Cerebral Palsy in Extremely Preterm Infants.

BACKGROUND AND OBJECTIVES: The risk of cerebral palsy (CP) is high in preterm infants and is often accompanied by additional neurodevelopmental comorbidities. The present study describes lifetime prevalence of CP in a population-based prospective cohort of children born extremely preterm, including the type and severity of CP and other comorbidities (ie, developmental delay and/or cognitive impairment, neurobehavioral morbidity, epilepsy, vision and hearing impairments), and overall severity of disability. In this study, we also evaluate whether age at assessment, overall severity of disability, and available sources of information influence outcome results. METHODS: All Swedish children born before 27 weeks' gestation from 2004 to 2007 were included (the Extremely Preterm Infants in Sweden Study). The combination of neonatal information, information from clinical examinations and neuropsychological assessments at 2.5 and 6.5 years of age, original medical chart reviews, and extended chart reviews was used. RESULTS: The outcome was identified in 467 (94.5%) of eligible children alive at 1 year of age. Forty-nine (10.5%) children had a lifetime diagnosis of CP, and 37 (76%) were ambulatory. Fourteen (29%) had CP diagnosed after 2.5 years of age, 37 (76%) had at least 1 additional comorbidity, and 27 (55%) had severe disability. The probability for an incomplete evaluation was higher in children with CP compared with children without CP. CONCLUSIONS: Children born extremely preterm with CP have various comorbidities and often overall severe disability. The importance of long-term follow-up and of obtaining comprehensive outcome information from several sources in children with disabilities is shown.

Obese children aged 4-6 displayed decreased fasting and postprandial ghrelin levels in response to a test meal.

AIM: Ghrelin is a hunger hormone that plays a role in glucose homoeostasis and its levels increase before a meal and decrease during and after eating. This study compared the fasting ghrelin and insulin levels of obese children aged 4-6 with those of normal weight children and tested postprandial ghrelin levels in the obese children after a standard breakfast. METHODS: We recruited 67 children at Lund University Hospital from 2008 to 2011. They comprised 30 obese children from a weight study and 37 normal weight children receiving minor elective surgery. Their mean ages were 4.7 ± 0.6 and 4.3 ± 0.8 years, respectively. The obese children ate a standard breakfast, and postprandial ghrelin was measured after 60 minutes. RESULTS: The obese children had lower ghrelin levels than the controls (p < 0.01). A significant inverse relation was found between body mass index and fasting ghrelin levels. Obese children had significantly lower fasting ghrelin levels after a standard breakfast (p < 0.01), but there were no gender-related differences. CONCLUSION: Obese children aged 4-6 years had reduced ghrelin and increased insulin levels in the fasting state and postprandial ghrelin was suppressed, suggesting that their energy metabolism was already dysregulated at this young age. Early obesity interventions are essential.

Effect of an occupation-focused family intervention on change in parents' time use and children's body mass index.

OBJECTIVE. This study explored factors related to changes in the time parents spent with their children with obesity and associated decreases in children's body mass index (BMI) z-scores after an occupation-focused intervention. METHOD. Parents participated in a 1-yr occupation-focused intervention to promote healthy family lifestyles. Data on 40 parents of 22 children with obesity ages 4-6 yr were collected before and after intervention and analyzed using linear and multiple regression methods. RESULTS. Parents increased time spent with their children by an average of 91 min/day. Parents' finances, perceived satisfaction in daily occupations, low BMI, and mastery at inclusion were associated with increased time spent with their children. Mothers' subjective health and high mastery and fathers' perceived occupational value and education explained 67% of the variance in children's BMI z-scores. CONCLUSION. The results indicate important factors to consider in developing interventions that facilitate occupational engagement and health among children with obesity and their families.

Changes in parents' time use and its relationship to child obesity.

OBJECTIVE: The aim was to explore any change in parents' time use together with their children, changes in their perceived occupational value, and its relationship to children's body mass index (BMI) over the course of a one-year occupation-focused family intervention. METHOD: The study sample consisted of participants in one arm of a randomized controlled trial, involving mothers and fathers (n = 30) of 17 children aged 4-6 years who were considered obese. Data were collected by time-geographical diaries during the intervention and by measuring the parents' occupational value and the children's BMI before and after the intervention. RESULTS: At the end of the intervention, an increase was shown in the amount of time parents spent together with their children during weekdays (p = .042) and the parents perceived occupational value (p = .013). Children's BMI z-score changed with -0.11 units. CONCLUSION: Collaboration with parents may be useful in interventions aiming at facilitating a normal weight development among children.

