Prevalence of and risk factors for self-reported menstrual changes following COVID-19 vaccination: a Danish cohort study.

STUDY QUESTION: Are there some characteristics that render individuals more susceptible to report menstrual changes following the Coronavirus disease 2019 (COVID-19) vaccination? SUMMARY ANSWER: We found that 30% of menstruating women reported menstrual changes following COVID-19 vaccination and several potential risk factors including stress, vaccine concerns, severe COVID-19 infection, and immediate vaccine symptoms were associated with these reports. WHAT IS KNOWN ALREADY: Studies suggest that COVID-19 vaccination might temporarily prolong menstrual cycle length by less than 1 day. Specific characteristics may trigger menstrual changes in temporal relation to the vaccination simply by chance or render women more vigilant to potential menstrual changes after being vaccinated. However, research investigating potential risk factors for reporting menstrual changes following COVID-19 vaccination is limited. STUDY DESIGN, SIZE, DURATION: A population-based Danish cohort study. Data were collected from May 2021 to December 2021 as a part of the BiCoVac Cohort with the aim of examining non-specific effects following COVID-19 vaccination. The main study population included 13 648 menstruating women aged 16-65 years who completed all surveys, received their first dose of a COVID-19 vaccine during the data collection period, and completed questions related to their menstrual cycle. PARTICIPANTS/MATERIALS, SETTING, METHODS: Potential risk factors included 14 biological, physical, or psychological measures. Information on most potential risk factors was self-reported and collected before the participants' first COVID-19 vaccination. Information about any menstrual change following COVID-19 vaccination was self-reported at the end of the data collection period. Logistic regression analyses were used to estimate crude and adjusted odds ratios (ORs) with 95% CIs for the association between each potential risk factor and reporting menstrual changes following COVID-19 vaccination. MAIN RESULTS AND THE ROLE OF CHANCE: Any menstrual change following COVID-19 vaccination was reported by 30% of menstruating women. Most of the potential risk factors were associated with reports of menstrual changes following COVID-19 vaccination. In particular, higher odds were found among women who reported ≥5 immediate vaccine symptoms; OR 1.67 [1.50-1.86], had had a prior severe COVID-19 infection; OR 2.17 [1.40-3.35], had a high-stress level at baseline; OR 1.67 [1.32-2.10], or were concerned about COVID-19 vaccines prior to vaccination; OR 1.92 [1.50-2.45]. Lower odds were found among women with regular menstrual cycles using hormonal contraception; OR 0.71 [0.65-0.78]. LIMITATIONS, REASONS FOR CAUTION: We were unable to address the causal effect of COVID-19 vaccination on the reported menstrual changes, as information about menstrual changes was not available among non-vaccinated women. WIDER IMPLICATIONS OF THE FINDINGS: The study identified several potential risk factors for reporting menstrual changes following COVID-19 vaccination. Further studies are needed to establish causal associations and the clinical impact of self-reported menstrual changes. STUDY FUNDING/COMPETING INTEREST(S): The BiCoVac data collection was funded by TrygFonden (id-number: 153678). No competing interests are declared. TRIAL REGISTRATION NUMBER: N/A.

Immediate adverse reactions following COVID-19 vaccination among 16-65-year-old Danish citizens.

INTRODUCTION: There is sparse knowledge of immediate adverse reactions following COVID-19 vaccination. OBJECTIVE: This study aimed to estimate the frequency and number of immediate adverse reactions following COVID-19 vaccination in a Danish population. METHODS: The study used data from the Danish population-based cohort study BiCoVac. The frequencies of 20 self-reported adverse reactions were estimated for each vaccine dose stratified by sex, age, and vaccine type. Also, the distributions of number of adverse reactions following each dose were estimated stratified by sex, age, vaccine type, and prior COVID-19 infection. RESULTS: A total of 889,503 citizens were invited and 171,008 (19 %) vaccinated individuals were included in the analysis. The most frequently reported adverse reaction following the first dose of COVID-19 vaccine was redness and/or pain at the injection site (20 %) while following the second and third dose, tiredness was the most frequently reported adverse reaction (22 % and 14 %, respectively). Individuals aged 26-35 years, females, and those with a prior COVID-19 infection were more likely to report adverse reactions compared with older individuals, males, and those with no prior COVID-19 infection, respectively. Following the first dose, individuals vaccinated with ChAdOx1-2 (AstraZeneca) reported more adverse reactions compared with individuals vaccinated with other vaccine types. Individuals vaccinated with mRNA-1273 (Moderna) reported more adverse reactions following the second and third dose compared with individuals vaccinated with BNT162b2 (Pfizer-BioNTech). CONCLUSION: The frequency of immediate adverse reactions was highest among females and younger persons, however, most of the Danish citizens did not experience immediate adverse reactions following COVID-19 vaccination.

Birth by cesarean section in relation to adult offspring overweight and biomarkers of cardiometabolic risk.

