Induction of labour care in the UK: A cross-sectional survey of maternity units.

OBJECTIVES: To explore local induction of labour pathways in the UK National Health Service to provide insight into current practice. DESIGN: National survey. SETTING: Hospital maternity services in all four nations of the UK. SAMPLE: Convenience sample of 71 UK maternity units. METHODS: An online cross-sectional survey was disseminated and completed via a national network of obstetrics and gynaecology specialist trainees (October 2021-March 2022). Results were analysed descriptively, with associations explored using Fisher's Exact and ANOVA. MAIN OUTCOME MEASURES: Induction rates, criteria, processes, delays, incidents, safety concerns. RESULTS: 54/71 units responded (76%, 35% of UK units). Induction rate range 19.2%-53.4%, median 36.3%. 72% (39/54) had agreed induction criteria: these varied widely and were not all in national guidance. Multidisciplinary booking decision-making was not reported by 38/54 (70%). Delays reported 'often/always' in hospital admission for induction (19%, 10/54) and Delivery Suite transfer once induction in progress (63%, 34/54). Staffing was frequently reported cause of delay (76%, 41/54 'often/always'). Delays triggered incident reports in 36/54 (67%) and resulted in harm in 3/54 (6%). Induction was an area of concern (44%, 24/54); 61% (33/54) reported induction-focused quality improvement work. CONCLUSIONS: There is substantial variation in induction rates, processes and policies across UK maternity services. Delays appear to be common and are a cause of safety concerns. With induction rates likely to increase, improved guidance and pathways are critically needed to improve safety and experience of care.

C-STICH2: emergency cervical cerclage to prevent miscarriage and preterm birth-study protocol for a randomised controlled trial.

BACKGROUND: Cervical cerclage is a recognised treatment to prevent late miscarriage and pre-term birth (PTB). Emergency cervical cerclage (ECC) for cervical dilatation with exposed unruptured membranes is less common and the potential benefits of cerclage are less certain. A randomised control trial is needed to accurately assess the effectiveness of ECC in preventing pregnancy loss compared to an expectant approach. METHODS: C-STICH2 is a multicentre randomised controlled trial in which women presenting with cervical dilatation and unruptured exposed membranes at 16 + 0 to 27 + 6 weeks gestation are randomised to ECC or expectant management. Trial design includes 18 month internal pilot with embedded qualitative process evaluation, minimal data set and a within-trial health economic analysis. Inclusion criteria are ≥16 years, singleton pregnancy, exposed membranes at the external os, gestation 16 + 0-27 + 6 weeks, and informed consent. Exclusion criteria are contraindication to cerclage, cerclage in situ or previous cerclage in this pregnancy. Randomisation occurs via an online service in a 1:1 ratio, using a minimisation algorithm to reduce chance imbalances in key prognostic variables (site, gestation and dilatation). Primary outcome is pregnancy loss; a composite including miscarriage, termination of pregnancy and perinatal mortality defined as stillbirth and neonatal death in the first week of life. Secondary outcomes include all core outcomes for PTB. Two-year development outcomes will be assessed using general health and Parent Report of Children's Abilities-Revised (PARCA-R) questionnaires. Intended sample size is 260 participants (130 each arm) based on 60% rate of pregnancy loss in the expectant management arm and 40% in the ECC arm, with 90% power and alpha 0.05. Analysis will be by intention-to-treat. DISCUSSION: To date there has been one small trial of ECC in 23 participants which included twin and singleton pregnancies. This small trial along with the largest observational study (n = 161) found ECC to prolong pregnancy duration and reduce deliveries before 34 weeks gestation. It is important to generate high quality evidence on the effectiveness of ECC in preventing pregnancy loss, and improve understanding of the prevalence of the condition and frequency of complications associated with ECC. An adequately powered RCT will provide the highest quality evidence regarding optimum care for these women and their babies. TRIAL REGISTRATION: ISRCTN Registry ISRCTN12981869 . Registered on 13th June 2018.

Type 2 Autoimmune Hepatitis and Nonadherence to Medication Correlate With Premature Birth and Risk of Postpartum Flare.

Autoimmune hepatitis (AIH) is an immune-mediated chronic liver disease that affects all ages, including women of childbearing age. Optimal management during pregnancy is poorly defined. We aimed to explore the clinical and biochemical course of AIH in the antenatal and postpartum periods, and assess factors associated with premature birth and postpartum flares. Pregnant women with AIH reviewed in the autoimmune liver disease clinic at the Queen Elizabeth Hospital Birmingham between 2009 and 2020 were identified retrospectively, and clinical, biochemical, and immunological data 1 year before conception to 1 year postpartum were collected. Analysis was performed to identify trends in blood markers over the antenatal period, with an interrupted time series approach used to assess postpartum trends. Data were available for n = 27 pregnancies (n = 20 women), with median gestation of 38 weeks (30% premature) and most having type 1 AIH (78%) and delivering via caesarean section (63%). Levels of alanine transaminase, aspartate transaminase, and immunoglobulin G all declined significantly during gestation, followed by significant step-change increases after delivery. Postpartum flare developed in 58% of pregnancies. AIH type 2 was associated with a higher rate of premature births (67% vs. 19%, P = 0.044), and a trend toward a higher rate of postpartum flare (100% vs. 48%, P = 0.053). Although not significant, medication nonadherence was associated with almost double the risk of prematurity (40% vs. 24%, P = 0.415) and postpartum flare (80% vs. 44%, P = 0.109). Conclusion: Biochemical and immunological remission of AIH occurs during pregnancy, although subsequent postpartum flare is common. Type 2 AIH is associated with a higher risk of premature birth and postpartum flare, although further research is required to validate and explain this finding.

