Aim:

To characterize postnatal changes in serum insulin-like growth factor-1 (IGF-I) in relation to development of bronchopulmonary dysplasia (BPD) in very preterm infants.

Methods:

Longitudinal study of 108 infants with mean (SD) gestational age (GA) 27.2 (2.2) weeks. Weekly serum samples of IGF-I were analysed from birth until postmenstrual age (PMA) 36 weeks. Multivariate models were developed to identify independent predictors of BPD.

Results:

Postnatal mean IGF-I levels at postnatal day (PND) 3–21 were lower in infants with BPD compared with infants with no BPD (16 vs. 26 μg/L, p < 0.001). Longitudinal postnatal change in IGF-I levels (IGF-I regression coefficient (β)), PNDs 3–21, was lower in infants with BPD compared with infants with no BPD (0.28 vs. 0.97, p = 0.002) and mean IGF-I during PMA 30–33 weeks was lower in infants with BPD as compared with infants without BPD (22 vs. 29 μg/L, p < 0.001). In a binomial multiple regression model, lower GA, male gender and lower mean serum IGF-I levels during PND 3–21 were the most predictive risk factors associated with BPD (r2 = 0.634, p < 0.001).

Conclusion:

Lower IGF-I concentrations during the first weeks after very preterm birth are associated with later development of BPD.

Background

Parental behavior described as “scaffolding” has been shown to influence outcomes in at-risk children. The purpose of this study was to compare maternal verbal scaffolding in toddlers born preterm and full term.

Methods

The scaffolding behavior of mothers of toddlers born preterm and healthy full term was compared during a 5 minute videotaped free play session with standardized toys. We compared two types of scaffolding and their associations with socio-demographic, neonatal medical factors, and cognition.

Results

The mothers of toddlers born full term used more complex scaffolding. Maternal education was associated with complex scaffolding scores for the preterm children only. Specifically, the preterm children who were sicker in the neonatal period, and whose mothers had higher education, used more complex scaffolding. In addition, children born preterm who had less days of ventilation, had higher cognitive scores when their mothers used more complex scaffolding. Similarly, cognitive and scaffolding scores were higher for children born full term.

Discussion

Our findings highlight early differences in mother-child interactive styles of toddlers born preterm compared to full term. Teaching parents play methods that support early problem solving skills may support a child’s method of exploration and simultaneously their language development.

Aim

To better understand differences between Bayley Scales 3rd edition (Bayley III) Cognitive Scale and Bayley Scales 2nd edition (Bayley II) Mental Developmental Index (MDI) in 18–22 month old children born term and preterm; and to create a conversion algorithm using Bayley II MDI to calculate Bayley III Cognitive score.

Methods

This study included 51 term and 26 preterm children between 18 and 22 months, ages adjusted for prematurity. Children’s scores on Bayley II MDI and Bayley III Cognitive Scale were compared using t-tests. The items from Bayley II MDI were used to calculate a score for the Bayley III Cognitive Scale. ANCOVA was used to create a conversion scale.

Results

Bayley III Cognitive scores were significantly higher than Bayley II MDI scores for term and preterm toddlers combined and separately (p<.0001). A conversion formula to convert Bayley II MDI to a Bayley III Cognitive score was calculated.

Conclusion

Term and preterm children had similarly elevated scores on the Bayley III calculated Cognitive score compared to the previous Bayley II MDI score. The use of a conversion algorithm maybe helpful in studies that used both Bayley editions in order to get comparable outcome measurements within a clinical or research paradigm.

Aim

To compare risk-adjusted outcomes at 18–22 months corrected age for extremely low birth weight (ELBW) infants who never received phototherapy (NoPTx) to those who received any phototherapy (PTx) in the NICHD Neonatal Research Network randomized trial of Aggressive vs. Conservative Phototherapy.

Methods

Outcomes at 18–22 months corrected age included death, neurodevelopmental impairment (NDI), and Bayley Scales Mental Developmental Index (MDI). Regression models evaluated the independent association of PTx with adverse outcomes controlling for center and other potentially confounding variables.

