Labour classified by cervical dilatation & fetal membrane rupture demonstrates differential impact on RNA-seq data for human myometrium tissues

High throughput sequencing has previously identified differentially expressed genes (DEGs) and enriched signalling networks in human myometrium for term (≥37 weeks) gestation labour, when defined as a singular state of activity at comparison to the non-labouring state. However, transcriptome changes that occur during transition from early to established labour (defined as ≤3 and >3 cm cervical dilatation, respectively) and potentially altered by fetal membrane rupture (ROM), when adapting from onset to completion of childbirth, remained to be defined. In the present study, we assessed whether differences for these two clinically observable factors of labour are associated with different myometrial transcriptome profiles. Analysis of our tissue (‘bulk’) RNA-seq data (NCBI Gene Expression Omnibus: GSE80172) with classification of labour into four groups, each compared to the same non-labour group, identified more DEGs for early than established labour; ROM was the strongest up-regulator of DEGs. We propose that lower DEGs frequency for early labour and/or ROM negative myometrium was attributed to bulk RNA-seq limitations associated with tissue heterogeneity, as well as the possibility that processes other than gene transcription are of more importance at labour onset. Integrative analysis with future data from additional samples, which have at least equivalent refined clinical classification for labour status, and alternative omics approaches will help to explain what truly contributes to transcriptomic changes that are critical for labour onset. Lastly, we identified five DEGs common to all labour groupings; two of which (AREG and PER3) were validated by qPCR and not differentially expressed in placenta and choriodecidua.

Prostaglandins in biofluids in pregnancy and labour: A systematic review

Prostaglandins are thought to be important mediators in the initiation of human labour, however the evidence supporting this is not entirely clear. Determining how, and which, prostaglandins change during pregnancy and labour may provide insight into mechanisms governing labour initiation and the potential to predict timing of labour onset. The current study systematically searched the existing scientific literature to determine how biofluid levels of prostaglandins change throughout pregnancy before and during labour, and whether prostaglandins and/or their metabolites may be useful for prediction of labour. The databases EMBASE and MEDLINE were searched for English-language articles on prostaglandins measured in plasma, serum, amniotic fluid, or urine during pregnancy and/or spontaneous labour. Studies were assessed for quality and risk of bias and a qualitative summary of included studies was generated. Our review identified 83 studies published between 1968–2021 that met the inclusion criteria. As measured in amniotic fluid, levels of PGE2, along with PGF2α and its metabolite 13,14-dihydro-15-keto-PGF2α were reported higher in labour compared to non-labour. In blood, only 13,14-dihydro-15-keto-PGF2α was reported higher in labour. Additionally, PGF2α, PGF1α, and PGE2 were reported to increase in amniotic fluid as pregnancy progressed, though this pattern was not consistent in plasma. Overall, the evidence supporting changes in prostaglandin levels in these biofluids remains unclear. An important limitation is the lack of data on the complexity of the prostaglandin pathway outside of the PGE and PGF families. Future studies using new methodologies capable of co-assessing multiple prostaglandins and metabolites, in large, well-defined populations, will help provide more insight as to the identification of exactly which prostaglandins and/or metabolites consistently change with labour. Revisiting and revising our understanding of the prostaglandins may provide better targets for clinical monitoring of pregnancies. This study was supported by the Canadian Institutes of Health Research.

Agreement between maternal recall of distant first birth events with hospital birth records: A cohort study

BACKGROUND Inter and intra-generational birth cohorts could be particularly useful for predicting the likelihood of labour and birth events for nulliparous women. However, maternal recall of their first childbirth may be imprecise, and hospital records can be inaccurate. Establishing the extent of agreement between mothers’ recall and hospital reports of historical first birth events could be the basis of a prediction tool that could contribute to better health care practices during daughter’s perinatal period. METHODS In 2015, women who had their first baby between 1967 and 1997 were asked to recall gravidity, method of labour onset, type of pain relief, length of labour, birth outcome, and infant’s gender, birthweight and gestational age ≥17 years postpartum. Responses were compared to hospital birth records. Agreement was evaluated using Bland-Altman’s plots and Kappa statistics (k). Logistic regression modeling was used to determine factors influencing discrepant recall. RESULTS Of 150 questionnaires distributed, 101 records were complete. Up to 49 years after birth there was strong agreement for birthweight measured at interval (mean discrepancy -28.69g, SD =170.91g, Bland-Altman 95% limits of agreement (-363.66g, 306.28g)) and category level birthweight k=0.83, good agreement for gestational age (GA) in weeks, at interval level (mean difference=0, SD =0.90, Bland-Altman 95% limits of agreement (-1.766, 1.766)) and at category level GA k=0.56. There was moderate agreement for labour length (≤10hrs/>10hrs) k=0.54; 43% of records did not record this information. For gravidity k=0.43, labour onset k=0.79; any pain relief k=0.61; and birth outcome k=0.91. Univariate logistic regression showed better agreement on infant birthweight in women with higher levels of education, lower agreement for onset of labour method with increasing maternal age at birth, and higher agreement for use of pethidine, but lower agreement for use of epidural in women who had their first babies more recently. CONCLUSIONS Mothers accounts of first birth events generally agree with hospital records. Familial birth data may contribute to more individualised care for nulliparous women, and may limit rising interventions based on population level guidelines. Future research in other settings is warranted before diagnostic criteria may be used in clinical settings.

