Publications by authors named "Claire Roberts"

184 Publications

Bioengineered Microphysiological Placental Models: Towards Improving Understanding of Pregnancy Health and Disease.

Trends Biotechnol 2021 May 5. Epub 2021 May 5.

ARC Centre of Excellence in Convergent BioNano Science and Technology and Future Industries Institute, University of South Australia, Mawson Lakes Campus, Mawson Lakes, South Australia, 5095, Australia.

Driven by a lack of appropriate human placenta models, recent years have seen the introduction of bioengineered in vitro models to better understand placental health and disease. Thus far, the focus has been on the maternal-foetal barrier. However, there are many other physiologically and pathologically significant aspects of the placenta that would benefit from state-of-the-art bioengineered models, in particular, integrating advanced culture systems with contemporary biological concepts such as organoids. This critical review defines and discusses the key parameters required for the development of physiologically relevant in vitro models of the placenta. Specifically, it highlights the importance of cell type, mechanical forces, and culture microenvironment towards the use of physiologically relevant models to improve the understanding of human placental function and dysfunction.
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http://dx.doi.org/10.1016/j.tibtech.2021.03.009DOI Listing
May 2021

EBV miRNAs are potent effectors of tumor cell transcriptome remodeling in promoting immune escape.

PLoS Pathog 2021 May 6;17(5):e1009217. Epub 2021 May 6.

Department of Pathology, Tulane University School of Medicine, Tulane Cancer Center, New Orleans, Louisiana, United States of America.

The Epstein Barr virus (EBV) contributes to the tumor phenotype through a limited set of primarily non-coding viral RNAs, including 31 mature miRNAs. Here we investigated the impact of EBV miRNAs on remodeling the tumor cell transcriptome. Strikingly, EBV miRNAs displayed exceptionally abundant expression in primary EBV-associated Burkitt's Lymphomas (BLs) and Gastric Carcinomas (GCs). To investigate viral miRNA targeting, we used the high-resolution approach, CLASH in GC and BL cell models. Affinity constant calculations of targeting efficacies for CLASH hits showed that viral miRNAs bind their targets more effectively than their host counterparts, as did Kaposi's sarcoma-associated herpesvirus (KSHV) and murine gammaherpesvirus 68 (MHV68) miRNAs. Using public BL and GC RNA-seq datasets, we found that high EBV miRNA targeting efficacies translates to enhanced reduction of target expression. Pathway analysis of high efficacy EBV miRNA targets showed enrichment for innate and adaptive immune responses. Inhibition of the immune response by EBV miRNAs was functionally validated in vivo through the finding of inverse correlations between EBV miRNAs and immune cell infiltration and T-cell diversity in BL and GC datasets. Together, this study demonstrates that EBV miRNAs are potent effectors of the tumor transcriptome that play a role in suppressing host immune response.
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http://dx.doi.org/10.1371/journal.ppat.1009217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8130916PMC
May 2021

The interaction between metabolic syndrome and physical activity, and risk for gestational diabetes mellitus.

Acta Diabetol 2021 Jul 20;58(7):939-947. Epub 2021 Mar 20.

Robinson Research Institute, University of Adelaide, North Adelaide, 5005, Australia.

Aims: Metabolic syndrome (MetS) is a cluster of risk factors which increases risk of cardiometabolic diseases in the adult population and increases risk for pregnancy complications such as gestational diabetes mellitus (GDM). Epidemiological data indicate that moderate-to-high levels of physical activity reduces the risk for GDM. The study aims to determine whether the association between MetS and GDM is affected by physical activity.

Methods: We performed a prospective cohort study among 1373 pregnant nulliparous women in Adelaide, South Australia. At 9-16 weeks' gestation, demographic, lifestyle and self-reported frequencies of physical activity were obtained, and a non-fasting blood sample was taken for assessment of MetS, defined using the International Diabetes Federation criteria. GDM was diagnosed at 24-28 weeks' gestation using the World Health Organization classification.

Results: 1158 pregnant women were included: 107 (9%) women had MetS in early pregnancy, and 184 (16%) developed GDM. Having MetS increased the risk of developing GDM (37.4% vs. 13.7%, adjusted RR 2.5; 95% CI 1.7, 3.6). The interaction effect (RR; (95% CI) between MetS and physical activity was not significant (vigorous physical activity: 2.60; 0.46, 14.71) for ≥ 4 times per week; less vigorous activity; 0.77; 0.15, 4.02 for ≥ 4 times per week; stair climbing ≥ once day (1.16; 0.54, 2.51), all compared to no physical activity).

Conclusions: Physical activity was not an effect modifier in the association between GDM and MetS. Information collected about the nature and extent of physical activity needs to be more detailed and granular to determine whether physical activity really has an effect.
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http://dx.doi.org/10.1007/s00592-021-01696-9DOI Listing
July 2021

Embedding changes in legislation for organ and tissue donation across England and Jersey.

Br J Nurs 2021 Mar;30(5):310-312

National Professional Development Specialist, Legislation Implementation, NHS Blood and Transplant.

([email protected]), , and , of NHS Blood and Transplant.
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http://dx.doi.org/10.12968/bjon.2021.30.5.310DOI Listing
March 2021

Effect of Selenium and Iodine on Oxidative Stress in the First Trimester Human Placenta Explants.

Nutrients 2021 Feb 28;13(3). Epub 2021 Feb 28.

School of Agriculture, Food and Wine, Waite Research Institute, and Robinson Research Institute, University of Adelaide, Adelaide, SA 5005, Australia.

