The Association between Growth and Neurodevelopment in Very Preterm Infants – A Follow-up Study in the PIPARI Study

Placental insufficiency is one major cause of intrauterine growth restriction and also relates to neurodevelopment. Preterm infants with very low birth weight are at risk of postnatal growth restriction as well as neurodevelopmental impairments. However, the optimal postnatal growth for long-term neurodevelopment is still unclear. The objective of this study was thus to investigate the association between growth and neurodevelopment in very preterm infants. The study populations consisted of 83 (I), 55 (II), 36 (III) and 181 (IV) infants with very low birth weight (below 1501 grams), and very or extremely low gestational age (below 32 and 26 weeks). Foetal blood circulation in relation to two-year neurodevelopment and the association between early growth and brain maturation at term age were studied. Postnatal growth, and its association with five-year cognitive outcome, was analysed. Changes in foetal blood circulation related to placental insufficiency associated with an adverse two-year cognitive outcome. Early postnatal growth in extremely preterm infants was comparable to a similar Swedish cohort. Preterm infants with slow intrauterine growth had less mature brains at term age; rapid catch-up growth until term age did not eliminate this difference. Weight gain and head circumference growth from birth until two years of age associated positively with five-year cognitive outcome in appropriate for gestational age infants. In small for gestational age infants, head circumference growth from term age to four months (corrected age) associated positively with their five-year cognitive outcome. The association between postnatal growth and neurodevelopment was different for prenatally normally grown versus slow grown preterm infants.

Diffusion Tensor Imaging as a Diagnostic and Research Tool: A Study on Preterm Infants

Diffusion tensor imaging (DTI) is an advanced magnetic resonance imaging (MRI) technique. DTI is based on free thermal motion (diffusion) of water molecules. The properties of diffusion can be represented using parameters such as fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity, which are calculated from DTI data. These parameters can be used to study the microstructure in fibrous structure such as brain white matter. The aim of this study was to investigate the reproducibility of region-of-interest (ROI) analysis and determine associations between white matter integrity and antenatal and early postnatal growth at term age using DTI. Antenatal growth was studied using both the ROI and tract-based spatial statistics (TBSS) method and postnatal growth using only the TBSS method. The infants included to this study were born below 32 gestational weeks or birth weight less than 1,501 g and imaged with a 1.5 T MRI system at term age. Total number of 132 infants met the inclusion criteria between June 2004 and December 2006. Due to exclusion criteria, a total of 76 preterm infants (ROI) and 36 preterm infants (TBSS) were accepted to this study. The ROI analysis was quite reproducible at term age. Reproducibility varied between white matter structures and diffusion parameters. Normal antenatal growth was positively associated with white matter maturation at term age. The ROI analysis showed associations only in the corpus callosum. Whereas, TBSS revealed associations in several brain white matter areas. Infants with normal antenatal growth showed more mature white matter compared to small for gestational age infants. The gestational age at birth had no significant association with white matter maturation at term age. It was observed that good early postnatal growth associated negatively with white matter maturation at term age. Growth-restricted infants seemed to have delayed brain maturation that was not fully compensated at term, despite catchup growth.

Genetic, prenatal and postnatal determinants of weight gain and obesity in young children – The STEPS Study

Genetic, Prenatal and Postnatal Determinants of Weight Gain and Obesity in Young Children – The STEPS Study University of Turku, Faculty of Medicine, Department of Paediatrics, University of Turku Doctoral Program of Clinical Investigation (CLIPD), Turku Institute for Child and Youth Research. Conditions of being overweight and obese in childhood are common health problems with longlasting effects into adulthood. Currently 22% of Finnish boys and 12% of Finnish girls are overweight and 4% of Finnish boys and 2% of Finnish girls are obese. The foundation for later health is formed early, even before birth, and the importance of prenatal growth on later health outcomes is widely acknowledged. When the mother is overweight, had high gestational weight gain and disturbances in glucose metabolism during pregnancy, an increased risk of obesity in children is present. On the other hand, breastfeeding and later introduction of complementary foods are associated with a decreased obesity risk. In addition to these, many genetic and environmental factors have an effect on obesity risk, but the clustering of these factors is not extensively studied. The main objective of this thesis was to provide comprehensive information on prenatal and early postnatal factors associated with weight gain and obesity in infancy up to two years of age. The study was part of the STEPS Study (Steps to Healthy Development), which is a follow-up study consisting of 1797 families. This thesis focused on children up to 24 months of age. Altogether 26% of boys and 17% of girls were overweight and 5% of boys and 4% of girls were obese at 24 months of age according to New Finnish Growth references for Children BMI-for-age criteria. Compared to children who remained normal weight, the children who became overweight or obese showed different growth trajectories already at 13 months of age. The mother being overweight had an impact on children’s birth weight and early growth from birth to 24 months of age. The mean duration of breastfeeding was almost 2 months shorter in overweight women in comparison to normal weight women. A longer duration of breastfeeding was protective against excessive weight gain, high BMI, high body weight and high weight-for-length SDS during the first 24 months of life. Breast milk fatty acid composition differed between overweight and normal weight mothers, and overweight women had more saturated fatty acids and less n-3 fatty acids in breast milk. Overweight women also introduced complementary foods to their infants earlier than normal weight mothers. Genetic risk score calculated from 83 obesogenic- and adiposity-related single nucleotide polymorphisms (SNPs) showed that infants with a high genetic risk for being overweight and obese were heavier at 13 months and 24 months of age than infants with a low genetic risk, thus possibly predisposing to later obesity in obesogenic environment. Obesity Risk Score showed that children with highest number of risk factors had almost 6-fold risk of being overweight and obese at 24 months compared to children with lowest number of risk factors. The accuracy of the Obesity Risk Score in predicting overweight and obesity at 24 months was 82%. This study showed that many of the obesogenic risk factors tend to cluster within children and families and that children who later became overweight or obese show different growth trajectories already at a young age. These results highlight the importance of early detection of children with higher obesity risk as well as the importance of prevention measures focused on parents. Keywords: Breastfeeding, Child, Complementary Feeding, Genes, Glucose metabolism, Growth, Infant Nutrition Physiology, Nutrition, Obesity, Overweight, Programming