<p>While constituting a well functioning interface with the aqueous environment in utero, the skin offers a poor barrier after very preterm birth. As a result, transepidermal water loss (TEWL) is high, a fact which has important clinical consequences in these infants. To investigate the transport of water through perinatal skin and the potential role of aquaporin (AQP), a water channel protein, in this process, we determined TEWL in a group of extremely preterm infants, and in an experimental rat model we analyzed the expression and distribution of AQP in perinatal skin in relation to TEWL, skin surface hydration and water content. The effects of antenatal corticosteroids (ANS) and of restricted intake of fluids and nutrients on barrier characteristics of the perinatal skin and its AQP expression were also studied.</p><p>In infants born at 24 and 25 weeks of gestation TEWL was very high in the first days after birth and decreased with increasing postnatal age. At a postnatal age of 4 weeks, TEWL was still twice as high as previously reported in infants born at a gestational age of 25-27 weeks and four times higher than in infants born at term. In the rat model, immunohistochemical analysis revealed that AQP1 and AQP3 are abundantly expressed in the skin. AQP1 was expressed exclusively in dermal capillaries and AQP3 in basal layers of the epidermis. AQP1 and AQP3 mRNA as assessed by semiquantitative RT-PCR was higher in fetal than in adult skin. As in infants, TEWL and skin surface hydration were inversely related to gestational age in the rat. In preterm rat pups exposed to ANS, TEWL and skin surface hydration were lower than in unexposed controls, and AQP3 expression was selectively induced by ANS. In term newborn rat pups, restriction of fluid and nutrient intake resulted in a higher skin water content and higher TEWL early after birth, while at an age of 7 days TEWL was lower in fasting rat pups than in controls, although skin water content was still higher.</p><p>To conclude, TEWL is very high in extremely preterm infants early after birth and then decreases at a slower rate than previously reported for a group of slightly more mature infants. </p><p>This is the first time that the distribution and gene expression of AQP1 and AQP3 have been demonstrated in perinatal skin. The localization and expression of AQP in the skin might indicate that these water channels are involved in the regulation of skin hydration and transepidermal water transport in the fetus and newborn infant.</p>

<p>Children with myelomeningocele (MMC) usually have problems with daily life activities, but the background to their problems is not altogether obvious. An understanding of the possible causes of activity problems is a prerequisite for the effectiveness of physical therapy. The overall aim of the present studies was to identify impairments above the cele level, which might influence mobility in children with MMC (study I) and to analyse sitting posture (study II) and the movement characteristics of reaching movements (study III and IV). </p><p>In total, 41 children and young adults with MMC and without mental retardation were investigated. Study I comprised 32 children, 6-11 years. Mobility and the caregiver assistance required for mobility were quantified according to the Paediatric Evaluation of Disability Inventory (PEDI) and correlation between mobility and neurological impairment, hand function and cognitive function were calculated. The results showed that nine children achieved independent mobility and that there was a moderate and significant correlation between the need for physical assistance and high cele level, impaired hand function and impaired cognitive function. In those children who used a wheelchair, only poor hand strength was significantly correlated with the need for caregiver assistance.</p><p>Study II comprised 11 children, 10-13 years, and a control group of 20 healthy children. Sitting posture was investigated by using a force plate and analysed from the frequency and the amplitude of the postural sway. The reaction forces before and during rapid arm lift were also analysed. The result showed that children with MMC had significantly lower sway frequency compared to the controls. In both groups, the ground reaction forces were registered before the children lifted their arms. Study III and IV comprised 31 children and young adults, 9-19 years and 31 matched controls. Reaching movements were investigated with a digitising tablet, linked to a computer. The ability to program and execute reaching movements was analysed and also the ability to adapt reaching to new visuomotor conditions. The results showed that the MMC group had poorer precision, less straight movements and shorter deceleration phases as compared to the controls. In both groups the movements were pre-programmed. In addition, adaptation of reaching to new visuomotor conditions was poor in the MMC group as compared to the controls. </p><p>In conclusion we found that impairments above the cele level influenced mobility and the control of sitting posture in children with MMC. Reduced precision and co-ordination of reaching, and also difficulties with motor adaptation, could partly explain thier problems with hand activities. These findings need to be considered in therapy programs for children and young adults with MMC.</p>

