• Animal models of preeclampsia; uses and limitations.

      McCarthy, F P; Kingdom, J C; Kenny, L C; Walsh, S K; Anu Research Centre, Department of Obstetrics & Gynaecology, University College, Cork, Cork University Maternity Hospital, Wilton, Cork, Ireland., fergusmccarthy@gmail.com (2012-01-31)
      Preeclampsia remains a leading cause of maternal and fetal morbidity and mortality and has an unknown etiology. The limited progress made regarding new treatments to reduce the incidence and severity of preeclampsia has been attributed to the difficulties faced in the development of suitable animal models for the mechanistic research of this disease. In addition, animal models need hypotheses on which to be based and the slow development of testable hypotheses has also contributed to this poor progress. The past decade has seen significant advances in our understanding of preeclampsia and the development of viable reproducible animal models has contributed significantly to these advances. Although many of these models have features of preeclampsia, they are still poor overall models of the human disease and limited due to lack of reproducibility and because they do not include the complete spectrum of pathophysiological changes associated with preeclampsia. This review aims to provide a succinct and comprehensive assessment of current animal models of preeclampsia, their uses and limitations with particular attention paid to the best validated and most comprehensive models, in addition to those models which have been utilized to investigate potential therapeutic interventions for the treatment or prevention of preeclampsia.
    • Antenatal interventions for preventing the transmission of cytomegalovirus (CMV) from the mother to fetus during pregnancy and adverse outcomes in the congenitally infected infant.

      McCarthy, Fergus P; Giles, Michelle L; Rowlands, Shelley; Purcell, Kara J; Jones, Cheryl A; Anu Research Centre, Department of Obstetrics and Gynaecology, University College, Cork, Cork University Maternity Hospital, Wilton, Cork, Ireland. (2012-01-31)
      BACKGROUND: Cytomegalovirus (CMV) is a herpesvirus and the most common cause of congenital infection in developed countries. Congenital CMV infection can have devastating consequences to the fetus. The high incidence and the serious morbidity associated with congenital CMV infection emphasise the need for effective interventions to prevent the antenatal transmission of CMV infection. OBJECTIVES: The aim of this review was to assess the benefits and harms of interventions used during pregnancy to prevent mother to fetus transmission of CMV infection. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 December 2010). SELECTION CRITERIA: All randomised controlled trials (RCTs) and quasi RCTs investigating antenatal interventions for preventing the transmission of CMV from the mother to fetus during pregnancy and adverse outcomes in the congenitally infected infant. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion. MAIN RESULTS: We identified six studies from the search. None of these studies met the pre-defined criteria for inclusion in this review. AUTHORS' CONCLUSIONS: To date, no RCTs are available that examine antenatal interventions for preventing the transmission of CMV from the infected mother to fetus during pregnancy and adverse outcomes in the congenitally infected infant. Further research is needed to assess the efficacy of interventions aimed at preventing the transmission of CMV from the mother to fetus during pregnancy including a long-term follow-up of exposed infants and a cost effective analysis.
    • Antenatal management of the expectant mother and extreme preterm infant at the limits of viability.

      Khan, R; Burgoyne, L; O'Connell, M; Dempsey, E M; Neonatal Intensive Care Unit, Cork University Maternity Hospital, Wilton, Cork. (2012-01-31)
      We explored the opinions of healthcare providers on the antenatal management and outcome of preterm delivery at less than 28 weeks gestation. An anonymous postal questionnaire was sent to health care providers. The response rate was 55% (74% Obstetrician, 70% neonatologist). Twenty four weeks is the limit at which most would advocate intervention. At 23 weeks 67% of neonatologists advocate antenatal steroids. 50% of all health care providers advocate cardiotocographic monitoring at 24 weeks gestation. Written information on survival and long-term outcome is provided by 8% of the respondents. Neonatologists (50%) were more likely than obstetrician (40%) to advocate caesarean section at 25 weeks. We conclude that 24 weeks is the limit at which most would advocate intervention. Significant variation exists both between and within each health care group at less than 25 weeks. Establishment and provision of national outcome data may aid decision making at the limits of viability.
    • Are fathers underused advocates for breastfeeding?

