Genetic counselling legislation and practice in cancer in EU Member States.

BACKGROUND: Somatic and germline genetic alterations are significant drivers of cancer. Increasing integration of new technologies which profile these alterations requires timely, equitable and high-quality genetic counselling to facilitate accurate diagnoses and informed decision-making by patients and their families in preventive and clinical settings. This article aims to provide an overview of genetic counselling legislation and practice across European Union (EU) Member States to serve as a foundation for future European recommendations and action. METHODS: National legislative databases of all 27 Member States were searched using terms relevant to genetic counselling, translated as appropriate. Interviews with relevant experts from each Member State were conducted to validate legislative search results and provide detailed insights into genetic counselling practice in each country. RESULTS: Genetic counselling is included in national legislative documents of 22 of 27 Member States, with substantial variation in legal mechanisms and prescribed details (i.e. the 'who, what, when and where' of counselling). Practice is similarly varied. Workforce capacity (25 of 27 Member States) and genetic literacy (all Member States) were common reported barriers. Recognition and/or better integration of genetic counsellors and updated legislation and were most commonly noted as the 'most important change' which would improve practice. CONCLUSIONS: This review highlights substantial variability in genetic counselling across EU Member States, as well as common barriers notwithstanding this variation. Future recommendations and action should focus on addressing literacy and capacity challenges through legislative, regulatory and/or strategic approaches at EU, national, regional and/or local levels.

Self-reported functioning among patients with ultra-rare nemaline myopathy or a related disorder in Finland: a pilot study.

BACKGROUND: Nemaline myopathy (NM) and related disorders (NMr) form a heterogenous group of ultra-rare (1:50,000 live births or less) congenital muscle disorders. To elucidate the self-reported physical, psychological, and social functioning in the daily lives of adult persons with congenital muscle disorders, we designed a survey using items primarily from the Patient Reported Outcomes Measurement Information System, PROMIS®, and conducted a pilot study in patients with NM and NMr in Finland. The items were linked to International Classification of Functioning, Disability and Health (ICF) categories. RESULTS: In total, 20 (62.5%) out of 32 invited persons resident in Finland participated in the study; 12 had NM and 8 NMr, 15 were women and 5 men aged 19-75 years. Sixteen (80%) were ambulatory and 4 (20%) NM patients used wheelchairs. The results from the PROMIS measuring system and ICF categories both indicated that non-ambulatory patients of this study faced more challenges in all areas of functioning than ambulatory ones, but the differences were smaller in the domains measuring psychological and social functioning than in physical functioning. In addition, the COVID-19 pandemic adversely affected the functioning of non-ambulatory patients more than that of ambulatory patients. The interindividual differences were, however, noticeable. CONCLUSIONS: To our knowledge, this pilot study is the first comprehensive survey-based study of the physical, psychological, and social functioning of adult persons with nemaline myopathy or related disorders. The results indicate vulnerability of non-ambulatory patients being at higher risk to a decrease in general functioning during global or national exceptional periods. The responses also gave directions for modifying and improving the survey for future studies.

Multi-exon COL5A1 deletion in a child with classical Ehlers-Danlos syndrome: A case report expanding the allelic spectrum and showing evidence of parental gonosomal mosaicism.

Classical Ehlers-Danlos syndrome (cEDS) is a rare inherited autosomal dominant connective tissue disorder with core clinical features including skin hyperextensibility, abnormal scarring, and generalized joint hypermobility. Classical EDS is predominantly caused by small pathogenic variants in the genes COL5A1 and COL5A2 and occasionally by a COL1A1 point mutation p.(Arg312Cys), while gross deletions or duplications are uncommon. Gonosomal mosaicism is thought to be exceedingly rare with only two cases reported in the literature. We report a child with cEDS due to a rare gross deletion of exons 2-65 in the COL5A1 gene, inherited from an unaffected mosaic father. The level of mosaicism in the father was approximately 43% in leucocyte cells and 30% in DNA extracted from skin. Our results expand the allelic spectrum of cEDS variants and suggest that parental mosaicism needs to be considered in patients with suspected cEDS, given its implication for genetic counseling.

