Diverse presentations of Cushing's syndrome during pregnancy - A case series.

BACKGROUND: Cushing's syndrome (CS) encompasses various causes of hypercortisolism including adrenocorticotropic hormone (ACTH) secreting pituitary adenoma with or without bilateral adrenal hyperplasia, an adrenal adenoma or carcinoma, ectopic ACTH or corticotrophin-releasing hormone (CRH) secretion by a neoplasm or exogenous corticosteroid therapy. The diagnosis of CS in pregnancy presents a challenge due to overlapping clinical features of pregnancy (weight gain, striae, acne). If untreated, CS in pregnancy is associated with increased risk of maternal and fetal complications. AIMS: With fewer than 250 cases currently published, we aim to review the clinical presentations, diagnostic methods, management, and outcomes of patients with CS in pregnancy to help optimise our clinical practice. MATERIALS AND METHODS: This is a single-centre, retrospective review of woman with documented hypercortisolism receiving antenatal care at a tertiary maternity hospital in Perth between 2006 to 2022. Data were collated from electronic and chart reviews. OMNI calculator was used for birthweight calculations. Local ethics and patient consent were obtained. RESULTS: Five women and seven pregnancies were identified. Four women had a pituitary source of ACTH-dependent CS as confirmed by brain magnetic resonance imaging. One woman had an ectopic source of ACTH. Two women were diagnosed during pregnancy. All pregnancies occurring prior to treatment of the Cushing's disease were complicated by secondary hypertension and diabetes. CONCLUSION: CS represents a rare and difficult to diagnose condition in pregnancy. When untreated, maternal and fetal outcomes are compromised. Close monitoring of the associated complications with involvement of a multidisciplinary team are recommended.

Familial hypercholesterolaemia in pregnancy: Australian case series and review.

BACKGROUND: Familial hypercholesterolaemia (FH) is associated with a significant increase in the risk of premature coronary artery disease. Pregnancy is likely a vulnerable time for atherosclerosis progression, with a physiological rise in low-density lipoprotein cholesterol (LDL-C) further exaggerated by the discontinuation of cholesterol-lowering therapy. MATERIALS AND METHODS: A retrospective review was undertaken of 13 women with familial hypercholesterolemia who were managed during pregnancy between 2007 and 2021 by a multidisciplinary team following individualised risk assessment. RESULTS: Overall, pregnancy outcomes were good, with no maternal or fetal complications, including congenital abnormalities, maternal cardiac events or hypertensive complications. Loss of statin treatment time ranged between 12 months and 3.5 years resulting from the accumulation of the preconception, pregnancy and lactation periods and was magnified in women having more than one pregnancy. Of seven women treated with cholestyramine, one developed abnormal liver function with an elevated international normalisation ratio which was corrected with vitamin K. CONCLUSION: Pregnancy is associated with prolonged cessation of cholesterol-lowering therapy, a concern with respect to the risk of coronary artery disease in FH. Continuation of statin therapy up to conception and even during pregnancy in patients at higher risk of cardiovascular disease may be justified, especially with increasing evidence supporting the safety of statin therapy during pregnancy. However, more long-term maternal and fetal data are required for the routine use of statins during pregnancy. Guideline-informed models of care covering family planning and pregnancy should be implemented for all women with FH.

Intrahepatic cholestasis of pregnancy - Diagnosis and management: A consensus statement of the Society of Obstetric Medicine of Australia and New Zealand (SOMANZ): Executive summary.

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy liver disease, characterised by pruritus and increased total serum bile acids (TSBA), Australian incidence 0.6-0.7%. ICP is diagnosed by non-fasting TSBA ≥19 µmol/L in a pregnant woman with pruritus without rash without a known pre-existing liver disorder. Peak TSBA ≥40 and ≥100 µmol/L identify severe and very severe disease respectively, associated with spontaneous preterm birth when severe, and with stillbirth, when very severe. Benefit-vs-risk for iatrogenic preterm birth in ICP remains uncertain. Ursodeoxycholic acid remains the best pharmacotherapy preterm, improving perinatal outcome and reducing pruritus, although it has not been shown to reduce stillbirth.

