Maternal obesity, gestational diabetes mellitus, and diet in association with neurodevelopment of 2-year-old children.

BACKGROUND: Maternal metabolic disturbances and diet may influence long-term infantile neurodevelopment. We investigated whether maternal gestational diabetes mellitus (GDM), obesity, and diet could affect the neurodevelopment of 2-year-old children. METHODS: Neurodevelopment of children (n = 243) born to mothers with overweight or obesity was assessed with the Bayley Scales of Infant and Toddler Development-Third Edition, and the Hammersmith Infant Neurological Examination. Maternal adiposity was determined by air displacement plethysmography, and GDM with an oral glucose tolerance test. Dietary assessment included diet quality and fish consumption questionnaires, and three-day food diaries, from which dietary inflammatory index (DII®) scores were computed. RESULTS: GDM was associated with weaker expressive language skills (adj.ß = -1.12, 95% CI = -2.10;-0.15), and higher maternal adiposity with weaker cognitive, language, and motor skills in children (adj.p < 0.05). Maternal good dietary quality (adj.ß = 0.87, 95% CI = 0.004;1.73) and higher fish consumption (adj.p = 0.02) were related to better expressive language skills. DII scores were not associated with children's neurodevelopment. CONCLUSIONS: Findings suggest that GDM and higher maternal adiposity may lead to weaker neurodevelopmental skills, although still within the mean normative range in this population of children. Good dietary quality and higher fish consumption during pregnancy could benefit a child's language development. IMPACT: Gestational diabetes mellitus and maternal higher adiposity may have unfavorable effects on a 2-year-old child's neurodevelopment. An overall good quality of diet and higher fish consumption during pregnancy may result in more favorable cognitive and language skills when the child is 2-year-old. Our findings reveal that women with overweight or obesity, a risk group for pregnancy complications, could benefit from dietary counseling to support their children's neurodevelopment.

Performance in Hand Coordination Tasks and Concurrent Functional MRI Findings in 13-Year-Olds Born Very Preterm.

BACKGROUND: Fine motor and coordination problems are frequently reported among adolescents born preterm. We aimed to assess performance in hand coordination tasks and to compare concurrent brain activation between adolescents born very preterm and at term at 13 years. METHODS: A total of 34 right-handed adolescents born very preterm (gestational age less than 32 weeks/birth weight ≤1500 grams) and 37 controls born at term during 2003 to 2006 in Turku University Hospital, Finland, were recruited. At 13 years, finger opposition and diadochokinesis were assessed, and brain functional magnetic resonance imaging data were acquired while the adolescents performed unimanual hand coordination tasks in response to visual cue. RESULTS: Adolescents born very preterm performed similar to controls in hand coordination tasks. The very preterm group evoked greater brain activation than the controls in the right precentral gyrus and in the right postcentral gyrus during left-hand finger opposition and in the right postcentral gyrus during left-hand diadochokinesis. Within the very preterm group, lower gestational age was associated with reduced activation in the left superior parietal lobule during right-hand diadochokinesis. Regarding left-hand tasks, lower gestational age was associated with stronger activation in the right cerebellar lobule V and left cerebellar lobule VI during finger opposition and stronger activation in the right superior parietal lobule during diadochokinesis. CONCLUSIONS: Very preterm birth affected hand coordination-related brain activation. Most of the effects were found for nondominant hand. Clinical performance during the hand coordination tasks was similar in adolescents born very preterm and controls.

Functional Magnetic Resonance Imaging during Visual Perception Tasks in Adolescents Born Prematurely.