<p>Glucose is the most important fetal nutrient and the production of this substrate increases in the pregnant woman. In the last trimester the increased insulin resistance directs energy substrates to the fetus. Fetal growth is sometimes disturbed, often without an obvious explanation.</p><p>After birth the newborn infant must produce its own glucose, primarily for the brain. Fatty acids from lipolysis are also important energy substrates. Hypoglycaemia can be a problem, occurring frequently in preterm infants and infants born small for gestational age (SGA). In addition, SGA infants are at risk of developing the metabolic syndrome in adulthood. Neonatal medication can influence energy metabolism. One such medication is theophylline, administered in preterm infants to prevent apnoea. </p><p>We investigated energy substrate production in women with normal and IUGR pregnancies, in preterm neonates, before and after theophylline treatment and in newborn SGA infants, using stable isotope-labelled compounds and gas chromatography-mass spectrometry. </p><p>We found that late pregnancy was associated with an almost twofold increase in the rate of lipolysis. This provides substrates for maternal energy metabolism, which may spare glucose for the fetus. Even though glucose production was comparable in the two groups of pregnant women, those with IUGR had a lower rate of lipolysis. A reduced supply of energy substrates could be one factor underlying IUGR. In spite of the insulin resistance of late pregnancy, insulin still had a regulatory role in energy substrate production in the women with normal pregnancies, but not in those with IUGR. </p><p>Although infants born preterm and/or SGA have limited energy stores, we demonstrated that they are capable of both lipolysis and glucose production. Theophylline had no adverse effects on energy substrate production. Data on insulin and IGFBP-1 in the SGA infants indicate that in such infants insulin sensitivity is increased peripherally but reduced in the liver.</p>

<p><b>Background. </b>Newborn infants, especially preterm infants, have an increased susceptibility to serious and overwhelming bacterial as well as fungal infections. Symptoms of septicaemia in especially the very preterm neonates are vague and unspecific. No really good biochemical parameter exists today that can confirm or exclude the existence of neonatal septicaemia. The access to such a test in neonates would be most valuable, not only to assure early institution of effective antibiotic therapy when needed, but also to avoid unnecessary use of antibiotics, thereby reducing the risk of further development of antimicrobial resistance. </p><p><b>Aim. </b>To investigate the possible use of the expression of the phagocyte receptor CD64 (FcγRI) on neutrophils for early diagnosis of bacterial infections with special reference to neonatal septicaemia. </p><p><b>Results. </b>Neutrophils from preterm and term newborn infants, older infants, children, and adults examined during the early phase of a bacterial infection showed a significantly higher expression of CD64 compared with non-infected controls (p<0.001). Neutrophils from even extremely preterm infants expressed CD64 to the same extent as did neutrophils from children and adult patients. The expression of CD64 was not affected by the respiratory distress syndrome (RDS) or by such factors as premature rupture of the membranes, gestational age, steroid treatment before delivery, method of delivery, birth weight or postnatal age.</p><p>Major surgery in adults (total hip replacement) did not affect the CD64 expression to an extent comparable to that found during bacterial infections. Indirectly CD64 was found to be at least equal to CRP for differentiation between Influenza A infection and bacterial infections in adults.</p><p><b>Conclusion.</b> CD64 was found to be a specific and reliable marker for early detection of bacterial infections in preterm and term newborn infants, as well as after surgery. For differentiation between bacterial and viral infections it is probably at least as effective as CRP.</p>

<p>In a Manila hospital, 204 mothers were randomized into three groups: two intervention groups receiving home-based counseling visits, one of them (n=68) by counselors trained to use a locally developed, two-tiered program of breastfeeding counseling, and the other by counselors trained in general childcare (n=67), were compared with a control group of mothers (n=69) who did not receive any counseling. All infants were scheduled for seven visits to the hospital for follow-up. During hospital visits, maternal and infant body measurements were made and an independent interviewer asked the mothers individually to recall how the infant had been fed. One study physician, blind to participant groups, was consulted at all scheduled and unscheduled infant visits.</p><p>At six months, 44% of the breastfeeding-counseled mothers, 7% of the childcare-counseled mothers and none of the mothers in the control group were exclusively breastfeeding. Twenty- four mothers breastfed exclusively during the first six months, of whom 22 received breastfeeding counseling and 2 had no breastfeeding counseling. Among 24 infants who were exclusively breastfed from birth to six months there were no episodes of diarrhea. All infants had gained in weight, length and head circumference. Mean maternal weight loss at six months was similar whether her breastfeeding was exclusive or partial.</p><p>The reasons why mothers without breastfeeding counseling introduced non-breast milk feeding before six months reflected lack of knowledge and support. Breastfeeding support during the first six months focusing on how to prevent and solve breastfeeding problems, particularly during the first two weeks, will enable mothers to choose to breastfeed exclusively up to six months. </p><p>This study has provided fundamental evidence of successful intervention by breastfeeding counseling to achieve six months of exclusive breastfeeding among term, low-birthweight infants. The locally developed training program in breastfeeding counseling, which successfully prepared volunteers to counsel mothers at home, could be incorporated into primary health care in the Philippines. Mothers who received breastfeeding counseling appreciated how this helped them to achieve their breastfeeding goals for the first six months. Improved breastfeeding practices as a result of breastfeeding counseling provided infants with protection from diarrhea and respiratory infections, contributing to their health and development.</p>