Imbalanced maternal micronutrient status, poor placentation, and oxidative stress are associated with greater risk of pregnancy complications, which impact mother and offspring health. As selenium, iodine, and copper are essential micronutrients with key roles in antioxidant systems, this study investigated their potential protective effects on placenta against oxidative stress. First trimester human placenta explants were treated with different concentrations of selenium (sodium selenite), iodine (potassium iodide), their combination or copper (copper (II) sulfate). The concentrations represented deficient, physiological, or super physiological levels. Oxidative stress was induced by menadione or antimycin. Placenta explants were collected, fixed, processed, and embedded for laser ablation inductively coupled plasma-mass spectrometry (LA ICP-MS) element imaging or immunohistochemical labelling. LA ICP-MS showed that placenta could uptake selenium and copper from the media. Sodium selenite and potassium iodide reduced DNA damage and apoptosis ( < 0.05). Following oxidative stress induction, a higher concentration of sodium selenite (1.6 µM) was needed to reduce DNA damage and apoptosis while both concentrations of potassium iodide (0.5 and 1 µM) were protective ( < 0.05). A high concentration of copper (40 µM) increased apoptosis and DNA damage but this effect was no longer significant after induction of oxidative stress. Micronutrients supplementation can increase their content within the placenta and an optimal maternal micronutrient level is essential for placenta health.
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http://dx.doi.org/10.3390/nu13030800DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997475PMC
February 2021

Influence of living in a multicat household on health and behaviour in a cohort of cats from the United Kingdom.

Vet Rec 2020 07;187(1):27

Bristol Veterinary School, University of Bristol, Bristol, UK.

Background: Living in a multicat household has been implicated as a risk factor for various feline issues, but evidence is often anecdotal or based on retrospective studies.

Methods: Data from the Bristol Cats Study, a UK longitudinal study of pet cats, were used. Cats were included if they had remained in either a single cat or multicat household between questionnaires 1 (two months old to four months old) and 5 (two-and-a-half years old). Univariable and multivariable logistic regression models were used to analyse associations between single cat/multicat households and measures of health and behaviour (overweight/obesity, abscesses/cat bites, negative interactions with owner and periuria). Multicat households were also subcategorised according to whether owners had reported agonistic behaviour between household cats.

Results: There was no evidence of association between household type and the likelihood of obesity, abscesses or periuria. The likelihood of negative interactions with the owner (eg, growling or hissing) was influenced by the cats' relationships; cats in non-agonistic multicat households had decreased odds of negative interactions with the owner, compared with single and agonistic multicat households (P<0.001).

Conclusion: Living in a multicat households per se was not a risk factor for the health and behaviour issues investigated, but the intercat relationship is important.
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http://dx.doi.org/10.1136/vr.104801DOI Listing
July 2020

Is the US failing women?

EClinicalMedicine 2021 Jan 6;31:100701. Epub 2021 Jan 6.

Flinders Health and Medical Research Institute, Flinders University, Bedford Park, South Australia, Australia 5042.

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http://dx.doi.org/10.1016/j.eclinm.2020.100701DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7806801PMC
January 2021

A sexually dimorphic murine model of IUGR induced by embryo transfer.

Reproduction 2021 Feb;161(2):135-144

Robinson Research Institute, University of Adelaide, Adelaide, Australia.

Animal models are needed to develop interventions to prevent or treat intrauterine growth restriction (IUGR). Foetal growth rates and effects of in utero exposures differ between sexes, but little is known about sex-specific effects of increasing litter size. We established a murine IUGR model using pregnancies generated by multiple embryo transfers, and evaluated sex-specific responses to increasing litter size. CBAF1 embryos were collected at gestation day 0.5 (GD0.5) and 6, 8, 10 or 12 embryos were transferred into each uterine horn of pseudopregnant female CD1 mice (n = 32). Foetal and placental outcomes were measured at GD18.5. In the main experiment, foetuses were genotyped (Sry) for analysis of sex-specific outcomes. The number of implantation sites (P = 0.033) and litter size (number of foetuses, P = 0.008) correlated positively with the number of embryos transferred, while placental weight correlated negatively with litter size (both P < 0.01). The relationship between viable litter size and foetal weight differed between sexes (interaction P = 0.002), such that foetal weights of males (P = 0.002), but not females (P = 0.233), correlated negatively with litter size. Placental weight decreased with increasing litter size (P < 0.001) and was lower in females than males (P = 0.020). Our results suggest that male foetuses grow as fast as permitted by nutrient supply, whereas the female maintains placental reserve capacity. This strategy reflecting sex-specific gene expression is likely to place the male foetus at greater risk of death in the event of a 'second hit'.
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http://dx.doi.org/10.1530/REP-20-0209DOI Listing
February 2021

The effect of zinc on human trophoblast proliferation and oxidative stress.

J Nutr Biochem 2021 04 31;90:108574. Epub 2020 Dec 31.

Robinson Research Institute, University of Adelaide, Adelaide, SA, Australia; School of Agriculture, Food and Wine, Waite Research Institute, University of Adelaide, Adelaide, SA, Australia. Electronic address:

Adequate Zinc (Zn) intake is required to prevent multiple teratogenic effects however deviations from adequate Zn intake, including high maternal Zn status, have been linked to increased incidence of pregnancy complications, including those associated with inadequate placentation. Using placental trophoblast HTR8/SVneo cells and first trimester human placental explants (n = 12), we assessed the effects of varying Zn concentrations on trophoblast proliferation, viability, apoptosis and oxidative stress. Compared to physiologically normal Zn levels (20 µM), HTR-8/SVneo cell proliferation index was significantly lower in the presence of physiologically elevated (40 µM; P = .020) and supra-physiological (80 µM; P = .007) Zn. The latter was also associated with reduced proliferation (P = .004) and viability (P < .0001) in cultured placental explants, but not apoptosis. Reactive oxygen species production in HTR8/SVneo cultures was significantly higher in the presence of 80 µM Zn compared to all physiologically relevant levels. Oxidative stress, induced by an oxidizing agent menadione, was further exacerbated by high (80 µM) Zn. Zn did not affect lipid peroxidation in either HTR8/SVneo cells or placental explants or antioxidant defense mechanisms that included glutathione reductase and superoxide dismutase. Further study should focus on elucidating mechanisms behind impaired trophoblast proliferation and increased oxidative stress as a result of elevated Zn levels.
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http://dx.doi.org/10.1016/j.jnutbio.2020.108574DOI Listing
April 2021

Safety of maternal pertussis vaccination on pregnancy and birth outcomes: A prospective cohort study.

Vaccine 2021 01 19;39(2):324-331. Epub 2020 Dec 19.

Vaccinology and Immunology Research Trials Unit, Women's and Children's Hospital, Adelaide, South Australia, Australia; Robinson Research Institute, Adelaide Medical School, University of Adelaide, Adelaide, SA, Australia. Electronic address:

Objective: To evaluate the safety of maternal pertussis vaccination on pregnancy and birth outcomes.

