Obstetrics & Gynaecology

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Abnormal placental cord insertion and adverse pregnancy outcomes: a systematic review and meta-analysis
(BioMed Central Ltd., 2017) Ismail, Khadijah Irfah; Hannigan, Ailish; O'Donoghue, Keelin; Cotter, Amanda
Background: Abnormal placental cord insertion (PCI) includes marginal cord insertion (MCI) and velamentous cord insertion (VCI). VCI has been shown to be associated with adverse pregnancy outcomes. This systematic review and meta-analysis aims to determine the association of abnormal PCI and adverse pregnancy outcomes. Methods: Embase, Medline, CINAHL, Scopus, Web of Science, ClinicalTrials.gov, and Cochrane Databases were searched in December 2016 (from inception to December 2016). The reference lists of eligible studies were scrutinized to identify further studies. Potentially eligible studies were reviewed by two authors independently using the following inclusion criteria: singleton pregnancies, velamentous cord insertion, marginal cord insertion, and pregnancy outcomes. Case reports and series were excluded. The methodological quality of the included studies was assessed using the Newcastle-Ottawa Scale. Outcomes for meta-analysis were dichotomous and results are presented as summary risk ratios with 95% confidence intervals. Results: Seventeen studies were included in the systematic review, all of which were assessed as good quality. Normal PCI and MCI were grouped together as non-VCI and compared with VCI in seven studies. Four studies compared MCI, VCI, and normal PCI separately. Two other studies compared MCI with normal PCI, and VCI was excluded from their analysis. Studies in this systematic review reported an association between abnormal PCI, defined differently across studies, with preterm birth, small for gestational age (SGA), low birthweight (< 2500 g), emergency cesarean delivery, and intrauterine fetal death. Four cohort studies comparing MCI, VCI, and normal PCI separately were included in a meta-analysis resulting in a statistically significant increased risk of emergency cesarean delivery for VCI (pooled RR 2.86, 95% CI 1.56–5.22, P = 0.0006) and abnormal PCI (pooled RR 1.77, 95% CI 1.33–2.36, P < 0.0001) compared to normal PCI. Conclusions: The available evidence suggests an association between abnormal PCI and emergency cesarean delivery. However, the number of studies with comparable definitions of abnormal PCI was small, limiting the analysis of other adverse pregnancy outcomes, and further research is required.
Adopting results based management in the non-profit sector: Trócaire’s experience
(UTS ePress, 2016-07) McKernan, Eoghan; Kennedy, Karen; Aldred, Allison
The increasing emphasis on aid effectiveness, accountability and impact measurement in international development and humanitarian work has generated a requirement for high quality internal systems for the management of programmes. To help to address this requirement, Trócaire adopted Results Based Management in the 20 countries in which it works. This paper provides an overview of Trócaire’s RBM journey, including the process of embedding the new approach in the organisation, lessons learnt from this process, the subsequent benefits that are emerging at field programme level and the challenges going forward.
Advanced maternal age and adverse pregnancy outcome: evidence from a large contemporary cohort
(Public Library of Science, 2013) Kenny, Louise C.; Lavender, Tina; McNamee, Roseanne; O'Neill, Sinéad M.; Mills, Tracey; Khashan, Ali S.
Background: Recent decades have witnessed an increase in mean maternal age at childbirth in most high-resourced countries. Advanced maternal age has been associated with several adverse maternal and perinatal outcomes. Although there are many studies on this topic, data from large contemporary population-based cohorts that controls for demographic variables known to influence perinatal outcomes is limited. Methods: We performed a population-based cohort study using data on all singleton births in 2004-2008 from the North Western Perinatal Survey based at The University of Manchester, UK. We compared pregnancy outcomes in women aged 30-34, 35-39 and >= 40 years with women aged 20-29 years using log-linear binomial regression. Models were adjusted for parity, ethnicity, social deprivation score and body mass index. Results: The final study cohort consisted of 215,344 births; 122,307 mothers (54.19%) were aged 20-29 years, 62,371(27.63%) were aged 30-34 years, 33,966(15.05%) were aged 35-39 years and 7,066(3.13%) were aged >= 40 years. Women aged 40+ at delivery were at increased risk of stillbirth (RR = 1.83, [95% CI 1.37-2.43]), pre-term (RR = 1.25, [95% CI: 1.14-1.36]) and very pre-term birth (RR = 1.29, [95% CI: 1.08-1.55]), Macrosomia (RR = 1.31, [95% CI: 1.12-1.54]), extremely large for gestational age (RR = 1.40, [95% CI: 1.25-1.58]) and Caesarean delivery (RR = 1.83, [95% CI: 1.77-1.90]). Conclusions: Advanced maternal age is associated with a range of adverse pregnancy outcomes. These risks are independent of parity and remain after adjusting for the ameliorating effects of higher socioeconomic status. The data from this large contemporary cohort will be of interest to healthcare providers and women and will facilitate evidence based counselling of older expectant mothers.