Results

Of 1972 infants, 216 were NoPTx and 1756 were PTx. For the entire 501–1000 g BW cohort, PTx was not independently associated with death or NDI (OR 0.85, 95% CI 0.60 –1.20), death, or adverse neurodevelopmental endpoints. However, among infants 501–750 g BW, the rate of significant developmental impairment with MDI<50 was significantly higher for NoPTx (29%) than PTx (12%) (p=0.004).

Conclusions

Phototherapy did not appear to be independently associated with death or NDI for the overall ELBW group. Whether PTx increases mortality could not be excluded due to bias from deaths before reaching conservative treatment threshold. The higher rate of MDI<50 in the 501–750g BW NoPTx group is concerning, and consistent with NRN Trial results.

Aims

To determine whether extremely low birth weight (ELBW) infants with bilateral compared to unilateral intraventricular hemorrhage (IVH) have worse neurodevelopmental outcomes at 18–22 months.

Methods

166 ELBW infants (<1000 g) admitted to a Cincinnati NICU from 1998–2005 with a head ultrasound showing Grade I–IV IVH and neurodevelopmental assessment at 18–22 months corrected age were included. Multivariable linear and logistic regression models were developed to determine the impact of laterality and grade of IVH and other clinical variables to predict scores on the Bayley Scales of Infant Development, Second Edition, Mental Development Index (MDI) and Psychomotor Development Index (PDI) and the combined outcome of neurodevelopmental impairment (NDI).

Results

Infants with bilateral grade IV IVH had lower adjusted mean Bayley scores compared with infants with unilateral grade IV IVH. For grades I, II, and III IVH, bilaterality of IVH was not associated with lower mean Bayley scores. Infants with grade IV IVH had the highest odds of NDI. The probability of NDI increased with sepsis and postnatal steroid use.

Conclusions

ELBW infants with bilateral compared to those with unilateral grade IV IVH had worse neurodevelopmental outcomes. Infants with grades I–III IVH had similar outcomes whether they had unilateral or bilateral IVH.

Aim

To examine risk and protective factors associated with behavioural problems of children and adolescents following prenatal alcohol exposure.

Methods

A total of 73 children and adolescents with foetal alcohol spectrum disorders (FASD) were assessed for internalizing, externalizing and total behavioural problems using the Child Behavior Checklist. Linear regression models were used to determine the effects of diagnostic and environmental risk and protective factors on behaviour, while controlling for age, sex and IQ.

Results

Length of time spent in residential care was the most pervasive risk factor associated with internalizing, externalizing and total behavioural problems. A low dysmorphology score was related to more internalizing and total problems.

Conclusions

Children and adolescents prenatally exposed to alcohol faced greater risk of substantive behavioural problems (i) if they were less visibly alcohol affected and (ii) the longer time they had spent in residential care. The results underscore the clinical importance of appropriate services and care for less visibly affected children with FASD and highlight the need to attend to children with FASD being raised in institutions.

Sex chromosome tetrasomy and pentasomy conditions occur in 1:18 000–1:100 000 male births. While often compared with 47,XXY/Klinefelter syndrome because of shared features including tall stature and hypergonadotropic hypogonadism, 48,XXYY, 48,XXXY and 49,XXXXY syndromes are associated with additional physical findings, congenital malformations, medical problems and psychological features. While the spectrum of cognitive abilities extends much higher than originally described, developmental delays, cognitive impairments and behavioural disorders are common and require strong treatment plans. Future research should focus on genotype–phenotype relationships and the development of evidence-based treatments.

Conclusion

The more complex physical, medical and psychological phenotypes of 48,XXYY, 48,XXXY and 49,XXXXY syndromes make distinction from 47,XXY important; however, all of these conditions share features of hypergonadotropic hypogonadism and the need for increased awareness, biomedical research and the development of evidence-based treatments.

Aim

To explore the association of serum bilirubin level and breast milk feeding with retinopathy of prematurity (ROP) in preterm infants.

Methods

We conducted a case-control study to examine the independent and combined effects of serum bilirubin and breast milk feeding on ROP risk in infants <32 weeks gestation or with birth weight <1500 grams. Cases (66 infants with ROP) were matched with controls (66 infants without ROP) based on factors know to affect ROP risk.