A novel MPLKIP-variant in three Finnish patients with non-photosensitive trichothiodystrophy type 4.

Trichothiodystrophy is a group of multisystem neuroectodermal disorders with dysplastic hair as the cardinal symptom. We describe three patients from two Finnish families in whom whole-exome sequencing revealed a novel homozygous variant, c.26del, p.(Pro9Glnfs*144) in the MPLKIP-gene, confirming the diagnosis of non-photosensitive trichothiodystrophy type 4 (TTD4). The variant was confirmed by Sanger sequencing and inherited from unaffected carrier parents. This report adds to the literature by expanding the genetic and phenotypic spectra of MPLKIP-related trichothiodystrophy. We describe dysmorphic features in the patients and provide a comparison of clinical characteristics in patients with TTD4 reported to date.

Migraine in children and adults born preterm: A nationwide register linkage study.

OBJECTIVE: Being born preterm is related to adverse health effects later in life. We studied whether preterm birth predicts the risk of migraine. METHODS: In this nationwide register study, we linked data from six administrative registers for all 235,624 children live-born in Finland (January 1987 to September 1990) and recorded in the Finnish Medical Birth Register. n = 228,610 (97.0%) had adequate data and were included. Migraine served as primary outcome variable and was stringently defined as a diagnosis from specialised health care and/or ≥2 reimbursed purchases of triptans. We applied sex- and birth year-stratified Cox proportional hazard regression models to compute hazard ratios and confidence intervals (95% confidence intervals) for the association between preterm categories and migraine. The cohort was followed up until an average age of 25.1 years (range: 23.3-27.0). RESULTS: Among individuals born extremely preterm (23-27 completed weeks of gestation), the adjusted hazard ratios for migraine was 0.55 (0.25-1.24) when compared with the full-term reference group (39-41 weeks). The corresponding adjusted hazard ratios and 95% confidence intervals for the other preterm categories were: Very preterm (28-31 weeks); 0.95 (0.68-1.31), moderately preterm (32-33 weeks); 0.96 (0.73-1.27), late preterm (34-36 weeks); 1.01 (0.91-1.11), early term (37-38 weeks); 0.98 (0.93-1.03), and post term (42 weeks); 0.98 (0.89-1.08). Migraine was predicted by parental migraine, lower socioeconomic position, maternal hypertensive disorder and maternal smoking during pregnancy. CONCLUSION: We found no evidence for a higher risk of migraine among individuals born preterm.

Adult outcomes of being born late preterm or early term - What do we know?

The literature on adult outcomes of people born late preterm (LPT, 34-36 completed weeks) or early term (ET, 37-38 weeks) was reviewed. In PubMed, 9547 articles were identified; 53 were eligible. Of these, 12 were based on clinical cohorts, 32 on medical birth register linkages, and nine on historical birth cohorts; 48 out of 53 on Nordic countries; 50 out of 53 reported on LPT and eight out of 53 reported on ET. LPT plus ET have increased early (<45 years) adult all-cause mortality. Despite increased cardiometabolic risk factors and slightly lower cardiorespiratory fitness in LPT, no studies showed increased risk for coronary heart disease, some showed increased risk for stroke, and all showed increased risk for type 2 diabetes. Most show increased risk for asthma and decreased allergic rhinitis. LPT have slightly lower cognitive abilities and higher rates of several mental disorders; ET have intermediate values. LPT and ET adults have slightly lower education, occupational status, and income. We recommend that authors report findings of LPT/ET separately from those born more preterm.

Detection of variants in dystroglycanopathy-associated genes through the application of targeted whole-exome sequencing analysis to a large cohort of patients with unexplained limb-girdle muscle weakness.