      Kenosi, M; Hawkes, C P; Dempsey, E M; Ryan, C A (Irish Medical Journal (IMJ), 2011-11)
      Fathers' knowledge base and attitudes influence breastfeeding practice. We aimed to evaluate if Irish fathers felt included in the breastfeeding education and decision process. 67 fathers completed questionnaires, which assessed their role in the decision to breastfeed, knowledge regarding the benefits of breastfeeding and attitude towards breastfeeding.Forty-two (62.7%) of their partners were breastfeeding. Antenatal classes were attended by 38 (56.7%); 59 (88.1%) discussed breastfeeding with their partners and 26 (38.8%) felt that the decision was made together. Twelve (48%) fathers of formula fed infants were unaware that breastfeeding was healthier for the baby. Most fathers (80.6%) felt that breastfeeding was the mother's decision and most (82.1%) felt that antenatal information was aimed at mothers only. Irish fathers remain relatively uninformed regarding the benefits of breastfeeding. This may contribute to their exclusion from the decision to breastfeed. Antenatal education should incorporate fathers more, and this may result in an improvement in our breastfeeding rates.
    • Benchmarking care for very low birthweight infants in Ireland and Northern Ireland.

      Murphy, B P; Armstrong, K; Ryan, C A; Jenkins, J G; Department of Neonatology, Cork University Maternity Hospital, Wilton, Cork,, Ireland. brendanpaul.murphy@hse.ie (2012-01-31)
      BACKGROUND: Benchmarking is that process through which best practice is identified and continuous quality improvement pursued through comparison and sharing. The Vermont Oxford Neonatal Network (VON) is the largest international external reference centre for very low birth weight (VLBW) infants. This report from 2004-7 compares survival and morbidity throughout Ireland and benchmarks these results against VON. METHODS: A standardised VON database for VLBW infants was created in 14 participating centres across Ireland and Northern Ireland. RESULTS: Data on 716 babies were submitted in 2004, increasing to 796 babies in 2007, with centres caring for from 10 to 120 VLBW infants per year. In 2007, mortality rates in VLBW infants varied from 4% to 19%. Standardised mortality ratios indicate that the number of deaths observed was not significantly different from the number expected, based on the characteristics of infants treated. There was no difference in the incidence of severe intraventricular haemorrhage between all-Ireland and VON groups (5% vs 6%, respectively). All-Ireland rates for chronic lung disease (CLD; 15-21%) remained lower than rates seen in the VON group (24-28%). The rates of late onset nosocomial infection in the all-Ireland group (25-26%) remained double those in the VON group (12-13%). DISCUSSION: This is the first all-Ireland international benchmarking report in any medical specialty. Survival, severe intraventricular haemorrhage and CLD compare favourably with international standards, but rates of nosocomial infection in neonatal units are concerning. Benchmarking clinical outcomes is critical for quality improvement and informing decisions concerning neonatal intensive care service provision.
    • Blood carbon dioxide levels and adverse outcome in neonatal hypoxic-ischemic encephalopathy.

      Nadeem, Montasser; Murray, Deirdre; Boylan, Geraldine; Dempsey, Eugene M; Ryan, C Anthony; Neonatal Intensive Care Unit, Cork University Maternity Hospital, Cork, Ireland. (2012-01-31)
      We investigated pCO(2) patterns and the relationship between pCO(2) levels and neurodevelopmental outcome in term infants with hypoxic-ischemic encephalopathy. Blood gases during the first 72 hours of life were collected from 52 infants with hypoxic-ischemic encephalopathy. Moderate hypocapnia (pCO(2) <3.3 kPa), severe hypocapnia (pCO(2) <2.6 kPa), and hypercapnia (pCO(2) >6.6 kPa) were correlated to neurodevelopmental outcome at 24 months. Normocapnia was documented in 416/551 (75.5%) of samples and was present during the entire 72 hours in only 6 out of 52 infants. Mean (standard deviation) pCO(2) values did not differ between infants with normal and abnormal outcomes: 5.43 (2.4) and 5.41 (2.03), respectively. There was no significant association between moderate hypocapnia, severe hypocapnia, or hypercapnia and adverse outcome (odds ratio [OR] = 1.84, 95% confidence interval [CI] = 0.49 to 6.89; OR = 3.16, CI = 0.14 to 28.45; and OR = 1.07, CI = 0.24 to 5.45, respectively). In conclusion, only one in nine newborns had normocapnia throughout the first 72 hours. Severe hypocapnia was rare and occurred only in ventilated babies. Hypercapnia and hypocapnia in infants with hypoxic-ischemic encephalopathy during the first 72 hours of life were not associated with adverse outcome.
    • Changes in the metabolic footprint of placental explant-conditioned medium cultured in different oxygen tensions from placentas of small for gestational age and normal pregnancies.

