Pregnancy in patients with mucopolysaccharidosis: a case series.

The mucopolysaccharidoses (MPS disorders) are rare inherited diseases associated with multi-organ accumulation of glycosaminoglycans, leading to musculoskeletal, respiratory, cardiac, neurological, ophthalmological, otolaryngological, and gastrointestinal abnormalities. As a result of improvements in diagnosis, multi-disciplinary care, and therapies such as enzyme replacement therapy and hematopoietic stem cell transplantation, an increasing number of patients with MPS are reaching adulthood and are involved in family planning. Data on fertility and pregnancy outcome in MPS is sparse and comprises primarily isolated case reports. To address this evidence gap, we present a case series on fertility and pregnancy in eight mothers and five fathers with MPS. This case series demonstrates that women with MPS have high-risk pregnancies and deliveries secondary to their underlying disease. However, with appropriate pre-conceptual multi-disciplinary evaluation, optimization and discussion regarding potential risks, combined with regular multi-disciplinary maternal and fetal surveillance in a tertiary center, the outcome of most pregnancies in this case series seems to be favorable with all babies developing normally. Partners of fathers with MPS had uncomplicated pregnancies and deliveries. All children were healthy, with normal growth and development.

Expert Opinions on Managing Fertility and Pregnancy in Patients With Mucopolysaccharidosis

Abstract The mucopolysaccharidosis (MPS) disorders are rare genetic diseases caused by deficiencies in lysosomal enzymes involved in the degradation of glycosaminoglycans, leading to pulmonary, cardiac and neurological dysfunctions, skeletal anomalies, impaired vision, and/or hearing and shortened life spans. Whereas in the past, few individuals with MPS reached adulthood, better diagnosis, multidisciplinary care, and new therapies have led to an increasing number of adult patients with MPS. Therefore, fertility and pregnancy questions in this patient population are becoming more important. Management of fertility issues and pregnancy in patients with MPS is challenging due to the lack of documented cases and a dearth in the literature on this topic. This review presents multidisciplinary expert opinions on managing fertility and pregnancy based on case studies and clinical experience presented at a meeting of MPS specialists held in Berlin, Germany, in April 2015. An overview of the existing literature on this subject is also included.

Effectiveness of earlier antenatal screening for sickle cell disease and thalassaemia in primary care: cluster randomised trial.

OBJECTIVE: To evaluate the effectiveness of offering antenatal screening for sickle cell disease and thalassaemia in primary care as a way of facilitating earlier uptake of screening. DESIGN: Partial factorial cluster randomised controlled trial. SETTING: 25 UK general practices from deprived inner city areas. PARTICIPANTS: Anonymised data on all pregnant women attending participating practices during a six month period before randomisation and a seven month period after randomisation. This included 1708 eligible women. INTERVENTION: Practices were randomised to three groups for seven months: parallel testing in general practice (tests for sickle cell disease and thalassaemia offered to both parents when pregnancy was first reported); sequential testing in general practice (tests offered to mothers when pregnancy was first reported, and subsequently to the partners of women who were found to be carriers); and midwife care (tests offered to mothers at first consultation with a midwife). MAIN OUTCOME MEASURES: The primary outcome (available for all women) was the proportion of eligible women screened before 10 weeks' (70 days') gestation. Secondary outcomes were an offer of screening to women before 10 weeks' gestation, gestational age at testing, mean interval from first visit to the general practice visit to screening, and women's knowledge of the carrier status of their baby's father before 77 days' (11 weeks') gestation. The study was designed to detect a 20% absolute increase in screening uptake. Cluster level analyses were adjusted for age group, parity, ethnic group, primary care organisation, and number of general practitioners per practice. RESULTS: Data were analysed for 1708 eligible women. In the midwife care arm, 2% (9/441) of women were screened before 10 weeks' gestation compared with 24% (161/677) in the GP parallel testing arm and 28% (167/590) in the GP sequential testing arm. The estimated adjusted difference between the midwife care and GP parallel testing arms was 16.5% (95% confidence interval 7.1% to 25.8%; P=0.002) and between the midwife care and GP sequential testing arms was 27.8% (14.8% to 40.7%; P<0.001). By 26 weeks' gestation the proportion of women screened across the three trial arms was similar (81%). The proportion of women who knew the carrier status of the baby's father by 11 weeks' gestation was 0% (0/441) in the midwife care arm, 2% (13/677) in the GP parallel testing arm (P=0.003), and 1% (3/590) in the GP sequential testing arm (P=0.374). CONCLUSION: Offering antenatal screening for sickle cell disease and thalassaemia as part of consultations for pregnancy confirmation in primary care increases the proportion of women screened before 10 weeks' gestation. Even with intervention, however, only a minority of women were screened before 10 weeks. Additional interventions should be considered to achieve testing early in pregnancy for most women wanting such tests so that couples with affected pregnancies have less time pressure to choose options, which may include termination of the pregnancy. TRIAL REGISTRATION: Current Controlled Trials ISRCTN00677850.

Telomere length dynamics differ in foetal and early post-natal human leukocytes in a longitudinal study.

