ORAL PRESENTATIONS
3Pregnancy outcomes in women with inflammatory conditions exposed to novel biological agents: a prospective cohort study via the UK Obstetric Surveillance System
Kate Duhig1, Marian Knight2, Kimme Hyrich1, Stuart Ralston3, Ken Hodson4, Catherine Nelson-Piercy5
1University of Manchester, 2University of Oxford, 3University of Edinburgh, 4UK Teratology Information Service, 5King's College London
Abstract
Pregnancy outcomes in women with inflammatory conditions exposed to novel biological agents: a prospective cohort study using the UK Obstetric Surveillance System (UKOSS)
Introduction: Biological therapies are increasingly used for various inflammatory conditions. There is reassuring data regarding the safety of anti-TNF biological therapies in pregnancy, however, data about the safety of novel biologics are sparse. The objective of this study was to use the UK Obstetric Surveillance System (UKOSS) to describe the incidence and outcomes of pregnant women and babies exposed to novel biological therapies antenatally.
Methods: Prospective case identification through UKOSS contact with 194 UK consultant-led maternity units in the UK , May’22 -October’24. All cases exposed to non-anti-TNF biological agents for treatment an inflammatory condition were eligible. Outcomes were incidence of exposure, and maternal and perinatal mortality and morbidity.
Results: 317 cases were reported: the incidence of exposure was 29/100,000 (95% CI 26-33). The largest group (82 women (26%)) contributing to the dataset were those with inflammatory bowel disease. There were no maternal deaths. 45 (14%) stopped their biologic antenatally; 34 (76%) stopped due to concerns regarding infant immunity and guideline compliance. 16 women (5%) newly commenced the agent in pregnancy due to worsening of their inflammatory condition. Six women (1.9%), and eight infants (2.5%) were treated for confirmed sepsis. 21 (6.6%) women experienced maternal morbidity: 90% maternal morbidity events were related to obstetric haemorrhage. There were no neonatal deaths, and only 4 infants were affected by major congenital abnormality.
Conclusion: This study provides reassuring data relating to outcomes for pregnancies exposed to novel biological agents. Severe morbidity rates were low for both women and neonates. Congenital abnormality rates were in line with the background population rate. These data should be used for informed, shared decision making discussions with families regarding treatment choice in pregnancy. Further research is needed into optimum treatment strategies including when to stop or continue biologics in pregnancy, and must assess the impact on neonatal immunity and infant vaccination response.
4Impact of a dedicated service for the management of nausea and vomiting in pregnancy: outcomes and service user experience in a tertiary centre
Charlotte Jones1, Ariane L'Heveder1, Hannah Lally1, Emily Hewitt1, Yasmin Jamil2, Luci Buxton1, David Williams1, Beth Laverick3, Diane Lambo1
1UCLH, 2NCL Maternal medicine, 3Norfolk and Norwich University Hospital
Abstract
Introduction: A multidisciplinary service for women with nausea and vomiting in pregnancy (NVP) was introduced at University College London Hospital (UCLH) in 2022. The aims of this service were to provide holistic care and alleviate the local economic and wider clinical impact of NVP. The service involves a weekly clinic, training of healthcare professionals, and out-patient provision of intravenous fluids and anti-emetics.
Objectives: Evaluate outcomes of women with NVP before and following implementation of the service.
Methods: Retrospective data collection of pregnancy characteristics and outcomes from Oct 2021 - Sept 2023. The cohort of women with NVP was divided into two groups: ‘1’ were pre-implementation of the service, ‘2’ were post-implementation. In addition, we collected qualitative data in group 2 through questionnaires.
Results: Total cohort included 356 women (group 1 n=157, group 2 n=199). The groups were matched in baseline demographic and pregnancy characteristics.
In group 2, there was a 56% reduction in need for hospital admission and the duration of hospital admission was also shorter. The proportion of women in group 1 staying one or more than one night in hospital was 20.4% and 16.6% respectively, compared to 7.0% and 9.5% in group 2.
Prior to the service, 75% of participants described their experience of management as poor with ‘not feeling listened to’ and difficulties in accessing appropriate medication and support. Participants expressed an appreciation for continuity of care by an expert and some could positively compare the addition of the service to prior experiences and described it as ‘life-changing’. Ongoing training of the wider team and improved ease of contact were identified as future improvements.
Conclusion: A dedicated multidisciplinary NVP pathway is not only highly valued by patients but also has a significant impact on need for and duration of hospital admission.
5Pregnancy-associated haemophagocytic lymphohistiocytosis: Case series from the national MDT
Bethan Goulden1, Eleanor Singer2, Benjamin Bennett3, Eman Elfar4, Kazi Fardeen5, Elizabeth Rankin6, Joanna Girling7, Kate Wiles8, Maria Mouyis9, Rachel Tattersall10, Alexis Jones1, Jessica Manson1
1University College London Hospital, 2Glasgow Royal Infirmary, 3West Middlesex Hospital, 4King's College Hospital, 5North Middlesex Hospital, 6University Hospitals Birmingham, 7Chelsea and Westminster Hospital NHS Foundation Trust, 8Royal London Hospital, 9Bedfordshire Hospitals NHS Trust, 10Sheffield Teaching Hospitals NHS Foundation Trust
Abstract
Background: Haemophagocytic lymphohistiocytosis (HLH) is a sepsis-like syndrome which should be considered in the presence of the 3 Fs (Fever, Falling cell counts and hyperFerritinaemia). Multi-organ dysfunction from hyperinflammation results in a high mortality rate - MBRRACE-UK report eight HLH-related maternal deaths in nine years. Very little is known about prevalence, timing and triggers in pregnancy.
Methods: All individuals discussed at the national HLH multi-disciplinary team (MDT) meeting with HLH onset during pregnancy or within six months post-partum were included. Individual patient consent was obtained.
Results: Seven pregnant/post-partum individuals developed HLH between 2022-2024. Median age 32 years old (range 23-41). 6/7 developed HLH post-partum (one following miscarriage, five following caesarean section delivery). Median time from delivery to symptom onset in post-partum HLH was 8.5 days (range 3-75). Median peak ferritin was 9348 µg/L (range 5964-71748). Common features at presentation were fever (7/7), rash (3/7), diarrhoea (2/7) and arthralgia (2/7). Two had severe biventricular failure, one had a cardiac arrest, five required Level 3 care, three were considered for extracorporeal membrane oxygenation.
6/7 received steroids, 6/7 anakinra, 2/7 intravenous immunoglobulin and 2/7 rituximab. None had an underlying malignancy; none had a confirmed viral or mycobacterial infection as a trigger. Four had a new or established autoimmune rheumatic disease. A further two remain under investigation for inflammatory disorders. There were no maternal deaths.
Learning points:
We encourage use of the 2023 consensus guideline for diagnosis and investigation of HLH1 and discussion at the national HLH MDT2
All had a sepsis-like presentation – if not improving with initial therapy for bacterial sepsis consider alternative diagnoses (e.g., disseminated herpes simplex virus, thrombotic microangiopathies, HLH)
There was a clear post-partum predilection for HLH in this series
Future directions: Funding is secured for a UK Obstetric Surveillance System study of pregnancy-associated HLH opening in late 2024.
References
1. Cox, M. F. et al. Diagnosis and investigation of suspected haemophagocytic lymphohistiocytosis in adults: 2023 Hyperinflammation and HLH Across Speciality Collaboration (HiHASC) consensus guideline. Lancet Rheumatol 6, e51–e62 (2024).
2. HLH Service. University College London Hospitals NHS Foundation Trust https://www.uclh.nhs.uk/our-services/find-service/medical-specialties-1/hlh-service.
6A UK tertiary referral unit experience of thrombotic thrombocytopenic purpura (TTP) in pregnancy
Hannah Irvine, Lucy Mackillop, Michael Desborough
Oxford University Hospitals NHS Foundation Trust
Abstract
Background & Purpose: Thrombotic thrombocytopenic purpura (TTP) is an acute, life-threatening thrombotic microangiopathy (TMA). The pathophysiology involves an acquired or genetic deficiency of ADAMTS-13, a protease responsible for cleavage of von Willebrand Factor.
Pregnancy is a known risk factor for developing TTP, most frequently observed in the 3rd trimester or early post-partum period. The heightened risk of TTP in pregnancy is related to haemostatic and immunological changes. Whilst VWF concentrations progressively rise throughout pregnancy, ADAMTS13 activity decreases, reaching levels as low as 25% in the early post-partum period.
Current TTP management includes plasma exchange, methylprednisolone, monoclonal anti-CD20 therapy and more recently, Caplacizumab. This novel therapy is an anti-von Willebrand factor which works to inhibit VWF dependent platelet aggregation and microthrombi formation. Caplacizumab is not currently recommended in pregnancy.
In this case-series, we present all women referred to a tertiary referral hospital in the south of England with TTP in pregnancy or the puerperium over the past 5-years.
Results: Our case series includes seven women diagnosed with acquired TTP; five presented in the antenatal period (mean gestation 24/40) and two postnatally (2 and 8 weeks respectively) . Clinical remission (sustained clinical response) was achieved in 100%, in a mean time of 4.7 weeks in those treated with Caplacizumab (n = 4) and 8.3 weeks in those treated without (n= 3). Currently only 71% have reached complete immunological remission (normal ADAMSTS-13 activity).
Conclusion: Acute TTP management in pregnancy has many challenges, including timing and delivery of obstetric interventions. Caplacizumab, for example, has been shown to reduce TTP-related mortality, improve TTP recurrence rates and enable a faster platelet count recovery but is also associated with higher rates of adverse bleeding. Concerns around placental transfer limits its use to the immediate post-partum period. This associated bleeding risk can complicate the intrapartum and immediate postpartum course.
Optimisation of maternal and fetal outcomes in acute TTP requires coordinated care between obstetric physicians, haematologists, obstetricians, anaesthetists and ITU.