Methods: The study population comprised 1272 healthy nulliparous pregnant women who participated in Screening Tests to identify poor Outcomes in Pregnancy (STOP) study at two obstetric hospitals in South Australia between 2015 and 2018. Participants were followed prospectively, with vaccination (confirmed by medical records), extensive amounts of pregnancy and birth outcome data collected by research midwives. Adjusted relative risks (aRRs) and hazard ratios (aHRs) were estimated accounting for time-varying vaccine exposure and the temporal nature of each outcome.

Results: Of the 1272 women included in this study, 80.1% (n = 1019) received maternal pertussis vaccination. Vaccinated women had an average 0.22 weeks (95% CI 0.001, 0.44) longer gestation at delivery compared to unvaccinated women. Maternal pertussis vaccination was not associated with chorioamnionitis (aRR 0.71, 95% CI 0.27,1.82), gestational hypertension (aHR 1.24, 95% CI, 0.66, 2.30), preeclampsia (aHR 0.75, 95% CI 0.47, 1.18) nor preterm birth (aHR 0.99, 95% CI 0.47, 2.07). Neither risk of low birth weight (aHR 0.72, 95% CI 0.41, 1.27) nor small for gestational age infants (aHR 0.67,95% CI 0.29, 1.55) were increased following maternal pertussis vaccination. No associations between pertussis vaccination during pregnancy and adverse birth outcomes including admission to the neonatal care unit, low Apgar scores, and mechanical ventilation were observed. Results were not materially changed after adjustment for maternal influenza vaccination.

Conclusion: Our study provides reassuring evidence of the safety of maternal pertussis vaccination with no increased risk of adverse pregnancy and birth outcomes. These findings support recommendations for pertussis vaccination during pregnancy to prevent morbidity and mortality associated with early-infant pertussis disease.
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http://dx.doi.org/10.1016/j.vaccine.2020.11.052DOI Listing
January 2021

Cardiovascular risk factors in women with previous gestational diabetes mellitus: A systematic review and meta-analysis.

Rev Endocr Metab Disord 2020 Oct 27. Epub 2020 Oct 27.

Adelaide Medical School and The Robinson Research Institute, The University of Adelaide, Adelaide, SA, Australia.

This systematic review and meta-analysis aimed to synthesize evidence on conventional cardiovascular disease (CVD) risk factors among women with previous Gestational Diabetes Mellitus (GDM). The review protocol is registered with PROSPERO (CRD42019118149). PubMed, CINAHL, SCOPUS, and EMBASE databases were searched. Studies reporting on CVD risk factors in women with previous GDM compared to women without previous GDM were selected. A total of 139 studies were eligible, of which 93 were included in the meta-analysis. Women with previous GDM have significantly higher systolic blood pressure (2.47 mmHg 95% CI 1.74 to 3.40, n = 48, 50,118 participants) diastolic blood pressure (1.89 mmHg 95% CI 1.32 to 2.46, n = 48, 49,495 participants), BMI (1.54 kg/m 95% CI 1.32 to 2.46, n = 78, 255,308 participants), total cholesterol (0.26 SMD 95% CI 0.15 to 0.37, n = 48, 38,561 participants), LDL cholesterol (0.19 SMD 95% CI 0.08 to 0.30, n = 44, 16,980 participants), triglycerides (0.56 SMD 95% CI 0.42 to 0.70, n = 46, 13,175 participants), glucose (0.69 SMD 95% CI 0.56 to 0.81, n = 55, 127,900 participants), insulin (0.41 SMD 95% CI 0.23 to 0.59, n = 32, 8881 participants) and significantly lower HDL cholesterol (-0.28 SMD 95% CI -0.39 to -0.16, n = 56, 35,882 participants), compared to women without previous GDM. The increased blood pressure, total cholesterol, triglycerides and glucose are seen as early as <1 year post-partum.Women with previous GDM have a higher risk of CVD based on significant increases in conventional risk factors. Some risk factors are seen as early as <1 year post-partum. Women with GDM may benefit from early screening to identify modifiable CVD risk factors.
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http://dx.doi.org/10.1007/s11154-020-09587-0DOI Listing
October 2020

Hypertensive disorders of pregnancy and later cardiovascular disease risk in mothers and children.

J Dev Orig Health Dis 2020 Oct 15:1-6. Epub 2020 Oct 15.

Robinson Research Institute, University of Adelaide, Adelaide, South Australia, Australia.

Preeclampsia (PE) and gestational hypertension (GH) are pregnancy-specific diseases that occur in around 10% of pregnancies worldwide. Increasing evidence suggests that women whose pregnancies were complicated by PE or GH, and their offspring, are at increased risk of cardiovascular disease (CVD) later in life. We hypothesised that PE and GH would associate with CVD risk factors 8-10 years after the first pregnancy in the mother and child and that differences in cardiovascular risk profile would be seen between 8- and 10-year-old male and female children. This is a follow-up study of the Adelaide SCOPE pregnancy cohort where 1164 nulliparous women and their babies were recruited between 2005 and 2008. Haemodynamic function was assessed using non-invasive USCOMBP+ and USCOM1A devices. Microvascular function was assessed by post-occlusive reactive hyperaemia. Of the 273 mother-child pairs followed up, 38 women had PE and 20 had GH during pregnancy. Augmentation index (Aix) and suprasystolic pulse pressure (ssPP) were increased, whereas measures of microvascular function were decreased in children who were born to PE compared to uncomplicated pregnancies. Female children had decreased Aix and ssPP compared to male children after in utero exposure to PE. Women who developed GH during their first pregnancy had increased systolic, diastolic and mean arterial pressures compared to women who had uncomplicated pregnancy. Our data suggest that GH is associated with increased cardiovascular risk in women 8-10 years after first pregnancy and PE is associated with increased offspring risk at 8-10 years of age, highlighting differences between these two hypertensive disorders of pregnancy.
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http://dx.doi.org/10.1017/S2040174420000896DOI Listing
October 2020

Maternal diet and offspring telomere length: a systematic review.

Nutr Rev 2021 01;79(2):148-159

Robinson Research Institute, University of Adelaide, Adelaide, South Australia, Australia.

