Accelerated placental aging in early onset preeclampsia pregnancies identified by DNA methylation.

Aim: To determine whether dynamic DNA methylation changes in the human placenta can be used to predict gestational age. Materials & methods: Publicly available placental DNA methylation data from 12 studies, together with our own dataset, using Illumina Infinium Human Methylation BeadChip arrays. Results & conclusion: We developed an accurate tool for predicting gestational age of placentas using 62 CpG sites. There was a higher predicted gestational age for placentas from early onset preeclampsia cases, but not term preeclampsia, compared with their chronological age. Therefore, early onset preeclampsia is associated with placental aging. Gestational age acceleration prediction from DNA methylation array data may provide insight into the molecular mechanisms of pregnancy disorders.Benjamin T Mayne, Shalem Y Leemaqz, Alicia K Smith, James Breen, Claire T Roberts, Tina Bianco-Miott

Partial identification in the statistical matching problem

The statistical matching problem involves the integration of multiple datasets where some variables are not observed jointly. This missing data pattern leaves most statistical models unidentifiable. Statistical inference is still possible when operating under the framework of partially identified models, where the goal is to bound the parameters rather than to estimate them precisely. In many matching problems, developing feasible bounds on the parameters is equivalent to finding the set of positive-definite completions of a partially specified covariance matrix. Existing methods for characterising the set of possible completions do not extend to high-dimensional problems. A Gibbs sampler to draw from the set of possible completions is proposed. The variation in the observed samples gives an estimate of the feasible region of the parameters. The Gibbs sampler extends easily to high-dimensional statistical matching problems.Daniel Ahfock, Saumyadipta Pyne, Sharon X. Lee, Geoffrey J. McLachla

Anxiety and Depression in Early Gestation and the Association with Subsequent Gestational Diabetes Mellitus in a Disadvantaged Population

Published online: 12 October 2023Objectives: Evaluate the association between poor mental health and risk of developing gestational diabetes mellitus (GDM) in a cohort of women from a socioeconomically disadvantaged community. Methods: A total of 1363 nulliparous women with singleton pregnancies recruited to the Screening Tests to Predict Poor Outcomes of Pregnancy study in Adelaide, Australia. Women were assessed for mental health in the first trimester, including likelihood of depression, high functioning anxiety, perceived stress and risk of developing a mental health disorder. GDM was diagnosed based on the International Association of Diabetes in Pregnancy Study Group (IADPSG) criteria. Socioeconomic status was measured using the New Zealand Socioeconomic Index (NZSEI). Results: Complete mental health data was available for 1281 participants. There was no statistically significant difference in SEI, depression, risk of mental health issues, high functioning anxiety and perceived stress between women who developed GDM and those who did not. There was no difference in history of depression nor risk of developing a high mental health disorder in first trimester after adjusting for SEI, BMI in first trimester, smoking status in first trimester and maternal age between women with a GDM pregnancy and those who did not. Conclusions for Practice: There was no difference in markers of poor mental health in early pregnancy between women who subsequently did or did not develop GDM. Cohort participants were socioeconomically disadvantaged, potentially contributing to the lack of apparent differences in depression observed between groups. Socioeconomically disadvantaged women should be targeted in pre-conception planning to reduce risk of GDM.Maleesa M. Pathirana, Prabha H. Andraweera, Shalem Leemaqz, Emily Aldridge, Margaret A. Arstall, Gustaaf A. Dekker, Claire T. Robert

Early pregnancy maternal trace mineral status and the association with adverse pregnancy outcome in a cohort of Australian women

Abstract not availableRebecca L. Wilson, Tina Bianco-Miotto, Shalem Y. Leemaqz, Luke E. Grzeskowiak, Gustaaf A. Dekker, Claire T. Robert

Cyproterone acetate or spironolactone in lowering testosterone concentrations for transgender individuals receiving oestradiol therapy