An altered gut microbiome in pre-eclampsia: cause or consequence
(Frontiers Media, 2024-05-07) Deady, Clara; McCarthy, Fergus P.; Barron, Aaron; McCarthy, Cathal M.; O'Keeffe, Gerard W.; O'Mahony, Siobhain M.; Irish Research Council
Hypertensive disorders of pregnancy, including pre-eclampsia, are a leading cause of serious and debilitating complications that affect both the mother and the fetus. Despite the occurrence and the health implications of these disorders there is still relatively limited evidence on the molecular underpinnings of the pathophysiology. An area that has come to the fore with regard to its influence on health and disease is the microbiome. While there are several microbiome niches on and within the body, the distal end of the gut harbors the largest of these impacting on many different systems of the body including the central nervous system, the immune system, and the reproductive system. While the role of the microbiome in hypertensive disorders, including pre-eclampsia, has not been fully elucidated some studies have indicated that several of the symptoms of these disorders are linked to an altered gut microbiome. In this review, we examine both pre-eclampsia and microbiome literature to summarize the current knowledge on whether the microbiome drives the symptoms of pre-eclampsia or if the aberrant microbiome is a consequence of this condition. Despite the paucity of studies, obvious gut microbiome changes have been noted in women with pre-eclampsia and the individual symptoms associated with the condition. Yet further research is required to fully elucidate the role of the microbiome and the significance it plays in the development of the symptoms. Regardless of this, the literature highlights the potential for a microbiome targeted intervention such as dietary changes or prebiotic and probiotics to reduce the impact of some aspects of these disorders.
Amniotic fluid C-reactive protein as a predictor of infection in caesarean section: a feasibility study
(Nature Publishing Group) Marchocki, Zbigniew; Vinturache, Angela; Collins, Kevin; O'Reilly, Paddy; O'Donoghue, Keelin
This study evaluated the feasibility of maternal C-reactive protein (CRP) in amniotic fluid (AF) as a predictor of post-partum infection in women who undergo emergency or elective caesarean section (CS). AF bacterial culture and levels of hs-CRP in maternal serum and AF were evaluated in Day 0 and three days thereafter (Day 3) in 79 women undergoing CS. Univariate analyses assessed the clinical and demographic characteristics, whereas the ROC curves assessed the feasibility of hs-CRP as marker of inflammation in women who undergo CS. There was no difference in AF, Day 0, and Day 3 serum hs-CRP levels between women with sterile compared to those with bacterial growth in AF. Among women with positive AF cultures, AF and Day 0 serum hs-CRP levels were higher in women who underwent emergency compared to those who had elective CS (p = 0.04, and p = 0.02 respectively). hs-CRP in Day 0 and Day 3 serum but not in AF has a fair predictor value of infection in emergency CS only (AUC 0.767; 95% CI 0.606-0.928, and AUC 0.791; 95% CI 0.645-0.036, respectively). We conclude that AF hs-CRP is not feasible in assessing the risk of post-cesarean inflammation or infection.
Antenatal risk factors associated with neonatal morbidity in large for gestational age infants: an international prospective cohort study
(John Wiley & Sons, Inc., 2018-05-12) Vieira, Matias C.; McCowan, Lesley M. E.; North, Robyn A.; Myers, Jenny E.; Walker, James J.; Baker, Philip N.; Dekker, Gustaaf A.; Kenny, Louise C.; Poston, Lucilla; Pasupathy, Dharmintra; Science Foundation Ireland; Coordenação de Aperfeiçoamento de Pessoal de Nível Superior; National Health and Medical Research Council; Foundation for Research, Science and Technology; Health Research Council of New Zealand; Health Research Board; National Institute for Health Research; Biotechnology and Biological Sciences Research Council; Guy's and St Thomas' Charity; Cerebra; Tommy's Baby Charity
Introduction: Large for gestational age (LGA) infants are associated with increased risk of neonatal morbidity and mortality, however most of them will not have adverse outcomes. Our aim was to identify antenatal clinical factors associated with neonatal morbidity in LGA infants. Material and methods: Nulliparous women from the Screening for Pregnancy Endpoints (SCOPE) study were included. We compared maternal and fetal factors between LGA infants (birthweight >90th customized centile) with and without neonatal morbidity, defined as admission to neonatal intensive care unit or severe neonatal morbidity. Factors were selected based on a‐priori hypotheses of association and included maternal demography, anthropometric measures and self‐reported physical activity (15 and 20 weeks), fetal biometry (20 weeks), and clinical information. Multivariable logistic regression was used to identify risk factors. Stratified analyses were performed by maternal obesity and physical activity. Results: Amongst term pregnancies, prevalence of LGA infants was 9.3% (491/5,255), with 11.8% (58/491) prevalence of neonatal morbidity. Random glucose at 20 weeks (OR 1.52; 95% CI1.17 to 1.97, per 1mmol/L increase) and no regular physical activity at 20 weeks (3.93; 1.75 to 8.83) were associated with increased risk of neonatal morbidity after adjustment for birthweight, gestational age at delivery and gestational diabetes. The increased risk associated with higher glucose levels was not evident in women with regular physical activity or without obesity. Conclusions: Regular physical activity in mid‐pregnancy is associated with lower risk for neonatal morbidity in LGA infants and seems to offer protection against the increased risk associated with higher maternal glucose levels.