Context: Many studies assert a negative influence of inappropriate maternal diet and nutritional status during pregnancy on offspring, not only in utero but throughout life, because of the role in the programing of noncommunicable diseases. Telomere length is a biomarker of aging, and shorter telomeres are associated with chronic disease later in life. Maternal nutrition and nutritional status may be an important determinant of offspring telomere length.

Objective: A systematic review was conducted to determine the effect of maternal nutrition and nutritional status in pregnancy on offspring telomere length.

Data Sources: This systematic review was conducted according to PRISMA guidelines. Database searches of PubMed, CINAHL, Scopus, Medline, and Web of Science were performed.

Study Selection: Included studies assessed the association between maternal nutrition (dietary intake and nutritional status) during pregnancy and offspring telomere length measured in cord blood, serum, plasma, and peripheral blood mononuclear cells.

Data Extraction: Three authors screened and determined the quality of the articles; disagreements were resolved by a fourth author. All authors compared the compiled data.

Results: Seven studies were extracted and evaluated. Studies comprised a double-blind placebo-controlled trial (n = 1), prospective cohort studies (n = 5), and a cross-sectional study (n = 1). Higher circulating maternal folate and 25-hydroxyvitamin D3 concentrations, along with higher maternal dietary caffeine intakes, were associated with longer offspring telomere length, whereas higher dietary intake of carbohydrate, folate, n-3 polyunsaturated fatty acids, vitamin C, or sodium was not.

Conclusion: The limited but suggestive evidence highlights the need for further research to be conducted in this area, particularly longitudinal studies involving larger cohorts of pregnant women.

Systematic Review Registration: PROSPERO registration no. CRD42019136506.
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http://dx.doi.org/10.1093/nutrit/nuaa097DOI Listing
January 2021

Safety and protective effects of maternal influenza vaccination on pregnancy and birth outcomes: A prospective cohort study.

EClinicalMedicine 2020 Sep 9;26:100522. Epub 2020 Sep 9.

Vaccinology and Immunology Research Trials Unit, Women's and Children's Health Network, Adelaide, South Australia, Australia.

Background: Our study aimed to assess the safety and protective effect of maternal influenza vaccination on pregnancy and birth outcomes.

Methods: The study population comprised 1253 healthy nulliparous pregnant women in South Australia between 2015 and 2018. Participants were followed prospectively, with vaccination status (confirmed by medical records), pregnancy, and birth outcome data collected by midwives. Adjusted relative risks (aRRs) and adjusted hazard ratios (aHRs) were estimated accounting for time-varying vaccine exposure and temporal nature of each outcome.

Findings: Maternal influenza vaccination (48%, 603 of 1253) reduced the risk for pre-delivery hospitalisation with influenza like illness (aHR 0•61; 95% CI 0•39, 0•97). Maternal influenza vaccination was not associated with spontaneous abortion (aHR 0•42, 95% CI 0•12, 1•45), chorioamnionitis (aRR 0•78, 95% CI, 0•32, 1•88), gestational hypertension (aHR 0•78, 95% CI 0•47, 1•29), pre-eclampsia (aHR 0.84, 95% CI 0•54, 1•27), gestational diabetes (aHR 1•16, 95% CI 0•82, 1•66) nor preterm birth (aHR 0•94, 95% CI 0•59, 1•49). No associations between antenatal influenza vaccination and congenital anomalies, admission to the neonatal care unit, low Apgar scores, and mechanical ventilation were observed. Results were not materially changed after adjustment for pertussis vaccination. We observed a protective effect of maternal influenza vaccination on low birth weight (aHR 0•46, 95% CI 0•23, 0•94) and a marginal protective effect on small for gestational age births (aHR 0•65, 95% CI 0•40, 1•04) during periods of high influenza activity.

Interpretation: These results support the safety of maternal influenza vaccination and suggest a protective effect in reducing the rates of low birthweight and small for gestational age births.

Funding: There was no funding for this study.
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http://dx.doi.org/10.1016/j.eclinm.2020.100522DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7490992PMC
September 2020

Association between metabolic syndrome and gestational diabetes mellitus in women and their children: a systematic review and meta-analysis.

Endocrine 2021 Feb 15;71(2):310-320. Epub 2020 Sep 15.

Adelaide Medical School and Robinson Research Institute, The University of Adelaide, Adelaide, SA, 5005, Australia.

Purpose: The primary aim of this systematic review and meta-analysis was to determine the association between gestational diabetes mellitus (GDM) and metabolic syndrome (MetS) in women and children. Our secondary aim was to assess the development of MetS with respect to the elapsed time postpartum at which MetS was diagnosed.

Methods: This review is registered with PROSPERO (CRD42020173319). PubMed, CINHAL, SCOPUS, and EMBASE databases were searched. Studies reporting on the rate of MetS in pregnant women with GDM, the rate of MetS in women with a history of GDM, and the rate of MetS in offspring exposed to GDM in utero compared to healthy controls were selected.

Results: We identified 588 articles from the literature search. Fifty-one studies were included in the review and of those 35 were included in the meta-analysis. Quantitative summary measures showed that women with a history of GDM had an increased risk of developing MetS compared to those without a history of GDM (RR 2.36, 95% CI 1.77-3.14, 29 studies, 13,390 participants; heterogeneity: χ p < 0.00001; I = 93%). Offspring exposed to GDM in utero have an increased risk of developing MetS compared to those not exposed to GDM in utero. (RR 2.07, 95% CI 1.26-3.42, three studies, 4,421 participants; heterogeneity: χ p = 0.33; I = 12%). Women diagnosed with GDM have an increased risk of developing MetS during pregnancy (RR 20.51, 95% CI 5.04-83.55; three studies, 406 participants; heterogeneity: χ p = 0.96; I = 0%). Subgroup analysis revealed that MetS is diagnosed as early as <1 year postpartum in women with a history of GDM.

Conclusions/interpretation: Women with GDM have an increased risk of developing MetS during pregnancy. Women with a history of GDM and offspring exposed to GDM in utero have higher risks of developing MetS compared to those with no history of GDM. Metabolic syndrome in women with a history of GDM is seen as early as <1 year postpartum.
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http://dx.doi.org/10.1007/s12020-020-02492-1DOI Listing
February 2021

Evaluation of staff training on legislation change in organ and tissue donation.

