[show abstract][hide abstract] ABSTRACT: 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.
Journal of Proteome Research 06/2011; 10(8):3660-73. · 5.06 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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.
[show abstract][hide abstract] ABSTRACT: 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.
Journal of obstetrics and gynaecology: the journal of the Institute of Obstetrics and Gynaecology 01/2010; 30(6):578-82. · 0.43 Impact Factor
[show abstract][hide abstract] ABSTRACT: Small for gestational age (SGA) can have lifelong consequences. Placental dysfunction is implicated in its pathophysiology. A reduced uterine perfusion pressure (RUPP) rat model can create an in vivo model of placental insufficiency. Metabolomics is the holistic study of the basic biochemistry within a biological system.The authors aimed to examine the metabolomic differences in (1) venous cord blood (VCB) plasma between SGA babies and normal controls and (2) plasma from the RUPP rat.Cord blood was collected from normally grown babies, and babies with confirmed SGA (n=7–8). Blood was also collected from RUPP, sham operated and control rats (n=7–9). All samples sets were analysed using Ultra Performance Liquid Chromatography/LTQ-Orbitrap Mass Spectrometry.In VCB, over 1700 metabolite features were detected, of which 900 (52%) showed significant difference between SGA and normally grown babies (p
Archives of Disease in Childhood-fetal and Neonatal Edition - ARCH DIS CHILD-FETAL NEONATAL. 01/2010; 95(1).
[show abstract][hide abstract] ABSTRACT: Pre-eclampsia (PE) is a multi-system disorder thought to be mediated by circulating factors released from damaged placental villous trophoblast. There is extensive evidence of changes in the villous tissue in PE, some of which may be replicated by culturing villous tissue in hypoxic conditions. Metabolic footprinting offers a hypothesis-generating strategy to investigate factors released from this tissue in vitro. This study investigated differences in the factors released from villous trophoblast from uncomplicated pregnancies (n=6) and those with PE (n=6). In both cases, explanted placental villous fragments were cultured for 96 h in 1% O(2) (hypoxia) or 6% O(2) (placental normoxia). Metabolites consumed from and released into serum-conditioned culture medium were analysed by Ultra Performance Liquid Chromatography-Mass Spectrometry (UPLC-MS). The relative concentration of 154 features of the metabolic footprint were observed to change in culture medium from uncomplicated pregnancies cultured in normoxic and hypoxic conditions (p<0.00005). 21 and 80 features were also different in culture medium from PE versus uncomplicated pregnancies cultured in hypoxic and normoxic conditions, respectively (p<0.00005). When comparing all 4 groups, 47 metabolic features showed a similar relative concentration in PE-derived media cultured in normoxic conditions to conditioned media from normal villous tissue cultured in hypoxic conditions. These data suggest that hypoxia may have a role in the placental pathogenesis of PE. Three areas of metabolism were highlighted for systems biology investigation; glutamate and glutamine, tryptophan metabolism and leukotriene or prostaglandin metabolism.
[show abstract][hide abstract] ABSTRACT: Note: The following files were submitted by the author for peer review, but cannot be converted to PDF. You must view these files (e.g. movies) online. Figure 2.emf Confidential American Journal of Perinatology
American Journal of Perinatology 09/2009; 26(8):605-612. · 1.57 Impact Factor
[show abstract][hide abstract] ABSTRACT: We set out to determine how women in pregnancy would like to be addressed and also to ascertain their preferred choice of title during pregnancy. A questionnaire was administered to 925 women attending the antenatal clinics at the Unified Maternity Hospitals, the private rooms of the consultants of these hospitals and the private rooms of the consultants of the Bons Secour Hospital. Midwifery and medical staff (183 in total) were also invited to respond to a similar questionnaire. The response rate was 71.2% from the survey of women. The vast majority (82.1%) preferred to be addressed by their first name. Only 1.7% expressed a preference for a formal mode of address and the remainder (16.1%) did not mind. The women were in favour of being called ‘patient’ (32.8%), followed closely by ‘mother’ (28.9%) and then ‘lady’ (12.1%) as their first choice. Women wishing to be called ‘patient’ for first choice did not significantly differ from the remainder of the study group in age and gestation but were significantly more likely to have a lower number of previous pregnancies and less children (P < 0.05). First choice of title was not significantly influenced by category of patient (public vs. private). The staff survey yielded a response rate of 73.8%. The majority (83.5%) of health professionals preferred to address women by their first name, 6% preferred to address them more formally and 10.5% did not mind. ‘Mother’ (29.2%) was the most popular first choice, followed by ‘lady’ (22.3%), ‘woman’ (16.9%) and then ‘patient’ (13.8%). Medical staff (doctors) were significantly more likely to choose ‘patient’ (OR 26.5, 95% CI 7.8, 89.7; P < 0.001) when compared to midwives.
