• Palivizumab use in preterm neonates.

      Kingston, S; Murphy, B P; Department of Neonatology, Cork University Maternity Hospital, Wilton, Cork. (2012-01-31)
      Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis in infants. Palivizumab is an immunoprophylactic agent for RSV prevention in preterm infants and those with neonatal chronic lung disease. This study examines its use across neonatal units in Ireland. A questionnaire was administered to one Consultant Neonatologist or Paediatrician in each of the 20 maternity centres in Ireland about their guidelines for Palivizumab administration. There is variation in administration of Palivizumab with little consistency found between protocols reported in terms of age and presence of chronic lung disease. Ten centres have in house protocols, 3 centres use the American Academy of Paediatrics (AAP) guidelines, 2 centres prefer the UK Joint Committee on Vaccination and Immunisation (JCVI) guidelines and 3 centres do not have a set protocol. Four participants felt its use has impacted on hospital admissions and 61% believe its use is cost effective. The budgetary implication for immunoprophylaxis with Palivizumab in Ireland is estimated at 1.5 to 2 million euros annually. Given current pharmacoeconomic constraints there is a need to implement a national protocol on RSV immunoprophylaxis.
    • Parents’ concerns about future pregnancy after stillbirth: a qualitative study

      Meaney, Sarah; Everard, Claire M.; Gallagher, Stephen; O'Donoghue, Keelin; National Perinatal Epidemiology Centre; University College Cork; Cork Ireland; Cork University Maternity Hospital; Cork Ireland; Centre for Social Issues Research; Department of Psychology; University of Limerick; Limerick Ireland; Pregnancy Loss Research Group; Department of Obstetrics and Gynaecology University College Cork; Ireland (2016-07)
      As stillbirth has a devastating impact, it is imperative to understand the importance of clinical and emotional care after stillbirth and how it influences subsequent pregnancies. The aim of the study was to gain insight into the consideration and planning of a subsequent pregnancy by parents in the weeks following stillbirth.
    • Patients' perception of privacy and confidentiality in the emergency department of a busy obstetric unit.

      Hartigan, Lucia; Cussen, Leanne; Meaney, Sarah; O'Donoghue, Keelin (BMC Health Services Research, 2018-12-18)
      Privacy and confidentiality are central components of patient care and are of particular importance in obstetrics and gynaecology, where clinical situations of a sensitive nature regularly occur. The layout of the emergency department (ED) in maternity units is often not conducive to maintaining privacy. Our study aimed to discover if changing the environment could improve patients' experiences in the ED. We surveyed patients and asked specific questions about their perception of privacy in the ED. We then repeated the survey following renovations to the ED which involved replacing curtained patient areas with walled cubicles. There were 75 pre-renovation surveys and 82 post-renovation surveys completed. Before the renovations took place, only 21% (n = 16) found their privacy to be adequate during their visit to the ED. However this rose to 89% (n = 73) post-renovation. Our study showed that patients' perception of privacy and confidentiality significantly improved following refurbishment of the ED.
    • Perinatal mortality in Ireland: annual report 2013

      Manning, E; Corcoran, P; Meaney, S; Greene, RA; National Perinatal Epidemiology Centre (National Perinatal Epidemiology Centre, Department of Obstetrics and Gynaecology, UCC, 2015)
      This is the third report of the national clinical audit on perinatal mortality in Ireland using the NPEC data collection tool and classification system. Anonymised data were reported by the 20 Irish maternity units on a total of 500 perinatal deaths occurring in 2013 arising from 69,146 births of at least 500g birthweight or at least 24 weeks gestation. Stillbirths, early neonatal and late neonatal deaths accounted for 301 (60.2%), 162 (32.4%) and 37 (7.4%) of the 500 deaths, respectively. The perinatal mortality rate was 6.7 per 1,000 births in 2013; corrected for congenital malformation, the rate was 4.4 per 1,000 births; the stillbirth rate was 4.4 per 1,000 births; and, the early neonatal death rate was 2.4 per 1,000 live births.
    • Permissive hypotension in the extremely low birthweight infant with signs of good perfusion.

