Consequences of domestication in eastern oyster: Insights from whole genomic analyses.

Selective breeding for production traits has yielded relatively rapid successes with high-fecundity aquaculture species. Discovering the genetic changes associated with selection is an important goal for understanding adaptation and can also facilitate better predictions about the likely fitness of selected strains if they escape aquaculture farms. Here, we hypothesize domestication as a genetic change induced by inadvertent selection in culture. Our premise is that standardized culture protocols generate parallel domestication effects across independent strains. Using eastern oyster as a model and a newly developed 600K SNP array, this study tested for parallel domestication effects in multiple independent selection lines compared with their progenitor wild populations. A single contrast was made between pooled selected strains (1-17 generations in culture) and all wild progenitor samples combined. Population structure analysis indicated rank order levels of differentiation as [wild - wild] < [wild - cultured] < [cultured - cultured]. A genome scan for parallel adaptation to the captive environment applied two methodologically distinct outlier tests to the wild versus selected strain contrast and identified a total of 1174 candidate SNPs. Contrasting wild versus selected strains revealed the early evolutionary consequences of domestication in terms of genomic differentiation, standing genetic diversity, effective population size, relatedness, runs of homozygosity profiles, and genome-wide linkage disequilibrium patterns. Random Forest was used to identify 37 outlier SNPs that had the greatest discriminatory power between bulked wild and selected oysters. The outlier SNPs were in genes enriched for cytoskeletal functions, hinting at possible traits under inadvertent selection during larval culture or pediveliger setting at high density. This study documents rapid genomic changes stemming from hatchery-based cultivation of eastern oysters, identifies candidate loci responding to domestication in parallel among independent aquaculture strains, and provides potentially useful genomic resources for monitoring interbreeding between farm and wild oysters.

Shoulder dystocia in babies born to Aboriginal mothers with diabetes: a population-based cohort study, 1998-2015.

BACKGROUND: Australian Aboriginal and Torres Strait Islander women with diabetes in pregnancy (DIP) are more likely to have glycaemic levels above the target range, and their babies are thus at higher risk of excessive fetal growth. Shoulder dystocia, defined by failure of spontaneous birth of fetal shoulder after birth of the head requiring obstetric maneuvers, is an obstetric emergency that is strongly associated with DIP and fetal size. The aim of this study was to investigate the epidemiology of shoulder dystocia in Aboriginal babies born to mothers with DIP. METHODS: Stratifying by Aboriginal status, characteristics of births complicated by shoulder dystocia in women with and without DIP were compared and incidence and time-trends of shoulder dystocia were described. Compliance with guidelines aiming at preventing shoulder dystocia in women with DIP were compared. Post-logistic regression estimation was used to calculate the population attributable fractions (PAFs) for shoulder dystocia associated with DIP and to estimate probabilities of shoulder dystocia in babies born to mothers with DIP at birthweights > 3 kg. RESULTS: Rates of shoulder dystocia from vaginal births in Aboriginal babies born to mothers with DIP were double that of their non-Aboriginal counterparts (6.3% vs 3.2%, p < 0.001), with no improvement over time. Aboriginal mothers with diabetes whose pregnancies were complicated by shoulder dystocia were more likely to have a history of shoulder dystocia (13.1% vs 6.3%, p = 0.032). Rates of guideline-recommended elective caesarean section in pregnancies with diabetes and birthweight > 4.5 kg were lower in the Aboriginal women (28.6% vs 43.1%, p = 0.004). PAFs indicated that 13.4% (95% CI: 9.7%-16.9%) of shoulder dystocia cases in Aboriginal (2.7% (95% CI: 2.1%-3.4%) in non-Aboriginal) women were attributable to DIP. Probability of shoulder dystocia among babies born to Aboriginal mothers with DIP was higher at birthweights > 3 kg. CONCLUSIONS: Aboriginal mothers with DIP had a higher risk of shoulder dystocia and a stronger association between birthweight and shoulder dystocia. Many cases were recurrent. These factors should be considered in clinical practice and when counselling women.

A second unveiling: Haplotig masking of the eastern oyster genome improves population-level inference.

