• The effects of maternal body mass index on pregnancy outcome.

      Khashan, A S; Kenny, L C; The Anu Research Centre, Department of Obstetrics and Gynaecology, Cork, University Maternity Hospital, University College Cork, Wilton, Cork, Ireland., a.khashan@ucc.ie (2012-01-31)
      The increasing prevalence of obesity is presenting a critical challenge to healthcare services. We examined the effect of Body Mass Index in early pregnancy on adverse pregnancy outcome. We performed a population register-based cohort study using data from the North Western Perinatal survey (N = 99,403 babies born during 2004-2006), based at The University of Manchester, UK. The main outcome measures were Caesarean section delivery, preterm birth, neonatal death, stillbirth, Macrosomia, small for gestational age and large for gestational age. The risk of preterm birth was reduced by almost 10% in overweight (RR = 0.89, [95% CI: 0.83, 0.95]) and obese women (RR = 0.90, [95% CI: 0.84, 0.97]) and was increased in underweight women (RR = 1.33, [95% CI: 1.16, 1.53]). Overweight (RR = 1.17, [95% CI: 1.09, 1.25]), obese (RR = 1.35, [95% CI: 1.25, 1.45]) and morbidly obese (RR = 1.24, [95% CI: 1.02, 1.52]) women had an elevated risk of post-term birth compared to normal women. The risk of fetal macrosomia and operative delivery increased with BMI such that morbidly obese women were at greatest risk of both (RR of macrosomia = 4.78 [95% CI: 3.86, 5.92] and RR of Caesarean section = 1.66 [95% CI: 1.61, 1.71] and a RR of emergency Caesarean section = 1.59 [95% CI: 1.45, 1.75]). Excessive leanness and obesity are associated with different adverse pregnancy outcomes with major maternal and fetal complications. Overweight and obese women have a higher risk of macrosomia and Caesarean delivery and lower risk of preterm delivery. The mechanism underlying this association is unclear and is worthy of further investigation.
    • The Expression of Inflammatory Mediators in Bladder Pain Syndrome.

      Offiah, Ifeoma; Didangelos, Athanasios; Dawes, John; Cartwright, Rufus; Khullar, Vik; Bradbury, Elizabeth J; O'Sullivan, Suzanne; Williams, Dic; Chessell, Iain P; Pallas, Kenny; et al. (European urology, 2016-08)
      Bladder pain syndrome (BPS) pathology is poorly understood. Treatment strategies are empirical, with limited efficacy, and affected patients have diminished quality of life.
    • Gitelman's syndrome in pregnancy: case report and review of the literature.

      McCarthy, Fergus P; Magee, Ciara N; Plant, William D; Kenny, Louise C; The ANU Research Centre, Department of Obstetrics and Gynaecology, University, College Cork, Cork University Maternity Hospital, Wilton, Cork., Fergus.mccarthy@ucc.ie (2012-01-31)
      Gitelman's syndrome (GS), a rare renal disorder, results in hypokalaemia, hypomagnesaemia, hypocalciuria and a metabolic alkalosis. It is unclear if an alteration in management is necessary or beneficial during pregnancy. A 32-year-old woman with GS was managed in her second pregnancy. Antenatally, the patient required 39 (principally day case) admissions to the hospital for intravenous (IV) therapy and received a cumulative total of 47 l of IV 0.9% saline solution, 47 doses of 20 mmol magnesium chloride and 46 doses of 80 mmol potassium chloride. She delivered a 2940-g female infant in excellent condition by caesarean section. We would suggest that close attention to maternal weight gain during pregnancy is an easily available clinical tool to assess adequacy of fluid and electrolyte repletion in this condition.
    • The impact of maternal celiac disease on birthweight and preterm birth: a Danish population-based cohort study.

