The Impacts of Periconceptional Alcohol on Neonatal Ovaries and Subsequent Adult Fertility in the Rat.

Maternal exposures during pregnancy can impact the establishment of the ovarian reserve in offspring, the lifetime supply of germ cells that determine a woman's reproductive lifespan. However, despite alcohol consumption being common in women of reproductive age, the impact of prenatal alcohol on ovarian development is rarely investigated. This study used an established rat model of periconceptional ethanol exposure (PCEtOH; 12.5% v/v ethanol) for 4 days prior to 4 days post-conception. Ovaries were collected from neonates (day 3 and day 10), and genes with protein products involved in regulating the ovarian reserve analyzed by qPCR. Adult offspring had estrous cycles monitored and breeding performance assessed. PCEtOH resulted in subtle changes in expression of genes regulating apoptosis at postnatal day (PN) 3, whilst those involved in regulating growth and recruitment of primordial follicles were dysregulated at PN10 in neonatal ovaries. Despite these gene expression changes, there were no significant impacts on breeding performance in adulthood, nor on F2-generation growth or survival. This contributes additional evidence to suggest that a moderate level of alcohol consumption exclusively around conception, when a woman is often unaware of her pregnancy, does not substantially impact the fertility of her female offspring.

Exploring the experience of service users following attendance at a student-led interprofessional neurodevelopmental clinic.

PURPOSE: The aim of the current study was to understand service users' experiences at a recently established student-led interprofessional neurodevelopmental clinic for children and adolescents with suspected or confirmed prenatal alcohol exposure. METHOD: Semi-structured interviews were completed at 3-months post-clinic attendance with 10 service users: eight parents/caregivers and two youth workers/case managers. Interview data were analysed thematically using NVivo12. RESULTS: Four main themes were developed: (1) clinic attendance seen as a positive event; (2) validation, clarification, and relief, but also challenges post-assessment; (3) need for further support and importance of advocacy; and (4) drawing on lived experiences for future service improvements. CONCLUSIONS: The current study demonstrated that service users reported benefits from tailored services delivered by student practitioners that were validating, supportive, and holistic. Findings from the current study can inform the development and implementation of future innovative service delivery models for individuals with suspected or confirmed prenatal alcohol exposure.

People with fetal alcohol spectrum disorder (FASD) can experience a range of neurocognitive impairments that impact their day-to-day living.Access to assessment, early diagnosis, and appropriate supports are important protective factors associated with improved outcomes for individuals with FASD.Results highlighted the benefits to rehabilitation professionals of listening to service users to understand the complexity of their lived experiences, including how this information can be used to improve service design and delivery.Results also highlighted the potential role of incorporating student-led clinics within models of healthcare and rehabilitation service delivery.Utilising student-led clinics can help to increase access to specialised services for underserved groups in our community, combat shortages in the health workforce, reduce burden on the public health system, and educate the future of rehabilitation professionals.

Diagnostic Accuracy and economic value of a Tiered Assessment for Fetal Alcohol Spectrum Disorder (DATAforFASD): Protocol.

INTRODUCTION: Australian practices for diagnosing fetal alcohol spectrum disorder (FASD) are lengthy and require specialist expertise. Specialist teams are based in urban locations; they are expensive and have prolonged waitlists. Innovative, flexible solutions are needed to ensure First Nations children living in rural/remote communities have culturally appropriate and equitable access to timely diagnosis and support. This study compares the accuracy of rapid assessments (index tests) that can be administered by a range of primary healthcare practitioners to specialist standardised FASD assessments (reference tests). The cost-efficiency of index tests will be compared with reference tests. METHODS AND ANALYSIS: At least 200 children aged 6-16 years at-risk of FASD will be recruited across at least seven study sites. Following standards for reporting diagnostic accuracy study (STARD) guidelines, all children will complete index and reference tests. Diagnostic accuracy statistics (including receiver operating curves, sensitivity, specificity, positive and negative predictive values and likelihood ratios) will identify whether rapid assessments can accurately identify: (1) the presence of an FASD diagnosis and (2) impairment in each neurodevelopmental domain, compared to comprehensive assessments. Direct and indirect healthcare costs for index tests compared to reference tests will be collected in primary healthcare and specialist settings. ETHICS AND DISSEMINATION OF RESULTS: Children's Health Queensland Hospital and Health Service Human Research Ethics Committee (HREC/20/QCHQ/63173); Griffith University Human Research Ethics Committee (2020/743). Results will assist in validating the use of index tests as part of a tiered neurodevelopmental assessment process that was co-designed with First Nations community and primary healthcare practitioners. Outcomes will be summarised and provided to participating practitioners and sites, and disseminated to community health services and consumers. Findings will be presented at national and international conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ACTRN12622000498796.

