Maternal creatine in pregnancy: a retrospective cohort study

Dickinson, Hayley; Davies‐Tuck, Miranda; Ellery, Stacey J.; Grieger, JA; Wallace, Euan M.; Snow, Rod J.; Dw, Walker; Clifton, Vicki L.

doi:10.1111/1471-0528.14237

Cited by 24 publications

(21 citation statements)

References 23 publications

(41 reference statements)

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“…Data and biobanked plasma samples from a cohort study undertaken at the Lyell McEwin Hospital, Adelaide, Australia, that was used to study the effects of asthma during pregnancy on the mother, placenta and baby, were examined (Dickinson et al, 2016). The study was approved by the Queen Elizabeth Hospital and Lyell McEwin Hospital Human Research Ethics Committee and the University of Adelaide Human Research Ethics Committee.…”

Section: Study Populationmentioning

confidence: 99%

Angiotensin Converting Enzyme 2 (ACE2) in Pregnancy: Preeclampsia and Small for Gestational Age

et al. 2020

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Introduction: An imbalance in angiotensin (Ang) peptides could contribute to the pathophysiology of preeclampsia (PE) and poor fetal growth. Methods: We measured maternal plasma levels of Ang peptides and converting enzymes in non-pregnant women (n = 10), in normal pregnant women (n = 59), women delivering small for gestational age babies (SGA, n = 25) across gestation (13-36 weeks) and in women with PE (n = 14) in their third trimester. Results: Plasma ACE, ACE2, and Ang-(1-7) levels, and ACE2 activity were significantly higher in normal pregnant women compared with non-pregnant women; neprilysin (NEP) levels were not changed. In SGA pregnancies, ACE and ACE2 levels were higher in early-mid pregnancy compared with normal pregnant women. In women with PE, plasma ACE, ACE2, NEP, and Ang-(1-7) levels and ACE2 activity were lower than levels in normal pregnant women. Conclusion: The higher plasma ACE2 levels and activity in pregnancy could be driving the higher Ang-(1-7) levels. The early gestation increases in ACE and ACE2 levels in SGA pregnancies highlights the possibility that these enzymes could be used as potential early biomarkers of poor fetal growth. In women with PE, the reduced ACE2 and NEP levels at term, could be contributing to the reduction in Ang-(1-7) levels. These findings suggest that dysfunctional relationships between two key enzymes in the circulating RAS are involved in the pathogenesis of PE and SGA. Since soluble ACE2 can prevent binding of the novel coronavirus, SARS-CoV-2, to membrane bound ACE2, the interplay between ACE2 and the coronavirus and its impact in pregnancy requires further investigation.

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Section: Study Populationmentioning

confidence: 99%

Angiotensin Converting Enzyme 2 (ACE2) in Pregnancy: Preeclampsia and Small for Gestational Age

et al. 2020

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“…Some 30 years later, randomized controlled trials showed that they were right, and folate supplementation was effective at protecting against neural tube defects ( 143 ). In addition to our extensive evidence from animal studies that support a benefit for the fetus of increasing tissue creatine content above normal levels, we have recently shown that women who deliver small babies have lower urine creatine concentrations ( 144 ), suggesting that inadequate creatine availability may impact fetal growth. We are currently testing this hypothesis in a large prospective cohort of low risk pregnant women.…”

Section: Current Treatment Strategies For Intrapartum Asphyxiamentioning

confidence: 91%

Understanding the Full Spectrum of Organ Injury Following Intrapartum Asphyxia

et al. 2017

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Birth asphyxia is a significant global health problem, responsible for ~1.2 million neonatal deaths each year worldwide. Those who survive often suffer from a range of health issues including brain damage—manifesting as cerebral palsy (CP)—respiratory insufficiency, cardiovascular collapse, and renal dysfunction, to name a few. Although the majority of research is directed toward reducing the brain injury that results from intrapartum birth asphyxia, the multi-organ injury observed in surviving neonates is of equal importance. Despite the advent of hypothermia therapy for the treatment of hypoxic–ischemic encephalopathy (HIE), treatment options following asphyxia at birth remain limited, particularly in low-resource settings where the incidence of birth asphyxia is highest. Furthermore, although cooling of the neonate results in improved neurological outcomes for a small proportion of treated infants, it does not provide any benefit to the other organ systems affected by asphyxia at birth. The aim of this review is to summarize the current knowledge of the multi-organ effects of intrapartum asphyxia, with particular reference to the findings from our laboratory using the precocial spiny mouse to model birth asphyxia. Furthermore, we reviewed the current treatments available for neonates who have undergone intrapartum asphyxia, and highlight the emergence of maternal dietary creatine supplementation as a preventative therapy, which has been shown to provide multi-organ protection from birth asphyxia-induced injury in our preclinical studies. This cheap and effective nutritional supplement may be the key to reducing birth asphyxia-induced death and disability, particularly in low-resource settings where current treatments are unavailable.

