Neurodevelopmental outcome after COX inhibitor treatment for patent ductus arteriosus

Aim

To compare neurodevelopmental results in very low birth weight (VLBW) infants two years after successful or failed cyclooxygenase inhibitor treatment with either indomethacin or ibuprofen for a haemodynamically significant patent ductus arteriosus (hsPDA).

Methods

We retrospectively evaluated closure rates and outcome parameters of VLBW infants with hsPDA 89 of whom were treated with indomethacin and 93 with ibuprofen.

Results

Indomethacin and ibuprofen therapy groups did not differ in their baseline clinical profile (median gestational age 26.0 and 26.2 wks d) in early (median CRIB 6 and 5, respiratory distress > 2° in 36 and 34 infants) and late morbidities (intraventricular hemorrhage > 2° in 9 and 10 infants, bronchopulmonary dysplasia in 31 and 27 infants, 80 and 85 survivors), PDA closure rates (63 and 58%) or neurodevelopmental outcome. The therapy failure group (54 infants) was characterized by lower median gestational age (25.0 wks d) and higher mortality (17%). No differences were found in the neurodevelopmental outcome of the surviving infants with ligation as compared to the survivors with successful pharmacological closure of the PDA at 24 months corrected age.

Conclusion

Use of either ibuprofen or indomethacin for closure of a hsPDA did not influence two year neurodevelopmental outcomes in VLBW infants.     

Skin conductance measurements as pain assessment in newborn infants born at 22-27 weeks gestational age at different postnatal age

Background

To assess pain or stress in newborn infants submitted to intensive care is important but difficult, as different observational pain scales are not always reliable in premature infants. As an indicator of pain, skin conductance (SC) measurements have detected increased sweating in newborn infants > 28 gestational age (GA) submitted to heel lancing.

Objective

To measure SC during heel lancing and routine care in newborn infants, born at 22 to 27 GA, with special relation to postnatal age (PNA).

Methods

In six infants < 28 + 0 GA and 4 infants ≥ 28 + 0 GA spontaneous SC activity and behavioural state (Neonatal Pain Agitation and Sedation Scale (N-PASS)) was measured before, during and after each intervention. Measurements were repeated in each patient at different PNA.

Results

Baseline SC prior to intervention took longer time to stabilise and was higher in < 28 than in ≥ 28 + 0 PNA. The combination of heel lancing and squeezing gave an increased SC in < 28 PNA, whereas heel lancing alone gave the same SC response in ≥ 28 + 0 PNA. A possibly continued immature response in SC measurements was not observed. Oral glucose admission prior to heel lancing increased SC. Routine care did not give any changes in SC. Except during orogastric tube placement no signs of discomfort or pain could be detected by the neonatal pain, agitation and sedation scale (N-PASS) in < 28 PNA.

Conclusion

Changes in SC could be detected in infants at < 28 + 0 PNA and related to the combination of heel lancing and squeezing. A maturational development of the SC was observed in infants born < 28 GA. SC seems to be able to differentiate between pain and discomfort.     

Cardiovascular biomarkers pro-atrial natriuretic peptide and pro-endothelin-1 to monitor ductus arteriosus evolution in very preterm infants

Background

The diagnostic and prognostic appraisal of patent ductus arteriosus (PDA) in preterm infants is still debatable.

Aims

To compare plasma cardiovascular biomarkers with echocardiographic indices alongside ductus arteriosus (DA) evolution in very preterm infants within the first week of life.

Methods

Mid-regional pro-atrial natriuretic peptide (MR-proANP) and C-terminal pro-endothelin-1 (CT-proET-1) levels were prospectively measured on the second and sixth days of life (DOL) in 52 preterm infants born before 32 weeks of gestation. Echocardiographic indices to define DA patency and significance were simultaneously obtained. Logistic regression and receiver operating characteristics (ROC) analyses were used to assess and quantify the biomarkers' diagnostic capacities.