<p>The overall aim of this thesis was to expand the knowledge and understanding of the processes of breastfeeding and becoming a mother in mothers of preterm infants. </p><p>For this purpose, in-depth interviews were conducted with 25 mothers, whose very preterm infants had received care in seven neonatal units (NU) in Sweden, 1-12 months after discharge (I-II). In addition, prospective population-based register studies were performed of infants born 1993-2001; among 35 250 term and 2093 preterm infants (III), and a subpopulation of 225 very preterm infants (IV). Data were obtained from the Child Health Service registry of breastfeeding in Uppsala and Örebro, the Medical Birth Registry, and Statistics Sweden. </p><p>The experiences of mother-infant separation, institutional authority, emotional exhaustion and disregard of breastfeeding as a relational interplay, comprised major hindrances to mothers’ experiences of breastfeeding as reciprocal and of a secure mother-infant relation, during and after the discharge from an NU (I-II). All studied socioeconomic factors, i.e. lower educational level, receiving unemployment benefit or social welfare or having a low equivalent disposable income, were individually adversely associated with breastfeeding up to six months of infants’ postnatal age, but were not found more decisive for weaning in mothers of preterm infants compared to those of term infants (III). Preterm infants were breastfed for a shorter time than term infants (III), but a long breastfeeding duration was evident. In addition, gestational age and neonatal disorders were not associated with breastfeeding duration in very preterm infants (IV).</p><p>In conclusion, this thesis shows that improvements in the NU environment and the caring paradigm are called for. Furthermore, as socioeconomic status clearly has an impact on breastfeeding duration, increased equity in health care in accordance with the individuals’ needs must be sought, where resources are allocated to ensure fulfilment of needs in more vulnerable mothers and infants. </p>

While constituting a well functioning interface with the aqueous environment in utero, the skin offers a poor barrier after very preterm birth. As a result, transepidermal water loss (TEWL) is high, a fact which has important clinical consequences in these infants. To investigate the transport of water through perinatal skin and the potential role of aquaporin (AQP), a water channel protein, in this process, we determined TEWL in a group of extremely preterm infants, and in an experimental rat model we analyzed the expression and distribution of AQP in perinatal skin in relation to TEWL, skin surface hydration and water content. The effects of antenatal corticosteroids (ANS) and of restricted intake of fluids and nutrients on barrier characteristics of the perinatal skin and its AQP expression were also studied. In infants born at 24 and 25 weeks of gestation TEWL was very high in the first days after birth and decreased with increasing postnatal age. At a postnatal age of 4 weeks, TEWL was still twice as high as previously reported in infants born at a gestational age of 25-27 weeks and four times higher than in infants born at term. In the rat model, immunohistochemical analysis revealed that AQP1 and AQP3 are abundantly expressed in the skin. AQP1 was expressed exclusively in dermal capillaries and AQP3 in basal layers of the epidermis. AQP1 and AQP3 mRNA as assessed by semiquantitative RT-PCR was higher in fetal than in adult skin. As in infants, TEWL and skin surface hydration were inversely related to gestational age in the rat. In preterm rat pups exposed to ANS, TEWL and skin surface hydration were lower than in unexposed controls, and AQP3 expression was selectively induced by ANS. In term newborn rat pups, restriction of fluid and nutrient intake resulted in a higher skin water content and higher TEWL early after birth, while at an age of 7 days TEWL was lower in fasting rat pups than in controls, although skin water content was still higher. To conclude, TEWL is very high in extremely preterm infants early after birth and then decreases at a slower rate than previously reported for a group of slightly more mature infants. This is the first time that the distribution and gene expression of AQP1 and AQP3 have been demonstrated in perinatal skin. The localization and expression of AQP in the skin might indicate that these water channels are involved in the regulation of skin hydration and transepidermal water transport in the fetus and newborn infant.

