Neurodevelopmental outcome over time of preterm born children ≤750 g at birth

Background

Extremely low birth weight (ELBW) infants are at risk of cognitive impairment and follow-up is therefore of major importance. The age at which their neurodevelopmental outcome (NDO) can reliably be predicted differs in the literature.

Aims

To describe NDO at 2, 3.5 and 5.5 years in an ELBW cohort. To examine the value of NDO at 2 years corrected age (CA) for prediction of NDO at 3.5 and 5.5 years.

Study design

A retrospective cross-sectional and longitudinal cohort study.

Subjects

101 children with a BW ≤ 750 g, born between 1996 and 2005, who survived NICU admission and were included in a follow-up program.

Outcome measures

NDO, measured with different tests for general development and intelligence, depending on age of assessment and classified as normal (Z-score ≥ − 1), mildly delayed (− 2 ≤ Z-score < − 1) or severely delayed (Z-score < − 2).

Results

At 2, 3.5 and 5.5 years 74.3, 82.2 and 76.2% had a normal NDO. A normal NDO at 2 years CA predicted a normal NDO at 3.5 and 5.5 years in 92% and 84% respectively. Of the children with a mildly or severely delayed NDO at 2 years CA the majority showed an improved NDO at 3.5 (69.2%) and 5.5 years (65.4%) respectively.

Conclusions

The majority of the children with a BW ≤ 750 g had a normal NDO at all ages. A normal NDO at 2 years CA is a good predictor for normal outcome at 3.5 and 5.5 years, whereas a delayed NDO at 2 years CA is subject to change with the majority of the children showing a better NDO at 3.5 and 5.5 years.     

Family functioning, burden and parenting stress 2 years after very preterm birth

Background

Examining rates of difficulties in family functioning following very preterm birth has been a relatively neglected area of research.

Aims

To examine family functioning, burden and parenting stress in families with very preterm compared with term born children, and investigate influences of parental mental health problems and child neurodevelopmental disability on family outcomes in families with preterm children.

Study design

Participants were 184 very preterm and 71 term children and their parents. Parents completed the Family Assessment Device, Parenting Stress Index and Impact on Family questionnaires when their children were 2 years old (corrected for prematurity). Parental mental health and social risk information were also collected. Children were assessed for neurodevelopmental disability.

Results

Families with very preterm children reported poorer family functioning (p = .03) compared with families with term born children, with less evidence for differences between families with very preterm and term born children in parenting stress and family burden. Within very preterm families, parental mental health problems were associated with higher levels of parenting stress (p = .001), and parents of children with a neurodevelopmental disability were more likely to report higher family burden (p = .04).

Conclusions

For families with very preterm children, parental mental health symptoms and child neurodevelopmental disability may identify families at risk of greater stress and burden who may benefit from additional support.     

Functional impairments at school age of preterm born children with late-onset sepsis

Background

Late-onset sepsis is a relatively common complication particularly of preterm birth that affects approximately a quarter of very low birth weight infants.

Aim

We aimed to determine the motor, cognitive, and behavioural outcome at school age of preterm children with late-onset sepsis compared to matched controls.

Study design and subjects

A prospective case-control study that included preterm infants (gestational age < 32 weeks and/or birth weight < 1500 g) admitted to our Neonatal Intensive Care Unit in 2000-2001 with a culture-proven late-onset sepsis, and controls matched for gestational age.

Outcome measures

At school age we assessed motor skills, intelligence, visual perception, visuomotor integration, verbal memory, attention, executive functioning, and behaviour.

Results

At 6-9 years, 21 of 32 children with late-onset sepsis (68%) had borderline or abnormal motor outcome with most problems in fine motor skills. Their total IQ was 89 compared to 98 in controls. In addition, verbal memory and attention were affected compared to controls (0.61 standard deviations (SD), 95% confidence interval (CI) 0.04-1.17, p = 0.033 and 0.94 SD, 95% CI 0.32-1.62, p = 0.011, respectively). Multiple episodes of sepsis and gram-negative sepsis were risk factors for worse cognitive outcome.

