Background Morbidities related to obesity are usually associated with its severity and duration. Yet, the onset of serious morbidities in early adulthood among otherwise healthy adolescents with obesity is understudied. We aimed to investigate the association between adolescent BMI and serious morbidities before age 25 years. Methods In this nationwide, retrospective cohort study, we included Israeli conscripts aged 17-21 years who underwent pre-recruitment medical evaluation between Jan 1, 1996, and Dec 31, 2017, were deemed medically eligible for military service, and were recruited to the Israeli Defense Forces between 1998 and 2018. Exclusion criteria were missing height or weight or service ineligibility for non-medical or medical reasons. Baseline BMI was converted into age- specific and sex-specific percentiles and classified using the US Centers for Disease Control and Prevention categories. The primary outcome was incidence of serious morbidity disqualifying individuals from completing mandatory service. Participants were followed from enlistment until end of service (3 years for males and 2 years for females), onset of serious morbidity, or Dec 31, 2021. Cox models with adjustment to various socio-economic confounders were applied to calculate the hazard ratio (HR) and 95% CI for serious morbidity for the BMI categories. Findings A total of 1 264 355 adolescents aged 16-20 years were assessed for military service. 145 702 were excluded; 144 705 were considered ineligible for service (133 112 for non-medical reasons and 11 593 for medical reasons), and 2867 had missing height or weight data. The study included 1 118 653 individuals (622 989 [557%] males and 495 664 [443%] females), with 23 347 cases of serious morbidity recorded over 2 534 873 person-years. Incidence of serious morbidity increased across BMI groups in both sexes. Among males, compared with those with normal BMI, the adjusted HRs were 089 (95% CI 083-095) for underweight, 121 (116-127) for overweight, 139 (132-147) for obesity class 1, 282 (260-306) for obesity class 2, and 514 (437-604) for obesity class 3. For females, the respective ratios were HR 095 (95% CI 084-109) for underweight, 127 (117-137) for overweight, 163 (145-182) for obesity class 1, 400 (346-461) for obesity class 2, and 730 (565-943) for obesity class 3. Results persisted in sensitivity analyses restricted to those with unimpaired health at baseline or those in civilian-equivalent office employments. Interpretation Obesity in otherwise healthy adolescents was linked with increased risk of serious morbidity before age 25 years. Reducing adolescent obesity will have substantial short-term and long-term health benefits in young adults.

BackgroundThe association between hearing impairment and attention-deficit/hyperactivity disorder (ADHD) is unclear. Therefore, we aimed to assess this association in Israel's national sample of over 1.1 million adolescents.MethodsWe conducted a nationwide, population-based, cross-sectional study of all Israeli adolescents (n = 1,175,534, 58% males; mean age, 17 yrs) who were examined before mandatory military service during 2004 to 2020. Board-certified specialists confirmed diagnoses of hearing impairment and severe ADHD.Main Outcomes and MeasuresWe compared the prevalence of severe ADHD in adolescents with and without hearing impairment. Associations were analyzed using logistic regression models and sensitivity analyses accounting for hearing impairment type (sensorineural vs. conductive) and severity.ResultsOf the 8,769 adolescents with hearing impairment, 57 were diagnosed with severe ADHD (prevalence = 0.65%). Of the 1,166,765 adolescents without hearing impairment, 3,936 were diagnosed with severe ADHD (prevalence = 0.29%). We found a significant association between hearing impairment and severe ADHD (odds ratio = 1.93 [95% confidence interval, 1.47-2.49]), which persisted in a multivariable model adjusted to age, sex, socioeconomic status, educational status, cognitive performance, and immigration status (odds ratio = 1.70 [95% confidence interval, 1.29-2.20]). The association also persisted when stratified by hearing impairment type (sensorineural vs. conductive) and severity.ConclusionsAdolescents with hearing impairment had 70% increased odds of severe ADHD. Study findings suggest that active screening of patients with hearing impairment for ADHD should be considered.

