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.     

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.     

High plasma cytokine levels, white matter injury and neurodevelopment of high risk preterm infants: assessment at two years

Background

Controversy exists regarding association of high levels of proinflammatory cytokines, neonatal morbidities and poor neurodevelopment outcome in very low birth weight infants.

Objective

To determine association between severity of early inflammatory response and neurodevelopment outcome in high risk very low birth weight infants.

Methods

Sixty-two very preterm infants with high risk for early-onset sepsis were followed up to 24 months corrected age. Blood sample was collected for IL-6, IL-8, IL-10, IL-1β, and TNF-α analysis. Neurodevelopment outcome by Bayley Scales of Infant Development II was assessed at 22 to 24 months. Magnetic Resonance Image was performed at least once during the first 12 months.

Results

In 24 (38.7%) MDI was < 85, and 16 (25.8%) had PDI < 85. Low birth weight was significantly associated with low MDI, and birth weight and periventricular leukomalacia were significantly associated with low PDI by multiple regression analysis. After controlling for birth weight and gestational age, none of the studied variables was associated with low MDI, and only periventricular leukomalacia with low PDI. Each additional 100 g in the birth weight reduced the probability of low MDI and PDI scores in 14%.

Conclusions

There was no association of high cytokines plasma levels with poor neurodevelopment outcome at 22 to 24 months' corrected age, suggesting that elevations of plasma proinflammatory cytokines early in life do not play an important role in pathophysiology of brain injury in high risk preterm infants.     

Episodes of hypocarbia and early-onset sepsis are risk factors for cystic periventricular leukomalacia in the preterm infant

Background

Septic episodes in preterm infants recently have been reported to be associated with periventricular leukomalacia (PVL). The role of hypocarbia as an independent risk factor for PVL in clinical studies raises many questions without conclusive answers.

Aims

To evaluate risk factors for cystic PVL focussing on the influence of hypocarbia.

Study design

Retrospective single centre case-control study.

Subjects

Preterm infants 24 to 35 weeks of gestational age and matched (1:2 for gender, birth year, gestational age and birth weight) controls.

Outcome measures

Multivariate analysis of perinatal factors being associated with cystic PVL diagnosed by serial ultrasound examinations.

Results

Univariate analysis of risk factors revealed lower 5 and 10 min Apgar scores, and higher rates of neonatal seizures, early-onset sepsis, neonatal steroids, respiratory distress syndrome with surfactant replacement therapy, and episodes of hypocarbia significantly being associated with PVL. Multivariate analysis using a logistic regression model revealed early-onset sepsis and hypocarbia being significantly associated with PVL (p = .022 and .024, respectively). Lowest PaCO₂ values did not differ as did not the duration of hypocarbia, but the onset of hypocarbia was significantly later in PVL cases compared to controls (mean 26 vs. 15 h, p = .033). Neurodevelopmental follow-up at a median time of 46 months was poor showing 88% of the cases having an adverse neurological outcome.

Conclusion

We found early-onset sepsis and episodes of hypocarbia within the first days of life being independently associated with PVL.     

CSF cytokine levels in preterm infants may reflect systemic inflammation and are independent of gestation

Background

Among preterm infants, high concentrations of inflammatory mediators in cerebrospinal fluid (CSF) are associated with poor outcome. Previous studies have not indicated whether CSF concentrations of inflammatory mediators are associated with important confounders such as gestational age.

Aims

To examine associations between CSF concentrations of inflammatory mediators and gestational age, maternal features suggestive of inflammation, characteristics of the CSF sample or the presence of a systemic inflammatory response.

Study design and subjects

Aliquots of CSF obtained during routine investigation of potential sepsis among infants born before 35 weeks gestation were assayed for 17 mediators of inflammation using a fluorescent multi-bead analyser. Other information was collected from routine clinical records.

Results

39 infants were assessed. CSF levels of mediators of inflammation were not correlated with gestational age. CSF red blood cell counts were correlated with CSF concentrations of IL-6, GM-CSF and IL-17 (each p < 0.003). CSF lactate was correlated with CSF concentrations of IL-1β, IL-6, GM-CSF, G-CSF, IFN-γ and MIP-1β. CSF concentrations of IL-1β, IL-6, G-CSF, TNF-α and IFN-γ were higher in infants with a raised CRP within 24 h of delivery (each p < 0.003).

Conclusions

CSF concentrations of inflammatory mediators most probably reflect inflammatory pathologies and are not influenced by gestational age. They may also, however, reflect contamination with blood or systemic inflammation. CSF concentrations of inflammatory mediators may not provide a specific indicator of CNS inflammation.     

Assessment of risk factors for survival of neonates born after second-trimester PPROM

Objective

Assess fetal risk factors which impact survival of infants delivered after second-trimester PPROM.