OBJECTIVES: Impairments in visual perception are among the most common developmental difficulties related to being born prematurely, and they are often accompanied by problems in other developmental domains. Neural activation in participants born prematurely and full-term during tasks that assess several areas of visual perception has not been studied. To better understand the neural substrates of the visual perceptual impairments, we compared behavioral performance and brain activations during visual perception tasks in adolescents born very preterm (birth weight ≤1500 g or gestational age <32 weeks) and full-term. METHODS: Tasks assessing visual closure, discrimination of a deviating figure, and discrimination of figure and ground from the Motor-Free Visual Perception Test, Third Edition were performed by participants born very preterm (n = 37) and full-term (n = 34) at 12 years of age during functional magnetic resonance imaging. RESULTS: Behavioral performance in the visual perception tasks did not differ between the groups. However, during the visual closure task, brain activation was significantly stronger in the group born very preterm in a number of areas including the frontal, anterior cingulate, temporal, and posterior medial parietal/cingulate cortices, as well as in parts of the cerebellum, thalamus, and caudate nucleus. CONCLUSIONS: Differing activations during the visual closure task potentially reflect a compensatory neural process related to premature birth or lesser neural efficiency or may be a result of the use of compensatory behavioral strategies in the study group born very preterm.

Visual Perceptual Skills in Very Preterm Children: Developmental Course and Associations With Neural Activation.

BACKGROUND: The objective of this study was to examine how nonverbal skills at age five years relate to visual perception and brain activation during visual perception tasks at age 12 years in very preterm subjects without visual or other neurodevelopmental impairments or major brain pathologies. METHODS: At age five years, 36 prematurely born (birth weight ≤1500 g or gestational age less than 32 weeks) and 31 term-born control children were assessed with the nonverbal subtests of the Wechsler Preschool and Primary Scale of Intelligence-Revised and the NEPSY-Second Edition. At age 12 years the same children were re-assessed with tasks from the Motor-Free Visual Perception Test, Third Edition, during functional magnetic resonance imaging. RESULTS: Test performance at age five years was significantly poorer in the very preterm group than the control subjects, but at age 12 years performance was similar in both groups. In the very preterm group, better nonverbal skills at age five years were significantly associated with stronger neural activation during the visual perception task at age 12 years. No associations between nonverbal skills at age five years and brain activation at age 12 years appeared in the control group. CONCLUSIONS: The associations between better nonverbal skills and stronger neural activation during visual perception task only observed in the very preterm group may reflect delayed development of the visual perception network and/or prematurity-related neural plasticity. The developmental follow-up of very preterm children should include psychological assessment of nonverbal skills at least until age five years.

Brain volumes in relation to loneliness and social competence in preadolescents born very preterm.

INTRODUCTION: The aim of the present study was to assess how regional brain volumes associate with self-experienced social and emotional loneliness and social competence in very preterm and term-born preadolescents. MATERIALS AND METHODS: Thirty-four very preterm subjects (birthweight ≤1,500 g and/or gestational age <32 weeks) without neurodevelopmental impairments and/or major brain pathologies and 31 term-born subjects underwent magnetic resonance imaging at 12 years of age. Regional brain volumes were measured using an automated image quantification tool. At 11 years of age, social and emotional loneliness were assessed with the Peer Network and Dyadic Loneliness Scale-self-report questionnaire and cooperating skills, empathy, impulsivity, and disruptiveness with the Multisource Assessment of Children's Social Competence Scale-self-report questionnaire. RESULTS: In the very preterm group, a number of significant associations were found between smaller regional brain volumes and self-experienced emotional loneliness, more impulsivity and more disruptiveness. In the control group, brain volumes and loneliness were not associated, and brain volumes and social competence were associated with a lesser degree than in the very preterm group. CONCLUSION: Experiences of emotional loneliness and poorer social competence appear to be more related to brain volumes in very preterm preadolescents than in those born full-term. It also appears that in very preterm preadolescents, emotional loneliness may be more reflected in brain development than social loneliness.

Predictive value of psychological assessment at five years of age in the long-term follow-up of very preterm children.