Applications of metabolomics to study the pathophysiology of adverse pregnancy outcomes
(University College Cork, 2020) Morillon, Aude-Claire; McCarthy, Fergus; English, Jane; Yakkundi, Shirish; Kenny, Louise; Baker, Philip; Science Foundation Ireland; Waters Corporation
Background: Clinical metabolomics is a growing field of research aiming to use metabolomic techniques to gain further knowledge into diseases, the use of biomarkers to predict their onset, or the effect of a potential therapeutic agent on the metabolome. Adverse pregnancy outcomes, such as small for gestation age (or fetal growth restriction), spontaneous preterm birth, and pre-eclampsia, lead to high maternal and fetal mortality and morbidity rates. However, despite research efforts to date, their pathophysiology remains poorly understood. Aim: The aims of this thesis was to determine the accuracy of metabolomics to predict small for gestation age (SGA) babies, to explore the metabolic pathways involved in the pathophysiology of SGA and spontaneous preterm birth (sPTB), to identify potential predictive biomarkers of sPTB, and investigate the use of a potential therapeutic agent in an animal model of pre-eclampsia. Methods: Firstly, a systematic review was undertaken to examine the predictive accuracy of metabolomics for the prediction of small for gestational age babies. The original search was conducted in February 2018 and the results are presented in Chapter 2. Secondly, we investigated the metabolic pathways involved in the pathophysiology of small for gestation age (SGA) using untargeted ultra-performance liquid chromatography coupled to quadrupole time of flight mass spectrometry (UPLC-Q-TOF-MS). Plasma (Cork) and urine (Cork, Auckland) samples were collected at 20 weeks of gestation from pregnant women participating in the SCreening fOr Pregnancy Endpoints (SCOPE) study, an international study that recruited 5,628 nulliparous women, with a singleton low-risk pregnancy. Cases were women with SGA (customised birthweight ≤ 10th centile) matched to controls who had uncomplicated pregnancies, according to age (±5 years), body mass index (BMI, ±3.5 kg/m2), and ethnicity. All samples were analysed in untargeted positive and negative ion modes, using UPLC-Q-TOF-MS. Data were processed, features were ranked based on p-values from empirical Bayes analysis adjusted for multiple testing, and significant features (adjusted p-values <0.05 were searched for identification (HMDB, LipidMaps)). Thirdly, we aimed to decipher the lipidomics pathways involved in pathophysiology of spontaneous preterm birth (sPTB). Our analysis focused on plasma samples from SCOPE in Cork, collected at 20 weeks of gestation. Samples were profiled using semi-targeted liquid chromatography-mass spectrometry lipidomics, and lipids significantly altered between sPTB (n=16) and Control (n=32) groups were identified using empirical Bayes testing, adjusting for multiple comparisons. Significantly altered lipids (adj. p-values <0.05) were database searched for identifications (HMDB, LipidMaps). Fourthly, in Chapter 5, we performed a discovery lipidomics experiment to determine potential biomarkers of sPTB, in plasma samples taken at 15 weeks of gestation in women who participated in SCOPE in Cork and Auckland. Selected participants were women who has sPTB before 34 weeks of gestation (n=16 from Cork, and n=23 from Auckland), matched to women who had an uncomplicated pregnancy (n=39) according to age (±5 years) and BMI (± 3 kg/m2). Lipidomics analysis was performed using UPLC-Q-TOF-MS. Statistical analysis using empirical Bayes, adjusted for multiple testing was used to create a list of potential biomarkers. Five potential biomarkers were selected for validation based on statistical analysis, and their identification was validated using standard mix and UPLC coupled to triple quadrupole mass spectrometer (TQ-MS) analyses. Their prediction potential was tested using samples taken at 15 and 20 weeks of gestation from women from SCOPE Cork who had sPTB before 37 weeks of gestation (n=54) matched to women who had an uncomplicated pregnancy (controls, n=108). In addition, plasma collected at time of delivery (ToD) was also analysed for six cases and their 12 matching controls. Cases were matched to controls according to age (±5 years) and BMI (± 3 kg/m2). Samples were analysed using UPLC-TQ-MS, and statistical analysis was performed using independent T tests on normalised data. In addition, independent T tests were performed to determine if the levels of each target were significantly different between cases and controls at each time point (15 or 20 weeks). We defined significance as p-value <0.05. Finally, in chapter 6 we performed metabolomics analysis of plasma from experiments examining L-Ergothioneine treatment in the Reduced Uterine Perfusion Pressure (RUPP) rat model of pre-eclampsia. The effect of L-Ergothioneine (ET) treatment was explored using in vivo treatment in rats: Sham control (SC, n=5), RUPP control (RC, n=5), Sham + ET (ST, n=5), RUPP + ET (RT, n=5). Metabolic profiles of plasma samples were obtained using UPLC-Q-TOF-MS, and statistical analysis of the data was performed on normalised data, using independent T tests adjusted with false discovery rate (FDR) to compare RC to SC, RT to RC and RT to ST. Metabolites significantly altered (FDR <0.05) were putatively identified through database search (HMDB). Results: The systematic review presented in Chapter 2 examining the predictive accuracy of metabolomics for small for gestational age babies showed that to date no combination of metabolites are able to predict small for gestational age accurately. However, the review revealed the potential of investigating lipids pathways, their involvement in the pathophysiology of small for gestational age, and their high predictive potential. The metabolomic studies performed on urine samples and reported in Chapter 3, showed lower levels of 4 metabolites of interest (sulfolithocholic acid, estriol-16-Glucuronide, Neuromedin N (1-4), and 4-Hydroxybenzaldehyde) in Cork were associated with SGA at 20 weeks of gestation, but not in Auckland samples. These urinary metabolites are associated with detoxification, nutrient transport and absorption pathways. The lipidomics analysis performed on plasma samples showed that higher levels of several glycerophospholipids (3 phosphatidylethanolamines, 5 phosphatidylserines, 3 phosphatidylcholines, 1 lyso phosphatidylcholine, 1 phosphatidylglycerophosphate, 1 lyso phosphatidylglycerophosphate, 2 phosphatidylinositols, 2 phosphatidylglycerophosphates, and 3 phosphatidylglycerols) in at 20 weeks of gestation were associated with the development of SGA in the Cork participants of the SCOPE pregnancy cohort. Chapter 4 demonstrated that twenty-six