Keywords: Pregnancy; Thrombotic thrombocytopenic purpura; Caplacizumab
POSTER PRESENTATIONS
7Acceptability of an mHealth behaviour change intervention in women with gestational diabetes mellitus risk in four countries
Anna Davies1, Ellen Greene2, Sharleen O'Reilly2, Cheryce Harrison3, Helena Teede3, Mercedes Bermudez4, Timothy Skinner5, Anna Davies1, Christy Burden1
1University of Bristol, 2University College Dublin, 3Monash University, 4University of Granada, 5University of Copenhagen
Abstract
Introduction: Impact Diabetes Bump2Baby&Me (IDB2B) is a multicentre randomised controlled trial investigating implementation and effectiveness of an mHealth behaviour-change programme for pregnant women with elevated gestational diabetes mellitus (GDM) risk, with a primary endpoint of body mass index. The intervention comprises 1-to-1 online coaching and an app. Intervention acceptability can impact patient engagement and outcomes. We evaluated trial and intervention acceptability in pregnant women with elevated GDM risk across four countries.
Method: Qualitative individual interviews were undertaken with IDB2B trial participants, who were pregnant women with GDM risk, in the UK, Australia, Ireland and Spain. 80 participants (20/site) were purposively recruited/had their transcript selected to represent each site’s demographic, clinical and engagement characteristics. Theory-informed questions explored acceptability of trial arm and study participation. Interviews were audio-recorded and transcribed verbatim. Two researchers undertook thematic deductive and inductive coding. Ethical approval was granted by each site’s research authority.
Results: Most participants were motivated by their GDM risk to engage in risk-reduction behaviours. The intervention was acceptable and perceived to be effective by many for supporting weight management. Intervention participants valued early intervention, personalisation and continuity of care provided through the coaching and goal-setting components, contrasting it with limited GDM prevention care in current maternity services. Some described limited app engagement and navigation challenges. Participants reported reduced intervention engagement postnatally compared with antenatally, due to demands of caring for their baby. Unintended impacts of monitoring and self-reporting weight on dietary behaviours were described. Trial processes were acceptable, with a minority describing completing self-report measures as burdensome.
Conclusion: The IDB2B trial and mHealth intervention programme are acceptable and perceived to be effective by pregnant women at high GDM risk for preventing supporting weight management. Addressing barriers to app engagement and continued postnatal intervention engagement may optimise impact on weight retention and diabetes risk-reduction behaviours.
8Cystic fibrosis in pregnancy: The impact of modulator therapy
Helen Boyd1, Rebecca Ashworth2, Dilip Nazareth3, Dennis Wat3, Freddy Frost3, Dyan Dickins2, David Cox2
1Mersey Deanery, 2Liverpool Womens Hospital, 3Liverpool Heart and Chest
Abstract
The introduction of Highly Effective Modulator Treatment (HEMT) has led to tremendous impacts on the health of person(s) living with CF (pwCF). In addition to improved lung function and reduced frequency of pulmonary exacerbations, an increase in the number of women becoming pregnant has been observed.
To study the impact of these medications in pregnancy and outcomes we collected data on pregnancies resulting in livebirths between August 2010 and October 2023 in a large adult CF centre, comparing outcomes of those on HEMT at the time of conception with individuals on other treatments. We looked at demographics, CF related complications through pregnancy, neonatal outcomes and medication in pregnancy.
There were 47 pregnancies resulting in livebirths in 39 women with 61% on HEMT at the time of conception. Two of the pwCF from the non-HEMT have since died. There were four women who had a pregnancy both with and without HEMT. The mean age (years) at conception (28 vs 29.5) and BMI (kg/m2) (24.4 vs 24.1) were similar between the two groups. The mean FEV1 (%) pre-pregnancy for non-HEMT was 79% vs 72% for HEMT pwCF with more women in the HEMT group being classed as a high-risk pregnancy (FEV1 <60%) [35% HEMT vs 10% in non-HEMT]. During pregnancy mean FEV1 78% for non-HEMT group and 72% for HEMT pwCF. Post pregnancy mean FEV1 was 81% for non-HEMT and 70% for HEMT individuals.
PwCF in the non-HEMT group were more likely to need IVF to conceive (39 vs 8%). The HEMT group have more unplanned pregnancies (38% vs 12%).
In conclusion, HEMT was associated with increased unplanned pregnancy and a reduction in IVF-based pregnancies. There was also a trend towards increased pregnancies in groups previously considered high-risk. Increased high-risk and unplanned pregnancies may reflect growing confidence following introduction of HEMT.
Ethics approval was granted from both Liverpool Heart and Chest and from Liverpool Womens Hospital.
9Demographic profiles and neonatal outcomes in obstetric epilepsy patients at the Maternal Medicine Hub in East London: a retrospective cohort study
Nadia Seksaf1, Manho Kwok2
1Queen Mary University of London, 2Barts Health NHS Trust
Abstract
Introduction: There has been an increasing number of pregnant patients with epilepsy. In response, the Royal London Hospital, the maternal medicine hub of East London, has established a specialized obstetric neurology clinic, where pregnant patients with epilepsy receive comprehensive management. This clinic is a collaborative effort between a consultant obstetrician and neurologist. The study presents the demographic characteristics of the East London population with epilepsy during pregnancy and analyses the associated neonatal outcomes.
Methods: This retrospective cohort study involved a review of electronic patient records to collect data on pregnant women with epilepsy from January 2023 to December 2023. The collected data was then analysed using Excel.
Results: A total of 70 patients were seen at the obstetric neurology clinic, with 33 being known epileptic patients. On average, these patients attended 2.2 appointments during their pregnancy, ranging from 1 to 7 visits. The patients' ages ranged from 19 to 42 years, with a standard deviation (SD) of 5.96. BMI ranged from 17.72 to 37.97, with 8 patients (24%) classified as overweight (BMI > 30) and 2 patients (6%) as underweight (BMI < 18.5). The age of first seizure ranged from 6 to 37 years. Among the patients, 19 (57.6%) were primigravida.
No fetal abnormalities were reported in any of the cases. Birthweight percentiles ranged from the 2.1st to the 99.7th centile, with 4 infants (12%) born at less than the 10th centile and 3 infants (9%) born at greater than the 90th centile. There were no neonatal deaths observed.
Conclusions: This study provides valuable insights into the demographics of the East London population attending the obstetric neurology clinic with a background of epilepsy. It highlights the importance of achieving good control of epilepsy during pregnancy through specialist care and appropriate follow-up. The positive neonatal outcomes observed underscore the effectiveness of this service. Therefore, continuing this specialized clinic is essential for maintaining high standards of care and ensuring favourable outcomes for both mothers and their infants.
10Does the Tommy’s decision making tool predict birth outcomes in pregnant patients with inflammatory bowel disease?
Grace Waxman, Gemma Govinden
Sheffield Teaching Hospitals
Abstract
Background: Sheffield Teaching Hospitals runs a monthly antenatal clinic for patients with inflammatory bowel disease (IBD) in pregnancy. We are also one of the pilot sites for “The Tommy’s Pathway”, an online decision making tool used to identify women at high risk of placental dysfunction and preterm delivery using information gathered from their antenatal booking appointment. Historically, women with IBD were thought to be at higher risk of preterm birth and low birthweight. We wanted to find out if this was still the case in our patient population, especially with the increasing use of biologics in pregnancy. We also wanted to see if the Tommy’s pathway was detecting at risk patients, independent of their IBD.
Methods: Retrospective data collection was carried out on all patients who attended the clinic over a two year period with a confirmed diagnosis of IBD. Data was gathered from the physical notes and the electronic patient record. Information about antenatal counselling, medication, mode of delivery and birth outcomes was collected. Data on the Tommy’s risk calculation was collected directly from the application.
Results: Data was collected from 44 patients. There appears to be inconsistent pre-natal counselling and 34% of patients had disease activity at conception. There were no preterm deliveries in the cohort. Rates of emergency caesarean were similar to local averages (30%) and rates of elective caesareans were higher (32%). The percentage of babies with a birth weight less than the 10th centile was 13%. Of these 6 cases, Tommy’s predicted the risk of placental dysfunction as either moderate or high in all cases. None of those 6 mothers had active disease at conception.
Discussion: The birth outcomes for this patient cohort are similar to our general population. The increased rates of elective caesarean is due to historic colorectal surgery and low rates of VBAC. The Tommy’s risk assessment tool appears to be accurate in predicting fetal outcomes in this group. Through further data collection, we should be able to validate its use in patients with maternal medical conditions, identifying high risk patients and reducing the need for routine fetal growth surveillance.
11Factors associated with pruritus deterioration in intrahepatic cholestasis of pregnancy, a longitudinal observational study
Xi Yang1, Nicholas Williamson1, Jenna Sajous1, Alice Mitchell2, Jenny Chambers2, Peter Dixon2, Catherine Williamson2, Caroline Ovadia1
1King's College London, 2Imperial College London
Abstract
Introduction: Pruritus is a common symptom in patients with intrahepatic cholestasis of pregnancy (ICP). There is limited longitudinal data assessing the change of pruritus and identifying the factors contributing to itch deterioration later in the pregnancy.
Method: Participants were recruited to a longitudinal observational study of cholestatic pregnancies from nine UK hospitals and via the patient charity, ICP Support, from 1997 to 2020. Maternal demographics and serial serum measurements of bile acid, alanine aminotransferase (ALT) and bilirubin concentrations were collected. Pruritus was measured using visual analogue scale (VAS) and further classified into 5 levels: no pruritus, mild, moderate, severe and very severe pruritus. Pruritus severity deterioration was defined as an increase of at least one severity level compared to baseline. Multiple logistic regression models were used to assess the association between maternal demographics, baseline serum measurements, and pruritus severity deterioration.
