Sarah J. Stock

Outcomes of elective induction of labour compared with expectant management: population based study

Objective To determine neonatal outcomes (perinatal mortality and special care unit admission) and maternal outcomes (mode of delivery, delivery complications) of elective induction of labour compared with expectant management. Design Retrospective cohort study using an unselected population database. Setting Consultant and midwife led obstetric units in Scotland 1981-2007. Participants 1 271 549 women with singleton pregnancies of 37 weeks or more gestation. Interventions Outcomes of elective induction of labour (induction of labour with no recognised medical indication) at 37, 38, 39, 40, and 41 weeks’ gestation compared with those of expectant management (continuation of pregnancy to either spontaneous labour, induction of labour or caesarean section at a later gestation). Main outcome measures Extended perinatal mortality, mode of delivery, postpartum haemorrhage, obstetric anal sphincter injury, and admission to a neonatal or special care baby unit. Outcomes were adjusted for age at delivery, parity, year of birth, birth weight, deprivation category, and, where appropriate, mode of delivery. Results At each gestation between 37 and 41 completed weeks, elective induction of labour was associated with a decreased odds of perinatal mortality compared with expectant management (at 40 weeks’ gestation 0.08% (37/44 764) in the induction of labour group versus 0.18% (627/350 643) in the expectant management group; adjusted odds ratio 0.39, 99% confidence interval 0.24 to 0.63), without a reduction in the odds of spontaneous vertex delivery (at 40 weeks’ gestation 79.9% (35 775/44 778) in the induction of labour group versus 73.7% (258 665/350 791) in the expectant management group; adjusted odds ratio 1.26, 1.22 to 1.31). Admission to a neonatal unit was, however, increased in association with elective induction of labour at all gestations before 41 weeks (at 40 weeks’ gestation 8.0% (3605/44 778) in the induction of labour group compared with 7.3% (25 572/350 791) in the expectant management group; adjusted odds ratio 1.14, 1.09 to 1.20). Conclusion Although residual confounding may remain, our findings indicate that elective induction of labour at term gestation can reduce perinatal mortality in developed countries without increasing the risk of operative delivery.

Innate immunity and disorders of the female reproductive tract

Sexually transmitted infections, and their associated sequelae, such as tubal infertility, ectopic pregnancy and preterm labour, are a major worldwide health problem. Chlamydia trachomatis infection is thought to be the leading global cause of tubal infertility and tubal ectopic pregnancy. Preterm birth occurs in around 10% of all deliveries, and nearly 30% of preterm deliveries are associated with intrauterine infection. The mucosal innate immune system of the female reproductive tract has evolved to eliminate such sexually transmitted pathogens whilst maintaining its ability to accommodate specialized physiological functions that include menstruation, fertilization, implantation, pregnancy and parturition. The aim of this review was to describe the role and distribution of key mediators of the innate immune system, the natural antimicrobial peptides (secretory leukocyte protease inhibitor, elafin and the defensins) and the pattern recognition toll-like receptors in the normal female reproductive tract and in the context of these pathological processes.

Effectiveness of progestogens to improve perinatal outcome in twin pregnancies: an individual participant data meta-analysis

In twin pregnancies, the rates of adverse perinatal outcome and subsequent long‐term morbidity are substantial, and mainly result from preterm birth (PTB).

Preterm and term labour in multiple pregnancies

The association between multiple pregnancy and preterm labour is well-established, with >50% of multiple births delivering before 37 weeks. However, there remains limited understanding of the factors predisposing to early delivery of twins. Physiological stimuli to the onset of parturition, including stretch, placental corticotrophin-releasing hormone and lung maturity factors, may be stronger in multiple pregnancies due to the increased fetal and placental mass. Pathological processes including infection and cervical insufficiency also have a role. Treatments that prevent preterm birth in singleton pregnancies, such as progesterone and cervical cerclage appear to be ineffective in multiple pregnancies. This article reviews aspects of preterm birth in twins and higher order multiples including epidemiology, prediction and prevention of preterm labour and potential mechanisms controlling onset of parturition. Evidence relating to the management of labour in preterm and term multiples is also discussed.

Effect of birth weight on adverse obstetric outcomes in vaginal birth after cesarean delivery.