The effect of bedtime snacks on fasting blood glucose levels in gestational diabetes mellitus.

AIM: To investigate the effect of different bedtime snacks (higher carbohydrate versus lower carbohydrate versus no snack) on first morning fasting blood glucose levels (BGLs) in women with diet-controlled gestational diabetes mellitus (GDM) and borderline fasting glucose levels. METHODS: This prospective randomised crossover trial enrolled women with diet controlled GDM between 24 and 34 weeks gestation who had two or more first morning fasting BGLs between 4.7 and 5.4 mmol/L in the week prior to recruitment. The women were randomly allocated to 6 different orders of 5 days each of a standardised higher carbohydrate bedtime snack, a lower carbohydrate bedtime snack and no bedtime snack. The primary outcome was fasting capillary BGL as measured with a home glucometer, and the secondary outcome was requirement for insulin as assessed by a physician. RESULTS: A total of 68 women with GDM were enrolled in and completed the study at a median gestation of 30.8 weeks. Compared with no bedtime snack, the higher carbohydrate snack (4.96 vs 4.87 mmol/L, mean difference: 0.09 mmol/L, 95% CI 0.05-0.13, p < 0.001) and the lower carbohydrate snack (5.01 vs 4.87 mmol/L, mean difference: 0.14 mmol/L, 95% CI 0.09-0.18, p < 0.001) were both associated with a slightly higher fasting BGL the following morning. CONCLUSIONS: Taking a bedtime snack was associated with slightly higher fasting BGLs in women with diet-controlled GDM compared with no bedtime snack (Clinical trial registration: ACTRN12617000659303).

Continuous glucose monitoring: A cost-effective tool to reduce pre-term birth rates in women with type one diabetes.

BACKGROUND: Women with type one diabetes experience poorer obstetric outcomes than normoglycaemic women in pregnancy. OBJECTIVE: To investigate the cost and clinical effectiveness of continuous glucose monitoring (GCM) compared to self-monitoring of blood glucose in improving obstetric outcomes in women with type one diabetes during pregnancy. MATERIALS AND METHODS: This retrospective cohort study included women with type one diabetes referred to a state-wide tertiary obstetric centre before and after the introduction of government-funded CGMs in Australia in March 2019. Forty-nine women using CGMs were propensity matched on a range of clinical features with a historical group of 49 women with type one diabetes who exclusively used intermittent self-monitoring of blood in the year prior to the introduction of funding of sensors. Medical records and administrative cost data were audited to quantify cost and clinical effectiveness. RESULTS: There were significantly lower pre-term (95% CI 0.39-0.922; P = 0.026) and very pre-term birth rates (95% CI 1.002-1.184; P = 0.041) in the CGM group. There was a significant reduction in the length of antenatal inpatient hospital stay (P < 0.01) and adult special care unit stay (P = 0.013) and neonatal admission to the neonatal intensive care unit (P = 0.0262) in the continuous glucose monitoring group. CGMs represented a net cost saving to the health care sector of $12 063 per pregnancy where the device was used, with an incremental cost-effectiveness ratio of $3275 per prevented pre-term birth. CONCLUSIONS: CGM use in pregnancy is a cost-effective intervention for reducing the risk of pre-term birth in women with type one diabetes, resulting in a net cost benefit to the health sector.

Associations between aspirin prophylaxis and fetal growth and preeclampsia in women with pregestational diabetes.

