Preterm Infant Outcomes Following COVID-19 Lockdowns in Melbourne, Australia.

Background Community lockdowns during the coronavirus disease 2019 (COVID-19) pandemic may influence preterm birth rates, but mechanisms are unclear. Methods We compared neonatal outcomes of preterm infants born to mothers exposed to community lockdowns in 2020 (exposed group) to those born in 2019 (control group). Main outcome studied was composite of significant neonatal morbidity or death. Results Median gestational age was 35 + 4 weeks (295 infants, exposed group) vs. 35 + 0 weeks (347 infants, control group) (p = 0.108). The main outcome occurred in 36/295 (12.2%) infants in exposed group vs. 46/347 (13.3%) in control group (p = 0.69). Continuous positive airway pressure (CPAP) use, jaundice requiring phototherapy, hypoglycaemia requiring treatment, early neonatal white cell and neutrophil counts were significantly reduced in the exposed group. Conclusions COVID-19 community lockdowns did not alter composite neonatal outcomes in preterm infants, but reduced rates of some common outcomes as well as early neonatal inflammatory markers.

Melatonin for the Management of Preeclampsia: A Review.

Preeclampsia is a disease specific to pregnancy characterised by new-onset hypertension with maternal organ dysfunction and/or fetal growth restriction. It remains a major cause of maternal and perinatal morbidity and mortality. For sixty years, antihypertensives have been the mainstay of treating preeclampsia and only recently have insights into the pathogenesis of the disease opened new avenues for novel therapies. Melatonin is one such option, an endogenous and safe antioxidant, that may improve the maternal condition in preeclampsia while protecting the fetus from a hostile intrauterine environment. Here we review the evidence for melatonin as a possible adjuvant therapy for preeclampsia, including in vitro evidence supporting a role for melatonin in protecting the human placenta, preclinical models, vascular studies, and clinical studies in hypertension and pregnancy.

Creatine Metabolism in Female Reproduction, Pregnancy and Newborn Health.

Creatine metabolism is an important component of cellular energy homeostasis. Via the creatine kinase circuit, creatine derived from our diet or synthesized endogenously provides spatial and temporal maintenance of intracellular adenosine triphosphate (ATP) production; this is particularly important for cells with high or fluctuating energy demands. The use of this circuit by tissues within the female reproductive system, as well as the placenta and the developing fetus during pregnancy is apparent throughout the literature, with some studies linking perturbations in creatine metabolism to reduced fertility and poor pregnancy outcomes. Maternal dietary creatine supplementation during pregnancy as a safeguard against hypoxia-induced perinatal injury, particularly that of the brain, has also been widely studied in pre-clinical in vitro and small animal models. However, there is still no consensus on whether creatine is essential for successful reproduction. This review consolidates the available literature on creatine metabolism in female reproduction, pregnancy and the early neonatal period. Creatine metabolism is discussed in relation to cellular bioenergetics and de novo synthesis, as well as the potential to use dietary creatine in a reproductive setting. We highlight the apparent knowledge gaps and the research "road forward" to understand, and then utilize, creatine to improve reproductive health and perinatal outcomes.

Risk of Adverse Outcomes in Females Taking Oral Creatine Monohydrate: A Systematic Review and Meta-Analysis.