A family-based intervention targeting parents of preschool children with overweight and obesity: conceptual framework and study design of LOOPS- Lund overweight and obesity preschool study.

BACKGROUND: As the rate of overweight among children is rising there is a need for evidence-based research that will clarify what the best interventional strategies to normalize weight development are. The overall aim of the Lund Overweight and Obesity Preschool Study (LOOPS) is to evaluate if a family-based intervention, targeting parents of preschool children with overweight and obesity, has a long-term positive effect on weight development of the children. The hypothesis is that preschool children with overweight and obesity, whose parents participate in a one-year intervention, both at completion of the one-year intervention and at long term follow up (2-, 3- and 5-years) will have reduced their BMI-for-age z-score. METHODS/DESIGN: The study is a randomized controlled trial, including overweight (n=160) and obese (n=80) children 4-6-years-old. The intervention is targeting the parents, who get general information about nutrition and exercise recommendations through a website and are invited to participate in a group intervention with the purpose of supporting them to accomplish preferred lifestyle changes, both in the short and long term. To evaluate the effect of various supports, the parents are randomized to different interventions with the main focus of: 1) supporting the parents in limit setting by emphasizing the importance of positive interactions between parents and children and 2) influencing the patterns of daily activities to induce alterations of everyday life that will lead to healthier lifestyle. The primary outcome variable, child BMI-for-age z-score will be measured at referral, inclusion, after 6 months, at the end of intervention and at 2-, 3- and 5-years post intervention. Secondary outcome variables, measured at inclusion and at the end of intervention, are child activity pattern, eating habits and biochemical markers as well as parent BMI, exercise habits, perception of health, experience of parenthood and level of parental stress. DISCUSSION: The LOOPS project will provide valuable information on how to build effective interventions to influence an unhealthy weight development to prevent the negative long-term effects of childhood obesity. TRIAL REGISTRATION: ClinicalTrials.gov NCT00916318.

The microbiota of the gut in preschool children with normal and excessive body weight.

The aim of this study was to investigate the gut microbiota in preschool children with and without overweight and obesity. Twenty overweight or obese children and twenty children with BMI within the normal range (age: 4-5 years) were recruited from the south of Sweden. The gut microbiota was accessed by quantitative PCR (qPCR) and terminal restriction fragment length polymorphism and calprotectin was measured in feces. Liver enzymes were quantified in obese/overweight children. The concentration of the gram-negative family Enterobacteriaceae was significantly higher in the obese/overweight children (P = 0.036), whereas levels of Desulfovibrio and Akkermansia muciniphila-like bacteria were significantly lower in the obese/overweight children (P = 0.027 and P = 0.030, respectively). No significant differences were found in content of Lactobacillus, Bifidobacterium or the Bacteroides fragilis group. The diversity of the dominating bacterial community tended to be less diverse in the obese/overweight group, but the difference was not statistically significant. Concentration of Bifidobacterium was inversely correlated to alanine aminotransferase (ALT) in obese/overweight children. The fecal levels of calprotectin did not differ between the study groups. These findings indicate that the gut microbiota differed among preschool children with obesity/overweight compared with children with BMI within the normal range.

Body mass index (BMI) and dental caries in 5-year-old children from southern Sweden.

OBJECTIVES: The aim of the present survey was to study the association between dental caries and body mass index (BMI) in Swedish preschool children (born in 1999). METHODS: A population-based and cross-sectional study design was used comprising all 920 5-year-old children in a defined area in and around the city of Lund. Anthropometric measures for the calculation of BMI were retrieved for each child from recordings at Child Health Care Centers (CHC). The occurrence of caries and fillings in the primary dentition, defined as deft (decayed, extracted, or filled primary teeth) and dt (decayed primary teeth), was collected from the children's dental records. RESULTS: The mean BMI was 16.1 (no differences between boys and girls). About 19.2% were overweight, of which 5.1% were obese. Overweight or obese children did not have higher deft or dt than others. However, children with low BMI (below -1 SD of national mean values for Swedish 5-year-olds) had statistically significantly higher deft and dt than children with normal BMI. CONCLUSIONS: Children with low BMI may be at risk of caries development. Low BMI may be associated with eating habits endangering dental health.