Results

When analyzed using the paired t test, the peak bilirubin levels were lower in ROP cases than in controls (mean 7.2 vs 7.9 mg/dl; P=0.045). Using conditional logistic regression, we found a negative association between highest serum bilirubin level and risk of ROP (OR=0.82 per 1-mg/dl change in bilirubin (P=0.06). There was no significant association between breast milk feeding and risk of ROP.

Conclusion

Bilirubin may help to protect preterm infants against ROP.

Aim

To explore risk patterns for presumed and definite, early and late neonatal bacteremia.

Methods

We studied 1106 ELGANs who survived until postnatal day 28. We defined early definite bacteremia as a positive bacterial culture in the first week and definite late bacteremia as a positive bacterial culture in week 2, 3 or 4. Bacteremia was presumed if antibiotics were given for more than 72 hours despite negative blood cultures.

Results

Risk patterns did not differ much for presumed and definite bacteremia in the first postnatal month. While maternal and pregnancy characteristics were associated with early bacteremia, neonatal co-morbidities, especially NEC, were the main antecedents/correlates of late bacteremia. All four categories of bacteremia were associated with younger gestational age and lower birth weight. Infants with presumed and definite bacteremia had similar distributions of days of ventilation and oxygenation.

Conclusion

Definite and presumed late bacteremia have rather similar risk patterns, while those of early and late bacteremia differ appreciably.

Aim

To investigate the relationship between low Apgar score and neonatal mortality in preterm neonates.

Methods

Infant birth and death certificate data from the U.S. National Center for Health Statistics for 2001-2002 were analyzed. Primary outcome was 28 day mortality for 690,933 neonates at gestational ages 24-36 weeks. Mortality rates were calculated for each combination of gestational age and five-minute Apgar score. Relative risks of mortality, by high vs. low Apgar score, were calculated for each age.

Results

Distribution of Apgar scores depended on gestational age, the youngest gestational ages having higher proportions of low Apgar scores. Median Apgar score ranged from 6 at 24 weeks, to 9 at 30-36 weeks gestation. The relative risk of death was significantly higher at Apgar scores 0-3 vs. 7-10, including at the youngest gestational ages, ranging from 3.1 (95% confidence interval 2.9, 3.4) at 24 weeks to 18.5 (95% confidence interval 15.7, 21.8) at 28 weeks.

Conclusion

Low Apgar score was associated with increased mortality in premature neonates, including those at 24 to 28 weeks gestational age, and may be a useful tool for clinicians in assessing prognosis and for researchers as a risk prediction variable.

Objective

To assess the blood pressure of former preterm and term matched adolescent controls, and identify risk factors associated with blood pressure at 16 years.

Design

Observational cohort study. Secondary analysis of a randomized clinical trial.

Setting

Three academic centers participating in the Multicenter Indomethacin IVH Prevention Trial.

Participants

296 children born in 1989–1992 with birth weights 600- <1250g who participated in the Multicenter Indomethacin IVH Prevention Trial and 95 term controls were evaluated at 16 years.

Main Outcome Measures

Blood pressure and predictors of blood pressure.

Results

The adjusted mean difference in blood pressure for preterm adolescents was 5.1 mm Hg; p=0.002 for systolic and 2.1 mm Hg; p=0.027 for diastolic blood pressure. Among preterms, the primary predictors of increased systolic blood pressure were weight gain velocity between birth and 36 months (b=8.54, p<.001), preeclampsia (b=5.67, p=0.020), non-white race (b=3.77, p=0.04) and male gender (b=5.09). Predictors of diastolic blood pressure were weight gain velocity between birth and 36 months, (b=4.69, p=0.001, brain injury (b=6.51, p=0.002 and male gender (b=−2.4, p=0.02).

Conclusions

Early programming secondary to increased early weight gain velocity, intrauterine stress and neonatal brain injury may all contribute to risk of increased blood pressure among former preterm adolescents.

Objectives

To assess the influence of clinical status on the association between total plasma bilirubin and unbound bilirubin on death or adverse neurodevelopmental outcomes at 18–22 months corrected age in extremely low birth weight infants.

Method

Total plasma biirubin and unbound biirubin were measured in 1,101 extremely low birth weight infants at 5±1 day of age. Clinical criteria were used to classify infants as clinically stable or unstable. Survivors were examined at 18–22 months corrected age by certified examiners. Outcome variables were death or neurodevelopmental impairment, death or cerebral palsy, death or hearing loss, and death prior to follow-up. For all outcomes, the interaction between bilirubin variables and clinical status was assessed in logistic regression analyses adjusted for multiple risk factors.