      Dempsey, E M; Al Hazzani, F; Barrington, K J; Neonatology, Cork University Maternity Hospital, Cork, Ireland. (2012-01-31)
      INTRODUCTION: Many practitioners routinely treat infants whose mean arterial blood pressure in mm Hg is less than their gestational age in weeks (GA). OBJECTIVE: To assess the effectiveness of utilising a combined approach of clinical signs, metabolic acidosis and absolute blood pressure (BP) values when deciding to treat hypotension in the extremely low birthweight (ELBW) infant. METHODS: Retrospective cohort study of all live born ELBW infants admitted to our neonatal intensive care unit over a 4-year period. Patients were grouped as either normotensive (BP never less than GA), hypotensive and not treated (BP
    • Peroxisome proliferator-activated receptor-gamma as a potential therapeutic target in the treatment of preeclampsia.

      McCarthy, Fergus P; Drewlo, Sascha; Kingdom, John; Johns, Edward J; Walsh, Sarah K; Kenny, Louise C; Anu Research Centre, University College Cork, Cork University Maternity Hospital,, Wilton, Cork, Ireland. fergusmccarthy@gmail.com (2012-01-31)
      Preeclampsia is a multisystemic disorder of pregnancy characterized by hypertension, proteinuria, and maternal endothelial dysfunction. It is a major cause of maternal and perinatal morbidity and mortality and is thought to be attributable, in part, to inadequate trophoblast invasion. Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a ligand-activated transcription factor expressed in trophoblasts, and the vasculature of which activation has been shown to improve endothelium-dependent vasodilatation in hypertensive conditions. We investigated the effects of the administration of a PPAR-gamma agonist using the reduced uterine perfusion pressure (RUPP) rat model of preeclampsia. The selective PPAR-gamma agonist, rosiglitazone, was administered to pregnant rats that had undergone RUPP surgery. To investigate whether any observed beneficial effects of PPAR-gamma activation were mediated by the antioxidant enzyme, heme oxygenase 1, rosiglitazone was administered in combination with the heme oxygenase 1 inhibitor tin-protoporphyrin IX. RUPP rats were characterized by hypertension, endothelial dysfunction, and elevated microalbumin:creatinine ratios. Rosiglitazone administration ameliorated hypertension, improved vascular function, and reduced the elevated microalbumin:creatinine ratio in RUPP rats. With the exception of microalbumin:creatinine ratio, these beneficial effects were abrogated in the presence of the heme oxygenase 1 inhibitor. Administration of a PPAR-gamma agonist prevented the development of several of the pathophysiological characteristics associated with the RUPP model of preeclampsia, via a heme oxygenase 1-dependent pathway. The findings from this study provide further insight into the underlying etiology of preeclampsia and a potential therapeutic target for the treatment of preeclampsia.
    • Placental FKBP51 mediates a link between second trimester maternal anxiety and birthweight in female infants.

      Togher, Katie L; O'Keeffe, Gerard W; Khashan, Ali S; Clarke, Gerard; Kenny, Louise C; Cork University Maternity Hospital and University College Cork (Scientific Reports, 2018-10-11)
      Prenatal distress is associated with adverse outcomes in affected offspring. Alterations in placental glucocorticoid signalling and subsequent foetal overexposure to glucocorticoids have been implicated as an underlying mechanism. Infant sex is emerging as an important factor in disease susceptibility. This study aimed to examine the effects of maternal distress across pregnancy on birth outcomes and placental glucocorticoid genes in a sex-dependent manner. Participants completed psychological distress questionnaires throughout pregnancy. Placental HSD11B2, NR3C1 and FKBP51 were analysed by real time PCR and cortisol was measured in new-born hair. Second trimester stress was negatively correlated with birthweight in males and positively correlated with placental NR3C1 mRNA in females. Second trimester anxiety was negatively correlated with birthweight and placental FKBP51 mRNA in females. In mediation analysis, placental FKBP51 mRNA expression was found to mediate the link between prenatal anxiety and birthweight. New-born cortisol was negatively correlated with second trimester anxiety and positively correlated with female placental FKBP51 mRNA levels. Again, FKBP51 mRNA was found to mediate the link between anxiety and new-born cortisol. These results highlight a role for FKBP51 in the placental response to prenatal distress in females. The precise role that placental FKBP51 has in foetal and infant development has not been extensively studied and warrants further investigations.
    • Plasma-mediated vascular dysfunction in the reduced uterine perfusion pressure model of preeclampsia: a microvascular characterization.