      Horgan, R P; Broadhurst, D I; Dunn, W B; Brown, M; Heazell, A E P; Kell, D B; Baker, P N; Kenny, L C; Department of Obstetrics and Gynaecology, University College Cork, Cork, University Maternity Hospital, The Anu Research Centre, Cork, Ireland., richard.horgan@ucc.ie (2012-01-31)
      Being born small for gestational age (SGA) confers significantly increased risks of perinatal morbidity and mortality. Accumulating evidence suggests that an SGA fetus results from a poorly perfused and abnormally developed placenta. Some of the placental features seen in SGA, such as abnormal cell turnover and impaired nutrient transport, can be reproduced by culture of placental explants in hypoxic conditions. Metabolic footprinting offers a hypothesis-generating strategy to investigate factors absorbed by and released from this tissue in vitro. Previously, metabolic footprinting of the conditioned culture media has identified differences in placental explants cultured under normoxic and hypoxic conditions and between normal pregnancies and those complicated by pre-eclampsia. In this study we aimed to examine the differences in the metabolic footprint of placental villous explants cultured at different oxygen (O(2)) tensions between women who deliver an SGA baby (n = 9) and those from normal controls (n = 8). Placental villous explants from cases and controls were cultured for 96 h in 1% (hypoxic), 6% (normoxic) and 20% (hyperoxic) O(2). Metabolic footprints were analysed by Ultra Performance Liquid Chromatography coupled to an electrospray hybrid LTQ-Orbitrap Mass Spectrometry (UPLC-MS). 574 metabolite features showed significant difference between SGA and normal at one or more of the oxygen tensions. SGA explant media cultured under hypoxic conditions was observed, on a univariate level, to exhibit the same metabolic signature as controls cultured under normoxic conditions in 49% of the metabolites of interest, suggesting that SGA tissue is acclimatised to hypoxic conditions in vivo. No such behaviour was observed under hyperoxic culture conditions. Glycerophospholipid and tryptophan metabolism were highlighted as areas of particular interest.
    • The decline of hysterectomy for benign disease.

      Horgan, R P; Burke, G; The Anu Research Centre, Department of Obstetrics and Gynaecology, University, College Cork, Cork University Maternity Hospital, Wilton, Cork., richard.horgan@ucc.ie (2012-01-31)
      Hysterectomy is one of the most common gynaecological surgical procedures performed but there appears to be a decline in the performance of this procedure in Ireland in recent times. We set out to establish the extent of the decline of hysterectomy and to explore possible explanations. Data for hysterectomy for benign disease from Ireland was obtained from the Hospital In-Patient Enquiry Scheme (HIPE) section of the Economic and Social Research Institute for the years 1999 to 2006. The total number of hysterectomies performed for benign disease showed a consistent decline during this time. There was a 36% reduction in the number of abdominal hysterectomy procedures performed.
    • Does caesarean delivery prevent anal incontinence?

      McLoughlin, Geraldine; Catherine McAuley School of Nursing and Midwifery University College Cork, Ireland. (2011-05)
    • Early blood glucose profile and neurodevelopmental outcome at two years in neonatal hypoxic-ischaemic encephalopathy.