Results: A total of 139 women were included in the analysis. Pruritus severity deterioration was observed in 42% to 69% of patients, depending on their baseline pruritus level (from no baseline pruritus to severe baseline pruritus). In the multiple logistic regression analysis, neither ALT nor bilirubin concentrations were significantly associated with pruritus severity deterioration. However, log-transformed bile acid concentrations and maternal BMI were positively associated with a 2.62-fold (95%CI 1.05-6.54, p=0.04) and a 2.49-fold (95%CI 1.15-5.39, p=0.02) increased risk, respectively, of pruritus deterioration. Patients with peak bile acid concentrations above 100 μmol/L had a 7.45-fold (95%CI 1.43-38.86, p=0.02) higher risk of pruritus severity deterioration compared to those whose peak bile acids remained below 40 μmol/L during pregnancy.
Conclusion: The change of pruritus can be variable regardless of the baseline pruritus level. Peak bile acid concentration and maternal BMI were identified as significant risk factors for developing worse pruritus later in the pregnancy.
12Identifying novel renal biomarkers to improve the clinical phenotyping of preeclampsia
Helena Alderson1, Alexandra Crawford1, Luke Pleva1, Josephine Naish1, Jenny Myes1, Alexander Heazell1, Kate Wiles2, Kate Bramham3, Kate Duhig1
1University of Manchester, 2Barts Health NHS Trust, 3Kings College London
Abstract
Introduction: Preeclampsia (PE) is associated with acute kidney injury, carrying an increased risk of future renal disease. Whilst serum creatinine informs the diagnosis of PE, renal biomarkers are not routinely used for prediction and prognosis of PE. Magnetic resonance imaging (MRI) biomarkers can non-invasively quantify tissue characteristics such as inflammation, oedema and fibrosis. We evaluated maternal renal MRI biomarkers in women at high risk of developing PE to see if they could provide mechanistic insight and improved risk stratification in PE.
Methods: MRI scans as part of the DAPHNE study were analysed (REC (22/YH/01/44)). DAPHNE is a prospective cohort study of women at high-risk of developing PE undergoing serial, longitudinal cardio-placental MRI. Regions of interest (ROIs) were drawn on T1/T2 maps around kidneys captured incidentally. Paired blood and urine samples were analysed to assess biomarkers correlations, and relation to clinical outcomes.
Results: 44 participants underwent 118 scans. 18 had a normal pregnancy outcome, 14 had CHT and 12 developed PE. None had underlying chronic kidney disease. The PE cohort had significantly higher blood creatinine than the normotensive (p=0.0021) and CHT (p=0.0095) cohorts. In PE, there was a trend towards increased T1 (p= 0.1441, r= 0.3959) and T2 of the renal cortex, and medullary T2 shortening (p=0.0706, r=0.5604). Some blood biomarkers correlated with these changes, and there were differences in these correlations depending on pregnancy outcome.
Conclusion: MRI biomarkers show promise for characterising renal injury in PE, showing increased cortical T2, which may represent inflammation, fluid accumulation and fibrosis as seen in non-pregnant imaging studies. In our PE cohort, this may reflect glomerular endotheliosis which is identified on renal histopathology in PE. Renal medullary T2 shortening may represent hypoxia due to an excess of deoxyhaemoglobin present in the tissues. Confirmation of these findings is needed in larger prospective cohort studies.
13Maternal and perinatal outcome of pregnant women with very advanced maternal age : A population-based cross-sectional study in United Kingdom
Prashanthi Swami Selvaraj, Ismini Panayotidis, Nasrin Omer, Ratna Das, Sivatharjini Sivarajasingam
Queens Hospital, BHRUT
Abstract
Background: Globally, the average age of childbearing has increased steadily. ‘Very Advanced Maternal Age’ (VAMA) refers to women aged 45 years and above at the time of delivery1. VAMA is an independent risk factor for adverse maternal and perinatal outcomes.
Objective: To analyse the demographics, maternal and perinatal outcomes, and the impact of pre-existing medical conditions among VAMA women.
Methodology: This population-based cross-sectional study evaluated 244 VAMA women who delivered at Barking, Havering and Redbridge Trust between January 2019 and December 2023.
Results: The mean age in the study was 46.56±2.38 years, (IQR e.g 45-57). Spontaneous conception occurred in 64%, though assisted reproductive technology (ART) was the most common conception type in women over 50. Among the ART conception 56.3% were using donor eggs and 59.5% were done outside UK. 46 % of VAMA women were obese (BMI >30). Only 6.3 % (10 in 157) spontaneous pregnancies were primigravida. Twenty two percent (n=60) of pregnancies end in miscarriage.
Common medical conditions complicating pregnancy in VAMA women were essential hypertension (13.1%) and thyroid disorders (10.2%). Gestational diabetes, pregnancy-induced hypertension and pre-eclampsia complicated 30.4% ,6.5% and 7.3% of pregnancies, respectively. Reassuringly, only 8% had fetal growth restriction and 5% was small for gestation. Eighty five percent of VAMA women delivered at term. Caesarean section rate among VAMA women was 68 %. Blood loss exceeding 1 litre occurred in 26.6%, and 12.5% of neonates required NICU admission.
Conclusion: This study provides valuable data that can aid healthcare providers in counselling women about tailored antenatal care and expected maternal and perinatal outcomes. Caesarean section and gestational diabetes rates were high compared to national data with comparable preterm birth rates. Optimising pre-existing medical conditions before conception and preconception counselling will aid in better pregnancy outcome in VAMA women.
Reference
1. Howell A, Blott M. Very advanced maternal age. The Obstetrician & Gynaecologist 2021; 23: 38–47. https://doi.org/10.1111/tog.12710
14Prediction of maternal and fetal outcomes using novel whole blood point-of-care Placental Growth Factor Testing in Sierra Leone
Dr Moses Tamba M'bayoh1, Dr Katy Khurt2, Dr Alice Hurrell2, Dr Alex Ridout2, Dr Andrew Shennan2
1Ministry of Health, 2Kings College London
Abstract
Background: Preeclampsia is the second leading cause of maternal mortality in Sierra Leone and globally. Early detection is key to facilitate prompt, life-saving interventions. Placental Growth Factor (PLGF) level has been found to be low in the blood of women with Pre-eclampsia. Recently, novel point-of-care (POC) PlGF has emerged, which could be especially impactful in Sierra Leone and other low-and middle-income settings (LMICs) where laboratories are limited.
Objective: A pilot evaluation of two novel POC PlGF devices for prediction of maternal and fetal outcomes in pregnancies affected by Preeclampsia.
Methods: Women who were hypertensive between 24 to 36 completed weeks of pregnancy were considered eligible and invited to provide informed consent. The RONIA TM device required a finger-stick whole blood sample, with a result available in 30 minutes, followed by a venous whole blood sample for the LEPZI Quanti device. Previously determined cutpoints of <20 (very abnormal) and < 60 (abnormal); and <10 (very abnormal) and <90 (abnormal) were used for the RONIATM and LEPZI devices respectively.
Results: Both devices predicted maternal mortality and HDU admission with 100% sensitivity. The Lepzi device was more sensitive in predicting maternal complications 16/18 than the Ronia device 13/18, whilst the RONIA Device was more sensitive for stillbirth)11/13 than the Lepzi device with 10/13.
Conclusion: Both devices were highly sensitive for prediction of adverse maternal and fetal outcomes, and could be valuable in identifying women with pre-eclampsia in need of prompt intervention. Further work is being carried out to determine user acceptability and feasibility of integrating the devices into low resource settings.
16Understanding the association between Very Advanced Maternal Age and Gestational Diabetes Mellitus : A population-based cross-sectional study in United Kingdom
Prashanthi Swami Selvaraj, Ismini Panayotidis, Nasrin Omer, Ratna Das, Sivatharjini Sivarajasingam
Queens Hospital, BHRUT
Abstract
Background: "Very advanced maternal age(VAMA)" refers to women aged 45 years and above at the time of delivery. Maternal age is a known risk factor for gestational diabetes mellitus(GDM),with rates ranging from 12.6% to 21% among VAMA women1.
Objective: To explore maternal and perinatal outcome of VAMA women with GDM.
Methodology: This population bases cross sectional study evaluated 244 VAMA women delivered at Barking, Havering and Redbridge Trust between January 2019 and December 2023. The analysis compared women with and without GDM.
Results: The mean age was 46.56(IQR e.g.45-57). GDM was diagnosed in 30.4 %(n=56) of VAMA women ,with a prevalence of 21 % under 50 years, and 40 % in women over 50 . 58% of those women were obese(body mass index>30),and 40 % from Black, Asian and Minority Ethnic groups. Donor Eggs assisted reproductive technology accounted for 68% of conceptions among women with GDM. 37% were managed with diet and lifestyle changes,46.4% with metformin ,and 16%with insulin. Small for gestational and fetal growth restriction rates were 10.7% and 8.9% respectively, with similar rates across all groups. Pregnancy induced hypertension was observed in 4/56 and pre-eclampsia in 8/56. Preterm birth rates were similar between women with (16%) and without GDM(15%), and all women requiring insulin delivered at term. Caesarean section rates were high among VAMA women with GDM (66%),particularly in the diet (85%) and insulin(77%)groups. Neonatal unit admission was needed for 16 % of infants born to GDM mothers, compared to 12.5% in those without GDM. Blood loss exceeding 1 litre seen in 19.6% of VAMA women with GDM.
Conclusion: GDM in VAMA women is high compared to national data, with doubling of incidence in women over 50 compared to 45-50 years. There is increased neonatal admissions and comparable caesarean section and preterm rates to those without GDM.
