Risk of stillbirth after a previous caesarean delivery: A Swedish nationwide cohort study.

OBJECTIVES: To investigate the risk of stillbirth in relation to (1) a previous caesarean delivery (CD) compared with those following a vaginal birth (VB); and (2) vaginal birth after caesarean (VBAC) compared with a repeat CD. DESIGN: Population-based cohort study. SETTING: The Swedish Medical Birth registry. POPULATION: Women with their first and second singletons between 1982 and 2012. METHODS: Multivariable logistic regression models were performed to estimate adjusted odds ratios (aOR) and 95% confidence intervals (CI) of the association between CD in the first pregnancy and stillbirth in the second pregnancy and the association between VBAC and stillbirth. Sub-group analyses were performed by types of CD and timing of stillbirth (antepartum and intrapartum). MAIN OUTCOME MEASURES: Stillbirth (antepartum and intrapartum fetal death). RESULTS: Of the 1 771 700 singleton births from 885 850 women, 117 114 (13.2%) women had a CD in the first pregnancy, and 51 755 had VBAC in the second pregnancy. We found a 37% increased odds of stillbirth (aOR 1.37; 95% CI 1.23-1.52) in women with a previous CD compared with VB. The odds of intrapartum stillbirth were higher in the previous pre-labour CD group (aOR 2.72; 95% CI 1.51-4.91) and in the previous in-labour CD group (aOR 1.35; 95% CI 0.76-2.40), although not statistically significant in the latter case. No increased odds were found for intrapartum stillbirth in women who had VBAC (aOR 0.99; 95% CI 0.48-2.06) compared with women who had a repeat CD. CONCLUSIONS: This study confirms that a CD is associated with an increased risk of subsequent stillbirth, with a greater risk among pre-labour CD. This association is not solely mediated by increases in intrapartum asphyxia, uterine rupture or attempted VBAC. Further research is needed to understand this association, but these findings might help healthcare providers to reach optimal decisions regarding mode of birth, particularly when CD is unnecessary.

Pregnancy and birth complications and long-term maternal mental health outcomes: A systematic review and meta-analysis.

BACKGROUND: Few studies have examined the associations between pregnancy and birth complications and long-term (>12 months) maternal mental health outcomes. OBJECTIVES: To review the published literature on pregnancy and birth complications and long-term maternal mental health outcomes. SEARCH STRATEGY: Systematic search of Cumulative Index to Nursing and Allied Health Literature (CINAHL), Excerpta Medica Database (Embase), PsycInfo®, PubMed® and Web of Science from inception until August 2022. SELECTION CRITERIA: Three reviewers independently reviewed titles, abstracts and full texts. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and appraised study quality. Random-effects meta-analyses were used to calculate pooled estimates. The Meta-analyses of Observational Studies in Epidemiology (MOOSE) guidelines were followed. The protocol was prospectively registered on the International Prospective Register of Systematic Reviews (PROSPERO: CRD42022359017). MAIN RESULTS: Of the 16 310 articles identified, 33 studies were included (3 973 631 participants). Termination of pregnancy was associated with depression (pooled adjusted odds ratio, aOR 1.49, 95% CI 1.20-1.83) and anxiety disorder (pooled aOR 1.43, 95% CI 1.20-1.71). Miscarriage was associated with depression (pooled aOR 1.97, 95% CI 1.38-2.82) and anxiety disorder (pooled aOR 1.24, 95% CI 1.11-1.39). Sensitivity analyses excluding early pregnancy loss and termination reported similar results. Preterm birth was associated with depression (pooled aOR 1.37, 95% CI 1.32-1.42), anxiety disorder (pooled aOR 0.97, 95% CI 0.41-2.27) and post-traumatic stress disorder (PTSD) (pooled aOR 1.75, 95% CI 0.52-5.89). Caesarean section was not significantly associated with PTSD (pooled aOR 2.51, 95% CI 0.75-8.37). There were few studies on other mental disorders and therefore it was not possible to perform meta-analyses. CONCLUSIONS: Exposure to complications during pregnancy and birth increases the odds of long-term depression, anxiety disorder and PTSD.