Results

Thirty infants exhibited PDA on DOL 2; in 21 of these infants, DA was characterized as hemodynamically significant. Treatment failure after a first course of indomethacin was noted in 8 infants (DOL 6), whereas 7 participants underwent later surgical ligation. The diagnostic accuracy of cardiovascular biomarkers was moderate on DOL 2 but high on DOL 6. PDA was the only significant predictor of MR-proANP levels on DOL 6, independent of the effect of clinical confounders (regression coefficient 0.426, R² 0.60). Infants with MR-proANP ≥ 850 pmol/l on DOL 2 had 3.9-fold higher risk (95% CI 1.01 to 14.5) of being diagnosed with significant DA, whereas infants with MR-proANP ≥ 700 pmol/l on DOL 6 had 7.1-fold higher risk (1.9 to 27.2) for pharmaceutical treatment failure.

Conclusion

The cardiovascular plasma biomarker MR-proANP is a promising candidate for monitoring PDA evolution in very preterm infants.     

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.     

Clinical determinants and utility of early postnatal maximum weight loss in fluid management of extremely low birth weight infants

Background

The early postnatal physiological body weight loss process is poorly understood in preterm infants. It is complicated by clinical conditions which adversely affect the body fluid balance during 1st two weeks of life. A lack of physiological weight loss potentially could result in significant morbidities. Body weight is utilized in determining daily fluid volume intakes. Extremely low birth weight infants (birth weight < 1000 g, ELBW) have the highest morbidity and mortality among all neonates.

Aim/objective

The objective was to evaluate the early postnatal weight changes and its clinical determinants in ELBW infants. We examined the maximum weight loss from birth weight (MWL) in ELBW infants and tested its association with clinical variables which could potentially implicate the body fluid balance during the first two weeks of life.

Study design

Prospectively entered data in the computerized radiology, biochemical and hematological records, and daily case notes were retrospectively extracted during a 3-year study period. The infants' and maternal demographic, clinical course and outcome variables relevant to body fluid balance during the first two weeks of life were correlated with MWL. Pearson's correlation coefficient and Pearson's partial correlation tests were utilized for data analysis.

Results

Data are presented as mean ± SD. MWL in the entire cohort (n = 102) was 14.2 ± 5.4%. Day of life of MWL was 5.5 ± 2.1 and that of birth weight regained 14.5 ± 4.2 days. MWL correlated negatively with gestational age, antenatal steroid receipt (ANS) and pregnancy associated hypertension and positively with total days on oxygen, fluid intake, urinary output and the day of life when birth weight was regained. All these correlations were lost after controlling for GA except for the day of life when birth weight was regained. MWL did not correlate with RDS or its severity, hypotension, PIE, IVH, PDA and length of stay. Over 91% infants had MWL within 3.1-25%. Male, Caucasian and ELBW infants unexposed to ANS tended to have weight loss in excess of 25%.

Conclusion

MWL is governed by maturation and is not affected by concurrent clinical factors including fluid intakes during the 1st two weeks of life in ELBW infants. MWL within the estimated range of 14.5 + 4.2% of birth weight does not promote morbidities. Male, Caucasian and ELBW infants unexposed to ANS are susceptible to excessively high weight losses in early postnatal period.     

Prenatal tobacco exposure influences cerebral oxygenation in preterm infants

Aim

Our aim was to determine the influence of prenatal tobacco exposure on regional cerebral tissue oxygen saturation (r_cSO₂) and fractional tissue oxygen extraction (FTOE) in preterm infants. We hypothesized that as a result of vasoconstriction caused by prenatal tobacco exposure r_cSO₂ would be lower and FTOE would be higher during the first days after birth in infants exposed to tobacco during pregnancy.

Methods

Sixty preterms were included in this prospective, observational cohort study (median gestational age 29.9 weeks, range 26.0-31.8, median birth weight 1248 g, range 615-2250). Fourteen infants had been exposed to tobacco during pregnancy. All mothers smoked more than five cigarettes a day till delivery. We measured r_cSO₂ and transcutaneous arterial oxygen saturation (tcSaO₂) in all infants on days 1-5, 8, and 15. FTOE was calculated: FTOE = (tcSaO₂ − r_cSO₂) / tcSaO₂.

Results

In preterm infants exposed to tobacco during pregnancy, r_cSO₂ was lower during days 1, 2, and 8 after birth, median 73% versus 81%, 73% versus 80% and 71% versus 78% respectively. FTOE was higher during days 1 and 8 after birth, median 0.24 versus 0.15 and 0.26 versus 0.19 respectively. On the second day, FTOE tended to be higher, 0.18 versus 0.14.