To the Editor: We read with interest the article by Jastrow et al,1 which concluded that “estimated fetal weight should be included in the decision-making process for all women contemplating a trial of labor after cesarean delivery.” It is our opinion that this recommendation is unhelpful. First, this was an observational trial that examined correlations between obstetric outcomes and birth weight (determined after delivery). To assume that the same associations apply to estimated fetal weight (determined antenatally) is flawed. It is well recognized that ultrasound for estimated fetal weight has limited diagnostic accuracy, and standard ultrasound techniques to diagnose macrosomia have high false–positive rates.2 The authors refer to techniques for assessment of estimated fetal weight using three-dimensional ultrasonography, but these have not been validated in large studies. Secondly, even if an accurate test of macrosomia were available, a retrospective observational study should not be used as proof that implementation of that test will improve outcome. The effectiveness of any diagnostic technology should be determined by trials assessing both the efficacy of the test in clinical practice and the effectiveness of interventions carried out in those with positive diagnoses. This study supports the substantial body of evidence that macrosomic neonates are a high-risk group. However, until we have accurate methods of diagnosing macrosomia and can prove benefits of avoiding trials of labor in this group, it is dangerous to advocate routine ultrasonography for estimated fetal weight. Doing so risks inappropriate avoidance of trial of labor and increased morbidity from cesarean delivery. Further, the inference that performing ultrasonography can prevent maternal morbidities is likely to be seized on by the legal profession: in the absence of an effective test to predict macrosomia antenatally, obstetricians will have no alternative other than to avoid vaginal birth after cesarean to protect themselves from litigation.

Elafin (SKALP/Trappin-2/proteinase inhibitor-3) Is Produced by the Cervix in Pregnancy and Cervicovaginal Levels Are Diminished in Bacterial Vaginosis

Objectives. To examine cervicovaginal elafin production in pregnancy and determine its relationship in bacterial vaginosis. Study Design. Samples of cervicovaginal secretions were collected from women with uncomplicated singleton pregnancies (n = 112) below 20 weeks gestation. Bacterial flora was assessed using Nugent’s criteria, and levels of elafin were measured by enzyme-linked immunosorbent serologic assay (ELISA). Elafin expression in the cervix was also examined by immunohistochemistry. In vitro expression of elafin was examined using cervix and vaginal cell lines. Results. Elafin is expressed in the cervical glandular epithelium. Elafin was found in all 112 samples of cervicovaginal secretions and levels were diminished in women with bacterial vaginosis (P < .05). Interleukin 1β (IL-1β) stimulated elafin expression in cells derived from the endocervix, but not in those derived from the vaginal epithelium. Conclusions. Elafin is a component of cervicovaginal secretions in pregnancy, and levels are diminished in bacterial vaginosis. It may be an important component of innate immunity in the lower genital tract.

Quantitative Fetal Fibronectin to Predict Preterm Birth in Asymptomatic Women at High Risk

OBJECTIVE: To evaluate the diagnostic accuracy of cervicovaginal fluid quantitative fetal fibronectin, measured by a bedside analyzer, to predict spontaneous preterm birth before 34 weeks of gestation. METHODS: We conducted a prospective masked observational cohort study of cervicovaginal fluid quantitative fetal fibronectin concentration in asymptomatic women at high risk of spontaneous preterm birth (n=1,448; 22–27 6/7 weeks of gestation) measured using a rapid bedside analyzer. The routine qualitative result (positive–negative) was made available to clinicians at the time of testing, but the quantitative result remained blinded until after delivery. RESULTS: Spontaneous preterm birth (less than 34 weeks of gestation) increased from 2.7%, 11.0%, 14.9%, 33.9%, and 47.6% with increasing concentration of fetal fibronectin (less than 10, 10–49, 50–199, 200–499, and 500 ng/mL or greater, respectively). A threshold of 200 ng/mL had a positive predictive value of 37.7 (95% confidence interval [CI] 26.9–49.4) with specificity 96% (95% CI 95.3–97.3). Women with a fetal fibronectin concentration of less than 10 ng/mL had a very low risk of spontaneous preterm birth at less than 34 weeks of gestation (2.7%), no higher than the background spontaneous preterm birth rate of the general hospital population (3.3%). The quantitative fetal fibronectin test predicted birth at less than 34 weeks of gestation with an area under the curve (AUC) of 0.78 (95% CI 0.73–0.84) compared with the qualitative test AUC 0.68 (95% CI 0.63–0.73). Quantitative fetal fibronectin discriminated risk of spontaneous preterm birth at less than 34 weeks of gestation among women with a short cervix (less than 25 mm); 9.5% delivered prematurely less than 10 ng/mL compared with 55.1% greater than 200 ng/mL (P<.001). DISCUSSION: Alternative risk thresholds (less than 10 ng/mL and greater than 200 ng/mL) improve accuracy when using quantitative fetal fibronectin measurements to define risk of spontaneous preterm birth. This is particularly relevant for asymptomatic women with a short cervix. LEVEL OF EVIDENCE: II

