• Can a more detailed evaluation of excision margins refine cytologic follow-up of women post-LLETZ for high-grade dysplasia?

      Treacy, Ann; Devaney, Deirdre; Mulligan, Niall J; Boyd, William; O'Keane, John Conor; Department of Histopathology, Mater Misericordiae University Hospital, Eccles Street, Dublin, Ireland. anntreacy@mac.com (2010-09)
      The relationship between dysplastic changes in the cervical epithelium and progression to in situ carcinoma and invasive carcinoma has been extensively studied. The removal of dysplastic epithelium through the long loop excision of the transformation zone (LLETZ) in 95% of the cases is curative. About 18% to 37% of LLETZ specimens with dysplasia at the margins have recurrent/residual disease. Earlier small studies suggest that the degree of dysplasia at the margins could predict for recurrence and allow a risk-based stratification of follow-up. We tested this hypothesis in a large group of women post-LLETZ for high-grade dysplasia with follow-up histology and cytology over a 12-year period. The cases were divided according to the excision margin status for dysplasia and if positive, low-grade or high-grade dysplasia. The groups were compared to assess whether the LLETZ specimens' margin status had an impact on the subsequent cytology or histology results. Positive follow-up results were defined as any grade of dysplasia in cytology or histology. Two thousand three hundred twenty-one women had LLETZs containing high-grade dysplasia over the 12-year period. One thousand five hundred thirty-four (66.1%) women had full histology and cytology follow-up available. Eight hundred twenty (53.4%) LLETZ specimens had positive margins and 714 (46.6%) had negative margins. The grade of dysplasia at the margins was available in 796 cases (97%) with 115 (15%) showing low-grade dysplasia and 680 (85%) high-grade dysplasia. One hundred seventy (20.7%) of the specimens with positive margins had positive follow-up results compared with 105 (14.7%) of the specimens with negative margins. The presence of dysplasia at an LLETZ margin is associated with dysplasia on follow-up cytology and histology (P=0.0021); however, the grade of dysplasia at the excision margin is not predictive of recurrent/residual dysplasia.
    • The impact of ultrasonographic placental architecture on antenatal course, labor and delivery in a low-risk primigravid population.

      Cooley, Sharon M; Donnelly, Jennifer C; Walsh, Thomas; McMahon, Corrina; Gillan, John; Geary, Michael P; Department of Obstetrics and Gynaecology, Rotunda Hospital, Dublin 1, Ireland., smcooley@hotmail.com (2012-02-01)
      OBJECTIVE: To ascertain the impact of placental architecture on antenatal course and labor delivery in a low-risk primigravid population. METHODS: This study involves prospective recruitment of 1011 low-risk primigravids with placental ultrasound at 22?24 weeks and 36 weeks. Detailed postnatal review of all mothers and infants was undertaken. Retrospective analysis of ultrasound and clinical outcome data was performed. RESULTS: Eight hundred ten women with complete outcome data were available. Anterior placentation was statistically associated with intrauterine growth restriction (IUGR) and preterm birth and fundal placentation was significantly associated with a higher incidence of pregnancy-induced hypertension and infants with a birthweight less than the 9th centile. Placental infarcts in the third trimester was significantly increased in cases complicated by pre-eclampsia (PET) and in cases with fetal acidosis. Placental calcification was associated a 40-fold increase in the incidence of IUGR. Placental lakes in the second trimester were more prevalent in patients with threatened miscarriage. Increased placental thickness was associated with a higher rate of fetal acidosis. The Grannum grade of the placenta was higher with threatened first or second trimester loss, PET and in infants born less than 9th centile for gestation. CONCLUSION: Placental site and architecture impact on the incidence of maternal and fetal disease.
    • The impact of ultrasonographic placental architecture on antenatal course, labor and delivery in a low-risk primigravid population.

      Cooley, Sharon M; Donnelly, Jennifer C; Walsh, Thomas; McMahon, Corrina; Gillan, John; Geary, Michael P; Department of Obstetrics and Gynaecology, Rotunda Hospital, Dublin 1, Ireland. smcooley@hotmail.com (2011-03)
      To ascertain the impact of placental architecture on antenatal course and labor delivery in a low-risk primigravid population.
    • The impact of umbilical and uterine artery Doppler indices on antenatal course, labor and delivery in a low-risk primigravid population.