Reference
1. Howell A, Blott M. Very advanced maternal age. The Obstetrician & Gynaecologist 2021; 23: 38–47. https://doi.org/10.1111/tog.12710
17Venous thromboembolism prevention in pregnancy and postpartum: a systematic review of international clinical practice guidelines
Laura A. Magee1, Fizzah Jivraj1, Roopen Arya1, Clare Boag2, Luci Buxton3, Matthew Coleman4, Rebecca Scott5, Peter von Dadelszen1
1King's College London, 2The Newcastle Upon Tyne Hospitals NHS Foundation Trust, 3University College London Hospitals NHS Foundation Trust, 4Southampton University Hospital Trust, 5Chelsea and Westminster Hospital NHS Foundation Trust
Abstract
Background: The most common direct cause of maternal mortality during pregnancy and up to 6 weeks postpartum is venous thromboembolism (VTE). However, systematic review of risk assessment models for pregnancy/postpartum has shown them to be of poor quality. We undertook a systematic review of published clinical practice guidelines (CPGs) on VTE prophylaxis in pregnancy and postpartum, to inform international clinical practice and aid the update of the Royal College of Obstetricians and Gynaecologists (RCOG) 37a Green-Top Guidelines.
Methods: Following review registration (Open Science Frameworks, https://doi.org/10.17605/OSF.IO/C7G8D), we searched bibliographic databases and applicable society websites for relevant papers published in 2014-24, using a search strategy developed in associated with a specialist librarian. We included any CPG on VTE prevention in pregnancy and postpartum. Papers identified were organised using Rayyan software, and reviewed by two independent assessors, with disagreements resolved through discussion and consensus. Data abstraction and guideline quality assessment (AGREE-II tool) followed a similar process.
Results: Included were 10 guidelines covering general VTE recommendations in pregnancy and postpartum. Eight were published more than five years prior. Guidelines were consistent regarding: individualised risk assessment; certain antenatal and postnatal risk factors significant enough to warrant prophylaxis alone (i.e., prior VTE and high-risk thrombophilia [e.g. Factor V Leiden homozygosity]); thromboprophylaxis agent safety; and duration of thromboprophylaxis recommended. However, there were inconsistencies, particularly with regards to risk factors of sufficient importance to alone warrant thromboprophylaxis, and importantly, there was no consensus on how the risks associated with individual risk factors should be integrated to estimate overall VTE risk, leaving clinicians to decide if prophylaxis is required.
Conclusions: There is a lack of up-to-date guidance on VTE prevention in pregnancy and postpartum. Current inconsistencies between CPGs should be the focus of future research.
18When should we recommend patients with uncomplicated gestational diabetes Mellitus give birth? A systematic review of international management guidelines
Nadejda Capatina1, Caroline Ovadia2
1Ipswich Hospital, 2King's College London
Abstract
Background: Gestational diabetes mellitus (GDM) affects 13.4% of pregnant women worldwide (1), with long-term health impacts on both baby and mother. Literature often reports the complications of GDM and how to prevent these, however evidence-based recommendations on the recommended timing of birth are limited. We aimed to systematically review international guidelines on when to offer delivery for patients with uncomplicated GDM.
Methods: We systematically searched for relevant guidelines up to May 2024, on PubMed, Google Scholar, national health institutions and medical specialty societies; international experts were also consulted. Articles identified during the searches were screened manually for relevance and for guidance on delivery in uncomplicated GDM. Guidelines included were those approved at national level or by a committee of international experts.
Results: Fifteen guidelines from 5 continents were included, with oldest being revised in 2010 (Ireland), whilst the most recently revised were in 2022 (Australia, China and South Africa). No guidelines clearly define the difference between “uncomplicated” and “complicated” GDM, although differentiate delivery recommendations based upon this definition. The recommended date for delivery in uncomplicated GDM ranges from earliest 38 weeks’ (Canada) to latest 42 weeks’ gestation (Sweden). If spontaneous labour has not started by the latest recommended date, some guidelines suggest labour induction (UK, Canada, India, Poland), and/or caesarean section (UK), whilst others advise to await spontaneous labour (Australia, FIGO, and Ireland).
Discussion: We demonstrate marked differences in international guidelines for GDM management. This reflects a paucity of definitive underlying evidence supporting these recommendations, and differences in care provision. To enable wider scale comparative research, and clarity of patient expectations, there is a pressing need for collaborative approaches to guideline recommendations - in particular, agreement on how to define GDM severity and complications. Improving underlying evidence, and personalised healthcare approaches, may enable individualised risk prediction and birth recommendations.
Reference
1. Adam S, McIntyre HD, Tsoi KY, et al. Pregnancy as an opportunity to prevent type 2 diabetes mellitus: FIGO Best Practice Advice. Int J Gynecol Obstet. 2023; 160(Suppl. 1): 56-67. doi:1002/ijgo.14537
19#ReadyForPregnancy Campaign: To improve pre-conceptional care across East Midlands
Shailja Verma, Anette Freyer, Farah Siddiqui
University Hospitals of Leicester NHS Trust
Abstract
#ReadyforPregnancy Campaign: To improve pre-conceptional care across East Midlands
Background: Almost half of women and birthing people do not plan the timing of their pregnancy. Two-thirds of maternal deaths occurred in those with pre-existing physical or mental health problems. Pre-pregnancy advice improves the outcome for both mother and babies, especially in women with underlying medical conditions.
Aim: To increase awareness of pre-conceptional counselling amongst women, focussing on high-deprivation areas across East Midlands.
Methods: University Hospitals of Leicester NHS Trust collaborated with the East Midlands Maternal Medicine Network for the campaign. NHS Creative received funding for Pre-Conceptional Care campaign. A search was done on existing public health campaigns. This was evaluated for suitability, including content & messaging, evidence of co-production, multi-ethnic acceptability & images and easy read access. We had permission to develop further with an emphasis on medical conditions.
Campaign design included Phase 1: designing a landing page and reaching out on social media platforms like Snapchat and Spotify; Phase 2: radio, primary & secondary care involvement. Currently, we are in second phase of broadcasting on radio channels like Capital and SABRAS. This co-production includes MNVP, ICB, Maternal Medicine team, Diabetes team, public health midwife, Health and Equity fellow, Obstetricians and EDI team. The target audience selected was women of the reproductive age group (16-44y) living in the EMMMN catchment area.
Results: The website http://east-midlands-maternal-medicine-network.nhs.uk/ was set up in the last financial year. The campaign resources included an easy-read booklet, a British sign language film, a #ReadyforPregnancy booklet with translation into ten different languages and a campaign landing page for social media platforms. Broadcasting rolled out from mid-July to mid-October. We liaise with GP surgeries and local pharmacies in high-deprivation areas to highlight pictorial posters and leaflets and have TV reels running in regional languages. It is challenging to evaluate the outcome of this public health campaign as the result is raising awareness. We analyse data from our campaign landing page through social media clicks and website hits over Phase 1 and 2 of the campaign. Furthermore, with direct contacts from patients, referrals from primary care and referrals/engagement with secondary care colleagues.
Conclusion: This endeavour to improve the provision of pre-conceptional care for women with medical conditions focuses on patient education and information accessibility. A hard launch is challenging, and a soft launch is ongoing. Further work is required in community centres, pharmacies, patient feedback, and colleague education.
20A novel CF-maternal health service
Amy Downes1, Ladina Weitnauer1, Rachel Robinson1, Natasha Singh2, Rebecca Scott2, Imogen Felton1
1Royal Brompton Hospital, 2Chelsea and Westminster Hospital
Abstract
Introduction: Pregnancy rates have significantly increased among females with cystic fibrosis (fwCF) since the availability of triple-modulator drug Elexacaftor/Tezacaftor/Ivacaftor (Kaftrio™) in 2020. Direct and indirect effects of this therapy have improved overall CF-health, including improving subfertility in fwCF. Historically CF-pregnancies were often unplanned (40-50%) and deemed high-risk. There is limited knowledge of how to optimise outcomes, management and experience of CF-pregnancies in this new therapeutic era.
Intervention: In response to increased demand and unmet clinical need, a dedicated, virtual CF Maternal Health MDT service was established by the largest adult CF centre in Europe in collaboration with the linked maternal medicine centre, comprising: CF and Obstetric Physicians; nurse specialists; physiotherapists; dietitians and pharmacists. Local maternity teams joined virtual ‘outreach’ consultations together with fwCF, facilitating births closer to home. Pre-conception counselling, monthly ante-natal and regular post-partum reviews were included. Evaluation was through retrospective review of outcomes from 2021-2024 and patient semi-structured interviews.
Outcomes: A total of 54 women (mean age=30y), completed 68 pregnancies. Thirty women received formal pre-pregnancy counselling. Unplanned pregnancy rates reduced from 53% (first year) to an average 23% over subsequent three years. Forty percent of fwCF delivered in their local obstetric unit; the remainder in the linked maternal medicine centre. There were no maternal or neonatal deaths. Median gestational age was 37+2 weeks; 24% pre-term births; 46% by caesarean section. Fifty-five percent developed GDM. Analysis of semi-structured interviews reported benefit of this novel service in the following areas: 'personalised care', 'excellent communication' and 'feeling safe'.
Discussion: The model of dedicated, co-ordinated, multi-professional CF Maternal Health clinics improves patient experience of CF-pregnancy, with reassuring outcomes and reduction in unplanned and therefore potentially higher risk pregnancies.
In the era of rising CF-pregnancies, there is wider utility in adopting this service model to minimise unwarranted variance of CF maternal medicine strategies.
21Directing the requesting practices for pre-eclampsia risk ratio (sFlt-1/PLGF)
Eleanor Ringland1, Emily Weisfeld2, Alina Vais2
1Chesterfield Royal Hospital, 2Chesterfield Royal Hospital NHS Trust
Abstract
Background: The Elecsys immunoassay sFlt-1/PLGF ratio has been recommended for use with clinical assessment to help rule in or rule out suspected preterm pre-eclampsia (NICE DG49). To ensure the requests for sFlt-1/PLGF remained in line with manufacturer and NICE guidance, the electronic order communication system was adapted to aid clinicians with requesting practices. The sFlt-1/PLGF ratio was available as a standalone test to request and removed from the pre-eclampsia monitoring panel. Upon requesting, prompts were added for multiple pregnancies and whether a diagnosis of pre-eclampsia was already confirmed. A minimum retesting interval was also integrated to reduce the number of unnecessary repeat tests.