Results

Regardless of clinical status, an increasing level of unbound bilirubin was associated with higher rates of death or neurodevelopmental impairment, death or cerebral palsy, death or hearing loss and death before follow-up. Total plasma bilirubin values were directly associated with death or neurodevelopmental impairment, death or cerebral palsy, death or hearing loss, and death before follow-up in unstable infants, but not in stable infants. An inverse association between total plasma bilirubin and death or cerebral palsy was found in stable infants.

Conclusions

In extremely low birth weight infants, clinical status at 5 days of age affects the association between total plasma and unbound bilirubin and death or adverse neurodevelopmental outcomes at 18–22 months of corrected age. An increasing level of UB is associated a higher risk of death or adverse neurodevelopmental outcomes regardless of clinical status. Increasing levels of total plasma bilirubin are directly associated with increasing risk of death or adverse neurodevelopmental outcomes in unstable, but not in stable infants.

Rasch S, Sangild PT, Gregersen H., Schmidt M., Omari T, Lau C. The Preterm Piglet – an Animal Model for the Oesophageal Maturation in Preterm Neonates. Acta Paediatr ...... Stockholm. ISSN ......

Aim

Preterm infants have difficulty attaining independent oral feeding. This can ensue from inadequate sucking, swallowing, and/or respiration. In impeding bolus transport, immature oesophageal motility may also be a cause. As studies on the development of oesophageal motility are invasive in preterm infants, the preterm piglet was investigated as a potential research model.

Methods

Oesophageal motility (EM) of term (n=6) and preterm (n=15) piglets were monitored by manometry for 10 min immediately following bottle feeding on days 1-2 and 3-4 of life.

Results

Piglets’ oral feeding performance and EM were similar to those of their human counterparts. Term piglets readily completed their feeding whereas their preterm counterparts did not. They also presented with greater peristaltic activity and propagating velocity. Peristaltic activity remained unchanged over time in preterm piglets, but an increase in synchronous and decrease in incomplete motor activity were noted. Preterm piglets that developed symptoms analogous to necrotizing enterocolitis (NEC) demonstrated uncharacteristic oesophageal activity.

Conclusion

Immature EM may cause oral feeding difficulties. NEC-like symptoms may adversely affect EM. The piglet is a valid research model for studying human infant oral feeding and oesophageal development.

Aim

Early working memory is emerging as an important indicator of developmental outcome predicting later cognitive, behavioural and academic competencies. The current study compared early working memory in a sample of toddlers (18–22 months) born very low birth weight (VLBW; n = 40) and full term (n = 51) and the relationship between early working memory, mental developmental index (MDI), and maternal communication in both samples.

Methods

Early working memory, measured by object permanence; Bayley mental developmental index; and maternal communication, coded during mother-toddler play interaction, were examined in 39 toddlers born VLBW and 41 toddlers born full term.

Results

Toddlers born VLBW were found to be 6.4 times less likely to demonstrate attainment of object permanence than were toddlers born full term, adjusting for age at testing. MDI and maternal communication were found to be positively associated with attainment of object permanence in the VLBW group only.

Conclusion

The difference found in the early working memory performance of toddlers born VLBW, compared with those born full term, emphasizes the importance of assessing early working memory in at-risk populations, while the maternal communication finding highlights potential targets of intervention for improving working memory in toddlers born VLBW.

Aim

To explore associations between acute otitis media in early childhood and prenatal and postnatal tobacco smoke exposure.

Methods

Subjects were 32,077 children born 2000 – 2005 in the Norwegian Mother and Child Study with questionnaire data on tobacco smoke exposure and acute otitis media up to 18 months of age. Multivariate regression models were used to obtain adjusted relative risks for acute otitis media.

Results

Acute otitis media was slightly more common in children exposed to parental smoking. The incidence from 0–6 months was 4.7% in unexposed children, and 6.0% in children exposed both pre-and postnatally. After adjusting for postnatal exposure and covariates, the relative risk for acute otitis media 0–6 months when exposed to maternal smoking in pregnancy was 1.34, 95% confidence interval: 1.06–1.69. Maternal smoking in pregnancy was associated with acute otitis media up to 12 months of age. Compared to non-exposed children, there was a slightly increased risk of recurrent acute otitis media for children exposed both pre- and postnatally with a relative risk of 1.24, 95% confidence interval: 1.01–1.52,.