Perinatal complications and socio-economic differences in cerebral palsy in Sweden - a national cohort study.

BACKGROUND: There is a controversy regarding the existence of a socio-economic gradient for cerebral palsy. Perinatal emergencies and preterm birth increase the risk for the offspring to develop cerebral palsy. The aim of this study was to investigate the association of socio-economic indicators with cerebral palsy (CP) and the role of perinatal health as mediator of this association. METHODS: Register study of a national cohort of 805,543 children born 1987-93, including 1,437 children with cerebral palsy that were identified in hospital discharge data from national registers. Socio-economic indicators of the household were taken from the Census of 1985. Logistic regression and chi-square analyses of linearity were used to test hypotheses. RESULTS: There was a linear association between the incidence of CP (excluding cases caused by registered injuries or malformations) as well as of major perinatal indicators and the socio-economic status (SES) of the household of the mother (p < 0.001). Children in households with low SES had a higher odds ratio of CP (OR 1.49 [95% C.I. 1.16-1.91]) compared with high SES after adjustment for demographic confounders. This OR decreased to 1.36 (1.05-1.71) after adjustment for perinatal indicators with preterm birth as the most important mediating variable. CONCLUSION: This study suggests that there is a continuous socio-economic gradient for CP in Sweden. Further studies in more complete populations of children with cerebral palsy are needed to confirm this. Perinatal complications seem to mediate some of this gradient.

How often is a low 5-min Apgar score in term newborns due to asphyxia?

OBJECTIVE: To evaluate how often low 5-min Apgar scores (AS(5-min)) at term are associated with asphyxia. STUDY DESIGN: A cohort- and case-control study, including all 183 term infants with AS(5-min) below 7 born at Lund University Hospital during 1993-2002, antepartum deaths excluded. The control group included 183 randomly selected term newborns with AS(5-min) 9-10. Cardiotocography (CTG) traces were assessed blinded to group and outcome. Obstetric and pediatric files were reviewed. RESULTS: After excluding infants with severe malformations, indications of hypoxia were found at the following rates in cases with AS(5-min) below 4 (N = 30), scores 4-6 (N = 143), and controls (N = 182)-abnormal admission CTG: 38%, 8% and 0.6%; abnormal CTG before birth: 88%, 69% and 18%; obstetrical catastrophe: 28%, 6% and 0.6%; interventions for fetal distress: 83%, 48% and 9%; cord artery pH below 7.15: 69%, 54% and 7%; hypoxic ischemic encephalopathy or hypoxic death: 70%, 14% and none. All differences between each case group and controls were statistically significant (p < 0.0001). CONCLUSIONS: In the absence of severe malformations, the vast majority of AS(5-min) below 4, and at least half of scores 4-6 could be attributed to birth asphyxia. Signs of hypoxia usually appeared during labor, but were present at admission in 38% of cases with AS(5-min) below 4.

Perinatal factors associated with cerebral palsy in children born in Sweden.