Study design

Clinical records of 87 patients, who all had second-trimester rupture of membranes between 14 + 0 and 24 + 6 weeks of gestation treated January 1998 to July 2005 were reviewed regarding perinatal outcome. This study is based on 25 surviving infants.

Results

13 of these 25 infants died in the hospital. Survivors had a higher birth weight (p = 0.008) and higher Apgar scores after 5 min (p = 0.005) than those infants dying. No differences in UA pH, the need of catecholamines and no association between histological verified chorioamnionitis and early onset sepsis were seen between survivors and nonsurvivors.

Conclusion

Higher gestational age at birth, higher birth weight, the absence of histologically verified chorioamnionitis and 5 min Apgar scores of ≥ than 6 have positive prognostic value for survival of neonates delivered preterm after second-trimester PPROM.     

Validation of transcutaneous bilirubin nomogram in identifying neonates not at risk of hyperbilirubinaemia: a prospective, observational, multicenter study

Background

Transcutaneous bilirubin (TcB) measurement is widely used as screening for neonatal hyperbilirubinaemia.

Aims

To prospectively validate TcB measurement using hour-specific nomogram in identifying newborn infants not at risk for severe hyperbilirubinaemia.

Study design

prospective, observational, multicenter.

Subjects

2167 term and late preterm infants born in 5 neonatal units in the Lazio region of Italy.

Methods

All neonates had simultaneous TcB and total serum bilirubin (TSB) measurements, when jaundice appeared and/or before hospital discharge. TcB and TSB values were plotted on a percentile-based hour-specific transcutaneous nomogram previously developed, to identify the safe percentile able to predict subsequent significant hyperbilirubinaemia defined as serum bilirubin > 17 mg/dL or need for phototherapy.

Results

Fifty-five babies (2.5%) developed significant hyperbilirubinaemia. The 50th percentile of our nomogram was able to identify all babies who were at risk of significant hyperbilirubinaemia, but with a high false positive rate. Using the 75th percentile, two false negatives reduced sensitivity in the first 48 hours but we were able to detect all babies at risk after the 48th hour of age. Conclusions: This study demonstrates that the 75th percentile of our TcB nomogram is able to exclude any subsequent severe hyperbilirubinaemia from 48 h of life ahead.     

CPAP combined with inhaled nitric oxide for treatment of lung hypoplasia and persistent foetal circulation due to prolonged PPROM

Background

Second trimester preterm premature rupture of the membranes (PPROM) before 24 weeks of gestation is associated with a high morbidity and mortality rate.

Aim

To demonstrate the efficacy of early continuous positive airway pressure (CPAP) combined with inhaled nitric oxide (iNO) for treatment of preterm infants with lung hypoplasia and persistent foetal circulation (PFC) due to very early PPROM and prolonged severe oligohydramnios.

Methods

Seven infants with prolonged PPROM, lung hypoplasia, respiratory distress and persistent foetal circulation were intubated in the delivery room for subsequent surfactant and iNO application. As our new treatment strategy was to keep the period of mechanical ventilation as short as possible, all infants were switched on nasal CPAP combined with iNO within the first 24 hours.

Results

Mean gestational age at PPROM was 19 + 6 weeks (range 14 + 2 to 23 + 6 weeks) and the average latency period between rupture of membranes and delivery was 10 + 3 weeks (7 + 3 to 16 + 4 weeks). Infants were born at 30 + 3 weeks of gestation (28 + 3 to 33 + 1 weeks) with an average birth weight of 1468 g (884 to 2200 g). In all neonates CPAP combined with iNO reversed PFC and 6 patients stabilised without the need for reintubation and mechanical ventilation. One infant had to be reintubated following 12 hours of CPAP combined with iNO due to respiratory insufficiency. All seven infants survived to discharge.

Conclusion

CPAP combined with iNO might be a promising approach for therapy of preterm infants with lung hypoplasia and persistent foetal circulation due to very early PPROM.     

A longitudinal study of differences in electroencephalographic activity among breastfed, milk formula-fed, and soy formula-fed infants during the first year of life

Background

The extent to which adequate nutrition from infant diets differentially influence developmental outcomes in healthy infants has not been determined.

Aim

To compare the effects of the major infant diets on the development of brain electrical activity during infancy.

Study design

Scalp EEG signals (124 sites) recorded from the same infants during quiet wakefulness at 3, 6, 9, and 12 months.

Subjects

Healthy, full-term infants (40/group; gender matched) either breastfed (BF) or fed milk formula (MF) or soy formula (SF) through the first 6 months.

Outcome measures

Power spectral values for frequencies in the 0.1-30 Hz range.