The aims of this study were to 1) assess the predictive value of psychological assessment at five years of age on the need for educational support in very preterm children, and 2) report the neuropsychological profile of very preterm children at eleven years of age and risk factors for poorer neuropsychological functions. A cohort of 167 very preterm children was included (birth weight ≤ 1500 g and/or gestational age < 32 weeks). At five years of age, intellectual functioning was assessed with Wechsler Preschool and Primary Scale of Intelligence-Revised and neuropsychological performance with NEPSY II. At eleven years of age, neuropsychological functions were assessed using NEPSY II and data on educational support services collected using a questionnaire. Lower full-scale intelligence quotient and poorer performance in subtests inhibition, comprehension of instructions, memory for designs, visuomotor precision and design copying at five years of age were associated with a need for educational support. Neuropsychological performance at eleven years of age was overall within the average range but below the mean, with the poorest performance in tasks assessing visual memory and visuospatial functions. The results offer a novel perspective to timing and measures of follow-up of very preterm children, since they show that need for long-term educational support can be identified at five years of age. The findings also highlight the clinical value of psychological assessments including evaluation of both intellectual functioning and neuropsychological performance, covering detailed information about non-verbal functions, in the follow-up of very preterm children up to eleven years of age.

Neurodevelopmental outcome of preterm twins at 5 years of age.

BACKGROUND: Twins are considered to be at an increased risk for perinatal mortality and morbidities, but it is unclear whether preterm twins are at an increased risk for poor developmental outcomes when compared to preterm singletons. Our aim was to compare the neurodevelopmental outcome of preterm twins vs singletons at 5 years of age. METHODS: Very low birth weight and very low gestational age infants (twins n = 66, singletons n = 157) were recruited as a part of the PIPARI project in the Turku University Hospital, covering a regional population. Cognitive development, neuropsychological performance, and neurodevelopmental impairments (including cerebral palsy, hearing deficit, visual impairment, and intellectual disability) were evaluated at 5 years of age. RESULTS: Twins and singletons had otherwise similar perinatal background factors, except for the higher proportion of preterm rupture of membranes in singletons. Twins had cognitive and neuropsychological outcomes that were otherwise comparable with singletons, but they had a slightly lower verbal intelligence quotient (estimate -5.81, 95% CI -11.14 to -0.48, p = 0.03). Being a twin was not a risk for neurodevelopmental impairments. CONCLUSIONS: Our study shows that, contrary to a common hypothesis, the overall neurodevelopment of very preterm twins does not significantly differ from that of preterm singletons.

Chorioamnionitis and Five-Year Neurodevelopmental Outcome in Preterm Infants.

BACKGROUND: Chorioamnionitis, a risk factor for preterm delivery, has been suggested to be associated with suboptimal neurological development in premature infants. OBJECTIVE: To evaluate the association between chorioamnionitis and neurodevelopment in preterm infants at 5 years of age. Methods Very low birth weight and very low gestational age infants (n = 197) were recruited. Placental samples (n = 117) were evaluated for histological chorioamnionitis. Fetal histological chorioamnionitis was analyzed as a subgroup. The diagnosis of clinical chorioamnionitis was derived from medical records. Neurodevelopmental impairments were evaluated at 2 years of age, and cognitive development (n = 188) and neuropsychological performance (n = 193) were evaluated at 5 years of age. RESULTS: There were no associations between histological or clinical chorioamnionitis and neurodevelopmental impairments at 2 years of age. Clinical chorioamnionitis and fetal histological chorioamnionitis were not associated with cognitive development or neuropsychological performance, but histological chorioamnionitis was associated with poorer cognitive outcome (regression coefficient = -7.22, 95% CI: -14.31 to -0.13) and weaker memory and learning functions (regression coefficient = -1.29, 95% CI: -2.40 to -0.18) at 5 years of age. CONCLUSION: Our study findings do not support clinical chorioamnionitis having a major independent role in the pathogenesis of neurodevelopmental problems in very preterm infants. Histological chorioamnionitis was associated with slightly less optimal performance at 5 years of age, but further studies are needed to verify the clinical significance of these findings.

The prevalence and predictive value of weak language skills in children with very low birth weight--a longitudinal study.