Conclusions

At school age, a majority of preterm children with late-onset sepsis had motor problems. Their IQ was considerably lower than matched controls, and memory and attention were specifically impaired. Outcome at school age of preterm children with late-onset sepsis was worse than previously thought.     

Behavior problems of 9-16 year old preterm children: biological, sociodemographic, and intellectual contributions

Background

Preterm children are at risk for behavior problems. Studies examining contributions of intellectual and environmental factors to behavior outcomes in preterm children are mixed.

Aims

(1) To identify the nature of maladaptive behaviors in preterm children age 9 to 16 years born across the spectrum of gestational age and birth weight (BW). (2) To examine contributions of BW as a biological factor, socioeconomic status as an environmental factor, and intelligence quotient (IQ) as indicative of intellectual ability to behavior outcomes.

Method

Using the Child Behavior Checklist, parent reports of behavior for 63 preterm children (gestational age 24 to < 36 weeks) were compared to 29 full term children of similar age, gender and socioeconomic status. Multiple regression models evaluated effects of prematurity, socioeconomic status, and intellectual ability on behavioral symptom scores.

Results

Preterm children had higher total and internalizing problem scores compared to full term children. They also had lower IQ. BW was a significant predictor of total and internalizing behavior problems. Among the syndrome scales, anxious/depressed and attention problems were elevated. Socioeconomic status did not contribute to behavior scores. IQ contributed to total, but not to internalizing or externalizing, scores. IQ contributed to attention problems, but not to anxious/depressed scores.

Conclusion

Preterm children had increased behavior problems, especially symptoms of inattention and anxiety. Lower BW predicted more behavior problems. IQ acted as a mediator between BW and attention scores, but not anxiety scores. These findings alert health care providers to assess anxiety in all preterm children regardless of intellectual ability and additional study on the influence of intellectual ability on behavioral outcomes in preterm children is needed.     

Long-term neurological outcome of term-born children treated with two or more anti-epileptic drugs during the neonatal period

Background

Neonatal seizures may persist despite treatment with multiple anti-epileptic drugs (AEDs).

Objective

To determine in term-born infants with seizures that required two or more AEDs, whether treatment efficacy and/or the underlying disorder were related to neurological outcome.

Design/methods

We included 82 children (born 1998-2006) treated for neonatal seizures. We recorded mortality, aetiology of seizures, the number of AEDs required, achievement of seizure control, and amplitude-integrated-EEG (aEEG) background patterns. Follow-up consisted of an age-adequate neurological examination. Surviving children were classified as normal, having mild neurological abnormalities, or cerebral palsy (CP).

Results

Forty-seven infants (57%) had status epilepticus. The number of AEDs was not related to neurological outcome. Treatment with three or four AEDs as opposed to two showed a trend towards an increased risk of a poor outcome, i.e., death or CP, odds ratio (OR) 2.74; 95% confidence interval (CI) 0.98-7.69; P = .055. Failure to achieve seizure control increased the risk of poor outcome, OR 6.77; 95%-CI 1.42-32.82, P = .016. Persistently severely abnormal aEEG background patterns also increased this risk, OR 3.19; 95%-CI 1.90-5.36; P < .001. In a multivariate model including abnormal aEEG background patterns, failure to achieve seizure control nearly reached significance towards an increased risk of poor outcome, OR 5.72, 95%-CI 0.99-32.97, P = .051. We found no association between seizure aetiology and outcome.

Conclusions

In term-born infants with seizures that required two or more AEDs outcome was poorer if seizure control failed. The number of AEDs required to reach seizure control and seizure aetiology had limited prognostic value.     

Movements and postures of infants aged 3 to 5 months: to what extent is their optimality related to perinatal events and to the neurological outcome?

Background

The quality of spontaneous general movements (GMs), assessed in the individual infant, has emerged as one of the most reliable and valid predictors especially of severe neurological impairments.