Creatine Monohydrate (CrM) is a dietary supplement routinely used as an ergogenic aid for sport and training, and as a potential therapeutic aid to augment different disease processes. Despite its increased use in recent years, studies reporting potential adverse outcomes of CrM have been mostly derived from male or mixed sex populations. A systematic search was conducted, which included female participants on CrM, where adverse outcomes were reported, with meta-analysis performed where appropriate. Six hundred and fifty-six studies were identified where creatine supplementation was the primary intervention; fifty-eight were female only studies (9%). Twenty-nine studies monitored for adverse outcomes, with 951 participants. There were no deaths or serious adverse outcomes reported. There were no significant differences in total adverse events, (risk ratio (RR) 1.24 (95% CI 0.51, 2.98)), gastrointestinal events, (RR 1.09 (95% CI 0.53, 2.24)), or weight gain, (mean difference (MD) 1.24 kg pre-intervention, (95% CI -0.34, 2.82)) to 1.37 kg post-intervention (95% CI -0.50, 3.23)), in CrM supplemented females, when stratified by dosing regimen and subject to meta-analysis. No statistically significant difference was reported in measures of renal or hepatic function. In conclusion, mortality and serious adverse events are not associated with CrM supplementation in females. Nor does the use of creatine supplementation increase the risk of total adverse outcomes, weight gain or renal and hepatic complications in females. However, all future studies of creatine supplementation in females should consider surveillance and comprehensive reporting of adverse outcomes to better inform participants and health professionals involved in future trials.

Acceptability of dietary or nutritional supplementation in pregnancy (ADONS) - Exploring the consumer's perspective on introducing creatine monohydrate as a pregnancy supplement.

BACKGROUND: Pre-clinical studies suggest maternal dietary creatine supplementation during pregnancy could protect babies against hypoxic intrapartum events, however creatine has not been used as a supplement in pregnancy. The aim of this study was to explore pregnant women and healthcare professional's general knowledge, behaviours, and attitudes toward nutritional supplements, and their thoughts on introducing creatine as a pregnancy supplement. METHODS: Pregnant women (n = 42) and partners (n = 23), attending a tertiary care pregnancy service in Melbourne, Australia, participated in focus groups or semi-structured interviews. Health professionals (n = 100), completed a semi-structured online survey. Descriptive data were analyzed using SPSS 25.0 and qualitative data was managed using NVivo 22.0. RESULTS: Use of branded nutritional supplements in pregnancy was commonplace and acceptable. All primary healthcare respondents discussed supplements with their patients at first consultation. Supplements consumed corresponded closely to those recommended. Women had good general awareness of commonly recommended nutritional supplements, however, were less aware of the rationale for supplement use. This aligned with health professional's perceptions. Women would consider taking creatine if recommended by their health professional. Health professionals would require detailed safety, beneficence, and efficacy information before recommending creatine supplementation. They would also be more likely to recommend a new supplement in higher-risk pregnancies, where benefits may outweigh any perceived side-effects. CONCLUSION: There is high acceptance of current recommended nutritional supplements in pregnancy. Implementing creatine as a new supplement will require substantive empirical evidence and changes to clinical guidelines. Public awareness and education would also be essential to consumer acceptability of creatine.

Prolong: a double-blind randomised placebo-controlled trial of broccoli sprout extract in women with early onset preeclampsia. A clinical trial protocol.

INTRODUCTION: Preeclampsia is a leading cause of maternal and perinatal morbidity and mortality. There is a need for adjuvant, targeted therapies to improve outcomes. Broccoli sprout extract, rich in the antioxidant sulforaphane, reduces oxidative stress and placental secretion of the antiangiogenic factors that contribute to vascular dysfunction in preeclampsia. We propose a phase III trial investigating broccoli sprout extract. We will assess broccoli sprout extract in women with early onset (<34 weeks) preeclampsia, investigating (1) the interval between enrolment and delivery (days), (2) biomarkers of placental and endothelial function and (3) maternal and fetal outcomes. METHODS: A double-blind, placebo-controlled randomised trial will be conducted at Monash Health, Melbourne, Australia. One hundred and eighty women (45 each arm of each stratum) with early onset preeclampsia (defined as per Society for Obstetric Medicine of Australia and New Zealand guidelines) will be recruited. Consenting women will be randomised to receive an oral dose of either broccoli sprout extract (24 mg of activated sulforaphane) or identical placebo, twice daily until delivery. Maternal blood will be collected antenatally for measurement of biomarkers of preeclampsia, including soluble fms-like tyrosine kinase 1 (sFlt-1), placental growth factor (PlGF), soluble endoglin (sEng) and activin A, as well as circulating sulforaphane metabolites. Maternal and perinatal outcomes will be monitored throughout. All clinical care decisions, including the timing of delivery, will be made by the treating team, blinded to treatment allocation. Participation in this trial will not affect routine care. At delivery, maternal and cord blood and placentae will be collected to measure sulforaphane metabolites and sFlt-1, PlGF, sEng and activin A. ETHICS AND DISSEMINATION: Approval to conduct the trial has been granted by Monash Health Human Research and Ethics Committee (RES-18-0000-109A). Deidentified data will be published in peer-reviewed journals and presented at learnt society conferences, both nationally and internationally. This study has not yet commenced and is pre-results.Trial registration numberACTRN12618000216213.