      Cooley, Sharon M; Donnelly, Jennifer C; Walsh, Thomas; MacMahon, Corrina; Gillan, John; Geary, Michael P; Department of Obstetrics and Gynaecology, Rotunda Hospital, Dublin 1, Ireland., smcooley@hotmail.com (2012-02-01)
      AIMS: To evaluate the impact of umbilical and uterine artery Doppler in the second and third trimester on antenatal course, labor and delivery in a low-risk primigravid population. METHODS: Prospective recruitment of 1011 low-risk primigravidas with uterine and umbilical artery Doppler assessment at 22-24 weeks and 36 weeks. All mothers and infants were reviewed postnatally with a retrospective analysis of ultrasound and clinical outcome data. RESULTS: Elevated uterine artery indices were associated with increased rates of threatened miscarriage, higher rates of pre-eclampsia (PET) and a higher incidence of fetal birth weight <2nd and 9th centile for gestation. Uterine artery pulsatility index (PI) >95th centile for gestation was associated with statistically higher rates of small-for-gestational age (SGA) infants. Elevated umbilical artery indices were associated with higher rates of induction of labor and a higher incidence of fetal birth weight infants <2nd and 9th centile for gestation. Umbilical artery PI >95th centile for gestation was associated with statistically higher rates of SGA infants. CONCLUSION: Elevated uterine and umbilical artery indices are associated with higher rates of maternal and fetal disease.
    • The impact of umbilical and uterine artery Doppler indices on antenatal course, labor and delivery in a low-risk primigravid population.

      Cooley, Sharon M; Donnelly, Jennifer C; Walsh, Thomas; MacMahon, Corrina; Gillan, John; Geary, Michael P; Department of Obstetrics and Gynaecology, Rotunda Hospital, Dublin 1, Ireland. smcooley@hotmail.com (2011-03)
      To evaluate the impact of umbilical and uterine artery Doppler in the second and third trimester on antenatal course, labor and delivery in a low-risk primigravid population.
    • Laboratory assessment of iron status in pregnancy.

      Walsh, Thomas; O'Broin, Sean D; Cooley, Sharon; Donnelly, Jennifer; Kennedy, John; Harrison, Robert F; McMahon, Corinna; Geary, Michael; Rotunda Hospital, Dublin, Ireland. (2012-02-01)
      BACKGROUND: Efforts to improve maternal nutrition during pregnancy prompted an observational study of the occurrence of maternal iron deficiency and its laboratory diagnosis in almost 500 pregnancies. METHODS: In this longitudinal study, the biochemical and haematological iron indices of women (n=492) attending a prenatal clinic in a Dublin maternity hospital were assessed at first booking (mean 15.9 weeks), and after 24 weeks, and 36 weeks of gestation. Full blood counts were measured. Serum ferritin (SF), zinc protoporphyrin (ZPP), and transferrin receptor (sTfR) concentrations were assayed and transferrin receptor index (sTfR-Index) was calculated. The occurrence of low values and their diagnostic values were considered. RESULTS: A high occurrence iron deficiency (ID) at first booking (SF<12 mug/L) had increased over six-fold by 24 weeks, and all biochemical iron indices reflected progressive iron depletion right up to term. The WHO recommended anaemia "cut-off" (Hb<110 g/L) was insensitive to biochemical iron deficiency at booking, missing over 90% of the low SF values (SF<12 mug/L) which were mostly associated with much higher Hb levels. CONCLUSIONS: This study stresses the importance of including a biochemical index of iron status in prenatal screening and supports SF as the best indicator of biochemical ID overall. sTfR was insensitive to iron deficiency in early pregnancy, whereas the sTfR-Index, as a ratio, has the potential to distinguish between ID and physiological anaemia, and may offer stability in the assessment of iron stores from early pregnancy to full term. A policy of early screening of both Hb and SF concentrations is recommended as the minimum requirement for surveillance of maternal iron status in pregnancy.
    • Laboratory assessment of iron status in pregnancy.

      Walsh, Thomas; O'Broin, Sean D; Cooley, Sharon; Donnelly, Jennifer; Kennedy, John; Harrison, Robert F; McMahon, Corinna; Geary, Michael; Rotunda Hospital, Dublin, Ireland. (2011-07)
      Efforts to improve maternal nutrition during pregnancy prompted an observational study of the occurrence of maternal iron deficiency and its laboratory diagnosis in almost 500 pregnancies.
    • Platelet reactivity changes significantly throughout all trimesters of pregnancy compared with the nonpregnant state: a prospective study.