Genome assembly can be challenging for species that are characterized by high amounts of polymorphism, heterozygosity, and large effective population sizes. High levels of heterozygosity can result in genome mis-assemblies and a larger than expected genome size due to the haplotig versions of a single locus being assembled as separate loci. Here, we describe the first chromosome-level genome for the eastern oyster, Crassostrea virginica. Publicly released and annotated in 2017, the assembly has a scaffold N50 of 54 mb and is over 97.3% complete based on BUSCO analysis. The genome assembly for the eastern oyster is a critical resource for foundational research into molluscan adaptation to a changing environment and for selective breeding for the aquaculture industry. Subsequent resequencing data suggested the presence of haplotigs in the original assembly, and we developed a post hoc method to break up chimeric contigs and mask haplotigs in published heterozygous genomes and evaluated improvements to the accuracy of downstream analysis. Masking haplotigs had a large impact on SNP discovery and estimates of nucleotide diversity and had more subtle and nuanced effects on estimates of heterozygosity, population structure analysis, and outlier detection. We show that haplotig masking can be a powerful tool for improving genomic inference, and we present an open, reproducible resource for the masking of haplotigs in any published genome.

Overweight/obesity and other predictors of gestational diabetes among Aboriginal and non-Aboriginal women in Western Australia.

This population-based study investigated the association of BMI and other predictors with gestational diabetes mellitus (GDM) among Australian Aboriginal and non-Aboriginal mothers. We conducted a state-wide retrospective cohort study that included all singleton births in Western Australia (n = 134,552) between 2012 and 2015 using population health datasets linked by the Western Australian Data Linkage Branch. Associations between GDM and its predictors were estimated as adjusted relative risks (aRRs) from multivariable generalised linear models. Adjusted ratio of relative risks (aRRRs) compared RRs in Aboriginal and non-Aboriginal mothers. Adjusted population attributable fractions estimated the contribution of overweight/obesity to GDM burden, and adjusted predicted probabilities for GDM were plotted against BMI levels. The following predictors had stronger associations with GDM in Aboriginal, compared to non-Aboriginal, mothers: maternal obesity (aRR [95% CI] 3.16 [2.54-3.93]; aRRR 1.57 [1.26-1.94]), previous LGA (aRR 1.70 [1.37-2.12]; aRRR 1.41 [1.13-1.76]) and previous macrosomia (birthweight ≥ 4 kg) (aRR 1.55 [1.24-1.94]; aRRR 1.53 [1.22-1.91]). 46.1% (95% CI: 36.6-54.1) of GDM cases in Aboriginal women (23.3% in non-Aboriginal mothers, 95% CI: 21.6-25.1) were attributed to overweight/obesity. Compared to non-Aboriginal mothers, adjusted GDM probabilities were higher at all BMI levels and showed greater increase with BMI. Overweight/obesity is a key driver of GDM among Aboriginal women. Association between BMI and GDM is stronger in Aboriginal, compared to non-Aboriginal, women especially at higher BMI.

Immune priming prior to pathogen exposure sheds light on the relationship between host, microbiome and pathogen in disease.

Dynamic interactions between host, pathogen and host-associated microbiome dictate infection outcomes. Pathogens including Batrachochytrium dendrobatidis (Bd) threaten global biodiversity, but conservation efforts are hindered by limited understanding of amphibian host, Bd and microbiome interactions. We conducted a vaccination and infection experiment using Eastern hellbender salamanders (Cryptobranchus alleganiensis alleganiensis) challenged with Bd to observe infection, skin microbial communities and gene expression of host skin, pathogen and microbiome throughout the experiment. Most animals survived high Bd loads regardless of their vaccination status and vaccination did not affect pathogen load, but host gene expression differed based on vaccination. Oral vaccination (exposure to killed Bd) stimulated immune gene upregulation while topically and sham-vaccinated animals did not significantly upregulate immune genes. In early infection, topically vaccinated animals upregulated immune genes but orally and sham-vaccinated animals downregulated immune genes. Bd increased pathogenicity-associated gene expression in late infection when Bd loads were highest. The microbiome was altered by Bd, but there was no correlation between anti-Bd microbe abundance or richness and pathogen burden. Our observations suggest that hellbenders initially generate a vigorous immune response to Bd, which is ineffective at controlling disease and is subsequently modulated. Interactions with antifungal skin microbiota did not influence disease progression.