Protect-me: a parallel-group, triple blinded, placebo-controlled randomised clinical trial protocol assessing antenatal maternal melatonin supplementation for fetal neuroprotection in early-onset fetal growth restriction.

INTRODUCTION: Fetal growth restriction (FGR) is a serious pregnancy complication, associated with increased rates of perinatal death and morbidity among survivors. Most commonly FGR results from placental insufficiency, where the placenta fails to deliver the oxygen and nutrients required for normal fetal growth. This leads to fetal oxidative stress, resulting in organ damage through lipid peroxidation. The early developing brain is particularly susceptible, such that FGR is associated with poorer neurodevelopment, witnessed as cognitive and behavioural dysfunction, and cerebral palsy. Promisingly, melatonin, a lipid soluble antioxidant is neuroprotective in animal models of FGR. We present a protocol outlining a randomised, placebo-controlled trial to explore whether antenatal maternal melatonin supplementation in pregnancies with severe, early-onset FGR can improve neurodevelopment among survivors at 2 years of age. METHODS AND ANALYSES: We will recruit 336 women with a singleton pregnancy complicated by FGR between 23+0 and 31+6 weeks gestation. Participants will be randomised, stratified by gestational age, to either 30 mg melatonin per day or a visually identical placebo, continued until birth. Measures of maternal and fetal health will be collected until birth. Timing of birth will be determined by the treating clinical team in discussion with the woman. Neonatal and infant neurodevelopmental assessments will be undertaken, consisting of brain MRI at term corrected age, general movements assessment at term and 3 months' corrected age, and Bayley Scales of Infant & Toddler Development-III and Infant Toddler Social Emotional Assessment at 2.5 years corrected age. Analyses will be on intention to treat. The primary outcome is a difference of 5 points in the cognitive domain of the Bayley-III. Secondary outcomes address maternal and fetal safety. ETHICS AND DISSEMINATION: This trial has Monash Health Human Research and Ethics committee approval (17-0000-583A). Findings will be disseminated through peer-reviewed publications, conference presentations and to participants. TRIAL REGISTRATION NUMBER: ACTRN12617001515381; Pre-results.

Current and emerging pharmacotherapy for emergency management of preeclampsia.

INTRODUCTION: Preeclampsia is a disease specific to pregnancy characterised by new onset hypertension with maternal organ dysfunction and/or fetal growth restriction. It remains a major cause of maternal and perinatal morbidity and mortality. For fifty years, antihypertensives have been the mainstay of treating preeclampsia, reducing maternal morbidity and mortality. With increased knowledge of the mechanisms underlying the disease has come opportunities for novel therapies that complement antihypertensives by protecting the maternal vasculature. Areas covered: In this review, the authors consider, in detail, the antihypertensives commonly used today in the emergency care of women with severe preeclampsia. They also review less common anti-hypertensive agents and discuss the role of magnesium sulphate in the management of preeclampsia and the prevention of eclampsia. Finally, they explore novel therapeutics for the acute management of preeclampsia. Expert opinion: The rapid control of maternal hypertension will, and must, remain the mainstay of emergency treatment for women with severe preeclampsia. The role of magnesium sulphate as a primary prevention for eclampsia is context dependant and should not displace a focus on correcting blood pressure safely. The exploration of novel adjuvant therapies will likely allow us to prolong pregnancy longer and improve perinatal outcomes safely for the mother.