Br J Nurs 2020 Sep;29(16):974-977

Professional Development Specialist, Legislation Implementation, NHS Blood and Transplant.

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http://dx.doi.org/10.12968/bjon.2020.29.16.974DOI Listing
September 2020

The metabolic syndrome in pregnancy and its association with child telomere length.

Diabetologia 2020 10 29;63(10):2140-2149. Epub 2020 Jul 29.

Robinson Research Institute, University of Adelaide, North Adelaide, SA, 5005, Australia.

Aims/hypothesis: The aim of this study was to determine whether presence of the metabolic syndrome in pregnancy associates with child telomere length or child anthropometry (weight, BMI) and BP, measured at 10 years of age.

Methods: The Screening for Pregnancy Endpoints study (SCOPE) was a multicentre, international prospective cohort of nulliparous pregnant women recruited from Australia, New Zealand, Ireland and the UK (N = 5628). The current analysis is a 10 year follow-up of SCOPE pregnant women and their children, from the Australian cohort. Clinical data collected at 14-16 weeks' gestation during the SCOPE study were used to diagnose the metabolic syndrome using IDF criteria. Telomere length, a biomarker of ageing, was assessed by quantitative PCR from children's saliva collected at 10 years of age.

Results: In women who completed follow-up (n = 255), 20% had the metabolic syndrome in pregnancy. After adjusting for a range of confounders, children of mothers who had the metabolic syndrome in pregnancy had 14% shorter telomeres than children of mothers without the metabolic syndrome in pregnancy (mean difference -0.36 [95% CI -0.74, 0.01]). Height- and weight-for-age, and BMI z scores were similar in children of mothers who did and did not have the metabolic syndrome during pregnancy.

Conclusions/interpretation: Children of mothers who had the metabolic syndrome in pregnancy have shorter telomeres, a biomarker of accelerated ageing. These findings warrant further studies in larger cohorts of children, as well as investigations into whether telomere length measured in cord blood associates with telomere length in childhood.
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http://dx.doi.org/10.1007/s00125-020-05242-0DOI Listing
October 2020

Maternal folate, one-carbon metabolism and pregnancy outcomes.

Matern Child Nutr 2021 01 28;17(1):e13064. Epub 2020 Jul 28.

Robinson Research Institute, University of Adelaide, Adelaide, South Australia, Australia.

Single nucleotide polymorphisms and pre- and peri-conception folic acid (FA) supplementation and dietary data were used to identify one-carbon metabolic factors associated with pregnancy outcomes in 3196 nulliparous women. In 325 participants, we also measured circulating folate, vitamin B12 and homocysteine. Pregnancy outcomes included preeclampsia (PE), gestational hypertension (GHT), small for gestational age (SGA), spontaneous preterm birth (sPTB) and gestational diabetes mellitus (GDM). Study findings show that maternal genotype MTHFR A1298C(CC) was associated with increased risk for PE, whereas TCN2 C766G(GG) had a reduced risk for sPTB. Paternal MTHFR A1298C(CC) and MTHFD1 G1958A(AA) genotypes were associated with reduced risk for sPTB, whereas MTHFR C677T(CT) genotype had an increased risk for GHT. FA supplementation was associated with higher serum folate and vitamin B12 concentrations, reduced uterine artery resistance index and increased birth weight. Women who supplemented with <800 μg daily FA at 15-week gestation had a higher incidence of PE (10.3%) compared with women who did not supplement (6.1%) or who supplemented with ≥800 μg (5.4%) (P < .0001). Higher serum folate levels were found in women who later developed GDM compared with women with uncomplicated pregnancies (Mean ± SD: 37.6 ± 8 nmol L vs. 31.9 ± 11.2, P = .007). Fast food consumption was associated with increased risk for developing GDM, whereas low consumption of green leafy vegetables and fruit were independent risk factors for SGA and GDM and sPTB and SGA, respectively. In conclusion, maternal and paternal genotypes, together with maternal circulating folate and homocysteine concentrations, and pre- and early-pregnancy dietary factors, are independent risk factors for pregnancy complications.
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http://dx.doi.org/10.1111/mcn.13064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7729528PMC
January 2021

Effect of Iodine and Selenium on Proliferation, Viability, and Oxidative Stress in HTR-8/SVneo Placental Cells.

Biol Trace Elem Res 2021 Apr 5;199(4):1332-1344. Epub 2020 Jul 5.

School of Agriculture, Food and Wine, Waite Research Institute, University of Adelaide, Adelaide, SA, 5005, Australia.

Adequate maternal micronutrition is vital for placental formation, fetal growth, and development. Oxidative stress adversely affects placental development and function and an association between deficient placental development, oxidative stress, and micronutrient deficiency has been observed. Selenium and iodine are two essential micronutrients with antioxidant properties. Epidemiological studies have shown that poor micronutrient status in pregnant women is associated with a higher incidence of pregnancy complications. The aim of this study was to determine how selenium, iodine, and their combination impact oxidative stress in placental trophoblast cells. HTR8/SVneo extravillous trophoblasts were supplemented with a concentration range of organic and inorganic selenium, potassium iodide, or their combination for 24 h. Oxidative stress was then induced by treating cells with menadione or HO for 24 h. Cell viability and lipid peroxidation as the biomarker of oxidative stress were assessed at 48 h. Both menadione and HO reduced cell viability and increased lipid peroxidation (P < 0.05). Greater cell viability was found in selenium-supplemented cells when compared with vehicle treated cells (P < 0.05). Selenium and iodine supplementation separately or together were associated with lower lipid peroxidation compared with vehicle control (P < 0.05). Supplementation with the combination of selenium and iodine resulted in a greater reduction in lipid peroxidation compared with selenium or iodine alone (P < 0.05). Oxidative stress negatively impacts trophoblast cell survival and cellular integrity. Selenium and iodine protect placental trophoblasts against oxidative stress. Further research is warranted to investigate the molecular mechanisms by which selenium and iodine act in the human placenta.
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http://dx.doi.org/10.1007/s12011-020-02277-7DOI Listing
April 2021

Folic acid supplementation is associated with size at birth in the Screening for Pregnancy Endpoints (SCOPE) international prospective cohort study.