Development and Evaluation of High-Density SNP Arrays for the Eastern Oyster Crassostrea virginica.

The eastern oyster Crassostrea virginica is a major aquaculture species for the USA. The sustainable development of eastern oyster aquaculture depends upon the continued improvement of cultured stocks through advanced breeding technologies. The Eastern Oyster Breeding Consortium (EOBC) was formed to advance the genetics and breeding of the eastern oyster. To facilitate efficient genotyping needed for genomic studies and selection, the consortium developed two single-nucleotide polymorphism (SNP) arrays for the eastern oyster: one screening array with 566K SNPs and one breeders' array with 66K SNPs. The 566K screening array was developed based on whole-genome resequencing data from 292 oysters from Atlantic and Gulf of Mexico populations; it contains 566,262 SNPs including 47K from protein-coding genes with a marker conversion rate of 48.34%. The 66K array was developed using best-performing SNPs from the screening array, which contained 65,893 oyster SNPs including 22,984 genic markers with a calling rate of 99.34%, a concordance rate of 99.81%, and a much-improved marker conversion rate of 92.04%. Null alleles attributable to large indels were found in 13.1% of the SNPs, suggesting that copy number variation is pervasive. Both arrays provided easy identification and separation of selected stocks from wild progenitor populations. The arrays contain 31 mitochondrial SNPs that allowed unambiguous identification of Gulf mitochondrial genotypes in some Atlantic populations. The arrays also contain 756 probes from 13 oyster and human pathogens for possible detection. Our results show that marker conversion rate is low in high polymorphism species and that the two-step process of array development can greatly improve array performance. The two arrays will advance genomic research and accelerate genetic improvement of the eastern oyster by delineating genetic architecture of production traits and enabling genomic selection. The arrays also may be used to monitor pedigree and inbreeding, identify selected stocks and their introgression into wild populations, and assess the success of oyster restoration.

Risk of kidney disease following a pregnancy complicated by diabetes: a longitudinal, population-based data-linkage study among Aboriginal women in the Northern Territory, Australia.

AIMS/HYPOTHESIS: The aim of this work was to investigate the risk of developing chronic kidney disease (CKD) or end-stage kidney disease (ESKD) following a pregnancy complicated by gestational diabetes mellitus (GDM) or pre-existing diabetes among Aboriginal women in the Northern Territory (NT), Australia. METHODS: We undertook a longitudinal study of linked healthcare datasets. All Aboriginal women who gave birth between 2000 and 2016 were eligible for inclusion. Diabetes status in the index pregnancy was as recorded in the NT Perinatal Data Collection. Outcomes included any stage of CKD and ESKD as defined by ICD-10 coding in the NT Hospital Inpatient Activity dataset between 2000 and 2018. Risk was compared using Cox proportional hazards regression. RESULTS: Among 10,508 Aboriginal women, the mean age was 23.1 (SD 6.1) years; 731 (7.0%) had GDM and 239 (2.3%) had pre-existing diabetes in pregnancy. Median follow-up was 12.1 years. Compared with women with no diabetes during pregnancy, women with GDM had increased risk of CKD (9.2% vs 2.2%, adjusted HR 5.2 [95% CI 3.9, 7.1]) and ESKD (2.4% vs 0.4%, adjusted HR 10.8 [95% CI 5.6, 20.8]). Among women with pre-existing diabetes in pregnancy, 29.1% developed CKD (adjusted HR 10.9 [95% CI 7.7, 15.4]) and 9.9% developed ESKD (adjusted HR 28.0 [95% CI 13.4, 58.6]). CONCLUSIONS/INTERPRETATION: Aboriginal women in the NT with GDM or pre-existing diabetes during pregnancy are at high risk of developing CKD and ESKD. Pregnancy presents an important opportunity to identify kidney disease risk. Strategies to prevent kidney disease and address the social determinants of health are needed.

The prevalence of diabetes distress and its association with glycaemia in young people living with insulin-requiring-diabetes in a regional centre in Australia.