Brief early life angiotensin-converting enzyme inhibition attenuates the diuretic response to saline loading in sheep with solitary functioning kidney.

A solitary functioning kidney (SFK) from birth predisposes to hypertension and kidney dysfunction, and this may be associated with impaired fluid and sodium homeostasis. Brief and early angiotensin-converting enzyme inhibition (ACEi) in a sheep model of SFK delays onset of kidney dysfunction. We hypothesized that modulation of the renin-angiotensin system via brief postnatal ACEi in SFK would reprogram renal sodium and water handling. Here, blood pressure (BP), kidney haemodynamics and kidney excretory function were examined in response to an isotonic saline load (0.13 ml/kg/min, 180 min) at 20 months of age in SFK (fetal unilateral nephrectomy at 100 days gestation; term 150 days), sham and SFK+ACEi sheep (ACEi in SFK 4-8 weeks of age). Basal BP was higher in SFK than sham (∼13 mmHg), and similar between SFK and SFK+ACEi groups. Saline loading caused a small increase in BP (∼3-4 mmHg) the first 2 h in SFK and sham sheep but not SFK+ACEi sheep. Glomerular filtration rate did not change in response to saline loading. Total sodium excretion was similar between groups. Total urine excretion was similar between SFK and sham animals but was ∼40% less in SFK+ACEi animals compared with SFK animals. In conclusion, the present study indicates that water homeostasis in response to a physiological challenge is attenuated at 20 months of age by brief early life ACEi in SFK. Further studies are required to determine if ACEi in early life in children with SFK could compromise fluid homeostasis later in life.

Maternal hypothyroidism in rats impairs placental nutrient transporter expression, increases labyrinth zone size, and impairs fetal growth.

INTRODUCTION: Hypothyroidism during pregnancy is associated with fetal growth restriction (FGR). FGR is commonly caused by placental insufficiency and yet the role of hypothyroidism in placental regulation of fetal growth is unknown. This study aimed to investigate the effects of maternal hypothyroidism on placental nutrient transporter expression, placental morphology, and placental metabolism. METHODS: Hypothyroidism was induced in female Sprague-Dawley rats by adding methimazole (MMI) to drinking water at moderate (MOD, MMI at 0.005% w/v) and severe (SEV, MMI at 0.02% w/v) doses from one week prior to pregnancy and throughout gestation. Maternal and fetal tissues were collected on embryonic day 20 (E20). RESULTS: Hypothyroidism reduced fetal weight (PTrt<0.001) despite causing fetal hyperglycaemia (PTrt = 0.016). Placental weight was not affected by hypothyroidism however placental efficiency was reduced (PTrt<0.001), as was the junctional zone (JZ):labyrinth zone (LZ) weight ratio (PTrt = 0.005). LZ glycogen content was increased (PTrt = 0.029) and while mRNA expression of glucose transporters was reduced by hypothyroidism, only GLUT1 protein expression was reduced in male LZs. Maternal hypothyroidism reduced mitochondrial content (PTrt = 0.031), particularly in SEV males relative to CON males (P = 0.004). Protein expression of Complex V (P < 0.001) and Complex III (P = 0.002) of the electron transport chain were also reduced in males. Maternal hypothyroidism reduced LZ (PTrt<0.001) and fetal plasma triglycerides (P = 0.019) while fetal free fatty acids and the expression of LZ lipid transporters was not affected. DISCUSSION: Overall, maternal hypothyroidism may lead to FGR through reduced maternal T4 availability, changes to placental morphology, altered nutrient transporter expression and sex-specific effects on placental metabolism. Changes to LZ glycogen and triglyceride stores as well as mitochondrial content suggest a metabolic shift from oxidative phosphorylation to anaerobic glycolysis in males. These changes also likely impact fetal substrate availability and therefore fetal growth.

