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.

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.

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.

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-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.

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.

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.

Parental bonding after preterm birth: child and parent perspectives in the Helsinki study of very low birth weight adults.

OBJECTIVE: To examine whether parenting behavior recalled by very low birth weight (VLBW) adults or their parents differs from that of term-born control subjects or their parents. STUDY DESIGN: A total of 164 VLBW and 172 control adults (mean age 22.5 years, SD 2.2) assessed retrospectively the parenting behavior of their parents by the Parental Bonding Instrument, which includes dimensions of care, protectiveness, and authoritarianism. A subgroup of 190 mothers and 154 fathers assessed their own parenting behavior by the Parent Behavior Inventory, which includes dimensions of supportive and hostile parenting. RESULTS: The VLBW women assessed their mothers as more protective and authoritarian than the control women. The VLBW and control men did not differ from each other. Both mothers and fathers of the VLBW adults assessed their own parenting as more supportive than those of the control subjects. CONCLUSIONS: Preterm birth at VLBW may promote a more protective, as well as more supportive, parenting style.

Glucose regulation in young adults with very low birth weight.

BACKGROUND: The association between small size at birth and impaired glucose regulation later in life is well established in persons born at term. Preterm birth with very low birth weight (<1500 g) is also associated with insulin resistance in childhood. If insulin resistance persists into adulthood, preterm birth with very low birth weight also may be associated with an increased risk of disease in adulthood. We assessed glucose tolerance and insulin sensitivity and measured serum lipid levels and blood pressure in young adults with very low birth weight. METHODS: We performed a standard 75-g oral glucose-tolerance test, measuring insulin and glucose concentrations at baseline and at 120 minutes in 163 young adults (age range, 18 to 27 years) with very low birth weight and in 169 subjects who had been born at term and were not small for gestational age. The two groups were similar with regard to age, sex, and birth hospital. We measured blood pressure and serum lipid levels, and in 150 very-low-birth-weight subjects and 136 subjects born at term, we also measured body composition by means of dual-energy x-ray absorptiometry. RESULTS: As compared with the subjects born at term, the very-low-birth-weight subjects had a 6.7% increase in the 2-hour glucose concentration (95% confidence interval [CI], 0.8 to 12.9), a 16.7% increase in the fasting insulin concentration (95% CI, 4.6 to 30.2), a 40.0% increase in the 2-hour insulin concentration (95% CI, 17.5 to 66.8), an 18.9% increase in the insulin-resistance index determined by homeostatic model assessment (95% CI, 5.7 to 33.7), and an increase of 4.8 mm Hg in systolic blood pressure (95% CI, 2.1 to 7.4). Adjustment for the lower lean body mass in the very-low-birth-weight subjects did not attenuate these relationships. CONCLUSIONS: Young adults with a very low birth weight have higher indexes of insulin resistance and glucose intolerance and higher blood pressure than those born at term.

Ambulatory blood pressure in young adults with very low birth weight.

OBJECTIVE: We hypothesized that, as compared with a matched control group born at term, young adults with very low birth weight (VLBW <1.5 kg) would have higher 24-hour ambulatory blood pressure. STUDY DESIGN: We studied 118 18- to 27-year-old subjects born with VLBW within the greater Helsinki area and 120 term-born control subjects with similar age, sex, and birth hospital. The mean birth weight for VLBW subjects was 1.1 kg (standard deviation [SD], 0.2) and for controls, 3.6 kg (SD, 0.5). Gestational ages were 29.2 (SD, 2.3) and 40.1 (SD, 1.0) weeks. Current education of higher-educated parents served as an indicator of childhood socioeconomic status. Ambulatory blood pressure was measured during a 24-hour period with an oscillometric device (Spacelabs 90207). RESULTS: VLBW subjects had, with sex, age, and body mass index adjustment, a 2.4 mm Hg (95% confidence interval, 0.2 to 4.6) higher 24-hour systolic pressure. We found hypertension in 11 VLBW subjects and in 3 term-born subjects, giving an adjusted odds ratio of 4.0 (1.1 to 14.8). When socioeconomic status was taken into account, results remained unchanged. CONCLUSIONS: Higher rates of hypertension and higher 24-hour blood pressure among young adults with VLBW may indicate higher risk for adverse cardiovascular outcomes.

