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With the increased prevalence of non-communicable disease and availability of medications to treat these and other conditions, a pregnancy free from prescribed medication exposure is rare. Up to 99% of women take at least one medication during pregnancy. These medications can be divided into those used to improve maternal health and wellbeing (e.g., analgesics, antidepressants, antidiabetics, antiasthmatics), and those used to promote the baby's wellbeing in either fetal (e.g., anti-arrhythmics) or postnatal life (e.g., antenatal glucocorticoids). These medications are needed for pre-existing or coincidental illnesses in the mother, maternal conditions induced by the pregnancy itself through to conditions that arise in the fetus or that will be encountered by the newborn. Thus, medications administered to the mother may be used to treat the mother, the fetus or both. Metabolism of medications is regulated by a range of physiological processes that change during pregnancy. Other pathological processes such as placental insufficiency can in turn have both immediate and lifelong adverse health consequences for babies. Individuals born growth restricted are more likely to require medications but may also have an altered ability to metabolise these medications in fetal and postnatal life. This review aims to determine the effect of suboptimal fetal growth on the fetal expression of the drug metabolising enzymes (DMEs) that convert medications into active or inactive metabolites, and the transporters that remove both these medications and their metabolites from the fetal compartment. Refereed/Peer-reviewed

At birth, weight of the neonate is used as a marker of the 9-month journey as a fetus. Those neonates born less than the 10th centile for their gestational age are at risk of being intrauterine growth restricted.However, this depends on their genetic potential for growth and the intrauterine environment in which they grew. Alterations in the supply of oxygen and nutrients to the fetus will decrease fetal growth, but these alterations occur due to a range of causes that are maternal, placental or fetal in nature. Consequently, IUGR neonates are a heterogeneous population. For this reason, it is likely that these neonates will respond differently to interventions compared not only to normally grown fetuses, but also to other neonates that are IUGR but have travelled a different path to get there. Thus, a range of models of IUGR should be studied to determine the effects of IUGR on the development and function of the heart and lung and subsequently the impact of interventions to improve development of these organs. Here we focus on a range of models of IUGR caused by manipulation of the maternal, placental or fetal environment on cardiorespiratory outcomes. Refereed/Peer-reviewed

Maternal asthma increases the risk of adverse pregnancy outcomes and may affect fetal growth and placental function by differential effects on the expression of glucocorticoid receptor (GR) isoforms, leading to altered glucocorticoid signalling. Our aim was to examine the effect of maternal asthma on placental GR profiles using a pregnant sheep model of asthma. Nine known GR isoforms were detected. There was a significant increase in the expression of placental GR isoforms that are known to have low trans-activational activity in other species including GR A, GR P and GRγ which may result in a pro-inflammatory environment in the presence of allergic asthma. Refereed/Peer-reviewed

The widespread uptake and use of emissive metal ion complexes for investigating cellular structure, composition and function, is evidence of the effectiveness and vast potential for this type of imaging probe. Metal ion complexes provide significant advantages over their organic fluorophore counterparts, including long emission lifetime, resistance to photobleaching and the capacity to readily modify their peripheral chemistry to target specific organelles, signalling pathways and individual molecules. This review will discuss recent progress in the development and use of metal ion complexes, specifically for studying metabolic diseases at the cellular level. Advanced metal ion complexes for organelle imaging and the detection of biorelevant species, to elaborate complexes for understanding cellular mechanisms and recent therapeutic applications will be reviewed. To align with the special issue, Coordination Chemistry Reviews: Coordination Chemistry in Australia, the work of Australian researchers actively engaged in this field is featured prominently, along with key developments from the global research community. Refereed/Peer-reviewed

There is a wealth of evidence to say that sleep impacts maternal health during pregnancy, however, little has been published on fetal health and maternal sleep. This scoping review summarises current literature on maternal sleep including sleep disordered breathing, sleep quality, sleep duration and supine sleep position, as these relate to fetal outcomes specifically birth weight, growth, preterm birth and stillbirth. An overall interpretation of the studies evaluated shows that events occurring during maternal sleep such as obstructive sleep apnea, sleep disruption and sleep position may have a negative effect on the fetus resulting in altered growth, gestational length and even death. These effects are biologically and physically plausible. In conclusion, there is limited and often conflicting information on maternal sleep and fetal outcomes. However, existing evidence suggests that this is an important area for future research. This area is ripe for investigation if there is to be reduction in the physical, emotional, and financial burden of poor fetal outcomes related to maternal sleep. Refereed/Peer-reviewed

The effects of intrauterine growth restriction (IUGR) extend well into postnatal life. IUGR is associated with an increased risk of adverse health outcomes, which often leads to greater medication usage. Many medications require hepatic metabolism for activation or clearance, but hepatic function may be altered in IUGR fetuses.Using a sheep model of IUGR, we determined the impact of IUGR on hepatic drug metabolism and drug transporter expression, both important mediators of fetal drug exposure, in late gestation and in neonatal life. In the late gestation fetus, IUGR decreased the gene expression of uptake drug transporter OATPC and increased Pglycoprotein protein expression in the liver, but there was no change in the activity of the drug metabolising enzymes CYP3A4 or CYP2D6. In contrast, at 3 weeks of age, CYP3A4 activity was reduced in the livers of lambsborn with low birth weight (LBW), indicating that LBW results in changes to drug metabolising capacity inneonatal life. Together, these results suggest that IUGR may reduce hepatic drug metabolism in fetal and neonatallife through different mechanisms. Refereed/Peer-reviewed

In the absence of randomised controlled trials, knowledge of outcomes associated with medication use during pregnancy is dependent on observational studies. Numerous observational study designs exist, with the decision on which is most appropriate depending on a number of factors, including the exposure and outcome under investigation and knowledge of key methodological issues. This review provides an overview of the key methodological issues involved in undertaking observational studies to investigate medication use during pregnancy, including selection bias, exposure and outcome classification, information bias, confounding and statistical analysis. This review also discusses observational study types used to investigate outcomes associated with medication use during pregnancy and summarises their relative strengths and weaknesses. Knowledge of the strengths, weaknesses and methodological issues associated with observational studies can assist clinicians in making assessments about the validity and applicability of results presented in order to provide the best recommendations to patients. Refereed/Peer-reviewed

This paper describes the development of a sensitive high performance liquid chromatography (HPLC) method for quantification of rosiglitazone in sheep plasma and amniotic fluid. Samples were prepared by liquid-liquid extraction using tert-butyl methyl ether, and rosiglitazone was quantitated by HPLC using a C18 column and fluorescence detector with an excitation wavelength of 247 nm and emission wavelength of 367 nm. The mobile phase consisted of ammonium acetate (10 mM, pH 5.2) and acetonitrile (56.5:43.5, v/v) with a flow rate of 1 ml/min. Ketoconazole was used as the internal standard (IS). The plasma calibration curve was linear over the range of 2.5-250 ng/ml (mean r2 = 0.9940 ± 0.0024; n = 6) with accuracy of 99.4-102.8% over the calibration range. The intra-day and inter-day coefficient of variation (%CV, percent coefficient of variation) were in the range of 0.01-8.68% in sheep plasma. Similar performance was achieved for amniotic fluid. The described method was successfully applied to quantitate rosiglitazone concentrations in the pregnant ewe and her fetus. Refereed/Peer-reviewed