Increased Placental Cell Senescence and Oxidative Stress in Women with Pre-Eclampsia and Normotensive Post-Term Pregnancies.

Up to 11% of pregnancies extend to post-term with adverse obstetric events linked to pregnancies over 42 weeks. Oxidative stress and senescence (cells stop growing and dividing by irreversibly arresting their cell cycle and gradually ageing) can result in diminished cell function. There are no detailed studies of placental cell senescence markers across a range of gestational ages, although increased levels have been linked to pre-eclampsia before full term. This study aimed to determine placental senescence and oxidative markers across a range of gestational ages in women with uncomplicated pregnancies and those with a diagnosis of pre-eclampsia. Placentae were obtained from 37 women with uncomplicated pregnancies of 37-42 weeks and from 13 cases of pre-eclampsia of 31+2-41+2 weeks. The expression of markers of senescence, oxidative stress, and antioxidant defence (tumour suppressor protein p16INK4a, kinase inhibitor p21, interleukin-6 (IL-6), NADPH oxidase 4 (NOX4), glutathione peroxidases 1, 3, and 4 (GPx1, GPx3, and GPx4), placental growth factor (PlGF), and soluble fms-like tyrosine kinase-1 (sFlt-1)) genes was measured (quantitative real-time PCR). Protein abundance of p16INK4a, IL-6, NOX4, 8-hydroxy-2'-deoxy-guanosine (8-OHdG), and PlGF was assessed by immunocytochemistry. Placental NOX4 protein was higher in post-term than term deliveries and further increased by pre-eclampsia (p < 0.05 for all). P21 expression was higher in post-term placentae (p = 0.012) and in pre-eclampsia (p = 0.04), compared to term. Placental P16INK4a protein expression was increased post-term, compared to term (p = 0.01). In normotensive women, gestational age at delivery was negatively associated with GPx4 and PlGF (mRNA and protein) (p < 0.05 for all), whereas a positive correlation was seen with placental P21, NOX4, and P16INK4a (p < 0.05 for all) expression. Markers of placental oxidative stress and senescence appear to increase as gestational age increases, with antioxidant defences diminishing concomitantly. These observations increase our understanding of placental health and may contribute to assessment of the optimal gestational age for delivery.

Ethnic differences in postmaturity syndrome in newborns. Reflections on different durations of gestation.

OBJECTIVE: To describe the prevalence, by weeks of gestation, of post-maturity signs in newborns by ethnic origins. STUDY DESIGN: Observational cohort study (2001-2018), of all consecutive singleton births delivered at Center Hospitalier Universitaire Hospitalier Sud Reunion's maternity (Reunion Island, French overseas department, Indian Ocean). The presence of clinical post-maturity signs was recorded by a week of gestation using Clifford's clinical post-maturity signs in newborns (desquamation, dry skin, wrinkling fingers and cracked skin). RESULTS: Of the 67,463 singleton births during the period, 58,503 newborns were from Reunion island, 5756 were of European origin (mainland France), and 4061 newborns from the archipelago of Comoros (North of Madagascar). Mean duration of gestation was 276 days in Caucasian women, 272 days in Comorian mothers and 273 days in Reunionese (p < .001). Post-maturity is defined by WHO as gestation greater than 293 days (41 weeks + 6 days). At 41 weeks (287 days) 12.1% of Caucasian babies presented post-maturity signs and 22.4% meconium-stained liquid versus respectively, 22.8 and 27.1% in Reunionese and 44 and 39.8% in Comorians (p < .001). CONCLUSION: Among African (Black) pregnancies, duration of gestation was approximately 7 days shorter than in Caucasian (White) pregnancies. In the Reunionese intermixed population and Comorians, the gestation was shorter by 3-4 days. Black newborns presented severe clinical post-maturity signs beginning around 40 weeks and 4-6 days, while it was 1 week later in white infants. Consequences of these differences, with respect to clinical outcomes, are discussed.

Membrane sweeping at term to promote spontaneous labour and reduce the likelihood of a formal induction of labour for postmaturity: a systematic review and meta-analysis.

