Systemic methotrexate (MTX) in early pregnancy: a retrospective study of a tertiary maternity hospital.

BACKGROUND: Methotrexate (MTX) is used in clinical practice as a medical treatment option in patients with early pregnancy complications like ectopic pregnancy. AIMS: To review systemic MTX therapy use in the first trimester of pregnancy in our hospital and to examine subsequent clinical outcomes. METHODS: Retrospective review of all women treated with systemic MTX in early pregnancy identified from electronic prescription records from 1 January 2018 to 31 December 2020 at Cork University Maternity Hospital, Ireland. Relevant data was transcribed from electronic health records. RESULTS: Indications for treatment were tubal ectopic pregnancy (70%, n = 51), persistent pregnancy of unknown location (22%, n = 16) and caesarean scar pregnancy (7%, n = 5). Treatment was successful in 88% (n = 44) of tubal ectopic pregnancies with 73% (n = 37) and 14% (n = 7) of women receiving a single dose and repeated doses, respectively. Only 8% (n = 4) of tubal ectopic pregnancies required emergency surgery for subsequent tubal rupture. In 93% (n = 15) of cases of persistent pregnancy of unknown location, treatment was successful with one patient requiring uterine evacuation. Women with caesarean scar pregnancy were treated with combined MTX and uterine evacuation without complication. CONCLUSIONS: The efficacy of medical treatment with systemic MTX for confirmed tubal ectopic pregnancy in our hospital is in line with national and international standards. Careful consideration should be given to treating caesarean scar pregnancy and persistent pregnancy of unknown location with systemic MTX. Systemic MTX use guided by clinicians specialised in early pregnancy complications and safe medication practices may improve treatment success and reduce adverse events.

Medical management of first trimester miscarriage: a quality improvement initiative.

INTRODUCTION: Medical management of first trimester pregnancy loss is a safe option that is well tolerated and affords women more autonomy in relation to their care. Recent trials provide robust evidence that mifepristone pretreatment is the optimal approach for women with missed miscarriage who desire medical management. METHODS: Following a change in medical management of first trimester miscarriage in our unit, we conducted a retrospective audit over a 3-month period of all women who had elected medical management as their primary treatment option. We compared the results with a previous audit that had been undertaken prior to the change in practice. RESULTS: The implementation of mifepristone resulted in an increased effectiveness of primary medical treatment for first trimester miscarriage from 53.8% to 85.2% (p=<0.001). DISCUSSION: The results of our study support the introduction of mifepristone into routine clinical practice for medical management of first trimester pregnancy loss across all maternity units.

A comparative study of two immunoassays of maternal placental growth factor.

Circulating maternal levels of placental growth factor correlates well with placental function and numerous studies advocate its role to help rule-out preterm pre-eclampsia. A number of automated immunoassay platforms to quantify placental growth factors are currently available. The aim of this study was to highlight the importance of developing and validating appropriate reference ranges and clinical cut-offs for immunoassays, by comparing the results obtained from two different immunoassays of placental growth factor; the Quantikine® ELISA and the automated Triage® test. This was a secondary subgroup analysis of samples collected as part of a prospective cross-sectional study of placental growth factors in twin pregnancy. Consenting pregnant women with a twin pregnancy, across a variety of gestations, had a single blood sample taken at a one-time point only during their pregnancy. The plasma was initially biobanked and then later analysed in batches using both immunoassays. Although the placental growth factor values of the two immunoassays correlated well (r = 0.88, n = 178, p < .001), the actual results obtained were significantly different (mean difference 238.1 pg/ml). Poor concordance between the two immunoassays was also present, with the Triage® test recording 36 cases as <100 pg/ml whereas the Quantikine® ELISA identified only 4 as <100 pg/ml. Biomarker levels may vary significantly between different immunoassay platforms, highlighting the importance of developing validated clinical cut-offs for any automated immunoassay before its clinical application. These differences need to be understood to facilitate clinical utility given that placental growth factor testing is likely to be introduced into widespread clinical practice.

The maternal and perinatal implications of hypertensive disorders of pregnancy in a multiple pregnancy cohort.