BACKGROUND: Birth by Cesarean section (C-section) may increase the risk for non-communicable diseases. We aimed to examine the relation of birth by C-section with offspring overweight and markers of cardiometabolic risk in a prospective observational cohort with 20 years of follow-up. METHODS: The Danish Fetal Origins Cohort enrolled 965 pregnant women in 1988-1989. In 2008, a follow-up study of the offspring was completed. The offspring were invited to participate in a clinical examination with measurements of anthropometry and a fasting blood sample (n=443). In addition, 252 offspring completed a self-administered questionnaire with questions on height and weight, leaving us with a study sample of 695 offspring. Offspring overweight at 20 years was defined as body mass index (BMI)⩾25 kg m-2. We also analyzed blood pressure and fasting blood samples for cardiometabolic risk factors including insulin, leptin and adiponectin, and lipid concentrations. RESULTS: In the cohort, 7% were born by C-section, and at age 20 years, 18% of the offspring had a BMI ⩾25 kg m-2. Birth by C-section was associated with increased odds of overweight or obesity at 20 years (Odds ratio=2.17 (95% confidence interval (CI): 1.10, 4.27)) after adjustment for potential confounders. Birth by C-section was also associated with higher serum concentrations of total cholesterol (8.5%, 95% CI: 1.1-16.5), low-density lipoprotein cholesterol (12.6%, 95% CI: 1.0, 25.5), leptin (73.1%, 95% CI: 5.9, 183.1) and Apolipoprotein B (0.08 g l-1, 95% CI: 0.04, 0.15). In contrast, birth by C-section was not related to blood pressure or serum concentrations of insulin, adiponectin, triglycerides, high-density lipoprotein or Apolipoprotein A. CONCLUSION: Birth by C-section was associated with higher frequency of dysmetabolic traits in offspring independently of shared risk factors. Further research aimed at replicating these findings and elucidating the underlying biological mechanisms of this relation is needed.

Prenatal exposure to persistent organic pollutants and offspring allergic sensitization and lung function at 20 years of age.

BACKGROUND: Prenatal exposures to persistent organic pollutants (POPs) have been associated with asthma medication use and self-reported symptoms, but associations with lung function and allergic sensitization have been minimally explored. The aim of the study was to examine the associations between prenatal exposures to POPs and allergic sensitization and lung function in 20-year-old offspring. METHODS: In a Danish cohort of 965 pregnant women established in 1988-1989, six polychlorinated biphenyl (PCB) congeners, hexachlorobenzene (HCB), and dichlorodiphenyldichloroethylene (p,p'-DDE) were quantified in archived maternal serum drawn in gestational week 30 (n = 872). Among those with available maternal exposure information, at age 20, 421 offspring attended attended a clinical examination including measurements of allergic sensitization (serum-specific IgE ≥ 0.35 kUA /L) (n = 418) and lung function [forced expiratory volume in one second (FEV1 ) and forced vital capacity (FVC)] (n = 414). RESULTS: There were no associations between maternal concentrations of POPs and offspring allergic sensitization at 20 years of age. Maternal concentrations of POPs were, however, positively associated with offspring airway obstruction (FEV1 /FVC < 75%). Compared to offspring in the first tertile of exposure, offspring in the third tertile of dioxin-like PCB exposure had an OR of 2.96 (95% CI: 1.14-7.70). Similar associations for non-dioxin-like PCBs, HCB, and p,p'-DDE were 2.68 (1.06-6.81), 2.63 (1.07, 6.46), and 2.87 (1.09, 7.57), respectively. No associations were observed with reduced lung function (FEV1 % of predicted value < 90%). CONCLUSION AND CLINICAL RELEVANCE: Our data indicate that prenatal exposure to POPs appears to be associated with airway obstruction but not allergic sensitization at 20 years of age. The findings support that chronic obstructive lung diseases may have at least part of their origins in early life.

Gestational weight gain in normal weight women and offspring cardio-metabolic risk factors at 20 years of age.

OBJECTIVE: Limited knowledge exists on the long-term implications of maternal gestational weight gain (GWG) on offspring health. Our objective was to examine whether high GWG in normal weight women is associated with adult offspring cardio-metabolic risk factors. METHODS: We used a cohort of 308 Danish women who gave birth in 1988-89 and whose offspring participated in a clinical examination at 20 years of age. Main outcome measures were offspring body mass index (BMI), waist circumference, weight-regulating hormones, blood lipids and glucose metabolism. Associations were assessed using multivariable linear and logistic regression models. RESULTS: A weak positive association was observed between GWG during the first 30 weeks and offspring anthropometry. Each 1-kg increase in maternal GWG was associated with 0.1-kg m(-2) higher (95% confidence interval (CI): 0.01, 0.2) offspring BMI and 10% (95% CI: 0.1%, 20%) higher odds of offspring overweight at the age of 20 years, with similar associations observed in both sexes. However, sex differences were observed for the association between maternal GWG and specific cardio-metabolic risk factors. Hence, a 1-kg increase in GWG was associated with 3.4% (95% CI; 0.8, 6.0%) higher homeostasis model assessment-estimated insulin resistance (HOMA-IR), 3.7% (95% CI: 1.4%, 6.2%) higher insulin and 10.7% (95% CI: 5.7%, 15.9%) higher leptin levels in male offspring. These associations were not observed in females, which may partly be explained by more frequent reports of dieting and physical exercise at follow-up among female offspring. CONCLUSIONS: In normal-weight women, high GWG may have modest long-term implications on offspring cardio-metabolic risk factors at adult age.