Early Hum Dev 2020 08 8;147:105058. Epub 2020 May 8.

Department of Obstetrics and Gynaecology, The University of Auckland, Auckland 1142, New Zealand.

Background: Small-for-gestational-age (SGA) is a significant cause of morbidity and mortality, and there are currently few preventive strategies.

Aim: The aim of this study was to investigate the relationship between maternal folic acid supplement (FAS) use pre-conception through to the second trimester, and small-for-gestational age (SGA) and birth size parameters.

Study Design: Women were recruited as part of the Screening for Pregnancy Endpoints (SCOPE) international prospective multi-centre cohort study: New Zealand, Australia, United Kingdom and Ireland. Information on FAS use pre-conception, during the first trimester and at 15 ± 1 weeks' gestation was collected via interview administered questionnaire. Participants were followed through to delivery. Pregnancy outcome data and birth measurements were collected within 72 h of birth. Multivariable regression analysis was used to investigate relationships between FAS and outcomes, adjusting for maternal sociodemographic and lifestyle factors.

Subjects: Nulliparous women with singleton pregnancies.

Outcome Measures: SGA (<10th customised birthweight centile).

Results: 5606 women were included. SGA prevalence was 11.3%. Pre-conception FAS was associated with a significantly lower risk of SGA: aOR = 0.82 (95% CI: 0.67-01.00 p = 0.047). Although the association between FAS at 15 weeks' gestation and SGA did not reach significance, FAS at 15 weeks was associated with a significantly higher customised birthweight centile (β 2.56 (95% CI: 0.87-4.26; p = 0.003). There was no significant effect of FAS on large-for-gestational-age births or head circumference.

Conclusions: In this international cohort, FAS was positively associated with fetal growth, without increasing risks associated with LGA. Further studies are required to confirm whether continuing FAS beyond the first trimester might lower the risk of SGA.
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http://dx.doi.org/10.1016/j.earlhumdev.2020.105058DOI Listing
August 2020

The Effect of Interactions between Folic Acid Supplementation and One Carbon Metabolism Gene Variants on Small-for-Gestational-Age Births in the Screening for Pregnancy Endpoints (SCOPE) Cohort Study.

Nutrients 2020 Jun 4;12(6). Epub 2020 Jun 4.

Department of Obstetrics and Gynaecology, The University of Auckland, Auckland 1010, New Zealand.

Small-for-gestational-age (SGA) is associated with significant perinatal morbidity and mortality. Our aim was to investigate gene-nutrient interactions between maternal one-carbon single nucleotide polymorphisms (SNPs) and folic acid supplement (FAS) use, and their association with SGA. Nulliparous New Zealand women with singleton pregnancy were recruited as part of the Screening for Pregnancy Endpoints prospective cohort study. Data on FAS use was collected via face-to-face interview at 15 weeks' gestation; participants were followed prospectively and birth outcome data collected within 72 h of delivery. Participants were genotyped for MTHFR 677, MTHFR 1298, MTHFD1 1958, MTR 2756, MTRR 66 and TCN2 776 SNPs. Genotype data for at least one SNP was available for 1873 (93%) of eligible participants. Analysis showed a significant SNP-FAS interaction for MTHFR 1298 ( = 0.020), MTHFR 677 ( = 0.019) and TCN2 776 ( = 0.017) in relation to SGA: MTHFR 1298 CC variant non-FAS users had an increased likelihood [Odds Ratio (OR) = 2.91 (95% Confidence Interval (CI) = 1.52, 5.60] compared with wild-type (MTHFR 1298 AA) FAS users. MTHFR 677 variant allele carrier (MTHFR 677 CT + MTHFR 677 TT) non-FAS users had an increased likelihood [OR = 1.87 (95% CI = 1.21, 2.88)] compared to wild-type (MTHFR 677 CC) FAS users. TCN2 776 variant (TCN2 776 GG) non-FAS users had an increased likelihood [OR = 2.16 (95% CI = 1.26, 3.71)] compared with wild type homozygote + heterozygote (TCN2 776 CC + TCN2 776 CG) FAS users. No significant interactions were observed for MTHFD1 1958, MTR 2756 or MTRR 66 ( > 0.05). We observed an overall pattern of FAS attenuating differences in the likelihood of SGA seen between genotype groups in FAS non-users. Future research should focus on how intake of other one-carbon nutrients might mediate these gene-nutrient interactions.
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http://dx.doi.org/10.3390/nu12061677DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352423PMC
June 2020

The deleterious effects of cannabis during pregnancy on neonatal outcomes.

Med J Aust 2020 06 25;212(11):519-524. Epub 2020 May 25.

Robinson Research Institute, University of Adelaide, Adelaide, SA.

Objectives: To evaluate whether cannabis use during pregnancy is associated with adverse neonatal outcomes that are independent of cigarette smoking.

Design: Prospective cohort study.

Setting: Adelaide (Australia), Auckland (New Zealand), Cork (Ireland), and Leeds, London and Manchester (United Kingdom).

Participants: 5610 pregnant nulliparous women with low risk pregnancies recruited for the Screening for Pregnancy Endpoints (SCOPE) study, November 2004 - February 2011. At 14-16 weeks of pregnancy, women were grouped by self-reported cannabis use.

Main Outcome Measures: Infant birthweight, head circumference, birth length, gestational age, and severe neonatal morbidity or mortality.

Results: 314 women (5.6%) reported using cannabis in the 3 months before or during their pregnancy; 97 (31%) stopped using it before and 157 (50%) during the first 15 weeks of pregnancy, while 60 (19%) were still using cannabis at 15 weeks. Compared with babies of mother who had never used cannabis, infants of those who still used it at 15 weeks had lower mean values for birthweight (adjusted mean difference [aMD], -127 g; 95% CI, -238 to -17 g), head circumference (aMD, -0.5 cm; 95% CI, -0.8 to -0.1 cm), birth length (aMD, -0.8 cm; 95% CI, -1.4 to -0.2 cm), and gestational age at birth (aMD, -8.1 days; 95% CI, -12.1 to -4.0 days). The differences for all outcomes except gestational age were greater for women who used cannabis more than once a week than for those who used it less frequently.

