Management of primary hyperparathyroidism in pregnancy: a case series

Summary Primary hyperparathyroidism (PHPT) is characterised by the overproduction of parathyroid hormone (PTH) due to parathyroid hyperplasia, adenoma or carcinoma and results in hypercalcaemia and a raised or inappropriately normal PTH. Symptoms of hypercalcaemia occur in 20% of patients and include fatigue, nausea, constipation, depression, renal impairment and cardiac arrythmias. In the most severe cases, uraemia, coma or cardiac arrest can result. Primary hyperparathyroidism in pregnancy is rare, with a reported incidence of 1%. Maternal and fetal/neonatal complications are estimated to occur in 67 and 80% of untreated cases respectively. Maternal complications include nephrolithiasis, pancreatitis, hyperemesis gravidarum, pre-eclampsia and hypercalcemic crises. Fetal complications include intrauterine growth restriction; preterm delivery and a three to five-fold increased risk of miscarriage. There is a direct relationship between the degree of severity of hypercalcaemia and miscarriage risk, with miscarriage being more common in those patients with a serum calcium greater than 2.85 mmol/L. Neonatal complications include hypocalcemia. Herein, we present a case series of three women who were diagnosed with primary hyperparathyroidism in pregnancy. Case 1 was diagnosed with multiple endocrine neoplasia type 1 (MEN1) in pregnancy and required a bilateral neck exploration and subtotal parathyroidectomy in the second trimester of her pregnancy due to symptomatic severe hypercalcaemia. Both case 2 and case 3 were diagnosed with primary hyperparathyroidism due to a parathyroid adenoma and required a unilateral parathyroidectomy in the second trimester. This case series highlights the work-up and the tailored management approach to patients with primary hyperparathyroidism in pregnancy. Learning points: Primary hyperparathyroidism in pregnancy is associated with a high incidence of associated maternal fetal and neonatal complications directly proportionate to degree of maternal serum calcium levels. Parathyroidectomy is the definitive treatment for primary hyperparathyroidism in pregnancy and was used in the management of all three cases in this series. It is recommended when serum calcium is persistently greater than 2.75 mmol/L and or for the management of maternal or fetal complications of hypercalcaemia. Surgical management, when necessary is ideally performed in the second trimester. Primary hyperparathyroidism is genetically determined in ~10% of cases, where the likelihood is increased in those under 40 years, where there is relevant family history and those with other related endocrinopathies. Genetic testing is a useful diagnostic adjunct and can guide treatment and management options for patients diagnosed with primary hyperparathyroidism in pregnancy, as described in case 1 in this series, who was diagnosed with MEN1 syndrome. Women of reproductive age with primary hyperparathyroidism need to be informed of the risks and complications associated with primary hyperparathyroidism in pregnancy and pregnancy should be deferred and or avoided until curative surgery has been performed and calcium levels have normalised. </jats:sec

Routine testing for group B streptococcus in pregnancy: protocol for a UK cluster randomised trial (GBS3)

Introduction It is unclear whether routine testing of women for group B streptococcus (GBS) colonisation either in late pregnancy or during labour reduces early-onset neonatal sepsis, compared with a risk factor-based strategy.Methods and analysis Cluster randomised trial.Sites and participants 320 000 women from up to 80 hospital maternity units.Strategies Sites will be randomised 1:1 to a routine testing strategy or the risk factor-based strategy, using a web-based minimisation algorithm. A second-level randomisation allocates routine testing sites to either antenatal enriched culture medium testing or intrapartum rapid testing. Intrapartum antibiotic prophylaxis will be offered if a test is positive for GBS, or if a maternal risk factor for early-onset GBS infection in her baby is identified before or during labour. Economic and acceptability evaluations will be embedded within the trial design.Outcomes The primary outcome is all-cause early (&lt;7 days of birth) neonatal sepsis, defined as either a positive blood/cerebrospinal fluid culture, early neonatal death from infection or a negative/unknown culture status with ≥3 agreed clinical signs or symptoms, who receive intravenous antibiotics ≥5 days. All women giving birth ≥24 weeks’ gestation, regardless of mode of birth, and all her babies will be included in the dataset. Cost-effectiveness will be expressed in terms of incremental cost per case of early neonatal sepsis avoided and incremental cost per quality-adjusted life-year associated with each strategy.Ethics and dissemination The trial received a favourable opinion from Derby Research Ethics Committee on 16 September 2019 (19/EM/0253). The allocated testing strategy will be adopted as standard clinical practice by the site. Women in the routine testing sites will give verbal consent for the test. The trial will use routinely collected data retrieved from National Health Service databases, supplemented with limited participant-level collection of process outcomes. Individual written consent will not be sought. The trial results, and parallel economic, qualitative, implementation and methodological results, will be published in the journal Health Technology Assessment.Trial registration number ISRCTN49639731