Screening for Preterm Birth: Potential for a Metabolomics Biomarker Panel

The aim of this preliminary study was to investigate the potential of maternal serum to provide metabolomic biomarker candidates for the prediction of spontaneous preterm birth (SPTB) in asymptomatic pregnant women at 15 and/or 20 weeks’ gestation. Metabolomics LC-MS datasets from serum samples at 15- and 20-weeks’ gestation from a cohort of approximately 50 cases (GA < 37 weeks) and 55 controls (GA > 41weeks) were analysed for candidate biomarkers predictive of SPTB. Lists of the top ranked candidate biomarkers from both multivariate and univariate analyses were produced. At the 20 weeks’ GA time-point these lists had high concordance with each other (85%). A subset of 4 of these features produce a biomarker panel that predicts SPTB with a partial Area Under the Curve (pAUC) of 12.2, a sensitivity of 87.8%, a specificity of 57.7% and a p-value of 0.0013 upon 10-fold cross validation using PanelomiX software. This biomarker panel contained mostly features from groups already associated in the literature with preterm birth and consisted of 4 features from the biological groups of “Bile Acids”, “Prostaglandins”, “Vitamin D and derivatives” and “Fatty Acids and Conjugates”

The terrorist attacks and the human live birth sex ratio: a systematic review and meta-analysis.

The live birth sex ratio is defined as male/total births (M/F). Terrorist attacks have been associated with a transient decline in M/F 3-5 months later with an excess of male losses in ongoing pregnancies. The early 21st century is replete with religious/politically instigated attacks. This study estimated the pooled effect size between exposure to attacks and M/F. Registration number CRD42016041220. PubMed and Scopus were searched for ecological studies that evaluated the relationship between terrorist attacks from 1/1/2000 to 16/6/2016 and M/F. An overall pooled odds ratio (OR) for the main outcome was generated using the generic inverse variance method. Five studies were included: 2011 Norway attacks; 2012 Sandy Hook Elementary School shooting; 2001 September 11 attacks; 2004 Madrid and 2005 London bombings. OR at 0.97 95% CI (0.94-1.00) (I2 = 63%) showed a small statistically significant 3% decline in the odds (p = 0.03) of having a male live birth 3-5 months later. For lone wolf attacks there was a 10% reduction, OR 0.90 95% CI (0.86-0.95) (p = 0.0001). Terrorist (especially lone wolf) attacks were significantly associated with reduced odds of having a live male birth. Pregnancy loss remains an important Public Health challenge. Systematic reviews and meta-analyses considering other calamities are warranted

Prenatal maternal stress and risk of neurodevelopmental disorders in the offspring: A systematic review and meta-analysis protocol

Background: Prenatal maternal stress (PNMS) is defined as the experience of significant levels of prenatal stress, depression or anxiety during pregnancy. PNMS has been associated with increased risk of autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD) in exposed offspring. However, these findings are inconsistent and other studies found no association, meaning a clear consensus on the impact of PNMS on ASD and ADHD risk is required. The purpose of this systematic review and meta-analysis is to summarize and critically review the existing literature on the effects of PNMS on ASD and ADHD risk. Methods: Electronic databases (PubMed, PsycINFO, Web of Science, Scopus and EMBASE) will be searched for articles following a detailed search strategy. We will include cohort and case-control studies that assessed maternal exposure to psychological and/or environmental stress and had ASD or ADHD as an outcome. Two reviewers will independently screen the titles, abstracts and full articles to identify eligible studies. We will use a standardised data extraction form for extracting data and a bias classification tool for assessing study quality. This systematic review will be reported according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). The generic inverse variance method will be used if possible to perform meta-analyses. Ethics and dissemination: Ethical approval is not required for this study because it will not involve the conduct or inclusion of any experimental or personal data that would require informed consent. The systematic review will be disseminated in peer-reviewed journals. PROSPERO registration number: CRD42018084222