"Our Mothers Have Handed That to Us. Her Mother Has Handed That to Her": Urban Aboriginal and Torres Strait Islander Yarning about Community Wellbeing, Healthy Pregnancies, and the Prevention of Fetal Alcohol Spectrum Disorder.

In Australia, fetal alcohol spectrum disorder (FASD) is a largely hidden disability that is currently under-recognized, under-resourced, and under- or misdiagnosed. Unsurprisingly, efforts to prevent FASD in urban Aboriginal and Torres Strait Islander communities are lacking. Further, mainstream approaches are not compatible with diverse and distinct Aboriginal and Torres Strait Islander ways of approaching family, pregnancy, and parenting life. To support the creation of culturally appropriate urban Aboriginal and Torres Strait Islander FASD prevention strategies, we sought to understand local perspectives, experiences, and priorities for supporting healthy and alcohol-free pregnancies. Using a narrative methodology, we undertook research yarns with eight female and two male community participants. Data were analyzed using a narrative, thematic analysis and guided by an Indigenist research practice of reflexive listening. Participant yarns provided important insights into local urban Aboriginal and Torres Strait Islander cultural, social, and structural determinants that support family and child health, alcohol-free pregnancies, and the prevention of FASD. The results provide critical guidance for Indigenizing and decolonizing FASD prevention strategies to support culturally safe, relevant, and strengths-based services. This approach has critical implications for all health and social professionals and can contribute to Aboriginal and Torres Strait Islander peoples' justice, recovery, and healing from colonization.

Beneficial effects of brief early life angiotensin-converting enzyme inhibition wane with time in sheep with solitary functioning kidney.

A child with a congenital solitary functioning kidney (SFK) may develop kidney disease from early in life due to hyperfiltration injury. Previously, we showed in a sheep model of SFK that brief angiotensin-converting enzyme inhibition (ACEi) early in life is reno-protective and increases renal functional reserve (RFR) at 8 months of age. Here we investigated the long-term effects of brief early ACEi in SFK sheep out to 20 months of age. At 100 days gestation (term = 150 days) SFK was induced by fetal unilateral nephrectomy, or sham surgery was performed (controls). SFK lambs received enalapril (SFK+ACEi; 0.5 mg/kg, once daily, orally) or vehicle (SFK) from 4 to 8 weeks of age. At 8, 14 and 20 months of age urinary albumin excretion was measured. At 20 months of age, we examined basal kidney function and RFR via infusion of combined amino acid and dopamine (AA+D). SFK+ACEi resulted in lower albuminuria (∼40%) at 8 months, but not at 14 or 20 months of age compared with vehicle-SFK. At 20 months, basal GFR (∼13%) was lower in SFK+ACEi compared with SFK, but renal blood flow (RBF), renal vascular resistance (RVR) and filtration fraction were similar to SFK. During AA+D, the increase in GFR was similar in SFK+ACEi and SFK animals, but the increase in RBF was greater (∼46%) in SFK+ACEi than SFK animals. Brief ACEi in SFK delayed kidney disease in the short-term but these effects were not sustained long-term.

Prenatal alcohol exposure risk perception dimensions and influencing factors: A systematic review and conceptual model.

