.3, 95% CI 1.4-8.0), gestational age ≥41 weeks (OR 1.9, 95% CI 1.09-3.36) and induction to delivery interval of 48 hours or more (OR 3.4, 95% CI 1.9-6.0). CONCLUSIONS: Use of balloon catheter in women with term PROM appears safe and was not associated with increased maternal or neonatal infectious morbidity.

Role of oxytocin in prevention of postpartum hemorrhage in unplanned out-of-hospital deliveries treated by emergency medical services.

INTRODUCTION: Intramuscular or intravenous oxytocin is used in out-of-hospital emergency care in Finland to prevent postpartum hemorrhage after unplanned out-of-hospital deliveries. However, the use of oxytocin by emergency medical services is based on in-hospital studies. The aim of this study was to determine whether the use of oxytocin is associated with diminished postpartum hemorrhage after unplanned out-of-hospital deliveries. MATERIAL AND METHODS: We studied patient records covering all unplanned out-of-hospital deliveries in the Helsinki University Hospital area between 1 January 2013 and 31 December 2017 inclusive. Oxytocin was available in ambulances responsible for half of the population of the study area and was not available in ambulances responsible for the other half. The study area corresponded to 25% of all deliveries in Finland. The primary outcome was the estimated total bleeding (mL). Secondary outcomes were (1) the first blood hemoglobin value measured in hospital (g/L), (2) whether blood hemoglobin was measured during the first 24 hours after delivery, (3) the need for red blood cell concentrate, (4) the need for uterotonic or prothrombotic medication in-hospital during the first 24 hours, (5) the need for any postpartum operation during the first 24 hours and (6) composite outcome combining the secondary outcomes 2-5. RESULTS: Of all ambulance responses in the study area, .04% concerned out-of-hospital deliveries. There were 216 analyzed out-of-hospital deliveries. Altogether, 111 of these occurred in the area with oxytocin available in ambulances and 105 in the area without. Oxytocin was administered in 57 of the 111 deliveries (51%) where it was available. No differences in the primary outcome (P = .548 for oxytocin available vs not available and P = .381 for oxytocin used vs not used) or secondary outcomes were detected between those deliveries where oxytocin was available vs not available or between those where it was used vs not used. CONCLUSIONS: Out-of-hospital oxytocin was not associated with diminished postpartum hemorrhage in this study setting. Oxytocin does not seem to be an essential drug for all ambulance units. The in-hospital use of oxytocin was not evaluated and thus is not disputed by this study.

Success of trial of labor in women with a history of previous cesarean section for failed labor induction or labor dystocia: a retrospective cohort study.

BACKGROUND: The rates of cesarean section (CS) are increasing worldwide leading to an increased risk for maternal and neonatal complications in the subsequent pregnancy and labor. Previous studies have demonstrated that successful trial of labor after cesarean (TOLAC) is associated with the least maternal morbidity, but the risks of unsuccessful TOLAC exceed the risks of scheduled repeat CS. However, prediction of successful TOLAC is difficult, and only limited data on TOLAC in women with previous failed labor induction or labor dystocia exists. Our aim was to evaluate the success of TOLAC in women with a history of failed labor induction or labor dystocia, to compare the delivery outcomes according to stage of labor at time of previous CS, and to assess the risk factors for recurrent failed labor induction or labor dystocia. METHODS: This retrospective cohort study of 660 women with a prior CS for failed labor induction or labor dystocia undergoing TOLAC was carried out in Helsinki University Hospital, Finland, between 2013 and 2015. Data on the study population was obtained from the hospital database and analyzed using SPSS. RESULTS: The rate of vaginal delivery was 72.9% and the rate of repeat CS for failed induction or labor dystocia was 17.7%. The rate of successful TOLAC was 75.6% in women with a history of labor arrest in the first stage of labor, 73.1% in women with a history of labor arrest in the second stage of labor, and 59.0% in women with previous failed induction. The adjusted risk factors for recurrent failed induction or labor dystocia were maternal height < 160 cm (OR 1.9 95% CI 1.1-3.1), no prior vaginal delivery (OR 8.3 95% CI 3.5-19.8), type 1 or gestational diabetes (OR 1.8 95% CI 1.0-3.0), IOL for suspected non-diabetic fetal macrosomia (OR 10.8 95% CI 2.1-55.9) and birthweight ≥4500 g (OR 3.3 95% CI 1.3-7.9). CONCLUSIONS: TOLAC is a feasible option to scheduled repeat CS in women with a history of failed induction or labor dystocia. However, women with no previous vaginal delivery, maternal height < 160 cm, diabetes or suspected neonatal macrosomia (≥4500 g) may be at increased risk for failed TOLAC.

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.

Umbilical artery pH and base excess at birth are poor predictors of neurodevelopmental morbidity in early childhood.

