Obstetrics & Gynaecology - Journal articles

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    Maternal hypertensive disorders of pregnancy and depression or anxiety in adolescence: Findings from the Millennium Cohort Study - a reply
    (Elsevier, 2024-03-19) Keenan, Martin; Khashan, Ali S.; O'Byrne, Laura J.; O'Keeffe, Gerard W.; Al Khalaf, Sukainah; Maher, Gillian M.
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    Maternal hypertensive disorders of pregnancy and depression or anxiety in adolescence: Findings from the Millennium Cohort Study
    (Elsevier, 2023-11-18) Keenan, Martin; Khashan, Ali S.; O'Byrne, Laura J.; O'Keeffe, Gerard W.; Al Khalaf, Sukainah; Maher, Gillian M.
    Background: The short-term effects of hypertensive disorders of pregnancy (HDP) on the health of the fetus are well known; however, their impacts on the risk of mental health in the exposed offspring are not fully understood. Our aim was to examine the association between HDP and depression/anxiety at age 17 years. Methods: We used data from The Millennium Cohort Study, a nationally representative longitudinal study of children born in the United Kingdom. Data on HDP and potential confounders were collected when children were 9-months. Data on depression and anxiety were collected as one variable when children were aged 17 years using self-reported doctor diagnosis, and reclassified as depression/anxiety (overall), depression/anxiety with treatment, and depression/anxiety without treatment. Crude and adjusted logistic regression models were performed to examine the association between HDP and depression/anxiety, adjusting for several maternal and socio-economic factors. Results: There were 9517 singleton mother-child pairs included in the analyses. Adjusted logistic regression suggested an association between HDP and depression/anxiety (adjusted odds ratio, (aOR):1.30 [95 % CI, 1.02–1.66]) at age 17 years. A similar association was observed for HDP and depression/anxiety with treatment (aOR:1.33 [95 % CI, 1.01–1.73]) and HDP and depression/anxiety without treatment (aOR: 1.30 [95 % CI, 0.80–2.12]), although the latter did not reach statistical significance. Limitations: Data on severity and classifications of HDP were not available. Conclusion: Exposure to HDP may be associated with an increased likelihood of depression or anxiety at age 17 years. Future research should consider severity and different classifications of HDP.
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    Maternal mid-gestation cytokine dysregulation in mothers of children with autism spectrum disorder
    (Springer, 2021-09-09) Casey, Sophie; Carter, Michael; Looney, Ann-Marie; Livingstone, Vicki; Moloney, Gerard M.; O'Keeffe, Gerard W. ; Taylor, Rennae S.; Kenny, Louise C.; McCarthy, Fergus P.; McCowan, Lesley M. E.; Thompson, John M. D.; Murray, Deirdre M.; SCOPE Consortium; Irish Research Council; National Children's Research Centre, Ireland; Health Research Board; Science Foundation Ireland; Health Research Board of Ireland; New Enterprise Research Fund, New Zealand; Foundation for Research, Science and Technology; Health Research Council of New Zealand; Evelyn Bond Fund, New Zealand; Auckland District Health Board Charitable Trust, New Zealand
    Autism spectrum disorder (ASD) is a developmental disorder characterised by deficits in social interactions and communication, with stereotypical and repetitive behaviours. Recent evidence suggests that maternal immune dysregulation may predispose offspring to ASD. Independent samples t-tests revealed downregulation of IL-17A concentrations in cases, when compared to controls, at both 15 weeks (p = 0.02), and 20 weeks (p = 0.02), which persisted at 20 weeks following adjustment for confounding variables. This adds to the growing body of evidence that maternal immune regulation may play a role in foetal neurodevelopment.
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    Maternal pre-eclampsia serum increases neurite growth and mitochondrial function through a potential IL-6-dependent mechanism in differentiated SH-SY5Y cells
    (Frontiers Media, 2023-01-12) Barron, Aaron; Manna, Samprikta; McElwain, Colm J.; Musumeci, Andrea; McCarthy, Fergus P.; O'Keeffe, Gerard W.; McCarthy, Cathal M.; Irish Research Council; Science Foundation Ireland; Health Research Board
    Pre-eclampsia (PE) is a common and serious hypertensive disorder of pregnancy, which affects 3%-5% of first-time pregnancies and is a leading cause of maternal and neonatal morbidity and mortality. Prenatal exposure to PE is associated with an increased risk of neurodevelopmental disorders in affected offspring, although the cellular and molecular basis of this increased risk is largely unknown. Here, we examined the effects of exposure to maternal serum from women with PE or a healthy uncomplicated pregnancy on the survival, neurite growth and mitochondrial function of neuronally differentiated human SH-SY5Y neuroblastoma cells, which are commonly used to study neurite growth. Neurite growth and mitochondrial function are two strongly linked neurodevelopmental parameters in which alterations have been implicated in neurodevelopmental disorders. Following this, we investigated the pleiotropic cytokine interleukin-6 (IL-6) levels as a potential mechanism. Cells exposed to 3% (v/v) PE serum for 72 h exhibited increased neurite growth ( < 0.05), which was validated in the human neural progenitor cell line, ReNcell VM ( < 0.01), and mitochondrial respiration (elevated oxygen consumption rate ( < 0.05), basal mitochondrial respiration, proton leak, ATP synthesis, and non-mitochondrial respiration) compared to control serum-treated cells. ELISA analysis showed elevations in maternal IL-6 in PE sera ( < 0.05) and placental explants ( < 0.05). In support of this, SH-SY5Y cells exposed to 3% (v/v) PE serum for 24 h had increased phospho-STAT3 levels, which is a key intracellular mediator of IL-6 signalling ( < 0.05). Furthermore, treatment with anti-IL-6 neutralizing antibody blocked the effects of PE serum on neurite growth ( < 0.05), and exposure to IL-6 promoted neurite growth in SH-SY5Y cells ( < 0.01). Collectively these data show elevated serum levels of maternal IL-6 in PE, which increases neurite growth and mitochondrial function in SH-SY5Y cells. This rationalizes the further study of IL-6 as a potential mediator between PE exposure and neurodevelopmental outcome in the offspring.
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    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.