Reduced body size and shape-related symptoms in young adults born preterm with very low birth weight: Helsinki study of very low birth weight adults.

OBJECTIVE: To test the hypothesis that being born prematurely with very low birth weight (VLBW) (birth weight

Adults born at very low birth weight exercise less than their peers born at term.

OBJECTIVE: To study the effects of very low birth weight (VLBW, <1500 g) birth on physical activity, an important protective and modifiable factor. STUDY DESIGN: VLBW participants (n=163) with no major disability and 188 individuals born at term (mean age, 22.3 years; range, 18.5-27.1) completed a standardized questionnaire of physical activity. RESULTS: VLBW participants reported less leisure-time conditioning physical activity. They were 1.61-fold more likely to "not exercise much," 1.61-fold more likely to exercise infrequently (once a week or less), 2.75-fold more likely to exercise with low intensity (walking), and 3.11-fold more likely to have short exercise sessions (<30 minutes). The differences were present even in subjects with no history of bronchopulmonary dysplasia or asthma and were only slightly attenuated when adjusted for height, parental education, lean body mass, and percent body fat. CONCLUSIONS: Unimpaired adults who were VLBW exercise less during their leisure time than adults born at term. Promoting physical activity may be particularly important in the VLBW population to counteract the risks of chronic disease in adult life.

Decreased bone mineral density in adults born with very low birth weight: a cohort study.

BACKGROUND: Very-low-birth-weight (VLBW, <1,500 g) infants have compromised bone mass accrual during childhood, but it is unclear whether this results in subnormal peak bone mass and increased risk of impaired skeletal health in adulthood. We hypothesized that VLBW is associated with reduced bone mineral density (BMD) in adulthood. METHODS AND FINDINGS: The Helsinki Study of Very Low Birth Weight Adults is a multidisciplinary cohort study representative of all VLBW births within the larger Helsinki area from 1978 to 1985. This study evaluated skeletal health in 144 such participants (all born preterm, mean gestational age 29.3 wk, birth weight 1,127 g, birth weight Z score 1.3), and in 139 comparison participants born at term, matched for sex, age, and birth hospital. BMD was measured by dual energy X-ray absorptiometry at age 18.5 to 27.1 y. Adults born with VLBW had, in comparison to participants born at term, a 0.51-unit (95% confidence interval [CI] 0.28-0.75) lower lumbar spine Z score and a 0.56-unit (95% CI 0.34-0.78) lower femoral neck Z score for areal BMD. These differences remained statistically significant after adjustment for the VLBW adults' shorter height and lower self-reported exercise intensity. CONCLUSIONS: Young adults born with VLBW, when studied close to the age of peak bone mass, have significantly lower BMD than do their term-born peers. This suggests that compromised childhood bone mass accrual in preterm VLBW children translates into increased risk for osteoporosis in adulthood, warranting vigilance in osteoporosis prevention.

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.

Sleep quality in young adults with very low birth weight--the Helsinki study of very low birth weight adults.

OBJECTIVE: To assess the relationship between very low birth weight (VLBW; <1,500 g) and quality and amount of sleep in young adults. METHODS: We compared 89 VLBW and 78 term-born 19- to 26-year-old adults, by actigraphy and the Basic Nordic Sleep Questionnaire. RESULTS: There were no group differences in sleep quality or amount (p's >.15), although VLBW adults went to bed on average 36 min earlier (95% confidence interval 6-66 min). Shorter gestational age was related to longer sleep latency both within VLBW (standardized regression coefficient beta = -.36, p =.040) and term-born adults (beta = -.25, p =.029). CONCLUSION: Adults with VLBW had similar quality and amount of sleep as those born at term, although VLBW adults went to bed earlier, suggesting an advanced sleep phase. Within each group, a lower gestational age was related to a longer sleep onset.

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.

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.

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.

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.