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STUDY QUESTION: Does BMI at 7-10 years of age differ in children conceived after frozen embryo transfer (FET) compared to children conceived after fresh embryo transfer (fresh-ET) or natural conception (NC)? SUMMARY ANSWER: BMI in childhood does not differ between children conceived after FET compared to children conceived after fresh-ET or NC. WHAT IS KNOWN ALREADY: High childhood BMI is strongly associated with obesity and cardiometabolic disease and mortality in adulthood. Children conceived after FET have a higher risk of being born large for gestational age (LGA) than children conceived after NC. It is well-documented that being born LGA is associated with an increased risk of obesity in childhood, and it has been hypothesized that ART induces epigenetic variations around fertilization, implantation, and early embryonic stages, which influence fetal size at birth as well as BMI and health later in life. STUDY DESIGN, SIZE, DURATION: The study 'Health in Childhood following Assisted Reproductive Technology' (HiCART) is a large retrospective cohort study with 606 singletons aged 7-10 years divided into three groups according to mode of conception: FET (n = 200), fresh-ET (n = 203), and NC (n = 203). All children were born in Eastern Denmark from 2009 to 2013 and the study was conducted from January 2019 to September 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS: We anticipated that the participation rate would differ between the three study groups owing to variation in the motivation to engage. To reach the goal of 200 children in each group, we invited 478 in the FET-group, 661 in the fresh-ET-group, and 1175 in the NC-group. The children underwent clinical examinations including anthropometric measurements, whole-body dual-energy x-ray absorptiometry-scan, and pubertal staging. Standard deviation scores (SDS) were calculated for all anthropometric measurements using Danish reference values. Parents completed a questionnaire regarding the pregnancy and the current health of the child and themselves. Maternal, obstetric, and neonatal data were obtained from the Danish IVF Registry and Danish Medical Birth Registry. MAIN RESULTS AND THE ROLE OF CHANCE: As expected, children conceived after FET had a significantly higher birthweight (SDS) compared to both children born after fresh-ET (mean difference 0.42, 95% CI (0.21; 0.62)) and NC (mean difference 0.35, 95% CI (0.14; 0.57)). At follow-up (7-10 years), no differences were found in BMI (SDS) comparing FET to fresh-ET, FET to NC, and fresh-ET to NC. Similar results were also found regarding the secondary outcomes weight (SDS), height (SDS), sitting height, waist circumference, hip circumference, fat, and fat percentage. In the multivariate linear regression analyses, the effect of mode of conception remained non-significant after adjusting for multiple confounders. When stratified on sex, weight (SDS), and height (SDS) were significantly higher for girls born after FET compared to girls born after NC. Further, FET-girls also had significantly higher waist, hip, and fat measurements compared to girls born after fresh-ET. However, for the boys the differences remained insignificant after confounder adjustment. LIMITATIONS, REASONS FOR CAUTION: The sample size was decided in order to detect a difference of 0.3 SDS in childhood BMI (which corresponds to an adult cardiovascular mortality hazard ratio of 1.034). Thus, smaller differences in BMI SDS may be overlooked. As the overall participation rate was 26% (FET: 41%, fresh-ET: 31%, NC: 18%), selection bias cannot be excluded. Regarding the three study groups, many possible confounders have been included but there might be a small risk of selection bias as information regarding cause of infertility is not available in this study. WIDER IMPLICATIONS OF THE FINDINGS: The increased birthweight in children conceived after FET did not translate into differences in BMI, however, for the girls born after FET, we observed increased height (SDS) and weight (SDS) compared to the girls born after NC, while for the boys the results remained insignificant after confounder adjustment. Since body composition in childhood is a strong biomarker of cardiometabolic disease later in life, longitudinal studies of girls and boys born after FET are needed. STUDY FUNDING/COMPETING INTEREST(S): The study was funded by the Novo Nordisk Foundation (grant number: NNF18OC0034092, NFF19OC0054340) and Rigshospitalets Research Foundation. There were no competing interests. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier: NCT03719703.

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CONTEXT: The prevalence of gestational diabetes mellitus (GDM) is increasing, and intrauterine hyperglycemia is suspected to affect offspring cognitive function. OBJECTIVE: We assessed academic performance by grade point average (GPA) in children aged 15 to 16 years at compulsory school graduation, comparing offspring exposed to GDM (O-GDM) with offspring from the background population (O-BP). METHODS: This register-based, cohort study comprised all singletons born in Denmark between 1994 and 2001 (O-GDM: n = 4286; O-BP: n = 501 045). Standardized and internationally comparable GPAs were compared in univariate and multivariable linear models. Main outcome measures included the adjusted mean difference in GPA. We also analyzed the probability of having a high GPA, a GPA below passing, and no GPA registered. RESULTS: O-GDM had a GPA of 6.29 (SD 2.52), whereas O-BP had a GPA of 6.78 (SD 2.50). The adjusted mean difference was -0.36 (95% CI, -0.44 to -0.29), corresponding to a Cohen's D of 0.14. O-GDM had a lower probability of obtaining a high GPA (adjusted odds ratio [aOR] 0.68; 95% CI, 0.59 to 0.79), while their risk of obtaining a GPA below passing was similar to O-BP (aOR 1.20; 95% CI, 0.96 to 1.50). O-GDM had a higher risk of not having a GPA registered (aOR 1.38; 95% CI, 1.24 to 1.53). CONCLUSION: Academic performance in O-GDM was marginally lower than in O-BP. However, this difference is unlikely to be of clinical importance.

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BACKGROUND: A myofascial trigger point is defined as a hyperirritable spot in skeletal muscle that is associated with a hypersensitive palpable nodule in a taut band. It has been suggested that myofascial trigger points take part in chronic pain conditions including primary headache disorders. The aim of this narrative review is to present an overview of the current imaging modalities used for the detection of myofascial trigger points and to review studies of myofascial trigger points in migraine and tension-type headache. FINDINGS: Different modalities have been used to assess myofascial trigger points including ultrasound, microdialysis, electromyography, infrared thermography, and magnetic resonance imaging. Ultrasound is the most promising of these modalities and may be used to identify MTrPs if specific methods are used, but there is no precise description of a gold standard using these techniques, and they have yet to be evaluated in headache patients. Active myofascial trigger points are prevalent in migraine patients. Manual palpation can trigger migraine attacks. All intervention studies aiming at trigger points are positive, but this needs to be further verified in placebo-controlled environments. These findings may imply a causal bottom-up association, but studies of migraine patients with comorbid fibromyalgia syndrome suggest otherwise. Whether myofascial trigger points contribute to an increased migraine burden in terms of frequency and intensity is unclear. Active myofascial trigger points are prevalent in tension-type headache coherent with the hypothesis that peripheral mechanisms are involved in the pathophysiology of this headache disorder. Active myofascial trigger points in pericranial muscles in tension-type headache patients are correlated with generalized lower pain pressure thresholds indicating they may contribute to a central sensitization. However, the number of active myofascial trigger points is higher in adults compared with adolescents regardless of no significant association with headache parameters. This suggests myofascial trigger points are accumulated over time as a consequence of TTH rather than contributing to the pathophysiology. CONCLUSIONS: Myofascial trigger points are prevalent in both migraine and tension-type headache, but the role they play in the pathophysiology of each disorder and to which degree is unclarified. In the future, ultrasound elastography may be an acceptable diagnostic test.

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