BACKGROUND: Dystroglycanopathies are a clinically and genetically heterogeneous group of disorders that are typically characterised by limb-girdle muscle weakness. Mutations in 18 different genes have been associated with dystroglycanopathies, the encoded proteins of which typically modulate the binding of α-dystroglycan to extracellular matrix ligands by altering its glycosylation. This results in a disruption of the structural integrity of the myocyte, ultimately leading to muscle degeneration. METHODS: Deep phenotypic information was gathered using the PhenoTips online software for 1001 patients with unexplained limb-girdle muscle weakness from 43 different centres across 21 European and Middle Eastern countries. Whole-exome sequencing with at least 250 ng DNA was completed using an Illumina exome capture and a 38 Mb baited target. Genes known to be associated with dystroglycanopathies were analysed for disease-causing variants. RESULTS: Suspected pathogenic variants were detected in DPM3, ISPD, POMT1 and FKTN in one patient each, in POMK in two patients, in GMPPB in three patients, in FKRP in eight patients and in POMT2 in ten patients. This indicated a frequency of 2.7% for the disease group within the cohort of 1001 patients with unexplained limb-girdle muscle weakness. The phenotypes of the 27 patients were highly variable, yet with a fundamental presentation of proximal muscle weakness and elevated serum creatine kinase. CONCLUSIONS: Overall, we have identified 27 patients with suspected pathogenic variants in dystroglycanopathy-associated genes. We present evidence for the genetic and phenotypic diversity of the dystroglycanopathies as a disease group, while also highlighting the advantage of incorporating next-generation sequencing into the diagnostic pathway of rare diseases.

A novel compound heterozygous mutation in the POMK gene causing limb-girdle muscular dystrophy-dystroglycanopathy in a sib pair.

We describe two Finnish siblings in whom an incidentally detected elevated creatine kinase activity eventually led to a diagnosis of limb-girdle muscular dystrophy-dystroglycanopathy (Type C12; MDDGC12). When diagnosed at age 10 and 13 years, they were mildly affected with a slow or non-progressive disease course. The main symptoms comprised infrequent hip cramps triggered by flexion, neck cramps triggered by yawning, transient growing pains, calf hypertrophy and mild proximal muscle weakness. Their cognitive and motor developments were unremarkable and they were physically active. Whole-exome sequencing revealed compound heterozygous mutations, both of which were novel, in the protein O-mannosyl kinase (POMK) gene in both siblings; a missense mutation, p.Pro322Leu (c.965C > T), and a nonsense mutation, p.Arg46Ter (c.136C > T). The results were confirmed by Sanger sequencing, showing that the parents were heterozygous carriers of one mutation each. This report adds to the literature by providing phenotype and genotype data on this ultra-rare POMK-related dystroglycanopathy.

Infant Growth after Preterm Birth and Mental Health in Young Adulthood.

OBJECTIVES: Faster growth after preterm birth benefits long-term cognitive functioning. Whether these benefits extend to mental health remains largely unknown. We examined if faster growth in infancy is associated with better self-reported mental health in young adults born preterm at very low birth weight (VLBW) (< 1500 g). STUDY DESIGN: As young adults, participants of the Helsinki Study of Very Low Birth Weight Adults self-reported symptoms of depression and attention deficit/hyperactivity disorder (ADHD) (n = 157) and other psychiatric problems (n = 104). As main predictors of mental health outcomes in linear regression models, we used infant weight, length, and head circumference at birth, term, and 12 months of corrected age, and growth between these time points. Growth data were collected from records and measures at term and at 12 months of corrected age were interpolated. Additionally, we examined the moderating effects of intrauterine growth restriction. RESULTS: Size at birth, term, or 12 months of corrected age, or growth between these time points were not associated with mental health outcomes (p-values >0.05). Intrauterine growth restriction did not systematically moderate any associations. CONCLUSIONS: Despite the high variability in early growth of VLBW infants, the previously described association between slow growth in infancy and poorer cognitive functioning in later life is not reflected in symptoms of depression, ADHD, and other psychiatric problems. This suggests that the development of cognitive and psychiatric problems may have dissimilar critical periods in VLBW infants.