Cytoreductive surgery plus chemotherapy versus chemotherapy alone for recurrent epithelial ovarian cancer.

OBJECTIVES: This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To evaluate the benefits and harms of secondary CRS and chemotherapy in comparison to chemotherapy alone for women with platinum-sensitive recurrent epithelial ovarian cancer.

Household energy poverty and trajectories of emotional and behavioural difficulties in children and adolescents: findings from two prospective cohort studies.

PURPOSE: The aim of this study is to examine the association between household energy poverty (EP) and trajectories of emotional and behavioural difficulties during childhood. METHODS: The Growing up in Ireland study is two nationally representative prospective cohorts of children. The Infant Cohort (n = 11,134) were recruited at age 9 months (9 m) and followed up at 3, 5, 7 and 9 years (y). The Child Cohort (n = 8,538) were recruited at age 9 y and followed up at 13 y and 17/18 y. EP was a composite of two relative measures of EP. Emotional and behavioural difficulties were repeatedly measured using the strengths and difficulties questionnaire (SDQ). Linear spline multilevel models were used, adjusted for confounders to examine the association between (1) EP (9 m or 3 y) and trajectories of emotional and behavioural difficulties from 3 to 9 y in the Infant Cohort and (2) EP at 9 y and the same trajectories from 9 to 18 y in the Child Cohort. RESULTS: In adjusted analyses, EP at 9 m or 3 y of age was associated with higher total difficulties score at 3 y (0.66, 95% CI 0.41, 0.91) and 5 y (0.77, 95% CI 0.48, 1.05) but not at 7 y or 9 y. EP at 9 y was associated with higher total difficulties score at 9 y (1.73, 95% CI 1.28, 2.18), with this difference reducing over time leading to 0.68 (95% CI 0.19, 1.17) at 17/18 y. CONCLUSIONS: Our study demonstrates a potential association between early life EP and emotional and behavioural difficulties that may be transient and attenuate over time during childhood. Further studies are required to replicate these findings and to better understand if these associations are causal.

The association between caesarean section delivery and obesity at age 17 years. Evidence from a longitudinal cohort study in the United Kingdom.

BACKGROUND: Childhood and adolescent obesity are major, preventable public health concerns. Studies to date are inconclusive regarding an association between caesarean section (CS) delivery and offspring obesity, with fewer studies conducted in late adolescence. This study examined the association between CS delivery, with a specific focus on planned CS, and induction of labour and adolescent body mass index (BMI) and body fat percentage (BF%) at age 17 years. METHODS: Data on 8,880 mother-child pairs from the United Kingdom Millennium Cohort Study were analysed. The exposures were mode of delivery (normal vaginal delivery (VD) (reference), assisted VD, planned CS and emergency CS) and mode of delivery by induction of labour status. Crude and adjusted binary logistic regression and linear regression models were fitted examining BMI and BF% at age 17 years respectively, adjusting for several potential confounders. RESULTS: Adolescents born by CS did not have an elevated BMI or BF% compared to those born by normal VD. The fully adjusted results for overweight and obesity in children born by planned CS, compared to VD, were 1.05 (95% CI: 0.86-1.28) and 0.94 (95% CI: 0.72-1.23), respectively. The results were similar for the associations between CS and BF%, and between induction of labour and BMI. CONCLUSION: Overall, this large longitudinal study did not support an association between CS or induction of labour and overweight, obesity or BF%. It is possible that previously reported associations are due to residual or unmeasured confounding and/or underlying indications for CS delivery.

Poverty trajectories and child and mother well-being outcomes in Ireland: findings from an Irish prospective cohort.