Aims

To implement a more detailed assessment of GMs and co-existing movements and postural patterns in a rehabilitation clinic, and to examine to what extend is the optimality of movements and postures of infants aged 3 to 5 months related to perinatal events and the neurological outcome.

Study design

Prospective study of 41 infants (15 boys and 26 girls; 11 infants born preterm) admitted to the Department of Paediatric Neurology and Rehabilitation of the St. Joseph's Hospital in Kyoto (Japan).

Outcome measures

Clinical, neurological and psychological status at age 5.

Results

Motor optimality at age 3 to 5 months correlated positively with neonatal optimality (r = 0.48, p < 0.01), especially regarding factors associated with hypoxic events. A non-optimal motor performance (lowest possible scores) predicted cerebral palsy with 100% accuracy. Other adverse outcomes such as developmental delays, developmental coordination disorders, pervasive developmental disorder or attention deficit hyperactivity disorder turned out not to be associated with early motor performance. In 13% of cases absence of fidgety movements proved to be false positives, but their normal appearance along with a smooth concurrent motor performance was solely found in infants with a normal neurological development.

Conclusion

Assessing the quality of motor performance at age 3 to 5 months considerably improves our ability to identify infants at risk for maldevelopment.     

Quantitative aspects of the early motor repertoire in preterm infants: do they predict minor neurological dysfunction at school age?

Background

Qualitative aspects of the motor repertoire, at 11-16 weeks post-term are predictive for minor neurological dysfunction (MND) at 7 to 11 years of age. Predictive value of quantitative aspects is unknown so far.

Aim

To investigate whether quantitative aspects of the motor repertoire between 6 and 24 weeks post-term also have predictive value for neurological outcome at 7 to 11 years of age.

Study design

Prospective cohort study.

Subjects

Preterm infants from whom several quantitative aspects of the motor repertoire were assessed between 6 and 24 weeks post-term.

Outcome measures

Neurological outcome at 7-11 years of age was assessed according to Touwens' neurological examination. Children were classified as neurologically normal, or as having complex MND or cerebral palsy (CP).

Results

Eighty-two children were included. At 7 to 11 years of age 15 children (18%) had developed CP, 49 (60%) were neurologically normal, and 18 (22%) had MND. Multiple logistic regression analysis showed that, when the qualitative aspects of the motor repertoire known to predict neurological outcome were taken into account, only the asymmetric tonic neck (ATN) posture provided additional predictive value. In case of normal fidgety movements (FMs) accompanied by an abnormal concurrent motor repertoire, the presence of an obligatory ATN increased the risk for developing complex MND to 75%; absence of an obligatory ATN reduced the risk to 15% (p < 0.05).

Conclusions

Quantitative aspects of the motor repertoire at 11-16 weeks post-term, in particular the presence of an obligatory ATN posture, contribute to the prediction of neurological outcome at 7 to 11 years of age.     

Postnatal growth of preterm born children ≤ 750g at birth

Background

Extremely low birth weight (ELBW) infants are at risk of impaired postnatal growth. Impaired postnatal growth has been reported to be associated with delayed cognitive and motor development.

Aims

To describe postnatal growth patterns of appropriate and small for gestational age (AGA and SGA) ELBW children in relation to their cognitive and motor outcome at age 5.5.

Study design

Retrospective cohort study.

Subjects

One hundred one children with a BW ≤ 750 g, born between 1996 and 2005 in the University Hospital Utrecht, The Netherlands.

Outcome measures

Height (Ht), weight (Wt), occipital-frontal circumference (OFC) at birth, 15 months and 2 years corrected age and 3.5 and 5.5 years.Cognitive and motor outcome at 5.5 years of age, classified as normal (Z-score ≥−1), mildly delayed (−2 ≤ Z-score <−1) or severely delayed (Z-score <−2). AGA (Ht, Wt or OFC at birth ≥−2 SDS) infants were compared with SGA (Ht, Wt or OFC at birth <−2 SDS) infants.