INTRODUCTION: Hypertensive disorders of pregnancy are common and may result in increased maternal and neonatal morbidity and mortality. Multiple pregnancies confer an increased risk of development of a hypertensive disorder of pregnancy. The purpose of this study was to examine a large cohort of women delivering a multiple pregnancy in a single large tertiary unit, and to evaluate the implications of hypertensive disorders of pregnancy on both maternal and perinatal outcomes. MATERIAL AND METHODS: Retrospective study of all twin pregnancies delivered at Cork University Maternity Hospital, Ireland over a 9-year period (2009-2017). The twin pregnancies were divided according to the presence or absence of hypertensive disorder of pregnancy and the two groups were compared. RESULTS: Maternal age >40 years, nulliparity, conception through use of a donor oocyte, and presence of obstetric cholestasis are all risk factors for the development of hypertensive disorders of pregnancy in women with a multiple pregnancy. When a hypertensive disorder complicates a twin pregnancy, it increases the incidence of iatrogenic late prematurity and neonatal hypoglycemia. CONCLUSIONS: This study is informative for clinicians caring for women with a multiple pregnancy with its relevant data on perinatal outcomes following a diagnosis of hypertensive disorder in pregnancy.

An exploration of women's experience of taking part in a randomized controlled trial of a diagnostic test during pregnancy: A qualitative study.

OBJECTIVE: To explore pregnant women's views of participation in a clinical research trial while pregnant. DESIGN: Prospective nested qualitative cohort study embedded within a national, multi-site randomized controlled trial of a diagnostic test for preeclampsia: Placental Growth Factor. One-to-one in-depth semi-structured interviews were undertaken with 19 women who had recently participated in the trial at a single recruiting site. The interviews were conducted in private, recorded digitally and transcribed verbatim. SETTING: Single tertiary maternity hospital currently recruiting eligible women onto an on-going randomized controlled trial (NCT02881073). PARTICIPANTS: Women who had participated in the PARROT Ireland randomized controlled trial during their recent pregnancy. METHODS: Thematic analysis was utilized. Each line of the transcribed interviews was coded into a category by two researchers. The resultant categories were reviewed, and those with similarities were pooled allowing the development of themes. MAIN OUTCOME MEASURES: Women's opinions and experience of participation in a randomized controlled trial of an interventional diagnostic test during their pregnancy. RESULTS: Four major themes were identified as follows: (a) Understanding of preeclampsia, (b) Motivators for clinical trial participation, (c) Barriers to decision making and (d) Influence of PARROT Ireland on pregnancy experience. CONCLUSIONS: Women are generally interested and positively inclined to participate in research during pregnancy. The potential of risk is an important consideration for eligible pregnant woman. Information and support by both researchers and clinicians are paramount in aiding women's understanding of a research trial.

PARROT Ireland: Placental growth factor in Assessment of women with suspected pre-eclampsia to reduce maternal morbidity: a Stepped Wedge Cluster Randomised Control Trial Research Study Protocol.

INTRODUCTION: Women presenting with suspected pre-eclampsia are currently triaged on the basis of hypertension and dipstick proteinuria. This may result in significant false positive and negative diagnoses resulting in increased morbidity or unnecessary intervention. Recent data suggest that placental growth factor testing may be a useful adjunct in the management of women presenting with preterm pre-eclampsia. The primary objective of this trial is to determine if the addition of placental growth factor testing to the current clinical assessment of women with suspected preterm pre-eclampsia, is beneficial for both mothers and babies. METHODS AND ANALYSIS: This is a multicentre, stepped wedge cluster, randomised trial aiming to recruit 4000 women presenting with symptoms suggestive of preterm pre-eclampsia between 20 and 36+6 weeks' gestation. The intervention of an unblinded point of care test, performed at enrolment, will quantify maternal levels of circulating plasma placental growth factor. The intervention will be rolled out sequentially, based on randomisation, in the seven largest maternity units on the island of Ireland. Primary outcome is a composite outcome of maternal morbidity (derived from the modified fullPIERS model). To ensure we are not reducing maternal morbidity at the expense of earlier delivery and worse neonatal outcomes, we have established a co-primary outcome which will examine the effect of the intervention on neonatal morbidity, assessed using a composite neonatal score. Secondary analyses will examine further clinical outcomes (such as mode of delivery, antenatal detection of growth restriction and use of antihypertensive agents) as well as a health economic analysis, of incorporation of placental growth factor testing into routine care. ETHICS AND DISSEMINATION: Ethical approval has been granted from each of the seven maternity hospitals involved in the trial. The results of the trial will be presented both nationally and internationally at conference and published in an international peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT02881073.