OBJECTIVE: To identify perinatal factors associated with cerebral palsy (CP). METHODS: This was a case-control study based on the Swedish Medical Birth Registry and the Swedish Hospital Discharge Registry, including 2,303 infants born in Sweden 1984-1998 with a diagnosis of CP and 1.6 million infants without this diagnosis. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. RESULTS: Infants born preterm had a highly increased risk for CP, and constituted 35% of all cases; OR 34 (95% CI 29-39) in weeks 23-27, OR 37 (95% CI 32-42) in weeks 28-29, OR 26 (95% CI 23-30) in weeks 30-31, and OR 3.9 (95% CI 3.4-4.4) in weeks 32-36. Boys had a higher risk (sex ratio 1.36:1), particularly before term (sex ratio 1.55:1). Other factors associated with CP were being small or large for gestational age at birth, abruptio placentae (OR 8.6, 95% CI 5.6-13.3), maternal insulin-dependent diabetes mellitus type 1 (OR 2.1, 95% CI 1.4-3.1), preeclampsia (OR 1.5, 95% CI 1.3-2.4), being a twin (OR 1.4, 95% CI 1.1-1.6), maternal age older than 40 years (OR 1.4, 95% CI 1.1-1.8) or 35-39 years (OR 1.2, 95% CI 1.1-1.4), primiparity (OR 1.2, 95% CI 1.1-1.3), and smoking (OR 1.2, 95% CI 1.1-1.3). In term infants, low Apgar scores were associated with a high risk for CP; OR 62 (95% CI 52-74) at score 6 at 5 minutes, OR 498 (95% CI 458-542) at score 3. Other factors associated with CP in term infants were breech presentation at vaginal birth (OR 3.0, 95% CI 2.4-3.7), instrumental delivery (OR 1.9, 95% CI 1.6-2.3), and emergency cesarean delivery (OR 1.8, 95% CI 1.6-2.0). CONCLUSION: Preterm birth entails a high risk for CP, but 65% of these children are born at term. Several obstetric factors and low Apgar scores are associated with CP. LEVEL OF EVIDENCE: II-2.

Perinatal adaptive response of the adrenal and carotid blood flow in sheep fetuses subjected to total cord occlusion.

OBJECTIVE: To investigate the perinatal adaptive response of the adrenal blood flow/adrenal fractional moving blood volume (AFMBV) and carotid blood flow (CBF), in sheep fetuses subjected to severe acute intrauterine hypoxia/asphyxia induced by total cord occlusion. METHODS: Adrenal blood flow velocity, AFMBV and CBF were measured in 13 exteriorized fetal sheep; eight of them underwent total umbilical cord occlusion to induce severe acute hypoxia/asphyxia. Five lambs were used as sham controls. Middle adrenal artery pulsatility index (MAAPI) and mean velocity (MAAMV) were recorded with pulsed Doppler ultrasound. AFMBV was estimated using power Doppler ultrasound. CBF was recorded with a transonic flowmeter. In the neonatal period, after resuscitation all lambs were followed for a 4-hour period and AFMBV and CBF were recorded. Mean arterial blood pressure (MABP) and fetal heart rate were recorded continuously. Arterial cortisol levels were measured at the beginning and at the end of the fetal and neonatal periods. RESULTS: Following the total cord occlusion, there was a significant reduction in the CBF, MABP, and heart rate and adrenal flow/AFMBV after 2, 4 and 5 min, respectively. Cortisol levels in the asphyctic lambs at the end of the cord occlusion were significantly lower than those in controls. After resuscitation, the asphyctic lambs showed increased AFMBV and cortisol levels, and reduced MABP as compared to control lambs. No differences were found in CBF, MAAPI and MAAMV. Thereafter, no differences were observed between the two groups in any of the studied parameters. At the end of the cord occlusion period, there was a significant correlation between AFMBV and MABP (r=0.69), between AFMBV and CBF (r =0.65) and between CBF and MABP (r=0.89). CONCLUSION: During severe acute intrauterine hypoxia, the fetal lamb is able to maintain the blood flow to the brain and the adrenal gland for 3-5 min. Changes in the AFMBV and the CBF were highly correlated to the changes in MABP. Adrenal FMBV and cortisol levels were higher in lamb neonates exposed to severe intrauterine asphyxia.

Different responses of myocardial and cerebral blood flow to cord occlusion in exteriorized fetal sheep.