Methods: A retrospective audit was conducted to identify the number of sFlt-1/PLGF ratio requests received in the laboratory for a three-month period either side of the changes to the electronic order communications Clinisys ICE. Information was extracted from the business reporting and analytics tool PathManager and manipulated using Microsoft Excel. Cost analysis was conducted using the costings presented in DG49 using the cost of £79.23 per test.
Results: A total of 155 requests were received in the laboratory over the three-month period post changes to the electronic order communications, with 308 requests received in the same period pre change. The number of unnecessary repeat requests received on the same patient fell by 83 requests. Cost savings over the three-month period was calculated at £12,122.
Conclusion: Additional guidance for electronic requesting for the sFlt-1/PLGF ratio directed appropriate requesting practices and generated subsequent cost-saving to the Trust.
22Enhancing care continuity in preeclampsia: A quality improvement project on optimising primary-secondary communication via electronic discharge summaries
Kareem Omran1, Hibah Kemal1, Karimah Khanum1, Aylur Rajasri2
1King's College London, 2Queen Elizabeth The Queen Mother Hospital, East Kent Trust
Abstract
Background: Pre-eclampsia is a prominent hypertensive disorder affecting pregnant women, leading to substantial maternal and foetal morbidity and mortality. Effective management of pre-eclampsia extends to primary care follow-up, in which the quality of Electronic Discharge Notes (EDNs) are crucial for interdisciplinary communication and care continuity. However, inadequate documentation can result in disjointed care and preventable complications. This quality improvement project is aimed to enhance the quality of EDNs, targeting a 50% documentation compliance rate for six essential criteria by February 2024.
Methods: A retrospective baseline audit of EDNs for pre-eclampsia patients over five months (April–October 2023) revealed a low compliance rate of 30.7%. Key documentation criteria was identified through literature review and meetings with senior consultants. Interventions included educational posters, presentations at audit meetings, and endorsement from both consultants and junior doctors. A cause-and-effect analysis, Pareto charts and a key driver diagram were employed to guide and prioritise interventions.
Results: Post-intervention, the median documentation compliance across all criteria showed a significant increase from 30.7% to 38.46% (p=0.041). While documentation of follow-up instructions and medication duration achieved 100% compliance, other critical areas, such as adequate safety netting instructions for general practitioners and information on future pre-pregnancy counselling, showed no measurable improvement, remaining at 0% compliance.
Conclusion: This initiative highlights the complexities of improving routine discharge documentation habits for pre-eclampsia patients. Although progress was made in certain areas, the overall goal was not met, emphasising the need for further iterative improvements. Key lessons learned include the importance of employing both hard and soft interventions. Hard interventions, such as structural changes to the electronic discharge templates (forcing functions), compel compliance by requiring specific information to be entered before electronic submission. The project highlights that while soft interventions may raise awareness and encourage better practice, hard interventions are necessary to ensure fortified and comprehensive documentation.
23Improving clinician confidence in managing medical problems in pregnancy and post-partum
Kate Williams, Ella Marson, Yasmin Jamil
Whittington Health NHS Trust
Abstract
Aim:
Increase clinicians’ confidence in medical management during pregnancy and post-partum.
Wider aim to reduce maternal mortality and morbidity in North Central London
Significance: Maternal mortality is rising in the UK1. Most deaths are due to medical problems in pregnancy but training in managing these problems is lacking in medical school and post-graduate curriculums2. Improving education, and thus clinician confidence and knowledge, should improve maternal outcomes.
Methods:
Cycle 1 – We created a Toolkit for ED clinicians to use when managing medical problems in pregnancy, detailing information on assessment, management and discharge, with hyperlinks to guidelines. This was published on our ED app and publicised via email and via a short teaching session. We assessed clinician’s confidence before and after this intervention.
Cycle 2- We delivered a one-hour teaching session to foundation doctors with interactive cases, assessing confidence before and after.
Results:
Cycle 1 – ED clinicians reported that the toolkit was an informative, helpful resource. Confidence scores remained the same after introduction of the toolkit, at a mean score of 2.7/5. However, only 50% of respondents post-intervention were aware of the toolkit.
Cycle 2 – The teaching session received excellent feedback, with doctors feeling well-equipped to manage these patients going forwards. They highlighted that they had not received any prior teaching on obstetric medicine. Confidence scores increased from a mean score of 2/5 to 3.9/5 following the teaching session.
Learning:
Focused teaching sessions can improve clinician confidence. The Toolkit needs increased awareness and publicity, and may be most successful in combination with a focused teaching session. Similar Toolkits are being introduced across North Central London hospitals and we will conduct further projects to derive impact.
Our aim is to incorporate this educational method (toolkit resource with teaching) into department inductions and educational curriculums, to improve our maternal outcomes.
Reference
1. MBRRACE-UK: Mothers and Babies: Reducing Risk through Audits and Confidential Enquiries across the UK | MBRRACE-UK Report 2023- Saving Lives, Improving Mothers’ Care | NPEU [Internet]. Available from: https://www.npeu.ox.ac.uk/mbrrace-uk
2. Prinja P. Education of medical problems in pregnancy – a survey of general internal medicine trainees in the West Midlands. Future Healthc J. 2019 Mar;6(Suppl 1):160.
24An unusual presentation of gestational diabetes insipidus in the postpartum period
Ismini Panayotidis, Elizabeth Phillips, Lina Eltayieb, Godwin Simon, Belayet Hossain, Gideon Mlawa, Sivatharjini Sivarajasingam
Barking, Havering and Redbridge University Hospitals NHS Trust
Abstract
Introduction: Gestational diabetes insipidus (GDI) is a rare complication of pregnancy caused by arginine vasopressin (AVP) metabolism by the placental enzyme vasopressinase. We describe an unusual case of GDI presenting in the early postpartum period, highlighting the diagnostic challenges posed by coexisting postpartum symptoms.
Case Presentation: A 29-year-old low-risk woman was noted to have an upward trending creatinine (96-232 umol/L) with normal electrolytes and liver function tests after undergoing an emergency caesarean section (EMCS) at 39-weeks-gestation. She was initially treated with intravenous fluids, and omission of nephrotoxic medications. Pre-eclampsia was excluded as blood pressure and urine protein-to-creatinine ratio were normal. CT imaging of the urinary tract excluded post renal causes, such as intraoperative ureteric injury. Autoimmune screen for renal causes was unremarkable.
On day 5 post EMCS she was observed to have polyuria and polydipsia, associated with a negative fluid balance and rising serum sodium (137-150 mmol/L). Endocrinology review suggested AVP deficiency secondary to GDI or hypophysitis as differentials; hence a trial of desmopressin was commenced. Further investigations showed raised serum osmolality (297 mmol/kg), low urine osmolality (177 mmol/kg) and normal pituitary hormonal profile. MRI pituitary showed non-specific features that could be suggestive of hypophysitis. Gradual clinical and biochemical improvement was noted on desmopressin, and she was discharged on day 13 post EMCS.
The case was discussed at the pituitary multi-disciplinary team (MDT) meeting, which recommended repeat MRI in 2-3 months. A water deprivation test at 6 weeks postpartum showed partial AVP deficiency and desmopressin was stopped. Follow-up at 6 months postpartum revealed complete clinical and biochemical resolution.
Conclusion: This case demonstrates the importance of considering GDI as a differential in obstetric patients who exhibit atypical metabolic disturbances. Additionally, it highlights the need for an MDT approach in managing rare and complex medical presentations in and out of pregnancy.
References
1. Quigley J, Shelton C, Issa B, Sripada S. Diabetes insipidus in pregnancy. Obstet Gynaecol. 2018;41(8):41–8.
25Autoimmune cerebellar ataxia - is a "low risk" pregnancy and delivery achievable?
Alina Vais, Leen Hamadeh, Janet Cresswell
Chesterfield Royal Hospital
Abstract
A 30-year-old Caucasian woman, previously diagnosed with autoimmune cerebellar ataxia aged 26, conceived naturally and aimed for normal antenatal care and delivery. Her condition restricted her motor function, speech, and caused tremors, which were managed with a deep brain stimulator placed in her abdomen. She could express her wishes verbally and cognitive function was not affected by the disease.
Her pregnancy was managed in her local hospital by a Maternal medicine obstetrician with regular input from the woman’s neurologist and anaesthetic assessments as delivery was approaching. Prenatal testing was not necessary because of the known autoimmune aetiology of her condition. She developed gestational diabetes mellitus which was diet controlled. A multidisciplinary team (MDT) meeting involving the patient and carers, obstetrics, anaesthetics and labour ward midwifery leads occurred to support her wish for a normal delivery. At 37 weeks, she presented with spontaneous rupture of membranes (SROM) and was experiencing contractions.She was 2 cm dilated and was admitted with a plan for labour augmentation. She was advised to have an early epidural and start labour augmentation with IV syntocinon. With shared decision making and normal fetal monitoring throughout, she progressed well in labour, reached full cervical dilation and had an hour of active pushing. She required assistance with vacuum due to maternal exhaustion.
Achieving a vaginal birth was deeply satisfying for both her and the team. This case illustrates that good support, involving the patient in decision-making, and respecting their wishes can empower them to achieve what might seem unachievable.
26Blue Rubber Bleb Naevus Syndrome: managing a rare disorder in pregnancy
Robin Hughes
York Teaching Hospitals NHS Foundation Trust
Abstract
A 30-year-old nulliparous women booked in pregnancy with a history of Blue Rubber Bleb Naevus Syndrome (BRBNS), a rare congenital disorder which is characterised by numerous venous malformations which may be cutaneous and/or visceral in origin. The patient denied the presence of any cutaneous manifestations in the vulvo-vaginal area and no blebs were noted on speculum examination performed early in pregnancy.