[show abstract][hide abstract] ABSTRACT: There are many established risk factors for babies who are small for gestational age (SGA) by population birth weight centiles (usually defined as <10th centile). The confirmed maternal risk factors include short stature, low weight, Indian or Asian ethnicity, nulliparity, mother born SGA, cigarette smoking and cocaine use. Maternal medical history of: chronic hypertension, renal disease, anti-phospholipid syndrome and malaria are associated with increased SGA. Risk factors developing in pregnancy include heavy bleeding in early pregnancy, placental abruption, pre-eclampsia and gestational hypertension. A short or very long inter-pregnancy interval, previous SGA infant or previous stillbirth are also risk factors. Paternal factors including changed paternity, short stature and father born SGA also contribute. Factors associated with reduced risk of SGA or increased birth weight include high maternal milk consumption and high intakes of green leafy vegetables and fruit. Future studies need to investigate risk factors for babies SGA by customised centiles as these babies have greater morbidity and mortality than babies defined as SGA by population centiles.
Best practice & research. Clinical obstetrics & gynaecology 07/2009; 23(6):779-93. · 1.87 Impact Factor
[show abstract][hide abstract] ABSTRACT: Despite widespread use of fetal heart rate monitoring, the timing of injury in hypoxic-ischemic encephalopathy (HIE) remains unclear. Our aim was to examine fetal heart rate patterns during labor in infants with clinical and electroencephalographic (EEG) evidence of HIE and to relate these findings to neurodevelopmental outcome. Timing of onset of pathological cardiotocographs (CTGs) was determined in each case by two blinded reviewers and related to EEG grade at birth and neurological outcome at 24 months. CTGs were available in 35 infants with HIE (17 mild, 12 moderate, 6 severe on EEG). Admission CTGs were normal in 24/35 (69%), suspicious in 8/35 (23%), and pathological in 3/35 (8%). All CTGs developed nonreassuring features prior to delivery. Three patterns of fetal heart rate abnormalities were seen: group 1, abnormal CTGs on admission in 11/35 (31%); group 2, normal CTGs on admission with gradual deterioration to pathological in 20/35 cases (57%); and group 3, normal CTGs on admission with acute sentinel events in 4/35 (11.5%). The median (interquartile range) duration between the development of pathological CTGs and delivery was 145 (81, 221) minutes in group 2 and 22 (12, 28) minutes in group 3. There was no correlation between duration of pathological CTG trace and grade of encephalopathy (R = 0.09, P = 0.63) or neurological outcome (P = 0.75). However, the grade of encephalopathy was significantly worse in group 3 (P = 0.001), with a trend to worse outcomes. The majority of infants with HIE have normal CTG traces on admission but develop pathological CTG patterns within hours of delivery. More severe encephalopathy was associated with normal admission CTG and acute sentinel events shortly before delivery.
American Journal of Perinatology 05/2009; 26(8):605-12. · 1.57 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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.
Irish medical journal 04/2009; 102(3):70, 72-3. · 0.51 Impact Factor
[show abstract][hide abstract] ABSTRACT: 'Omic' technologies represent a strategy towards high-throughput, simultaneous analysis of thousands of biological molecules. Their development has been accelerated in the post-genomic era since these molecules represent the interaction of genes and environment or the 'functional genome'. Omic domains are of particular interest in the search for predictive disease biomarkers and have additional relevance in understanding pathophysiology and the development of molecularly targeted therapeutics. This review examines the fields of proteomics and metabolomics in the context of obstetrics and gynaecology, including a discussion of methodology, challenges, potential applications and current research.
BJOG An International Journal of Obstetrics & Gynaecology 02/2009; 116(2):173-81. · 3.76 Impact Factor
[show abstract][hide abstract] ABSTRACT: Female sterilisation is an extensively used method of contraception all over the world but there appears to be a decline in the performance of this procedure in Ireland. There also appears to be an increased uptake of safe, long-acting contraceptive alternatives. We set out to establish the extent of the decline of laparoscopic sterilisation and to explore possible explanations. Data for female sterilisation 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 2004. Recent sales figures for long acting reversible contraceptives, specifically the levo-norgestrel-loaded intrauterine system (LNG-IUS) (Mirena) and the etonogestrel implant (Implanon) were also obtained. Laparoscopic tubal ligations reduced from 2,566(1999) to 910 (2004). In the corresponding period the use of Mirena coils increased from 4,840 (1999) to 17,077 (2004).
Irish medical journal 03/2008; 101(2):53-5. · 0.51 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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.
Irish medical journal 03/2005; 98(2):55-7. · 0.51 Impact Factor