Type and duration of fetal asphyxial insult affect the distribution of blood flow to the heart and brain. The purpose of this study was to describe dynamic and quantitative changes in regional myocardial and cerebral blood flow (CBF) during fetal asphyxia induced by total occlusion of the umbilical cord. Eleven exteriorized fetal sheep were subjected to total umbilical cord occlusion and five fetal sheep served as sham controls. Regional blood flow (BF) to the brain and heart was quantified using radioactive microspheres before and after 5 min of occlusion and finally when fetal mean arterial blood pressure had decreased below 25 mm Hg, 9.8 (0.8) [mean (SD)] min after occlusion. Right coronary arterial (RCA) blood flow velocity and carotid BF were registered continuously. Mean values of arterial pH and oxygen content (mL O(2)/100 mL) were 7.08 (0.11) and 4.4 (2.9) before cord occlusion and decreased to 6.83 (0.05) and 1.4 (0.9) at 5 min after occlusion (p < 0.01, respectively). Carotid BF was significantly below preocclusion values by 2.5 min (p < 0.05), whereas RCA velocity time integral per minute remained above preocclusion values for 9 min. CBF decreased from 316 (24) before cord occlusion to 156 (30) mL/min/100 g at 5 min (p < 0.01), whereas right myocardial BF was maintained at 792 (125) and 751 (183) mL/min/100 g, respectively. CBF decreased rapidly after total cord occlusion whereas myocardial BF increased and was maintained until shortly before cardiac arrest, suggesting the myocardium to be better preserved during this type of insult in already partially asphyxiated fetuses.

S100 protein in serum as a prognostic marker for cerebral injury in term newborn infants with hypoxic ischemic encephalopathy.

The astroglial protein S100 is an established biochemical marker for CNS injury in the adult. The aim was to investigate whether S100 in serum is a prognostic marker of cerebral injury in term newborn infants with hypoxic ischemic encephalopathy (HIE) after perinatal asphyxia. Serum S100 was measured on postnatal days 1-4 in 62 term infants with birth asphyxia. The infants were classified for HIE and had follow-up for at least 18 mo. Infants with moderate and severe HIE had significantly higher S100 levels on postnatal day 1 (p = 0.031) and day 2 (p = 0.008) than infants with mild or no HIE. The levels of S100 decreased on days 2 and 3 in all infants with HIE. The median S100 level on postnatal day 1 was higher in nine infants who died neonatally and in 10 infants who developed cerebral palsy (CP), compared with 43 infants with no signs of impairment at follow up, 14.0 (0.5-60.0) microg/L, 20.7 (0.2-64.0) microg/L and 5.5 (0.7-120.0) microg/L, respectively. A level of S100 above 12 microg/L the first day of life was significantly more frequent in infants who died or developed CP than in infants with no impairment at follow up (p = 0.02). Increased S100 levels were significantly inversely correlated with perinatal pH in the infants and associated with abnormal CTG at admission to the labor ward. Early determination of serum S100 may reflect the extent of brain damage in infants with HIE after asphyxia.

Cerebral glucose metabolism and early EEG/aEEG in term newborn infants with hypoxic-ischemic encephalopathy.

The objective was to investigate how early electrocortical background pattern, as recorded with amplitude integrated EEG (aEEG), correlates with global and regional cerebral glucose metabolism (CMRgl) measured by positron emission tomography during the subacute phase after birth asphyxia. Nineteen term infants with hypoxic-ischemic encephalopathy were investigated. The aEEG background was evaluated at 0-6, 6-12, 12-24, 24-48, and 48-72 h postnatal age, and classified into four categories according to increasing degree of abnormality. The aEEG were also evaluated for sleep-wake cycling and epileptic seizure activity. CMRgl was measured by positron emission tomography with 2-(18F) fluoro-2-deoxy-d-glucose at a median (range) postnatal age 10 (4-24) d. Increasing degree of abnormality in aEEG correlated significantly with decreasing CMRgl: at 6-12 h (-0.593; 0.012) (r value; p value), 12-24 h (-0.669; 0.003), and 24-48 h (-0.569; 0.014) postnatal age. Presence of sleep-wake cycling at 0-6 h (0.697; 0.012), 6-12 h (0.668; 0.003), and 12-24 h (0.612; 0.009) of age correlated with increased CMRgl. Delayed seizure activity at 12-24 h correlated with decreased CMRgl (-0.661; 0.004). Infants with abnormal aEEG at 6-12 h had lower CMRgl in all regions of the brain compared with infants with normal aEEG. CMRgl of any specific region of the brain was not significantly more correlated to aEEG than CMRgl of other regions. Early electrocortical background patterns, early presence of sleep-wake cycling, and delayed seizure activity were highly correlated with global CMRgl measured during the subacute phase after asphyxia, but did not correlate with any specific pattern of regional uptake.