Results

Between birth and 5.5 years catch-up growth in Ht, weight for height (Wt/Ht), Wt and OFC was seen in 72.2%, 55.2%, 28.6% and 68.9% respectively of the SGA infants. For AGA infants we found substantial catch-down growth in Ht (15.4%) and Wt (33.8%). Cognitive and motor outcome was normal in 76.2% and 41.6% of the 101 children. A significantly higher percentage of normal cognitive outcome was found in AGA infants with Wt growth remaining at ≥−2 SDS compared to AGA infants with catch-down growth (83% vs 63%). Next, SGA infants who caught-up in OFC had a higher prevalence of normal cognitive outcome compared to SGA infants who did not catch-up in OFC. Furthermore, a higher percentage of severely delayed motor outcome was found in SGA infants without catch-up growth in Wt compared to SGA infants who caught-up in Wt (61.5% vs 32.2%).

Conclusions

Catch-up growth in Ht, Wt/Ht and OFC occurred in the majority of the SGA infants with a BW ≤ 750 g, but was less common in Wt. AGA children who remained their Wt at ≥−2 SDS have a better cognitive and motor developmental outcome at 5.5 years of age. Catch-up growth in OFC was associated with a better cognitive outcome at 5.5 years of age.     

Power spectrum analysis of fetal heart rate variability at near term and post term gestation during active sleep and quiet sleep

Background

Spectral analysis of fetal heart rate variability is promising for assessing fetal condition. Before using spectral analysis for fetal monitoring it has to be determined whether there should be a correction for gestational age or behavioural state.

Aims

Compare spectral values of heart rate variability between near term and post term fetuses during active and quiet sleep.

Study design

Case-control. Cases had a gestational age of ≥ 42 weeks; controls were 36 to 37 weeks. Fetuses were matched for birth weight percentile.

Subjects

STAN^® registrations from healthy fetuses. For each fetus one 5-minute segment was selected during active and one during quiet sleep.

Outcome measures

Absolute and normalized low (0.04-0.15 Hz) and high frequency power (0.4-1.5 Hz) of heart rate variability.

Results

Twenty fetuses were included. No significant differences were found between cases and controls in absolute (481 and 429 respectively, P = 0.88) or normalized low (0.78 and 0.80 respectively, P = 0.50) or absolute (41 and 21 respectively, P = 0.23) or normalized high frequency power (0.08 and 0.07 respectively, P = 0.20) during active state. During rest, normalized low frequency power was lower (0.58 and 0.69 respectively, P = 0.03) and absolute (16 and 10 respectively, P = 0.04) and normalized high frequency power were higher (0.21 and 0.14 respectively, P = 0.01) in cases compared to controls. Absolute and normalized low frequency power were higher during active state compared to rest in both groups (all P values < 0.05).

Conclusions

We found sympathetic predominance during active state in fetuses around term. Post term parasympathetic modulation during rest was increased compared to near term.     

Early identification of the risk for free radical-related diseases in preterm newborns

Background

Despite recent advances in preterm newborns healthcare, perinatal pathologies and disabilities are increasing. Oxidative stress (OS) is determinant for the onset of an unbalance between free radicals (FRs) production and antioxidant systems which plays a key role in pathogenesis of pathologies such as retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH), grouped as ‘free radical-related diseases’ (FRD).

Aim

This study tests the hypothesis that OS markers levels in cord blood may predict the onset of FRD pathologies.

Patients and methods

168 preterm newborns of GA: 24-32 weeks (28.09 ± 1.99); and BW: 470-2480 gr (1358.11 ± 454.09) were consecutively recruited. Markers of potential OS risk (non-protein bound iron, NPBI; basal superoxide anion, BSA; under stimulation superoxide anion, USSA) and markers of OS-related damage (total hydroperoxides, TH; advanced oxidation protein products, AOPP) were assessed in cord blood. Associations between FRD onset and OS markers were checked through inferential analysis (univariate logistic regression).