OBJECTIVE: This paper aims to explore the available literature to understand how risks regarding prenatal alcohol exposure are perceived. METHODS: A systematic review (PROSPERO; CRD 42020212887) was undertaken. PubMed, Embase, PsycINFO, and CINAHL were searched for relevant quantitative and qualitative studies. A thematic analysis of the studies was performed. RESULTS: Fifteen articles-nine quantitative and six qualitative studies met the inclusion criteria. Three dimensions of risk perceptions were identified-perceived susceptibility, perceived severity, and affective risk perception. Three influencing factors of these dimensions were also identified: information (i.e., consistency, confirmation bias, strength of the evidence, and perceived relevance), sociocultural (i.e., social inclusivity, cultural context, and risk interpretation), and individual (i.e., risks versus benefits, controllability, and experience). These dimensions and influencing factors were brought together to create the proposed novel Pregnancy Alcohol Risk Perception (PARP) conceptual model. CONCLUSIONS: The novel PARP conceptual model developed from the current literature provides a framework to guide understanding of risk perceptions, which includes a wide range of potential influencing factors. IMPLICATIONS FOR PUBLIC HEALTH: The novel PARP conceptual model provides the groundwork for further refinement with stakeholders, which could in turn be used to inform the design of interventions and health promotional materials to support harm reduction approaches and prevention of prenatal alcohol exposure.

Periconceptional alcohol alters in vivo heart function in ageing female rat offspring: Possible involvement of oestrogen receptor signalling.

NEW FINDINGS: What is the central question of this study? What are the cardiovascular consequences of periconceptual ethanol on offspring throughout the lifespan? What is the main finding and its importance? It is shown for the first time that periconceptional alcohol has sex-specific effects on heart growth, with ageing female offspring exhibiting decreased cardiac output. Altered in vivo cardiac function in ageing female offspring may be linked to changes in cardiac oestrogen receptor expression. ABSTRACT: Alcohol exposure throughout gestation is detrimental to cardiac development and function. Although many women decrease alcohol consumption once aware of a pregnancy, exposure prior to recognition is common. We, therefore, examined the effects of periconceptional alcohol exposure (PC:EtOH) on heart function, and explored mechanisms that may contribute. Female Sprague-Dawley rats received a liquid diet ±12.5% v/v ethanol from 4 days prior to mating until 4 days after mating (PC:EtOH). Cardiac function was assessed via echocardiography, and offspring were culled at multiple time points for assessment of morphometry, isolated heart and aortic ring function, protein and transcriptional changes. PC:EtOH-exposed embryonic day 20 fetuses (but not postnatal offspring) had larger hearts relative to body weight. Ex vivo analysis of hearts at 5-7 months old (mo) indicated no changes in coronary function or cardiac ischaemic tolerance, and apparently improved ventricular compliance in PC:EtOH females (compared to controls). At 12 mo, vascular responses in isolated aortic rings were unaltered by PC:EtOH, whilst echocardiography revealed reduced cardiac output in female but not male PC:EtOH offspring. At 19 mo, left ventricular transcript and protein for type 1 oestrogen receptor (ESR1), HSP90 transcript and plasma oestradiol levels were all elevated in female PC:EtOH exposed offspring. Summarising, PC:EtOH adversely impacts in vivo heart function in mature female offspring, associated with increased ventricular oestrogen-related genes. PC:EtOH may thus influence age-related heart dysfunction in females through modulation of oestrogen signalling.

The role of maternal choline, folate and one-carbon metabolism in mediating the impact of prenatal alcohol exposure on placental and fetal development.

Prenatal alcohol consumption (PAE) may be associated with a broad spectrum of impacts, ranging from no overt effects, to miscarriage, fetal growth restriction and fetal alcohol spectrum disorder. A major mechanism underlying the effects of PAE is considered to be altered DNA methylation and gene expression. Maternal nutritional status may be an important factor in determining the extent to which PAE impacts pregnancy outcomes, particularly the dietary micronutrients folate and choline because they provide methyl groups for DNA methylation via one carbon metabolism. This review summarises the roles of folate and choline in development of the blastocyst, the placenta and the fetal brain, and examines the evidence that maternal intake of these micronutrients can modify the effects of PAE on development. Studies of folate or choline deficiency have found reduced blastocyst development and implantation, reduced placental invasion, vascularisation and nutrient transport capability, impaired fetal brain development, and abnormal neurodevelopmental outcomes. PAE has been shown to reduce absorption and/or metabolism of folate and choline and to produce similar outcomes to maternal choline/folate deficiency. A few studies have demonstrated that the effects of PAE on brain development can be ameliorated by folate or choline supplementation; however, there is very limited evidence on the effects of supplementation in early pregnancy on the blastocyst and placenta. Further studies are required to support these findings and to determine optimal supplementation parameters.