BACKGROUND: Current guidelines recommend low-dose aspirin for preeclampsia prophylaxis in all women with pregestational (type one and type two) diabetes mellitus. Most trials showing the efficacy of low-dose aspirin in reducing preeclampsia risk have either excluded or included only small numbers of such women. AIM: To evaluate the association of low-dose aspirin prophylaxis in women with pregestational diabetes with the incidence of large for gestational age (LGA) infants and preeclampsia. MATERIALS AND METHODS: A retrospective observational study of pregnancies to women with pregestational diabetes. Outcomes included rates of LGA and preeclampsia. Women were prescribed low-dose aspirin prophylaxis from early pregnancy according to physician discretion after considering preeclampsia risk. Statistical analyses assessed the group overall and with stratification by diabetes type and other preeclampsia risk factors. RESULTS: Of 716 pregnancies, aspirin was prescribed in 296 (41%). Preeclampsia occurred more frequently in women who received aspirin (58 of 296, 20%) than those who did not (39 of 420, 9%, P < 0.001). This association was maintained after adjustment for diabetes type and other preeclampsia risk factors (adjusted odds ratio (aOR) 1.78; 95% CI 1.02-3.11). LGA infants were commoner in women with type one diabetes of short duration who took aspirin (aOR 2.21; 95% CI 1.05-4.66). CONCLUSION: Low-dose aspirin use in women with pregestational diabetes may be associated with an increased risk of preeclampsia. In women with type one diabetes of short duration aspirin use may be associated with an increased risk of LGA infants. The retrospective nature of this study is acknowledged and assessment of such prophylaxis by further studies is warranted.

Introduction of diabetic retinopathy screening into an antenatal clinic: Impact on maternal screening and diagnosis rates.

Pregnancy is a risk factor for the development and progression of diabetic retinopathy (DR) in women with pre-gestational diabetes. However, a minority of pregnant women with diabetes adhere to retinal screening recommendations. The introduction of an onsite retinal camera at our tertiary maternity hospital significantly increased the proportion of women who received at least one retinal screen during pregnancy (93.0% vs 54.3%, P < 0.001) and the identification of both DR and DR progression. We conclude that the use of a retinal camera in similar clinics is a feasible option to improve DR screening and diagnosis rates in pregnancy.

Management of familial hypercholesterolemia in pregnancy.

PURPOSE OF REVIEW: To highlight quandaries and review options for the management of familial hypercholesterolemia (FH) during pregnancy. RECENT FINDINGS: Women with FH face barriers to effective care and consequently face significant disease related long term morbidity and mortality.Pregnancy includes major maternal physiological changes resulting in exacerbation of maternal hypercholesterolemia compounded by the current practice of cessation or reduction in the dose of lipid-lowering therapy during pregnancy and lactation that may impact short and long term cardiac morbidity and mortality. Although lipoprotein apheresis is the treatment of choice for high- risk FH patients, reassuring safety evidence for the use of statins during pregnancy is mounting rapidly. However, it will be some time before subtle effects on the development of the offspring can be definitively excluded. Women with homozygous FH or with an established atherosclerotic vessel or aortic disease should be offered therapy with statins during pregnancy if lipoprotein apheresis is not readily available. Pregnancy outcomes tend to be favourable in women with FH. We have reviewed the currently available evidence regarding the risks and benefits of treatment options for FH during pregnancy.

A multi-centre, open label, randomised, parallel-group, superiority Trial to compare the efficacy of URsodeoxycholic acid with RIFampicin in the management of women with severe early onset Intrahepatic Cholestasis of pregnancy: the TURRIFIC randomised trial.