      Khashan, A S; Henriksen, T B; Mortensen, P B; McNamee, R; McCarthy, F P; Pedersen, M G; Kenny, L C; Anu Research Centre, Department of Obstetrics and Gynecology, University College , Cork, Cork University Maternity Hospital, Cork, Ireland. a.khashan@ucc.ie (2012-01-31)
      BACKGROUND: Adverse pregnancy outcomes have been associated with maternal celiac disease (CD). In this study, we investigate the effect of treated and untreated maternal CD on infant birthweight and preterm birth. METHODS: A population-based cohort study consisted of all singleton live births in Denmark between 1 January 1979 and 31 December 2004 was used. A total of 1,504,342 babies were born to 836,241 mothers during the study period. Of those, 1105 babies were born to women with diagnosed CD and 346 were born to women with undiagnosed CD. Women with diagnosed CD were considered as treated with a gluten free diet while women with undiagnosed CD were considered as untreated. The outcome measures were: birthweight, small for gestational age (SGA: birthweight <10th centile), very small for gestational age (VSGA: birthweight <5th centile) and preterm birth. We compared these measures in treated and untreated women with those of a reference group (no history of CD). RESULTS: Women with untreated CD delivered smaller babies [difference = -98 g (95% CI: -130, -67)], with a higher risk of SGA infants [OR = 1.31 (95% CI: 1.06, 1.63)], VSGA infants [OR = 1.54 (95% CI: 1.17, 2.03)] and preterm birth [OR = 1.33 (95% CI: 1.02, 1.72)] compared with women without CD. Women with treated CD had no increased risk of reduced mean birthweight, risk of delivering SGA and VSGA infants or preterm birth compared with women without CD. CONCLUSION: Untreated maternal CD increases the risk of reduced birthweight, the risk of delivering SGA and VSGA infants and preterm birth. Diagnosis and presumed treatment of maternal CD with a gluten-free diet appeared to result in a birthweight and preterm birth rate similar to those in women without CD.
    • Life and death decisions for incompetent patients: determining best interests--the Irish perspective.

      Armstrong, K; Ryan, C A; Hawkes, C P; Janvier, A; Dempsey, E M; Department of Neonatology, Cork University Maternity Hospital, Cork, Ireland. (2011-04)
      To determine whether healthcare providers apply the best interest principle equally to different resuscitation decisions.
    • Life and death decisions for incompetent patients: determining best interests--the Irish perspective.

      Armstrong, K; Ryan, C A; Hawkes, C P; Janvier, A; Dempsey, E M; Department of Neonatology, Cork University Maternity Hospital, Cork, Ireland. (2012-01-31)
      AIMS: To determine whether healthcare providers apply the best interest principle equally to different resuscitation decisions. METHODS: An anonymous questionnaire was distributed to consultants, trainees in neonatology, paediatrics, obstetrics and 4th medical students. It examined resuscitation scenarios of critically ill patients all needing immediate resuscitation. Outcomes were described including survival and potential long-term sequelae. Respondents were asked whether they would intubate, whether resuscitation was in the patients best interest, would they accept surrogate refusal to initiate resuscitation and in what order they would resuscitate. RESULTS: The response rate was 74%. The majority would wish resuscitation for all except the 80-year-old. It was in the best interest of the 2-month-old and the 7-year-old to be resuscitated compared to the remaining scenarios (p value <0.05 for each comparison). Approximately one quarter who believed it was in a patient best interests to be resuscitated would nonetheless accept the family refusing resuscitation. Medical students were statistically more likely to advocate resuscitation in each category. CONCLUSION: These results suggest resuscitation is not solely related to survival or long-term outcome and the best interest principle is applied differently, more so at the beginning of life.
    • Midwives' experiences of facilitating normal birth in an obstetric-led unit: a feminist perspective.

      Keating, Annette; Fleming, Valerie E M; Centre of Midwifery Education, Fifth floor, Cork University Maternity Hospital,, Wilton, Cork, Ireland. Annette.Keating@mailp.hse.ie (2012-01-31)
      OBJECTIVE: to explore midwives' experiences of facilitating normal birth in an obstetric-led unit. DESIGN: a feminist approach using semi-structured interviews focusing on midwives' perceptions of normal birth and their ability to facilitate this birth option in an obstetric-led unit. SETTING: Ireland. PARTICIPATION: a purposeful sample of 10 midwives with 6-30 years of midwifery experience. All participants had worked for a minimum of 6 years in a labour ward setting, and had been in their current setting for the previous 2 years. FINDINGS: the midwives' narratives related to the following four concepts of patriarchy: 'hierarchical thinking', 'power and prestige', 'a logic of domination' and 'either/or thinking' (dualisms). Two themes, 'hierarchical thinking' and 'either/or thinking', (dualisms) along with their subthemes are presented in this paper. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: this study identified some of the reasons why midwives find it difficult to facilitate normal birth in an obstetric unit setting, and identified a need for further research in this area. Midwifery education and supportive management structures are required if midwives are to become confident practitioners of normal birth.
    • The natural history of anencephaly.