      Nadeem, Montasser; Murray, Deirdre M; Boylan, Geraldine B; Dempsey, Eugene M; Ryan, Cornelius A; Neonatal Intensive Care Unit, Cork University Maternity Hospital, Cork, Ireland. (2012-01-31)
      BACKGROUND: To examine the blood glucose profile and the relationship between blood glucose levels and neurodevelopmental outcome in term infants with hypoxic-ischaemic encephalopathy. METHODS: Blood glucose values within 72 hours of birth were collected from 52 term infants with hypoxic-ischaemic encephalopathy. Hypoglycaemia [< 46.8 mg/dL (2.6 mmol/L)] and hyperglycaemia [> 150 mg/dL (8.3 mmol/L)] were correlated to neurodevelopmental outcome at 24 months of age. RESULTS: Four fifths of the 468 blood samples were in the normoglycaemic range (392/468:83.8%). Of the remaining 76 samples, 51.3% were in the hypoglycaemic range and (48.7%) were hyperglycaemic. A quarter of the hypoglycaemic samples (28.2%:11/39) and a third of the hyperglycaemic samples (32.4%:12/37) were recorded within the first 30 minutes of life. Mean (SD) blood glucose values did not differ between infants with normal and abnormal outcomes [4.89(2.28) mmol/L and 5.02(2.35) mmol/L, p value = 0.15] respectively. In term infants with hypoxic-ischaemic encephalopathy, early hypoglycaemia (between 0-6 hours of life) was associated with adverse outcome at 24 months of age [OR = 5.8, CI = 1.04-32)]. On multivariate analysis to adjust for grade of HIE this association was not statistically significant. Late hypoglycaemia (6-72 hours of life) was not associated with abnormal outcome [OR = 0.22, CI (0.04-1.14)]. The occurrence of hyperglycaemia was not associated with adverse outcome. CONCLUSION: During the first 72 hours of life, blood glucose profile in infants with hypoxic-ischaemic encephalopathy varies widely despite a management protocol. Early hypoglycaemia (0-6 hours of life) was associated with severe HIE, and thereby; adverse outcome.
    • Early blood glucose profile and neurodevelopmental outcome at two years in neonatal hypoxic-ischaemic encephalopathy.

      Nadeem, Montasser; Murray, Deirdre M; Boylan, Geraldine B; Dempsey, Eugene M; Ryan, Cornelius A; Neonatal Intensive Care Unit, Cork University Maternity Hospital, Cork, Ireland. (2011-02)
      To examine the blood glucose profile and the relationship between blood glucose levels and neurodevelopmental outcome in term infants with hypoxic-ischaemic encephalopathy.
    • Early continuous video electroencephalography in neonatal stroke.

      Walsh, Brian H; Low, Evonne; Bogue, Conor O; Murray, Deirdre M; Boylan, Geraldine B; Neonatal Brain Research Group, Cork University Maternity Hospital, Wilton, Cork, , Ireland. Bh.walsh@ucc.ie (2012-01-31)
      Perinatal stroke is the second most common cause of neonatal seizures, and can result in long-term neurological impairment. Diagnosis is often delayed until after seizure onset, owing to the subtle nature of associated signs. We report the early electroencephalographic (EEG) findings in a female infant with a perinatal infarction, born at 41 weeks 2 days and weighing 3.42 kg. Before the onset of seizures, the EEG from 3 hours after delivery demonstrated occasional focal sharp waves over the affected region. After electroclinical seizures, focal sharp waves became more frequent, complex, and of higher amplitude, particularly in 'quiet sleep'. In 'active sleep', sharp waves often disappeared. Diffusion-weighted imaging confirmed the infarct, demonstrating left frontal and parietal diffusion restriction. At 9 months, the infant has had no further seizures, and neurological examination is normal. To our knowledge, this report is the first to describe the EEG findings in perinatal stroke before seizures, and highlights the evolution of characteristic background EEG features.
    • 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.
    • Hemostasis in pre-eclampsia.

      Ismail, Siti Khadijah; Higgins, John R; Anu Research Centre, Department of Obstetrics and Gynaecology, University College, Cork, Cork University Maternity Hospital, Ireland. k.ismail@ucc.ie (2012-01-31)
      Pre-eclampsia (P-EC) is a multisystem disorder exclusive to pregnancy. It complicates ~2 to 8% of all pregnancies and remains a major cause of maternal mortality. P-EC is characterized by a profound hypercoagulable state. The delicate hemostatic balance that must be maintained in the uteroplacental circulation during pregnancy makes this system vulnerable to perturbation. An abnormal hemostatic pattern occurs within the uteroplacental circulation in P-EC compared with normal pregnancy. Much recent research has focused on the epidemiological link between inherited thrombophilia and P-EC. The data suggest a weak statistical association, indicating an improbable primary role in the pathogenesis. Without clear evidence, low molecular weight heparins have been widely used to reduce recurrence of P-EC in thrombophilia-positive women. This practice now should be reviewed. Future research needs to focus on improving our basic scientific understanding of the role of the hemostatic system in human placentation.
    • Hemostasis in pre-eclampsia.