      Walsh, Sarah K; English, Fred A; Johns, Edward J; Kenny, Louise C; Anu Research Centre, Department of Obstetrics and Gynaecology, University College, Cork, Cork University Maternity Hospital, Wilton, Cork, Ireland. S.Walsh@ucc.ie (2012-01-31)
      Preeclampsia is associated with widespread maternal vascular dysfunction, which is thought to be mediated by circulating factor(s). The aim of the study was to characterize vascular function in the reduced uterine perfusion pressure (RUPP) rat model of preeclampsia and to investigate the role of plasma factors in mediating any observed changes in vascular reactivity. Mean arterial blood pressure and vascular function were measured in RUPP and control rats. Mesenteric vessels from both virgin and pregnant rats were exposed for 1 hour or overnight to plasma from both RUPP and control rats and their vascular function assessed. RUPP rats were characterized by severe hypertension, restricted fetal growth, and reduced placental weight (P<0.001). Vasorelaxation was impaired in resistance vessels from RUPP compared with control rats (acetylcholine: R(max) 70+/-3 versus 92+/-1 [NP] and 93+/-3% [sham], P<0.01; bradykinin: 40+/-2 versus 62+/-2 [NP] and 59+/-4% [sham], P<0.001). Incubation of vessels from pregnant (but not virgin) animals with RUPP plasma overnight resulted in an attenuation of vasorelaxant responses (acetylcholine: 63+/-7 versus 86+/-2%, P<0.05; bradykinin: 35+/-5 versus 55+/-6%, P<0.001). The residual relaxant response in RUPP plasma-treated vessels was not further attenuated after treatment with N(omega)-nitro-l-arginine methyl ester (acetylcholine: 57+/-7 versus 63+/-7%, ns; bradykinin: 37+/-5 versus 35+/-5%, ns). The RUPP rat model is characterized by an impaired response to vasodilators which may be attributable to one or more circulating factors. This plasma-mediated endothelial dysfunction appears to be a pregnancy-dependent effect. Furthermore, nitric oxide-mediated vasorelaxation appears to be absent in RUPP plasma-treated vessels.
    • The pool chlorine hypothesis and asthma among boys.

      Cotter, A; Ryan, C A; Department of Paediatrics and Child Health, UCC, Cork University Maternity, Hospital, Wilton, Cork. (2012-01-31)
      Swimming pool sanitation has largely been concerned with the microbiological quality of pool water, which is normally treated using a number of chlorine products. Recent studies have pointed to the potential hazards of chlorine by-products to the respiratory epithelium, particularly in indoor, poorly ventilated, pools. The aim of our study was to elucidate whether chronic exposure to indoor chlorinated swimming pools was associated with an increased likelihood of the development of asthma in boys. METHODS: The subjects were boys aged between 6 and 12 years. Data was collected by means of parental responses to a standardized asthma questionnaire (ISAAC: International Study of Asthma and Allergies in Childhood), supplemented with additional questions regarding frequency of attendance, number of years attendance, whether the child is a swimming team member. The questionnaire return rate was 71/% (n = 121). 23 boys were excluded on the basis that they had asthma before they started swimming (n = 97). There was a significant association between number of years a boy had been swimming and the likelihood of wheezing in the last 12 months (p = 0.009; OR = 1.351; 95% CI = 1.077-1.693) and diagnosed asthma (p = 0.046; OR = 1.299; 95% CI = 1.004-1.506). The greater the number the number of years a boy had been attending an indoor, chlorinated pool, the greater the likelihood of wheezing in the last 12 months or "had asthma". Age, parental smoking habits and being a swimming team member had no association with any of the asthma variables examined. Swimming pool attendance may be a risk factor in asthma in boys.
    • Potential hazard of the Neopuff T-piece resuscitator in the absence of flow limitation.