Results

The development of FRD was significantly associated to high cord blood levels of TH, AOPP and NPBI (respectively p = 0.000, OR = 1.025, 95%CI = 1.013-1.038; p = 0.014, OR = 1.092, 95%CI = 1.018-1.172; p = 0.007, OR = 1.26995%CI = 1.066-1.511).

Conclusions

Elevated levels of TH, AOPP and, above all, NPBI, in cord blood are associated with increased risk for FRD. OS markers allow the early identification of infants at risk for FRD because of perinatal oxidant exposure. This can be useful in devising strategies to prevent or ameliorate perinatal outcome.     

Intrauterine growth restriction in a low-income country: Risk factors, adverse perinatal outcomes and correlation with current WHO Multicenter Growth Reference

Objective

To determine risk factors and adverse perinatal outcomes including nutritional status in the first week of life for newborns with intrauterine growth restriction-low birth weight (IUGR-LBW) in settings lacking facilities for routine intrauterine growth monitoring.

Methods

A cross-sectional study of all infants in an inner-city hospital in Lagos, Nigeria. IUGR-LBW was defined as full-term (gestational age ≥ 37 weeks) infant with low birth weight (< 2500 g). Nutritional/growth status at enrolment was determined by z-scores for length-for-age (HAZ), head circumference-for-age (HCZ), weight-for-age (WAZ) and weight-for-length (WHZ) based on current World Health Organization's Multicentre Growth Reference (WHO-MGR). Factors and adverse outcomes associated with IUGR-LBW were explored with multivariable logistic regression analyses.

Results

Some 145 (4.3%) infants were IUGR-LBW out of 2619 eligible singletons enlisted for this study. IUGR-LBW was significantly associated with teenage mothers (OR:2.90, 95% CI:1.22-6.89), lack of antenatal care (OR:1.88, 95% CI:1.33-2.65) and female gender (OR:1.38, 95% CI: 0.98-1.93; p = 0.062). The incidence of adverse outcomes across gestational age showed significant linear trend only for low five-minute Apgar scores (p = 0.024) and WAZ (p = 0.065). IUGR-LBW was associated with poor nutritional status across all four indices (p < 0.001) as well as low 5-minute Apgar scores (p = 0.095), sepsis (p = 0.053), hyperbilirubinemia (p < 0.001) and admission into special care baby unit (p = 0.009) after multivariable logistic regression analyses.

Conclusions

IUGR-LBW correlates with poor nutritional status in the first week of life based on WHO-MGR and affected infants can be detected early for effective surveillance in resource-poor settings. Improved prenatal care among teenage mothers is necessary for reducing IUGR-LBW burden.     

The quality of fetal arm movements as indicators of fetal stress

Background

Although a number of studies have found that maternal stress affects the fetus, it is unclear whether jerky fetal movements observed on ultrasound scans are indicative of fetal stress, or whether they are part of normal development.

Aims

The present study was designed to examine the relationship between jerky fetal arm movements in relation to fetal age and stress.

Methods

Video recordings were made of routine ultrasound scans of 57 fetuses (age range 8 to 33 weeks) classified into three age groups: 1st trimester (8-12 weeks, N = 9), 2nd trimester (13-24 weeks, N = 38), and 3rd trimester (26-33 weeks, N = 10). Following previous research on stress behaviour in neonates, a fetal index of stress was derived from frequency of hiccup, back arch and rhythmical mouthing.

Results

Results indicated that while stress level was unrelated to fetal age, jerkiness of arm movements was significantly associated with the fetal stress index but not age.

Conclusions

Our findings suggest that jerky arm movements in fetuses are suggestive of fetal stress.     

Circulating adipocyte fatty acid binding protein levels in healthy preterm infants: Positive correlation with weight gain and total-cholesterol levels

Background

Adipocyte fatty acid binding protein (a-FABP) has been suggested to play an important role in the pathogenesis of metabolic syndrome. Preterm infants are at risk for the later development of insulin resistance, and, possibly, other components of metabolic syndrome.