      Ismail, Siti Khadijah; Higgins, John R; Anu Research Centre, Department of Obstetrics and Gynaecology, University College Cork, Cork University Maternity Hospital, Ireland. k.ismail@ucc.ie (2011-03)
      Pre-eclampsia (P-EC) is a multisystem disorder exclusive to pregnancy. It complicates ~2 to 8% of all pregnancies and remains a major cause of maternal mortality. P-EC is characterized by a profound hypercoagulable state. The delicate hemostatic balance that must be maintained in the uteroplacental circulation during pregnancy makes this system vulnerable to perturbation. An abnormal hemostatic pattern occurs within the uteroplacental circulation in P-EC compared with normal pregnancy. Much recent research has focused on the epidemiological link between inherited thrombophilia and P-EC. The data suggest a weak statistical association, indicating an improbable primary role in the pathogenesis. Without clear evidence, low molecular weight heparins have been widely used to reduce recurrence of P-EC in thrombophilia-positive women. This practice now should be reviewed. Future research needs to focus on improving our basic scientific understanding of the role of the hemostatic system in human placentation.
    • 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.
    • The management of reduced fetal movements in an uncomplicated pregnancy at term: results from an anonymous national online survey in the Republic of Ireland.

      Unterscheider, J; Horgan, R P; Greene, R A; Higgins, J R; The Anu Research Centre, Department of Obstetrics and Gynaecology, University, College Cork, Cork University Maternity Hospital, Wilton, Cork, Ireland., julia_unterscheider@hotmail.com (2012-01-31)
      There is currently inconsistent evidence and clinical guidance on how to best manage a pregnancy complicated by reduced fetal movements. This novel, web-based, anonymous questionnaire evaluated 96 assessment and management approaches from doctors working in obstetrics in the Republic of Ireland who were presented with a clinical scenario of a primigravida concerned about reduced fetal movements at 39+3 weeks' gestation. This study identified a lack of clinical practice guidelines available in maternity hospitals in the Republic of Ireland. We demonstrated that almost all clinicians applied more than one assessment method and that most incorporated a cardiotocograph into their assessment. There was a low uptake of simple symphysio-fundal height measurement and high usage of kickcharts. The minority of clinicians admitted or induced their patients. This survey identified the need for national and international guidelines to ensure safe antepartum care and delivery.
    • Metabolic profiling uncovers a phenotypic signature of small for gestational age in early pregnancy.

      Horgan, Richard P; Broadhurst, David I; Walsh, Sarah K; Dunn, Warwick B; Brown, Marie; Roberts, Claire T; North, Robyn A; McCowan, Lesley M; Kell, Douglas B; Baker, Philip N; et al. (2012-01-31)
      Being born small for gestational age (SGA) confers increased risks of perinatal morbidity and mortality and increases the risk of cardiovascular complications and diabetes in later life. Accumulating evidence suggests that the etiology of SGA is usually associated with poor placental vascular development in early pregnancy. We examined metabolomic profiles using ultra performance liquid chromatography-mass spectrometry (UPLC-MS) in three independent studies: (a) venous cord plasma from normal and SGA babies, (b) plasma from a rat model of placental insufficiency and controls, and (c) early pregnancy peripheral plasma samples from women who subsequently delivered a SGA baby and controls. Multivariate analysis by cross-validated Partial Least Squares Discriminant Analysis (PLS-DA) of all 3 studies showed a comprehensive and similar disruption of plasma metabolism. A multivariate predictive model combining 19 metabolites produced by a Genetic Algorithm-based search program gave an Odds Ratio for developing SGA of 44, with an area under the Receiver Operator Characteristic curve of 0.9. Sphingolipids, phospholipids, carnitines, and fatty acids were among this panel of metabolites. The finding of a consistent discriminatory metabolite signature in early pregnancy plasma preceding the onset of SGA offers insight into disease pathogenesis and offers the promise of a robust presymptomatic screening test.