Background We describe post-COVID symptomatology in a non-hospitalised, national sample of adolescents aged 11–17 years with PCR-confirmed SARS-CoV-2 infection compared with matched adolescents with negative PCR status. Methods In this national cohort study, adolescents aged 11–17 years from the Public Health England database who tested positive for SARS-CoV-2 between January and March, 2021, were matched by month of test, age, sex, and geographical region to adolescents who tested negative. 3 months after testing, a subsample of adolescents were contacted to complete a detailed questionnaire, which collected data on demographics and their physical and mental health at the time of PCR testing (retrospectively) and at the time of completing the questionnaire (prospectively). We compared symptoms between the test-postive and test-negative groups, and used latent class analysis to assess whether and how physical symptoms at baseline and at 3 months clustered among participants. This study is registered with the ISRCTN registry (ISRCTN 34804192). Findings 23 048 adolescents who tested positive and 27 798 adolescents who tested negative between Jan 1, 2021, and March 31, 2021, were contacted, and 6804 adolescents (3065 who tested positive and 3739 who tested negative) completed the questionnaire (response rate 13·4%). At PCR testing, 1084 (35·4%) who tested positive and 309 (8·3%) who tested negative were symptomatic and 936 (30·5%) from the test-positive group and 231 (6·2%) from the test-negative group had three or more symptoms. 3 months after testing, 2038 (66·5%) who tested positive and 1993 (53·3%) who tested negative had any symptoms, and 928 (30·3%) from the test-positive group and 603 (16·2%) from the test-negative group had three or more symptoms. At 3 months after testing, the most common symptoms among the test-positive group were tiredness (1196 [39·0%]), headache (710 [23·2%]), and shortness of breath (717 [23·4%]), and among the test-negative group were tiredness (911 [24·4%]), headache (530 [14·2%]), and other (unspecified; 590 [15·8%]). Latent class analysis identified two classes, characterised by few or multiple symptoms. The estimated probability of being in the multiple symptom class was 29·6% (95% CI 27·4–31·7) for the test-positive group and 19·3% (17·7–21·0) for the test-negative group (risk ratio 1·53; 95% CI 1·35–1·70). The multiple symptoms class was more frequent among those with positive PCR results than negative results, in girls than boys, in adolescents aged 15–17 years than those aged 11–14 years, and in those with lower pretest physical and mental health. Interpretation Adolescents who tested positive for SARS-CoV-2 had similar symptoms to those who tested negative, but had a higher prevalence of single and, particularly, multiple symptoms at the time of PCR testing and 3 months later. Clinicians should consider multiple symptoms that affect functioning and recognise different clus...

Objective To investigate whether size at birth and rate of fetal growth influence the risk of breast cancer in adulthood. Design Cohort identified from detailed birth records, with 97% follow up. Setting Uppsala Academic Hospital, Sweden. Participants 5358 singleton females born during 1915-29, alive and traced to the 1960 census. Main outcome measures Incidence of breast cancer before (at age < 50 years) and after (> 50 years) the menopause. Results Size at birth was positively associated with rates of breast cancer in premenopausal women. In women who weighed >4000 g at birth rates of breast cancer were 3.5 times (95% confidence interval 1.3 to 9.3) those in women of similar gestational age who weighed < 3000 g at birth. Rates in women in the top fifths of the distributions of birth length and head circumference were 3.4 (1.5 to 7.9) and 4.0 (1.6 to 10.0) times those in the lowest fifths (adjusted for gestational age). The effect of birth weight disappeared after adjustment for birth length or head circumference, whereas the effects of birth length and head circumference remained significant after adjustment for birth weight. For a given size at birth, gestational age was inversely associated with risk (P=0.03 for linear trend). Adjustment for markers of adult risk factors did not affect these findings. Birth size was not associated with rates of breast cancer in postmenopausal women. Conclusions Size at birth, particularly length and head circumference, is associated with risk of breast cancer in women aged < 50 years. Fetal growth rate, as measured by birth size adjusted for gestational age, rather than size at birth may be the aetiologically relevant factor in premenopausal breast cancer.

Summary This is the first prospective study of unnary measures of the two major competing pathways of oestrogen metabolism, 16a-hydroxyoestrone (16a-OHE1) and 2-hydroxyoestrone (2-OHEl), in Correspondence to: EN Meilahn two irreversible and mutually exclusive pathways to form: (1) 16a-hydroxyoestrone or (2) 2-hydroxyoestrone. These are the major metabolic pathways for oestrogen with 4-hydroxylation as a minor pathway. albeit one that produces a carcinogenic product. The 2-and l6a-hydroxylation appear to compete for the limited oestrone substrate pool. and a rise in the extent of one hydroxvlation pathway will result in a shift of substrate towards the alternate and will reduce the absolute amount of the product of the competing, pathway.The 16at-and 2-OHE I metabolites are thought to have markedlv different biological properties. The major metabolites of oestrogen hydroxylated at the C-16a position (16a-hydroxyoestrone and oestriol) are oestrogenic (Martucci and Fishman.

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There has been recent interest in the possibility that breast cancer can have a prenatal origin (Trichopoulos, 1990). Various studies have reported on the relationship between birthweight, taken as a marker of prenatal environment, and breast cancer, but with differing results. One study (Ekbom et al, 1992; reported no association between birthweight and breast cancer, two (Le Marchand et al, 1988;Sanderson et al, 1996) an inverse relationship, and one (Michels et al, 1996) a positive association. The latter was a case-control study nested within the US Nurses' Cohort, which found that the odds of breast cancer for women who weighed 4 kg or more at birth was twice that of women who weighed less than 2.5 kg (Michels et al, 1996). The relationship was strongest for women aged 50 or younger.Various factors might explain the inconsistency of these results. In some studies the information on birthweight was based on recall by the women themselves or their mothers (Michels et al, 1996;Sanderson et al, 1996), in most no account was taken of adult-life risk factors for breast cancer (Ekbom et al, 1992;Le Marchand et al, 1988), and no account was taken in any of childhood and pubertal factors.The present study examines the relationship between birthweight and breast cancer in a UK national cohort of 2221 women who have been followed since their birth in 1946, and for whom data on birthweight, markers of childhood growth and adult-life risk factors for breast cancer have been recorded. The Medical Research Council National Survey of Health and Development (NSHD) is a socially stratified birth cohort of 2548 women and 2814 men born in the UK during the week 3-9 March 1946 (Wadsworth, 1991;Wadsworth and Kuh, 1997). The cohort comprised single, legitimate births to wives of all non-manual and agricultural workers and to 1 in 4 wives of manual workers. There have been 19 follow-up contacts with the cohort members between their birth and age 43 years, most by home interviews. The sample interviewed at age 43 years were, in most respects, representative of the native population of that age (Wadsworth et al, 1992). Since 1993, when the cohort members were 48 years of age, a postal health questionnaire has been sent annually to all women in the study with whom there was still direct contact. At these separate contacts, breast cancer diagnosis was self-reported and recorded. In 1971, when the National Health Service Central Register (NHSCR) started to record cancers occurring in the population of the UK, all cohort members (including those with whom there was no longer direct contact) were 'flagged' at the NHSCR. This provided notification of registrations of cancer, death and emigration for the cohort.Information on birthweight was extracted from the birth records of the cohort members and categorized into four groups: < 3.000 kg, 3.000-3.499 kg, 3.500-3.999 kg, ≥ 4.000 kg, in accord with previous studies (Ekbom et al, 1997;Michels et al, 1996). Data on maternal age and birth order were collected at the original h...