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.

Childbirth experience in induced labor: A prospective study using a validated childbirth experience questionnaire (CEQ) with a focus on the first birth.

OBJECTIVE: First birth and labor induction are risk factors for negative childbirth experiences. As labor inductions are increasing, research into this high-risk group's childbirth experiences is important. We aimed to investigate whether nulliparity or factors related to labor induction, labor, and delivery explain the association. METHODS: This was a prospective study of 711 women undergoing labor induction at Helsinki University Hospital, Finland, between January 1, 2019, and January 31, 2020. The participants answered the Childbirth Experience Questionnaire (CEQ) after delivery (response rate 69.4%). The patient characteristics and delivery outcomes were collected from patient records. We analyzed the results for nulliparous and parous women. RESULTS: The mean CEQ scores were 2.9 (SD 0.5) for nulliparous women (n = 408) and 3.2 (SD 0.5) for parous women (n = 303), on a scale of 1-4; higher scores represent more positive experiences. However, 7.3% of the women had negative childbirth experiences (8.8% nulliparous; 5.3% parous, p = 0.08). Negative experiences were associated with a cesarean section (OR 6.7, 95% CI 1.8-9.3, p < 0.001) and a hemorrhage ≥ 1500 ml in vaginal delivery (OR 2.8, 95% CI 1.1-7.5, p = 0.03). In the separate CEQ domains analyses, nulliparity was associated with negative experiences in the "Own Capacity" domain (OR 1.6, 95% CI 1.0-2.4, p = 0.03). Cervical ripening, oxytocin use, and daytime delivery were associated with negative experiences in at least one domain, whereas epidural or spinal analgesia was regarded positively in two domains and negatively in one. CONCLUSIONS: Nulliparous women undergoing labor induction risk negative childbirth experiences mainly due to labor and delivery-related factors, similar to parous women. Their perceptions of their capacity and preparedness for labor and delivery should be enhanced antenatally. An effective labor induction protocol promoting as high a rate of vaginal delivery as possible and preparedness to promptly respond to postpartum hemorrhage are key for avoiding negative childbirth experiences.

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.

Cervicovaginal Complement Activation and Microbiota During Pregnancy and in Parturition.

Background: Vaginal microbiome and the local innate immune defense, including the complement system, contribute to anti- and proinflammatory homeostasis during pregnancy and parturition. The relationship between commensal vaginal bacteria and complement activation during pregnancy and delivery is not known. Objective: To study the association of the cervicovaginal microbiota composition to activation and regulation of the complement system during pregnancy and labor. Study design: We recruited women during late pregnancy (weeks 41 + 5 to 42 + 0, n=48) and women in active labor (weeks 38 + 4 to 42 + 2, n=25). Mucosal swabs were taken from the external cervix and lateral fornix of the vagina. From the same sampling site, microbiota was analyzed with 16S RNA gene amplicon sequencing. A Western blot technique was used to detect complement C3, C4 and factor B activation and presence of complement inhibitors. For semiquantitative analysis, the bands of the electrophoresed proteins in gels were digitized on a flatbed photo scanner and staining intensities were analyzed using ImageJ/Fiji win-64 software. Patient data was collected from medical records and questionnaires. Results: The vaginal microbiota was Lactobacillus-dominant in most of the samples (n=60), L. iners and L. crispatus being the dominant species. L. gasseri and L. jensenii were found to be more abundant during pregnancy than active labor. L. jensenii abundance correlated with C4 activation during pregnancy but not in labor. Gardnerella vaginalis was associated with C4 activation both during pregnancy and labor. The amount of L. gasseri correlated with factor B activation during pregnancy but not during labor. Atopobium vaginae was more abundant during pregnancy than labor and correlated with C4 activation during labor and with factor B activation during pregnancy. Activation of the alternative pathway factor B was significantly stronger during pregnancy compared to labor. During labor complement activation may be inhibited by the abundant presence of factor H and FHL1. Conclusions: These results indicate that bacterial composition of the vaginal microbiota could have a role in the local activation and regulation of complement-mediated inflammation during pregnancy. At the time of parturition complement activation appears to be more strictly regulated than during pregnancy.

Breaking the myth: the association between the increasing incidence of labour induction and the rate of caesarean delivery in Finland - a nationwide Medical Birth Register study.