AIM: We sought to evaluate the associations between umbilical artery pH and base excess and neurodevelopmental outcome at four years of age. METHODS: This study comprised 84 588 singleton children born alive at term in 2005-2011 in the hospital district of Helsinki and Uusimaa in Finland. Data from the maternity hospital information system were linked to the data from the Medical Birth Register and the Hospital Discharge Register. Neurodevelopmental morbidity included cerebral palsy, epilepsy, intellectual or sensorineural impairment. RESULTS: After adjustment for maternal and perinatal factors, a combination of pH <7.00 and base excess <-16.00 was associated with infant death (adjusted odds ratio 19.97; 95% confidence interval 5.38-74.17). Values of pH 7.00-7.10 were associated with cerebral palsy (adjusted odds ratio 2.40; 95% confidence interval 1.05-5.47). A combination of low five-minute Apgar score and umbilical artery base excess <-16.00 showed the highest positive predictive value (9.1%) for neurodevelopmental impairments. When umbilical artery pH <7.00 was included, a positive predictive value of 25.0% was observed for infant mortality. CONCLUSION: Low umbilical artery pH and base excess at birth were the poor predictors of long-term neurodevelopmental morbidity in an unselected population. However, these parameters might be useful in assessing the risk of infant mortality.

Cervical and Amniotic Fluid Matrix Metalloproteinase-8 and Interleukin-6 Concentrations in Preterm Pregnancies with or without Preterm Premature Rupture of Membranes.

INTRODUCTION: Intra-amniotic inflammation is defined by elevated inflammatory biomarkers in the amniotic fluid (AF), either due to microbial invasion of the amniotic cavity (MIAC) or sterile inflammation. Amniocentesis being an invasive procedure, we wanted to investigate whether elevated matrix metalloproteinase-8 (MMP-8) or interleukin-6 (IL-6) concentrations could be detected from cervical fluid samples. MATERIALS AND METHODS: This prospective study included 67 women with singleton nondiabetic pregnancies with or without preterm premature rupture of membranes (PPROM) between 22+0 and 37+0 weeks of gestation. Simultaneous AF and cervical samples were obtained. RESULTS: In women without PPROM, cervical MMP-8 concentrations correlated with AF MMP-8 concentrations (rS = 0.466, p = 0.002), but cervical IL-6 did not correlate with AF IL-6 (rS = 0.277, p = 0.076). In PPROM cases no correlations were found. Women with MIAC had higher concentrations of AF MMP-8 and AF IL-6 compared to women without MIAC regardless of membrane status. However, only women without PPROM had higher concentrations of cervical MMP-8 in proven MIAC. CONCLUSION: In women without PPROM, cervical MMP-8 concentration reflects the magnitude of AF MMP-8, thus potentially guiding the selection of patients benefitting from amniocentesis.

Low Apgar scores at both one and five minutes are associated with long-term neurological morbidity.

AIM: This study evaluated the associations between low Apgar scores at one and five minutes and long-term neurological impairments. METHODS: This study used population-based data on 399,815 singletons born in Finland in 2004-2010 and multivariable logistic regression to examine any associations between low (0-3) and intermediate (4-6) Apgar scores and cerebral palsy, epilepsy, intellectual disability and sensorineural defects by the age of four years. RESULTS: The odd ratios (OR) and 95% confidence intervals (95% CI) showed that low Apgar scores were associated with cerebral palsy at one and five minutes (ORs 2.08, 95% CI 1.32-3.26 and 5.19, 95% CI 3.06-8.80), epilepsy (ORs 1.62, 95% CI 1.13-2.33 and 4.79, 95% CI 3.03-7.56), and intellectual disability (ORs 2.46, 95% CI 1.45-4.16 and 6.21, 95% CI 3.33-11.58). Only a low five-minute Apgar score was associated with sensorineural defects (OR 3.13, 95% CI 1.95-5.02). Neurological impairment risks were increased by low Apgar scores at both one and five minutes (OR 11.1, 95% CI 8.6-14.5), but 90.3% of children with persistent low Apgar scores had no impairment. CONCLUSION: Low one-minute and five-minute Apgar scores were associated with long-term neurological morbidity, especially when both scores were low.

Neurodevelopmental outcome at the age of 4 years according to the planned mode of delivery in term breech presentation: a nationwide, population-based record linkage study.

PURPOSE: To evaluate whether a trial of planned vaginal breech labor affects neurologic development in children. METHODS: This is a nationwide, Finnish, population-based record linkage study. An odds ratio with 95% confidence intervals was used to estimate the relative risk that a child delivered by planned vaginal breech labor would be diagnosed with adverse neurodevelopmental outcome (cerebral palsy, epilepsy, intellectual disability, sensor neural developmental outcome, hyperactivity, speech and language problems) at the age of 4 years. The reference group were children born by planned cesarean section. RESULTS: During a study period of 7 years, 8374 infants were delivered in breech position. Among them, 3907 (46.7%) had an attempted labor and 4467 (53.3%) infants were delivered by planned cesarean section. There were no differences in the neurodevelopmental outcome. In the planned vaginal labor group, 133 (3.4%) children had an abnormal neurodevelopmental outcome at the age of 4 years compared to 142 (3.2%) in the planned cesarean section group. CONCLUSION: The absolute risk of abnormal neurological outcome in breech deliveries at term was low, regardless of planned mode of birth. Planned vaginal breech labor did not increase the risk for abnormal neurological outcome compared to planned cesarean section.

