Aulikki Lano

Behavioural symptoms of attention deficit/hyperactivity disorder in preterm and term children born small and appropriate for gestational age: A longitudinal study

BackgroundIt remains unclear whether it is more detrimental to be born too early or too small in relation to symptoms of attention deficit/hyperactivity disorder (ADHD). Thus, we tested whether preterm birth and small body size at birth adjusted for gestational age are independently associated with symptoms of ADHD in children.MethodsA longitudinal regional birth cohort study comprising 1535 live-born infants between 03/15/1985 and 03/14/1986 admitted to the neonatal wards and 658 randomly recruited non-admitted infants, in Finland. The present study sample comprised 828 children followed up to 56 months. The association between birth status and parent-rated ADHD symptoms of the child was analysed with multiple linear and logistic regression analyses.ResultsNeither prematurity (birth < 37 weeks of gestation) nor lower gestational age was associated with ADHD symptoms. However, small for gestational age (SGA < -2 standard deviations [SD] below the mean for weight at birth) status and lower birth weight SD score were significantly, and independently of gestational age, associated with higher ADHD symptoms. Those born SGA, relative to those born AGA, were also 3.60-times more likely to have ADHD symptoms scores above the clinical cut-off. The associations were not confounded by factors implicated as risks for pregnancy and/or ADHD.ConclusionsIntrauterine growth restriction, reflected in SGA status and lower birth weight, rather than prematurity or lower gestational age per se, may increase risk for symptoms of ADHD in young children.

Two-year follow-up of a randomised trial with repeated antenatal betamethasone

Background: Weekly repeated antenatal corticosteroid treatment improves respiratory outcome but decreases fetal growth and may impair neurodevelopmental outcome. We have previously reported that a single repeat betamethasone (BM) dose neither decreased fetal growth nor improved the outcome of preterm infants during the first hospitalisation. Objective: To study prospectively whether a single repeat dose of BM influences neurodevelopment and growth within 2 years. Design: Women with imminent delivery before 34.0 gestational weeks were eligible if they remained undelivered for >7 days after a single course of antenatal BM. After stratification, a single repeat dose of BM (12 mg) or placebo was given. The children underwent neurological and psychometric examinations and a speech evaluation at a corrected age of 2 years. Setting: Prospective, blinded evaluation following the randomised multicentre trial. Patients: 259 (82%) surviving infants completed the 2-year follow-up, 120 in the BM group and 139 in the placebo group. Results: The rate of survival without severe neurodevelopmental impairment was similar in both groups (BM 98%, placebo 99%). The risk of cerebral palsy (BM 2%, placebo 1%), growth or re-hospitalisation rates (BM 60%, placebo 50%) did not differ between the groups. Conclusions: A single repeat dose of antenatal BM tended not to influence physical growth or neurodevelopment at 2 years of age.

Trial of Early Neonatal Hydrocortisone: Two-Year Follow-Up

Background: Dexamethasone treatment is associated with an increased risk of cerebral palsy (CP). Early hydrocortisone (HC) treatment may decrease the incidence of bronchopulmonary dysplasia; however, the long-term effects are still under evaluation. Follow-up of randomized studies concerning early HC treatment is essential to confirm the long-term safety. Objective: We hypothesized that early HC treatment in very preterm infants does not impair the neurologic outcome. Methods: We report follow-up data from a randomized trial of early HC given for 10 days. Before the HC or placebo treatment, serum cortisol levels were measured. Receiver-operating characteristic was defined. Values below the median were classified as low endogenous cortisol and those above the median as high endogenous cortisol. A meta-analysis was performed. Results: Altogether 98% of the 46 surviving infants participated in a follow-up study at a corrected age of 2 years. The growth characteristics were similar between the study groups. The developmental quotients (DQs) of the children with high endogenous cortisol and placebo treatment shortly after birth (100 ± 13) and those with low endogenous cortisol and HC (97 ± 7) were not lower than the DQs of the children with high endogenous cortisol and HC (92 ± 3) or low cortisol and placebo (96 ± 2). According to a meta-analysis of three available trials (411 children), the rate of CP and survival without neurosensory or cognitive impairment was not influenced by HC. Conclusion: Early low-dose HC administration had no adverse effects at 2 years of age. Further studies are required to define the target group for neonatal HC.

Phase synchrony in the early preterm EEG: development of methods for estimating synchrony in both oscillations and events.