lipids showed lower levels in sPTB compared to controls (adjusted p <0.05), including 20 glycerophospholipids (12 phosphatidylcholines, 7 phosphatidylethanolamines, 1 phosphatidylinositol) and 6 sphingolipids (2 ceramides and 4 sphingomyelines). In addition, a diaglyceride, DG (34:4), was detected in higher levels in sPTB compared to controls. In Chapter 4, we reported that reduced levels of phospholipids (glycerophospholipids and sphingolipids) are associated with the pathophysiology of sPTB. In the UPLC-Q-TOF-MS discovery phase of the study presented in Chapter 5, a list of 120 potential lipid biomarkers were reported. Most were tentatively identified as glycerophospholipids and detected in lower levels in sPTB. From this list of features, 5 potential biomarkers predictive of sPTB were selected and used in a targeted UPLC-TQ-MS analysis. The results obtained showed that two of the targets showed significant differences between cases and controls and over time (between 15 and 20 weeks of gestation), PC (15:0/22:6) and TG (18:3/18:2/18:3). In Chapter 6, using untargeted UPLC-Q-TOF-MS, we tested the effect of L-Ergothioneine (ET) as a potential therapeutic agent for the treatment of pre-eclampsia in the RUPP rat model. We reported significantly higher levels of L-palmitoylcarnitine, fatty acyl substrate involved in beta-oxidation in the mitochondria, in RUPP rats compared to Sham rats. When comparing plasma metabolic profiles of RUPP + ET rats to RUPP rats, we reported 10 metabolites associated with inflammation significantly altered (FDR <0.05, e.g. 20-COOH-leukotriene E4). Glutamylcysteine, a metabolite associated with oxidative stress, was detected at significantly higher levels (FDR <0.05) when comparing RUPP + ET rats to RUPP rats, and RUPP + ET rats to Sham + ET rats. These results show that the therapeutic properties of L-Ergothioneine might be related to mitochondrial function preservation, by attenuating inflammatory response evident in pre-eclampsia in addition to increasing antioxidant levels. Conclusions: Overall, these results show that glycerophospholipids appear to play a key role in the pathophysiology of SGA and sPTB, and dysregulated glycerophospholipids are potential makers of adverse pregnancy outcomes. Further research is needed to understand their precise associations, whether they are a cause or effect of SGA and sPTB, as well as to validate their potential as predictive biomarkers in independent pregnancy cohorts. In addition, we have shown that the use of L-Ergothioneine for the treatment of pre-eclampsia in the RUPP rat model reduces the oxidative stress induced by pre-eclampsia, via amino acid and glycerophospholipids metabolism pathways. Future work should focus on a testing L-Ergothioneine as a treatment for pre-eclampsia in a clinical trial. This thesis has demonstrated the potential for metabolomics to help understand the pathophysiology of adverse pregnancy outcomes and has explored its use in assessing biological pathways, predictive biomarkers and potential therapeutic pharmacological interventions. To date results are limited with significant further validation required.
Area-level deprivation as a risk factor for stillbirth in upper-middle and high-income countries: A scoping review
(Elsevier B.V., 2025-12-06) Keane, Jessica; Robinson, Laura A.; Greene, Richard A.; Corcoran, Paul; Leitao, Sara
Background: Socioeconomic deprivation has been associated with health inequalities and poor perinatal outcomes. Deprivation is described as a multidimensional concept, with composite indicators (e.g. area-based) developed internationally to study population health. Aim: This scoping review aims to examine published literature on the relationship between area-level deprivation and stillbirth in upper-middle to high-income countries. Methods: The Joanna Briggs Institute methodology for scoping reviews was utilised. The research question based on the Population (studies that examined stillbirth) Concept (area-level deprivation and its impact on stillbirth) Context (upper-middle- to high-income countries) framework. Six scientific databases were searched. Results were screened and reference lists searched to identify relevant literature. Data extraction on study characteristics and evidence of association provided was completed and a narrative summary reported the main findings. Results: A total of 29 studies were included, from 9 countries (majority UK-based: n = 20) published between 1998 and 2023. A variety of composite deprivation indices were utilised, the UK's Index of Multiple Deprivation (IMD) was the most common (n = 8), followed by the Townsend and Jarman indices (n = 6 and n = 3, respectively). Income, employment, education and access to services were the most common factors included as measures of deprivation in the indices. Twenty-two of the 29 studies (75.9%) showed positive correlations between stillbirth and areas identified more socioeconomically deprived. Conclusion: This review suggests that area-level deprivation seems an influencing factor on stillbirth in upper-middle to high-income countries. Focused initiatives to reduce stillbirth among those at higher deprivation related risk may be useful in improving maternal and perinatal outcomes.
Ascertaining women’s preferred mode of address and preferred choice of title during pregnancy and childbirth
(Irish Medical Organisation, 2005-02) Horgan, Richard P.; Guha, S.; O'Sullivan, K.; Higgins, John R.
To determine how women in pregnancy would like to be addressed and to ascertain their preferred choice of title during pregnancy. A questionnaire was administered to 925 antenatal women. Midwifery and medical staff (183) were invited to respond to a similar questionnaire.The response rate was 71.2% from the survey of pregnant women. The vast majority (82.1%) preferred to be addressed by their first name. Women were in favour of being called ’patient’ (32.8%) as their first choice. The staff survey yielded a response rate of 77%. The majority (81.8%) of health professionals preferred to address women by their first name. ’Mother’ (28.7%) was the most popular first choice. We conclude that women in pregnancy do have a preference on how they would like to be addressed and this is predominantly by first name. Health professionals also prefer to call pregnant women by their first name. The term ’patient’ was the most popular first choice of title of women in pregnancy but the term ’mother’ was the preferred choice of the health professionals. Medical staff were more likely to choose ’patient’ than midwives.
The association between caesarean section and cognitive ability in childhood
(Springer, 2019-10-22) Hanrahan, Michael; McCarthy, Fergus P.; O'Keeffe, Gerard W.; Khashan, Ali S.
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.
