The effect of maternal iron status and intake during pregnancy on cardiovascular disease risk in the offspring

Iron is an important micronutrient essential in carrying oxygen and maintaining the function of many body enzymes. It is of particular importance during gestation as body demands increase leading to iron deficiency in women with inadequate iron stores at the start of pregnancy. Animal studies have shown that iron deficiency in pregnancy leads to offspring with adverse cardiovascular risk profiles compared to offspring of iron replete mothers. This thesis aimed to examine the association of maternal iron intake and status in pregnancy with short and long term birth outcomes that are considered cardiovascular risk indicators later in life. Analysis of data from three cohorts and one Mendelian randomisation study was included in this thesis. Total maternal iron intake in early, but not late, pregnancy was positively associated with birth size. There was no evidence of association between taking iron-containing supplements in pregnancy and size at birth. However, taking multivitamin-mineral supplements, which contain iron, in late pregnancy was associated with an increased risk of preterm birth. Also taking iron supplements up to 32 weeks gestation was associated with lower offspring systolic blood pressure at 10 years. Maternal iron deficiency and anaemia in early pregnancy were associated with an increased risk of giving birth to a SGA baby. Infant brachio-femoral PWV measured at 2-6 weeks of age was found to be higher in women who were anaemic in early pregnancy, but not in those who were only iron deficient. Finally, using a Mendelian randomisation design, maternal iron status measured by serum ferritin with C282Y mutation as an instrumental variable, was not found to be associated with adult offspring BP and adiposity. In conclusion, maternal iron intake and status in early pregnancy seem to be associated with short term birth outcomes like size at birth, while associations with long term offspring cardiovascular indicators were not detected in this thesis

Maternal iron status in early pregnancy and birth outcomes : insights from the Baby's Vascular health and Iron in Pregnancy study

Date of Acceptance: 16/03/2015 Acknowledgements N. A. A. was funded by a Wellcome Trust Research Training Fellowship (WT87789). H. J. M. and H. E. H. are supported by the Scottish Government’s Rural and Environment Science and Analytical Services. N. A. B. S. is supported by Cerebra. The authors’ contributions are as follows: N. A. A. was responsible for organising the study conduct, data collection and database management, performed the statistical analysis, interpreted the results and drafted the paper. N. A. A., N. A. B. S., J. E. C., H. J. M. and D. C. G. contributed to the study concept and design, and interpretation of results. H. J. M. and H. E. H. analysed the laboratory samples. J. E. C. and D. C. G. provided advice on statistical strategy and analysis. All authors have fully participated in the reporting stage and have critically reviewed and approved the final draft of the paper. The authors declare no conflict of interestPeer reviewedPublisher PD

Why the Patient-Made Term 'Long Covid' is needed

The patient-made term ‘Long Covid’ is, we argue, a helpful and capacious term that is needed to address key medical, epidemiological and socio-political challenges posed by diverse symptoms persisting beyond four weeks after symptom onset suggestive of coronavirus disease 2019 (COVID-19). An international movement of patients (which includes all six authors) brought the persistence and heterogeneity of long-term symptoms to widespread visibility. The same grassroots movement introduced the term ‘Long Covid’ (and the cognate term ‘long-haulers’) to intervene in relation to widespread assumptions about disease severity and duration. Persistent symptoms following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are now one of the most pressing clinical and public health phenomena to address: their cause(s) is/are unknown, their effects can be debilitating, and the percentage of patients affected is unclear, though likely significant. The term ‘Long Covid’ is now used in scientific literature, the media, and in interactions with the WHO. Uncertainty regarding its value and meaning, however, remains. In this Open Letter, we explain the advantages of the term ‘Long Covid’ and bring clarity to some pressing issues of use and definition. We also point to the importance of centring patient experience and expertise in relation to ‘Long Covid’ research, as well as the provision of care and rehabilitation.</ns4:p

Risk of new-onset Long Covid following reinfection with SARS-CoV-2: community-based cohort study