Conclusions: Continuing to use cannabis during pregnancy is an independent risk factor for poorer neonatal outcomes.
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http://dx.doi.org/10.5694/mja2.50624DOI Listing
June 2020

Sex- and growth-specific characteristics of small for gestational age infants: a prospective cohort study.

Biol Sex Differ 2020 05 5;11(1):25. Epub 2020 May 5.

The Robinson Research Institute and Adelaide Medical School, University of Adelaide, Adelaide, Australia.

Background: Asymmetric fetal growth and male sex are both associated with adverse neonatal outcome. However, less is known about the influence of asymmetric growth and fetal sex within SGA neonates, a group of infants already at increased risk for adverse neonatal outcomes. The aim of the present study was to provide insight into variance in risk factors for SGA in a fetal sex- and growth symmetry-specific way.

Methods: For this prospective, multicenter cohort study, data from the Screening for Pregnancy Endpoints (SCOPE) study were used with 5628 nulliparous participants, of which 633 (11.3%) pregnancies were complicated with SGA and 3376 (60.0%) women had uncomplicated pregnancies. Association between risk factors for SGA, SGA subgroups, and uncomplicated pregnancies were assessed with multivariable analyses.

Results: Prevalence of asymmetric growth varied from 45.8% of SGA infants to 5.5% of infants with a customized birthweight > 90th percentile (p < 0.001). Significantly more SGA males had asymmetric growth compared to SGA female infants (51.2% vs 40.4%, p = 0.009). Maternal pre-pregnancy diet and BMI < 20 and ≥ 30 were significantly associated with symmetric SGA but not with asymmetric SGA. Asymmetric SGA infants had not only lower customized birthweight percentile (4.4 (SD 2.8) vs 5.0 (SD 3.0), p < 0.001), but also lower rates of stillbirth (p = 0.041) and less often Apgar scores < 7 (p = 0.060).

Conclusions: Among SGA infants, low customized birthweight percentiles and male sex are associated with asymmetric growth. Only symmetric SGA is significantly associated with maternal risk factors in early pregnancy. There is a substantial variance in risk factors and neonatal outcomes for SGA based on growth symmetry, implying a different pathogenesis.

Trial Registration: ACTRN12607000551493.
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http://dx.doi.org/10.1186/s13293-020-00300-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7201715PMC
May 2020

Author response: cardiovascular risk factors in offspring exposed to gestational diabetes mellitus in utero: systematic review and meta-analysis.

J Dev Orig Health Dis 2020 06 13;11(3):244-245. Epub 2020 Apr 13.

Adelaide Medical School, The Robinson Research Institute, The University of Adelaide, Adelaide5005, Australia.

This commentary is an author response to Lu and Wang, regarding the manuscript entitled 'Cardiovascular risk factors in offspring exposed to gestational diabetes mellitus in utero: Systematic review and meta-analysis'. We address their concern regarding duplication of studies in the meta-analysis and the quality of included studies.
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http://dx.doi.org/10.1017/S2040174420000185DOI Listing
June 2020

Animal Models of Preeclampsia: Causes, Consequences, and Interventions.

Hypertension 2020 06 6;75(6):1363-1381. Epub 2020 Apr 6.

From the Adelaide Medical School and Robinson Research Institute, The University of Adelaide, Australia.

Preeclampsia is a common pregnancy complication, affecting 2% to 8% of pregnancies worldwide, and is an important cause of both maternal and fetal morbidity and mortality. Importantly, although aspirin and calcium are able to prevent preeclampsia in some women, there is no cure apart from delivery of the placenta and fetus, often necessitating iatrogenic preterm birth. Preclinical models of preeclampsia are widely used to investigate the causes and consequences of preeclampsia and to evaluate safety and efficacy of potential preventative and therapeutic interventions. In this review, we provide a summary of the published preclinical models of preeclampsia that meet human diagnostic criteria, including the development of maternal hypertension, together with new-onset proteinuria, maternal organ dysfunction, and uteroplacental dysfunction. We then discuss evidence from preclinical models for multiple causal factors of preeclampsia, including those implicated in early-onset and late-onset preeclampsia. Next, we discuss the impact of exposure to a preeclampsia-like environment for later maternal and progeny health. The presence of long-term impairment, particularly cardiovascular outcomes, in mothers and progeny after an experimentally induced preeclampsia-like pregnancy, implies that later onset or reduced severity of preeclampsia will improve later maternal and progeny health. Finally, we summarize published intervention studies in preclinical models and identify gaps in knowledge that we consider should be targets for future research.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.119.14598DOI Listing
June 2020

Pregnancy, but not dietary octanoic acid supplementation, stimulates the ghrelin-pituitary growth hormone axis in mice.

J Endocrinol 2020 05;245(2):327-342

Robinson Research Institute, The University of Adelaide, Adelaide, Australia.

Circulating growth hormone (GH) concentrations increase during pregnancy in mice and remain pituitary-derived. Whether abundance or activation of the GH secretagogue ghrelin increase during pregnancy, or in response to dietary octanoic acid supplementation, is unclear. We therefore measured circulating GH profiles in late pregnant C57BL/6J mice and in aged-matched non-pregnant females fed with standard laboratory chow supplemented with 5% octanoic or palmitic (control) acid (n = 4-13/group). Serum total and acyl-ghrelin concentrations, stomach and placenta ghrelin mRNA and protein expression, Pcsk1 (encoding prohormone convertase 1/3) and Mboat4 (membrane bound O-acyl transferase 4) mRNA were determined at zeitgeber (ZT) 13 and ZT23. Total and basal GH secretion were higher in late pregnant than non-pregnant mice (P < 0.001), regardless of diet. At ZT13, serum concentrations of total ghrelin (P = 0.004), but not acyl-ghrelin, and the density of ghrelin-positive cells in the gastric antrum (P = 0.019) were higher, and gastric Mboat4 and Pcsk1 mRNA expression were lower in pregnant than non-pregnant mice at ZT23. In the placenta, ghrelin protein was localised mostly to labyrinthine trophoblast cells. Serum acyl-, but not total, ghrelin was lower at mid-pregnancy than in non-pregnant mice, but not different at early or late pregnancy. In conclusion, dietary supplementation with 5% octanoic acid did not increase activation of ghrelin in female mice. Our results further suggest that increases in maternal GH secretion throughout murine pregnancy are not due to circulating acyl-ghrelin acting at the pituitary. Nevertheless, time-dependent increased circulating total ghrelin could potentially increase ghrelin action in tissues that express the acylating enzyme and receptor.
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http://dx.doi.org/10.1530/JOE-20-0072DOI Listing
May 2020

Psychosocial determinants of pertussis and influenza vaccine uptake in pregnant women: A prospective study.