Association between caesarean section delivery and obesity in childhood: a longitudinal cohort study in Ireland
(BMJ Publishing Group, 2019-03-15) Masukume, Gwinyai; McCarthy, Fergus P.; Baker, Philip N.; Kenny, Louise C.; Morton, Susan M. B.; Murray, Deirdre M.; Hourihane, Jonathan O'B.; Khashan, Ali S.; Health Research Board; National Children’s Research Centre, Ireland; Food Standards Agency, United Kingdom
Objectives: To investigate the association between caesarean section (CS) birth and body fat percentage (BF%), body mass index (BMI) and being overweight or obese in early childhood. Design: Prospective longitudinal cohort study. Setting: Babies After Screening for Pregnancy Endpoints: Evaluating the Longitudinal Impact on Neurological and Nutritional Endpoints cohort. Participants: Infants born to mothers recruited from the Screening for Pregnancy Endpoints study, Cork University Maternity Hospital between November 2007 and February 2011.Outcome measure: Overweight or obese defined according to the International Obesity Task Force criteria.Results: Of the 1305 infants, 362 (27.8%) were delivered by CS. On regression analysis, BF% at 2 months did not differ significantly by delivery mode. Infants born by CS had a higher mean BMI at 6 months compared with those born vaginally (adjusted mean difference=0.24; 95% CI 0.06 to 0.41, p value=0.009). At 2 years, no difference was seen across the exposure groups in the risk of being overweight or obese. At 5 years, the association between prelabour CS and the risk of overweight or obesity was not statistically significant (adjusted relative risk ratio, aRRR=1.37; 95% CI 0.69 to 2.69) and the association remained statistically nonsignificant when children who were macrosomic at birth were excluded from the model (aRRR=0.86; 95% CI 0.36 to 2.08).Conclusion: At 6 months of age, children born by CS had a significantly higher BMI but this did not persist into future childhood. There was no evidence to support an association between mode of delivery and long-term risk of obesity in the child.
Association between hypertensive disorders of pregnancy and the risk of asthma, eczema and allergies in offspring: A systematic review and meta-analysis
(John Wiley & Sons, Inc., 2020-10-09) Conlan, Nicola; Maher, Gillian M.; Al Khalaf, Sukainah; McCarthy, Fergus P.; Khashan, Ali S.; Health Research Board
Objective: Conduct a systematic review and meta‐analysis examining the association between hypertensive disorders of pregnancy (HDP) and risk of asthma, eczema, food allergies and allergic rhinitis in the offspring. Design: A systematic review and random‐effects meta‐analyses were used to synthesize the published literature. PRISMA guidelines were followed throughout. Two independent reviewers carried out data extraction and quality assessment of included studies. Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to assess certainty of findings. Data Sources: A systematic search of PubMed, Embase, Web of Science and CINAHL was performed from inception of databases‐21 April 2020, supplemented by hand‐searching reference lists of included articles. Eligibility Criteria: Two reviewers independently reviewed titles, abstracts and full‐text articles. English language, cohort, case‐control and cross‐sectional published studies examining the association between HDP (primary exposure: pre‐eclampsia; secondary exposures: all other HDP) and asthma, eczema, food allergies and allergic rhinitis were included. Results: Of the 2833 studies retrieved, 14 studies met inclusion criteria. Of these, 11 studies reported evidence of association between HDP and atopic disorders. Thirteen studies reported estimates for asthma. Seven of these included adjusted estimates (including 3 645 773 participants) for a pre‐eclampsia‐asthma relationship resulting in a pooled odds ratio (OR) of 1.14 (95% CI: 1.04, 1.26) (I2 = 62%). However, this OR was reduced to 1.08 (95% CI: (0.78, 1.48) when the large registry‐based cohort studies were excluded, and only studies using parent‐reported measures to determine a diagnosis of asthma were included. Four studies included adjusted estimates (including 254 998 participants) for other HDP and asthma (pooled OR: 1.02, 95% CI: 0.96, 1.09) (I2 = 0%). Two studies provided adjusted estimates (including 1 699 663 participants) for a pre‐eclampsia‐eczema relationship (pooled OR: 1.06, 95% CI: 0.98, 1.14) (I2 = 0%). One study including pre‐eclampsia‐food allergies was identified (OR: 1.28, 95% CI: 1.11, 1.46). Three studies examined a HDP (including pre‐eclampsia) and allergic rhinitis relationship, with effect estimates ranging from 1.14 to 2.10. Studies were classified as low or low‐moderate risk of bias, while GRADE certainty of findings were low to very low. Conclusions: While pre‐eclampsia was associated with a possible increased risk of asthma in offspring, there was no evidence for a relationship between other HDP and asthma. There is a lack of published literature examining the association between HDP and eczema, food allergy and allergic rhinitis. Further primary research is warranted to gain a better understanding of the association between HDP and the risk of childhood atopic disease.