Antimicrobial peptides and pregnancy

Antimicrobial peptides (AMPs) are small proteins produced by epithelial surfaces and inflammatory cells, which have broad-spectrum antimicrobial and immunomodulatory activities. They are known to be important in a number of infectious and inflammatory conditions and have been shown to be present in a number of sites throughout the female reproductive tract. Inflammation and infection are associated with a number of complications of pregnancy including preterm labor, and AMPs may play a key role in maintaining and protecting pregnancy. The aim of this review is to describe the expression and function of AMPs in the pregnant female reproductive tract and their relation to preterm labor.

Maternal Intravenous Treatment with either Azithromycin or Solithromycin Clears Ureaplasma parvum from the Amniotic Fluid in an Ovine Model of Intrauterine Infection

ABSTRACT Intrauterine infection with Ureaplasma spp. is strongly associated with preterm birth and adverse neonatal outcomes. We assessed whether combined intraamniotic (IA) and maternal intravenous (IV) treatment with one of two candidate antibiotics, azithromycin (AZ) or solithromycin (SOLI), would eradicate intrauterine Ureaplasma parvum infection in a sheep model of pregnancy. Sheep with singleton pregnancies received an IA injection of U. parvum serovar 3 at 85 days of gestational age (GA). At 120 days of GA, animals (n = 5 to 8/group) received one of the following treatments: (i) maternal IV SOLI with a single IA injection of vehicle (IV SOLI only); (ii) maternal IV SOLI with a single IA injection of SOLI (IV+IA SOLI); (iii) maternal IV AZ and a single IA injection of vehicle (IV AZ only); (iv) maternal IV AZ and a single IA injection of AZ (IV+IA AZ); or (v) maternal IV and single IA injection of vehicle (control). Lambs were surgically delivered at 125 days of GA. Treatment efficacies were assessed by U. parvum culture, quantitative PCR, enzyme-linked immunosorbent assay, and histopathology. Amniotic fluid (AF) from all control animals contained culturable U. parvum. AF, lung, and chorioamnion from all AZ- or SOLI-treated animals (IV only or IV plus IA) were negative for culturable U. parvum. Relative to the results for the control, the levels of expression of interleukin 1β (IL-1β), IL-6, IL-8, and monocyte chemoattractant protein 2 (MCP-2) in fetal skin were significantly decreased in the IV SOLI-only group, the MCP-1 protein concentration in the amniotic fluid was significantly increased in the IV+IA SOLI group, and there was no significant difference in the histological inflammation scoring of lung or chorioamnion among the five groups. In the present study, treatment with either AZ or SOLI (IV only or IV+IA) effectively eradicated macrolide-sensitive U. parvum from the AF. There was no discernible difference in antibiotic therapy efficacy between IV-only and IV+IA treatment regimens relative to the results for the control.

Interventions to improve rates of post-mortem examination after stillbirth

OBJECTIVE Despite recognition of the value of post-mortem examination following stillbirth, worldwide rates have declined since the early 1990s. There is a paucity of published evidence relating to factors that can improve post-mortem uptake. The aim of this study was to assess post-mortem rates following stillbirth and identify trends in the past 18 years that may have affected acceptance of the investigation. STUDY DESIGN Retrospective cohort study. RESULTS Sharp declines in post-mortems coincided with publicity surrounding unlawful organ retention. Although nationally post-mortem rates have continued to fall, in our unit there was recovery in post-mortem rates. This increase was associated with implementation of policies to promote the uptake of perinatal post-mortem, including availability of specialist perinatal pathologists, education in the value of post-mortem, and senior staff involvement in counselling regarding the procedure. CONCLUSION The need to improve uptake of post-mortem examination following stillbirth is internationally recognized. The results of this study suggest that increased local availability of specialist perinatal pathologists, who can support education in the value of post-mortem, along with senior staff obtaining consent, may help achieve this goal.