Cardiovascular outcomes 50 years after antenatal exposure to betamethasone: Follow-up of a randomised double-blind, placebo-controlled trial.

BACKGROUND: Antenatal corticosteroids for women at risk of preterm birth reduce neonatal morbidity and mortality, but there is limited evidence regarding their effects on long-term health. This study assessed cardiovascular outcomes at 50 years after antenatal exposure to corticosteroids. METHODS AND FINDINGS: We assessed the adult offspring of women who participated in the first randomised, double-blind, placebo-controlled trial of antenatal betamethasone for the prevention of neonatal respiratory distress syndrome (RDS) (1969 to 1974). The first 717 mothers received 2 intramuscular injections of 12 mg betamethasone or placebo 24 h apart and the subsequent 398 received 2 injections of 24 mg betamethasone or equivalent volume of placebo. Follow-up included a health questionnaire and consent to access administrative data sources. The co-primary outcomes were the prevalence of cardiovascular risk factors (any of hypertension, hyperlipidaemia, diabetes mellitus, gestational diabetes mellitus, or prediabetes) and age at first major adverse cardiovascular event (MACE) (cardiovascular death, myocardial infarction, coronary revascularisation, stroke, admission for peripheral vascular disease, and admission for heart failure). Analyses were adjusted for gestational age at entry, sex, and clustering. Of 1,218 infants born to 1,115 mothers, we followed up 424 (46% of survivors; 212 [50%] female) at mean (standard deviation) age 49.3 (1.0) years. There were no differences between those exposed to betamethasone or placebo for cardiovascular risk factors (159/229 [69.4%] versus 131/195 [67.2%]; adjusted relative risk 1.02, 95% confidence interval [CI] [0.89, 1.18;]; p = 0.735) or age at first MACE (adjusted hazard ratio 0.58, 95% CI [0.23, 1.49]; p = 0.261). There were also no differences in the components of these composite outcomes or in any of the other secondary outcomes. Key limitations were follow-up rate and lack of in-person assessments. CONCLUSIONS: There is no evidence that antenatal corticosteroids increase the prevalence of cardiovascular risk factors or incidence of cardiovascular events up to 50 years of age. Established benefits of antenatal corticosteroids are not outweighed by an increase in adult cardiovascular disease.

High rates of the SDHB p.Arg46Gln pathogenic variant predisposes New Zealand Maori to phaeochromocytoma/paraganglioma.

BACKGROUND: Phaeochromocytomas (PCC) and paragangliomas (PGL; together PPGL) are rare tumours of the adrenal medulla or extra-adrenal paraganglia. They may secrete catecholamines with significant cardiovascular effects. Management of PPGL is predominantly surgical, despite the anaesthetic risks related to potential haemodynamic instability. Meticulous pre-treatment and intra-operative management are required to improve cardiovascular outcomes. AIMS: There are limited local data regarding the incidence of PPGL and the clinical characteristics of individuals diagnosed with these tumours in New Zealand. We undertook a retrospective study investigating the local practice and patient characteristics with an additional focus on intra-operative haemodynamic stability and post-operative outcomes. METHODS: Electronic patient records were searched for individuals with a diagnosis of PPGL. Clinical records and electronic databases were interrogated for pre-operative, intra-operative and post-operative data points. Particular attention was paid to rates and types of germline mutations, intra-operative haemodynamic stability and post-operative renal and cardiovascular outcomes. RESULTS: We identified 49 individuals with PPGL, of whom 34 were from the local area. This gave a local incidence of PPGL of around five cases per million people per year. Maori were significantly over-represented in our cohort, with this being in part due to high rates of the SDHB R46Q mutation. Over 95% of our cohort met pre-specified pre-operative blood pressure parameters. Intra-operative monitoring revealed a tendency to hypotension, but this did not translate into adverse post-operative outcomes, which were infrequent. CONCLUSIONS: Maori were over-represented due to high rates of germline SDHB R46Q mutations. There were few post-operative adverse outcomes in this contemporary cohort.

The ADIPS Pilot National Diabetes in Pregnancy Benchmarking Programme.

BACKGROUND: To test the feasibility of benchmarking the care of women with pregnancies complicated by hyperglycaemia. METHODS: A retrospective audit of volunteer diabetes services in Australia and New Zealand involving singleton pregnancies resulting in live births between 2014 and 2020. Ranges are shown and compared across services. RESULTS: The audit included 10,144 pregnancies (gestational diabetes mellitus (GDM) = 8696; type 1 diabetes (T1D) = 435; type 2 diabetes (T2D) = 1013) from 11 diabetes services. Among women with GDM, diet alone was used in 39.4% (ranging among centres from 28.8-57.3%), metformin alone in 18.8% (0.4-43.7%), and metformin and insulin in 10.1% (1.5-23.4%); when compared between sites, all p < 0.001. Birth was by elective caesarean in 12.1% (3.6-23.7%) or emergency caesarean in 9.5% (3.5-21.2%) (all p < 0.001). Preterm births (<37 weeks) ranged from 3.7% to 9.4% (p < 0.05), large for gestational age 10.3-26.7% (p < 0.001), admission to special care nursery 16.7-25.0% (p < 0.001), and neonatal hypoglycaemia (<2.6 mmol/L) 6.0-27.0% (p < 0.001). Many women with T1D and T2D had limited pregnancy planning including first trimester hyperglycaemia (HbA1c > 6.5% (48 mmol/mol)), 78.4% and 54.6%, respectively (p < 0.001). CONCLUSION: Management of maternal hyperglycaemia and pregnancy outcomes varied significantly. The maintenance and extension of this benchmarking service provides opportunities to identify policy and clinical approaches to improve pregnancy outcomes among women with hyperglycaemia in pregnancy.