      Hawkes, C P; Oni, O A; Dempsey, E M; Ryan, C A; Department of Neonatology, Cork University Maternity Hospital, Wilton, Cork,, Ireland. (2012-01-31)
      OBJECTIVE: (1) To assess peak inspiratory pressure (PIP), positive end expiratory pressure (PEEP) and maximum pressure relief (P(max)) at different rates of gas flow, when the Neopuff had been set to function at 5 l/min. (2) To assess maximum PIP and PEEP at a flow rate of 10 l/min with a simulated air leak of 50%. DESIGN: 5 Neopuffs were set to a PIP of 20, PEEP of 5 and P(max) of 30 cm H(2)O at a gas flow of 5 l/min. PIP, PEEP and P(max) were recorded at flow rates of 10, 15 l/min and maximum flow. Maximum achievable pressures at 10 l/min gas flow, with a 50% air leak, were measured. RESULTS: At gas flow of 15 l/min, mean PEEP increased to 20 (95% CI 20 to 21), PIP to 28 (95% CI 28 to 29) and the P(max) to 40 cm H(2)O (95% CI 38 to 42). At maximum flow (85 l/min) a PEEP of 71 (95% CI 51 to 91) and PIP of 92 cm H(2)O (95% CI 69 to 115) were generated. At 10 l/min flow, with an air leak of 50%, the maximum PEEP and PIP were 21 (95% CI 19 to 23) and 69 cm H(2)O (95% CI 66 to 71). CONCLUSIONS: The maximum pressure relief valve is overridden by increasing the rate of gas flow and potentially harmful PIP and PEEP can be generated. Even in the presence of a 50% gas leak, more than adequate pressures can be provided at 10 l/min gas flow. We recommend the limitation of gas flow to a rate of 10 l/min as an added safety mechanism for this device.
    • 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.
    • Pregnancy and the risk of autoimmune disease: An exploration.

      Department of Obstetrics and Gynaecology; Anu Research Centre; Cork University, Maternity Hospital; University College Cork; Wilton, Cork Ireland. (2012-01-31)
      Fetal microchimerism is the study of persisting fetal cells in the mother years after pregnancy and the purported implications for her health and longevity. Due to the association between pregnancy and autoimmune disease (AID), and the preponderance of these diseases in women, laboratory studies have for years attempted to link microchimeric fetal cells with the onset of AID after pregnancy. This new study gave us the opportunity to examine for the first time if this theory could be proven clinically in a large cohort of women. By examining whether different types of delivery affected the onset of AID, we also aimed to indirectly relate this finding to fetal microchimerism. The results did suggest an association between pregnancy and the risk of subsequent maternal AID, with increased risks noted after caesarean section (CS) and decreased risks after abortion. This is the first epidemiological study on the risk of AID following pregnancy.
    • Pregnancy risk assessment monitoring system in Ireland: methods and response rates

      O’Keeffe, Linda M.; Kearney, Patricia M.; Greene, Richard A. (Maternal and Child Health Journal, 2014-06)
      To describe response rates and characteristics associated with response to the Pregnancy Risk Assessment Monitoring System study in Ireland (PRAMS Ireland). Using hospital discharge records of live births at a large, urban, obstetric hospital, a sampling frame of approximately 2,400 mother-infant pairs were used to alternately sample 1,200 women. Mothers’ information including name, address, parity, age and infant characteristics such as sex and gestational age at delivery were extracted from records. Modes of contact included an invitation letter with option to opt out of the study, three mail surveys, a reminder letter and text message reminder for remaining non-respondents. Sixty-one per cent of women responded to the PRAMS Ireland survey over a 133 day response period. Women aged <30, single women, multiparous women and women with a preterm delivery were less likely to respond. Women participating in PRAMS Ireland were similar to the national birth profile in 2011 which had a mean age of 32, were 40 % primiparous, 33 % single or never married and had a 28 % caesarean section rate. Survey and protocol changes are required to increase response rates above recommended Centers for Disease Control and Prevention (CDC) thresholds of 65 % within the recommended 90 day data collection cycle. Additional efforts such as stratification and over-sampling are required to increase representativeness among hard to reach groups such as younger, single and multiparous women before expanding the project to an ongoing, national surveillance system in Ireland.
    • Prevalence of subclinical and undiagnosed overt hypothyroidism in a pregnancy loss clinic

      Khalid, AS; Joyce, C; O’Donoghue, K (Irish Medical Journal, 2013-04)
    • Procedural training in neonatal care

      Braima, O; Akinlabi, OL (Irish Medical Journal, 2011-03)
    • Prolonged faecal excretion following a single dose of probiotic in low birth weight infants.

      McGee, Richard; O'Connor, Paula M; Russell, David; Dempsey, Eugene M; Ryan, Anthony C; Ross, Paul R; Stanton, Catherine; Department of Neonatology, Cork University Maternity Hospital, Ireland. (2012-01-31)
    • A prospective cohort study investigating associations between hyperemesis gravidarum and cognitive, behavioural and emotional well-being in pregnancy.