Review article: chronic liver disease and pregnancy.

BACKGROUND: The prevalence of chronic liver disease in women of child bearing age is increasing, leading to a higher incidence of pregnancy in this cohort. Chronic medical conditions have a significant adverse effect on maternal morbidity and mortality. To date, reviews on this topic have been written either from a hepatology or obstetrics viewpoint, and no specific guidelines are available solely for the management of chronic liver disease in pregnancy. AIMS: To produce a comprehensive review on the clinical management of women with chronic liver disease during pregnancy, addressing the risks of pregnancy to mother and child, how these risks can be ameliorated, and what additional considerations are required for management of chronic liver disease in pregnancy. METHODS: Data were collected up to May 2020 from the biomedical database PubMed, national and international guidelines in gastroenterology and hepatology. RESULTS: During pregnancy, women with cirrhosis are more likely to develop decompensated disease, worsening of portal hypertension, and to deliver premature infants. CONCLUSIONS: The risks associated with pregnancy can be ameliorated by advanced planning, assessing risk using the model for end stage liver disease score and risk reduction through varices screening. A multidisciplinary approach is paramount in order to minimise complications and maximise the chance of a safe pregnancy and birth for mother and baby.

Outcomes of pregnancy in patients with known Budd-Chiari syndrome.

AIM: To analyse the risk of pregnancy (a prothrombotic state) in patients with Budd-Chiari Syndrome (BCS). METHODS: Retrospective study of pregnancy in women with known BCS at single center from January 2001 to December 2015. RESULTS: Out of 53 females with BCS, 7 women had 16 pregnancies. Median age at diagnosis of BCS in these women was 25 years (range 21-34 years). At least one causal factor for BCS was identified in 6 women (86%). Six women had undergone radiological decompressive treatment. All patients had anticoagulation. Six fetuses were lost before 20 wk gestation in 2 women. There were 9 deliveries over 32 wk gestation and one delivery at 27 wk. All infants did well. Seven babies were born by emergency caesarean section. There were no cases of thrombosis. Two patients had notable vaginal (PV) bleeding in 3 pregnancies. None of the patients had variceal haemorrhage. Two patients were diagnosed with pulmonary hypertension, one during pregnancy and the other in the post-partum period. There was no maternal mortality. CONCLUSION: Maternal outcomes in patients with treated BCS are favourable and fetal outcomes beyond 20 wk gestation are good. There has been increased rate of caesarean section. Pulmonary hypertension is an important finding that needs further validation. These patients should be managed in centers experienced in treating high-risk pregnancies.

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.

Successful emergency cardiac pacing and permanent pacemaker insertion in a preterm 29-week gestation hydropic baby with congenital complete heart block.

A preterm 29-week gestation baby was delivered because of gross foetal hydrops secondary to congenital complete heart block. Despite a poor prognosis, she survived stabilisation and received emergency epicardial pacing followed by permanent pacemaker insertion on day 13, weighing 1.2 kg.

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.

Chronic pain and obstetric management of a patient with tuberous sclerosis.

Chronic nonmalignant pain is very disabling and carries a heavy financial strain on the individual and society as a whole. This case describes a woman with tuberous sclerosis, in her fourth pregnancy. Approximately 18 months prior to pregnancy, intractable left loin pain, thought to be secondary to hemorrhage within a tuberous lesion in the left kidney, had led to the siteing of an intrathecal morphine pump. The risks of system failure (dislodgement, dislocation), escalating dosage, infection, use in labor, and neonatal opioid withdrawal are all explored and discussed. While data are limited, with increasing use of intrathecal opioids for nonmalignant pain, such patients may be seen more regularly in obstetric clinics. With a multidisciplinary team approach, risks can be minimized and outcome for mother and baby optimized.

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.

Placental lactate transporter activity and expression in intrauterine growth restriction.

OBJECTIVES: To compare lactate uptake in the microvillous plasma membrane (maternal facing [MVM]) in term and preterm placentas in intrauterine growth restriction (IUGR) and appropriate weight for gestational age (AGA) controls, and in the basal plasma membrane (fetal facing [BM]) at term. In addition, we examine the expression of monocarboxylate transporters (MCT1 and MCT4). METHODS: We measured [14C] L-lactate uptakes into vesicles prepared from MVM and BM, stimulated by an inwardly directed H+ gradient. MCT expression was examined by Western blotting. RESULTS: In term placentas, mean (+/- SE) [14C] L-lactate uptake into MVM vesicles of the IUGR (n = 6) and AGA (n = 11) groups at initial rate was similar (15.4 +/- 2.3 versus 15.0 +/- 1.1 pmol/mg protein/20 s). In preterm placentas, in IUGR (n = 3) and AGA (n = 3) groups, [14C] l-lactate uptake into MVM was also not significantly different. In BM vesicles from term placentas, [14C] L-lactate uptake was significantly lower in IUGR (n = 5) than in AGA (n = 6) controls (3.6 +/- 0.4 versus 5.6 +/- 0.6 pmol/mg protein/20 s, P <.05). MCT1 and MCT4 were expressed in BM vesicles, but there was no difference in expression between the IUGR and AGA groups. CONCLUSIONS: These findings suggest that in IUGR placental lactate transport capacity in the BM is reduced, which may adversely affect placental lactate clearance.