Results

Significant diet-related differences were present across frequency bands and included effects that were time- [peaks in 0.1-3 Hz at 6 (MF,SF) and 9 months (BF); 3-6 Hz at 6 months (MF, SF > BF); increases in 6-9 Hz from 3 to 6 months (MF > BF) and from 6 to 9 months (MF > SF)] and gender-related (9-12 Hz and 12-30 Hz: at 9 months BF > MF, SF boys, and MF > SF girls).

Conclusions

The development of brain electrical activity during infancy differs between those who are breastfed compared with those fed either milk or soy formula, but is generally similar for formula-fed groups. These variations in EEG activity reflect diet-related influences on the development of brain structure and function that could put infants on different neurodevelopmental trajectories along which cognitive and brain function development will proceed.     

Perinatal cerebral insults alter auditory event-related potentials

Background

Auditory event-related potentials (AERPs) can be used as indices of neural information processing. Altered AERPs have been reported in children and young adults with frontal lobe infarction.

Aim

To test the hypothesis that perinatal brain injury affects cortical auditory processing.

Methods

We assessed AERPs at term, 6 and 12 months of age in preterm infants [n = 9, median gestational age (GA) 27.9, range 23.9-30.0 wk], term infants with perinatal intracerebral hemorrhage (ICH) [n = 5, GA 40.3, range 37.4-42.3 wk], and term infants with perinatal asphyxia [n = 4, GA 39.4, range 37.9-40.3 wk]. Healthy preterm (n = 16) and term infants (n = 22) served as controls. A harmonic tone of 500-Hz frequency was used as standard and of 750-Hz as deviant stimulus. Mean AERP amplitudes were calculated over 100 ms periods from 50 to 350 ms. The developmental outcome was followed until 2 years of age.

Results

The term ICH (p = 0.012) and asphyxia (p = 0.0016) group had smaller or more negative responses to the deviant, resulting in smaller or more negative MMR amplitudes than those of the controls. The preterm ICH group did not differ significantly from their preterm born controls. MMR varied in all patient groups and was not associated with adverse outcome.

Conclusion

AERP alterations suggest that perinatal cerebral insults affect cortical auditory processing.     

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.     

Postural control of pre-term infants at 6 and 12 months corrected age

Background

Pre-term infants are at high risk for motor disabilities. Postural control, the basis for motor development, develops rapidly during the first year of life. An early start to extra-uterine life with an immature motor system may influence a pre-term infant's postural control.

Aims

To identify important prognostic factors and determine the difference in postural control between full-term and pre-term infants.

Method

Medical records of 93 pre-term infants with birth weight of less than 1501 g (mean birth weight = 1136.03 ± 243.86 g; mean gestational age = 29.14 ± 2.78 weeks) were reviewed. Data was collected from the preemie clinical follow-up program at the National Cheng Kung University, Taiwan.

Results

Results demonstrated that pre-term infants had poorer postural control than full-term infants both at 6 and 12 months adjusted age, and that medical complication as measured by the Neonatal Medical Index was the best predictor of postural control in pre-term infants in the first year of life. In addition, our findings confirmed that the development of postural control at 6 months adjusted age predicts the development of postural control at 12 months adjusted age after controlling for prognostic factors.

Conclusions

Both biological and social environmental factors appeared to be associated with pre-term infants' postural control at 6 and 12 months adjusted age. The development of postural control at 6 months adjusted age predicted the development of postural control at 12 months adjusted age. This suggested the value of early follow-up examinations at 6 months adjusted age.     

Sepsis-associated electroencephalographic changes in extremely low gestational age neonates

Background

Sepsis in premature infants is associated with adverse neurodevelopmental outcomes. No previous studies have assessed acute changes in brain function during sepsis that might precede these adverse outcomes.

Methods

We performed amplitude-integrated electroencephalography (aEEG) monthly, from 28 weeks until 36 weeks of postmenstrual age, on 108 premature infants born before 28 weeks of gestation. Additional aEEG recordings were performed during infants' first episode of sepsis. Two independent readers who were blinded to the infant's gestational age at birth and chronologic age, as well as to whether the infant had sepsis, evaluated aEEG recordings for the presence of burst suppression and assigned a maturation score.

Results

Burst supression was found in 22% of aEEG recordings from infants without sepsis and 57% of recordings from infants with sepsis at the time of the recording (odds ratio = 4.2; 95% confidence limits = 2.4, 7.2; p < 0.001). After adjustment for postmenstrual age at the time of the recording, the association between sepsis and burst suppression persisted (odds ratio = 2.4; 95% confidence limits = 1.2, 4.8; p = 0.01). No statistically significant difference was found in the rate of increase in aEEG maturation score between infants with sepsis and those without.

Conclusion

Sepsis is associated with acute electroencephalographic changes, as indicated by burst supression, but not with a decreased rate of brain wave maturation.     