BACKGROUND: Poverty is associated with poor outcomes, yet exposure to distinct poverty trajectories in early childhood is not well understood. OBJECTIVE: To understand the prevalence of different trajectories of household poverty and their association with mid-childhood and mother indicators of physical health and psychopathology in Ireland. METHODS: We used a nationally representative, prospective cohort (Growing Up in Ireland-Infant Cohort). Household poverty included lowest third income decile, subjective poverty and material deprivation when children were aged 9 months, and 3, 5, 9 years. We used group-based multitrajectory cluster modelling to classify trajectories of poverty. Using multivariable logistic regression, adjusted with separate child and mother confounders, we assessed the association of poverty trajectories from 9 months to 9 years with child outcomes (overweight, any longstanding illness and psychopathology) at age 9 years and the same poverty trajectories over the same 9-year period with mother outcomes (overweight, any longstanding illness and depression). RESULTS: Of 11 134 participants, 4 trajectories were identified: never in poverty (43.1%), material/subjective>monetary poverty (16.1%), monetary>material poverty (25.6%) and persistent poverty (15.2%). Children in persistent poverty compared with those in never in poverty experienced higher odds of being overweight at 9 years (adjusted OR (aOR) 1.70, 95% CI 1.34, 2.16), having a longstanding illness (aOR 1.51, 95% CI 1.20, 1.91), and psychopathology (aOR 2.06, 95% CI 1.42, 2.99). The outcomes for primary parents (99.7% were mothers) were as follows: having higher odds of being overweight (aOR 1.49, 95% CI 1.16, 1.92), having a longstanding illness (aOR 2.13, 95% CI 1.63, 2.79), and depression (aOR 3.54, 95% CI 2.54, 4.94). CONCLUSIONS: Any poverty trajectory was associated with poorer psychopathology and physical well-being in late childhood for children and their mothers in Ireland.

The Association between Threatened Miscarriage and Autism Spectrum Disorder and Attention-Deficit/Hyperactivity Disorder in Offspring by Age 14 Years.

OBJECTIVE: To examine the association between threatened miscarriage, and neurodevelopmental disorders, including autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) in offspring by age 14 years. METHODS: We used data from the Millennium Cohort Study, a nationally representative longitudinal study of children born in the UK. Data on threatened miscarriage and potential confounders were maternal-reported and collected at 9 months postpartum. Data on ASD and ADHD were based on maternal-reported doctor diagnoses and collected when children were aged 5, 7, 11 and 14 years. A diagnosis of ASD or ADHD was assumed if parents reported ASD or ADHD at age 5, 7, 11 or 14 years. Crude and adjusted logistic regression examined threatened miscarriage and ASD and ADHD relationship, adjusting for several sociodemographic, maternal and lifestyle factors. RESULTS: A total of 18,294 singleton babies were included at baseline, and 1,104 (6.0%) women experienced a threatened miscarriage during their pregnancy. Adjusted results suggested an association between threatened miscarriage and ASD (OR: 1.55, 95% CI 1.15, 2.08), and ADHD (OR: 1.51, 95% CI 1.09, 2.10) by age 14 years. E-values for threatened miscarriage and ASD were 2.47, while the lower limits of the 95% CI were 1.57. E-values for threatened miscarriage and ADHD were 2.39, while the corresponding lower limits of the 95% CI were 1.40. CONCLUSION: Threatened miscarriage was associated with an increased likelihood of ASD and ADHD by the age of 14 years, however, residual confounding cannot be ruled out. Placental pathology may be a potential mechanism for the observed associations.

Prenatal stress impacts foetal neurodevelopment: Temporal windows of gestational vulnerability.

Prenatal maternal stressors ranging in severity from everyday occurrences/hassles to the experience of traumatic events negatively impact neurodevelopment, increasing the risk for the onset of psychopathology in the offspring. Notably, the timing of prenatal stress exposure plays a critical role in determining the nature and severity of subsequent neurodevelopmental outcomes. In this review, we evaluate the empirical evidence regarding temporal windows of heightened vulnerability to prenatal stress with respect to motor, cognitive, language, and behavioural development in both human and animal studies. We also explore potential temporal windows whereby several mechanisms may mediate prenatal stress-induced neurodevelopmental effects, namely, excessive hypothalamic-pituitary-adrenal axis activity, altered serotonin signalling and sympathetic-adrenal-medullary system, changes in placental function, immune system dysregulation, and alterations of the gut microbiota. While broadly defined developmental windows are apparent for specific psychopathological outcomes, inconsistencies arise when more complex cognitive and behavioural outcomes are considered. Novel approaches to track molecular markers reflective of the underlying aetiologies throughout gestation to identify tractable biomolecular signatures corresponding to critical vulnerability periods are urgently required.