Conclusions

During the first two days and day 8 after birth cerebral oxygen saturation is lower and oxygen extraction higher in preterm infants following prenatal tobacco exposure. Our data suggest that prenatal tobacco exposure may have an effect on cerebral oxygenation of the infant.     

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.     

Quantitative analysis of maturational changes in EEG background activity in very preterm infants with a normal neurodevelopment at 1 year of age

Background

The electroencephalographic (EEG) background pattern of preterm infants changes with postmenstrual age (PMA) from discontinuous activity to continuous activity. However, changes in discontinuity have been investigated by visual analysis only.

Aim

To investigate the maturational changes in EEG discontinuity in healthy preterm infants using an automated EEG detection algorithm.

Study design

Weekly 4 h EEG recordings were performed in preterm infants with a gestational age (GA) < 32 weeks and normal neurological follow-up at 1 year. The channel C3-C4 was analyzed using an algorithm which automatically detects periods of EEG inactivity (interburst intervals). The interburst-burst ratio (IBR, percentage of EEG inactivity during a moving time window of 600 s) and mean length of the interburst intervals were calculated. Using the IBR, discontinuous background activity (periods with high IBR) and continuous background activity (periods with low IBR) were automatically detected and their mean length during each recording was calculated. Data were analyzed with regression and multivariate analysis.

Results

79 recordings were performed in 18 infants. All recordings showed a cyclical pattern in EEG discontinuity. With advancing PMA, IBR (R² = 0.64; p < 0.001), interburst interval length (R² = 0.43; p < 0.001) and length of discontinuous activity (R² = 0.38; p < 0.001) decreased, while continuous activity increased (R² = 0.50; p < 0.001). Multivariate analysis showed that all EEG discontinuity parameters were equally influenced by GA and postnatal age.

Conclusion

Analyzing EEG background activity in preterm infants is feasible with an automated algorithm and shows maturational changes of several EEG derived parameters. The cyclical pattern in IBR suggests brain organisation in preterm infant.     

Treatment of patent ductus arteriosus with bidirectional flow in neonates

Background

Patent ductus arteriosus is a common occurrence among prematurely born neonates and is believed to play a role in the development of other complications of prematurity including intraventricular hemorrhage, bronchopulmonary dysplasia, and necrotizing enterocolitis. The clinical decision to treat the patent ductus arteriosus is complicated by the lack of evidence available regarding clinical conditions under which closure should be attempted.

Study aims

To compare clinical outcomes for neonates who underwent treatment of patent ductus arteriosus exhibiting bidirectional blood flow versus those with flow that was left to right.

Study design

Cohort study of all neonates with patent ductus arteriosus in which medical closure was attempted at the Duke University between January 2002 and October 2007.

Outcome measures

Death and other important clinical conditions.

Results

We identified 20 neonates with bidirectional flow out of 317 cases in which medical closure of patent ductus arteriosus was attempted. There was no significant increase in overall complications due to closure of a bidirectional patent ductus arteriosus [40% (8/20)] versus ones with left to right shunting [38% (111/297) p = 0.82]. Death occurred in 15% (3/20) with bidirectional PDA compared to 11% (34/297) in the left to right group, p = 0.72.

Conclusion

The trend in mortality is worrisome but does not contraindicate an aggressive approach to the clinically significant PDA that has bidirectional flow at the time of the echocardiogram.     

High-resolution computed tomography in young patients with cystic fibrosis: distribution of abnormalities and correlation with pulmonary function tests

Objective

To assess pulmonary abnormalities detected by high-resolution computed tomography (HRCT) in young children with cystic fibrosis (CF) and mild to moderate lung disease.

Study design

High-resolution computed tomography was performed in 60 children, 6 to 10 years old, with mild to moderate lung disease (forced expiratory volume in 1 minute [FEV₁], 52-137; mean, 102; SD, 15% predicted). HRCTs were scored by using a system that evaluates each lobe for severity and extent of CF lung disease. Findings of CF lung disease were tabulated in all subjects and in a subgroup with normal pulmonary function tests. HRCT scores were correlated with FEV₁, forced vital capacity (FVC), and forced expiratory flow between 25% and 75% of expired vital capacity (FEF_25-75) in 57 patients.