OBJECTIVES: To determine the association between the rate of labour induction and caesarean delivery. DESIGN: Medical Birth Register-based study. We used data from the nationwide Medical Birth Register collecting data on delivery outcomes on all births from 22+0 weeks and/or birth weight of at least 500 g. SETTING: Finland. PARTICIPANTS: 663 024 live births in Finland from 2008 to 2019. MAIN OUTCOME MEASURES: The rates of labour induction and caesarean delivery. RESULTS: The rate of labour induction increased from 17.8% to 30.3%; p<0.001, during the study. The total caesarean delivery rate was 16.5% (n=109 178). An increase of approximately 0.5% in the caesarean delivery rate occurred during the study period. The rate of caesarean delivery following labour induction slightly decreased (15.41% vs 15.35%; p<0.001). In multivariate logistic regression analysis, induction of labour was associated with a reduced risk for caesarean delivery (OR 0.72, 95% CI 0.71 to 0.74). The frequency of advanced maternal age (18.0% vs 23.5%; p<0.001), obesity (11.4% vs 15.1%; p<0.001) and gestational diabetes (9.8% vs 23.3%; p<0.001) increased during the study. CONCLUSIONS: The 70% increase in the rate of labour induction in Finland has not led to a significant increase in the rate of caesarean delivery, which has remained one of the lowest in the world. Pregnant women in Finland are more frequently obese, older and diagnosed with gestational diabetes, which may partly explain the increase in the rate of labour induction.

Parity and gestational age are associated with vaginal microbiota composition in term and late term pregnancies.

BACKGROUND: Vaginal microbiota and its potential contribution to preterm birth is under intense research. However, only few studies have investigated the vaginal microbiota in later stages of pregnancy or at the onset of labour. METHODS: We used 16S rRNA gene amplicon sequencing to analyse cross-sectional vaginal swab samples from 324 Finnish women between 37-42 weeks of gestation, sampled before elective caesarean section, at the onset of spontaneous labour, and in pregnancies lasting ≥41 weeks of gestation. Microbiota data were combined with comprehensive clinical data to identify factors associated with microbiota variation. FINDINGS: Vaginal microbiota composition associated strongly with advancing gestational age and parity, i.e. presence of previous deliveries. Absence of previous deliveries was a strong predictor of Lactobacillus crispatus dominated vaginal microbiota, and the relative abundance of L. crispatus was higher in late term pregnancies, especially among nulliparous women. INTERPRETATION: This study identified late term pregnancy and reproductive history as factors underlying high abundance of gynaecological health-associated L. crispatus in pregnant women. Our results suggest that the vaginal microbiota affects or reflects the regulation of the duration of gestation and labour onset, with potentially vast clinical utilities. Further studies are needed to address the causality and the mechanisms on how previous labour, but not pregnancy, affects the vaginal microbiota. Parity and gestational age should be accounted for in future studies on vaginal microbiota and reproductive outcomes. FUNDING: This research was supported by EU H2020 programme Sweet Crosstalk ITN (814102), Academy of Finland, State Research Funding, and University of Helsinki.

Comparison of delivery outcomes in low-dose and high-dose oxytocin regimens for induction of labor following cervical ripening with a balloon catheter: A retrospective observational cohort study.

A variety of oxytocin regimens are used for labor induction and augmentation. Considering the increasing rates of labor induction, it is important to assess the most optimal oxytocin regimen without compromising maternal and fetal safety. The aim of this study was to compare delivery outcomes of low-dose and high-dose oxytocin induction protocols. This retrospective cohort study of 487 women comparing low-dose oxytocin protocol (n = 280) and high-dose oxytocin protocol (n = 207) in labor induction following cervical ripening by balloon catheter was performed in Helsinki University Hospital after implementation of a new oxytocin induction protocol. The study included two six-month cohorts from 2016 and 2019. Women with vital singleton pregnancies ≥37 gestational weeks, cephalic presentation, and intact amniotic membranes were included. The primary outcome was the rate of vaginal delivery. The secondary outcomes were the rates of maternal and neonatal infections, postpartum hemorrhage, umbilical artery blood pH-value, admission to neonatal intensive care, and induction-to-delivery interval. Statistical analyses were performed by using IBM SPSS Statistics for Windows (Armonk, NY, USA). The rate of vaginal delivery was higher [69.9% (n = 144) vs. 47.9% (n = 134); p<0.004] and the rates of maternal and neonatal infection were lower during the new high-dose oxytocin protocol [maternal infections 13.6% (n = 28) vs. 22.1% (n = 62); p = 0.02 and neonatal infection 2.9% (n = 6) vs. 14.6% (n = 41); p<0.001, respectively]. The rates of post-partum hemorrhage, umbilical artery blood pH-value <7.05 or neonatal intensive care admissions did not differ between the cohorts. The median induction-to-delivery interval was shorter in the new protocol [32.0 h (IQR 18.5-42.7) vs. 37.9 h (IQR 27.8-52.8); p<0.001]. In conclusion, implementation of the new continuous high-dose oxytocin protocol resulted in higher rate of vaginal delivery and lower rate of maternal and neonatal infections. Our experience supports the use of high-dose continuous oxytocin induction regimen with a practice of stopping oxytocin once active labor is achieved, and a 15-18-hour maximum duration for oxytocin induction in the latent phase of labor following cervical ripening with a balloon catheter.

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.

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.

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.

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.

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.