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.

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.

The objective of this study was to determine the duration between onset of symptoms of early symptomatic syphilis and diagnosis among men who have sex with men (MSM). A review of cases of primary and secondary syphilis among MSM presented to the Melbourne Sexual Health Centre between January 2003 and August 2007. The mean age of the 123 MSM included was 37 years. Fifty-two percent ( n = 64) presented with primary syphilis and 48% ( n = 59) with secondary syphilis. Twenty-five percent were HIV-positive. The median rapid plasma reagin titre was 1:32. Of the 34 men referred by general practitioners, referring practitioners did not consider the diagnosis of syphilis in 10 cases of primary syphilis and 20 cases of secondary syphilis. For primary and secondary cases combined, the median duration between onset of symptoms and diagnosis, and onset of symptoms and treatment, was 15 (3–56) and 20 (1–57) days, respectively. The respective durations for secondary syphilis (17 and 23 days) was longer than for primary syphilis (13 and 15 days) ( P < 0.05). The mean number of sex partners reported for the prior three months was 8.8 (range 1–15). If early detection and treatment of syphilis is to be optimized in order to improve syphilis control, greater awareness of its symptoms and signs of syphilis need to be promoted among both health-care providers and affected communities.

Maternal vitamin D deficiency has been associated with adverse neonatal outcomes, however, existing results are inconsistent. Current data focus on total 25-hydroxyvitamin D (25(OH)D) as the common measure of vitamin D status, while additional measures including vitamin D-binding protein (VDBP) and free and bioavailable metabolites have not been explored in relation to neonatal outcomes. We examined whether VDBP and total, free, and bioavailable vitamin D metabolites in early pregnancy are associated with subsequent neonatal outcomes. In this retrospective analysis of 304 women in early pregnancy (<20 weeks gestation), demographic and anthropometric data were collected and total 25(OH)D (chemiluminescent assay), VDBP (polyclonal enzyme-linked immunosorbent assay (ELISA)) and albumin (automated colorimetry) were measured in bio-banked samples. Free and bioavailable 25(OH)D were calculated using validated formulae. Neonatal outcomes were derived from a medical record database. Higher maternal total and free 25(OH)D concentrations were associated with higher neonatal birthweight (β = 5.05, p = 0.002 and β = 18.06, p = 0.02, respectively), including after adjustment for maternal covariates including age, body mass index (BMI) and ethnicity (all p ≤ 0.04). Higher total 25(OH)D and VDBP concentrations were associated with a lower likelihood of neonatal jaundice (odds ratio [OR] [95%CI] = 0.997 [0.994, 1.000], p = 0.04 and 0.98 [0.96, 0.99], p = 0.03, respectively), but these were attenuated after adjustment for the above maternal covariates (both p = 0.09). Our findings suggest a novel association between free 25(OH)D and neonatal birthweight. Total 25(OH)D concentrations were also associated with birthweight, and both total 25(OH)D and VDBP were associated with jaundice, but the latter were not significant after adjustment. These results suggest a potential link between these metabolites and neonatal outcomes; however, further large-scale prospective studies are warranted.

Background: Vitamin D-binding protein (VDBP) has been implicated in several adverse pregnancy outcomes either directly or indirectly via influencing the concentrations of biologically active vitamin D metabolites. However, human studies exploring these metabolites in pregnancy remain sparse. Here, we examine whether VDBP and total, free, and bioavailable 25-hydroxyvitamin D (25(OH)D) metabolites in early pregnancy are associated with subsequent adverse pregnancy outcomes. Methods: We conducted a retrospective analysis of 304 pregnant women in early pregnancy (<20 weeks gestation). The demographic characteristics, anthropometric data, and total 25(OH)D were measured and plasma or serum samples were collected and bio-banked. Using these samples, we measured VDBP (polyclonal ELISA) and albumin (automated colorimetry), and calculated free and bioavailable 25(OH)D using validated formulae. Pregnancy outcomes were derived from scanned medical records. Regression models were used to analyse the relationships between vitamin D metabolites in early pregnancy and subsequent pregnancy outcomes (gestational diabetes mellitus (GDM), pre-eclampsia, preterm birth), with adjustment for predetermined clinically relevant maternal factors including age, body mass index (BMI), and ethnicity. Results: Lower VDBP concentrations were associated with higher glucose levels and a greater likelihood of developing GDM at 26–28 weeks gestation (odds ratio [OR] (95% CI) = 0.98 (0.97,0.99), p = 0.015). This finding remained significant after adjustment for maternal covariates including age, BMI, and ethnicity (β = −0.003, p = 0.03). Lower total, free and bioavailable 25(OH)D, but not VDBP, were associated with a shorter length of gestation, but only the relationship with total 25(OH)D remained significant after adjustment for the above maternal covariates (β = 0.02, p = 0.006). Conclusions: This is the first study to examine VDBP, and total, free and bioavailable 25(OH)D in relation to pregnancy outcomes in a well characterised multi-ethnic cohort of pregnant women. Our findings show that VDBP and total 25(OH)D are associated with GDM and length of gestation, respectively; however, further investigations using large-scale prospective studies are needed to confirm our findings.