      Obeidi, Nidaa; Russell, Noirin; Higgins, John R; O'Donoghue, Keelin; Anu Research Centre, Department of Obstetrics and Gynaecology, University College, Cork, Cork University Maternity Hospital, Ireland. (2012-01-31)
      OBJECTIVE: Early elective termination of pregnancy is the most common outcome of a diagnosis of anencephaly in developed countries. Experience and expertise with management of ongoing pregnancies is limited. We aimed to investigate the natural history of these pregnancies from diagnosis to delivery and to determine timing of death. METHOD: A retrospective review of cases of anencephaly diagnosed between 2003 and 2009 in tertiary-referral university teaching hospitals in Cork. RESULTS: The majority of cases (25/26; 96%) were diagnosed prenatally at a median gestation of 21(+2) weeks (range 13(+4)-32(+4)). The median maternal age was 30 years (range 17-41) and 50% were primigravidae. Seven pregnancies were complicated by polyhydramnios and four deliveries were complicated by shoulder dystocia. The median gestation at delivery was 35 weeks (range 22(+5)-42(+6)); 69% of labours were induced at a median gestation of 34 weeks. Six women (6/26; 23%) had a pre-labour intrauterine fetal death and nine women (9/26; 35%) had an intrapartum fetal death. Median neonatal survival time was 55 min (range 10 min to 8 days). Six parents donated neonatal organs for transplantation. CONCLUSION: This study provides useful information for health professionals caring for patients with a diagnosis of anencephaly. The majority of these infants die prior to delivery but short-term survival is possible.
    • Pregnancy and the risk of autoimmune disease.

      Khashan, Ali S; Kenny, Louise C; Laursen, Thomas M; Mahmood, Uzma; Mortensen, Preben B; Henriksen, Tine B; O'Donoghue, Keelin; Anu Research Centre, Department of Obstetrics and Gynaecology, Cork University, Maternity Hospital, University College Cork, Wilton, Cork, Republic of Ireland. (2012-01-31)
      Autoimmune diseases (AID) predominantly affect women of reproductive age. While basic molecular studies have implicated persisting fetal cells in the mother in some AID, supportive epidemiological evidence is limited. We investigated the effect of vaginal delivery, caesarean section (CS) and induced abortion on the risk of subsequent maternal AID. Using the Danish Civil Registration System (CRS) we identified women who were born between 1960 and 1992. We performed data linkage between the CRS other Danish national registers to identify women who had a pregnancy and those who developed AID. Women were categorised into 4 groups; nulligravida (control group), women who had 1st child by vaginal delivery, whose 1st delivery was by CS and who had abortions. Log-linear Poisson regression with person-years was used for data analysis adjusting for several potential confounders. There were 1,035,639 women aged >14 years and 25,570 developed AID: 43.4% nulligravida, 44.3% had their first pregnancy delivered vaginally, 7.6% CS and 4.1% abortions. The risk of AID was significantly higher in the 1st year after vaginal delivery (RR = 1.1[1.0, 1.2]) and CS (RR = 1.3[1.1, 1.5]) but significantly lower in the 1st year following abortion (RR = 0.7[0.6, 0.9]). These results suggest an association between pregnancy and the risk of subsequent maternal AID. Increased risks of AID after CS may be explained by amplified fetal cell traffic at delivery, while decreased risks after abortion may be due to the transfer of more primitive fetal stem cells. The increased risk of AID in the first year after delivery may also be related to greater testing during pregnancy.
    • Risk of affective disorders following prenatal exposure to severe life events: a Danish population-based cohort study.

      Khashan, Ali S; McNamee, Roseanne; Henriksen, Tine B; Pedersen, Marianne G; Kenny, Louise C; Abel, Kathryn M; Mortensen, Preben B; Anu Research Centre, Department of Obstetrics and Gynecology, University College , Cork, Cork University Maternity Hospital, Cork, Ireland. a.khashan@ucc.ie (2012-01-31)
      OBJECTIVE: To examine the effect of prenatal exposure to severe life events on risk of affective disorders in the offspring. METHODS: In a cohort of 1.1 million Danish births from May 1978 until December 1997, mothers were considered exposed if one (or more) of their close relatives died or was diagnosed with serious illness up to 6 months before conception or during pregnancy. Offspring were followed up from their 10th birthday until their death, migration, onset of affective disorder or 31 December 2007; hospital admissions were identified by linkage to the Central Psychiatric Register. Log-linear Poisson regression was used for data analysis. RESULTS: The risk of affective disorders was increased in male offspring whose mothers were exposed to severe life events during the second trimester (adjusted RR 1.55 [95% CI 1.05-2.28]). There was an increased risk of male offspring affective disorders in relation to maternal exposure to death of a relative in the second trimester (adjusted RR 1.74 [95% CI 1.06-2.84]) or serious illness in a relative before pregnancy (adjusted RR 1.44 [95% CI 1.02-2.05]). There was no evidence for an association between prenatal exposure to severe life events and risk of female offspring affective disorders. CONCLUSIONS: Our population-based study suggests that prenatal maternal exposure to severe life events may increase the risk of affective disorders in male offspring. These findings are consistent with studies of populations exposed to famine and earthquake disasters which indicate that prenatal environment may influence the neurodevelopment of the unborn child.
    • Robust early pregnancy prediction of later preeclampsia using metabolomic biomarkers.