Maternal milk consumption, birth size and adult height of offspring: a prospective cohort study with 20 years of follow-up.

BACKGROUND/OBJECTIVES: Previous studies have suggested that milk consumption during pregnancy may have growth-promoting effects on the offspring in utero. Whether this effect tracks beyond the prenatal period remains unclear. We examined whether milk consumption during pregnancy is associated with infant size at birth and offspring's height- and growth-related biomarkers at ∼20 years of age. SUBJECT/METHODS: A prospective cohort of 809 Danish pregnant women was recruited in 1988-1989, with offspring follow-up at ∼20 years of age (n=685). Milk consumption was assessed at gestational week 30 using a food frequency questionnaire. Birth weight and birth length were measured according to standard procedures at delivery and converted to specific z-scores, adjusted for gestational age and gender. RESULTS: In adjusted models, maternal milk consumption of ≥150 ml/day vs <150 ml/day was associated with 0.32 higher z-scores for birth weight (95% confidence interval (CI) 0.06; 0.58) and 0.34 higher z-scores for birth length (95% CI 0.04; 0.64). At follow up, ∼20 years later, those offspring whose mothers had consumed < 150 ml milk/day tended to have 0.19 higher z-scores for height (P=0.16), ∼8% higher levels of insulin-like growth factor I (P=0.12) and ∼14% higher insulin levels (P=0.11) compared with offspring whose mothers consumed <150 ml milk/day. CONCLUSIONS: Our findings add to recent observations that maternal milk consumption may have a growth-promoting effect with respect to weight and length at birth. Furthermore, the results provide some suggestion that this effect may even track into early adult age, although further studies with more statistical power are needed for that purpose.

The effect of adrenaline and high Ca2+ on the mechanical performance and oxygen consumption of the isolated perfused trout (Oncorhynchus mykiss) heart.

In heart muscle from mammals, catecholamines frequently evoke an oxygen waste and reduce efficiency. It was examined if this also applies to fish in which heart muscle activity is often restricted by oxygen availability. In the isolated perfused heart from rainbow trout, adrenaline (0.5 microM) increased power output by approximately 97%, when afterload was adjusted to maximum both before and after adrenaline addition, and by approximately 68%, when afterload remained at the maximum obtained before adrenaline addition. Oxygen consumption was enhanced by a similar amount (approximately 70%) in both situations. Hence, efficiency, i.e. power output/oxygen consumption, increased significantly from 25 to 30% for the heart always exposed to maximal afterload, whereas it stayed unchanged at 24% for the heart exposed to control afterload only. Adrenaline increases the Ca2+ activity participating in activation, but doing this by elevating perfusate Ca2+ from 1.5 to 5 mM instead of applying adrenaline did not change the mechanical efficiency, although afterload was maximized. The results suggest that catecholamines enhance heart pump activity in the living trout without any oxygen waste. On the contrary, the oxygen budget may even improve when the peripheral resistance is increased by catecholamines.

Hypolipidemic arylthioalkanoic acids.

A series of arylthioalkanoic acids related to probucol was studied for hypolipidemic activity. Homologation of the alkyl side chain led to marked changes in the serum cholesterol and serum triglyceride lowering activity in rats with the best combination of properties appearing in compound 7, 2-[3,5-di-tert-butyl-4-hydroxyphenyl)thio]hexanoic acid. Modification of the ring substitution failed to improve the activity despite the empirical observation that lipophilic substitution was necessary. Removal of the phenolic hydroxyl produced compound 23 with properties similar to 7 but of somewhat lower activity. Replacement of the sulfur by oxygen increased the toxicity of the series. Resolution of racemic 7 did not change the activity of the compound. The LD50 in mice of 7 was between 5000 and 10 000 mg/kg and compound 7 has been submitted for human clinical evaluation.

An overview of the biochemical pharmacology of probucol.

Probucol was effective in lowering serum total cholesterol in mice at dietary livels as low as 0.0075%. It was also effective after a single 100 mg/kg I.V. dose in mice. The incorporation of acetate-(14)C into liver lipids of rats and mice was not significantly affected by probucol, although the results, especially in mice, make it impossible to rule out such an effect. Cholesterol absorption was estimated in rats using a dual isotope technique. The observed reductions were not statistically significant. Several liver enzyme activities were determined after probucol treatment in rats, and a significant elevation (32%) was observed in only one, glutamic dehydrogenase. Serum cholesterol was lowered markedly in cholesterol-fed cynomolgus monkeys by probucol. There was no effect on the excretion of neutral steroids and the observed increase in fecal bile acids after drug treatment could not be confirmed statistically.