Conclusion

Even in a cohort with relatively low exposure levels of parental smoking, maternal smoking in pregnancy was associated with an increased risk of acute otitis media in early childhood.

Aim

To examine bone mass changes in 321 black and white South African children in relation to habitual physical activity (PA) levels and calcium intakes.

Methods

Children underwent two bone mass scans at ages nine and 10 years using dual x-ray absorptiometry. PA levels and calcium intakes were assessed using questionnaires. Data were analysed by regressing change in bone mineral content (BMC) and bone area (BA) from age nine to 10, against bone area (for BMC), height and body weight. The residuals were saved and called residualized BMCGAIN and BAGAIN. Residualized values provide good indication of weight, height and bone area matched accumulation rates.

Results

White children had significantly higher physical activity levels and calcium intakes than black children. Most active white males had significantly higher residualized BMCGAIN and BAGAIN at the whole body, hip and spine but not at the radius, than those who were less active. Most active white females had significantly higher residualized BAGAIN at all sites except the radius than less active girls. No such effects were seen in black children. There was no interactive effect on residualized BMCGAIN for calcium intake and PA (except at the spine in white girls).

Conclusion

Bone mass and area gain is accentuated in pre- and early pubertal children with highest levels of habitual physical activity. Limited evidence of an effect of dietary calcium intakes on BMC was found.

Aim

To estimate the effect of baby swimming the first six months of life on respiratory diseases from 6 to 18 months.

Methods

We used data from The Norwegian Mother and Child Cohort Study (MoBa) conducted by the Norwegian Institute of Public Health in children born 1999 – 2005 followed from birth to the age of 18 months (n = 30,870). Health outcomes: lower respiratory tract infections (LRTI), wheeze and otitis media between 6 and 18 months of age. Exposure: baby swimming at age 6 months. The effect of baby swimming was estimated by logistic regression analysis adjusting for potential confounders.

Results

About 25% of the children participated in baby swimming. The prevalence of LRTI was 13.3%, wheeze 40.0% and otitis media 30.4%. Children who were baby swimming were not more likely to have LRTI, to wheeze or to have otitis media. However, children with atopic mothers who attended baby swimming had an increased risk of wheeze, aOR 1.24 (95% CI 1.11, 1.39), but not LRTI or otitis media. This was also the case for children without respiratory diseases before 6 months aOR 1.08 (95%CI 1.02–1.15).

Conclusion

Baby swimming may be related to later wheeze. However, these findings warrant further investigation.

Aim

This study aimed to test the association of individual adipose depots on cardiometabolic outcomes; whether the association varied by depot; and if the associations differed by race/ethnicity or sex in early pubertal children.

Methods

320 children (53% male) aged 7–12y self-identified as African- (AA; n=114), European- (EA; n=120), or Hispanic American (HA; n=86) participated. Insulin dynamics were assessed by intravenous glucose tolerance test; body composition with DXA; fat distribution with CT.

Results

AA had the least fat in each depot and HA had the most. Fat accumulation negatively impacted cardiometabolic outcomes independent of race/ethnicity or sex. AA and females were reproductively more mature. In AA and HA each measure of adiposity influenced the insulin sensitivity index (SI), whereas intra-abdominal adipose tissue (IAAT) did not contribute to SI in EA. IAAT was positively associated with blood pressure in AA, only. In females, adiposity adversely influenced cardiometabolic outcomes, such that total fat mass, IAAT, and/or SAAT was inversely associated with SI, and positively associated with blood pressure and fasting insulin.

Conclusions

IAAT is uniquely related to metabolic risk factors in Hispanic Americans, African Americans, and girls, suggesting that either the threshold for adverse effects of IAAT is lower, or that IAAT metabolism differs in these groups.

Aim

This study was to measure changes in frontal brain activation in young children during picture book reading with their mothers.