Development of neuronal connections relies on proper neuronal activity, and it starts during the time when early preterm babies are treated in the neonatal intensive care units. While synchrony has been a key element in visual assessment of neonatal EEG signals, there has been no unambiguous definitions for synchrony, and no objective measures available for neonatal signals. Estimation of phase locking value (PLV) has been an established paradigm in adults, but many unique characteristics of the neonatal EEG have precluded its applicability in them. In the present paper, we developed the existing PLV-based methods further to be applicable for neonatal signals at two different temporal scales, oscillations and events, where the latter refers technically to quantitating phase synchrony (PS) between band-specific amplitude envelopes (bafPS). In addition, we present a measure for quantitation based on assessing cumulative proportion of time with statistically significant synchrony between the given signal pair. The paper uses real EEG examples and the prior neurobiological knowledge in the process of defining optimal parameters in each step of the procedure. Finally, we apply the method to a set of dense array EEG recordings from very early preterm babies, recorded at conceptional age of less than 30 weeks. By comparing PS and bafPS from babies without and with major cerebrovascular lesion, we show that the effects of brain lesions may be selective both in space and in frequency. These findings do by nature escape visual detection in the conventional EEG reading, however they have intriguing correlates in the current concept of how somatosensory networks are thought to develop and/or become disorganized in the early preterm babies.

Trajectories of growth and symptoms of attention-deficit/hyperactivity disorder in children: a longitudinal study

BackgroundEmpirical evidence suggests that prenatal growth is associated with attention deficit/hyperactivity disorder (ADHD) and its symptoms. Data on the importance of postnatal growth is, however scanty. We studied whether pre- and postnatal growth up to 56 months is associated with symptoms of ADHD in children.MethodA longitudinal regional birth cohort study comprising 893 children followed up to 56 months. The associations between pre- and postnatal growth and parent-rated ADHD symptoms of the child were analyzed with multiple linear regression analyses and repeated-measures analyzes of covariance.ResultsChildren born lighter, thinner, shorter, and with a smaller head circumference, adjusted for length of gestation, received higher parent-rated ADHD symptoms scores at 56 months. Further, smaller head circumference throughout the period of growth from birth up to 56 months was related to higher ADHD symptoms scores. The associations changed only little after adjusting for several pre- and neonatal factors. The associations were not modified by sex and there were no evidence of non-linear associations.ConclusionsSlower prenatal growth in weight, body-mass index, length, and head circumference may pose a risk for higher ADHD symptoms in childhood. The consistently smaller head circumference from birth up to 56 months characterizing children with higher ADHD symptoms may point to a lack of catch-up growth in head circumference in childhood as a predisposing factor.

Neurodevelopment in children with hypoplastic left heart syndrome.

OBJECTIVEnTo assess neurodevelopment in children with hypoplastic left heart syndrome (HLHS) or other types of functionally single ventricle (univentricular heart, UVH) and to estimate the effect of possible clinical predictors on outcome.nnnSTUDY DESIGNnA total of 22 patients with HLHS and 14 with UVH, surviving after palliative surgery performed in the same center, and 42 healthy control subjects were examined at a median age of 30.2 months neurologically and according to the Bayley Scales of Infant Development in a population based prospective neurodevelopmental follow-up study.nnnRESULTSnThe mean Mental Developmental Index was significantly lower (89.9) in patients with HLHS than in control subjects (105.5, P<.001), whereas there was no difference between patients with UVH (98.5) and control subjects. The mean Psychomotor Developmental Index in patients with HLHS (80.7, P<.001) as well as in those with UVH (94.5, P=.016) was significantly inferior to that in control subjects (105.3).nnnCONCLUSIONSnIn patients with HLHS, mean Mental Developmental Index lags behind control subjects. Psychomotor Developmental Index is impaired in patients with both HLHS and UVH. Routine neurodevelopmental follow-up is recommended for this seriously ill patient group.

Physical Activity, Body Composition and Metabolic Syndrome in Young Adults

Objective Low physical activity (PA) is a major risk factor for cardiovascular and metabolic disorders in all age groups. We measured intensity and volume of PA and examined the associations between PA and the metabolic syndrome (MS), its components and body composition among young Finnish adults. Research Design and Methods The study comprises 991 men and women born 1985-86, who participated in a clinical study during the years 2009-11 which included assessments of metabolism, body composition and PA. Objectively measured (SenseWear Armband) five-day PA data was available from 737 participants and was expressed in metabolic equivalents of task (MET). Results The prevalence of MS ranged between 8-10%. Higher total mean volume (MET-hours) or intensity (MET) were negatively associated with the risk of MS and separate components of MS, while the time spent at sedentary level of PA was positively associated with MS. Conclusions MS was prevalent in approximately every tenth of the young adults at the age of 24 years. Higher total mean intensity and volume rates as well as longer duration spent at moderate and vigorous PA level had a beneficial impact on the risk of MS. Longer time spent at the sedentary level of PA increased the risk of MS.

