Myometrial inflammation is thought to have a pivotal role in the onset of term and some forms of preterm labour. This is based on the comparison of samples taken from women undergoing term elective CS prior to the onset of labour with those taken from women in established labour. Consequently, it is not clear whether myometrial inflammation is a cause or a consequence of labour. Our objective is to test the hypothesis that myometrial inflammation is a consequence of the onset of labour. To test this hypothesis, we have obtained myometrial samples from women at various stages of pregnancy and spontaneous labour and studied the activation of the AP-1 (c-Jun) and NFκB (p65) systems, cytokine mRNA expression and protein levels and inflammatory cell infiltration and activation. We found that the activation of p65 declined from preterm to term not in labour samples and thereafter increased in early and established labour. Cytokine mRNA expression and protein levels increased in established labour only. Using flow cytometry of myometrial tissue, we found that the number of neutrophils did increase with the onset of labour, but on tissue section, these were seen to be intravascular and not infiltrating into the myometrium. These data suggest that myometrial inflammation is a consequence rather than a cause of term labour.

Preterm birth involves the interaction of societal and environmental factors potentially modulating the length of gestation via the epigenome. An established form of epigenetic regulation is DNA methylation where promoter hypermethylation is associated with gene repression. We hypothesized we would find differences in DNA methylation in the myometrium of women with preterm labor of different phenotypes versus normal term labor. Myometrial tissue was obtained at cesarean section at term with or without labor, preterm without labor, idiopathic preterm labor, and twin gestations with labor. Genomic DNA was isolated, and samples in each group were combined and analyzed on a NimbleGen 2.1M human DNA methylation array. Differences in methylation from −8 to +3 kb of transcription start sites of 22 contraction-associated genes were determined. Cytosine methylation was not present in CpG islands of any gene but was present outside of CpG islands in shores and shelves in 19 genes. No differential methylation was found across the tissue groups for six genes (PTGES3L, PTGER2, PTGER4, PTGFRN, ESR2, and GJA1). For 13 genes, differential methylation occurred in several patterns between tissue groups. We find a correlation between hypomethylation and increased mRNA expression of PTGES/mPGES-1, indicating potential functional relevance of methylation, but no such correlation for PTGS2/COX-2, suggesting other regulatory mechanisms for PTGS2 at labor. The majority of differential DNA methylation of myometrial contraction-associated genes with different labor phenotypes occurs outside of CpG islands in gene promoters, suggesting that the entirety of DNA methylation across the genome should be considered.

Enhanced recovery after surgery (ERAS) aims to improve perioperative care, hasten recovery to the normal physiological state and shorten length of stay (LoS). There is evidence that ERAS programmes following elective caesarean section (ELCS) confer benefit through faster return to physiological state and reduced LoS for mother and baby. Baseline audit of ELCS in 2013 revealed a mean LoS of 3 days. We piloted an ERAS discharge pathway promoting day 2 discharge, which rose from 5.0% to 40.2%. 19.2% of women went home on day 1. Many women fed back that they would prefer day 1 discharge. We hypothesised that a day 1 discharge pathway for low-risk women could benefit both women and services at our maternity unit. From October 2015, we developed a ‘fast-track pathway’ (FTP) using a Plan-Do-Study-Act approach. Between October 2015 and April 2016, we prospectively audited clinical outcomes, LoS and maternal satisfaction from all women placed on the FTP. We held regular multidisciplinary team meetings to allow contemporaneous analysis. Satisfaction was analysed by Likert scale at postoperative surveys. Women were identified in antenatal clinic after meeting predefined low-risk criteria. 27.3% of women (n=131/479) delivering by ELCS entered the FTP. 76.2% of women on the FTP were discharged on day 1. Mean LoS fell to 1.31 days. 94.2% of women who established breast feeding at day 1 were still breast feeding at 7 days. Overall satisfaction at day 7 was 4.71 on a 5-point Likert scale. 73.1% of women reported good pain control. Additional financial savings are estimated at £99 886 annually. There were no related cases of readmission. Day 1 discharge after ELCS is safe and acceptable in carefully selected, low-risk women and has high satisfaction. There may be resultant financial savings and improved flow through a maternity unit with no detected adverse effect on breast feeding, maternal morbidity or postnatal readmissions.

Gestational diabetes (GDM) changes the maternal metabolic and uterine environment, thus increasing the risk of short- and long-term adverse outcomes for both mother and child. Children of mothers who have GDM during their pregnancy are more likely to develop Type 2 Diabetes (T2D), early-onset cardiovascular disease and GDM when they themselves become pregnant, perpetuating a multigenerational increased risk of metabolic disease. The negative effect of GDM is exacerbated by maternal obesity, which induces a greater derangement of fetal adipogenesis and growth. Multiple factors, including genetic, epigenetic and metabolic, which interact with lifestyle factors and the environment, are likely to contribute to the development of GDM. Genetic factors are particularly important, with 30% of women with GDM having at least one parent with T2D. Fetal epigenetic modifications occur in response to maternal GDM, and may mediate both multi- and transgenerational risk. Changes to the maternal metabolome in GDM are primarily related to fatty acid oxidation, inflammation and insulin resistance. These might be effective early biomarkers allowing the identification of women at risk of GDM prior to the development of hyperglycaemia. The impact of the intra-uterine environment on the developing fetus, “developmental programming”, has a multisystem effect, but its influence on adipogenesis is particularly important as it will determine baseline insulin sensitivity, and the response to future metabolic challenges. Identifying the critical window of metabolic development and developing effective interventions are key to our ability to improve population metabolic health.

Article published by the Endocrine Society Article published by the Endocrine Society