Methods

The cross-sectional sample consisted of 15 young Japanese children (8 girls and 7 boys, mean age 23.1±3.4). Two experimental tasks were presented as follows: Task 1 (picture book reading with their mothers); Task 2 (viewing of book-on-video). Duration of task stimulus was 180 sec and the 60 sec interval was filled. Brain activation was measured using an optical topography system.

Results

Significant increases in oxy-Hb were observed in both right and left frontal areas in response to Task 1 compared to Task 2. There were significant correlations between child’s brain activity and mothers’ and children’s verbal – nonverbal behaviors.

Conclusion

There was greater frontal lobe activation in children when they were engaged in a picture book reading task with their mothers, as opposed to passive viewing of a videotape in which the story was read to them. Social and verbal engagement of the mother in reading picture books with her young child may mediate frontal brain activity in the child.

Aim:

Hypothermia is often induced to reduce brain injury in newborns, following perinatal hypoxic–ischaemic events, and in adults following traumatic brain injury, stroke or cardiac arrest. We aimed to devise a method, based on diffusion-weighted MRI, to measure non-invasively the temperature of the cerebrospinal fluid in the lateral ventricles.

Methods:

The well-known temperature dependence of the water diffusion constant was used for the estimation of temperature. We carried out diffusion MRI measurements on a 3T Philips Achieva Scanner involving phantoms (filled with water or artificial cerebrospinal fluid while slowly cooling from 41 to 32°C) and healthy adult volunteers.

Results:

The estimated temperature of water phantoms followed that measured using a mercury thermometer, but the estimates for artificial cerebrospinal fluid were 1.04°C lower. After correcting for this systematic difference, the estimated temperature within the lateral ventricles of volunteers was 39.9°C. Using diffusion directions less sensitive to cerebrospinal fluid flow, it was 37.7°C, which was in agreement with the literature.

Conclusion:

Although further improvements are needed, measuring the temperature within the lateral ventricles using diffusion MRI is a viable method that may be useful for clinical applications. We introduced the method, identified sources of error and offered remedies for each.

Aim

The aim of the study was to describe the frequency of viral pathogens and relative frequency of co-infections in nasal specimens obtained from young children with bronchiolitis receiving care at a children’s hospital.

Methods

We conducted a study of nasal wash specimens using real-time PCR and fluorescent-antibody assay results from children less than two with an ICD-9-CM code for bronchiolitis. All specimens were collected for clinical care at Children’s Hospital in Seattle, WA, USA, during the respiratory season from October 2003 to April 2004.

Results

Viruses were detected in 168 (93%) of the 180 children with bronchiolitis. A single virus was identified in 127 (71%) children and multiple viruses in 41 (23%). Respiratory syncytial virus (RSV) was the most common virus detected (77%), followed by adenovirus (15%), human metapneumovirus (11%), coronavirus (8%), parainfluenza (6%) and influenza (1%). Of the 139 samples with RSV detected, 34 (24%) were co-infected with another viral pathogen.

Conclusion

Molecular diagnostic techniques identified a high frequency of viruses and viral co-infections among children evaluated for bronchiolitis. Further study of the role of viral pathogens other than RSV and co-infections with RSV in children with bronchiolitis appears warranted.

Aim

In June 2006, the human papillomavirus (HPV) vaccine, Gardasil, was licensed for use in the United States. We examined whether paediatricians would recommend the vaccine, obstacles they encountered and characteristics associated with not recommending the HPV vaccine to all eligible patients.

Methods

Four hundred fifty general paediatricians, 200 members of the section of infectious diseases and 200 members of the section of adolescent medicine of the American Academy of Pediatrics web-based directory were surveyed.

Results

Of 752 eligible paediatricians, 373 (50%) responded. Eighty-eight percent (292 of 332) of respondents stated that they would give the vaccine to all, 36 (11%) would give it to some and 4 (1%) would give it to none of their eligible patients. The main obstacles were cost and safety; a minority expressed concern about the vaccine’s potential impact on adolescent sexual activity. Physicians who would not recommend HPV vaccination to all eligible patients were more likely to be generalists, have higher intrinsic religiosity, self-describe as conservative, report later adoption of new drugs/vaccines, and would not encourage vaccinating their own daughter or the daughter of a close friend.

Conclusion

Although paediatricians are highly supportive of the HPV vaccine, certain characteristics may predict reluctance to immunize.