There is a paucity of case reports on BRBNS in pregnancy and no established guidance on its management. The concern is that malformations (which may also arise de novo during pregnancy) can be associated with life-threatening haemorrhage should they be in close proximity to the genital tract during vaginal birth or encountered intra-abdominally at the time of caesarean section. Lesions may also be found in soft tissue surrounding the spine or upper airway leading to issues relating to regional or general anaesthesia.
The nature of the condition warrants specialist input which was sought from the wider multidisciplinary team comprising obstetricians, anaesthetists, ENT surgeons and radiologists. In order to mitigate the risks associated with either mode of delivery, MR imaging (whole spine and pelvis), flexible naso-endoscopic assessment and a further speculum examination were arranged in the third trimester.
MR imaging showed no malformations in the soft tissues close to the spine or within the abdomen/pelvis (including the lower genital tract). Naso-endoscopy noted a slight blueish discolouration deep within the laryngeal vestibule but a clear view of the airway. Speculum examination showed no new cutaneous blebs.
With the reassuring third-trimester findings, the MDT concluded that both vaginal birth and caesarean section were safe options. The patient opted for a planned caesarean section which was performed uneventfully at 39 weeks with an estimated blood loss for 600mls. Of note, there were no overt manifestations of the disease in the newborn.
27Case report of acute haemorrhagic leukoencephalitis in pregnancy
Victoria Wallis1, Beth Laverick2, Mark Andrews2, Monica Morosan2
1West Suffolk Hospital, 2Norfolk and Norwich University Hospital
Abstract
Introduction: Acute Haemorrhagic Leukoencephalitis (AHLE) is a rare, demyelinating disease of the central nervous system. It is a severe variant of acute disseminated encephalomyelitis, most commonly manifesting after viral upper respiratory illness. The course is marked by rapidly progressive acute inflammation of white matter, resulting in disability or death. Early diagnosis can reduce maternal morbidity and mortality.
Case: 33-year-old, primigravida presented at 29+1 weeks with dizziness, vomiting and headache with photophobia. Past medical history included migraine, ulcerative colitis and recurrent DVT. She was taking prednisolone for colitis flare and reported URTI four weeks prior. Vital signs and bloods were normal except WCC 15.7. CT Head demonstrated sinusitis, no intracranial pathology. MR venogram excluded thrombosis. She was discharged and re-presented at 29+4 weeks with lethargy, dysphasia and dyspraxia. Vitals, CTG and blood glucose were normal. GCS 13/15. Initial neurological examination normal. Repeat bloods showed WCC 16.0, CRP 50 and uPCR 50. CT Head showed no intracranial pathology. GCS rapidly deteriorated (9/15) and she urgently transferred to intensive care, sedated and ventilated. During transfer, fever, hyperreflexia, incontinence and left-sided nystagmus developed. Intravenous levetiracetam was commenced alongside ceftriaxone, hydrocortisone and aciclovir for suspected meningoencephalitis. Lumbar puncture showed elevated CSF protein. EEG and transthoracic ECHO were normal. Extensive virology, blood cultures and antibody screen were negative. After failing to wake off sedation, repeat CT head showed diffuse brain injury with bilateral basal ganglionic, hemispheric and cerebellar infarcts, accompanied with swelling and petechial haemorrhage with early effacement of basal cisterns heralding coning. Multidisciplinary plans were made for caesarean birth to allow mannitol use. A baby girl was born at 30+0 weighing 1792g. CT Head day 1 was unchanged. MRI day 3 showed extensive haemorrhagic abnormalities with oedema representing a severe haemorrhagic leukoencephalopathy. She transferred to neurosciences critical care for plasma exchange and Anakinra. Day 72 she was discharged to the rehabilitation unit.
Discussion: This presentation highlights the importance of involvement of the obstetric medicine team and their role in advocacy and persistence in challenging the wider MDT to re-evaluate diagnosis and reconsider treatment options in rare presentations. AHLE has been likened to haemophagocytic lymphohistiocytosis (HLH) and there is overlap in treatment modalities. It is important to raise awareness of AHLE to include as differential in rapidly progressive neurological symptoms in pregnancy - clinical suspicion may prevent fatal outcomes. Authors wish to highlight the availability of a national encephalitis MDT for such complex cases with diagnostic uncertainty.
28Navigating peripartum cardiomyopathy with Wolff-Parkinson-White syndrome
Waseem Khamboo, Ahmed Haggag,
Nadia Sunni
Walsall Manor Hospital
Abstract
Wolf-Parkinson-White (WPW) syndrome is a congenital disorder where an accessory pathway connects the atria and ventricles, bypassing the atrioventricular node. In patients with cardiomyopathy, particularly peripartum cardiomyopathy (PPCM), WPW syndrome significantly increases the risk of complications.
We present a case of a young woman in her late teens, at 35 weeks' gestation with monochorionic diamniotic twins, who underwent an emergency caesarean section under spinal anaesthesia due to suspected twin-twin transfusion syndrome (TTTS). She had no prior medical history, but her brother had postural tachycardia syndrome; there was no known family history of heart failure.
During the caesarean, the patient developed tachycardia with a heart rate of 160 bpm, though she remained haemodynamically stable. Postoperative electrocardiogram (ECG) findings showed sinus rhythm, a short PR interval, delta waves, a broad QRS complex, incomplete right bundle branch block (RBBB), and ST depressions in leads V1-V3, consistent with WPW. She was discharged with flecainide and advised against breastfeeding and future pregnancies.
Within a month post-discharge, echocardiography indicated early postpartum cardiomyopathy with an ejection fraction of around 45%. A three-day Holter monitor revealed no further arrhythmias, but WPW characteristics persisted. She was started on perindopril and bisoprolol for heart failure, and flecainide was discontinued.
An electrophysiological study was conducted, leading to a successful ablation of the WPW pathway. The patient remained symptom-free, and her left ventricular function normalised on cardiac MRI.
Although peripartum cardiomyopathy is rare, it is associated with significant morbidity and mortality, particularly when occurring in conjunction with WPW syndrome. Tachyarrhythmias associated with WPW during pregnancy commonly present as palpitations and should be regarded with seriousness due to their potential life-threatening consequences for both the mother and the fetus. Such patients require close monitoring. Catheter ablation is often effective in resolving the arrhythmia and can improve the likelihood of left ventricular recovery.
29Neonatal thrombocytopenia – a rare complication of natalizumab therapy
Hira Amer, Lucy Mackillop
John Radcliffe Hospital, Oxford University Hospitals NHS Foundation Trust
Abstract
Background: Neonatal thrombocytopenia occurs in 1% to 5% of newborns and can result from various maternal and fetal factors, such as infections, pre-eclampsia, autoimmune diseases, or fetal/neonatal alloimmune thrombocytopenia (FNAIT) 1. Multiple sclerosis (MS) is a chronic autoimmune disease affecting the central nervous system. Managing MS during pregnancy often requires modifying treatment due to limited safety data, especially for newer therapies. Natalizumab, a monoclonal antibody used to treat MS, has immunomodulatory effects. 2 Since its first approval for RRMS in 2004, significant side effects including immune-mediated hematologic complications have been reported. 3
Case Presentation: We present a case of a male neonate born at 38 weeks via elective caesarean section to a 33-year-old woman with relapsing-remitting MS treated with Natalizumab during pregnancy. Diagnosed with MS in late 2019, she was intolerant to peginterferon beta-1a and copaxone and experienced two relapses in 2020. She began natalizumab therapy in February 2021 pre-conception, with the last infusion at 34 weeks of gestation. The neonate, weighing 2.95 kg at birth, had a platelet count of 70x109/L, which dropped to 32x109/L by day 11, necessitating a platelet transfusion. There was no significant bleeding, and the platelet count rose to 119x109/L by day 15 and 235x109/L at 8 weeks. Other causes of neonatal thrombocytopenia, including FNAIT, were excluded. In 2024 she is pregnant again and after extensive multidisciplinary discussions has continued natalizumab until 28 weeks. We will report the outcome of second gestation at the MOMS meeting.
Conclusion: This case suggests a potential link between natalizumab use during pregnancy and neonatal thrombocytopenia. The decision to continue natalizumab therapy should involve a multidisciplinary approach, balancing maternal disease control with potential neonatal risks, and support informed decision-making.
Keywords: Neonatal thrombocytopenia, natalizumab, multiple sclerosis, maternal-fetal medicine.
Reference
1. Al Ghadeer HA, Aldhahi RA, Al Dandan FK, Alamer MH, Almulaifi LF, Al Muaibid AF, Al-Ali QA, Aljubran TM, Alarbash AA, Alabbad ZE, Alsultan AS, Aldoukhi ZH, Albahrani AA, Alramadan HA, Albahrani QA. The Prevalence and Associated Risk Factors for Neonatal Thrombocytopenia Among Newborns Admitted to the Neonatal Intensive Care Unit. Cureus. 2024 Mar 13;16(3):e56108. doi: 10.7759/cureus.56108. PMID: 38618311; PMCID: PMC11014734.
2. NICE. (2007). Natalizumab for the treatment of adults with highly active relapsing-remitting multiple sclerosis. NICE Technology Appraisal Guidance 127. Link.
3. Azimi A, Abna Z, Ghadiri F, Mehrabi F. Natalizumab-induced thrombocytopenia: A case report. Curr J Neurol 2022; 21(1): 64-5.
30Paget-Schroetter Syndrome: Effort-induced thrombosis in the left subclavian vein in a primiparous women at 21 weeks’ gestation
Rebecca Braithwaite1, Leila Fahel2
1York Teaching Hospital, 2York and Scarborough Teaching Hospital
Abstract
Case: A primiparous women presented at 21+6 weeks’ gestation with a 2/7 history left bicep pain, swelling, blue discolouration of the skin and visible venous congestion over this area. These symptoms started whilst swimming.
