Amanda Dennis

Iron Deficiency Anaemia in Pregnancy and Postpartum: Pathophysiology and Effect of Oral versus Intravenous Iron Therapy

Nutritional iron-deficiency anaemia (IDA) is the most common disorder in the world, affecting more than two billion people. The World Health Organizations global database on anaemia has estimated a prevalence of 14% based on a regression-based analysis. Recent data show that the prevalence of IDA in pregnant women in industrialized countries is 17.4% while the incidence of IDA in developing countries increases significantly up to 56%. Although oral iron supplementation is widely used for the treatment of IDA, not all patients respond adequately to oral iron therapy. This is due to several factors including the side effects of oral iron which lead to poor compliance and lack of efficacy. The side effects, predominantly gastrointestinal discomfort, occur in a large cohort of patients taking oral iron preparations. Previously, the use of intravenous iron had been associated with undesirable and sometimes serious side effects and therefore was underutilised. However, in recent years, new type II and III iron complexes have been developed, which offer better compliance and toleration as well as high efficacy with a good safety profile. In summary, intravenous iron can be used safely for a rapid repletion of iron stores and correction of anaemia during and after pregnancy.

A prospective randomized, controlled trial of intravenous versus oral iron for moderate iron deficiency anaemia of pregnancy.

Abstract.u2002 Khalafallah A, Dennis A, Bates J, Bates G, Robertson IK, Smith L, Ball MJ, Seaton D, Brain T, Rasko JEJ Launceston General Hospital (LGH), Australia; University of Tasmania, Australia; and Centenary Institute, University of Sydney, NSW, Australia) A prospective randomized, controlled trial of intravenous versus oral iron for moderate iron deficiency anaemia of pregnancy. J Intern Med 2010; 268: 286–295.

Three-year follow-up of a randomised clinical trial of intravenous versus oral iron for anaemia in pregnancy

Background To date, there are no data available concerning the impact of iron therapy on the long-term well-being and health-related quality of life (HRQoL) in pregnancy. Objective To assess the long-term effect of iron therapy on HRQoL in pregnancy. Design This is a follow-up study conducted between January 2010 and January 2011 of an earlier randomised open-label clinical trial of intravenous and oral iron versus oral iron for pregnancy-related iron deficiency anaemia. We used a modified version of the SF-36 questionnaire together with the original prospective HRQoL data collected during and after pregnancy. Participants and interventions Of the original evaluable 183 pregnant Caucasian women randomised to receive oral iron or a single intravenous iron polymaltose infusion followed by oral iron maintenance, 126 women completed the follow-up HRQoL study. Methods The participants were followed up 4u2005weeks after treatment, predelivery and postdelivery for a median period of 32u2005months (range, 26–42) with a well-being and HRQoL questionnaire using a modified SF-36 QoL-survey and child growth charts as set by the Australasian Paediatric Endocrine Group (APEG). Results Patients who received intravenous iron demonstrated significantly higher haemoglobin and serum ferritin levels (p<0.001). There were strong associations between iron status and a number of the HRQoL parameters, with improved general health (p<0.001), improved vitality (physical energy) (p<0.001), less psychological downheartedness (p=0.005), less clinical depression (p=0.003) and overall improved mental health (p<0.001). The duration of breastfeeding was longer (p=0.046) in the intravenous iron group. The babies born in both groups recorded similarly on APEG growth chart assessments. Conclusions Our data suggest that HRQoL is improved until after pregnancy in anaemic pregnant women by repletion of their iron stores during pregnancy. About 80% of the intravenous iron group showed a maintained normal ferritin until delivery with long-term benefits. Further studies to confirm these findings are warranted.

D-Dimer levels at different stages of pregnancy in Australian women: a single centre study using two different immunoturbidimetric assays.