Insulin sensitivity and secretory response in adults born preterm: the Helsinki Study of Very Low Birth Weight Adults.

CONTEXT: Preterm birth is associated with an increased risk of type 2 diabetes in adult life. The mechanisms are poorly known. OBJECTIVE: We studied insulin sensitivity and secretion in adults born preterm at very low birth weight (VLBW; < 1500 g). DESIGN: Longitudinal Birth Cohort Study (Helsinki Study of Very Low Birth Weight Adults). SETTING: The study was conducted at Uusimaa, Finland. PARTICIPANTS: One hundred seven adults born at VLBW and 100 controls born at term not small for gestational age (SGA), group-matched for sex, age, and birth hospital. The mean age was 25.0 years. MAIN OUTCOME MEASURES: We performed a 14-sample intravenous glucose tolerance test and calculated insulin sensitivity (Si), insulin secretory response (AIR), and disposition index, by Minimal Model (Minmod Millennium®). RESULTS: Compared with controls, VLBW adults had lower Si (mean difference -11.9%, 95% CI -22.1 to -0.4%, adjusted for sex, age, and body mass index) and higher AIR (19.9%; 4.4-37.7%). The association with Si attenuated when further adjusted for height, parental diabetes, parental education, smoking, maternal smoking, hormonal contraception, and physical activity, but the association with AIR remained. Disposition index was similar. There was no difference between the 40 VLBW adults born SGA and the remaining VLBW adults. CONCLUSIONS: Adults born preterm at VLBW have lower insulin sensitivity than their term-born peers with a similar body size. In young adulthood, this remains compensated by higher insulin secretion. We suggest that this represents an early stage in the pathway leading to type 2 diabetes. Our results underline the importance of a healthy lifestyle and prompt vigilance in the screening of type 2 diabetes and impaired glucose tolerance in adults born preterm.

Very low birth weight, infant growth, and autism-spectrum traits in adulthood.

OBJECTIVES: We examined whether adults born preterm at very low birth weight (VLBW; <1500 g) differ from term-born adults in autism-spectrum traits, and whether among VLBW adults, growth in infancy is associated with these traits. METHODS: A total of 110 VLBW and 104 term-born adults of the Helsinki Study of Very Low Birth Weight Adults completed the Autism-Spectrum Quotient yielding total, social interaction, and attention to detail sum scores. Growth in weight, length, and head circumference from birth to term and from term to 1 year of corrected age was determined as standardized residuals reflecting growth conditional on previous history. RESULTS: VLBW adults scored higher than term-born controls on social interaction sum score, indicating higher autism-spectrum traits. In contrast, they scored lower on attention to detail sum score, indicating lower autism-spectrum traits. Within the VLBW group, faster growth in weight, length, and head circumference from birth to term was associated with lower total and social interaction sum scores. In this group, growth from term to 1 year was not associated with autism-spectrum traits. CONCLUSIONS: Among those born preterm at VLBW, the risk for higher levels of autism-spectrum traits, particularly related to social interaction, may persist into adulthood. Faster growth from birth to term may ameliorate these effects, suggesting that targeted interventions could aid long-term neurodevelopment.

Infant growth after preterm birth and neurocognitive abilities in young adulthood.