BACKGROUND:Estradiol with or without an antiandrogen (cyproterone acetate or spironolactone) is commonly prescribed in transfeminine individuals who have not had orchidectomy, however there is no evidence to guide optimal treatment choice. OBJECTIVE:We aimed to compare add-on cyproterone acetate versus spironolactone in lowering endogenous testosterone concentrations in transfeminine individuals. DESIGN:Retrospective cross-sectional study. METHODS:We analysed 114 transfeminine individuals who had been on estradiol therapy for >6 months in two gender clinics in Melbourne, Australia. Total testosterone concentrations were compared between three groups; estradiol alone (n=21), estradiol plus cyproterone acetate (n=21) and estradiol plus spironolactone (n=38). Secondary outcomes included serum estradiol concentration, estradiol valerate dose, blood pressure, serum potassium, urea and creatinine. RESULTS:Median age was 27.0 years (22.5, 45.1) and median duration of hormone therapy was 1.5 years (0.9, 2.6), which was not different between groups. On univariate analysis, the cyproterone group had significantly lower total testosterone concentrations (0.8nmol/L (0.6, 1.20)) compared with the spironolactone group (2.0nmol/L (0.9, 9.4), p=0.037) and estradiol alone group (10.5nmol/L (4.9, 17.2), p<0.001), which remained significant (p=0.005) after adjustments for estradiol concentration, dose and age. Serum urea was higher in the spironolactone group compared with the cyproterone group. No differences were observed in total daily estradiol dose, blood pressure, serum estradiol, potassium or creatinine. CONCLUSIONS:The cyproterone group achieved serum total testosterone concentrations in the female reference range. As spironolactone may cause feminisation without inhibition of steroidogenesis, it is unclear which anti-androgen is more effective at feminisation. Further prospective studies are required.Lachlan Angus, Shalem Leemaqz, Olivia Ooi, Pauline Cundill, Nicholas Silberstein, Peter Locke, Jeffrey D Zajac and Ada S Cheun

Effectiveness of a nurse practitioner-led cardiovascular prevention clinic at reduction of metabolic syndrome following maternal complications of pregnancy: a preliminary analysis

Aim Maternal complications of pregnancy, including hypertensive disorders of pregnancy, gestational diabetes mellitus, intrauterine growth restriction, preterm labour, and placental abruption, are associated with increased risk of future cardiometabolic disease. Lifestyle interventions that focus on preventative strategies for this young, high-risk population of women may assist in cardiometabolic disease risk reduction. The aim of this preliminary registry analysis was to observe the change in maternal metabolic syndrome status after receiving a nurse practitioner-led lifestyle intervention delivered soon after a complicated pregnancy. Method This preliminary analysis included 64 eligible women who had attended both baseline (approximately 6 months postpartum) and review (approximately eighteen months postpartum) appointments at the postpartum lifestyle clinic after an index pregnancy complicated by at least one maternal complication of pregnancy. Metabolic syndrome status at both appointments was assessed. Results At the baseline appointment, 22 (34.4%) women met the criteria for metabolic syndrome. This number reduced at the review appointment to 19 (29.7%). This difference was not statistically significant. There were some modest improvements in the individual cardiometabolic risk factors, as well as marked improvements in the women who had recovered from metabolic syndrome over twelve months Conclusion There was a high percentage of metabolic syndrome present early in the postpartum period. The results of this preliminary analysis highlight the importance of continuing preventative care and ongoing research for this group of high-risk women.Emily Aldridge, Maleesa Pathirana, Melanie Wittwer, Susan Sierp, Shalem Y. Leemaqz, Claire T. Roberts, Gustaaf A. Dekker, and Margaret A. Arstal

A prospective registry analysis of psychosocial and metabolic health between women with and without metabolic syndrome after a complicated pregnancy

Purpose: Pregnancy complications afect over one quarter of Australian pregnancies, and this group of mothers is vulnerable and more likely to experience adverse cardiometabolic health outcomes in the postpartum period. Metabolic syndrome is common in this population and may be associated with postpartum mental health issues. However, this relationship remains poorly understood. To compare the diferences in psychosocial parameters and mental health outcomes between women with metabolic syndrome and women without metabolic syndrome 6 months after a complicated pregnancy. Methods: This study is prospective registry analysis of women attending a postpartum healthy lifestyle clinic 6 months following a complicated pregnancy. Mental health measures included 9-item Patient Health Questionnaire (PHQ-9), 7-item Generalised Anxiety Disorder questionnaire (GAD-7), self-reported diagnosed history of depression, anxiety and/or other psychiatric condition, and current psychotropic medication use. Results: Women with metabolic syndrome reported signifcantly more subjective mental health concerns, were more likely to have a history of depression and other psychiatric diagnoses and were more likely prescribed psychotropic medications. However, there were no signifcant diferences in PHQ-9 and GAD-7 scores. Conclusion: Amongst new mothers who experienced complications of pregnancy, those with metabolic syndrome represent a particularly vulnerable group with regards to psychosocial disadvantage and mental health outcomes. These vulnerabilities may not be apparent when using common standardised cross-sectional mental health screening tools such as PHQ-9 and GAD-7.Emily Aldridge, K. Oliver Schubert, Maleesa Pathirana, Susan Sierp, Shalem Y. Leemaqz, Claire T. Roberts, Gustaaf A. Dekker, and Margaret A. Arstal

The effect of Vdr gene ablation on global gene expression in the mouse placenta

Abstract not availableSam Buckberry, Fleur Spronk, Rebecca L. Wilson, Jessica A. Laurence, Tina Bianco-Miotto, Shalem Leemaqz, Sean O'Leary, Paul H. Anderson, Claire T. Robert

Vitamin D receptor gene ablation in the conceptus has limited effects on placental morphology, function and pregnancy outcome