BACKGROUNDnTo date there is minimal data available on D-Dimer levels at different stages of pregnancy.nnnPATIENTS AND METHODSnWe prospectively measured D-Dimer levels in 632 consecutive pregnant women from March 2007 to January 2009. The median age of the participants was 31 years (range; 18-42) with a median weight of 78 kilograms (range; 46-137). All subjects were investigated during each trimester with two different immunoturbidimetric assays; D-Dimer PLUS and INNOVANCE D-Dimer. D-Dimer levels were determined using a Sysmex® CA 1500 analyser.nnnRESULTSnOur data demonstrate that D-Dimer levels in pregnancy show different patterns of rise within the first trimester, depending on the assay used; D-Dimer PLUS=0.88 (SD: mean ratio), INNOVANCE D-Dimer=0.72 (SD: mean ratio). Furthermore, the rise in mean results was greater for the INNOVANCE D-Dimer assay compared to the D-Dimer PLUS assay as shown by the ratio of third to first trimester results of 3.68 and 1.96 respectively. Both D-Dimer assays demonstrated moderate levels of intra-subject variability, with overall mean CVs of 16.5% (D-Dimer PLUS) and 16.9% (INNOVANCE D-Dimer). Furthermore, we studied the association between D-Dimer levels and occurrence of diseases of pregnancy. For both assays, there was no consistently interpretable evidence of an association between raised mean D-Dimer levels or rising D-Dimer levels and any of the diseases or conditions associated with pregnancy.nnnCONCLUSIONnOur data suggest that the INNOVANCE D-Dimer assay increases significantly with the advancement of pregnancy, and is more sensitive than D-Dimer PLUS assay in the pregnant population.

Fasting blood glucose predicts response to extended-release metformin in gestational diabetes mellitus

Metformin is increasingly accepted as an alternative to insulin therapy in gestational diabetes mellitus (GDM). The Metformin in Gestational Diabetes (MiG) trial reported similar pregnancy outcomes for metformin versus insulin; however, supplemental insulin was required in 46% of women on metformin.

Analysis of emergency peripartum hysterectomy in Northern Tasmania.

OBJECTIVEnThere is a need for emerging Australian data on emergency peripartum hysterectomy (EPH) especially in rural areas due to the associated high maternal morbidity and mortality. The aim of this study is to review the incidence and complications of EPH in the northern region of Tasmania.nnnDESIGNnA retrospective cohort study at a single health care institution during a 10 year period.nnnSETTINGnLaunceston General Hospital, the main maternity referral centre for the northern region of Tasmania.nnnPARTICIPANTSnCase notes of women coded with hysterectomy during childbirth were included and analysed.nnnMAIN OUTCOME MEASURESnPrimary outcomes were maternal and neonatal morbidity and mortality.nnnRESULTSnEighteen women were identified, giving an incidence of 1.01 per 1000 births. Indications for surgery were abnormal placentation, uterine atony and uterine rupture. Maternal morbidity was high, and included intensive care admissions (55%), disseminated intravascular coagulopathy (50%), hypovolemic shock (38%), febrile illness (27%) and urinary tract injuries (22%). The mean estimated total blood loss was 4091.6u2009mL, and 88% of women received blood transfusions. All women received prophylactic antibiotics. Women with morbidly adherent placenta were likely to experience more complications and transfusions. There were no maternal or neonatal deaths identified.nnnCONCLUSIONnThe rate of peripartum hysterectomy in rural Tasmania is higher compared with other Australian tertiary-level hospitals, suggesting that Australian women birthing in rural and regional areas might be at greater risk. Maternal morbidity associated with abnormal placentation is high; hence, better diagnostic modalities and multidisciplinary antenatal management are required to improve maternal outcomes.Objective n nThere is a need for emerging Australian data on emergency peripartum hysterectomy (EPH) especially in rural areas due to the associated high maternal morbidity and mortality. The aim of this study is to review the incidence and complications of EPH in the northern region of Tasmania. n n n nDesign n nA retrospective cohort study at a single health care institution during a 10 year period. n n n nSetting n nLaunceston General Hospital, the main maternity referral centre for the northern region of Tasmania. n n n nParticipants n nCase notes of women coded with hysterectomy during childbirth were included and analysed. n n n nMain outcome measures n nPrimary outcomes were maternal and neonatal morbidity and mortality. n n n nResults n nEighteen women were identified, giving an incidence of 1.01 per 1000 births. Indications for surgery were abnormal placentation, uterine atony and uterine rupture. Maternal morbidity was high, and included intensive care admissions (55%), disseminated intravascular coagulopathy (50%), hypovolemic shock (38%), febrile illness (27%) and urinary tract injuries (22%). The mean estimated total blood loss was 4091.6u2009mL, and 88% of women received blood transfusions. All women received prophylactic antibiotics. Women with morbidly adherent placenta were likely to experience more complications and transfusions. There were no maternal or neonatal deaths identified. n n n nConclusion n nThe rate of peripartum hysterectomy in rural Tasmania is higher compared with other Australian tertiary-level hospitals, suggesting that Australian women birthing in rural and regional areas might be at greater risk. Maternal morbidity associated with abnormal placentation is high; hence, better diagnostic modalities and multidisciplinary antenatal management are required to improve maternal outcomes.