      McCarthy, Fergus P; Khashan, Ali S; North, Robyn A; Moss-Morris, Rona; Baker, Philip N; Dekker, Gus; Poston, Lucilla; Kenny, Louise C; Department of Obstetrics and Gynecology, The Anu Research Centre, Cork University, Maternity Hospital, University College Cork, Cork, Ireland., Fergus.mccarthy@ucc.ie (2012-01-31)
      OBJECTIVES: To investigate the association between hyperemesis gravidarum and altered cognitive, behavioural and emotional well-being in pregnancy. METHODS: The study cohort consisted of 3423 nulliparous women recruited in the Screening for Pregnancy Endpoints (SCOPE) study performed in Auckland, New Zealand; Adelaide, Australia; Cork, Ireland; Manchester and London, United Kingdom between November 2004 and August 2008. Women were interviewed at 15+/-1 weeks' gestation and at 20+/-1weeks' gestation. Women with a diagnosis of hyperemesis gravidarum (HG) were compared with women who did not have a diagnosis of HG. Main outcome measures included the Short form State- Trait Anxiety Inventory (STAI) score (range 6-24), Perceived Stress Scale score (PSS, range 0-30), Edinburgh Postnatal Depression Scale (EPDS) score (range 0-30 or categories a-c) and behavioural responses to pregnancy score (limiting/resting [range 0-20] and all-or-nothing [range 0-28]). RESULTS: During the study period 164 women suffered from HG prior to their 15 week interview. Women with HG had significantly higher mean STAI, PSS, EPDS and limiting response to pregnancy scores compared to women without HG. These differences were observed at both 15+/-1 and 20+/-1 weeks' of gestation. The magnitude of these differences was greater in women with severe HG compared to all women with HG. Women with severe HG had an increased risk of having a spontaneous preterm birth compared with women without HG (adjusted OR 2.6 [95% C.I. 1.2, 5.7]). CONCLUSION: This is the first large prospective study on women with HG. Women with HG, particularly severe HG, are at increased risk of cognitive, behavioural and emotional dysfunction in pregnancy. Women with severe HG had a higher rate of spontaneous preterm birth compared to women without HG. Further research is required to determine whether the provision of emotional support for women with HG is beneficial.
    • Reference standard for serum bile acids in pregnancy.

      Anu Research Centre, Department of Obstetrics and Gynaecology, University College, Cork, Cork University Maternity Hospital, Cork, Ireland Department of Medicine,, University of Alberta, Edmonton, Alberta, Canada Department of Biochemistry, Cork, University Hospital, Cork, Ireland. (2012-01-31)
      Please cite this paper as: Egan N, Bartels A, Khashan A, Broadhurst D, Joyce C, O'Mullane J, O'Donoghue K. Reference standard for serum bile acids in pregnancy. BJOG 2012;00:000-000. DOI: 10.1111/j.1471-0528.2011.03245.x. Objective Obstetric cholestasis (OC) is a liver disorder characterised by pruritus and elevated serum bile acids (SBA) that affects one in 200 pregnant women. It is associated with adverse perinatal outcomes such as premature delivery and stillbirth. Mild OC is defined as SBA levels of 10-39 mumol/l, and severe OC is defined by levels >40 mumol/l. SBA levels in normal pregnancy have not been investigated. We aimed to establish reference values for SBA in healthy pregnant women across different trimesters of pregnancy. Design Cross-sectional analysis of SBA levels. Setting A large tertiary referral university teaching maternity hospital. Population Healthy pregnant women with a singleton pregnancy and a body mass index (BMI) < 40, excluding women with significant alcohol intake, history of liver disease, prior cholecystectomy and OC. Methods Cross-sectional analysis of SBA levels at 12, 20, 28 and 36 weeks of gestation, and on days 1-3 postpartum. Main outcome measures SBA levels in mumol/l. Results A total of 219 women attending for antenatal care were recruited, and SBA levels were assayed at 12, 20, 28 and 36 weeks of gestation, and up to 72 hours postpartum (n = 44-49 cases at each stage). The majority were white European women, with a median age of 30 years (range 17-46 years) and median BMI of 25 (range 18-38). Values of SBA ranged from 0.3 to 9.8 mumol/l in 216 women, with only three measurements outside this range. There were no significant changes throughout pregnancy. Conclusions SBA values in uncomplicated pregnancies are consistent, regardless of gestation, and are not elevated in pregnancy. The current reference values for the diagnosis of OC appear to be appropriate.
    • 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.