The social predictors of paternal antenatal mental health and their associations with maternal mental health in the Queensland Family Cohort prospective study.

Antenatal depression (AND) affects 1 in 10 fathers, potentially negatively impacting maternal mental health and well-being during and after the transition to parenthood. However, few studies have assessed the social predictors of paternal AND or their possible associations with maternal mental health. We analysed data from 180 couples participating in the Queensland Family Cohort longitudinal study. Both parents completed surveys measuring mental health, relationship quality, social support, and sleep quality at 24 weeks of pregnancy. Mothers also completed the same surveys 6 weeks' postpartum. Antenatal depression, stress, and anxiety were highest among fathers reporting lower social support and higher sleep impairment. Maternal AND, stress, and anxiety were higher among mothers reporting higher physical pain and poor sleep quality. Postnatally, mothers reporting lower social support also reported higher depression, anxiety, stress, and psycho-social well-being. While there were no significant associations between AND among fathers and maternal antenatal or postnatal depression, an exploratory analysis revealed that mothers whose partners reported lower antenatal social support also reported lower postnatal social support and higher postnatal depression. Our findings highlight the importance of including data among fathers to achieve a whole family approach to well-being during the transition to parenthood.

Associations of maternal and foetoplacental factors with prehypertension/hypertension in early childhood.

OBJECTIVE: To evaluate whether characterization of maternal and foetoplacental factors beyond birthweight can enable early identification of children at risk of developing prehypertension/hypertension. METHODS: We recruited 693 mother-offspring dyads from the GUSTO prospective mother-offspring cohort. Prehypertension/hypertension at age 6 years was identified using the simplified paediatric threshold of 110/70 mmHg. We evaluated the associations of pregnancy complications (gestational diabetes, excessive/inadequate gestational weight gain, hypertensive disorders of pregnancy), foetal growth deceleration (decline in foetal abdominal circumference at least 0.67 standard deviations between second and third trimesters), high foetoplacental vascular resistance (third trimester umbilical artery systolic-to-diastolic ratio ≥90th centile), preterm birth, small-for-gestational age and neonatal kidney volumes with risk of prehypertension/hypertension at age 6 years, after adjusting for sex, ethnicity, maternal education and prepregnancy BMI. RESULTS: Pregnancy complications, small-for-gestational age, preterm birth, and low neonatal kidney volume were not associated with an increased risk of prehypertension/hypertension at age 6 years. In contrast, foetal growth deceleration was associated with a 72% higher risk [risk ratio (RR) = 1.72, 95% confidence interval (CI) 1.18-2.52]. High foetoplacental vascular resistance was associated with a 58% higher risk (RR = 1.58, 95% CI 0.96-2.62). Having both these characteristics, relative to having neither, was associated with over two-fold higher risk (RR = 2.55, 95% CI 1.26-5.16). Over 85% of the foetuses with either of these characteristics were born appropriate or large for gestational age. CONCLUSION: Foetal growth deceleration and high foetoplacental vascular resistance may be helpful in prioritizing high-risk children for regular blood pressure monitoring and preventive interventions, across the birthweight spectrum.

Prevalence and Patterns of Prenatal Alcohol Exposure in Australian Cohort and Cross-Sectional Studies: A Systematic Review of Data Collection Approaches.