There was a history of long haul travel 3 weeks ago, followed by 1 week of nausea and vomiting. No significant past medical history or family history of venous thromboembolism and or cardiac disease.
Initial investigations included ECG, chest X-ray and bloods including a Troponin T which were all negative.
An upper limb ultrasound was performed which was initially negative.
The patient presented again at 23 weeks with ongoing pain and swelling in the left arm.
Repeat ultrasound confirmed an occlusive thrombus in the left subclavian vein extending into the jugular vein (consistent with upper limb deep vein thrombosis).
The patient was commenced on low molecular weight heparin (LMWH), with a recommended treatment time of 3 months (with 6 weeks postnatal prophylaxis).
Screening bloods for antiphospholipid syndrome confirmed high levels of anti-cardiolipin and B2 glycoprotein 1 antibodies.
Discussion: Paget-Schroetter Syndrome, or effort-induced thrombosis refers to primary thrombosis of the subclavian vein at the costoclavicular junction.
This is a relatively rare condition, with an extrapolated incidence of 2 per 100,000 in the general population.
It is more common in the right side (due to right hand dominance) and 60-80% of cases report precipitating vigorous exercise involving the upper limb proceeding onset.
The anatomy of the region is such that the subclavian vein can be compressed as it re-enters the chest anteriorly, passing adjacent to the the clavicle and the first rib.
Conclusion: It is likely that the precipitating events leading to the development of the upper limb thrombus are multifactorial.
It is unclear at present if the positive antiphospholipid screen represents a true diagnosis, or whether this is reactive to a recent viral illness. The results would typically be repeated in 12 weeks to confirm the result. In the absence of confirmed APS; pregnancy, with a history of long haul travel and dehydration are all risk factors for thrombosis.
The site and nature of acute presentation would suggest Paget-Schroetter syndrome. Antiphospholipid syndrome, also classically presents with upper limb thrombosis. Whether either of these syndromes is the cause of the patients presentation or this is an unfortunate cumulative effect of multiple pre-disposing risk factors is yet to be confirmed.
31Persistently elevated liver enzymes in pregnancy – beyond intrahepatic cholestasis of pregnancy, with illustrative cases
Demi Blair, Mark Andrews, Beth Laverick
Norfolk and Norwich University Hospital
Abstract
Elevated liver enzymes are not uncommonly identified during pregnancy, with abnormal levels found in around 3-5% of women, often explained by pregnancy specific conditions e.g. ICP. The severity of the derangement is variable and doesn’t necessarily correspond to the condition. In most cases the derangement is mild and transient but for those where it is more marked it can lead to diagnostic quandary, and consideration for other non-pregnancy dependent causes.
We present 2 clinical cases where the initial diagnosis was ICP but investigations and clinical picture drove diagnostic curiosity and MDT working to reach an accurate diagnosis.
Case 1: Para 1 female in her previous pregnancy developed severe jaundice, was diagnosed with ICP and spontaneously delivered at 27 weeks. She subsequently presented at 18 weeks with pruritus and jaundice. Bloods revealed a bilirubin 60, ALT 973 and bile acids 64 (peak 245). Inter-pregnancy liver enzymes had improved but not normalised. Genetic testing demonstrated a bile salt transport defect as a result of ABCB11 gene mutation homozygosity, which can result in chronic liver disease. A wide multidisciplinary team considered her case, offering treatment options such as rifampicin, ursodeoxycholic acid and bezafibrate, and elective delivery at 34 weeks.
Case 2: Para 1 female with a previous uncomplicated pregnancy presented at 31+1 with pruritus. Bloods revealed bile acids 24 (peak) and ALT 774, autoimmune screen was negative. The working diagnosis was viral hepatitis (without serological confirmation). Diagnostic uncertainty persisted and resulted in challenges in management.
Discussion: These cases highlight the importance of involving the wider MDT in the management of elevated liver enzymes in pregnancy. Support from the maternal medicine team ensured timely review and instilled confidence so that appropriate investigations and treatment options were offered. A systematic approach to elevated liver enzymes considering evidenced based guidance is required.
References
1. EASL guideline https://easl.eu/publication-category/clinical-practice-guidelines/
2. Royal College of Obstetricians and Gynaecologists. Intrahepatic Cholestasis of pregnancy: Green-top Guideline no. 43. London: RCOG; 2022
3. Zollner, J., Williamson C, Dixon, Peter. ICP Miniseries: Genetic ISssues in ICP. Obstetric Medicine July 2024.
32Radiation-induced brain necrosis during pregnancy: a delayed complication of gestational trophoblastic disease
Jessica Phillips1, Mandish Dhanjal1, Pooja Dassan1, Michael Seckl2, Charlotte Frise1
1Queen Charlotte and Chelsea Hospital, 2Imperial College Healthcare NHS Trust
Abstract
Introduction: Radiation-induced brain necrosis is an uncommon but serious complication of intracerebral radiotherapy generally occurring 6 months to several years following initial treatment. Outside of pregnancy, management options include glucocorticoids and surgical resection but the monoclonal VEGF inhibitor bevacizumab is preferred for its efficacy and improved side effect profile.1,2
Case: A 34-year-old woman multiparous woman presented at 26 weeks’ gestation with a new right homonymous inferior quadrantanopia. Past medical history included gestational trophoblastic disease with lung and brain metastases diagnosed 10 years prior. She had received chemoradiotherapy, complicated by radiation-induced brain necrosis treated with bevacizumab 4 years after initial diagnosis.
MRI during pregnancy showed increased perilesional oedema affecting previously treated bi-occipital and right cerebellar lesions suggestive of reactive change related to previous radiation necrosis. There was evidence of haemorrhage into the left occipital lesion. Reassuringly, beta-HCG levels declined on serial measurements. She commenced a course of oral prednisolone, complicated by steroid-induced diabetes requiring insulin. Reinitiation of bevacizumab was considered but not undertaken due to stability of her visual symptoms and concern about systemic use in pregnancy.
Her pregnancy was otherwise uncomplicated and she underwent induction of labour at 39 weeks’ gestation, delivering a 3.1kg infant. At the time of most recent review at 16 months postpartum, she had stable symptoms, beta-HCG was negative and imaging showed no progression of disease.
Lessons learnt:
Radiation-induced brain necrosis (RN) can be exacerbated during pregnancy, with diagnosis reliant on careful clinical history, examination and appropriate imaging findings
Bevacizumab is the treatment of choice for RN but is not used in pregnancy (outside of intravitreal injections)3
Serial beta-HCG levels in patients with previous gestational trophoblastic disease can be used later in pregnancy if there is concern regarding progressive malignant disease.
Reference
1. Khan M, Zhao Z, Arooj S, Liao G. Bevacizumab for radiation necrosis following radiotherapy of brain metastatic disease: a systematic review & meta-analysis. BMC Cancer. 2021 Feb 16;21(1):167. doi: 10.1186/s12885-021-07889-3. PMID: 33593308; PMCID: PMC7885379.
2. Liao G, Khan M, Zhao Z, Arooj S, Yan M, Li X. Bevacizumab Treatment of Radiation-Induced Brain Necrosis: A Systematic Review. Front Oncol. 2021 Mar 25;11:593449. doi: 10.3389/fonc.2021.593449. PMID: 33842309; PMCID: PMC8027305.
3. Ong AY, Kiire CA, Frise C, Bakr Y, de Silva SR. Intravitreal anti-vascular endothelial growth factor injections in pregnancy and breastfeeding: a case series and systematic review of the literature. Eye (Lond). 2024 Apr;38(5):951-963. doi: 10.1038/s41433-023-02811-6. Epub 2023 Nov 18. PMID: 37980398; PMCID: PMC10966053.
33Renal graft dysfunction in pregnancy requiring dialysis: A case report
Esme Gardiner1, Ellen Knox2, Graham Lipkin1, Nadia Sarween1
1University Hospitals Birmingham NHS Foundation Trust, 2Birmingham Women's and Children's NHS Foundation Trust,
Abstract
Introduction: With advances in transplant medicine, increasing numbers of pregnant women with kidney transplants are being reported. Despite an increased risk of adverse pregnancy outcomes in these women, the rates of acute rejection do not appear to be increased1.
Case details: This case follows a primiparous women who had a live donor kidney transplant for end stage renal failure secondary to Alport Syndrome. Her immunosuppression regime was tacrolimus, prednisolone and azathioprine. At booking, blood tests revealed an acute kidney injury in conjunction with low tacrolimus levels. An ultrasound of the transplant showed good perfusion however moderate hydronephrosis caused by a fibroid pressing onto her transplant ureter. A nephrostomy was inserted via fluoroscopy. Despite radiological improvement of the hydronephrosis, her kidney function did not improve. Her nephrostomy was removed after becoming dislodged causing severe abdominal pain. A biopsy, at 16 weeks gestation, demonstrated acute T-cell mediated rejection (TCMR) requiring treatment with high dose methylprednisolone. Her transplant function continued to decline with a repeat biopsy showing severe TCMR requiring another course of methylprednisolone and further up-titration of tacrolimus. Her renal function continued to worsen with a biopsy at 17 weeks’ gestation showing no evidence of rejection. Her imaging demonstrated persistent hydronephrosis. A second nephrostomy was inserted and unfortunately, despite this, her renal function worsened further with her antenatal scan showing fetal growth restriction. She was started on haemodialysis via a tunnelled line at 22 weeks’ gestation.
At 27 weeks, she presented with premature rupture of membranes, resulting in an emergency caesarean section. She received her final haemodialysis one-week post-partum with subsequent ongoing spontaneous improvement of graft function.