ImportanceStudies on the familial effects of body mass index (BMI) status have yielded a wide range of data on its heritability. ObjectiveTo assess the heritability of obesity by measuring the association between the BMIs of fathers, mothers, and their offspring at the same age. Design, Setting, and ParticipantsThis cohort study used data from population-wide mandatory medical screening before compulsory military service in Israel. The study included participants examined between January 1, 1986, and December 31, 2018, whose both parents had their BMI measurement taken at their own prerecruitment evaluation in the past. Data analysis was performed from May to December 2023. Main Outcomes and MeasuresSpearman correlation coefficients were calculated for offsprings' BMI and their mothers', fathers', and midparental BMI percentile (the mean of the mothers' and fathers' BMI cohort- and sex-specific BMI percentile) to estimate heritability. Logistic regression models were applied to estimate the odds ratios (ORs) and 95% CIs of obesity compared with healthy BMI, according to parental BMI status. ResultsA total of 447 883 offspring (235 105 male [52.5%]; mean [SD] age, 17.09 [0.34] years) with both parents enrolled and measured for BMI at 17 years of age were enrolled in the study, yielding a total study population of 1 343 649 individuals. Overall, the correlation between midparental BMI percentile at 17 years of age and the offspring's BMI at 17 years of age was moderate (rho = 0.386). Among female offspring, maternal-offspring BMI correlation (rho = 0.329) was somewhat higher than the paternal-offspring BMI correlation (rho = 0.266). Among trios in which both parents had a healthy BMI, the prevalence of overweight or obesity in offspring was 15.4%; this proportion increased to 76.6% when both parents had obesity and decreased to 3.3% when both parents had severe underweight. Compared with healthy weight, maternal (OR, 4.96; 95% CI, 4.63-5.32), paternal (OR, 4.48; 95% CI, 4.26-4.72), and parental (OR, 6.44; 95% CI, 6.22-6.67) obesity (midparent BMI in the >= 95th percentile) at 17 years of age were associated with increased odds of obesity among offspring. Conclusions and RelevanceIn this cohort study of military enrollees whose parents also underwent prerecruitment evaluations, the observed correlation between midparental and offspring BMI, coupled with a calculated narrow-sense heritability of 39%, suggested a substantive contribution of genetic factors to BMI variation at 17 years of age.

IMPORTANCE:The increased incidence of adolescent obesity over recent decades may be associated with lower cognitive performance than the expected potential. OBJECTIVE:We aimed to assess the association between adolescent body mass index (BMI) and cognitive function. DESIGN:A nationwide, cross-sectional, population-based study. SETTING:Pre-recruitment evaluation for military service during 1967-2018. PARTICIPANTS:All Israeli-born adolescents, 1 459 522 males and 1 027 953 females aged 16 to ≤20 years. EXPOSURES:Weight and height were measured to calculate BMI. MAIN OUTCOME:Cognitive performance was assessed by using a validated intelligence-quotient-equivalent test and was standardized to the year- and sex-Z-score. For 445 385 persons, parental cognitive scores could be identified. Multinomial logistic regression models were applied. RESULTS:Among male adolescents with severe obesity, 29.4% achieved a cognitive score below the 25th percentile, compared with 17.7% among their normal-weight (50th-84th percentile) counterparts. A J-shaped relation was observed between BMI and the odds ratio (OR) for a low cognitive score among male adolescents: underweight, 1.45 (1.43-1.48); overweight, 1.13 (1.12-1.15); mild obesity, 1.36 (1.33-1.39); and severe obesity, 1.58 (1.52-1.64). Similar findings were observed in females. For both sexes, point estimates were overall consistent in models adjusted for sociodemographic confounders, coexisting morbidities, and parental cognitive scores. Examinees with abnormal BMI had higher ORs for a lower-than-expected cognitive score, based on their parents' data as adolescents, in a manner that depends on obesity severity. CONCLUSION AND RELEVANCE:Obesity, is associated with increased odds for a lower cognitive performance, and the inability to fully achieve cognitive potential, regardless of sociodemographic background.

BackgroundThe association between body mass index (BMI) and migraine in adults has been well established. However, studies in children and adolescents are inconclusive. We aimed to study the association between BMI and migraine using a national dataset that comprises the electronic medical records of more than two million adolescents.MethodsThis study included all Israeli adolescents (57.7% males, 42.3% females; mean age 17 years) who were medically assessed before mandatory military service during 1990-2020. As part of the pre-recruitment medical assessment, all the adolescents were screened for migraine and their height and weight were measured. Diagnoses of migraine were confirmed by board-certified neurologists. Prevalences and odds ratios (ORs) for migraine were computed across BMI subgroups. Spline models were applied.ResultsA total of 2,094,862 adolescents were included, of whom 57,385 (2.8%) had active migraine. Among males, the adjusted ORs for migraine were 1.11 (95% confidence interval, 1.06-1.16), 1.13 (1.08-1.17), and 1.24 (1.19-1.30), for the underweight, overweight, and obesity subgroups, respectively, compared to the reference group of low-normal BMI (5th-49th percentile). Among females, the respective adjusted ORs were 1.12 (1.05-1.19), 1.23 (1.19-1.28), and 1.38 (1.31-1.46). Results persisted in sensitivity analyses accounting for other medical and psychiatric comorbidities and parental history of migraine. Spline models demonstrated a J-shaped relation between BMI and migraine.ConclusionsBoth adolescent obesity and underweight were associated with migraine in a sex-dependent manner. This association peaked in female adolescents with overweight and obesity.