The aim of this study was to evaluate the efficacy and the safety of membrane sweeping in promoting spontaneous labour and reducing a formal induction of labour for postmaturity. Based on articles published between 2005 and 2016, 12 electronic databases were searched. Relative risk (RR) and its 95% confidence interval (CI) were used as pooled statistics. A total of seven studies consisting of 2252 participants were selected for the review and meta-analysis. The results revealed that membrane sweeping is advantageous in promoting spontaneous labour (RR = 1.205, 95% CI: 1.133-1.282, p = <.001), and reducing the formal induction of labour for postmaturity (RR = 0.523, 95% CI: 0.409-0.669, p = <.001). The studies reported several varying outcomes for both maternal and foetal morbidities; meta-analyses were performed where possible on each of these and found there to be no statistically significant differences in outcome between the intervention and control groups. Impact Statement What is already known on this subject? Research suggests that a pregnancy which exceeds 42 weeks of gestation is associated with an increased risk of perinatal morbidity and mortality (Gulmezoglu et al. 2012 ). Consequently, a formal induction of labour is usually offered to low-risk pregnant women between 41 and 42 weeks of pregnancy. However, all of the induction methods carry some degree of risk in terms of the associated morbidities and effectiveness (Cunningham 2005 ; Simpson and James 2008 ; Thomas et al. 2014 ), as well as having an impact on NHS resources (Department of Health 2015 ), and the birth experience of women (Gatward et al. 2010 ). For these reasons, it is currently recommended by The National Institute for Health and Care Excellence (NICE 2008 ) that women are offered a membrane sweep to promote spontaneous labour prior to arranging a formal induction of labour. What the results of this study add? The results from this meta-analysis add to the body of existing evidence around membrane sweeping. This study clearly demonstrates that membrane sweeping is effective in promoting a spontaneous labour and thereby reducing the need for a formal induction of labour. However, the results of this review suggest that this effect is significant from 38 weeks of gestation, and is not dependent upon the number or timing of membrane sweeps performed. What the implications are of these findings for clinical practice and/or further research? There is no evidence supporting any increase in maternal or foetal morbidity suggesting that membrane sweeping is a safe procedure to offer to all low risk pregnant women. We recommend therefore that there could be a reduction in the gestation at which membrane sweeping is offered from 40 weeks for primiparous women and 41 weeks for multiparous women to 38 weeks onwards for all low risk women without any increased risk of maternal or foetal morbidity. This may result in a decreased risk of requiring a formal induction of labour for postmaturity.

Outpatient cervical ripening in a district general hospital: a five-year retrospective cohort study.

The number of women undergoing induction of labour has risen steadily in recent years. Outpatient induction is becoming more common in the UK in response to the required increase in resources, although evidence supporting its safety is lacking. We reviewed the notes of low-risk women presenting for outpatient cervical ripening using prostaglandins over a five-year period, and compared our neonatal and maternal outcomes to local and national data. Of the 502 eligible women, 400 underwent outpatient treatment. Most women returned early, in labour. There were no foetal, neonatal or maternal deaths, and our neonatal morbidity compared favourably with local rates. Mode of delivery and major maternal complication rates were comparable to national maternity indicators. We conclude that outpatient cervical ripening following careful case selection does not appear to increase neonatal or maternal mortality or morbidity. It offers patients an alternative to traditional inpatient induction and may improve allocation of hospital resources. Impact statement We present a retrospective cohort study of neonatal and maternal outcomes in 502 women selected for outpatient cervical ripening for postmaturity at Bedford Hospital over the five-year period from 2010 to 2015. This study was conceived following a previous publication in this journal from Bedford Hospital in 2002 by Neale et al., which described the outcomes of 100 women who underwent outpatient cervical ripening. Our conclusions compare the results from the two studies. Out of our combined sample of 602 women, 491 were discharged home following administration of prostaglandins. This represents the largest sample size in the published literature on outpatient induction of labour, which was first undertaken in our unit in 1998 and is now widely practiced within the UK. Several publications, including the 2013 Cochrane review by Kelly et al. and a recent large survey of practice (Sharp et al. 2016 ) have highlighted the paucity of available data regarding the safety of this procedure as an outpatient. We therefore hope that the results of our study will be of interest to many maternity units who currently undertake or are considering to provide the facility for outpatient cervical ripening as a prelude to induction of labour.

Temporal trends in fetal mortality at and beyond term and induction of labor in Germany 2005-2012: data from German routine perinatal monitoring.