Results

Bronchiectasis was present in 35% of subjects, mucous plugging in 15%, and air trapping in 63%. No abnormality was detected in 25%. In 37 subjects with FEV₁, FVC, and FEF_25-75 >85% predicted, bronchiectasis was present in 30%. In 17% of these subjects, bronchiectasis was seen in ≥4 lobes. Correlations between HRCT scores and FEV₁ were significant and showed fair to moderate correlation (r = 0.36-0.46).

Conclusions

High-resolution computed tomography demonstrated a broad range of pulmonary abnormalities in young patients with CF with mild to moderate lung disease. In this study, abnormalities, including bronchiectasis, were common in young children with CF and normal pulmonary function tests.     

Diagnostic markers in combination improve the identification of growth-restricted neonates

Background

The identification of growth-restricted neonates is hampered by the lack of an appropriate diagnostic tool.

Aim

To determine the value of combining diagnostic markers in detecting growth-restricted neonates.

Methods

A set of anthropometric indices, nutritional status and placental weight were assessed in the study population soon after birth. Insulin-like growth factor I (IGF-I) and its binding protein 3 (IGFBP-3) were assayed in cord blood. Babies having low values (≤25th centile for gestational age) in 0, 1 or more of four anthropometric indices were classified as Group₂₅0, Group₂₅1 and Group₂₅2, respectively. For statistical evaluation the Mann-Whitney test and a multiple regression analysis were performed.

Results

One hundred-eighty (180) singleton babies of over 36 weeks of gestational age (GA) were studied. IGF-I, IGFBP-3 levels and placental weight were significantly lower in Group₂₅2 than both Group₂₅0 (P < 0.0001) and Group₂₅1 (p < 0.0001 to p = 0.03). Group₂₅1 and Group₂₅0 did not differ significantly regarding IGF-I and IGFBP-3 levels (p values 0.09 and 0.13, respectively). The combination of anthropometric indices enhanced their ability to predict IGF-I, IGFBP-3 levels and placental weight; the nutritional status of the babies added power to all individual models in predicting the three outcome variables. Analogous results were obtained when the 10th (instead of the 25th) centile for GA was used for the anthropometric indices.

Conclusion

The combination of simple diagnostic markers of growth restriction can define a reference test with enhanced diagnostic potential compared to the potential of the same markers in isolated use.     

The influence of extrauterine life on the aEEG maturation in normal preterm infants

Objective

To study, the maturational changes of the amplitude-integrated electroencephalogram (aEEG) in preterm infants without neurological disorders and especially the influence of the duration of extrauterine life, over this process.

Methods

96 preterm infants, 25-34 weeks' gestational age (GA) at birth, clinically stable and without ultrasonographic evidence of neurological abnormalities, were studied. The aEEG recordings were obtained within 72 h of life and then weekly until discharge. Four aspects of each tracing (continuity, sleep-wake cycling, bandwidth, and lower border), were evaluated by visual analysis, applying pre-established criteria.

Results

We analysed 624 aEEG recordings at postmenstrual age (PMA) of 25-42 weeks. With advanced GA the aEEG becomes more continuous (p: 0.022), it displays definite sleep-wake cycles (p: 0.011), and its bandwidth acquires the mature pattern (p: 0.012). A positive significant interaction of GA and PMA in the evolution of aEEG was found regarding continuity (p: 0.002), sleep-wake cycling (p: 0.002), and bandwidth (p: 0.02).

Conclusion

The evolution of the aEEG tracing depends on both GA and PMA. The older the infants at birth the more mature the aEEG pattern. At the same PMA, preterm infants of lower GA display an advanced maturation of the aEEG comparing with others of higher GA.     

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.     

Early assessment of visual function in preterm infants: How early is early?

Background

Several studies reported on various aspects of visual function at term age and in the first months after birth but less has been reported in preterm infants before they reach termequivalent age.

Aims

To assess the suitability of a battery of tests of visual function for use in infants born at < 33 weeks gestation (GA) and assessed before 34 weeks post-menstrual age (PMA); to evaluate the distribution of the findings according to GA, and to compare the data with those previously published on preterm infants assessed at 35 weeks PMA.

Study design

Cross-sectional study.

Subjects

Sixty-four preterm infants with a GA < 33 weeks were studied.