Reporting on data monitoring committees in neonatal randomised controlled trials is inconsistent

Aim: To evaluate the reported use of Data Monitoring Committees (DMCs), the frequency of interim analysis, pre-specified stopping rules and early trial termination in neonatal randomised controlled trials (RCTs). Methods: We reviewed neonatal RCTs published in four high impact general medical journals, specifically looking at safety issues including documented involvement of a DMC, stated interim analysis, stopping rules and early trial termination. We searched all journal issues over an 11-year period (2003-2013) and recorded predefined parameters on each item for RCTs meeting inclusion criteria. Results: Seventy neonatal trials were identified in four general medical journals: Lancet, New England Journal of Medicine (NEJM), British Medical Journal and Journal of American Medical Association (JAMA). 43 (61.4%) studies reported the presence of a DMC, 36 (51.4%) explicitly mentioned interim analysis; stopping rules were reported in 15 (21.4%) RCTs and 7 (10%) trials were terminated early. The NEJM most frequently reported these parameters compared to the other three journals reviewed. Conclusion: While the majority of neonatal RCTs report on DMC involvement and interim analysis there is still scope for improvement. Clear documentation of safety related issues should be a central component of reporting in neonatal trials involving newborn infants

Women's experiences of interventions for fear of childbirth in the perinatal period: A meta-synthesis of qualitative research evidence

Issue Fear of childbirth (FOC) can be debilitating, impacting women's lives in pregnancy, the puerperium and beyond. Research investigated various interventions for FOC in the perinatal period, but there been no synthesis of the experiences of women who engaged with these interventions, which would inform clinical practice guidance and the development of future interventions. Aim To conduct a review and synthesis of qualitative studies of interventions for fear of childbirth in the perinatal period and women's experiences of them. Methods A meta-synthesis was performed to examine all relevant qualitative studies describing women's experiences of interventions for FOC, in all languages. A comprehensive search of relevant databases from 1978 to 2019 was conducted. In total, following appraisal, seven qualitative studies were eligible for inclusion. The findings were integrated using thematic synthesis for the final stages in the thematic analysis. Findings One overarching theme “Ownership of Childbirth” and three analytical themes “Facing the fear”, “Feeling empowered”, “Managing the fear with a sense of security” were generated through the synthesis. There were no studies outside of Scandinavia located. Discussion This meta-synthesis provides a new way to describe the process of moving from fear to “Ownership of childbirth”. The first step in the process appears to be acknowledging and identifying the individual's fears. Women can be empowered to self-manage FOC but may be influenced by external factors such as the support of partners and staff. Conclusion These findings provide evidence to inform the development of future interventions for FOC and highlight the need for further qualitative research globally

Hypertensive disorders of pregnancy and risk of neurodevelopmental disorders in the offspring: a systematic review and meta-analysis protocol

Introduction Hypertensive disorders of pregnancy (HDPs), that is chronic hypertension, gestational hypertension, pre-eclampsia (de novo or superimposed on chronic hypertension) and white coat hypertension, affect approximately 5%–15% of pregnancies. HDP exposure has been linked to an increased risk of autism spectrum disorder, attention deficit/hyperactivity disorder and other neurodevelopmental disorders in children. However, findings are inconsistent, and a clear consensus on the impact of HDPs on the risk of neurodevelopmental disorders is needed. Therefore, we aim to synthesise the published literature on the relationship between HDPs and the risk of neurodevelopmental disorders in the form of a systematic review and meta-analysis. Methods and analysis We will include cohort, case– control and cross-sectional studies in which diagnosis of an HDP was reported, and neurodevelopmental disorders were the outcome of interest based on a preprepared protocol. A systematic search of PubMed, CINAHL, Embase, PsycINFO and Web of Science will be conducted in accordance with a detailed search strategy. Two authors will independently review the titles and abstracts of all studies, perform data extraction using a standardised data collection form and assess study quality using a bias classification tool. Meta-analyses will be performed to calculate overall pooled estimates using the generic inverse variance method. This systematic review will be reported according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses. Ethics and dissemination This proposed systematic review and meta-analysis is based on published data, therefore, does not require ethics approval. Findings will be presented at scientific conferences and disseminated through publication in a peer-reviewed journal. Registration CRD42017068258