Haemopoietic stem cells (HSC) undergo a process of self renewal to constantly maintain blood cell turnover. However, it has become apparent that adult HSC lose their self-renewal ability with age. Telomere shortening in peripheral blood leukocytes has been seen to occur with age and it has been associated with loss of HSC proliferative capacity and cellular ageing. In contrast foetal HSC are known to have greater proliferative capacity than post-natal stem cells. However it is unknown whether they undergo a similar process of telomere shortening. In this study we show a more accentuated rate of telomere loss in leukocytes from pre term infants compared to human foetuses of comparable age followed longitudinally for 8-12 weeks in a longitudinal study. Our results point to a difference in HSC behaviour between foetal and early postnatal life which is independent of age but may be influenced by events at birth itself.

Post partum haemorrhage secondary to uterine atony, complicated by platelet storage pool disease and partial placenta diffusa: a case report.

INTRODUCTION: Uterine atony is the most common cause of primary post partum haemorrhage. We report a case where this was complicated by two rare conditions, platelet storage pool disease and placenta diffusa. Platelet storage pool disease is a platelet aggregation disorder associated with mild to moderate bleeding diathesis. There are limited cases reported in pregnancy. Placenta diffusa is a rare anomaly where all or part of the fetal membranes remain covered by chorionic villi, and is associated with post partum haemorrhage. CASE PRESENTATION: A 37-year-old woman was referred to the obstetric haematology clinic for prenatal counselling with a history of three severe post partum haemorrhages, two of which were complicated by placental retention. Platelet aggregation studies confirmed a diagnosis of platelet storage pool disease. She was counselled regarding her risk of a recurrent haemorrhage and a planned delivery was discussed. She subsequently presented at 15 weeks' gestation. Following an uneventful pregnancy, she was covered with prophylactic desmopressin and tranexamic acid before a planned induction of labour. She had a normal delivery but placenta was retained. In theatre, an uncomplicated manual removal was followed by massive haemorrhage secondary to uterine atony. Aggressive medical management and B lynch sutures at laparotomy failed to contract the uterus. Hysterectomy was therefore performed. Placental histology later showed evidence of partial placenta diffusa. CONCLUSION: Post partum haemorrhage continues to be a leading cause of maternal morbidity and mortality. In this patient, despite identification and attempts at correction of an identified clotting disorder, major obstetric haemorrhage was not avoided. An additional rare placental abnormality was later found. This case highlights the need for medical staff to be aware and alert to unusual risk factors. However, these factors may be unavoidable and early surgical intervention as per local protocol is recommended to minimise maternal morbidity.

Hematopoietic progenitor cell deficiency in fetuses and children affected by Down's syndrome.

OBJECTIVES: There is an increased risk of myeloid malignancy in individuals with Down's syndrome (DS), which is associated with a mutation in exon 2 of the transcription factor GATA-1. It is recognized that there is accelerated telomere shortening in blood cells of children with DS similar to that in conditions such as Fanconi anemia and dyskeratosis congenita. The latter conditions are associated with stem cell deficiency and clonal change, including acute myeloid leukemia. In this study we address the questions 1) whether the accelerated telomere shortening is associated with progenitor/stem cell deficiency in individuals with DS, predisposing to clonal change and 2) whether the occurrence of reduced numbers of stem/progenitor cells precede the incidence of mutations in exon 2 of GATA-1. MATERIAL AND METHODS: Peripheral blood from fetuses (23-35 weeks gestation) and/or bone marrow from children affected by DS and age-matched hematologically healthy controls were analyzed for telomere length, content of stem/progenitor cells, and mutations in exon 2 of GATA-1. RESULTS: We found that hematopoietic stem/progenitor cell deficiency and telomere shortening occurs in individuals with DS in fetal life. Moreover, the presence of a low number of progenitor cells was not associated with mutations in exon 2 of GATA-1. CONCLUSIONS: We propose that stem cell deficiency may be a primary predisposing event to DS leukemia development.

Outcomes of labours augmented with oxytocin.

OBJECTIVE: To highlight the differences in mode of delivery between women augmented with intravenous oxytocin because of failure to progress in labour with those who labour without the need for augmentation. STUDY DESIGN: An incidence study over a 5-year-period in a tertiary referral hospital comparing 1097 nulliparous women who were augmented in labour with 2745 nulliparous women who did not need augmentation. Only labours of spontaneous onset in the pregnancies of women at term were studied. The incidence of pregnancy outcomes were assessed by presenting estimates of relative risk (RR) and their 95% confidence intervals (CI). RESULTS: Only 51.1% of women who received augmentation achieved a normal vaginal delivery compared with 76.5% of women who did not need augmentation (RR 0.67; CI 0.63-0.71). Contributory factors to this disparity included a greater number of Caesarean sections (14.4% versus 6.6%; RR 2.18 CI 1.74-2.67), forcep deliveries (12.8% versus 5.3%; RR 2.41 CI 1.93-3.01) and ventouse deliveries (21.7% versus 11.5%; RR 1.89 CI 1.62-2.21) being performed among augmented labours as compared to normal progressive labours. CONCLUSION: Significant improvements in the management of labours which fail to progress are needed if normal vaginal delivery rates are to approach those seen in labours which progress without the need for augmentation.

Neonatal death following termination of pregnancy.

The aim of this study was to look at neonatal death following termination of pregnancy in 31 cases over a six-year period in our region and to determine why this was occurring. We have highlighted two main areas of concern: failure to perform feticide in keeping with RCOG advice, and classification and registration below the clinical limit of viability. In these circumstances, appropriate counselling of the family and an antenatal plan for the postnatal care of the dying infant made prior to delivery are essential. We question the rationale of the existing classification and registration requirements below the clinical limit of viability.