Vaccine 2020 04 16;38(17):3358-3368. Epub 2020 Feb 16.

Vaccinology and Immunology Research Trials Unit, Women's and Children's Hospital, Adelaide, South Australia, Australia. Electronic address:

Objective: To identify the psychosocial factors influencing women's uptake and willingness to receive pertussis and influenza vaccine during pregnancy.

Methods: The study population comprised 1364 healthy nulliparous pregnant women who participated in a prospective cohort study at two obstetric hospitals in South Australia between 2015 and 2017. Information on women's vaccination status, sociodemographic, lifestyle and psychological state were collected at 9-16 weeks' gestation and medical case notes were checked post-delivery to verify the reported vaccination status. Poisson regression models were used to estimate the crude and adjusted prevalence ratios (aPRs) to identify psychosocial factors influencing uptake of vaccination during pregnancy.

Results: Willingness to receive the recommended maternal vaccines was high (90%). Overall, 79% and 48% received maternal pertussis and influenza vaccines respectively. There was no evidence to support the influence of psychosocial factors on women's willingness to receive immunization during pregnancy. High levels of anxiety (aPR 0.98, 95% CI: 0.87-1.09) was not associated with uptake of maternal pertussis vaccine. However, elevated depressive symptoms (aPR 1.14, 95% CI: 1.00-1.30) and very high-perceived stress during pregnancy were significantly associated with receipt of pertussis vaccination (aPR 0.87; 95% CI 0.76-0.99). Women with mild depressive symptoms (aPR 1.21, 95% CI 1.00-1.44) and mild anxiety symptoms (aPR 1.21, 95% CI: 0.99-1.48) were more likely to receive influenza vaccine during pregnancy (aPR 1.27, 95% CI: 1.08-1.49). A history of major depressive disorder was independently associated with receipt of pertussis (aPR 1.16, 95% CI 1.06-1.26) and influenza vaccination during pregnancy (aPR 1.32; 95% CI 1.14-1.58).

Conclusion: Regardless of psychosocial factors, most women reported a positive willingness to receive the recommended vaccinations during pregnancy. However, psychosocial factors influenced the uptake of pertussis and influenza vaccines during pregnancy. Psychosocial factors should be taken into consideration in designing interventions and implementation of maternal pertussis and influenza immunization programs.
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http://dx.doi.org/10.1016/j.vaccine.2020.02.020DOI Listing
April 2020

Mechanisms linking exposure to preeclampsia and the risk for cardiovascular disease.

J Dev Orig Health Dis 2020 06 19;11(3):235-242. Epub 2020 Feb 19.

Adelaide Medical School, The University of Adelaide, Adelaide, Australia.

Preeclampsia (PE) is now recognised as a cardiovascular risk factor for women. Emerging evidence suggests that children exposed to PE in utero may also be at increased risk of cardiovascular disease (CVD) in later life. Individuals exposed to PE in utero have higher systolic and diastolic blood pressure and higher body mass index (BMI) compared to those not exposed to PE in utero. The aim of this review is to discuss the potential mechanisms driving the relationship between PE and offspring CVD. Exposure to an adverse intrauterine environment as a consequence of the pathophysiological changes that occur during a pregnancy complicated by PE is proposed as one mechanism that programs the fetus for future CVD risk. Consistent with this hypothesis, animal models of PE where progeny have been studied demonstrate causality for programming of offspring cardiovascular health by the preeclamptic environment. Shared alleles between mother and offspring, and shared lifestyle factors between mother and offspring provide alternate pathways explaining associations between PE and offspring CVD risk. In addition, adverse lifestyle habits can also act as second hits for those programmed for increased CVD risk. PE and CVD are both multifactorial diseases and, hence, identifying the relative contribution of PE to offspring risk for CVD is a very complex task. However, considering the emerging strong association between PE and CVD, those exposed to PE in utero may benefit from targeted primary CVD preventive strategies.
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http://dx.doi.org/10.1017/S2040174420000094DOI Listing
June 2020

Implementing a legislation change in organ and tissue donation in England.

Br J Nurs 2020 Feb;29(3):168-169

National Professional Development Specialist, Legislation Implementation, NHS Blood and Transplant.

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http://dx.doi.org/10.12968/bjon.2020.29.3.168DOI Listing
February 2020

Reduced Dietary Calcium and Vitamin D Results in Preterm Birth and Altered Placental Morphogenesis in Mice During Pregnancy.

Reprod Sci 2020 06 1;27(6):1330-1339. Epub 2020 Jan 1.

Robinson Research Institute, The University of Adelaide, Adelaide, South Australia, Australia.

Vitamin D and calcium are essential micronutrients for reproductive success. Vitamin D deficiency during pregnancy is associated with increased risk of pregnancy complications including pre-eclampsia and preterm birth (PTB). However, inconsistencies in the literature reflect uncertainties regarding the true biological importance of vitamin D but may be explained by maternal calcium intakes. We aimed to determine whether low dietary consumption of calcium along with vitamin D deficiency had an additive effect on adverse pregnancy outcome by investigating placental morphogenesis and foetal growth in a mouse model. Female mice were randomly assigned to one of four diets: control-fed (+Ca+VD), reduced vitamin D only (+Ca-VD), reduced calcium only (-Ca+VD) and reduced calcium and vitamin D (-Ca-VD), and sacrificed at gestational day (GD) 18.5. Maternal serum 25-hydroxyvitamin D (25(OH)D) levels were lower in each reduced diet group when compared with levels in +Ca+VD-fed mice. While the pregnancy rate did not differ between groups, in the -Ca-VD-fed group, 55% (5 out of 9 pregnant of known gestational age) gave birth preterm (
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http://dx.doi.org/10.1007/s43032-019-00116-2DOI Listing
June 2020