BACKGROUND: Severe early onset (less than 34 weeks gestation) intrahepatic cholestasis of pregnancy (ICP) affects 0.1% of pregnant women in Australia and is associated with a 3-fold increased risk of stillbirth, fetal hypoxia and compromise, spontaneous preterm birth, as well as increased frequencies of pre-eclampsia and gestational diabetes. ICP is often familial and overlaps with other cholestatic disorders. Treatment options for ICP are not well established, although there are limited data to support the use of ursodeoxycholic acid (UDCA) to relieve pruritus, the main symptom. Rifampicin, a widely used antibiotic including in pregnant women, is effective in reducing pruritus in non-pregnancy cholestasis and has been used as a supplement to UDCA in severe ICP. Many women with ICP are electively delivered preterm, although there are no randomised data to support this approach. METHODS: We have initiated an international multicentre randomised clinical trial to compare the clinical efficacy of rifampicin tablets (300 mg bd) with that of UDCA tablets (up to 2000 mg daily) in reducing pruritus in women with ICP, using visual pruritus scores as a measuring tool. DISCUSSION: Our study will be the first to examine the outcomes of treatment specifically in the severe early onset form of ICP, comparing "standard" UDCA therapy with rifampicin, and so be able to provide for the first-time high-quality evidence for use of rifampicin in severe ICP. It will also allow an assessment of feasibility of a future trial to test whether elective early delivery in severe ICP is beneficial. TRIAL IDENTIFIERS: Australian New Zealand Clinical Trials Registration Number (ANZCTR): 12618000332224p (29/08/2018). HREC No: HREC/18/WCHN/36. EudraCT number: 2018-004011-44. IRAS: 272398. NHMRC registration: APP1152418 and APP117853.

Impact of the new IADPSG gestational diabetes diagnostic criteria on pregnancy outcomes in Western Australia.

BACKGROUND: There is debate as to the most appropriate diagnostic criteria to diagnose gestational diabetes mellitus (GDM). The proposed International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria have recently been endorsed by various bodies, but there remains no national consensus. AIM: To assess the perinatal outcomes of women with GDM classified according to the 1998 Australasian Diabetes in Pregnancy Society (ADIPS) criteria compared to those with GDM by the IADPSG criteria. MATERIALS AND METHODS: Results of glucose tolerance tests performed between January 2011 and January 2014 were linked with the perinatal data of those who delivered singleton fetuses after 24 weeks' gestation. Analysed data included birthweight, gestational age at birth, macrosomia, mode of delivery, perinatal mortality, nursery admission, maternal body mass index, and gestational weight gain. RESULTS: Of 3571 women, 466 (13%) and 559 (16%) met the criteria for the 1998 ADIPS and IADPSG criteria for GDM, respectively. Those with GDM according to the IADPSG criteria only (6%) were more obese (95% CI 2.3-4.8 kg/m(2) ), delivered neonates on average 106 g heavier (95% CI 19-193 g) and had more fetal macrosomia (18% vs 11%, P = 0.002) than those with normal glucose tolerance. CONCLUSIONS: The IADPSG criteria for GDM identified a group of women at previously unrecognised increased risk of adverse perinatal outcomes. Adopting the IADPSG criteria would increase the number of women diagnosed with GDM by 20%; however, the improvements in perinatal morbidity, in addition to potential long-term benefits, may justify the increase in healthcare workload.

Determinants of progression of diabetic retinopathy in pregnancy.

AIMS: To assess the rate of diabetic retinopathy (DR) progression in an Australian cohort and to identify the determinants of DR progression in pregnancy. METHODS: A total of 367 pregnancies of women with Type 1 or 2 diabetes mellitus attending King Edward Memorial Hospital, Western Australia, between June 2020 and July 2023 were included. These women were screened for the presence and severity of DR in the first trimester and/or at 28-32 weeks gestation via retinal imaging with a DRS camera. RESULTS: DR was seen in 121 (33 %) pregnancies at baseline and DR progression was seen in 62 (17 %) pregnancies. Only 11 (4 %) women with no baseline DR developed DR and none of these progressed to more than moderate non-proliferative DR. A total of 51 (42 %) women with baseline DR had DR progression. The presence of baseline DR was the only significant predictor for DR progression on multivariate analysis (OR 9.88 (4.43-22.07), p < 0.001). CONCLUSIONS: Women without DR at baseline are unlikely to progress to more severe forms of DR and usually do not require treatment. The presence of DR at baseline screening during pregnancy is a strong predictor of DR progression during pregnancy.

Pregnancy-associated haemolytic anaemia: A cause not to be forgotten.