Mother-child interaction is associated with neurocognitive outcome in extremely low gestational age children

Early mother-child interaction is one of the factors suggested to have an impact on neurocognitive development of extremely low gestational age (ELGA) children. Our aim was to examine associations of mother-child interaction with neurocognitive outcome, neurological impairments and neonatal brain injuries in ELGA children. A prospective study of 48 ELGA children, born before 28 gestational weeks (26.3 ± 1.2 weeks, birth weight 876 g ± 194 g), and 16 term controls. Brain MRI was performed at term-equivalent age. At two years of corrected age, the mother-child interaction was assessed in a structured play situation using the Erickson Scales and Mutually Responsive Orientation Scales. Neurocognitive outcome was assessed with Griffiths Mental Developmental Scales (GMDS) and Bayley Scales of Infant and Toddler Development - Third Edition (BSID-III) and with Hempel neurological examination. Among ELGA children, higher quality of dyadic relationship and maternal sensitivity, responsiveness, and supportiveness were associated with positive neurocognitive outcome measured both with GMDS and BSID-III (adjusted p < 0.05). This association remained after adjusting for mothers educational level. Neurological impairments at two years, white matter or gray matter abnormalities in MRI at term-equivalent age, and grade III-IV intraventricular hemorrhage during the neonatal period were not associated with mother-child interaction. This study emphasizes the importance of the quality of mother-child interaction after extremely preterm birth for neurocognitive development. Neonatal brain injury and neurological impairments were not associated with worse parent-child interaction after two years.

Activation of T Cells in Preterm Infants with Respiratory Distress Syndrome

Background: Preterm infants with respiratory distress syndrome (RDS) present with systemic inflammation. The role of lymphocytes in RDS is less studied. Activation of lymphocytes could mediate chronic inflammation and development of bronchopulmonary dysplasia (BPD). Objective: To evaluate whether T cells are activated in preterm infants with RDS and whether T cell activation is associated with the development of BPD. Methods: Thirty-four infants with RDS [mean gestational age 27.1 (SD 2.0) weeks, birth weight 900 (216) g] were compared with 21 infants without RDS [32.6 (1.4) weeks, 1,697 (406) g]. From blood samples taken on postnatal days 1, 3, and 7, CD4 and CD8 cell counts and their expressions of co-stimulatory molecule CD54 and adhesion molecule CD62L were determined by flow cytometry. In activated cells, expression of CD54 is increased and CD62L is decreased. Results:As compared with infants without RDS, infants with RDS had less CD4 and CD8 cells on day 3 (both p = 0.02). On day 1 and day 3, RDS was associated with increased CD54 expression on CD4 cells (p = 0.001; p = 0.03) and decreased CD62L expression on CD8 cells (both p = 0.02). Infants with RDS who developed BPD (n = 18) had higher CD54 expression on CD4 cells on day 3 (p = 0.01) and on CD8 cells on day 1 and day 3 (p = 0.01; p = 0.04) as compared with infants without BPD (n = 16). Conclusions: In preterm infants, RDS is associated with a lower T cell count and a higher proportion of activated cells. Increased proportion of activated T cells predicts the development of BPD. Systemic T cell activation could mediate inflammation and development of BPD.

Longitudinal study of smoking cessation before pregnancy and children's cognitive abilities at 56 months of age

BACKGROUNDnAn inverse relationship exists between the rates of maternal smoking during pregnancy and childrens cognitive abilities. The effect of maternal cessation of smoking before pregnancy on childs cognitive development is less clear.nnnAIMSnTo study whether maternal cessation of smoking before pregnancy is associated with childrens cognitive abilities.nnnSTUDY DESIGN AND SUBJECTSnThe original cohort included all 1535 live-born infants admitted to the neonatal wards during 1 year and 658 randomly recruited non-admitted infants. The present study sample comprised 1019 (68.2%) children of the original sample born at term and free of any major impairment followed up to 56 months.nnnOUTCOME MEASURESnChilds general reasoning, visual-motor integration, verbal competence, and language comprehension at 56 months of age.nnnRESULTSnThe results showed that children whose mothers smoked >10 cigarettes per day before pregnancy but none during pregnancy, fared 12.07 (95% confidence interval [CI]: 4.07 to 20.08) and 11.23 (95% CI: 2.81 to 19.66) age-standardized points poorer in general reasoning and in language comprehension tests, respectively, than children of never-smokers. All results were adjusted for the sex, gestational age-adjusted birth weight, multiple/singleton pregnancy, birth order, preeclampsia, maternal diabetes, admission to neonatal ward, 5-minute Apgar score (<7), breastfeeding, parental level of education, maternal age, BMI at the end of pregnancy and single parenting.nnnCONCLUSIONSnHeavy smoking before pregnancy is associated with childrens lower cognitive abilities even if the mother has quit smoking before pregnancy. Identification and intervention of heavy smoking women of fertile age would potentially improve not only their odds to become pregnant but also benefit the offsprings cognitive functioning.