Review of Management and Outcomes in Women with Thrombophilia Risk during Pregnancy at a Single Institution

Pregnancy is a hypercoagulable state associated with an increased risk of venous thromboembolic disease (VTE). We retrospectively studied 38 Caucasian pregnant women with thrombophilia risk and compared their obstetric outcomes with a matched cohort without known thrombophilia risk during the period between January 2007 and December 2010. There were (2) cases with factor V Leiden, (6) prothrombin gene mutation, (1) antithrombin III deficiency, (2) protein C deficiency, (3) protein S deficiency, (10) MTHFR mutation, (7) anti-cardiolipin antibodies, and (1) lupus anticoagulant. Patients without thrombophilia who presented with recurrent unprovoked VTE were considered as high risk (6 cases). Most patients received anticoagulation (34/38) with aspirin only (6), enoxaparin (27), and warfarin (1). Twenty-six out of thirty-eight pregnant women (68.4%) with an increased risk of thrombophilia experienced one or more obstetric complications defined as hypertension, preeclampsia, placenta abruptio, VTE, and oligohydramnios, compared with 15 out of 40 (37.5%) pregnant women in the control group (OR 3.6; 95% CI 1.42, 9.21, P < 0.001). The incidence of obstetric complications was significantly higher in the thrombophilia group compared to the controls. However, these complications were the lowest among patients who received full-dose anticoagulation. Our study suggests that strict application of anticoagulation therapy for thrombophilia of pregnancy is associated with an improved pregnancy outcome. The study was registered in the Australian and New Zealand Clinical Trials Registry under ACTRN12612001094864.

A prospective randomised controlled trial of a single intravenous infusion of ferric carboxymaltose, versus single intravenous iron polymaltose or daily oral ferrous sulphate in the treatment of iron deficiency anaemia in pregnancy

Iron deficiency anaemia (IDA) is the most common nutritional deficiency affecting pregnant women worldwide. This study aims to compare the efficacy and safety of a newly available intravenous (IV) iron preparation, ferric carboxymaltose (FCM), against IV iron polymaltose (IPM), and standard oral iron (ferrous sulphate) for the treatment of IDA in pregnancy. This is an open-labelled prospective randomised controlled trial (RCT) with intention-to-treat analysis conducted at a primary health care facility with a single tertiary referral centre in Launceston. Tasmania, Australia. A 3-arm randomised controlled trial was conducted comparing a single IV infusion of 1000mg of FCM (n = 83 patients) over 15 minutes against a single IV infusion of 1000mg of IPM (n = 82) over 2 hours against 325mg daily oral ferrous sulphate (n = 81) until delivery, for the treatment of IDA in pregnancy. A total of 246 consecutive pregnant women were recruited between September 2013 and July 2014. The median age was 28 years, with a median and mean gestation of 27 weeks. The median serum ferritin was 9µg/L, with a mean of 13µg/L. The mean haemoglobin (Hb) was 114g/L. The primary outcome was the change in ferritin and Hb levels at 4 weeks after intervention. Secondary outcomes included ferritin and Hb improvements at predelivery, safety, tolerability, quality of life (QoL), cost utility, and fetal outcomes. The mean Hb level differences between the baseline intervention time point and 4 weeks thereafter were significantly higher in the FCM versus the oral group by 4.35g/L (95% CI: 1.64-7.05; P = 0.0006) and in the IPM vs the oral group by 4.08g/L (95% CI: 1.57-6.60; P = 0.0005), but not different between the FCM and IPM groups (0.26g/L; 95% CI: -2.59 to 3.11; P = 0.9740). The mean ferritin level differences were significantly higher at 4 weeks in the FCM vs oral iron group by 166µg/L (95% CI: 138-194; P < 0.0001) and in the IPM vs oral iron group by 145µg/L (95% CI: 109-1180, P < 0.0001), but not between the 2 IV groups (21.5µg/L; 95% CI: -23.9 to 66.9; P = 0.4989). Administration of IV FCM during pregnancy was safe and better tolerated than IV IPM or oral iron. Compliance to oral iron was the lowest amongst treatment groups with one-third of the patients missing doses of daily iron tablets. Significant improvement in overall QoL scores was observed in both IV iron supplement groups by achieving normal ferritin following effective and prompt repletion of iron stores, compared to the oral iron group (P = 0.04, 95% CI: 21.3, 1.8). The overall cost utility of IV FCM and IV IPM appear to be similar to oral iron. There were no differences in the fetal outcomes between the 3 trial arms. In conclusion, this study demonstrates that a single IV iron infusion is an effective and safe option for treatment of IDA during pregnancy. FCM was more convenient than other treatments. Rapid parenteral iron repletion can improve iron stores, Hb levels and QoL in pregnant women, with ongoing benefits until delivery. Integration of IV iron for IDA in pregnancy can potentially improve pregnancy outcomes for the mother. Update of guidelines to integrate the use of new IV iron preparations in pregnancy is warranted.