The association between caesarean section and cognitive ability in childhood

Purpose: Global rates of caesarean section (CS) rates have increased rapidly in recent years. This is a growing public health concern as it has been proposed that CS may impact cognitive outcomes in childhood. However, the evidence for this association is limited and inconsistent. Therefore, the aim of this study was to investigate the relationship between obstetric mode of delivery and longitudinal cognitive outcomes in childhood. Methods: We examined this question using data from a longitudinal cohort study of 8845 participants from the Millennium Cohort Study, a nationally representative UK cohort, who completed a range of verbal and visual-spatial cognitive assessments at ages 3, 5, 7 and 11 years. Results: We found a statistically significant association between planned CS and visual-spatial cognitive delay in the pattern construction assessment at age 5 (OR 1.31, 95% CI 0.99–1.72) and age 7 (OR 1.42, 95% CI 1.12–1.81). Additionally planned CS was also associated with increased odds of “early childhood delay” (OR 1.70, 95% CI 1.15–2.50) and borderline increased odds of “persistent delay” (OR 1.37, 95% CI 0.99–1.89) in visual-spatial cognitive tests. Mode of delivery was not associated with verbal ability or with patterns of delay at any age point in verbal cognitive tests. Conclusion: We have reported a small association between planned CS and visual-spatial cognitive delay in childhood. However, while this result should be interpreted with caution, it highlights the need to further explore this potential relationship and the causal basis of such an association

Pregnancy outcomes in women with severe fear of childbirth

Objective: To compare pregnancy outcomes for women with and without severe fear of childbirth (FOC) reported in the second trimester of pregnancy. Methods: In a prospective cohort study, 389 singleton pregnancies were followed up using medical records of participants in a study investigating FOC in Cork, Republic of Ireland. FOC was measured using the Wijma Delivery Experience Questionnaire Part A (W-DEQ A). Severe FOC was defined as W-DEQ A ≥ 85, moderate FOC, W-DEQ-A 66-84 and low FOC, W-DEQ A 0-65. Outcome measures were birthweight, birthweight centile, gestational age, and Apgar scores at 1 min and Apgar at 5 min. Linear regression was used to assess the association between FOC and each outcome measure with adjustment for maternal age, smoking, parity and marital status. Results: There was no statistically significant difference in mean birthweight (mean difference = −0.03; [95% CI: -444.69, 315.82]), mean birthweight centile (mean difference = 0.03; [95%CI: -15.97, 23.53]), or mean gestational age (mean difference = −0.06; [95%CI: -11.69, 4.82]) in women with severe FOC (n = 18) compared with women with low FOC (n = 371). In the adjusted models, there was only a slight correlation between severe FOC and Apgar scores at 1 min (mean difference = −0.09 [95%CI: -1.28, 0.32]) and Apgar scores at 5 min (mean difference = −0.18 [95%CI: -1.16, 1.08]). Conclusion: While a slight association was noted between severe FOC and Apgar scores, overall findings are reassuring and could inform educational interventions which may alleviate FOC. Awareness of FOC for health care professionals is vital to consider women's mental well-being

Trial of labour after caesarean section and the risk of neonatal and infant death: a nationwide cohort study