      Burke, N; Flood, K; Murray, A; Cotter, B; Dempsey, M; Fay, L; Dicker, P; Geary, M P; Kenny, D; Malone, F D; et al. (2013-12)
      Platelets play an important role in the pathophysiology of uteroplacental disease and platelet reactivity may be an important marker of uteroplacental disease activity. However, platelet reactivity has not been evaluated comprehensively in normal pregnancy. We sought to evaluate platelet reactivity using a number of agonists at defined time points in pregnancy using a novel platelet assay and compare these with a nonpregnant cohort.
    • Should children with inherited metabolic disorders receive varicella vaccination?

      Varghese, M; Cafferkey, M; O'Regan, M; Monavari, A A; Treacy, E P; National Centre for Inherited Metabolic Disorders, Children's University Hospital, Dublin, Ireland. (2011-01)
      The aim was to determine the rate of varicella infection and complications in children with disorders of intermediary metabolism (IEM) between the ages of 1 and 16 years attending our national metabolic referral centre. Of 126 children identified, a response was received from 122. A history of previous varicella infection was identified in 64 cases (53%) and of varicella vaccination in 5 (4%). Fifty-three (43%) patients apparently did not have a history of clinical varicella infection. Of the 64 children with a history of varicella infection, five required hospitalisation for complications, including life-threatening lactic acidosis in one patient with mitochondrial disease and metabolic decompensation in four patients. In conclusion, varicella infection may cause an increased risk of metabolic decompensation in patients with IEMs. We propose that a trial of varicella vaccination be considered for this cohort of patients with monitoring of its safety and efficacy.
    • Teenage pregnancy in type 1 diabetes mellitus.

      Carmody, David; Doyle, Aoife; Firth, Richard G R; Byrne, Maria M; Daly, Sean; Mc Auliffe, Fionnuala; Foley, Micheal; Coulter-Smith, Samuel; Kinsley, Brendan T; Dublin Diabetes in Pregnancy Service, Mater Misericordiae University Hospital, National Maternity Hospital, Coombe Women's Hospital and Rotunda Hospitals, Dublin, Ireland. (2010-03)
      Younger maternal age at delivery has been linked to adverse reproductive outcomes. Pregnancy complicated by type 1 diabetes mellitus (T1DM) is also associated with adverse pregnancy outcomes. Optimising diabetic glycaemic control prior to pregnancy is known to reduce the rate of congenital abnormalities and improve pregnancy outcomes. Teenage pregnancies are not usually planned and little data exist on teenage pregnancy complicated by T1DM. We sought to identify the glycemic control achieved in teenage pregnancy with T1DM and to clarify if there is an associated increase in adverse pregnancy outcomes compared to those seen in older women with T1DM. We compared outcomes in 18 teenagers (TG) with 582 older women with T1DM (CON) from 1995-2007. TG booked to the combined diabetes-obstetrical service at a median gestational age of 11 weeks (range 6-22) compared to 7 weeks in CON (range 4-40, p < 0.02). Glycaemic was worse in TG compared to CON at 13, 26 and 35 weeks gestation, despite higher insulin doses. First trimester miscarriage rate did not differ between groups. Major congenital anomaly rate was 6.2% (1/16) compared to 3.2% in CON. This preliminary study has demonstrated that pregnant teenage women with T1DM book later to specialised care and have worse glycaemic control in pregnancy compared to older women with T1DM. This group also appear to be more insulin resistant than older women in early pregnancy. Our data would suggest that teenagers with type 1 diabetes mellitus may constitute a high-risk group for adverse pregnancy outcomes.
    • Utility of therapeutic drug monitoring in the management of HIV-infected pregnant women in receipt of lopinavir.

      Caswell, R J; Phillips, D; Chaponda, M; Khoo, S H; Taylor, G P; Ghanem, M; Poulton, M; Welch, J; Gibbons, S; Jackson, V; et al. (2011-01)
      The pharmacokinetics of antiretroviral drugs in pregnancy is poorly understood. We reviewed the use of therapeutic drug monitoring (TDM) in clinical settings to document plasma concentrations of lopinavir during pregnancy and investigated how clinicians acted upon TDM results. A retrospective review was carried out of all HIV-infected pregnant women taking boosted lopinavir-based highly active antiretroviral therapy (HAART) at five National Health Service (NHS) centres in the UK between May 2004 and March 2007. Seventy-three women in receipt of lopinavir were identified, of whom 89% had plasma lopinavir concentrations above the suggested minimum recommended for wild-type HIV. Initial TDM results prompted dosage change in 10% and assessment of adherence and/or pharmacist review in 11%. TDM was repeated in 29%. TDM can play an important role in the clinical management of HIV-positive pregnant women, allowing informed dose modification and an alternative measure of adherence.