Pregnancy outcomes among multi-ethnic women with different degrees of hyperglycaemia during pregnancy in an urban New Zealand population and their association with postnatal HbA1c uptake.

BACKGROUND: Adverse pregnancy outcomes are more common in women with hyperglycaemia. Many women have suboptimal uptake of HbA1c testing postdelivery. AIMS: To compare pregnancy outcomes among multi-ethnic women with different degrees of hyperglycaemia during pregnancy, and their association with postnatal HbA1c uptake after the introduction of email reminders. MATERIALS AND METHODS: A retrospective and prospective single-centre study was conducted in South Auckland in 2639 women with early gestational diabetes mellitus (GDM) (diagnosed < 20 weeks), late GDM (diagnosed ≥ 20 weeks), overt diabetes in pregnancy, or known type 2 diabetes (T2DM) during pregnancy. Automated email reminders were sent to general practitioners to increase postnatal HbA1c screening. RESULTS: HbA1c during pregnancy increased across the late GDM (n = 1425), early GDM (n = 148), overt diabetes (n = 573) and T2DM (n = 493) groups (P < 0.001). Stillbirth was least common in the late GDM group (0, 0.7, 0.5, and 1.9%, respectively, P < 0.001), as were caesarean delivery (32.7, 45.1, 39.4, and 53.5%, respectively, P < 0.001), large for gestational age (LGA) (14.7, 18.2, 22.3, and 30.5%, respectively, P < 0.001), small for gestational age (8.8, 16.7, 11.0, and 11.1%, respectively, P = 0.02), and preeclampsia/eclampsia (7.7, 9.2, 13.0, and 14.8%, respectively, P < 0.001). LGA and preeclampsia/eclampsia were more common among Pacific and Maori women than European women (LGA, 30.1, 22.7, 10.3%, respectively, P < 0.001; preeclampsia/eclampsia, 13.5, 14.0, and 8.1%, respectively, P < 0.001). Postpartum HbA1c screening increased among women with GDM/overt diabetes after the introduction of the reminder emails (39.6% vs 34.0%, P = 0.03). CONCLUSIONS: Women with late GDM are least likely to experience adverse outcomes. Email reminders to improve postpartum HbA1c screening warrant further investigation.

Treatment of Paget's Disease of Bone with Denosumab: Case Report and Literature Review.

Paget's disease is a condition involving focal overactivity of bone cells (osteoblasts and osteoclasts), which can result in significant skeletal morbidity. It is unclear in which bone cells the causative lesion resides. It is managed effectively with potent bisphosphonates, but treatment is difficult if these drugs are contraindicated. We describe a 75-year-old woman with Paget's disease involving the skull who was intolerant of bisphosphonates, so was treated with denosumab. This intervention normalized serum alkaline phosphatase for 4-8 months after each injection and led to some symptomatic improvement. Scintigraphic activity in the lesion was improved but not normalized. We conclude that reduction in RANKL activity by denosumab only partially corrects pagetic activity, indicating that the osteoclast overactivity of Paget's disease is not wholly mediated by RANKL. Denosumab has some clinical utility in Paget's disease and may become a second-line agent in those with contraindications to intravenous bisphosphonates.

Impact of using the International Association of Diabetes and Pregnancy Study Groups criteria in South Auckland: prevalence, interventions and outcomes.

INTRODUCTION: Adopting the modified International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria for diagnosing gestational diabetes mellitus (GDM) will increase the prevalence of GDM resulting in increased resource utilisation and an unknown effect on clinical outcomes. AIMS: To determine the prevalence of GDM by the modified IADPSG criteria and compare characteristics and pregnancy outcomes between women with GDM by IADPSG-additional, those with GDM by the New Zealand Society for the Study of Diabetes (NZSSD) criteria and those with a normal oral glucose tolerance test (OGTT). METHODS: All women who delivered at Counties Manukau District Health Board (CMDHB) for a 12-month period from July 2012 to June 2013 had demographic, pregnancy and laboratory data obtained from hospital databases and clinical records. RESULTS: Of the 6376 (85%) of eligible women screened for GDM, 381 (6%) had GDM by NZSSD criteria and an additional 238 (4%) by the modified IADPSG-additional criteria, a relative increase of 62%. Women with GDM by NZSSD criteria had similar characteristics compared to women with GDM by IADPSG-additional. The outcomes between the two groups were also similar with the exception of a higher induction of labour (IOL) rate in women with GDM by NZSSD and a higher mean birthweight in the GDM by IADPSG-additional. CONCLUSION: Adopting the modified IADPSG criteria will result in a 62% increase in the number of GDM cases with a significant impact on workload and resources. Currently, there is insufficient evidence to support the introduction of the IADPSG criteria for our service.