Anaemia in pregnancy is common, however, only a few cases of pregnancy-associated autoimmune haemolytic anaemia have been documented. Typically, such cases involve a positive direct antiglobulin test and have the potential to cause haemolytic disease of the fetus and newborn. Rarely, no autoantibodies are detected. We report two cases of direct antiglobulin test negative haemolytic anaemia occurring in multiparous women with no cause found. Both women had a haematological response to corticosteroid therapy and delivery.

Crigler-Najjar type II in pregnancy: A case report.

Crigler-Najjar is a rare, autosomal recessive disorder that results in mutations causing a complete absence (type I) or deficiency (type II) of the hepatic uridine diphospho-glucuronosyl transferase (UDPGT) enzyme. Both forms, however, result in unconjugated hyperbilirubinaemia which can lead to kernicterus and potentially death. Phenobarbitone can be used as an enzyme inducer in Type II to facilitate a reduction in total serum bilirubin. We report two consecutive pregnancies in a 29-year-old woman with Crigler-Najjar Type II syndrome. Phenobarbitone therapy was commenced in the first pregnancy at 16 weeks' gestation and was associated with favorable biochemical and clinical outcomes. There were no reports of long-term neonatal neurological sequelae. Tertiary center, multidisciplinary care is recommended for optimal pregnancy outcomes.

Preeclampsia in women with lupus - Influence of aspirin and hydroxychloroquine on pregnancy outcome.

Systemic lupus erythematosus is associated with increased rates of preeclampsia. Both aspirin and hydroxychloroquine are recommended for preeclampsia prophylaxis in women with lupus but there are no studies examining related outcomes in an Australian cohort. This was a single centre retrospective study of lupus affected pregnancies. The association between hydroxychloroquine, aspirin and preeclampsia was examined using adjusted logistic regression models. In 95 pregnancies, hydroxychloroquine was associated with a significantly lower risk of preeclampsia (adjusted OR 0.16, 95 % CI 0.04-0.64) but there was no association between aspirin and preeclampsia (adjusted OR 1.34, 95 % CI 0.33-5.40).

Utilisation of preconception care in women with pregestational diabetes in Western Australia.

This study investigated the level of awareness of the availability of preconception care in a tertiary obstetric hospital for women with type 1 and 2 diabetes, the willingness of these women to attend for preconception counselling and the barriers that may impact upon access to preconception care in Western Australia. The results show greater effort is needed to improve the awareness of women about the importance of preconception care and their willingness to attend the clinic. Access to consistent preconception care should be available for all women with diabetes. The counselling process should be individualised to accommodate different needs.

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.

A case of hypertension with virilisation during pregnancy.

This case report describes the onset of hypertension and virilisation during pregnancy due to a Brenner tumour.

Maternal Pyrexia and Villitis of Unknown Etiology.

BACKGROUND: Villitis of unknown etiology is an inflammatory placental condition associated with adverse pregnancy outcomes, including fetal growth restriction and preterm birth. CASE: We describe maternal pyrexia with daily rigors in the third trimester of two consecutive pregnancies in the same woman. In her second pregnancy, we found no evidence of infection despite an extensive antenatal investigation (blood and urine cultures, serologies, chest X-ray, abdominal ultrasonogram, echocardiogram). The fetus was closely monitored for growth and well-being until spontaneous labor ensued at 36 weeks of gestation, followed by the birth of a vigorous female neonate who weighed 2.235 kg and was healthy. Placental pathology was consistent with villitis of unknown etiology and displayed more prominent abscess formation than is usually described. The patient's first pregnancy 4 years previously followed a similar but milder pattern, without preterm delivery but with similar placental pathology. CONCLUSION: Maternal pyrexia in both pregnancies was ultimately attributed to placental inflammation secondary to a maternal immunologic response to the fetal-placental unit. A placental origin for maternal pyrexia should be considered in cases in which a maternal cause cannot be identified and the pregnancy managed in light of the possible association with adverse fetal outcomes.