At what price? A cost-effectiveness analysis comparing trial of labour after previous caesarean versus elective repeat caesarean delivery
(Public Library of Science, 2013-03-06) Fawsitt, Christopher G.; Bourke, Jane; Greene, Richard A.; Everard, Claire M.; Murphy, Aileen; Lutomski, Jennifer E.; National Perinatal Epidemiology Centre, College of Medicine and Health, University College Cork
Background: Elective repeat caesarean delivery (ERCD) rates have been increasing worldwide, thus prompting obstetric discourse on the risks and benefits for the mother and infant. Yet, these increasing rates also have major economic implications for the health care system. Given the dearth of information on the cost-effectiveness related to mode of delivery, the aim of this paper was to perform an economic evaluation on the costs and short-term maternal health consequences associated with a trial of labour after one previous caesarean delivery compared with ERCD for low risk women in Ireland.Methods: Using a decision analytic model, a cost-effectiveness analysis (CEA) was performed where the measure of health gain was quality-adjusted life years (QALYs) over a six-week time horizon. A review of international literature was conducted to derive representative estimates of adverse maternal health outcomes following a trial of labour after caesarean (TOLAC) and ERCD. Delivery/procedure costs derived from primary data collection and combined both "bottom-up" and "top-down" costing estimations.Results: Maternal morbidities emerged in twice as many cases in the TOLAC group than the ERCD group. However, a TOLAC was found to be the most-effective method of delivery because it was substantially less expensive than ERCD ((sic)1,835.06 versus (sic)4,039.87 per women, respectively), and QALYs were modestly higher (0.84 versus 0.70). Our findings were supported by probabilistic sensitivity analysis.Conclusions: Clinicians need to be well informed of the benefits and risks of TOLAC among low risk women. Ideally, clinician-patient discourse would address differences in length of hospital stay and postpartum recovery time. While it is premature advocate a policy of TOLAC across maternity units, the results of the study prompt further analysis and repeat iterations, encouraging future studies to synthesis previous research and new and relevant evidence under a single comprehensive decision model.
Audit of antenatal clinic for high-risk obstetric patients; activity and outcomes
(Irish Medical Organization, 2007-10) Allen, C.; Greene, Richard A.; Higgins, John R.
A specialised clinic for the antenatal care of high-risk patients was established in Cork in January 2004. It is led by 2 specialists in materno-fetal medicine and provides care for patients from a large catchment area. Small clinic numbers, specialised midwives, ready access to medical experts and fetal assessment facilities, facilitate an efficient use of resources. We report on the experience and outcomes of this clinic after the first year in operation. A database was set up to store relevant information on patients who attended the clinic in 2004. 143 patients attended. Risk categories included maternal medical disease (62%); multiple pregnancy (11%); previous poor obstetric history (10%); fetal anomaly (8%). Average gestation; 35.9 weeks, average birth weight; 2598g. Caesarean section rate; 41%. Perinatal mortality rate 67 per 1000 (uncorrected); and 20% neonates required NICU care. This approach to highrisk obstetric care resulted in favourable outcomes. The management strategy applied in Cork may be a suitable prototype for comparable areas throughout Ireland.
Axis of placental ageing in adverse pregnancy outcomes
(University College Cork, 2023) Manna, Samprikta; McCarthy, Fergus; McCarthy, Cathal; European Chiropractors' Union
Background: Pre-eclampsia (PE), an adverse pregnancy outcome affects 2-5% pregnancies worldwide and significantly adversely impacts both maternal and fetal outcomes. Intrauterine growth restriction (IUGR) is defined as the inability of the fetus to reach normal growth potential within the uterus as a result of various genetic, environmental, or placental factors. Premature ageing of the placenta in pregnancy outcomes such as PE and IUGR is associated with the persistent presence of oxidative stress and placental insufficiency reducing its functional capacity. Placental proteomics has been instrumental in improving our understanding of molecular mechanisms involved in the pathophysiology of placental insufficiency as well as identifying biomarkers to predict and diagnose pregnancy outcomes. In this study, we investigated cellular senescence phenotypes of PE and IUGR pregnancies by simultaneously measuring several biomarkers of senescence, as well as the proteomic signature of the placenta in healthy and adverse pregnancy outcomes PE and IUGR. Method: Maternal plasma and placental samples were collected at term (>37 weeks) and preterm (<37 weeks) gestation from nulliparous women undergoing prelabour elective Caesarean section with PE without intrauterine growth restriction (PE; n=5), PE associated with intrauterine growth restriction (n=8), intrauterine growth restriction (IUGR <10th centile) (n=6) and age-matched controls (n=20) from Cork University Maternity Hospital, Cork, Ireland. To assess cellular senescence absolute telomere length (aTL) and senescence associated genes in the placentas was performed by RTqPCR. Cyclin-dependent kinase inhibitors (p21 and p16) expression were determined by Western blotting. Senescence Associated Secretory Phenotype (SASP) were evaluated in maternal plasma by multiplex ELISA assay. Proteomic analysis of placental samples dissected into 3 sub-anatomical regions (maternal, middle, fetal) taken from 3 nulliparous healthy placentas was performed by mass-spectrometry and pathway analysis was conducted. Based on the differentially expressed proteins (DEPs), a placenta specific disease map using NaviCenta focusing on functional analysis to include the placenta specific context for healthy (n=4) compared to PE affected (n=4) and IUGR affected (n=4) placentas. Results: Placental expression of senescence associated genes CHEK1, PCNA, PTEN, CDKN2A, CCNB-1 was significantly upregulated in PE, while TBX-2, PCNA, ATM and CCNB-1 expression were significantly decreased in IUGR compared to controls. Moreover, placental p16 protein expression was significantly decreased in PE only when compared to controls placentas. We also observed that IL-6 was significantly increased in maternal circulation in PE when compared to controls; while IFN-γ was significantly increased in maternal circulation in women affected with IUGR when compared to controls. Proteomic profiling of healthy placentas divided into three sub-anatomical regions identified 1081, 1086, and 1101 proteins in maternal, middle, and fetal sub-anatomical regions respectively. Depending on sample site location and sub-anatomical regions, 374 differentially expressed proteins (DEP) were identified. When we investigated the proteomic variations between PE and IUGR placentas when compared to controls we observed 314, 391, and 378 proteins in healthy control, PE, and IUGR placenta, respectively. We performed functional analysis by combining ClusterCompare and NaviCenta to analyse a placenta-centric context, and observed regulatory elements predominantly involved in the immune regulation, complement cascade and antioxidant activities in PE and IUGR compared to control placentas. Conclusion: This thesis provides evidence of premature senescence in IUGR, while in PE, evidence of activated cell cycle checkpoint regulators is suggestive of cellular repair and proliferation rather than progression to cellular senescence. The heterogeneity within senescence molecular markers of these phenotypes highlights the complexity and disparity between pathophysiological insults unique to each obstetric complication. Proteomic profiling of sub-anatomical placental regions highlighted the variabilities between regions particularly providing evidence of senescence in these regions. Placental proteomic mapping of healthy placentas compared to adverse pregnancy outcomes PE and IUGR revealed the importance of complement system, inflammatory response, and antioxidant activity in placental function in PE placentas. The identification of novel targets such as transcription factor activity and synergistic miRNAs elements within the core regulatory network, might enlighten future placental research within adverse pregnancy outcomes.