Outcome measures

We used a battery of visual function tests previously validated at 35 and 40 weeks PMA in low-risk preterm infants. All the infants in this current study underwent the same assessment before 34 weeks PMA.

Results

Before 31 weeks PMA most infants could not be reliably assessed because of clinical instability, whilst after 31 weeks PMA most infants could be assessed and they showed progressive maturation in their responses with PMA. Some items (spontaneous ocular motility, horizontal tracking, tracking a coloured stimulus, and ocular fixation) showed similar results at 32-33 weeks PMA to those found in low-risk preterm at 35 weeks PMA. Ocular movements to a target and arc tracking were the items with the most immature responses.

Conclusions

Our results provide further evidence that a structured assessment of visual function can be used in clinical routine and for research purposes in infants as young as 31 weeks PMA.     

Inhaled nitric oxide treatment inhibits neuronal injury after meconium aspiration in piglets

Background

Meconium aspiration-induced hypertensive lung injury is frequently associated with neuronal damage. Inhaled nitric oxide (iNO) is widely used in the treatment of pulmonary hypertension, but its effects on the brain are poorly known.

Aims

The aim of this study was to determine the effects of iNO treatment on the neuronal tissue after meconium aspiration.

Study design

71 anesthetized, catheterized and ventilated newborn piglets were studied for 6 h. Thirty-five piglets were instilled with a bolus of human meconium intratracheally and 36 piglets with saline instillation served as controls. Nineteen meconium piglets and 17 control piglets were continuously treated with 20 ppm of iNO, started at 30 min after the insult. The extent of neuronal injury was analysed histologically, and the levels of brain tissue lipid peroxidation products, reduced glutathione (GSH), myeloperoxidase activity and oxidized DNA were analysed as indicators of oxidative stress.

Results

iNO treatment diminished the pulmonary hypertensive response caused by meconium aspiration, but did not change systemic or carotid hemodynamics. NO administration was associated with reduced neuronal injury and diminished amount of oxidized DNA in the hippocampus of the meconium piglets. Further, iNO treatment was associated with decreased level of GSH in the cortex, but no change in lipid peroxidation production or myeloperoxidase activity was detected in any of the studied brain areas.

Conclusions

Our results suggest that iNO treatment may inhibit DNA oxidation and neuronal injury in the hippocampus, associated with newborn meconium aspiration.     

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.     

Comparison of salivary cortisol, heart rate, and oxygen saturation between early skin-to-skin contact with different initiation and duration times in healthy, full-term infants

Background

There are few studies that compare the physiological and biological efficacies between different early skin-to-skin contacts (SSC) post birth.

Aim

To investigate physiologically and biochemically how early SSC with different initiation and duration time influence the stress post birth for full-term infants.

Study design

Non-experimental study.

Subjects

Study I; Thirty-two infants who began SSC 5 min or less [birth SSC, mean initiation time (standard deviation): 1.6 (1.1) min] after birth and 36 infants who did so more than 5 min [very early SSC, 26.3 (5.0) min] in heart rate (HR) and oxygen saturation (SpO₂) analysis. Study II; Eighteen infants who underwent SSC for 60 min or less [mean initiation time: 7.5 (12.2) min] and 61 infants who did so for more than 60 min [15.3 (12.5) min] in salivary cortisol analysis.

Outcome measures

HR and SpO₂ measured for 30 min post birth. Salivary cortisol concentration measured at 1 min, 60 min, and 120 min post birth.

Results

Birth SSC group reached HR stability of 120-160 bpm significantly faster than very early SSC group by Kaplan-Meier analysis (P = 0.001 by log-rank test). As for SpO₂ stability of 92% and 96%, no significantly between-group difference was found. Salivary cortisol levels were significantly lower between 60 and 120 min after birth in SSC group, continuing for more than 60 min compared with SSC group for 60 min or less after adjustment for salivary cortisol level at 1 min besides the infant stress factors (P = 0.046).

Conclusions

Earlier SSC beginning within 5 min post birth and longer SSC continuing for more than 60 min within 120 min post birth are beneficial for stability of cardiopulmonary dynamics and the reduction of infant stress during the early period post birth.     

Impact of histological chorioamnionitis, funisitis and clinical chorioamnionitis on neurodevelopmental outcome of preterm infants

Background

The role of chorioamnionitis in neurodevelopment of preterm infants is not fully understood.