This study sought to determine data collection approaches in Australian cohort studies and explore the potential impact on reported prenatal alcohol exposure (PAE) prevalence and patterns. Inclusion criteria were that studies related to a general Australian antenatal population where PAE was assessed and reported. Studies were excluded if they were not peer reviewed, examined the prevalence of PAE in pregnancies complicated by alcohol-use disorders, or were published in a language other than English. A systematic search of five electronic databases (PubMed, Embase, CINAHL, Web of Science, and Scopus) was conducted. Risk of bias was assessed using the Effective Public Health Practice Project quality assessment tool. Results were synthesised using MetaXL. Data from 16 separate birth cohorts (n = 78 articles) were included. Included cohorts were either general cohorts that included alcohol as a variable or alcohol-focused cohorts that were designed with a primary focus on PAE. PAE prevalence was estimated as 48% (95% CI: 38 to 57%). When subgroup analysis was performed, estimates of PAE prevalence when self-administered surveys and interviews were used for data collection were 53% (95% CI: 41% to 64%) and 43% (95% CI: 28% to 59%), respectively. Use of trained assessors was an influencing factor of the prevalence estimates when data were collected via interview. Alcohol-focused studies reported higher prevalence of PAE, regardless of method of survey administration. Where interviewer training is not possible, self-administered questionnaires will likely provide the most reliable PAE estimates. No funding sources are relevant to mention. Review was registered with PROSPERO (CRD42020204853).

Expression of TRPM6 and TRPM7 in the preterm piglet heart.

Preterm infants are at increased risk of death and disability, and cardiovascular instability after birth is a contributing factor. Immaturity of calcium handling in the preterm heart may limit myocardial contractility and cardiac output. Two transmembrane cation channels, TRPM6 and TRPM7, may regulate intracellular cardiac calcium in the neonatal period. The aim of this study was to determine TRPM6 and TRPM7 mRNA expression in piglet hearts in late gestation, and the effects of sex, maternal glucocorticoids, and the transition to extrauterine life. Left and right ventricular tissue was collected at a range of gestational ages from cesarean delivered piglets at birth and at 6 h old. Additional groups included piglets exposed to maternal glucocorticoid treatment and spontaneously born term piglets at 12-24 h old. TRPM6 and TRPM7 mRNA expression was measured using RT-qPCR. Males had significantly lower TRPM7 expression in the left ventricle across all gestational ages compared to females. At term, both ventricles had higher TRPM7 expression at 6 h old than at birth. In preterm piglets, TRPM7 expression only increased postnatally in the right ventricle following maternal glucocorticoid exposure. At 12-24 h old, TRPM7 expression in both ventricles was lower than levels in 6 h old term Caesar piglets (113 days). Male preterm piglets may have immature myocardial Ca2+ handling and this could contribute to their poorer outcomes. Increased TRPM7 expression is the mature response to birth that is missing in preterm neonates. TRPM7 could serve as a novel target to improve cardiac function in preterm neonates.

Altered bone and body composition in children and adolescents with confirmed prenatal alcohol exposure.

Prenatal alcohol exposure can contribute to long term adverse health outcomes. Development of the skeletal system begins at the early embryonic stage and continues into early adulthood but the effect of prenatal alcohol exposure on skeletal growth is relatively unexplored in a clinical population. Here, we performed dual X-ray absorptiometry to examine bone, fat, and muscle accrual in children and adolescents diagnosed with, or at risk of, fetal alcohol spectrum disorders (FASDs). Children (aged 4-9 years) with FASD or at risk of FASD (n = 10) had similar growth to age matched controls (n = 27). By adolescence (aged ≥10 years), those with FASDs (n = 13) were shorter and had lower areal bone mineral density and lean tissue mass than typically developing peers (n = 29). Overall, adolescents diagnosed with FASDs had greater odds of impairments to bone and body composition. These findings highlight the importance of early FASD diagnosis and appropriate post-diagnostic medical follow-up to enable timely, effective interventions to optimize bone and body composition during paediatric growth.

Associations between COVID-19 lockdown and post-lockdown on the mental health of pregnant women, postpartum women and their partners from the Queensland family cohort prospective study.