Children with myelomeningocele (MMC) usually have problems with daily life activities, but the background to their problems is not altogether obvious. An understanding of the possible causes of activity problems is a prerequisite for the effectiveness of physical therapy. The overall aim of the present studies was to identify impairments above the cele level, which might influence mobility in children with MMC (study I) and to analyse sitting posture (study II) and the movement characteristics of reaching movements (study III and IV). In total, 41 children and young adults with MMC and without mental retardation were investigated. Study I comprised 32 children, 6-11 years. Mobility and the caregiver assistance required for mobility were quantified according to the Paediatric Evaluation of Disability Inventory (PEDI) and correlation between mobility and neurological impairment, hand function and cognitive function were calculated. The results showed that nine children achieved independent mobility and that there was a moderate and significant correlation between the need for physical assistance and high cele level, impaired hand function and impaired cognitive function. In those children who used a wheelchair, only poor hand strength was significantly correlated with the need for caregiver assistance. Study II comprised 11 children, 10-13 years, and a control group of 20 healthy children. Sitting posture was investigated by using a force plate and analysed from the frequency and the amplitude of the postural sway. The reaction forces before and during rapid arm lift were also analysed. The result showed that children with MMC had significantly lower sway frequency compared to the controls. In both groups, the ground reaction forces were registered before the children lifted their arms. Study III and IV comprised 31 children and young adults, 9-19 years and 31 matched controls. Reaching movements were investigated with a digitising tablet, linked to a computer. The ability to program and execute reaching movements was analysed and also the ability to adapt reaching to new visuomotor conditions. The results showed that the MMC group had poorer precision, less straight movements and shorter deceleration phases as compared to the controls. In both groups the movements were pre-programmed. In addition, adaptation of reaching to new visuomotor conditions was poor in the MMC group as compared to the controls. In conclusion we found that impairments above the cele level influenced mobility and the control of sitting posture in children with MMC. Reduced precision and co-ordination of reaching, and also difficulties with motor adaptation, could partly explain thier problems with hand activities. These findings need to be considered in therapy programs for children and young adults with MMC.

Glucose is the most important fetal nutrient and the production of this substrate increases in the pregnant woman. In the last trimester the increased insulin resistance directs energy substrates to the fetus. Fetal growth is sometimes disturbed, often without an obvious explanation. After birth the newborn infant must produce its own glucose, primarily for the brain. Fatty acids from lipolysis are also important energy substrates. Hypoglycaemia can be a problem, occurring frequently in preterm infants and infants born small for gestational age (SGA). In addition, SGA infants are at risk of developing the metabolic syndrome in adulthood. Neonatal medication can influence energy metabolism. One such medication is theophylline, administered in preterm infants to prevent apnoea. We investigated energy substrate production in women with normal and IUGR pregnancies, in preterm neonates, before and after theophylline treatment and in newborn SGA infants, using stable isotope-labelled compounds and gas chromatography-mass spectrometry. We found that late pregnancy was associated with an almost twofold increase in the rate of lipolysis. This provides substrates for maternal energy metabolism, which may spare glucose for the fetus. Even though glucose production was comparable in the two groups of pregnant women, those with IUGR had a lower rate of lipolysis. A reduced supply of energy substrates could be one factor underlying IUGR. In spite of the insulin resistance of late pregnancy, insulin still had a regulatory role in energy substrate production in the women with normal pregnancies, but not in those with IUGR. Although infants born preterm and/or SGA have limited energy stores, we demonstrated that they are capable of both lipolysis and glucose production. Theophylline had no adverse effects on energy substrate production. Data on insulin and IGFBP-1 in the SGA infants indicate that in such infants insulin sensitivity is increased peripherally but reduced in the liver.

<b>Background. </b>Newborn infants, especially preterm infants, have an increased susceptibility to serious and overwhelming bacterial as well as fungal infections. Symptoms of septicaemia in especially the very preterm neonates are vague and unspecific. No really good biochemical parameter exists today that can confirm or exclude the existence of neonatal septicaemia. The access to such a test in neonates would be most valuable, not only to assure early institution of effective antibiotic therapy when needed, but also to avoid unnecessary use of antibiotics, thereby reducing the risk of further development of antimicrobial resistance. <b>Aim. </b>To investigate the possible use of the expression of the phagocyte receptor CD64 (FcγRI) on neutrophils for early diagnosis of bacterial infections with special reference to neonatal septicaemia. <b>Results. </b>Neutrophils from preterm and term newborn infants, older infants, children, and adults examined during the early phase of a bacterial infection showed a significantly higher expression of CD64 compared with non-infected controls (p&lt;0.001). Neutrophils from even extremely preterm infants expressed CD64 to the same extent as did neutrophils from children and adult patients. The expression of CD64 was not affected by the respiratory distress syndrome (RDS) or by such factors as premature rupture of the membranes, gestational age, steroid treatment before delivery, method of delivery, birth weight or postnatal age. Major surgery in adults (total hip replacement) did not affect the CD64 expression to an extent comparable to that found during bacterial infections. Indirectly CD64 was found to be at least equal to CRP for differentiation between Influenza A infection and bacterial infections in adults. <b>Conclusion.</b> CD64 was found to be a specific and reliable marker for early detection of bacterial infections in preterm and term newborn infants, as well as after surgery. For differentiation between bacterial and viral infections it is probably at least as effective as CRP.