Objective: To assess the association between hypermobility spectrum disorders/hypermobile type Ehlers Danlos Syndrome (HSD/hEDS) and migraine in a national sample of adolescents in Israel.Background: The association between HSD/hEDS and migraine is unclear, even more so in pediatric populations.Methods: This population-based, cross-sectional study included 1,627,345 Israeli adolescents (945,519/1,626,407 [58%] males; mean age 17 +/- 0.5 years) who were medically assessed before mandatory military service during 1998-2020. Diagnoses of migraine with at least one attack per month (active migraine) and HSD/hEDS were confirmed by certified specialists. The prevalences of active migraine in adolescents with and without HSD/hEDS were computed and the association between HSD/hEDS and active migraine was examined.Results: Active migraine was significantly more prevalent in adolescents with HSD/hEDS (307/4686 [6.5%]) compared to those without HSD/hEDS (51,931/1,621,721 [3.2%]) (OR = 2.16, 95% CI 1.90-2.45). The association between HSD/hEDS and active migraine persisted in a multivariable analysis (OR = 2.08, 95% CI 1.85-2.34) and in several sensitivity analyses.Conclusions: We found a significant association between HSD/hEDS and active migraine in both male and female adolescents. Clinical awareness of the association can promote early diagnosis and treatment of migraine. Further research is required to identify appropriate pharmacologic and nonpharmacologic migraine treatment strategies for individuals with HSD/hEDS.

The association between hypermobility spectrum disorders/hypermobile type Ehlers–Danlos syndrome (HDS/hEDS) and irritable bowel syndrome (IBS) is yet to be clarified. We aimed to assess this association in a national sample of adolescents.

In brief: The impact of immigration on the risk of early-onset T2DM (before age 40 years) was assessed in a nationwide cohort. Data on 93 806 native Israelis and 27 684 Israelis of Ethiopian origin, assessed at a mean age 17.5 years, were linked to the Israeli National Diabetes Registry. After adjustment for sociodemographic confounders, the hazard ratios for T2DM among Ethiopian men with normal and high BMI were 3.4 (2.3–5.1) and 15.8 (8.3–30.3), respectively, compared to third-generation Israelis with normal BMI. When the analysis was limited to Israeli-born Ethiopian men, the hazard ratios increased to 4.4 (1.7–11.4) and 29.1 (12.9–70.6), respectively.

Background. Gliomas manifest in a variety of histological phenotypes with varying aggressiveness. The etiology of glioma remains largely unknown. Taller stature in adulthood has been linked with glioma risk. The aim of this study was to discern whether this association can be detected in adolescence. Methods. The cohort included 2 223 168 adolescents between the ages of 16 and 19 years. Anthropometric measurements were collected at baseline. Incident cases of glioma were extracted from the Israel National Cancer Registry over a follow-up period spanning 47 635 745 person-years. Cox proportional hazard models were used to estimate the hazard ratio (HR) for glioma and glioma subtypes according to height, body mass index (BMI), and sex. Results. A total of 1195 patients were diagnosed with glioma during the study period. Mean (SD) age at diagnosis was 38.1 (11.7) years. Taller adolescent height (per 10-cm increase) was positively associated with the risk for glioma of any type (HR: 1.15; P= .002). The association was retained in subgroup analyses for low-grade glioma (HR: 1.17; P = .031), high-grade glioma (HR: 1.15; P = .025), oligodendroglioma (HR: 1.31; P = .015), astrocytoma (HR: 1.12; P= .049), and a category of presumed IDH-mutated glioma (HR: 1.17; P= .013).There was a trend toward a positive association between height and glioblastoma, however this had borderline statistical significance (HR: 1.15; P= .07). After stratification of the cohort by sex, height remained a risk factor for men but not for women. Conclusions. The previously established association between taller stature in adulthood and glioma risk can be traced back to adolescence.The magnitude of association differs by glioma subtype.

Background: We assessed in a nationwide cohort the association between adolescent BMI and early-onset (<40 years) type 2 diabetes among Israelis of Ethiopian origin. Methods: Normoglycemic adolescents (range 16-20 years old), including 93,806 native Israelis (≥3 rd generation in Israel) and 27,684 Israelis of Ethiopian origin, were medically assessed for military service between 1996 and 2011. Weight and height were measured. Data were linked to the Israeli National Diabetes Registry. Incident type 2 diabetes by December 31, 2016 was the outcome. Cox regression models stratified by sex and BMI categories were applied. Results: 226 (0.29%) men and 79 (0.18%) women developed diabetes during 992,980 and 530,814 person-years follow-up, respectively, at a mean age of 30.4 and 27.4 years, respectively. Among native Israeli men with normal and high (overweight and obese) BMI, diabetes incidence was 9.5 and 62.0 (per 10 5 person-years), respectively. The respective incidences were 46.9 and 112.3 among men of Ethiopian origin. After adjustment for sociodemographic confounders, the hazard ratios for type 2 diabetes among Ethiopian men with normal and high BMI were 3.4 (2.3-5.1) and 15.8 (8.3-30.3) respectively, compared to third-generation Israelis with normal BMI. When this analysis was limited to Israeli-born Ethiopian men, the hazard ratios were 4.4 (1.7-11.4) and 29.1 (12.9-70.6), respectively. Results persisted when immigrants of other white Caucasian origin were the reference; and among women with normal, but not high, BMI. Conclusions: Ethiopian origin is a risk factor for early-onset type 2 diabetes among young men at any BMI, and may require selective interventions.