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“…[130][131][132] Studies in larger animal models with more prolonged hypoxic injury are ongoing. Low maternal serum and urine creatine levels have been associated with poor fetal growth, 133 but no randomized trials of maternal dietary creatine supplementation in humans have been undertaken. 134 N-acetylcysteine N-acetylcysteine scavenges reactive oxygen species and forms the antioxidant glutathione, thereby counteracting oxidative stress and increasing the bioavailability of nitric oxide.…”

Section: Creatinementioning

confidence: 99%

The role of aspirin, heparin, and other interventions in the prevention and treatment of fetal growth restriction

Groom

David

2018

American Journal of Obstetrics and Gynecology

131

101

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Fetal growth restriction and related placental pathologies such as preeclampsia, stillbirth, and placental abruption are believed to arise in early pregnancy when inadequate remodeling of the maternal spiral arteries leads to persistent high-resistance and low-flow uteroplacental circulation. The consequent placental ischaemia, reperfusion injury, and oxidative stress are associated with an imbalance in angiogenic/antiangiogenic factors. Many interventions have centered on the prevention and/or treatment of preeclampsia with results pertaining to fetal growth restriction and small-for-gestational-age pregnancy often included as secondary outcomes because of the common pathophysiology. This renders the study findings less reliable for determining clinical significance. For the prevention of fetal growth restriction, a recent large-study level meta-analysis and individual patient data meta-analysis confirm that aspirin modestly reduces small-for-gestational-age pregnancy in women at high risk (relative risk, 0.90, 95% confidence interval, 0.81-1.00) and that a dose of ≥100 mg should be recommended and to start at or before 16 weeks of gestation. These findings support national clinical practice guidelines. In vitro and in vivo studies suggest that low-molecular-weight heparin may prevent fetal growth restriction; however, evidence from randomized control trials is inconsistent. A meta-analysis of multicenter trial data does not demonstrate any positive preventative effect of low-molecular-weight heparin on a primary composite outcome of placenta-mediated complications including fetal growth restriction (18% vs 18%; absolute risk difference, 0.6%; 95% confidence interval, 10.4-9.2); use of low-molecular-weight heparin for the prevention of fetal growth restriction should remain in the research setting. There are even fewer treatment options once fetal growth restriction is diagnosed. At present the only management option if the risk of hypoxia, acidosis, and intrauterine death is high is iatrogenic preterm birth, with the use of peripartum maternal administration of magnesium sulphate for neuroprotection and corticosteroids for fetal lung maturity, to prevent adverse neonatal outcomes. The pipeline of potential therapies use different strategies, many aiming to increase fetal growth by improving poor placentation and uterine blood flow. Phosphodiesterase type 5 inhibitors that potentiate nitric oxide availability such as sildenafil citrate have been extensively researched both in preclinical and clinical studies; results from the Sildenafil Therapy In Dismal Prognosis Early-Onset Intrauterine Growth Restriction consortium of randomized control clinical trials are keenly awaited. Targeting the uteroplacental circulation with novel therapeutics is another approach, the most advanced being maternal vascular endothelial growth factor gene therapy, which is being translated into the clinic via the doEs Vascular endothelial growth factor gene therapy safEly impRove outcome in seveRe Early-onset fetal growth reSTriction co...

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Maternal creatine in pregnancy: a retrospective cohort study

Abstract: Maternal creatine is altered by pregnancy; fetal growth measures are associated with maternal creatine concentrations.

Cited by 24 publications

References 23 publications

Angiotensin Converting Enzyme 2 (ACE2) in Pregnancy: Preeclampsia and Small for Gestational Age

Angiotensin Converting Enzyme 2 (ACE2) in Pregnancy: Preeclampsia and Small for Gestational Age

Understanding the Full Spectrum of Organ Injury Following Intrapartum Asphyxia

The role of aspirin, heparin, and other interventions in the prevention and treatment of fetal growth restriction

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