This thesis is concerned with the responses of human infants to novel visual stimuli. Novelty is defined in terms of a time dimension so that a stimulus which is presented to the subject for a period of time (familiarisation period) is said to be novel relative to a stimulus which has not been so presented. Experiments demonstrated that infants will fixate a novel stimulus longer than they fixate a familiar stimulus. This effect was shown to be greater when familiar and novel stimuli differ from each other in two dimensions than when they differ in only one dimension. The decline in responsiveness to stimuli presented for a familiarisation period was shown to be a linear function of time. / Thesis / Master of Arts (MA)

Human functional laterality, typically involving a right-sided preference in most sensory-motor activities, is still a poorly understood issue. This is perhaps particularly true in terms of what underlying mechanisms that may govern lateral biases, as well as the developmental origins and course of events. The present thesis aims at investigating functional asymmetries in the upper and lower body movements of young human infants. In Study I, the presence of side biases in the stepping and placing responses and head turning in healthy fullterm newborns were explored. No evident lateral bias for the leg responses in terms of the first foot moved or direction of head turning was found. However, a lateral bias was revealed for onset latency in relation to the first foot moved in both stepping and placing. Asymmetries in head turning did not correspond to asymmetries in leg movements. In Study II, functional asymmetries in the stepping response of newborn infants were investigated in more detail by means of 3-D kinematic movement registration. Evident side differences were found in relation to smoother movement trajectories of the right leg by means of less movement segmentation compared to the left leg. Side differences were also found in relation to intralimb coordination in terms of stronger ankle-knee couplings and smaller phase shifts in the right leg than the left. In Study III, using the same movement registration technique, the kinematics of left and right arm movements during goal-directed reaching in infants were prospectively studied over the ages 6, 9, 12, and 36 months. Main findings included side differences and developmental trends related to the segmentation of the reaching movements and the reaching trajectory, as well as the distribution of arm-hand-use frequency. The results from Study I and II are discussed in relation to underlying neural mechanisms for lateral biases in leg movements and the important role of a thorough methodology in investigating newborn responses. Findings from Study III are discussed in terms of what they imply about the developmental origins for hand preference. An emphasis is also put on developmental differences between fullterm and preterm infants. Overall, the studies of the present thesis show that an increased understanding of subtle expressions of early functional asymmetries in the upper and lower body movements of young infants may be gained by means of refined measurements. Furthermore, such knowledge may provide an insight into the underlying neural mechanisms subserving asymmetries in the movements of young infants. The present studies also add new information to the current understanding of the development of human lateralized functions, in particular the findings derived from the longitudinal data. Apart from theoretical implications, the present thesis also involves a discussion with regard to the clinical relevance of investigating functional asymmetries in the movements of young infants.

The aim of this thesis was to study maternal and infant effects of delayed cord clamping (≥180 seconds, DCC) compared to early (≤10 seconds, ECC) in a randomised controlled trial. Practice and guidelines regarding when to clamp the cord vary globally, and different meta-analyses have shown contradictory conclusions on benefits and disadvantages of DCC and ECC. The study population consisted of 382 term infants born after normal pregnancies and randomised to DCC or ECC after birth. The primary objective was iron stores and iron deficiency at 4 months of age, but the thesis was designed to investigate a wide range of suggested effects associated with cord clamping. Paper I showed that DCC was associated with improved iron stores at 4 months (45% higher ferritin) and that the incidence of iron deficiency was reduced from 5.7% to 0.6%. Neonatal anaemia at 2-3 days was less frequent in the DCC group, 1.2% vs. 6.3%. There were no differences between the groups in respiratory symptoms, polycythaemia, or hyperbilirubinaemia. In paper II we demonstrated that DCC versus ECC was not associated with higher risk for maternal post partum haemorrhage and rendered a comparable ratio of valid umbilical artery blood gas samples. In paper III, the Ages and Stages Questionnaire was used to assess neurodevelopment at 4 months. The total scores did not differ, but the DCC group had a higher score in the problem-solving domain and a lower score in the personal-social domain. Immunoglobulin G level was 0.7 g/L higher in the DCC group at 2–3 days, but did not differ at 4 months. Symptoms of infection up to 4 months were comparable between groups. Finally, in paper IV, iron stores and neurodevelopment were similar between groups at 12 months. Gender specific outcome on neurodevelopment at 12 months was discovered, implying positive effects from DCC on boys and negative on girls. We conclude that delaying umbilical cord clamping for 180 seconds is safe and associated with a significantly reduced risk for iron deficiency at 4 months, which may have neurodevelopmental effects at a later age.

Background Due to small iron stores and rapid growth during the first months of life, infants with low birth weight (LBW) are at risk of iron deficiency (ID). ID in infancy is associated with irreversible impaired neurodevelopment. Preventive iron supplementation may reduce the risk of ID and benefit neurodevelopment, but there is also a possible risk of adverse effects. More than 50% of all LBW infants are born with marginally LBW (MLBW, 2000-2500g), and it is not known if they benefit from iron supplementation. Methods We randomized 285 healthy, Swedish, MLBW infants to receive 3 different doses of oral iron supplements; 0 (Placebo), 1, and 2 mg/kg/day from six weeks to six months of age. Iron status, during and after the intervention was assessed and so was the prevalence of ID and ID anemia (IDA), growth, morbidity and the interplay with iron and the erythropoetic hormones hepcidin and erythropoietin (EPO). As a proxy for conduction speed in the developing brain, auditory brainstem response (ABR) was analyzed at six months. In a follow up at 3.5 years of age, the children were assessed with a cognitive test (WPPSI-III) and a validated parental checklist of behavioral problems (CBCL), and compared to a matched reference group of 95 children born with normal birth weight. Results At six months of age, the prevalence of ID and IDA was significantly higher in the placebo group compared to the iron supplemented infants. 36% had ID in the placebo group, compared to 8% and 4 % in the 1 and 2mg/kg/day-groups, respectively. The prevalence of IDA was 10%, 3% and 0%, respectively. ABR-latencies did not correlate with the iron intake and was not increased in infants with ID or IDA. ABR wave V latencies were similar in all three groups. Hepcidin correlated to ferritin and increased in supplemented infants while EPO, which was negatively correlated to iron status indicators, decreased. At follow up there were no differences in cognitive scores between the groups but the prevalence of behavioral problems was significantly higher in the placebo group compared to those supplemented and to controls. The relative risk increase of CBCL-scores above a validated cutoff was 4.5 (1.4 – 14.2) in the placebo-group compared to supplemented children. There was no detected difference in growth or morbidity at any age. Conclusion MLBW infants are at risk of ID in infancy and behavioral problems at 3 years of age. Iron supplementation at a dose of 1-2 mg/kg/day from six weeks to six months of age reduces the risks with no adverse effects, suggesting both short and long term benefit. MLBW infants should be included in general iron supplementation programs during their first six months of life.