Myo-inositol – A potential prophylaxis against premature onset of labour and preterm birth

The incidence of preterm birth (PTB), delivery before 37 completed weeks of gestation, is rising in most countries. Several recent small clinical trials of myo-inositol supplementation in pregnancy, which were primarily aimed at preventing gestational diabetes, have suggested an effect on reducing the incidence of PTB as a secondary outcome, highlighting the potential role of myo-inositol as a preventive agent. However, the underlying molecular mechanisms by which myo-inositol might be able to do so remain unknown; these may occur through directly influencing the onset and progress of labour, or by suppressing stimuli that trigger or promote labour. This paper presents hypotheses outlining the potential role of uteroplacental myo-inositol in human parturition and explains possible underlying molecular mechanisms by which myo-inositol might modulate the uteroplacental environment and inhibit preterm labour-onset. We suggest that a physiological decline in uteroplacental inositol levels to a critical threshold with advancing gestation, in concert with an increasingly pro-inflammatory uteroplacental environment, permits spontaneous membrane rupture and labour-onset. A higher uteroplacental inositol level, potentially promoted by maternal myo-inositol supplementation, might affect lipid metabolism, eicosanoid production, and secretion of pro-inflammatory chemocytokines, that overall dampen the pro-labour uteroplacental environment responsible for labour-onset and progress, thus, reducing the risk of PTB. Understanding how and when inositol may act to reduce PTB risk would facilitate the design of future clinical trials of maternal myo-inositol supplementation and definitively address the efficacy of myo-inositol prophylaxis against PTB.

1056Maternal dyslipidaemia is associated with shorter gestational length in a UK cohort of 7440 pregnancies

Background Mechanisms for human labour are unknown because of difficulties in human pregnancy experimentation, limiting our ability to prevent preterm birth. Maternal metabolism is potentially involved. This study aimed to explore associations of multiple maternal metabolic traits with gestational age at delivery (GA). Methods Women with singleton pregnancies recruited to the Born in Bradford cohort study were included. A total of 157 maternal blood metabolites sampled between 26-28 weeks were measured using high-throughput NMR metabolomics. Associations between each metabolite and GA was modelled using linear (GA continuous) and logistic (GA binary) regressions; adjusted for age, BMI, ethnicity, socioeconomical status, alcohol, smoking, parity, pre-existing and gestational diabetes and hypertension, pre-eclampsia, and labour onset. Results The complete case sample included 7440 pregnancies (12308 eligible; 4540 had missing data). 1SD increases in large and very large HDLs were associated with longer mean GAs of 0.5-1 day, including 1SD increased HDL mean diameter associated with +0.5 day mean GA (95%CI:0.2to0.8;p=9.1E-4). 1SD increases in VLDLs and LDLs were associated with shorter mean GAs of 0.5-1 day, including 1SD increase in large VLDL associated with -0.7 days difference in GA (95%CI:-1.021to-0.465;p=2.299E-07). Conclusions Our findings suggest for the first time that maternal dyslipidaemia is related to differences in GA even after adjusting for multiple key confounders. Further studies are needed to clarify whether lipoprotein metabolism is causally involved in human labour. Key messages Human labour may involve pathways related to lipoprotein metabolism.

Proximate Predictors of Vaginal Delivery in Primigravid women at a Tertiary Health Facility in Ibadan, Nigeria

Background Successful vaginal delivery (VD) is the desire of every parturient. This is however not always so especially for primigravid women. Predictive factors can help the counselling process and allay the anxiety that this group of parturients experience. Objective To determine the prevalence and predictors of vaginal delivery among primigravid women at a tertiary health facility. Methods This was a 6-month cross-sectional study of 200 primigravid women that were planned for vaginal delivery. Information was obtained using structured proforma. Bivariate and multivariable analysis was used to identify the proximate predictors of VD. Results The prevalence of vaginal delivery was 50.0%. Labour onset was spontaneous in 78.0%; 10.0% had engaged fetal head prior to labour onset while labour was augmented in 18.0% of the parturients. Labour lasted ≤12 hours in majority (67.5%) with about half (49.5%) having successful vaginal delivery. Factors predicting successful vaginal delivery were spontaneous labour onset (OR=3.555, 95% CI=1.626-7.774), booked pregnancy (OR=3.008, 95%CI=1.361-6.647), and early fetal head engagement (OR=6.484, 95% CI=1.686-24.943). Conclusion The identified predictive factors of vaginal delivery in this study will aid counselling of primigravid women regarding the likelihood of successful vaginal delivery especially in the absence of other obstetric complications. Rwanda J Med Health Sci 2021;4(1):20-36

Transcriptional Control of Parturition: Insights from Gene Regulation Studies in the Myometrium

The onset of labour is a culmination of a series of highly coordinated and preparatory physiological events that take place throughout the gestational period. In order to produce the associated contractions needed for fetal delivery, smooth muscle cells in the muscular layer of the uterus (i.e. myometrium) undergo a transition from quiescent to contractile phenotypes. Here, we present the current understanding of the roles transcription factors play in critical labour-associated gene expression changes as part of the molecular mechanistic basis for this transition. Consideration is given to both transcription factors that have been well-studied in a myometrial context, i.e. activator protein 1 (AP-1), progesterone receptors (PRs), estrogen receptors (ERs), and nuclear factor kappa B (NF-κB), as well as additional transcription factors whose gestational event-driving contributions have been demonstrated more recently. These transcription factors may form pregnancy- and labour- associated transcriptional regulatory networks in the myometrium to modulate the timing of labour onset. A more thorough understanding of the transcription factor-mediated, labour-promoting regulatory pathways holds promise for the development of new therapeutic treatments that can be used for the prevention of preterm labour in at-risk women.