PURPOSE: While a variety of factors may play a role in fetal and neonatal deaths, postmaturity as a cause of stillbirth remains a topic of debate. It still is unclear, whether induction of labor at a particular gestational age may prevent fetal deaths. METHODS: A multidisciplinary working group was granted access to the most recent set of relevant German routine perinatal data, comprising all 5,291,011 hospital births from 2005 to 2012. We analyzed correlations in rates of induction of labor (IOL), perinatal mortality (in particular stillbirths) at different gestational ages, and fetal morbidity. Correlations were tested with Pearson's product-moment analysis (α = 5 %). All computations were performed with SPSS version 22. RESULTS: Induction rates rose significantly from 16.5 to 21.9 % (r = 0.98; p < 0.001). There were no significant changes in stillbirth rates (0.28-0.35 per 100 births; r = 0.045; p = 0.806). Stillbirth rates 2009-2012 remained stable in all gestational age groups irrespective of induction. Fetal morbidity (one or more ICD-10 codes) rose significantly during 2005-2012. This was true for both children with (from 33 to 37 %, r = 0.784, p < 0.001) and without (from 25 to 31 %, (r = 0.920, p < 0.001) IOL. CONCLUSIONS: An increase in IOL at term is not associated with a decline in perinatal mortality. Perinatal morbidity increased with and without induction of labor.

Racial disparities in the optimal for induction of labor in low-risk term pregnancies: a national population-based study.

OBJECTIVE: The recommendation for elective induction of labor (IOL) is to await ≥ 39 weeks. Studies show earlier maturity of Blacks compared to Whites. The objective was to examine the effect of the Black race on the risk of intrapartum and neonatal complications after IOL. METHODS: Black women with non-indicated IOL at 37-42 weeks were selected from the CDC-Birth Cohorts 2007-2010. Congenital anomalies, hypertension/diabetes, low-birth weight, breech presentation, previous cesarean and premature rupture of membranes were excluded. Intrapartum/neonatal complications were analyzed. Logistic regression was used to calculate adjusted odds ratios, using 39 weeks as reference. RESULTS: 311,264 black were compared with 2,451,774 deliveries of other races. For Blacks, the risks of cesarean delivery and intrapartum complications were lower at 38 weeks. Chance of vaginal delivery was greater at 38 weeks. Risks of neonatal complications was not increased at 38 compared to 39 weeks. CONCLUSIONS: Intrapartum complications were lower at 38 than at 39 weeks in Blacks with no increased risk of neonatal complications. Meconium staining and fetal distress were higher as early as at 40 weeks, perhaps due to accelerated maturation. While a 39-week goal is simple and benefits many patients, a more "personalized medicine" approach may benefit even more mothers and babies.

Randomized clinical trial evaluating the frequency of membrane sweeping with an unfavorable cervix at 39 weeks.

BACKGROUND: Despite the widely accepted use of membrane sweeping to prevent postmaturity pregnancies, the optimal frequency for this procedure has not been established. AIM: To determine if the frequency of membrane sweeping in women with an unfavorable cervix at term results in fewer labor inductions. METHODS: This was a randomized trial of women with an unfavorable cervix (Bishop's score of ≤4) at 39 weeks randomized into three groups: control, once-weekly membrane sweeping, and twice-weekly membrane sweeping. RESULTS: Between January 2005 and June 2008, 350 women were randomized into the study (groups: control [n = 116], once weekly [n = 117], and twice weekly [n = 117]). Randomization of Bishop's score was different between groups (P = 0.019), with 67%, 71%, and 83% of control, once-, and twice-weekly groups, respectively, having scores of 3-4. There was no difference in the unadjusted rate of labor induction between the groups (35% versus 27% versus 23%, P = 0.149), and after the adjustment for the randomization of Bishop's score (adjusted odds ratio [OR] = 0.73, 95% confidence interval [CI] 0.41-1.29 and OR = 0.65, 95% CI 0.36-1.18 for once- and twice-weekly groups, respectively). A Bishop's score of 3-4 at randomization was the only statistically significant factor that decreased the likelihood of induction at 41 weeks (OR = 0.42, 95% CI 0.25-0.69). CONCLUSION: Frequency of membrane sweeping does not influence the likelihood of remaining undelivered at 41 weeks of pregnancy. The Bishop's score at around 39 weeks is the important factor as a predictor of the duration of pregnancy, and further studies would be required to determine whether membrane sweeping influences pregnancy duration.