Background: Caesarean section (CS) rates are increasing worldwide and as a result repeat CS is common. The optimal mode of delivery in women with one previous CS is widely debated and the risks to the infant are understudied. The aim of the current study was to evaluate if women with a trial of labour after caesarean (TOLAC) had an increased odds of neonatal and infant death compared to women with an elective repeat CS (ERCS). Methods: A population register-based cohort study was conducted in Denmark between 1982 and 2010. All women with two deliveries [in which the first was a CS, and the second was an uncomplicated, term delivery (n = 61,626)] were included in the study. Logistic regression models were used to report adjusted odds ratios (AOR) and 95% confidence intervals (CI) of the odds of death according to mode of delivery. The main outcome measures were neonatal death (early and late) and infant death. Results: Women with a TOLAC had an increased odds of neonatal death (AOR 1 · 87, 95% CI 1 · 12 to 3 · 12) due to an increased risk of early neonatal death (AOR 2 · 06, 95% CI 1 · 19 to 3 · 56) and no effect on late neonatal death (AOR 0 · 97, 95% CI 0 · 22 to 4 · 32), or infant death (AOR 1 · 12, 95% CI 0 · 79 to 1 · 59) when compared to the reference group of women with an ERCS. There was evidence of a cohort effect as the increased odds of neonatal death (AOR 3 · 89, 95% CI 1 · 33 to 11 · 39) was most significant in the earlier years (1982–1991) and gradually disappeared (AOR 1 · 01, 95% CI 0 · 44 to 2 · 31) in the later years (2002–2010). Conclusions: Although an increased risk of neonatal death was found in women with a TOLAC, there was evidence of a cohort effect, which showed this increased odds disappearing over time. Advances in modern healthcare including improved monitoring and earlier detection of underlying pregnancy complications may explain the findings

What is to blame for postnatal pelvic floor dysfunction in primiparous women — Pre-pregnancy or intrapartum risk factors?

Background: The aetiology of pelvic floor dysfunction (PFD) is still poorly understood. However childbearing is recognized as a major risk factor. Objectives: To elucidate the natural history of PFD by investigating the impact of the mode of delivery on postnatal pelvic floor dysfunction in primiparas, when PFD existing before the first pregnancy is taken into consideration. Study design: 4P-study (Prevalence and Predictors of Pelvic floor dysfunction in Primips) is a prospective cohort study, nested within the Screening for Pregnancy Endpoints (SCOPE) study set in a tertiary referral teaching hospital with 9000 deliveries annually. Established and proposed risk factors for urinary, fecal, prolapse and sexual dysfunction and the severity of symptoms for each of these outcomes were assessed using the Australian Pelvic Floor Questionnaire in 1482 nulliparous women, who each completed the questionnaire in early pregnancy. Of these, 1060 (72%) repeated the questionnaire 12 months postpartum. Outcomes were analyzed using multivariate ordinal logistic regression. Results: Significant (p < 0.05) risk factors for postpartum PFD were pre-pregnancy presence of similar symptoms Odds Ratio (OR) (5.0–30.0), smoking (OR 2.2–4.6), recurrent UTI (OR 2.2–17.3), high hip circumference (OR1.4–1.6), vigorous exercising (OR 3.1–17.9), induction of labor (OR 1.5–2.3), forceps delivery (OR 1.8–8.8), and 3rd degree perineal tear (OR 2.4–2.7). Cesarean section was associated with a lower risk of stress urinary incontinence (OR 0.3–0.5). Other common pre-pregnancy significant (p < 0.05) risk factors for various PFD types prior to the first pregnancy were: diagnosed depression – (OR 1.6–2.1), high BMI (OR 3.1), strenuous exercising (OR 1.3–2.2), recurrent UTI (OR 1.5–2.5) and lower educational achievement (OR 1.5–1.6). Conclusions: Pre-pregnancy PFD was mainly associated with modifiable risk factors such as smoking and exercising. The main risk factor for postpartum PFD was the presence of similar symptoms prior to pregnancy, followed by anthropometric and intrapartum factors. Hip circumference seems to be a better predictor of PFD compared to BMI. When pre-pregnancy PFD was included in the analysis, Cesarean section was protective only for stress urinary incontinence, while delivery by forceps increased the risk of prolapse