Aim

To determine circulating levels of a-FABP in preterm infants and examine possible associations of a-FABP with metabolic indices (serum lipids, glucose, and insulin levels, and homeostasis model assessment index of insulin resistance [HOMA-IR]), levels of leptin and adiponectin, anthropometric parameters and weight gain.

Study design

Prospective cohort study.

Subjects

55 healthy preterm (mean [SD] gestational age 32.8 [1.8] weeks) and 23 fullterm infants (reference group).

Outcome measures

Serum a-FABP, lipids, glucose, insulin, leptin and adiponectin levels at 31.9 [10.4] days of life.

Results

Serum a-FABP levels did not differ significantly between preterm and fullterm infants. A-FABP levels correlated positively with total-cholesterol [total-C] in both preterm and fullterm infants (β = 0.33; p = 0.01 and β = 0.33; p = 0.04, respectively). In addition to total-C, weight gain correlated independently with a-FABP levels in preterm infants (β = 0.36, p = 0.01).

Conclusions

An association between a-FABP levels and indices of insulin resistance was not present in infants studied. As the development of insulin resistance in children born prematurely is possibly associated with weight gain in early postnatal life, follow-up of our study population is necessary to demonstrate whether a-FABP levels, shown to correlate with weight gain in preterm infants, are a predictive marker for the later development of insulin resistance in these infants.     

An infant and child feeding index is associated with child nutritional status in rural China

Background

Some researchers have developed child feeding indices to summarize child feeding practices so that they can compare child feeding practices across countries and monitor changes over time within a given country.

Aims

An adapted version of the infant and child feeding index (ICFI) developed by Ruel and Menon was used to examine its association with nutritional status of infants living in a rural community in China.

Methods

A cross-sectional survey of 501 children aged 6-11 mo was conducted with their mothers in 8 townships between May 2006 and March 2007. ICFI was developed based on 24-h dietary recall and food frequency information. The associations between ICFI and anthropometric indices including length-for-age (LAZ), weight-for-age (WAZ), and weight-for-length (WLZ) Z-scores were examined separately. General linear regression models were used to adjust for potential confounders including the children's, parents' and households' sociodemographic characteristics.

Results

The ICFI was associated with both WAZ (adjusted WAZ means: 0.39, 0.47, and 0.54 for the 1st, 2nd, and 3rd tercile, respectively, P < 0.05) and WLZ (adjusted WLZ means: 0.47, 0.74, and 0.79 for the 1st, 2nd, and 3rd tercile, respectively, P < 0.05). But it was not associated with children's LAZ. Among the components of ICFI, dietary diversity, meal frequency and bottlefeeding were positively associated with the children's anthropometric indices.

Conclusions

ICFI and its components could be used to assess effect of complementary feeding practices on child growth.     

Antioxidant vitamin status during pregnancy in relation to cognitive development in the first two years of life

Objective

To investigate the correlation of the antioxidant vitamins status (vitamins A, E and C) during pregnancy and the intellectual development of early childhood.

Method

A total of 150 paired maternal-neonatal subjects were recruited into the present study. The serum concentrations of antioxidant vitamins (vitamins A, E and C) in maternal blood and cord blood after delivery were determined by high performance liquid chromatography and the intellectual development was evaluated by Gesell Development Schedules (GDS) at two-years-old.

Result

Children with higher cord serum vitamin E level showed higher scores of motor, adaptive domain and average compared to children with lower cord serum vitamin E level (p < 0.01 or 0.05), respectively. Cord serum vitamin A level had significant positive correlation with effect on motor DQs (β = 4.227, p < 0.05), and vitamin E level in cord blood showed a positive relation with motor DQ and average DQ (β = 0.329 and 0.1875, respectively, p < 0.05) in multiple linear regression model.The language and social DQs were influenced by placental vitamin E transport rate (β = 3.1968 and 3.0194, respectively, p < 0.05). The placental transport rate of vitamin E also was a protective factor for the prevalence of motor behavior developmental delay [OR: 0.118, 95% confident interval (95% CI), 0.018-0.765, p = 0.0251], personal and social behavior developmental delay (OR: 0.052, 95% CI: 0.004-0.610, p = 0.0185) and average developmental delay (OR: 0.041, 95% CI: 0.003-0.642, p = 0.0229) in logistic multiple regression model.