OBJECTIVES: To examine whether faster growth from birth to term (40 postmenstrual weeks) and during the first year thereafter was associated with better neurocognitive abilities in adults born preterm with very low birth weight (VLBW; <1500 g). STUDY DESIGN: Weight, length, and head circumference data of 103 VLBW participants of the Helsinki Study of Very Low Birth Weight Adults were collected from records. Measures at term and at 12 months of corrected age were interpolated. The participants underwent tests of general neurocognitive ability, executive functioning, attention, and visual memory at mean age of 25.0 years. RESULTS: Faster growth from birth to term was associated with better general neurocognitive abilities, executive functioning, and visual memory in young adulthood. Effect sizes in SD units ranged from 0.23-0.43 per each SD faster growth in weight, length, or head circumference (95% CI 0.003-0.64; P values <.05). After controlling for neonatal complications, faster growth in head circumference remained more clearly associated with neurocognitive abilities than weight or length did. Growth during the first year after term was not consistently associated with neurocognitive abilities. CONCLUSIONS: Within a VLBW group with high variability in early growth, faster growth from birth to term is associated with better neurocognitive abilities in young adulthood. Neurocognitive outcomes were predicted, in particular, by early postnatal head growth.

Advanced sleep-wake rhythm in adults born prematurely: confirmation by actigraphy-based assessment in the Helsinki Study of Very Low Birth Weight Adults.

OBJECTIVE: Previous studies have suggested a propensity towards morningness in teenagers and adults born preterm. We set out to study sleep in a subsample from The Helsinki Study of Very Low Birth Weight Adults cohort, with emphasis on sleep timing, duration, and quality. We compared young adults who were born prematurely at very low birth weight (VLBW; <1500 g) with controls born at term. METHODS: We measured sleep by actigraphy in young adults aged 21-29 years. A total of 75 individuals (40 VLBW and 35 controls) provided adequate data. Group differences in sleep parameters were analyzed using t-test and linear regression models. RESULTS: VLBW adults woke up on average 40 min earlier [95% confidence interval (CI), 9-70] and reported 40 min earlier get up time (95% CI, 8-71) than did the controls. The difference remained after adjustment for confounders. We found no group difference in sleep duration or measures of sleep quality. CONCLUSION: Our findings of earlier rising in the VLBW group are suggestive of an advanced sleep phase in that group. These results reinforce previous suggestions that chronotype may be programmed early during life.

Maternal preeclampsia and bone mineral density of the adult offspring.

OBJECTIVE: Preterm birth at very low birthweight (<1500 g) is associated with cardiometabolic risk factors and reduced bone mineral density in the adult offspring. Preeclampsia is a frequent cause of preterm birth and is also associated with cardiometabolic risk factors in the offspring. Whether it is associated with bone mineral density is not known. STUDY DESIGN: We evaluated skeletal health in participants of the Helsinki Study of Very Low Birthweight Adults: 144 born at very low birthweight and 139 born at term. From the very low birthweight and term offspring a respective 32 and 11 were born from pregnancy complicated by preeclampsia. We measured bone mineral density at age 18.5 to 27.1 years by dual X-ray absorptiometry. RESULTS: Very low birthweight adults exposed to maternal preeclampsia had higher lumbar spine Z score (mean -0.44, compared with -1.07 in very low birthweight unexposed adults, P = .002), femoral neck Z score (-0.05 vs -0.53, P = .003) and whole body bone mineral density Z score (-0.14 vs -0.72, P = .001). Corresponding Z scores for those born at term were -0.02 (preeclampsia) and -0.45 (no preeclampsia) for lumbar spine (P = .2), 0.78 and 0.08 for femoral neck (P = .02) and 0.02 and -0.31 for whole body bone mineral density Z score (P = .08). The results survived adjustment for offspring current height, body mass index, leisure time physical activity, socioeconomic position, smoking, and maternal smoking during pregnancy, and maternal prepregnancy body mass index. CONCLUSION: Young adults exposed to maternal preeclampsia have higher bone mineral density than those not exposed. This difference is seen among those born at very low birthweight and seems also to be present among those born at term.

Self- and parent-rated executive functioning in young adults with very low birth weight.