Utility of antenatal clinical factors for prediction of postpartum outcomes in women with gestational diabetes mellitus (GDM)

Gestational diabetes mellitus (GDM) is associated with life‐long increased risk of type 2 diabetes: affected women are advised to undergo oral glucose tolerance testing (OGTT) at 6–12 weeks postpartum, then glucose screening every 1–3 years.

Obstetric and perinatal morbidity in northern Tasmanian Aboriginal population: a retrospective cohort study

INTRODUCTIONnAboriginal and Torres Strait Islander women are at increased risk of maternal morbidity and mortality as compared to non-Aboriginals. Similarly, aboriginal babies are at increased risk of low birth weight and infant mortality.nnnAIMnTo investigate the independent association of aboriginality with Tasmanian maternal and neonatal morbidity.nnnMATERIALS AND METHODSnA retrospective analysis of all the births (gestation more than 20 weeks) from June 2013 to May 2014 was conducted at the Launceston General Hospital, Tasmania. The study compared 66 Aboriginal (4.2% of the total births) to 1477 non-aboriginal births for maternal and neonatal morbidity. Comparisons were made using logistic regression. The outcome measures were maternal and neonatal morbidity.nnnRESULTSnSignificantly higher number of aboriginal women (49% vs 19%; OR 4.15 90%CI 2.52- 6.85) smoked and used illicit drugs (15% vs 2%; OR 9.24; 95%CI 4.28-19.96) than the non-aboriginal women (both p<0.001). Maternal morbidity was not significantly different between aboriginal compared to non-aboriginal women (OR 0.64; 95%CI 0.36-1.14; p=0.13; adjusted OR 1.00; 95%CI 0.52-1.93; p=0.99). Factors positively associated with maternal morbidity included: age (OR 1.28; 95%CI 1.13-1.46; p<0.01) and BMI (OR 1.50; 95%CI 1.33-1.70; p<0.01). The unadjusted OR of neonatal morbidity for aboriginality was 1.98 (95%CI 1.17-3.34; p=0.01) and adjusted was 1.45 (95%CI 0.77-2.72; p=0.25). Factors positively associated with neonatal morbidity included smoking (OR 2.24; 95%CI 1.59-3.14; p<0.01), illicit drug use 95%CI 1.49-(OR 3.26; 95%CI 1.49-7.13; p <0.01), hypertension (OR 2.49; 95%CI 1.61-3.84; p<0.01) and diabetes (OR 1.92; 95%CI 1.33-2.78; p<0.01).nnnCONCLUSIONnThe composite Aboriginal maternal morbidity does not differ, however the increased rates of smoking and illicit drug use are largely responsible for neonatal morbidity. Along with strengthening strategies to decrease medical comorbidities in aboriginals, we recommend intensifying smoking and illicit drug cessation programs.