Vitamin D deficiency has been implicated in the pathogenesis of several pregnancy complications attributed to impaired or abnormal placental function, but there are few clues indicating the mechanistic role of vitamin D in their pathogenesis. To further understand the role of vitamin D receptor (VDR)-mediated activity in placental function, we used heterozygous Vdr ablated C57Bl6 mice to assess fetal growth, morphological parameters and global gene expression in Vdr null placentae. Twelve Vdr+/- dams were mated at 10-12 weeks of age with Vdr+/- males. At day 18.5 of the 19.5 day gestation in our colony, females were euthanised and placental and fetal samples were collected, weighed and subsequently genotyped as either Vdr+/+, Vdr+/- or Vdr-/-. Morphological assessment of placentae using immunohistochemistry was performed and RNA was extracted and subject to microarray analysis. This revealed 25 genes that were significantly differentially expressed between Vdr+/+ and Vdr-/- placentae. The greatest difference was a 6.47-fold change in expression of Cyp24a1 which was significantly lower in the Vdr-/- placentae (P<0.01). Other differentially expressed genes in Vdr-/- placentae included those involved in RNA modification (Snord123), autophagy (Atg4b), cytoskeletal modification (Shroom4), cell signalling (Plscr1, Pex5) and mammalian target of rapamycin (mTOR) signalling (Deptor and Prr5). Interrogation of the upstream sequence of differentially expressed genes identified that many contain putative vitamin D receptor elements (VDREs). Despite the gene expression differences, this did not contribute to any differences in overall placental morphology, nor was function affected as there was no difference in fetal growth as determined by fetal weight near term. Given our dams still expressed a functional VDR gene, our results suggest that cross-talk between the maternal decidua and the placenta, as well as maternal vitamin D status, may be more important in determining pregnancy outcome than conceptus expression of VDR.Rebecca L. Wilson, Sam Buckberry, Fleur Spronk, Jessica A. Laurence, Shalem Leemaqz, Sean O, Leary, Tina Bianco-Miotto, Jing Du, Paul H. Anderson, Claire T. Robert

Breastfeeding outcomes in late preterm infants: A multi-centre prospective cohort study

OBJECTIVES: To describe (1) infant feeding practices during initial hospitalisation and up to 6 months corrected age (CA) in infants born late preterm with mothers intending to breastfeed, (2) the impact of early feeding practices on hospital length of stay and (3) maternal and infant factors associated with duration of breastfeeding. METHODS: We conducted a prospective cohort study of infants born at 34⁺⁰ to 36⁺⁶ weeks gestational age during 2018-2020. Families were followed up until the infant reached 6 months of age (corrected for prematurity). Feeding practices during the birth hospitalisation, length of initial hospital stay, and the prevalence of exclusive or any breastfeeding at 6 weeks, 3 months, and 6 months CA were examined. Associations between maternal and infant characteristics and breastfeeding at 6 weeks, 3 months and 6 months CA were assessed using multivariable logistic regression models. RESULTS: 270 infants were enrolled, of these, 30% were multiple births. Overall, 78% of infants received only breastmilk as their first feed, and 83% received formula during the hospitalisation. Seventy-four per cent of infants were exclusively breastfed at discharge, 41% at 6 weeks CA, 35% at 3 months CA, and 29% at 6 months CA. The corresponding combined exclusive and partial breastfeeding rates (any breastfeeding) were 72%, 64%, and 53% of babies at 6 weeks CA, 3 months CA, and 6 months CA, respectively. The mean duration of hospitalisation was 2.9 days longer (95% confidence interval (CI) 0.31, 5.43 days) in infants who received any formula compared with those receiving only breastmilk (adjusted for GA, maternal age, multiple birth, site, and neonatal intensive care unit admission). In multivariable models, receipt of formula as the first milk feed was associated with a reduction in exclusive breastfeeding at 6 weeks CA (odds ratio = 0.22; 95% CI 0.09 to 0.53) and intention to breastfeed >6 months with an increase (odds ratio = 4.98; 95% CI 2.39 to 10.40). Intention to breastfeed >6 months remained an important predictor of exclusive breastfeeding at 3 and 6 months CA. CONCLUSIONS: Our study demonstrates that long-term exclusive breastfeeding rates were low in a cohort of women intending to provide breastmilk to their late preterm infants, with approximately half providing any breastmilk at 6 months CA. Formula as the first milk feed and intention to breastfeed >6 months were significant predictors of breastfeeding duration. Improving breastfeeding outcomes may require strategies to support early lactation and a better understanding of the ongoing support needs of this population.Amy Keir, Alice Rumbold, Carmel T. Collins, Andrew J. McPhee, Jojy Varghese, Scott Morris, Thomas R. Sullivan, Shalem Leemaqz, Philippa Middleton, Maria Makrides, Karen P. Bes