Beyond the numbers: Impact of obesity on obstetric anal sphincter injury (OASI) outcomes in women
(John Wiley and Sons Inc, 2025) Rotem, Reut; Galvin, Daniel; McCormack, Kate; O'Sullivan, Orfhlaith E.; Hayes-Ryan, Deirdre
Objective: To compare the risk profiles, anatomical, and functional outcomes between obese and non-obese women who experienced obstetric anal sphincter injury (OASI). Methods: A retrospective electronic database study was conducted at Cork University Maternity Hospital (CUMH). Women with missing data/repairs conducted outside CUMH were excluded. Participants were categorized into obese (BMI ≥30 kg/m2) and non-obese (BMI <30 kg/m2) groups. Primary measure was a composite adverse outcome assessed 6 months post-delivery, including one or more of the following: resting pressure <40 mmHg, squeezing pressure <100 mmHg, defects in the internal and/or external anal sphincter. Statistical analyses were performed using SPSS version 28. Results: Among the 349 women included in the study, 285 (81.7%) had a BMI <30 kg/m2 and 64 (18.3%) had a BMI ≥30 kg/m2. Gestational diabetes was significantly higher in obese women. No significant differences were observed in newborn weight or mode of delivery. The majority of tears were classified as grade 3B in both groups. Attendance rates at the OASI clinic did not differ between the groups. Among those attending, no statistical differences were noted in manometry results, which were reduced in both groups. Rates of internal anal sphincter defects were lower in the obese group (7.0% vs 15.6%, P = 0.15) and external anal sphincter defects were significantly lower in obese women (0% vs 9.1%, P = 0.04). No difference was found in the rates of composite adverse outcomes between the groups. Conclusion: Functional outcomes and manometry results did not differ, but non-obese women had higher rates of anatomical defects in OASI, requiring further study. © 2024 The Author(s). International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.
Birth by caesarean section and school performance in Swedish adolescents- a population-based study
(BioMed Central, 2017-04-17) Curran, Eileen A.; Kenny, Louise C.; Dalman, Christina; Kearney, Patricia M.; Cryan, John F.; Dinan, Timothy G.; Khashan, Ali S.; Science Foundation Ireland; Health Research Board; Brain and Behavior Research Foundation; European Commission; Seventh Framework Programme
Background: Our objective was to assess the impact of obstetric mode of delivery, and in particular birth by Caesarean section (CS), on school performance in adolescents using a large, population-based cohort. Methods: We extracted data from the Swedish Medical Birth Register and National School Register. We included all live singleton births in Sweden from 1982–1995 (n = 1,489,925). School grades were reported on a scale from 0 to 320, scores less than 160 (i.e. “pass”) were considered to be “poor school performance.” Mode of delivery was categorised as: unassisted vaginal delivery (VD), assisted VD, elective CS and emergency CS. We measured the association between mode of delivery and “poor school performance” using logistic regression. We then used quantile regression to assess the association between mode of delivery and school performance across the distribution of scores. We adjusted for maternal age, parity, small and large for gestational age, gestational age, maternal country of birth, maternal depression, non-affective disorder or bipolar disorder, parental income at time of birth, and parental social welfare at time of birth. We also conducted sensitivity analyses to investigate the association further. Results: With logistic regression analysis, the adjusted odds ratio (aOR) of assisted VD and poor school performance, compared to unassisted VD, was 1.06 (95% CI: 1.03–1.08). For elective CS it was 1.06 (95% CI:1.03-1.09) and for emergency CS it was 1.12 (95% CI: 1.09–1.15). With quantile regression, assisted VD showed little difference in scores, when compared to unassisted VD, at any point across the distribution. Elective CS was associated with a 1–3 point decrease in scores, and emergency CS was associated with a 2–5 point decrease in scores. Conclusion: A slight association was found between birth by CS and school performance. However, the effect was quite small and given the complex nature of the relationship, should be interpreted with caution.