AIM: Previous findings regarding the prevalence and predictive value of weak language skills in preterm children with very low birth weight (VLBW) are unclear. This study analysed the prevalence of weak language skills, the predictive value of early weak language skills on later weak language skills, and the sensitivity and specificity of cognitive scores for identifying concurrent weak language skills in a longitudinal sample of VLBW children (n = 141) and their full-term controls (n = 146). METHODS: Data on language skills and cognitive development were gathered at two and five years of age. Weak language skills were defined by the 10th percentile value of the controls. RESULTS: In VLBW children, the prevalence of weak language skills varied between 16% and 18% at 2 years of age (controls: 8 to 10%) and between 20% and 27% at 5 years of age (controls: 10%). Early weak language skills predicted later weak language skills in VLBW children. Cognitive scores were specific, but their sensitivity for identifying concurrent weak language skills was low. CONCLUSION: The prevalence of weak language skills in VLBW children increased during the follow-up period and was higher than the controls. Language-sensitive methods should be used in the clinical follow-up of VLBW children.

Antenatal and postnatal growth and 5-year cognitive outcome in very preterm infants.

OBJECTIVES: To study how antenatal growth affects cognitive outcome in very preterm infants and to determine whether there is an association between growth in any particular time period between birth and 5 years of age and cognitive outcome. Small for gestational age (SGA) and non-SGA infants were analyzed separately, because antenatal growth may affect postnatal growth. METHODS: Very low birth weight (<1501 g) infants born between 2001 and 2006 and infants born at <32 gestational weeks between 2004 and 2006 who were treated at Turku University Hospital (n = 181) were followed. Weight, length, and head circumference (HC) of the infants were measured at 9 time points between birth and 5 years. The growth was determined as a z score change between measurement points. Cognitive development was assessed at 5 years of age with the Wechsler Preschool and Primary Scales of Intelligence-Revised. The association between growth and full-scale IQ (FSIQ) was studied. RESULTS: Growth in length and height was not associated with 5-year cognitive outcome. However, weight (r = 0.18, P = .04) and HC growth (r = 0.25, P = .01) between birth and 2 years of corrected age correlated to FSIQ in non-SGA children. In SGA children, HC growth (r = 0.33, P = .03) around term age correlated to FSIQ. CONCLUSIONS: Cognitive outcome was similar in SGA and non-SGA very preterm infants. Growth affected cognition positively in both subgroups, but the critical time period was different.

Predictive value of neonatal brain MRI on the neurodevelopmental outcome of preterm infants by 5 years of age.

AIM: To study the prognostic value of MRI in preterm infants at term equivalent age for cognitive development at 5 years of age. METHODS: A total of 217 very low birth weight/very low gestational age infants who all received brain MRI at term equivalent age were categorized into 4 groups based on the brain MRI findings. Cognitive development was assessed at 5 years of chronological age by using a short form of Wechsler Preschool and Primary Scale of Intelligence - Revised. This information was combined with neurosensory diagnoses by 2 years of corrected age. RESULTS: Of all infants 31 (17.0%) had Full Scale Intelligence Quotient (FSIQ) <85, 14 (6.5%) had cerebral palsy and 4 (1.8%) had severe hearing impairment. A total of 41 (22.0%) infants had some neurodevelopmental impairment at 5 years of age. Considering cognitive outcome (FSIQ <85), the positive predictive value of several major MRI pathologies was 43.8%, and the negative predictive value of normal finding or minor pathologies was 92.0% and 85.7%, respectively. CONCLUSION: The MRI of the brain at term equivalent age may be valuable in predicting neurodevelopmental outcome in preterm infants by 5 years of age. The findings should always be interpreted alongside the clinical information of the infant. Furthermore, MRI should not replace a long-term clinical follow-up for very preterm infants.

Associations between regional brain volumes at term-equivalent age and development at 2 years of age in preterm children.