Diagnostic category agreement and malignancy rates in clinician-categorised, non-standardised thyroid cytology reports.

AIM: Standardised reporting of thyroid cytology is recommended but not universally practiced. We compared agreement between clinicians categorising non-standardised thyroid cytology reports, and determined malignancy rates in clinician-assigned cytology categories. METHODS: We identified all thyroid cytology reports from 2008-9 and any reports prior to histology samples from 2008-9 at Middlemore Hospital. Two clinicians independently classified these cytology reports using the Bethesda System, and we assessed agreement between their classifications. We classified histology results following the cytology sample as benign or malignant according to the primary diagnosis in the histology report, and calculated malignancy rates for each cytology category. RESULTS: Agreement between the classifications of 259 cytology results from 227 patients was moderate (kappa=0.67, 95% confidence interval 0.61-0.74), with good agreement (>80%) for only 3 of the 6 Bethesda categories. 122 patients had subsequent thyroid histology samples. 88% had benign primary diagnoses, with 15 (12%) primary thyroid cancers and an additional 11 (9%) incidental cancers. Malignancy rates for each Bethesda category varied from published rates for the majority of clinician-assigned categories. CONCLUSIONS: Low agreement between interpretation of non-standardised thyroid cytology reports suggests that standardised reporting should be universally adopted. Malignancy rates for thyroid cytology categories should be reported to inform local clinical practice.

Evaluation of chronic hypertension in pregnant young women.

Women with chronic hypertension are at higher risk of adverse obstetric outcomes. It is essential that the condition is identified and evaluated appropriately in early pregnancy. Therefore, an audit has been carried out to assess how well young pregnant women with chronic hypertension were investigated for secondary cause in South Auckland, compared with the recommendations of the Australasian Society for the Study of Hypertension in Pregnancy. The evaluation of chronic hypertension by history taking, physical examination, laboratory assessment and radiology tests was highly variable. Only 76% of women had appropriate follow-up for their hypertension. Screening for secondary causes was not consistent, and the majority had incomplete investigation.

Toxic epidermal necrolysis after paroxetine treatment.

Toxic epidermal necrolysis (TEN) is a rare complication of paroxetine treatment and can be life-threatening. We report a case of paroxetine-induced TEN in an 80-year-old Maori female. She was started on paroxetine 10 mg once daily 6 days prior to hospital admission. The patient then developed extensive vesiculobullous skin eruptions. She was treated with intravenous fluid, corticosteroid, and local dressings and concurrently her paroxetine was stopped. A series of laboratory investigations were carried out and a final diagnosis of TEN was made from skin biopsy. The patient was discharged home after 2 weeks of treatment. Her skin lesions improved gradually.

Vitamin D deficiency in pregnant New Zealand women.

AIM: This aim of this study was to identify the prevalence of vitamin D deficiency in pregnant women of a Wellington general practice where 10 cases of childhood rickets had been diagnosed over the past 3 years. METHODS: Ninety pregnant women were screened for vitamin D deficiency by measuring 25-hydroxy vitamin D by DiaSorin radioimmunoassay. Recruitment into the study was over a 12-month period. A second appointment was arranged for clinical review and drawing of blood for parathyroid hormone, adjusted calcium, and alkaline phosphatase. RESULTS: 100% of women presenting to the general practice for antenatal care consented to the study. 87% of women had 25-hydroxy vitamin D levels below 50 nmol/L. 61.2% of women had a vitamin D level below 25 nmol/L consistent with severe vitamin D deficiency. 10 women had an elevated parathyroid hormone consistent with secondary hyperparathyroidism. Only 22% of our patients were veiled, and included a diverse ethnic population, including African, Maori, European, Middle Eastern, and Polynesian women. CONCLUSIONS: Vitamin D deficiency is common in young pregnant women in this general practice, and it was not only confined to veiled women or women with dark skin. This highlights the magnitude of vitamin D deficiency in the pregnant population in a New Zealand setting; this vitamin D deficiency is responsible for the re-emergence of childhood rickets.

Combined sellar fibrosarcoma and prolactinoma with neuronal metaplasia: report of a case unassociated with radiotherapy.

We report the occurrence of a primary pituitary fibrosarcoma causally unrelated to radiotherapy, admixed in association with a prolactin cell pituitary adenoma showing neuronal metaplasia. These unique findings were associated with multiple endocrine neoplasia type 1 (MEN 1). Primary fibrosarcoma involving the sella is a very rare tumor. The majority of cases have been associated with prior irradiation of either a pituitary adenoma or a craniopharyngioma. Pituitary adenoma with neuronal metaplasia is also rare and usually occurs in the setting of acromegaly. Despite the intimate association of both elements in our lesion, no transition of adenoma to sarcoma was demonstrable by immunohistochemistry or in situ hybridization studies.