Cervical biomarkers as predictors of successful induction of labour by Foley catheter.

The prediction of successful labour induction is difficult, indicating a need for a biomarker test. Little is known about the effect of Foley catheter (FC) induction on biochemical mediators in the cervix, such as the insulin-like growth factor binding protein-1 (IGFBP-1), matrix metalloproteinases (MMP) and their inhibitors (TIMP). We enrolled 35 nulliparous women with singleton pregnancies, intact amniotic membranes and cephalic presentation ≥40 gestational weeks scheduled for labour induction by FC. Serial cervical swab samples were collected at FC insertion and expulsion. The concentrations of IGFBP-1, PhIGFBP-1, MMP-8, MMP-2, MMP-9, TIMP-1 and TIMP-2 were analysed. The IGFBP-1 and phIGFBP-1 concentrations increased during the FC-induced cervical ripening. In contrast, MMP-8 and MMP-9 concentrations decreased. However, these changes did not predict the outcome of the labour induction, thus appearing not suitable for clinical use. Impact statement What is already known on this subject? During cervical ripening, various constituents interact in a complex network. Insulin-like growth factor binding protein-1 (IGFBP-1), matrix metalloproteinases (MMP) and their tissue inhibitors (TIMP) appear to play a role in cervical ripening. The mechanism of Foley catheter on cervical ripening consists of direct mechanical stretching of the cervix and lower uterine segment, and the stimulation of local secretion of endogenous prostaglandins. What do the results of this study add? This study investigated the role of cervical biochemical mediators during Foley catheter-induced cervical ripening, and their predictive value in a successful labour induction and vaginal delivery. The IGFBP-1 and phosphorylated IGFBP-1 concentrations increased, whereas MMP-8 and MMP-9 concentrations decreased during the Foley catheter-induced cervical ripening in nulliparous women. However, these changes did not predict the outcome of labour induction, thus appearing not suitable for clinical use. What are the implications of these findings for clinical practice and/or further research? Prediction of a successful labour induction is difficult, indicating a need for a biomarker test. Future studies with larger data are needed for investigating the role of these cervical biomarkers in successful labour induction, and in developing a future bedside a screening tool for clinical use.

Risk factors associated with adverse perinatal outcome in planned vaginal breech labors at term: a retrospective population-based case-control study.

BACKGROUND: Vaginal breech delivery is associated with adverse perinatal outcome. The aim of this study was to identify factors associated with adverse perinatal outcome in term breech pregnancies, and to provide clinicians an aid in selecting women for a trial of vaginal labor with the fetus in breech position. METHODS: We conducted a retrospective, nationwide, Finnish population-based case-control study. All planned singleton vaginal deliveries at term with the fetus in breech position between the years 2005 and 2014 were analyzed. The study's end point was a composite set of adverse perinatal outcomes. All infants with an adverse outcome were compared to the infants with normal outcomes. A multivariate logistic regression model was used to analyze the data. RESULTS: An adverse perinatal outcome was recorded for 73 (1.5%) infants. According to the study results fetal growth restriction (adjusted odds ratio, 2.94; 95% CI, 1.30-6.67), oligohydramnios (adjusted odds ratio, 2.94; 95% CI, 1.15-7.18), a history of cesarean section (adjusted odds ratio, 2.94; 95% CI, 1.28-6.77, gestational diabetes (adjusted odds ratio, 2.89; 95% CI, 1.54-5.40), epidural anesthesia (adjusted odds ratio, 2.20; 95% CI, 1.29-3.75) and nulliparity (adjusted odds ratio, 1.84; 95% CI, 1.10-3.08) were associated with adverse perinatal outcome. CONCLUSIONS: Adverse perinatal outcome in planned vaginal breech labor at term is associated with fetal growth restriction, oligohydramnios, previous cesarean delivery, gestational diabetes, nulliparity and epidural anesthesia.

Breech presentation at term and associated obstetric risks factors-a nationwide population based cohort study.

PURPOSE: The aim of this study was to estimate whether breech presentation at term was associated with known individual obstetric risk factors for adverse fetal outcome. METHODS: This was a retrospective, nationwide Finnish population-based cohort study. Obstetric risks in all breech and vertex singleton deliveries at term were compared between the years 2005 and 2014. A multivariable logistic regression model was used to determine significant risk factors. RESULTS: The breech presentation rate at term for singleton pregnancies was 2.4%. The stillbirth rate in term breech presentation was significantly higher compared to cephalic presentation (0.2 vs 0.1%). The odds ratios (95% CIs) for fetal growth restriction, oligohydramnios, gestational diabetes, a history of cesarean section and congenital fetal abnormalities were 1.19 CI (1.07-1.32), 1.42 CI (1.27-1.57), 1.06 CI (1.00-1.13), 2.13 (1.98-2.29) and 2.01 CI (1.92-2.11). CONCLUSIONS: The study showed that breech presentation at term on its own was significantly associated with antenatal stillbirth and a number of individual obstetric risk factors for adverse perinatal outcomes. The risk factors included oligohydramnios, fetal growth restriction, gestational diabetes, history of caesarean section and congenital anomalies.