Discussion:
Managing pregnancy in women with transplants
Evaluating causes of renal graft dysfunction during pregnancy
Indications for dialysis in pregnancy
Importance of exploring psychological health in complex pregnancies
Managing immunosuppression in pregnancy
Reference
1. Shah, S., Venkatesan, R.L., Gupta, A. et al. Pregnancy outcomes in women with kidney transplant: Metaanalysis and systematic review. BMC Nephrol 20, 24 (2019). https://doi.org/10.1186/s12882-019-1213-5
34Stiff Person Syndrome and type 1 diabetes in pregnancy
Kavita Narula1, Mandish Dhanjal1, Victoria Singh-Curry2, Kerry Munro1, Charlotte Frise1
1Queen Charlotte’s and Chelsea Hospital 2Imperial College Healthcare NHS Trust
Abstract
Background: Stiff Person Syndrome (SPS) is a rare autoimmune neurological disorder often associated with anti-GAD antibodies, characterized by muscle rigidity, spasms, and heightened sensitivity to stimuli, occurring predominantly in the axial musculature. Managing SPS in pregnancy, especially in patients with concurrent Type 1 diabetes (T1D) presents significant challenges. This case report discusses the multidisciplinary management of a pregnant woman with SPS and T1D, focusing on her pregnancy, treatment adjustments, and delivery planning.
Case Report: A 32-year-old woman with a history of T1D and SPS, diagnosed in 2015, presented for obstetric care at 13 weeks' gestation after undergoing pre-pregnancy counselling. Her SPS, associated with anti-GAD antibodies, had been managed with intravenous immunoglobulin (IVIg) since diagnosis. Initially, her symptoms included brief freezing episodes, progressing to more severe episodes of muscle spasms and falls triggered by loud noises. Her T1D was controlled with a continuous subcutaneous insulin infusion.
During pregnancy, her treatment regimen was adjusted. A dose of IVIg was omitted in the second trimester due to symptomatic improvement, but this improvement was not sustained. Diazepam and baclofen doses were reduced after counselling about their limited safety data in pregnancy, aiming for the minimal effective dose. Diazepam was switched to clonazepam near the due date, with breastfeeding in mind (clonazepam potentially preferred to diazepam). Her T1D remained well controlled. Delivery planning involved discussions around her unpredictable SPS spasms, risks of shoulder dystocia, and recovery time from a caesarean delivery.
Conclusion: SPS is rare in women of childbearing age, and the effect of SPS on pregnancy (and vice versa) is not well known. Individualized treatment planning is essential, with the possibility of using baclofen, benzodiazepines, and IVIg during pregnancy if necessary. Multidisciplinary team involvement is critical for both ongoing management and delivery planning.
35Successful management of a multiparous woman with refractory immune thrombocytopenia with romiplostim: a case report
Jhia Jiat Teh1, Suparna Sinha2, Zoe Rekesius2, Sarah Jane Lam2
1Imperial College London, 2Hillingdon Hospital
Abstract
Objective: Immune thrombocytopenic purpura (ITP) affects 0.1 to 1 per 1000 pregnancies and is the most common cause of severe maternal thrombocytopenia. In rare cases where there is a poor response to established first-line treatments such as steroids and intravenous immunoglobulin (IVIG), second-line therapies may be considered, however, data regarding these agents in pregnancy is limited. We present a case of successful management of a pregnant woman with refractory ITP with romiplostim, a thrombopoietin receptor agonist.
Case report: We present a case of 39-year-old multiparous woman of Afro-Caribbean ethnicity who had two uncomplicated vaginal deliveries. She required steroids and IVIG during intrapartum and postpartum period in her second pregnancy. Her platelets have remained stable at 30-70x109/L without any further treatment. She presented in the community with spontaneous bruising over thighs and bleeding gums and was referred to gynaecology with a platelet count of 8x109/L. She was aware of the pregnancy but was unbooked at 20 weeks’ gestation. Her platelet levels were refractory to high-dose prednisolone, IVIG, azathioprine and multiple rituximab infusions. A multidisciplinary discussion with haematologist recommended a trial of romiplostim, which successfully increased her platelet count to 85x109/L upon discharge after 63 days of admission. She was found to have a subchorionic haematoma of 52x42x35mm in her anomaly scan, but repeated scans demonstrated stable size and it was not identified from 33 weeks. She had induction of labour at 39 weeks upon maternal request with a platelet count of 180x109/L. She had a successful vaginal delivery with an estimated blood loss of 250ml and was discharged the following day with a platelet count of 216x109/L.
Conclusion: We demonstrated that transient use of romiplostim in the second trimester in refractory cases of severe ITP is a reasonable option when other treatments fail.
36The use of parenteral nutrition in severe hyperemesis gravidarum
Harsha Shah, Stephanie Smith, Kerry Munro, Annabel Lazarus, Charlotte Frise
Imperial College Healthcare NHS Trust
Abstract
Introduction: Hyperemesis gravidarum (HG) affects up to 3.6% of pregnancies1 and has been associated with significant psychological morbidity including depression, suicidal ideation and termination of pregnancy2.
Case: A 33-year-old woman with previous HG and a history of anxiety and depression developed unremitting vomiting in her second pregnancy from the early first trimester, which did not respond to multiple anti-emetics or steroids. She had an endoscopy performed at 17 weeks to rule out other causes of vomiting and thereafter a nasogastric tube (NGT) inserted, but she developed worsening vomiting and abdominal pain with NGT feeding. In view of her severe, treatment resistant HG, a peripherally-inserted central catheter was sited for parental nutrition (PN) which was commenced at 19 weeks. Social and mental health factors (depression and suicidal thoughts) impacted nutrition optimisation and her nutritional requirements were unable to be met despite home PN being facilitated. PN was ultimately stopped at 25 weeks mainly due to debilitating diarrhoea that she attributed to the PN, and resolved when the PN was stopped. From that point she had intravenous fluids thrice weekly with vitamin supplementation, and managed some oral intake of frozen nutritional supplement drinks and ice lollies.
She was delivered at 36 weeks’ gestation by elective repeat caesarean section. Postnatally she was monitored for features of refeeding syndrome and quetiapine and sertraline were commenced.
Conclusions:
HG is a risk factor for adverse pregnancy outcomes; protective factors include a holistic approach to treatment and support from healthcare providers2.
Input from dietetics, nutrition team and other specialists including perinatal mental health is essential.
PN support during pregnancy is complex, requiring careful electrolyte monitoring and input from specialist teams but is associated with decreased perinatal morbidity3.
PN can lead to complications so it is not always the solution for severe HG.
References
1. Einarson TR, Piwko C, Koren G. Quantifying the global rates of nausea and vomiting of pregnancy: a meta analysis. J Popul Ther Clin Pharmacol. 2013;20(2):e171-83.
2. Nana M, Tydeman F, Bevan G, et al. Termination of wanted pregnancy and suicidal ideation in hyperemesis gravidarum: A mixed methods study. Obstetric Medicine. 2022;15(3):180-184.
3. Peled Y, Melamed N, Hiersch L, Pardo J, Wiznitzer A, Yogev Y. The impact of total parenteral nutrition support on pregnancy outcome in women with hyperemesis gravidarum. J Matern Fetal Neonatal Med. 2014 Jul;27(11):1146-50. doi: 10.3109/14767058.2013.851187.
37X-linked protoporphyria: management during pregnancy
Jessica Phillips1, Esther Park1, Mandish Dhanjal1, Robert Sarkany2, Charlotte Frise1
1Queen Charlotte and Chelsea Hospital, 2Guy's and St Thomas' Hospital
Abstract
Introduction: Protoporphyria is a rare, genetic disorder of the haem metabolic pathway. Protoporphyrin accumulates in blood and tissues resulting in severe painful bouts of skin photosensitivity lifelong. 1-5% of patients develop hepatic cirrhosis complicated by rapidly progressive liver failure, requiring orthotopic liver transplantation.
Clinically indistinguishable from erythropoietic protoporphyria (autosomal recessive inheritance), X-linked Dominant Protoporphyria (XLDP) represents 2-10% of protoporphyria cases and is transmitted as an X-linked, dominant trait. Protoporphyria is not known to increase the risk of any complications of pregnancy, and pregnancy does not increase the severity or risks associated with protoporphyria.1
Case: A 34-year-old woman presented in her first pregnancy. She had a diagnosis of protoporphyria, diagnosed biochemically as a teenager after she developed photosensitivity. This had been complicated by moderate hepatic fibrosis without evidence of cirrhosis. She had a strong family history of protoporphyria, including a maternal uncle who died of hepatic complications.
Given her family history suggesting a dominant inheritance pattern, genetic testing was performed during pregnancy. This confirmed a diagnosis of XLDP with the classical pathogenic mutation of ALAS2 gene.
Pregnancy was complicated by progressive thrombocytopenia. There was extensive multidisciplinary discussion and planning around delivery management. She underwent caesarean section under general anaesthesia, delivering a 3.4kg infant at 39 weeks’ gestation. Light filters were used to limit transmission of 340-470nm wavelengths of light during her procedure.
Post-natal genetic testing confirmed that her infant had not inherited XLDP.
Lessons learnt:
It is possible that supplementary iron can worsen the liver disease in protoporphyria, so iron supplementation in women with this condition should be undertaken with extreme caution.
Genetic testing during pregnancy can add valuable information, and allow for accurate genetic counselling for patients and their families
Unlike the acute porphyrias, there are no medication precautions required for patients with protoporphyria.
Reference
1. Dickey AK, Naik H, Keel SB, Levy C, Beaven SW, Elmariah SB, Erwin AL, Goddu RJ, Hedstrom K, Leaf RK, Kazamel M, Mazepa M, Philpotts LL, Quigley J, Raef H, Rudnick SR, Saberi B, Thapar M, Ungar J, Wang B, Balwani M; Porphyrias Consortium of the Rare Diseases Clinical Research Network. Evidence-based consensus guidelines for the diagnosis and management of erythropoietic protoporphyria and X-linked protoporphyria. J Am Acad Dermatol. 2023 Dec;89(6):1227-1237. doi: 10.1016/j.jaad.2022.08.036. Epub 2022 Aug 27. PMID: 36041558; PMCID: PMC9968824.
