Neonatal fatty acid status and cardiometabolic health at 9years.

BACKGROUND: Long chain polyunsaturated fatty acid (LCPUFA) status is associated with risk of cardiovascular diseases in adulthood. We previously demonstrated no effect of LCPUFA supplementation after birth on BP and anthropometrics. Little is known about the association between fatty acid status at birth and cardiometabolic health at older ages. AIM: To evaluate associations between docosahexaenoic acid (DHA) and arachidonic acid (AA) levels in the umbilical cord and blood pressure (BP) and anthropometrics at 9years. STUDY DESIGN: Observational follow-up study. Multivariable analyses were carried out to adjust for potential confounders. SUBJECTS: 229 children who took part in a randomized controlled trial (RCT) on the effects of LCPUFA formula supplementation. OUTCOME MEASURES: BP was chosen as primary outcome; heart rate and anthropometrics as secondary outcomes. RESULTS: AA levels in the wall of the umbilical vein and artery were negatively associated with diastolic BP (B: vein -0.831, 95% CI: -1.578; -0.083, p=0.030; artery: -0.605, 95% CI: -1.200; -0.010, p=0.046). AA was not associated with systolic BP; DHA not with diastolic nor systolic BP. The AA:DHA ratio in the umbilical vein was negatively associated with diastolic BP (B: -1.738, 95% CI: -3.141; -0.335, p=0.015). Heart rate and anthropometrics were not associated with neonatal LCPUFA status. CONCLUSIONS: Higher AA levels and a higher AA:DHA ratio at birth are associated with lower diastolic BP at age 9. This suggests that the effect of LCPUFAs at early age is different from that in adults, where DHA is regarded anti-adipogenic and AA as adipogenic.

Neonatal fatty acid status and neurodevelopmental outcome at 9 years.

BACKGROUND: Long-chain polyunsaturated fatty acids (LCPUFA) are important for prenatal brain development. Previous studies of others assessed outcome until 7 years. The associations between neonatal LCPUFA status and long-term developmental outcome are debated. AIM: To investigate the relationship between fatty acid status at birth and neurodevelopment at 9 years. Age 9 is a unique age after a significant neurodevelopmental transition. STUDY DESIGN: Correlation study. Multivariable analyses were carried out to adjust for potential confounders. SUBJECTS: 317 children who participated in a trial on effects of postnatal LCPUFA supplementation were eligible. 235 children (74%) were reassessed at age 9. OUTCOME MEASURES: At birth, docosahexaenoic acid (DHA) and arachidonic acid (AA) were determined in the wall of the umbilical vein. We primarily studied the correlation between DHA and AA with the complex form of minor neurological dysfunction (cMND). Secondary correlations that were studied were DHA and AA levels with cognitive development in terms of full IQ, and with behavioural development in terms of a total problem score. RESULTS: Boys with cMND showed lower DHA values in the umbilical vein than children with better neurological condition (p=0.033). A similar association was absent in girls. Neonatal AA values were not associated with neurological outcome. Neither neonatal DHA nor AA values were associated with cognition and behaviour at 9. CONCLUSIONS: Higher umbilical DHA levels in boys are associated with better neurological development at 9 years. AA status at birth was not associated with neurodevelopment at 9 years.

Minor neurological dysfunction and behaviour in 9-year-old children born at term: evidence for sex dimorphism.

AIM: The aim of the study was to assess associations between minor neurological dysfunction (MND) and behaviour, with specific attention to sex differences. METHOD: This was an observational cohort study in which 341 9-year-old children (177 male, 164 female) without perinatal risk were neurologically assessed, with attention to severity and type of MND. Eight domains of dysfunction were distinguished, including posture and muscle tone, fine manipulative ability and coordination. Severity of MND was based on the number of dysfunctional domains. Behaviour was assessed by parents and teachers using the Child Behavior Checklist and Teacher's Report Form (TRF); outcomes were internalizing and externalizing behaviour and total score of behavioural problems. RESULTS: Females with complex MND or dysfunctional posture and muscle tone had increased risk for externalizing behavioural problems (OR 4.52, 95% CI 1.01-20.2, and OR 4.05, 95% CI 1.06-15.5, respectively). In males, these associations were absent. However, males with simple MND had an increased risk for behavioural problems indicated by the total TRF-score (OR 7.52, 95% CI 1.36-41.4). INTERPRETATION: In children without perinatal risk, associations between MND and behaviour are sex-specific. In females, dysfunction of complex neural networks, including the cerebellum, is associated with externalizing behaviour. In males, neurobehavioural relationships are limited, suggesting a larger role of psychosocial factors in the genesis of behavioural problems.