AIM: Emotional responses, such as feeling overwhelmed with diabetes-related treatment, burnt-out and anxiety, are known as 'diabetes distress'. This study aimed to determine diabetes distress among children, adolescents and parents/carers managing insulin-requiring diabetes in a regional Australian setting, and to assess association with glycaemia. METHODS: All children, adolescents and their parents/carers attending a regional hospital outpatient diabetes clinic between March 2018 and June 2019 were invited to complete a validated child, adolescent or parent/carer diabetes distress questionnaire. Demographics and time-matched clinical data were obtained from hospital records. A cross-sectional analysis was performed. RESULTS: A total of 43 young people and 30 parents/carers completed a diabetes distress questionnaire during the study period. Diabetes distress was common, with 63% of young people and 67% of parents/carers nominating at least one serious concern. After adjustment for potential confounding factors, higher glycaemia (HbA1c %) was associated with higher distress scores among both young people (ß 6.2, 95% confidence interval (CI): 3.2-9.2, P < 0.001) and carers/parents (ß 5.6, 95% CI:1.5-9.8, P < 0.001). Diabetes distress did not differ by child age, duration of diagnosis or mode of insulin administration. For children, adolescents and carers, 'serious concerns' most commonly related to the impact of diabetes upon family and peer relationships. CONCLUSIONS: Diabetes distress was common and associated with sub-optimal glycaemia. Routine screening for diabetes distress should be considered in paediatric services. Development of strategies to minimise diabetes distress for youth and families is required.

Glucagon-like peptide-1 receptor agonist (GLP1-RA) therapy in type 2 diabetes.

BACKGROUND: Type 2 diabetes (T2D) is a national health priority. Its rising prevalence is accompanied by a high burden of diabetes-related complications, many of which are preventable. Numerous glucose-lowering medications have been developed in recent years with growing evidence relating to their efficacy and safety. These advances have increased the complexity of prescribing decisions in T2D. OBJECTIVE: This review provides clinicians with relevant evidence and practical advice concerning glucagon-like peptide-1 receptor agonists (GLP1-RAs) in T2D. DISCUSSION: The Royal Australian College of General Practitioners recommends GLP1-RAs as an option for second-line therapy in T2D. GLP1-RAs contribute to weight loss and glycated haemoglobin reduction. GLP1-RAs also reduce incidence of cardiovascular events in selected populations, and available evidence suggests renoprotective effects. Common adverse effects include gastrointestinal symptoms, especially in the weeks following treatment initiation. GLP1-RAs should be considered for people with T2D at high cardiovascular risk or where weight loss is a priority.

Prevalence and incidence of diabetes among Aboriginal people in remote communities of the Northern Territory, Australia: a retrospective, longitudinal data-linkage study.

OBJECTIVES: To assess the prevalence and incidence of diabetes among Aboriginal peoples in remote communities of the Northern Territory (NT), Australia. DESIGN: Retrospective cohort analysis of linked clinical and administrative data sets from 1 July 2012 to 30 June 2019. SETTING: Remote health centres using the NT Government Primary Care Information System (51 out of a total of 84 remote health centres in the NT). PARTICIPANTS: All Aboriginal clients residing in remote communities serviced by these health centres (N=21 267). PRIMARY OUTCOME MEASURES: Diabetes diagnoses were established using hospital and primary care coding, biochemistry and prescription data. RESULTS: Diabetes prevalence across all ages increased from 14.4% (95% CI: 13.9% to 14.9%) to 17.0% (95% CI: 16.5% to 17.5%) over 7 years. Among adults (≥20 years), the 2018/2019 diabetes prevalence was 28.6% (95% CI: 27.8% to 29.4%), being higher in Central Australia (39.5%, 95% CI: 37.8% to 41.1%) compared with the Top End region (24.2%, 95% CI: 23.3% to 25.1%, p<0.001). Between 2016/2017 and 2018/2019, diabetes incidence across all ages was 7.9 per 1000 person-years (95% CI: 7.3 to 8.7 per 1000 person-years). The adult incidence of diabetes was 12.6 per 1000 person-years (95% CI: 11.5 to 13.8 per 1000 person-years). CONCLUSIONS: The burden of diabetes in the remote Aboriginal population of the NT is among the highest in the world. Strengthened systems of care and public health prevention strategies, developed in partnership with Aboriginal communities, are needed.