      Kenny, Louise C; Broadhurst, David I; Dunn, Warwick; Brown, Marie; North, Robyn A; McCowan, Lesley; Roberts, Claire; Cooper, Garth J S; Kell, Douglas B; Baker, Philip N; et al. (2012-01-31)
      Preeclampsia is a pregnancy-specific syndrome that causes substantial maternal and fetal morbidity and mortality. The etiology is incompletely understood, and there is no clinically useful screening test. Current metabolomic technologies have allowed the establishment of metabolic signatures of preeclampsia in early pregnancy. Here, a 2-phase discovery/validation metabolic profiling study was performed. In the discovery phase, a nested case-control study was designed, using samples obtained at 15+/-1 weeks' gestation from 60 women who subsequently developed preeclampsia and 60 controls taking part in the prospective Screening for Pregnancy Endpoints cohort study. Controls were proportionally population matched for age, ethnicity, and body mass index at booking. Plasma samples were analyzed using ultra performance liquid chromatography-mass spectrometry. A multivariate predictive model combining 14 metabolites gave an odds ratio for developing preeclampsia of 36 (95% CI: 12 to 108), with an area under the receiver operator characteristic curve of 0.94. These findings were then validated using an independent case-control study on plasma obtained at 15+/-1 weeks from 39 women who subsequently developed preeclampsia and 40 similarly matched controls from a participating center in a different country. The same 14 metabolites produced an odds ratio of 23 (95% CI: 7 to 73) with an area under receiver operator characteristic curve of 0.92. The finding of a consistent discriminatory metabolite signature in early pregnancy plasma preceding the onset of preeclampsia offers insight into disease pathogenesis and offers the tantalizing promise of a robust presymptomatic screening test.
    • Soluble Flt-1 and PlGF: new markers of early pregnancy loss?

      Muttukrishna, Shanthi; Swer, Michelle; Suri, Sangeeta; Jamil, Amna; Calleja-Agius, Jean; Gangooly, Subrata; Ludlow, Helen; Jurkovic, Davor; Jauniaux, Eric; Department of Obstetrics and Gynaecology, Anu Research Centre, University College, Cork, Cork University Maternity Hospital, Wilton, Cork, Republic of Ireland., S.Muttukrishna@ucc.ie (2012-01-31)
      Recent data have indicated a relationship between placental oxygen and angiogenic protein levels in the first trimester of normal pregnancies. Our objective was to investigate if maternal serum levels of angiogenic factors Soluble vascular endothelial growth factor (VEGF) receptor 1 (sFlt-1), soluble Endoglin and placental growth factor (PlGF) are altered in women with symptoms of threatened miscarriage (TM) and if they are predictive of a subsequent miscarriage. Blood samples were collected at 6-10 weeks from women presenting with TM (n = 40), from asymptomatic controls (n = 32) and from non- pregnant women in their luteal phase (n = 14). All samples were assayed for serum level of sFLT-1, PlGF, sEndoglin and HSP70 using commercial ELISAs. Samples were analysed retrospectively on the basis of pregnancy outcome. TM group included 21 women with a normal pregnancy outcome and 19 with subsequent complete miscarriage. The latter subgroup had significantly lower mean maternal serum (MS) sFlt-1 (83%, P<0.001) and PlGF (44%, P<0.001) compared to those with a normal pregnancy outcome. Asymptomatic control pregnant women had similar MS levels of sFlt-1 and PlGF compared to the TM patients with a normal outcome. The mean MS sFlt-1 (>10 fold) and MS PlGF ( approximately 2 fold) levels were significantly (P<0.001) higher in control pregnant women compared to the non-pregnant group in the luteal phase of the menstrual cycle. Soluble Endoglin was not altered in the normal pregnant women compared to non pregnant women, although lower in the TM subgroup with a subsequent miscarriage ( approximately 25%, P<0.001) compared to TM with a live birth. There was no significant difference in the mean MS HSP 70 levels between the different groups. This study shows that sFlt1 and PlGF MS levels are increased by several folds in early pregnancy and that MS sFlt-1 and MS PlGF are markedly decreased in threatened miscarriage patients who subsequently have a miscarriage suggesting these proteins are sensitive predictive markers of subsequent pregnancy loss.
    • Soluble Flt-1 and PlGF: new markers of early pregnancy loss?