BACKGROUND AND OBJECTIVE: Adults born preterm score lower on performance-based tests of executive functioning (EF) than their term-born peers. These test scores do not necessarily translate to application of these skills in an everyday environment. The objective of the study was to test differences between very low birth weight (VLBW; <1500 g) adults and their term-born peers in self- and parent-rated EF and examine concordance between self- and parent-rated EF and performance-based tests of EF. METHODS: A longitudinal study of 90 VLBW adults and 93 term-born controls (aged 21-30 years) was performed. The young adults and their parents filled in the Behavioral Rating Inventory of Executive Functioning-Adult Version, and the adults underwent performance-based tests of EF. RESULTS: VLBW young adults and especially those born appropriate for gestational age reported fewer problems in behavioral regulation and global EF than term-born controls; however, parents of VLBW adults born small for gestational age reported more problems for their children in all EF scales than parents of the controls. Compared with their parents, VLBW young adults reported fewer problems in behavioral regulation. Adults' ratings and their parents' ratings correlated significantly among VLBW and control groups. In the VLBW and VLBW/small-for-gestational-age groups, parent ratings of EF were correlated to performance-based tests, whereas among term-born adults, self-reports correlated. CONCLUSIONS: These findings reveal that VLBW adults may have learned to compensate in the everyday environment for their EF deficits apparent in performance-based tests. Alternatively, VLBW adults may have positively skewed views of their abilities.

PP083. Maternal pre-eclampsia and bone mineral density of the adult offspring.

INTRODUCTION: Preterm birth at very low birth weight (VLBW; <1500g) is associated with cardiometabolic risk factors and reduced bone mineral density (BMD) in the adult offspring. Pre-eclampsia (PE) is a frequent cause of preterm birth and is also associated with cardiometabolic risk factors in the offspring. Whether it is associated with BMD is not known. OBJECTIVE: To study BMD in adult offspring of mothers with pre-eclampsia. METHODS: We studied participants of the Helsinki Study of Very Low Birth Weight Adults: 144 born at VLBW and 139 born at term. From the VLBW and term offspring a respective 32 and 11 were born from pregnancy complicated by preeclampsia. We measured BMD at age 18-27 years by dual X-ray absorptiometry. We express BMD in Z scores which indicate the difference in SD units from the value expected for sex and age. RESULTS: VLBW adults exposed to maternal pre-eclampsia had higher lumbar spine Z score (mean -0.44 SD units, compared to -1.07 in unexposed VLBW adults, p=0.002) and femoral neck Z score (-0.05 vs. -0.53, p=0.003). Corresponding Z scores for those born at term were -0.02 (PE) and -0.45 (no PE) for lumbar spine (p=0.2), 0.78 and 0.08 for femoral neck (p=0.02). The Table shows mean differences after adjustment for offspring current body size and potential confounders. CONCLUSIONS: Young adults exposed to maternal PE have higher BMD than those not exposed. This suggests that preeclampsia has a long-term protective effect on offspring bone health.

Lower conditioning leisure-time physical activity in young adults born preterm at very low birth weight.

BACKGROUND: Adults born preterm at very low birth weight (VLBW, <1500 g) have elevated levels of risk factors for cardiovascular diseases and type 2 diabetes. Preliminary observations suggest that this could partly be explained by lower rates of physical activity. The aim of this study was to assess physical activity in healthy young adults born preterm at very low birth weight compared with term-born controls. METHODOLOGY/PRINCIPAL FINDINGS: We studied 94 unimpaired young adults, aged 21-29 years, born at VLBW and 101 age-, sex-, and birth hospital-matched term-born controls from one regional center in Southern Finland. The participants completed a validated 30-item 12-month physical activity questionnaire and the NEO-Personality Inventory based on the Big Five taxonomy, the most commonly used classification of personality traits. Yearly frequency, total time, total volume and energy expenditure of conditioning and non-conditioning leisure-time physical activity (LTPA) and commuting physical activity were compared between VLBW and term-born subjects. A subset of participants underwent dual-energy x-ray absorptiometry for body composition measurement. Data were analyzed by multiple linear regression. Compared with controls, VLBW participants had lower frequency [-38.5% (95% CI; -58.9, -7.7)], total time [-47.4% (95% CI; -71.2, -4.1)], total volume [-44.3% (95% CI; -65.8, -9.2)] and energy expenditure [-55.9% (95% CI; -78.6, -9.4)] of conditioning LTPA when adjusted for age, sex, body mass index, smoking, parental education and personality traits. Adjusting for lean body mass instead of body mass index attenuated the difference. There were no differences in non-conditioning LTPA or commuting physical activity. CONCLUSIONS/SIGNIFICANCE: Compared with term-born controls, unimpaired VLBW adults undertake less frequent LTPA with lower total time and volume of exercise resulting in lower energy expenditure. Differences in personality that exist between the VLBW and term-born groups do not seem to explain this association.