Association between intrapartum fetal pulse oximetry and adverse perinatal and long-term outcomes: a systematic review and meta-analysis protocol.

Background: Current methods of intrapartum fetal monitoring based on heart rate, increase the rates of operative delivery but do not prevent or accurately detect fetal hypoxic brain injury. There is a need for more accurate methods of intrapartum fetal surveillance that will decrease the incidence of adverse perinatal and long-term neurodevelopmental outcomes while maintaining the lowest possible rate of obstetric intervention. Fetal pulse oximetry (FPO) is a technology that may contribute to improved intrapartum fetal wellbeing evaluation by providing a non-invasive measurement of fetal oxygenation status. Objective: This systematic review and meta-analysis aims to synthesise the evidence examining the association between intrapartum fetal oxygen saturation levels and adverse perinatal and long-term outcomes in the offspring. Methods: We will include randomised control trials (RCTs), cohort, cross-sectional and case-control studies which examine the use of FPO during labour as a means of measuring intrapartum fetal oxygen saturation and assess its effectiveness at detecting adverse perinatal and long-term outcomes compared to existing intrapartum surveillance methods. A detailed systematic search of PubMed, EMBASE, CINAHL, The Cochrane Library, Web of Science, ClinicalTrials.Gov and WHO ICTRP will be conducted following a detailed search strategy until February 2024. Three authors will independently review titles, abstracts and full text of articles. Two reviewers will independently extract data using a pre-defined data extraction form and assess the quality of included studies using the Risk of Bias tool for RCTs and Newcastle-Ottawa Scale for observational studies. The grading of recommendations, assessment, development, and evaluation (GRADE) approach will be used to evaluate the certainty of the evidence. We will use random-effects meta-analysis for each exposure-outcome association to calculate pooled estimates using the generic variance method. This systematic review will follow the Preferred Reporting Items for Systematic reviews and Meta-analyses and MOOSE guidelines. PROSPERO registration: CRD42023457368 (04/09/2023).

Cohort profile: Improved Pregnancy Outcomes via Early Detection (IMPROvED), an International Multicentre Prospective Cohort.

Background: Improved Pregnancy Outcomes via Early Detection (IMPROvED) is a multi-centre, European phase IIa clinical study. The primary aim of IMPROvED is to enable the assessment and refinement of innovative prototype preeclampsia risk assessment tests based on emerging biomarker technologies. Here we describe IMPROvED's profile and invite researchers to collaborate. Methods: A total of 4,038 low-risk nulliparous singleton pregnancies were recruited from maternity units in Ireland (N=1,501), United Kingdom (N=1,108), The Netherlands (N=810), and Sweden (N=619) between November 2013 to August 2017. Participants were interviewed by a research midwife at ~11 weeks (optional visit), ~15 weeks, ~20 weeks, ~34 weeks' gestation (optional visit), and postpartum (within 72-hours following delivery). Findings to date: Clinical data included information on maternal sociodemographic, medical history, and lifestyle factors collected at ~15 weeks' gestation, and maternal measurements, collected at each study visit. Biobank samples included blood, urine, and hair collected at each study visit throughout pregnancy in all units plus umbilical cord/blood samples collected at birth in Ireland and Sweden. A total of 74.0% (N=2,922) had an uncomplicated pregnancy, 3.1% (N=122) developed preeclampsia, 3.6% (N=143) had a spontaneous preterm birth, and 10.5% (N=416) had a small for gestational age baby. We evaluated a panel of metabolite biomarkers and a panel of protein biomarkers at 15 weeks and 20 weeks' gestation for preeclampsia risk assessment. Their translation into tests with clinical application, as conducted by commercial entities, was hampered by technical issues and changes in test requirements. Work on the panel of proteins was abandoned, while work on the use of metabolite biomarkers for preeclampsia risk assessment is ongoing. Future plans: In accordance with the original goals of the IMPROvED study, the data and biobank are now available for international collaboration to conduct high quality research into the cause and prevention of adverse pregnancy outcomes.