Assessment of quantitative polymerase chain reaction for BCR-ABL1 transcripts in chronic myeloid leukaemia: Are improved outcomes in patients with e14a2 transcripts an artefact of technology?

The clinical outcome of chronic myeloid leukaemia patients has vastly improved since the introduction of tyrosine kinase inhibitor treatment, with a significant proportion of patients able to achieve treatment-free remission. However, studies have shown that patients with the e13a2 transcript were less likely to achieve major molecular response compared to those with e14a2 transcripts. Most quantitative polymerase chain reaction (PCR) assays for detection of the BCR-ABL1 fusion gene do not differentiate between the two transcripts and we therefore hypothesised that technical bias linked to the qPCR assay could partially explain the discrepancy in outcomes. We designed an e14a2-specific assay and identified no difference in results compared to an e13a2 standard assay. We then demonstrated that the commercial e14a2 standards were causing a significant overestimation of the e13a2 transcripts. Finally, we reviewed patient management after the qPCR values were corrected, using our new evaluation. We concluded that despite statistically significant differences in qPCR results, there was no impact on patient management or outcome. We conclude that, at least in our institution, it would be inappropriate to perform separate assays for patients with e13a2 or e14a2.

Does a complex life cycle affect adaptation to environmental change? Genome-informed insights for characterizing selection across complex life cycle.

Complex life cycles, in which discrete life stages of the same organism differ in form or function and often occupy different ecological niches, are common in nature. Because stages share the same genome, selective effects on one stage may have cascading consequences through the entire life cycle. Theoretical and empirical studies have not yet generated clear predictions about how life cycle complexity will influence patterns of adaptation in response to rapidly changing environments or tested theoretical predictions for fitness trade-offs (or lack thereof) across life stages. We discuss complex life cycle evolution and outline three hypotheses-ontogenetic decoupling, antagonistic ontogenetic pleiotropy and synergistic ontogenetic pleiotropy-for how selection may operate on organisms with complex life cycles. We suggest a within-generation experimental design that promises significant insight into composite selection across life cycle stages. As part of this design, we conducted simulations to determine the power needed to detect selection across a life cycle using a population genetic framework. This analysis demonstrated that recently published studies reporting within-generation selection were underpowered to detect small allele frequency changes (approx. 0.1). The power analysis indicates challenging but attainable sampling requirements for many systems, though plants and marine invertebrates with high fecundity are excellent systems for exploring how organisms with complex life cycles may adapt to climate change.

Type 2 diabetes after a pregnancy with gestational diabetes among first nations women in Australia: The PANDORA study.

AIMS: To determine among First Nations and Europid pregnant women the cumulative incidence and predictors of postpartum type 2 diabetes and prediabetes and describe postpartum cardiovascular disease (CVD) risk profiles. METHODS: PANDORA is a prospective longitudinal cohort of women recruited in pregnancy. Ethnic-specific rates of postpartum type 2 diabetes and prediabetes were reported for women with diabetes in pregnancy (DIP), gestational diabetes (GDM) or normoglycaemia in pregnancy over a short follow-up of 2.5 years (n = 325). Pregnancy characteristics and CVD risk profiles according to glycaemic status, and factors associated with postpartum diabetes/prediabetes were examined in First Nations women. RESULTS: The cumulative incidence of postpartum type 2 diabetes among women with DIP or GDM were higher for First Nations women (48%, 13/27, women with DIP, 13%, 11/82, GDM), compared to Europid women (nil DIP or GDM p < 0.001). Characteristics associated with type 2 diabetes/prediabetes among First Nations women with GDM/DIP included, older age, multiparity, family history of diabetes, higher glucose values, insulin use and body mass index (BMI). CONCLUSIONS: First Nations women experience a high incidence of postpartum type 2 diabetes after GDM/DIP, highlighting the need for culturally responsive policies at an individual and systems level, to prevent diabetes and its complications.

Current evidence and practical guidance for the use of sodium-glucose co-transporter-2 inhibitors in type 2 diabetes.