      Muttukrishna, Shanthi; Swer, Michelle; Suri, Sangeeta; Jamil, Amna; Calleja-Agius, Jean; Gangooly, Subrata; Ludlow, Helen; Jurkovic, Davor; Jauniaux, Eric; Department of Obstetrics and Gynaecology, Anu Research Centre, University College Cork, Cork University Maternity Hospital, Wilton, Cork, Republic of Ireland. S.Muttukrishna@ucc.ie (2011)
      Recent data have indicated a relationship between placental oxygen and angiogenic protein levels in the first trimester of normal pregnancies. Our objective was to investigate if maternal serum levels of angiogenic factors Soluble vascular endothelial growth factor (VEGF) receptor 1 (sFlt-1), soluble Endoglin and placental growth factor (PlGF) are altered in women with symptoms of threatened miscarriage (TM) and if they are predictive of a subsequent miscarriage. Blood samples were collected at 6-10 weeks from women presenting with TM (n = 40), from asymptomatic controls (n = 32) and from non- pregnant women in their luteal phase (n = 14). All samples were assayed for serum level of sFLT-1, PlGF, sEndoglin and HSP70 using commercial ELISAs. Samples were analysed retrospectively on the basis of pregnancy outcome. TM group included 21 women with a normal pregnancy outcome and 19 with subsequent complete miscarriage. The latter subgroup had significantly lower mean maternal serum (MS) sFlt-1 (83%, P<0.001) and PlGF (44%, P<0.001) compared to those with a normal pregnancy outcome. Asymptomatic control pregnant women had similar MS levels of sFlt-1 and PlGF compared to the TM patients with a normal outcome. The mean MS sFlt-1 (>10 fold) and MS PlGF (∼2 fold) levels were significantly (P<0.001) higher in control pregnant women compared to the non-pregnant group in the luteal phase of the menstrual cycle. Soluble Endoglin was not altered in the normal pregnant women compared to non pregnant women, although lower in the TM subgroup with a subsequent miscarriage (∼25%, P<0.001) compared to TM with a live birth. There was no significant difference in the mean MS HSP 70 levels between the different groups. This study shows that sFlt1 and PlGF MS levels are increased by several folds in early pregnancy and that MS sFlt-1 and MS PlGF are markedly decreased in threatened miscarriage patients who subsequently have a miscarriage suggesting these proteins are sensitive predictive markers of subsequent pregnancy loss.
    • Trial of labour after caesarean section and the risk of neonatal and infant death: a nationwide cohort study.

      O'Neill, Sinéad M; Agerbo, Esben; Khashan, Ali S; Kearney, Patricia M; Henriksen, Tine Brink; Greene, Richard A; Kenny, Louise C (BMC Pregnancy and Childbirth, 2017-02-27)
      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).
    • Undiagnosed coeliac disease in a father does not influence birthweight and preterm birth.

      Khashan, Ali S; Kenny, Louise C; McNamee, Roseanne; Mortensen, Preben B; Pedersen, Marianne G; McCarthy, Fergus P; Henriksen, Tine B; Anu Research Centre, Department of Obstetrics and Gynaecology, University College, Cork, Cork University Maternity Hospital, Ireland. a.khashan@ucc.ie (2012-01-31)
      There is conflicting evidence regarding the effect of coeliac disease (CD) in the father on birthweight and preterm birth. We investigated the association between paternal CD and birthweight and preterm birth. Medical records of all singleton live-born children in Denmark between 1 January 1979 and 31 December 2004 were linked to information about parents' diseases. Fathers who were diagnosed with CD were then identified. Fathers with CD were considered treated if they were diagnosed before pregnancy and untreated if they were diagnosed after the date of conception. The outcome measures were: birthweight, small-for-gestational age (birthweight<10th centile for gestational age) and preterm birth (<37 weeks). We compared the offspring of men without CD (n = 1 472 352) and offspring of those with CD [untreated (n = 138) and treated (n = 473)]. There was no significant association between untreated CD in the father and birthweight (adjusted mean difference = -3 g; [95% CI -46, 40]) or preterm birth (adjusted odds ratio (OR) = 0.86, [95% CI 0.53, 1.37]) (compared with no CD). There was some evidence for an association between treated paternal CD and birthweight (adjusted mean difference = -81 g; [95% CI -161, -3]), but not preterm birth (adjusted OR = 1.76, [95% CI 0.95, 3.26]). Untreated paternal CD was not associated with an increased risk of reduced birthweight, or of preterm birth. There was some evidence that diagnosis and presumed treatment of paternal CD with a gluten-free diet is associated with reduced birthweight.