Minor neurological dysfunction and cognition in 9-year-olds born at term.

BACKGROUND: In children with developmental disorders, motor problems often co-occur with cognitive difficulties. Associations between specific cognitive deficits underlying learning problems and minor neurological dysfunction (MND) are still unknown. AIMS: To assess associations between specific types of MND as clinical markers of non-optimal brain function and performance in specific cognitive domains. STUDY DESIGN: Part of a randomized controlled trial. SUBJECTS: Three hundred and forty one 9-year-old children born at term (177 boys, 164 girls). OUTCOME MEASURES: Children were neurologically assessed to detect eight types of MND: mild dysfunction in posture and muscle tone, reflexes, coordination, fine manipulative ability, sensory function, cranial nerve function, choreiform dyskinesia and excessive associated movements. Cognitive function in the domains of attention, memory and language was evaluated using the Test of Everyday Attention for Children (TEA-Ch), a developmental neuropsychological assessment (NEPSY) and the Children's Memory Scale. RESULTS: Fine manipulative disability and coordination problems were associated with lower scores on attention, memory and learning and language, other types of MND were not. Girls with coordination problems performed significantly worse on attention/executive function than those without this dysfunction; however, in boys, such association was absent. CONCLUSION: Particularly, fine manipulative disability and coordination problems were associated with worse cognitive function in the domains of attention, learning and memory and language. Previous and present data suggest a minor sex difference in neurocognitive associations: in girls dysfunction of the cerebello-thalamo-cortical pathways may be associated with cognitive deficits, while in boys cognitive impairment may be associated with dysfunction of cortico-striato-thalamo-cortical pathways.

Effects of long-chain polyunsaturated fatty acid supplementation of infant formula on cognition and behaviour at 9 years of age.

AIM: Long-chain polyunsaturated fatty acid (LCPUFA) supplementation of infant formula may have a beneficial effect on cognitive development. This study aimed to investigate the effect of LCPUFA formula supplementation primarily on cognition and secondarily on behaviour at age 9 years. Special attention was paid to the potentially modifying effect of maternal smoking during pregnancy. METHOD: A double-blind, randomized control study was performed in two groups of healthy infants born at term: one group, constituting the control group, received standard formula (n=169) and another group received standard formula supplemented with LCPUFAs (n=146). A breastfed group (n=159) served as an additional reference. At 9 years of age, 72% of the children (control group: n=123; 71 males, 52 females; LCPUFA group: n=91; 42 males, 49 females; breastfed group: n=127, 64 males, 63 females) underwent extensive cognitive and behavioural testing. RESULTS: An interaction between infant nutrition and smoking during pregnancy was found. Among children exposed to smoking during pregnancy, LCPUFA supplementation was associated with higher mean verbal IQ scores (p=0.007) and learning and memory (p=0.006). Among children not exposed to smoking during pregnancy, LCPUFA supplementation was associated with lower mean verbal memory scores (p=0.003). Executive function scores were significantly lower in the LCPUFA-supplemented group than in the control group (p=0.001). Breastfeeding was associated with better performance on IQ (p=0.005). INTERPRETATION: No consistent beneficial effect of LCPUFA formula supplementation on cognitive development in term-born infants was found. The study confirmed that breastfeeding is associated with better cognition.

The Groningen LCPUFA study: No effect of short-term postnatal long-chain polyunsaturated fatty acids in healthy term infants on cardiovascular and anthropometric development at 9 years.

Conflicting evidence exists on the effect of long-chain polyunsaturated fatty acid (LCPUFA) formula supplementation on cardiovascular health in term infants. It is known that LCPUFA supplementation does not affect infant growth, but long term outcome data are not available. The current study investigates whether 2 mo LCPUFA formula supplementation affects cardiovascular and anthropometric development at 9 y. A prospective, double-blind, randomized trial was performed in healthy term infants: a standard formula control group (CF, n = 169) and a LCPUFA-supplemented group [LF, n = 145; 0.45% (by wt) AA and 0.30% (by wt) docosahexaenoic acid (DHA)]. A breastfed group (BF; n = 159) served as reference. At the age of 9 y, systolic and diastolic blood pressure, heart rate, head circumference, weight, and height were measured. Univariate and multivariate analyses were performed; 63 to 79% of children were assessed. None of the cardiovascular or anthropometric measurements differed between the formula groups. Breastfed children had a marginally lower heart rate than formula-fed children, in particular compared with children fed control formula. Blood pressure and parameters of growth including BMI of breast and formula-fed children did not differ. In conclusion, the study suggests that short-term LCPUFA supplementation does not influence cardiovascular and anthropometric development at 9 y.