Conclusion

Data suggested that vitamin A, E status and vitamin E transfer rate at delivery had beneficial influence on children's cognitive and behavior development quotients.     

Gender-related effects of prenatal administration of estrogen and progesterone receptor antagonists on VEGF and surfactant-proteins and on alveolarisation in the developing piglet lung

Background

Vascular endothelial growth factor (VEGF) is essential for embryonic lung development and has been shown to be regulated by estradiol (E2) and progesterone (P).

Aim

To investigate the effects of prenatal E2 and P withdrawal by specific receptor antagonists on the mRNA expression of VEGF, surfactant proteins (SP-B and SP-C) and on alveolarisation in lung tissue of male and female pig fetuses.

Methods

Fetuses from 10 sows were randomized to receive either both an intramuscular injection of the E2 receptor blocker ICI 182.780 and the P receptor blocker RTI 3021-022 (ICI + RTI, n = 5) or a placebo injection (n = 5) at 90 days of gestation (DOG, 115 = term). After delivery by cesarean section on 114 DOG, tissue of the left lingula of the piglet's lung (28 placebo, 26 ICI + RTI) was obtained to determine the mRNA expression of VEGF, SP-B and SP-C. Lungs from 15 placebo and 14 ICI + RTI group piglets were removed and alveolar counts performed.

Results

The ICI + RTI group showed significantly lower SP-C mRNA expression and alveolar counts compared to the placebo group (p = 0.04 and 0.03, respectively). Diminished alveolarisation in the ICI + RTI group was mainly due to the reduction of alveolar counts in male piglets (p = 0.02). Within the placebo group VEGF and SP-B mRNA expression in male piglets were significantly lower compared to female piglets (p = 0.01 and 0.004, respectively). ICI + RTI treatment abolished this gender-related difference.

Conclusion

Estradiol and P antagonism affected gender-related differences of key proteins for pulmonary function and development and especially in males was associated with diminished alveolarisation.     

Chronic rhinosinusitis in young children differs from adults: a histopathology study

Objective

A histopathologic study of children with chronic rhinosinusitis (CRS) was undertaken to compare the sinus mucosa in pediatric and adult CRS.

Study design

CRS has been defined as persistent or recurrent sinusitis symptoms for ≥12 weeks despite conventional medical therapy, with abnormal computed tomography of the maxillary sinuses. Maxillary mucosal biopsies were obtained from pediatric CRS subjects for inflammatory cell and morphologic studies. Archival sinus mucosal tissues from adults with CRS were used as histologic controls. Sinus lavages were performed on children with and without CRS for microbiologic studies.

Results

Sinus mucosal biopsies were obtained from 19 children with CRS (median age, 3.0 years; range 1.4-8.2 years). Pediatric CRS biopsies, as compared with adult CRS controls, had a higher density of submucosal lymphocytes (median 469 versus 294 cells/mm² per 5 high-power fields [HPF]; P = .02), lower density of submucosal eosinophils (medians 13 versus 82 cells/mm² per 5 HPF; P = .01), thinner and more intact epithelium (P = .01 and .07, respectively), thinner basement membranes (P = .002), and fewer submucosal mucous glands (P = .004).

Conclusion

The sinus mucosa of young children with CRS has less eosinophilic inflammation, basement membrane thickening, and mucus gland hyperplasia characteristic of adult CRS.     

Sensorimotor skills associated with motor dysfunction in children born extremely preterm

Background

Children born prematurely, despite being free of intellectual and sensorineural deficits, are at risk of motor dysfunction.

Aim

To investigate the association of sensorimotor processing skills and Developmental Coordination Disorder (DCD) in “apparently normal” extreme preterm children.