BACKGROUND: There are very few developed countries where physical isolation and low community transmission has been reported for COVID-19 but this has been the experience of Australia. The impact of physical isolation combined with low disease transmission on the mental health of pregnant women is currently unknown and there have been no studies examining the psychological experience for partners of pregnant women during lockdown. The aim of the current study was to examine the impact of the first COVID-19 lockdown in March 2020 and post lockdown from August 2020 on the mental health of pregnant women or postpartum women and their partners. METHODS: Pregnant women and their partners were prospectively recruited to the study before 24 weeks gestation and completed various questionnaires related to mental health and general wellbeing at 24 weeks gestation and then again at 6 weeks postpartum. The Depression, Anxiety and Stress Scale (DASS-21) and the Edinburgh Postnatal Depression Scale (EPDS) were used as outcome measures for the assessment of mental health in women and DASS-21 was administered to their partners. This analysis encompasses 3 time points where families were recruited; before the pandemic (Aug 2018-Feb 2020), during lockdown (Mar-Aug 2020) and after the first lockdown was over (Sept-Dec 2020). RESULTS: There was no significant effect of COVID-19 lockdown and post lockdown on depression or postnatal depression in women when compared to a pre-COVID-19 subgroup. The odds of pregnant women or postpartum women experiencing severe anxiety was more than halved in women during lockdown relative to women in the pre-COVID-19 period (OR = 0.47; 95%CI: 0.27-0.81; P = 0.006). Following lockdown severe anxiety was comparable to the pre-COVID-19 women. Lockdown did not have any substantial effects on stress scores for pregnant and postpartum women. However, a substantial decrease of over 70% in the odds of severe stress was observed post-lockdown relative to pre-COVID-19 levels. Partner's depression, anxiety and stress did not change significantly with lockdown or post lockdown. CONCLUSION: A reproductive age population appear to be able to manage the impact of lockdown and the pandemic with some benefits related to reduced anxiety.

Associations of maternal periconceptional alcohol consumption with offspring prehypertension/hypertension at age 6 years: the Growing Up in Singapore Towards healthy Outcomes prospective mother-offspring cohort study.

OBJECTIVE: To evaluate the relationship of the levels of maternal alcohol consumption during the 1 year before pregnancy recognition with childhood cardiorenal, metabolic, and neurocognitive health. METHODS: In 1106 women and their children from the Growing Up in Singapore Towards healthy Outcomes mother-offspring cohort, quantity of maternal alcohol consumption in the 12 months prior to pregnancy recognition was categorized as high (≥75th percentile: 1.9 g/day), low (<1.9 g/day), and none, and frequency of alcohol consumption was categorized as high (≥2-3 times/week), low (<2-3 times/week), and none. Offspring MRI-based abdominal fat depot, kidney, and brain volumes, blood pressure, metabolic syndrome score, and cognitive intelligence scores were assessed. Child prehypertension/hypertension at age 6 years was defined using a simplified pediatric threshold of 110/70 mmHg. RESULTS: The average maternal alcohol consumption in the year prior to pregnancy recognition was 2.5 g/day, which is lower than the daily maximal limit of one standard drink (10 g) recommended for women by Singapore's Ministry of Health. After adjusting for participant characteristics, alcohol consumption at least 1.9 g/day was associated with over two-fold higher risk (risk ratio = 2.18, P = 0.013) of child prehypertension and 15% greater kidney growth between early infancy and age 6 years (P = 0.040) compared with abstinence. Alcohol consumption was not associated with metabolic and neurocognitive health at age 6-7 years. The associations with high frequency of alcohol consumption were concordant with those obtained for quantity of alcohol consumption. CONCLUSION: Maternal self-reported alcohol consumption at least 1.9 g/day prior to pregnancy recognition was associated with increased risk of child prehypertension and rapid kidney growth. Our findings highlight the potential detrimental effects of low periconceptional alcohol consumption, below national guidelines on offspring cardiorenal health.

Key Stakeholder Priorities for the Review and Update of the Australian Guide to Diagnosis of Fetal Alcohol Spectrum Disorder: A Qualitative Descriptive Study.