Minor neurological dysfunction and IQ in 9-year-old children born at term.

AIM: The aim of this study was to examine the relationship between the severity and type of minor neurological dysfunction (MND) and IQ in 9-year-old children born at term. METHOD: Three hundred and forty-one children (177 males, 164 females; mean age 9y, SD 3mo, range 8y 10mo-9y 7mo) who were born at term were neurologically assessed according to Touwen. Children with perinatal risk or with a congenital disorder were excluded. Special attention was paid to the severity and type of MND. Eight domains of dysfunction were distinguished, including fine manipulative ability and coordination. On the basis of the number of dysfunctional domains, the severity of dysfunction was expressed as simple MND (sMND) or complex MND (cMND). Verbal, Performance, and Full-scale IQ (FSIQ) were assessed with the Wechsler Abbreviated Scale of Intelligence. Univariate and multivariate statistical analyses were performed. RESULTS: Neurologically normal children had higher IQ scores than those with sMND and cMND (mean FSIQ 104 [95% confidence interval (CI) 102-106] to 100 [95% CI 97-102] and 95 [95% CI 91-98] respectively). Multivariate statistics confirmed that the IQ scores of children with sMND and cMND did not differ. Fine manipulative disability and coordination problems were associated with lower IQ scores but other dysfunctions were not. INTERPRETATION: The type of MND rather than the severity is associated with lower IQ in children born at term.

The Groningen LCPUFA study: no effect of postnatal long-chain polyunsaturated fatty acids in healthy term infants on neurological condition at 9 years.

Long-chain PUFA (LCPUFA) supplementation of formula can have beneficial effects on neurodevelopmental outcome in early infancy, but uncertainty exists regarding effects after 6 months. The present study is the first to investigate whether consumption by term infants of formula containing LCPUFA for the first 2 months after birth improves neurological condition of these children at 9 years of age. A prospective, double-blind, randomised control study was performed in two groups of healthy term infants: a control group with standard formula (n 169) and a LCPUFA-supplemented group (LF; n 146). A breast-fed group (BF; n 159) served as a reference. At age 9 years, children were neurologically assessed according to Touwen, resulting in a Neurological Optimality Score and information on severity and type of minor neurological dysfunction (MND). Information on potential confounders was collected at enrollment and follow-up. Multivariate analyses were carried out to evaluate the effect of nutrition while adjusting for confounders. Attrition (28 %) was selective: drop-outs in the LF group were more often boys and had a significantly lower mental developmental index at 18 months. Neurological optimality and severity and type of MND at 9 years did not differ between the two formula groups. Children in the BF group showed significantly less often fine manipulative dysfunction than formula-fed children. In conclusion, LCPUFA supplementation of formula during the first 2 postnatal months in healthy term infants does not alter neurological function at school age. The study confirmed that breast-fed infants have a slightly better neurodevelopmental outcome than formula-fed infants.

Maternal anxiety is related to infant neurological condition, paternal anxiety is not.

BACKGROUND: Parental anxiety and stress may have consequences for infant neurological development. AIMS: To study relationships between parental anxiety or well-being and infant neurological development approximately one year after birth. STUDY DESIGN: Longitudinal study of a birth cohort of infants born to subfertile couples. SUBJECTS: 206 parent-child dyads. OUTCOME MEASURES: Infant neurology was assessed with the Touwen Infant Neurological Examination (TINE) at 10 months and a developmental questionnaire at 12 months. Parental measures included trait anxiety measured by the State-Trait Anxiety Inventory (STAI) and well-being measured by the General Health Questionnaire (GHQ). RESULTS: Maternal trait anxiety was associated with a less optimal neurological condition (r(s)= -0.19, p<0.01) of the infant. This association persisted after adjusting for confounders and results were confirmed by the outcome of the developmental questionnaire. Paternal trait anxiety and parental well-being were not related to the infant's neurodevelopmental outcome. CONCLUSIONS: Infants of mothers with high trait anxiety have an increased vulnerability to develop a non-optimal nervous system. The association may be mediated in part by early programming of monoaminergic systems. Future research should include an exploration of specific windows of vulnerability to maternal anxiety.