Study design

In a matched case-control study, 50 preterm children born less than 29 weeks or birthweight < 1000 g, with an IQ > 85 and no identified sensorineural disability, were assessed at 8 years of age along with 50 gender and birth date matched classroom controls born at full term. A battery of sensorimotor tests was administered, which examined visual-motor, visual perception, tactile perception, kinaesthesia, and praxis.

Results

For preterm children with DCD (n = 21), significantly lower scores were found for the visual processing and praxis tests, with the exception of verbal command, in comparison to those 29 preterm children without DCD and term controls (median visual perception scores were 92, 96 and 108 respectively; design copying was 0.07, 0.46 and 0.95; constructive praxis was 0.09, 0.27 and 0.63; and sequencing praxis was 0.14, 0.73 and 0.96). There were no difference on the tactile sensitivity and kinaesthetic processing tests.

Conclusions

Preterm children with DCD have difficulty with visual processing tasks. Praxis or motor planning poses a particular challenge for them. Motor dysfunction in extremely preterm children was related to poorer visual processing and motor planning and may relate to a cognitive processing problem.     

Neurophysiological evaluation in children with Friedreich's ataxia

Introduction

In children with Friedreich's ataxia (FRDA children), clinical ataxia outcomes are hardly substantiated by underlying neurophysiological parameters. In young FRDA children, some reports (based upon International Cooperative Ataxia Rating Scale scores (ICARS)) mention transient neurological improvement upon idebenone treatment. However, these outcomes are obtained with adult instead of pediatric reference values. It is unknown whether age-related neurophysiological parameters can really substantiate neurologic improvement.

Aim

In young FRDA children, we aimed to determine longitudinal neurophysiological parameters during idebenone treatment.

Methods

During a two-year study period, 6 genetically proven FRDA children with cardiomyopathy (6-18 years) were longitudinally assessed for neurophysiological parameters [sensory evoked potentials (SEPs), F response, peripheral nerve conduction and dynamometry] in association with age-matched ICARS-scores.

Results

In all FRDA children, SEPs remained absent during the two-year study period. Peroneal nerve conduction velocity declined (from − 1SD to − 2SD; p < .05), whereas F responses remained essentially unaltered. Total muscle force and leg muscle force decreased (from − 2 to − 3SD and − 2.5 to − 3.5SD; both p < .05) and age-related ICARS-scores deteriorated (median increase + 41%; p < .05).

Conclusion

In FRDA children, age-related neurophysiological and ataxia parameters deteriorate during idebenone treatment. Although we cannot exclude some (subjective) disease stabilization, age-related neurophysiological parameters do not substantiate neurologic improvement.     

Effect of ibuprofen on bilirubin-albumin binding in vitro at concentrations observed during treatment of patent ductus arteriosus

Background

In vitro studies have shown that ibuprofen (IBU) may interfere with bilirubin-albumin binding at concentrations of 100 µg/mL and above.

Objectives

The present study evaluates the in vitro bilirubin displacement over the range of IBU plasma concentrations observed in vivo during curative treatment of patent ductus arteriosus in preterm infants.

Methods

Considering that individual plasma concentrations obtained during the clinical development of IBU in preterm infants were ranging between 10 and 70 µg/mL and exceptionally above 100 µg/mL, we used the modified peroxidase method to determine total and unbound bilirubin concentrations without IBU and with IBU over this specific concentration range.

Results

Total bilirubin and albumin concentrations were respectively 6.6 mg/dL and 2.87 g/dL in pooled newborn plasma. No displacement of bilirubin from its albumin binding sites by IBU was observed over a range of concentrations from 10 to 100 µg/mL. Only a concentration of 200 µg/mL significantly increased the unbound bilirubin by 1.5-fold (p = 0.0008).

Conclusions

This in vitro study confirms displacement of bilirubin by a high IBU concentration of 200 µg/mL, however it retrieves no significant displacement over a range of concentrations up to and including 100 µg/mL, i.e. within the range of in vivo concentrations at the recommended dose regimen.