BACKGROUND: The burden of type 2 diabetes (T2D) and its associated complications continues to grow in Australia. In recent years, sodium-glucose co-transporter-2 (SGLT2) inhibitors have become a key component of diabetes care with rapid uptake into routine clinical practice. There is growing evidence of their clinical efficacy, but also potential adverse effects. OBJECTIVE: The aim of this article is to review the use of SGLT2 inhibitors in T2D by exploring data surrounding clinical efficacy and safety as well as providing practical advice for prescribing clinicians. DISCUSSION: SGLT2 inhibitors have multiple metabolic benefits including reducing glycated haemoglobin, weight and blood pressure. Additionally, there are strong cardiovascular benefits and renoprotective effects in selected populations. Current evidence suggests that SGLT2 inhibitors should be considered for the secondary prevention of cardiovascular disease and to delay progression of early chronic kidney disease in people with T2D. Clinicians should also be aware of common side effects and potential rare severe complications.

Clinical, psychological and demographic factors in a contemporary adult cohort with diabetic ketoacidosis and type 1 diabetes.

BACKGROUND: Diabetic ketoacidosis (DKA) is a potentially life-threatening but often preventable acute complication of type 1 diabetes (T1D). Understanding clinical and psychosocial characteristics of people with DKA, particularly those with multiple presentations, may aid the development of prevention strategies. AIMS: To describe clinical, psychological and demographic factors in adults with DKA and particularly those factors associated with recurrent admissions. METHODS: A retrospective analysis was performed of all admissions with DKA in people with T1D over a 4-year period from 1 November 2013 to 31 October 2017 at a metropolitan tertiary hospital in Australia. Potential cases were identified by International Classification of Diseases-10th Revision coding data. Data were then manually extracted by clinicians from the electronic medical record. RESULTS: There were 154 clinician-adjudicated admissions for DKA among 128 people with T1D. Of these, 16 (13%) had multiple DKA admissions. Forty-one (32%) had a history of depression. The most common factors contributing to presentation included insulin omission (54%), infection (31%), alcohol excess (26%) and new diabetes diagnosis (16%). Compared to people with single admissions, those with recurrent DKA were more likely to smoke (69% vs 27%, P = 0.003), be unemployed (31% vs 11%, P = 0.04) and use illicit substances (44% vs 17%, P = 0.02). CONCLUSIONS: There is a high prevalence of psychiatric illness, illicit substance use and social disadvantage among people admitted with DKA, particularly those with recurrent presentations. Insulin omission, often due to inappropriate sick day management, was the most common reason for DKA occurrence. Innovative multidisciplinary models of care are required to address these challenges.

Are bivalves susceptible to domestication selection? Using starvation tolerance to test for potential trait changes in eastern oyster larvae.

Conservation efforts are increasingly being challenged by a rapidly changing environment, and for some aquatic species the use of captive rearing or selective breeding is an attractive option. However, captivity itself can impose unintended artificial selection known as domestication selection (adaptation to culture conditions) and is relatively understudied for most marine species. To test for domestication selection in marine bivalves, we focused on a fitness-related trait (larval starvation resistance) that could be altered under artificial selection. Using larvae produced from a wild population of Crassostrea virginica and a selectively bred, disease-resistant line we measured growth and survival during starvation versus standard algal diet conditions. Larvae from both lineages showed a remarkable resilience to food limitation, possibly mediated by an ability to utilize dissolved organic matter for somatic maintenance. Water chemistry analysis showed dissolved organic carbon in filtered tank water to be at concentrations similar to natural river water. We observed that survival in larvae produced from the aquaculture line was significantly lower compared to larvae produced from wild broodstock (8 ± 3% and 21 ± 2%, respectively) near the end of a 10-day period with no food (phytoplankton). All larval cohorts had arrested growth and depressed respiration during the starvation period and took at least two days to recover once food was reintroduced before resuming growth. Respiration rate recovered rapidly and final shell length was similar between the two treatments Phenotypic differences between the wild and aquaculture lines suggest potential differences in the capacity to sustain extended food limitation, but this work requires replication with multiple selection lines and wild populations to make more general inferences about domestication selection. With this contribution we explore the potential for domestication selection in bivalves, discuss the physiological and fitness implications of reduced starvation tolerance, and aim to inspire further research on the topic.

Familial Hypocalciuric Hypercalcemia in Pregnancy: Diagnostic Pitfalls.