Withdrawn
Caesarean delivery and subsequent pregnancy interval: a systematic review and meta-analysis
Caesarean section and subsequent pregnancy outcome: a Danish register-based cohort study
(University College Cork, 2014) O'Neill, Sinéad M.; Agerbo, Esben; Kenny, Louise C.; Greene, Richard A.; Kearney, Patricia M.; Khashan, Ali S.; National Perinatal Epidemiology Centre, College of Medicine and Health, University College Cork; Health Research Board
Background and Aims: Caesarean section rates have increased in recent decades and the effects on subsequent pregnancy outcome are largely unknown. Prior research has hypothesised that Caesarean section delivery may lead to an increased risk of subsequent stillbirth, miscarriage, ectopic pregnancy and sub-fertility. Structure and Methods: Papers 1-3 are systematic reviews with meta-analyses. Papers 4-6 are findings from this thesis on the rate of subsequent stillbirth, miscarriage, ectopic pregnancy and live birth by mode of delivery. Results Systematic reviews and meta-analyses: A 23% increased odds of subsequent stillbirth; no increase in odds of subsequent ectopic pregnancy and a 10% reduction in the odds of subsequent live birth among women with a previous Caesarean section were found in the various meta-analyses. Danish cohorts: Results from the Danish Civil Registration System (CRS) cohort revealed a small increased rate of subsequent stillbirth and ectopic pregnancy among women with a primary Caesarean section, which remained in the analyses by type of Caesarean. No increased rate of miscarriage was found among women with a primary Caesarean section. In the CRS data, women with a primary Caesarean section had a significantly reduced rate of subsequent live birth particularly among women with primary elective and maternal-requested Caesarean sections. In the Aarhus Birth Cohort, overall the effect of mode of delivery on the rate and time to next live birth was minimal. Conclusions: Primary Caesarean section was associated with a small increased rate of stillbirth and ectopic pregnancy, which may be in part due to underlying medical conditions. No increased rate of miscarriage was found. A reduced rate of subsequent live birth was found among Caesarean section in the CRS data. In the smaller ABC cohort, a small reduction in rate of subsequent live birth was found among women with a primary Caesarean section and is most likely due to maternal choice rather than any ill effects of the Caesarean. The findings of this study, the largest and most comprehensive to date will be of significant interest to health care providers and women globally.
Caesarean section delivery and childhood obesity
(University College Cork, 2020-07-17) Masukume, Gwinyai; Khashan, Ali; McCarthy, Fergus; Kenny, Louise C.; O’Neill, Sinéad M.; Baker, Philip N.; Morton, Susan M.B.; Science Foundation Ireland
Background and aims: Caesarean section (CS) birth, in particular elective/planned CS, has been found to be associated with an increased risk of childhood obesity. Various mechanisms that differ by birth mode, including differences in the vaginal and faecal microflora and stress hormone concentration have been suggested to underpin this association. The literature describing this association, often derived from non-nationally representative cohorts has been inconsistent, limited by small sample size, often unable to distinguish between elective and emergency CS, have publication bias favouring positive effects and often unable to adjust for key confounders like maternal pre-pregnancy body mass index (BMI). Given the rising global use of CS with some countries having CS rates above 50%, the aim of this thesis was to critically evaluate the association between CS birth and childhood obesity and to use three large contemporary nationally representative prospective longitudinal cohort studies and one smaller cohort, with detailed phenotypic data, to investigate this association. Structure and methods: The existing published literature relating to CS birth and childhood obesity was critically evaluated and synthesised to identify major conceptual themes and research gaps (Chapter 1). Chapter 2 details and justifies the thesis’ methodological approach. The following four longitudinal birth cohort studies were utilised: Screening for Pregnancy Endpoints (SCOPE) and Babies After SCOPE: Evaluating the Longitudinal Impact on Neurological and Nutritional Endpoints (BASELINE); Growing Up in Ireland (GUI); Growing Up in New Zealand (GUiNZ) and the Millennium Cohort Study (MCS) cohorts. In order to facilitate comparison between different cohorts (Chapters 3 through to 7), children were classified, on the basis of their BMI, as obese, overweight, normal or underweight according to the sex and age specific International Obesity Task Force criteria. A range of statistical analytic approaches including linear, multinomial and mixed-effects regression were employed. Multiple imputation was used to handle substantial missing data. In addition to our primary outcome BMI, which was modeled as continuous or categorical variable, the association between our exposure CS birth and BF% was investigated in cohorts that had this data available. Where the sample size permitted, the association between CS birth and transition into or out of obesity was examined. The overall results in the context of the published literature were discussed including limitations and strengths and future research directions (Chapter 7). Results: SCOPE-BASELINE cohorts: At two months of age, children born by CS, had a similar BF% to those born vaginally. At age six months, children born by CS had a significantly higher BMI, adjusted mean difference=0.24; 95% confidence interval (CI) 0.06 to 0.41, but this did not persist into future childhood, at age five years. There was no evidence to support an association between mode of delivery and long-term risk of obesity in the child. GUI cohort: We found insufficient evidence to support a relationship between elective CS and childhood obesity at age three and five years. An increased risk of obesity in children born by emergency CS, adjusted relative risk ratio (aRRR) = 1.56; [95% CI 1.20 to 2.03], but not elective, suggests that the influence of vaginal microflora in developing childhood obesity was minimal. The association with emergency CS was likely due to its indications. GUiNZ cohort: Planned CS was an independent predictor of obesity in early childhood at age two years aRRR=1.59; [95% CI 1.09 to 2.33] but this association was not apparent by four and a half years This suggests that birth mode is associated with early growth, at least in the short term. This association occurred during a critical phase of human development, the first two years of life. Given the developmental origins of health and disease hypothesis this may lead to long-term detrimental cardiometabolic changes. MCS cohort: Infants born by planned CS did not have a significantly higher BMI at ages three, five, seven, eleven and fourteen years adjusted mean difference=0.00; [95% CI -0.10 to 0.10], or BF% at ages seven 0.13; [95% CI -0.23; 0.49] and fourteen compared to those born by normal VD. This may suggest that the association, described in the literature, could be due to the indications/reasons for CS birth or residual confounding. Conclusions: The hallmark finding of the thesis was an association between CS birth in general, elective CS in particular, and childhood obesity during the first two years of life. This association had dissipated by age three through to fourteen. Whether this association remerges in adulthood or is a risk factor for cardiometabolic disease is an area for future research. The association observed with emergency CS is possibly due to confounding by the underlying reasons for CS, confounding by indication. There is potential to improve consistency and robustness in this research field by better and standardised definition particularly of the exposure, CS birth. Better consistency in the timing of obesity assessment is also warranted.

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