BACKGROUND: Altered brain volumes and associations between volumes and developmental outcomes have been reported in prematurely born children. OBJECTIVES: To assess which regional brain volumes are different in very low birth weight (VLBW) children without neurodevelopmental impairments ([NDI] cerebral palsy, hearing loss, blindness and significantly delayed cognitive performance) compared with VLBW children with NDI, and to evaluate the association between regional brain volumes at term-equivalent age and cognitive development and neurological performance at a corrected age of 2 years. MATERIALS AND METHODS: The study group consisted of a regional cohort of 164 VLBW children, divided into one group of children without NDI (n = 148) and one group of children with NDI (n = 16). Brain (MRI) was performed at term-equivalent age, from which brain volumes were manually analysed. Cognitive development was assessed with the Bayley Scales of Infant Development II (BSID-II), and neurological performance with the Hammersmith Infant Neurological Examination at the corrected age of 2 years. RESULTS: The volumes of total brain tissue, cerebrum, frontal lobes, basal ganglia and thalami, and cerebellum were significantly smaller, and the volume of the ventricles significantly larger, in the children with NDI than in those without NDI. Even in children without NDI, a smaller cerebellar volume was significantly correlated with poor neurological performance at 2 years of corrected age. CONCLUSION: Volumetric analysis at brain MRI can provide an additional parameter for early prediction of outcome in VLBW children.

Cognitive and neuropsychological outcomes at 5 years of age in preterm children born in the 2000s.

AIM: The aim of this study was to assess the cognitive level and neuropsychological performance at 5 years of age in children with a very low birthweight (VLBW; birthweight <1501 g) born in 2001 to 2003. METHOD: A regional cohort of 97 children with a VLBW (mean gestational age 28 wks [SD 3 wks]; mean birthweight 1054 g [SD 259 g]; 50 male; 47 female) and a comparison group of 161 healthy children born at term (mean gestational age 40 wks [SD 1 wks]; mean birthweight 3644 g [SD 446 g]; 80 male; 81 female) were included in this study. At 5 years of age (SD 2 mo) cognitive level was assessed with the Wechsler Preschool and Primary Scale of Intelligence - revised and neuropsychological performance was assessed using NEPSY II. RESULTS: The mean intelligence of the VLBW group corresponded to the normative mean of 100 but was lower than the mean of the low-risk comparison group (p<0.001). Neuropsychological performance was also significantly poorer than that of the comparison group. In NEPSY II, 25% of the VLBW group had a significantly impaired performance in one of 11 subtests and 33% had a significantly impaired performance in more than one, while 19% of the comparison group had a significantly impaired performance in one subtest and 10% had a significantly impaired performance in more than one. INTERPRETATION: The mean cognitive capacity of the VLBW cohort corresponded to the normative mean. However, assessments of cognitive level only at preschool age do not provide the information on neuropsychological deficit that is necessary for planning adequate educational support.

Relations between brain volumes, neuropsychological assessment and parental questionnaire in prematurely born children.

The objective of this study is to assess the relationship between brain volumes at term equivalent age and neuropsychological functions at 5 years of age in very low birth weight (VLBW) children, and to compare the results from a neuropsychological assessment and a parental questionnaire at 5 years of age. The study group included a regional cohort of 97 VLBW children and a control group of 161 children born at term. At term equivalent age, brain magnetic resonance imaging (MRI) was performed on the VLBW children, and analysed for total and regional brain volumes. At 5 years of age, a psychologist assessed the neuropsychological performance with NEPSY II, and parents completed the Five to fifteen (FTF) questionnaire on development and behaviour. The results of the control group were used to give the age-specific reference values. No significant associations were found between the brain volumes and the NEPSY II domains. As for the FTF, significant associations were found between a smaller total brain tissue volume and poorer executive functions, between a smaller cerebellar volume and both poorer executive functions and motor skills, and, surprisingly, between a larger volume of brainstem and poorer language functions. Even after adjustment for total brain tissue volume, the two associations between the cerebellar volume and the FTF domains remained borderline significant (P = 0.05). The NEPSY II domains Executive Functioning, Language and Motor Skills were significantly associated with the corresponding FTF domains. In conclusion, altered brain volumes at term equivalent age appear to affect development still at 5 years of age. The FTF seems to be a good instrument when used in combination with other neuropsychological assessment.