Background: Little is known about the risk of Long Covid following reinfection with SARS-CoV-2. We estimated the likelihood of new-onset, self-reported Long Covid after a second SARS-CoV-2 infection, and compared to a first infection. // Methods: We included UK COVID-19 Infection Survey participants who tested positive for SARS-CoV-2 between 1 November 2021 and 8 October 2022. The primary outcome was self-reported Long Covid 12 to 20 weeks after each infection. Separate analyses were performed for those <16 years and ≥16 years. We estimated adjusted odds ratios (aORs) for new-onset Long Covid using logistic regression, comparing second to first infections, controlling for socio-demographic characteristics and calendar date of infection, plus vaccination status in those ≥16 years. // Results: Overall, Long Covid was reported by those ≥16 years after 4.0% and 2.4% of first and second infections, respectively; the corresponding estimates among those <16 years were 1.0% and 0.6%. The aOR for Long Covid after second compared to first infections was 0.72 (95% confidence interval: 0.63–0.81) for those ≥16 years and 0.93 (0.57–1.53) for those <16 years. // Conclusions: The risk of new-onset Long Covid after a second SARS-CoV-2 infection is lower than that after a first infection for those ≥16 years, though there is no evidence of a difference in risk for those <16 years. However, there remains some risk of new-onset Long Covid after a second infection, with around 1 in 40 of those ≥16 years and 1 in 165 of those <16 years reporting Long Covid after a second infection

Systematic Review of the Prevalence of Long COVID

BACKGROUND: Long COVID occurs in those infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) whose symptoms persist or develop beyond the acute phase. We conducted a systematic review to determine the prevalence of persistent symptoms, functional disability, or pathological changes in adults or children at least 12 weeks postinfection. METHODS: We searched key registers and databases from January 1, 2020 to November 2, 2021, limited to publications in English and studies with at least 100 participants. Studies in which all participants were critically ill were excluded. Long COVID was extracted as prevalence of at least 1 symptom or pathology, or prevalence of the most common symptom or pathology, at 12 weeks or later. Heterogeneity was quantified in absolute terms and as a proportion of total variation and explored across predefined subgroups (PROSPERO ID CRD42020218351). RESULTS: One hundred twenty studies in 130 publications were included. Length of follow-up varied between 12 weeks and 12 months. Few studies had low risk of bias. All complete and subgroup analyses except 1 had I2 ≥90%, with prevalence of persistent symptoms range of 0%-93% (pooled estimate [PE], 42.1%; 95% prediction interval [PI], 6.8% to 87.9%). Studies using routine healthcare records tended to report lower prevalence (PE, 13.6%; PI, 1.2% to 68%) of persistent symptoms/pathology than self-report (PE, 43.9%; PI, 8.2% to 87.2%). However, studies systematically investigating pathology in all participants at follow up tended to report the highest estimates of all 3 (PE, 51.7%; PI, 12.3% to 89.1%). Studies of hospitalized cases had generally higher estimates than community-based studies. CONCLUSIONS: The way in which Long COVID is defined and measured affects prevalence estimation. Given the widespread nature of SARS-CoV-2 infection globally, the burden of chronic illness is likely to be substantial even using the most conservative estimates

The role of parity in the relationship between endometriosis and pregnancy outcomes: a systematic review and meta-analysis

Endometriosis is a chronic and debilitating condition which can affect the entire reproductive life course of women with a potentially detrimental effect on pregnancy. Pregnancy (and increasing parity) can affect endometriosis by modulating disease severity and suppressing symptoms. Multiparous women could be less likely to suffer from endometriosisrelated pregnancy complications than primiparous women. We aimed to systematically review the evidence examining the role of parity in the relationship between pregnancy outcomes and endometriosis. A systematic search of MEDLINE, EMBASE, CINAHL, Web of Science, and Cochrane Library was performed from inception to May 2022. We searched for experimental and observational studies. Grading of Recommendations, Assessment, Development, and Evaluation was used to assess the quality of evidence with the risk of bias in non-randomised studies of interventions tool incorporated. Eleven studies were included in the meta-analysis. Primiparous women with endometriosis had almost double the risk of hypertensive disorders of pregnancy (OR: 1.99, 95% CI: 1.50–2.63, P < 0.001) compared to multiparous women with endometriosis. Primiparous women with endometriosis were at significantly increased risk of preterm delivery, caesarean delivery, and placenta praevia compared to primiparous women without endometriosis. There were no significant differences in outcomes when multiparous women with endometriosis were compared to multiparous women without endometriosis. There is limited evidence to suggest that primiparous women with endometriosis may be at higher risk of adverse pregnancy outcomes compared to multiparous women. The modulatory role of parity in the pathophysiology of endometriosis and its impact on pregnancy outcomes should be investigated

[Opinion] How can we make attendance at scientific conferences inclusive?