Since the 2016 release of the Australian Guide to the Diagnosis of Fetal Alcohol Spectrum Disorder (FASD), considerable progress has been made in the identification and diagnosis of the disorder. As part of a larger process to review and update the Guide, the aim of this study was to identify review priorities from a broad range of stakeholders involved in the assessment and diagnosis of FASD. Sixty-two stakeholders, including healthcare practitioners, researchers, other specialists, individuals with cultural expertise, lived experience and consumer representatives completed an online survey asking them to describe up to five priorities for the review of the Australian Guide to the Diagnosis of FASD. A total of 267 priorities were described. Content analysis of responses revealed priority areas relating to diagnostic criteria (n = 82, 30.7%), guideline content (n = 91, 34.1%), guideline dissemination (n = 15, 5.6%) and guideline implementation (n = 63, 23.6%). Other considerations included prevention and screening of FASD (n = 16, 6%). Engaging stakeholders in setting priorities will ensure the revised Australian Guide can be as relevant and meaningful as possible for the primary end-users and that it meets the needs of individuals with lived experience who will be most affected by the diagnosis.

Prenatal Choline Supplementation Alters One Carbon Metabolites in a Rat Model of Periconceptional Alcohol Exposure.

Prenatal alcohol exposure disturbs fetal and placental growth and can alter DNA methylation (DNAm). Supplementation with the methyl donor choline can increase fetal and placental growth and restore DNAm, suggesting converging effects on one-carbon metabolism (1CM). We investigated the impact of periconceptional ethanol (PCE) exposure and prenatal choline supplementation on 1CM in maternal, placental, and fetal compartments. Female Sprague Dawley rats were given a liquid diet containing 12.5% ethanol (PCE) or 0% ethanol (control) for 4 days before and 4 days after conception. Dams were then placed on chow with different concentrations of choline (1.6 g, 2.6 g, or 7.2 g choline/kg chow). Plasma and tissues were collected in late gestation for the analysis of 1CM components by means of mass spectrometry and real-time PCR. PCE reduced placental components of 1CM, particularly those relating to folate metabolism, resulting in a 3−7.5-fold reduction in the ratio of s-adenosylmethionine:s-adenosylhomocysteine (SAM:SAH) (p < 0.0001). Choline supplementation increased placental 1CM components and the SAM:SAH ratio (3.5−14.5-fold, p < 0.0001). In the maternal and fetal compartments, PCE had little effect, whereas choline increased components of 1CM. This suggests that PCE impairs fetal development via altered placental 1CM, highlighting its role in modulating nutritional inputs to optimize fetal development.

Serum and urinary biomarkers to predict acute kidney injury in premature infants: a systematic review and meta-analysis of diagnostic accuracy.

BACKGROUND: Premature infants are at high risk for acute kidney injury (AKI) and current diagnostic criteria are flawed. The objective of this study was to determine the diagnostic accuracy of urine and serum biomarkers not currently used in routine clinical practice to predict AKI in premature infants. METHOD: A systematic review was performed that followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses of Diagnostic Test Accuracy Studies (PRISMA-DTA). Data were extracted on the diagnostic accuracy of AKI biomarkers using serum creatinine or urine output as the reference standard. Quality and validity were assessed using modified Standards for Reporting Diagnostic Accuracy (STARD) criteria. RESULTS: We identified 1024 articles, with 15 studies (791 infants) eligible for inclusion. Twenty-seven biomarkers were identified including serum cystatin C and urinary neutrophil gelatinase-associated lipocalin (uNGAL), osteopontin, kidney injury molecule-1, epidermal growth factor, and protein S100-P. However, many were only reported by one study each. A meta-analysis could only be conducted on uNGAL (288 infants from 6 studies) using a hierarchical, random-effects logistic-regression model. uNGAL had a summary sensitivity of 77% (95% CI 58-89%), specificity of 76% (95% CI 57-88%) and AUC-SROC of 0.83 (95% CI 0.80-0.86) for the diagnosis of AKI. By utilising uNGAL, the post-test probability of AKI increased to 52% (95% CI 37-66%) with a positive test and decreased to 9% (95% CI 5-16%) with a negative test if the pre-test probability was 25%. CONCLUSION: uNGAL shows promise as a diagnostically accurate biomarker for AKI in premature infants.