Resting energy expenditure in young adults born preterm--the Helsinki study of very low birth weight adults.

BACKGROUND: Adults born preterm with very low birth weight (VLBW; < 1500 g) have higher levels of cardiovascular and metabolic risk factors than their counterparts born at term. Resting energy expenditure (REE) could be one factor contributing to, or protecting from, these risks. We studied the effects of premature birth with VLBW on REE. METHODOLOGY/PRINCIPAL FINDINGS: We used indirect calorimetry to measure REE and dual x-ray absorptiometry (DXA) to measure lean body mass (LBM) in 116 VLBW and in 118 term-born control individuals (mean age: 22.5 years, SD 2.2) participating in a cohort study. Compared with controls VLBW adults had 6.3% lower REE (95% CI 3.2, 9.3) adjusted for age and sex, but 6.1% higher REE/LBM ratio (95% CI 3.4, 8.6). These differences remained similar when further adjusted for parental education, daily smoking, body fat percentage and self-reported leisure time exercise intensity, duration and frequency. CONCLUSIONS/SIGNIFICANCE: Adults born prematurely with very low birth weight have higher resting energy expenditure per unit lean body mass than their peers born at term. This is not explained by differences in childhood socio-economic status, current fat percentage, smoking or leisure time physical activity. Presence of metabolically more active tissue could protect people with very low birth weight from obesity and subsequent risk of chronic disease.

Preterm birth reduces the incidence of atopy in adulthood.

BACKGROUND: Immunologic pathways are primed in early life. Preterm birth can influence this process and thereby affect whether a person will have atopy later in life. Previous studies on the effects of preterm birth on atopy in adulthood have been inconclusive and limited to children or subjects born moderately preterm. OBJECTIVE: Our aim was to compare the incidence of atopy among young adults who were born preterm and at very low birth weight (≤ 1500 g) with that of term-born young adults (control subjects). METHODS: The study comprised 166 adults who were born preterm and at very low birth weight and 172 control subjects, all of whom were from the Helsinki Study of Very Low Birth Weight Adults. We assessed atopic predisposition at ages 18 to 27 years using skin prick tests for 6 common aeroallergens and measurements of serum concentrations of total IgE and 3 types of allergen-specific (cat, birch, and timothy) IgE. We asked the subjects whether they had been given a diagnosis of asthma or allergic rhinitis or had atopic eczema and analyzed data by using logistic or linear regression, adjusting for potential confounding factors. RESULTS: The risk for having at least 1 positive reaction on a skin prick test was reduced (adjusted odds ratio, 0.43; 95% CI, 0.23-0.79, P = .007), and the concentration of cat-specific IgE was less (25% less; 95% CI, 43% to 2.3% less; P = .033) in sera from very-low-birth-weight subjects compared with that seen in sera from control subjects. Within the very-low-birth-weight group, those born at an earlier gestational age were less likely to have positive skin prick test reactions (adjusted odds ratio for 1 week, 0.82; 95% CI, 0.68-0.98, P = .029) and less likely to have high levels of allergen-specific IgE. Cumulative incidences of atopic disease were similar between adults of very low birth weight and control subjects. CONCLUSIONS: Young adults born prematurely and at very low birth weight have a lower incidence of atopy than adults who were born full term. This finding supports the hypothesis that the risk for atopy is determined during early stages of development.