Familial hypocalciuric hypercalcemia (FHH) is a group of autosomal dominant disorders caused by dysfunction of the calcium sensing receptor (CaSR) and its downstream signaling proteins, leading to generally asymptomatic hypercalcemia. During pregnancy, distinguishing FHH from primary hyperparathyroidism (PHPT) is important, as the latter is associated with adverse outcomes and can be treated surgically during pregnancy, whereas the former is benign. This case report highlights the difficulties in diagnosing FHH during pregnancy. A 32-year-old woman was found to have asymptomatic hypercalcemia at 14-weeks' gestation. Investigations showed a corrected calcium (cCa) of 2.61 mmol/L (2.10 to 2.60), ionized Ca (iCa) of 1.40 mmol/L (1.15 to 1.28), 25OHD of 33 nmol/L (75 to 250), and PTH of 9.5 pmol/L (1.5 to 7.0). The patient was treated with 2000 IU cholecalciferol daily with normalization of 25OHD. The urine calcium / creatinine clearance ratio (CCCR) was 0.0071, and neck US did not visualize a parathyroid adenoma. Upon a retrospective review of the patient's biochemistry from 2 years prior, hypercalcemia was found that was not investigated. The patient was monitored with serial iCa levels and obstetric US. She delivered a healthy boy at 38-weeks' gestation. Postnatal iCa was 1.48 mmol/L and remained elevated. Her son had elevated iCa at birth of 1.46 mmol/L (1.15 to 1.33), which rose to 1.81 mmol/L by 2 weeks. He was otherwise well. Given the familial hypercalcemia, a likely diagnosis of FHH was made. Genetic testing of the son revealed a missense mutation, NM_000388.3(CASR):c.2446A > G, in exon 7 of the CaSR, consistent with FHH type 1. To our knowledge, there are only three existing reports of FHH in pregnancy. When differentiating between FHH and PHPT in pregnancy, interpretation of biochemistry requires an understanding of changes in Ca physiology, and urine CCCR may be unreliable. If the decision is made to observe, clinical symptoms, calcium levels, and fetal US should be monitored, with biochemistry and urine CCCR performed postpartum, once lactation is completed © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

Diabetes during pregnancy and birthweight trends among Aboriginal and non-Aboriginal people in the Northern Territory of Australia over 30 years.

BACKGROUND: Early-life risk factors, including maternal hyperglycaemia and birthweight, are thought to contribute to the high burden of cardiometabolic disease experienced by Indigenous populations. We examined rates of pre-existing diabetes in pregnancy, gestational diabetes mellitus (GDM) and extremes of birthweight over three decades in the Northern Territory (NT) of Australia. METHODS: We performed a retrospective cohort analysis of the NT Perinatal Data Collection from 1987 to 2016, including all births >20 weeks gestation, stratified by maternal Aboriginal identification. Key outcomes were annual rates of pre-existing diabetes, GDM, small-for-gestational-age, large-for-gestational-age, low birthweight (<2500 g), and high birthweight (>4000 g). Logistic regression was used to assess trends and interactions. FINDINGS: 109 349 babies were born to 64 877 mothers, 36% of whom identified as Aboriginal ethnicity. Among Aboriginal women, rates of GDM and pre-existing diabetes, respectively, were 3 ·â€¯4% and 0 ·â€¯6% in 1987 and rose to 13% and 5 ·â€¯7% in 2016 (both trends p<0 ·â€¯001). Among non-Aboriginal women, rates of GDM increased from 1 ·â€¯9% in 1987 to 11% in 2016 (p<0 ·â€¯001), while pre-existing diabetes was uncommon (≤0 ·â€¯7% throughout). Rates of small-for-gestational-age decreased, while rates of large-for-gestational-age and high birthweight increased in both groups (all trends p<0 ·â€¯001). Multivariable modelling suggests that hyperglycaemia was largely responsible for the growing rate of large-for-gestational-age births among Aboriginal women. INTERPRETATION: The burden of hyperglycaemia in pregnancy has grown substantially in the NT over three decades and is impacting birthweight trends. The prevalence of pre-gestational diabetes in Aboriginal women is among the highest in the world. FUNDING: Diabetes Australia Research Program.