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Changes in the trajectory of Long Covid symptoms following COVID-19 vaccination: community-based cohort study

OBJECTIVE: To estimate associations between COVID-19 vaccination and Long Covid symptoms in adults who were infected with SARS-CoV-2 prior to vaccination. DESIGN: Observational cohort study using individual-level interrupted time series analysis. SETTING: Random sample from the community population of the UK. PARTICIPANTS: 28,356 COVID-19 Infection Survey participants (mean age 46 years, 56% female, 89% white) aged 18 to 69 years who received at least their first vaccination after test-confirmed infection. MAIN OUTCOME MEASURES: Presence of Long Covid symptoms at least 12 weeks after infection over the follow-up period 3 February to 5 September 2021. RESULTS: Median follow-up was 141 days from first vaccination (among all participants) and 67 days from second vaccination (84% of participants). First vaccination was associated with an initial 12.8% decrease (95% confidence interval: -18.6% to -6.6%, p<0.001) in the odds of Long Covid, with the data being compatible with both increases and decreases in the trajectory (+0.3% per week, 95% CI: -0.6% to +1.2% per week, p=0.51) after this. Second vaccination was associated with an 8.8% decrease (95% CI: -14.1% to -3.1%, p=0.003) in the odds of Long Covid, with the odds subsequently decreasing by 0.8% (-1.2% to -0.4%, p<0.001) per week. There was no statistical evidence of heterogeneity in associations between vaccination and Long Covid by socio-demographic characteristics, health status, whether hospitalised with acute COVID-19, vaccine type (adenovirus vector or mRNA), or duration from infection to vaccination. CONCLUSIONS: : The likelihood of Long Covid symptoms reduced after COVID-19 vaccination, and there was evidence of a sustained improvement after the second dose, at least over the median follow-up time of 67 days. Vaccination may contribute to a reduction in the population health burden of Long Covid, though longer follow-up time is needed

Long Covid stigma: estimating burden and validating scale in a UK-based sample

Background Stigma can be experienced as perceived or actual disqualification from social and institutional acceptance on the basis of one or more physical, behavioural or other attributes deemed to be undesirable. Long Covid is a predominantly multisystem condition that occurs in people with a history of SARSCoV2 infection, often resulting in functional disability. This study aimed to develop and validate a Long Covid Stigma Scale (LCSS); and to quantify the burden of Long Covid stigma. Methods Data from the follow-up of a co-produced community-based Long Covid online survey using convenience non-probability sampling was used. Thirteen questions on stigma were designed to develop the LCSS capturing three domains-enacted (overt experiences of discrimination), internalised (internalising negative associations with Long Covid and accepting them as self-applicable) and anticipated (expectation of bias/poor treatment by others) stigma. Confirmatory factor analysis tested whether LCSS consisted of the three hypothesised domains. Model fit was assessed and prevalence was calculated. Results 966 UK-based participants responded (888 for stigma questions), with mean age 48 years (SD: 10.7) and 85% female. Factor loadings for enacted stigma were 0.70-0.86, internalised 0.75-0.84, anticipated 0.58-0.87, and model fit was good. The prevalence of experiencing stigma at least 'sometimes' and 'often/always' was 95% and 76% respectively. Anticipated and internalised stigma were more frequently experienced than enacted stigma. Those who reported having a clinical diagnosis of Long Covid had higher stigma prevalence than those without. Conclusion This study establishes a scale to measure Long Covid stigma and highlights common experiences of stigma in people living with Long Covid