Aim

To examine the association between different indicators of intrauterine inflammation (clinical chorioamnionitis, histological chorioamnionitis and funisitis) and neurodevelopmental impairment in very preterm infants.

Methods

Preterm infants with a birth weight of < 1500 g or a gestational age of < 32 weeks were included. Follow-up evaluation up to 2 years of age consisted of neurological examination, neurodevelopmental assessment and visual and audiologic tests. Outcome data were compared between the chorioamnionitis and the control groups, controlling for gestational age, birth weight and Apgar score at 5 min.

Results

One hundred seventy-seven patients comprised the study population (mean gestational age 29 ± 2 weeks, mean birth weight 1167 ± 344 g). Histological chorioamnionitis was present in 49% of placentas, whereas funisitis was observed in 25%. In 57% cases clinical maternal chorioamnionitis was suspected. Follow-up was available for 130 (82%) patients. Infants with funisitis, compared with controls, had a significantly higher incidence of moderate to severe disability (18% vs 5%, OR 4.07; 95% CI 1.10-15.09).

Conclusion

The results of this study suggest that, unlike a broad definition of histological chorioamnionitis including inflammation of maternal or fetal placental tissues, funisitis may entail a higher risk of moderate to severe disability at 2 years of age in preterm infants.     

Amplitude integrated electroencephalographic activity in infants with congenital heart disease before surgery

Background

Infants with congenital heart disease (CHD) are at risk for brain injury. An accurate tool to monitor brain function is amplitude integrated EEG (aEEG). It records both background patterns and electrographic seizure activity (EA).

Aims

Our aim was to determine aEEG patterns in infants with CHD and to determine the differences between infants with a cyanotic or an acyanotic CHD.

Study design and subjects

Sixty-two full term newborns had either a cyanotic CHD (transposition of the great arteries (n = 24)) or an acyanotic CHD (hypoplastic left heart syndrome (n = 26), critical aortic valve stenosis (n = 1) or aortic coarctation (n = 11)). The background patterns, sleep-wake cycling (SWC), and EA were assessed. The first 72 h after starting prostaglandin E₁-therapy were used for analysis.

Results

The background patterns were mildly abnormal in 45% of the infants and severely abnormal at some point during the recording in 14% of the infants. We found no differences in background patterns between the two groups. EA was present in 12 (19%) infants. EA was more frequent in infants with acyanotic CHD (OR 9.4, 95% CI 1.1-78, p = 0.039). SWC was equally frequent in infants with cyanotic and infants with acyanotic CHD. A severely abnormal aEEG and EA were associated with more profound acidosis.

Conclusions

Before surgery the majority of infants with a CHD had an abnormal aEEG. aEEG helped to identify EA and it was a useful tool to evaluate brain function prior to surgery in CHD.     

Placental pathology is associated with illness severity in preterm infants in the first twenty-four hours after birth

Background

Placental pathology is associated with long-term neurological morbidity. Little is known about the association of placental pathology and illness severity directly after birth in preterm infants.

Objective

To determine the association between placental pathology and illness severity in preterm infants during the first 24 h after birth.

Study design

Placentas of 40 preterm infants, born after singleton pregnancies (gestational age 25.4-31.7 weeks, birth weight 560-2250 g) were assessed for histopathology. Illness severity was measured using the Score of Neonatal Acute Physiology Perinatal Extension (SNAPPE). A high SNAPPE reflects high illness severity.

Results

Examination of the 40 placentas revealed: pathology consistent with maternal vascular underperfusion (MVU) (n = 24), ascending intrauterine infection (AIUI) (n = 17), villitis of unknown aetiology (VUE) (n = 6), foetal thrombotic vasculopathy (FTV) (n = 6), elevated nucleated red blood cells (NRBCs) (n = 6), and chronic deciduitis (n = 10). SNAPPE ranged from 1 to 53 (median 10). Infants with elevated NRBCs had a higher SNAPPE than infants without elevated NRBCs (median 30 vs. 10, p = 0.014). The same was found for the presence of FTV (median 30 vs. 10, p = 0.019). No relation existed between SNAPPE and the other placental pathologies.

Conclusions

Elevated NRBCs and FTV were associated with higher illness severity during the first 24 h after birth in preterm infants. Ascending intrauterine infection was not associated with high illness severity.