Intrapartum fetal heart rate patterns in infants (≥ 34 weeks) with poor neurological outcome

Background

Cases suggestive of non-acidemia related cerebral palsy (CP) are likely misdiagnosed as acidemia related CP because of the presence of nonreasuring fetal heart rate (FHR) patterns.

Aims

Our purpose was to compare intrapartum FHR patterns between the cases of neurological damage and the cases without disability after severe metabolic acidemia and neonatal encephalopathy, and also to compare the FHR patterns between cases with CP due to asphyxia and cases with CP of other etiology in infants born after 34 weeks.

Study design

From 1998 to 2003, our peer review conferences determined 136 infants with high-risk factors for neurological impairment in the unselected 65,197 live births. High-risk infants were chosen according to our criteria. Among them 58 were eligible infants because they were born at ≥ 34 weeks of gestation and also had legible FHR traces.

Outcome measures

Incidence of nonreassuring FHR patterns.

Results

Fifteen infants were acidemia related and 43 were non-acidemia related high-risk infants. Ten of the 15 acidemia infants developed CP and all had shown bradycardia ≥ 13 min with a nadir < 80 bpm. In the 43 non-acidemia infants, 35 had CP, mental retardation, epilepsy, or hearing loss and 74% (26/35) of them had shown nonreassuring FHR patterns. Incidence of severe bradycardia was significantly elevated in the acidemia related CP compared with acidotic infants without disability, and those with non-acidemia related CP.

Conclusions

Even in infants with non-acidemia related CNS impairments, who were born at ≥ 34 weeks of gestation, 74% had shown intrapartum nonreassuring FHR patterns.     

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.     

A patient care system for early 3.0 Tesla magnetic resonance imaging of very low birth weight infants

Background

Very low birth weight (VLBW) infants (weight < 1500 g) are increasingly cared for without prolonged periods of positive pressure ventilation (PPV).

Aims

To develop a system for 3.0 T magnetic resonance (MR) image acquisition from VLBW infants who are not receiving PPV, and to test the clinical stability of a consecutive cohort of such infants.

Design

Seventy VLBW infants whose median weight at image acquisition was 940 g (590-1490) underwent brain MR imaging with the developed care system as participants in research. Twenty infants (29%) received nasal continuous positive airway pressure (nCPAP), 28 (40%) received supplemental oxygen by nasal cannulae, and 22 (31%) breathed spontaneously in air during the MR examination.

Results

There were no significant adverse events. Seventy-six percent had none or transient self-correcting oxygen desaturations. Desaturations that required interruption of the scan for assessment were less common among infants receiving nCPAP (2/20) or breathing spontaneously in air (2/22), compared with those receiving nasal cannulae oxygen (13/28), p = 0.003. Sixty-four (91%) infants had an axillary temperature ≥ 36 °C at completion of the scan (lowest 35.7 °C), There was no relationship between weight (p = 0.167) or use of nCPAP (p = 0.453) and axillary temperature < 36 °C. No infant became hyperthermic.

Conclusion

VLBW infants who do not require ventilation by endotracheal tube can be imaged successfully and safely at 3.0 T, including those receiving nCPAP from a customised system.     

Maternal anxiety is related to infant neurological condition, paternal anxiety is not

Background

Parental anxiety and stress may have consequences for infant neurological development.

Aims

To study relationships between parental anxiety or well-being and infant neurological development approximately one year after birth.

Study design

Longitudinal study of a birth cohort of infants born to subfertile couples. Subjects: 206 parent-child dyads.

Outcome measures

Infant neurology was assessed with the Touwen Infant Neurological Examination (TINE) at 10 months and a developmental questionnaire at 12 months. Parental measures included trait anxiety measured by the State-Trait Anxiety Inventory (STAI) and well-being measured by the General Health Questionnaire (GHQ).

Results

Maternal trait anxiety was associated with a less optimal neurological condition (r_s = − 0.19, p < 0.01) of the infant. This association persisted after adjusting for confounders and results were confirmed by the outcome of the developmental questionnaire. Paternal trait anxiety and parental well-being were not related to the infant's neurodevelopmental outcome.

Conclusions

Infants of mothers with high trait anxiety have an increased vulnerability to develop a non-optimal nervous system. The association may be mediated in part by early programming of monoaminergic systems. Future research should include an exploration of specific windows of vulnerability to maternal anxiety.     

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.     

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.     

Uniform treatment thresholds for hyperbilirubinemia in preterm infants: background and synopsis of a national guideline

Background

To prevent severe hyperbilirubinemia and bilirubin neurotoxicity, the American Academy of Pediatrics' management guideline for hyperbilirubinemia in near term infants is used worldwide. A leading guideline for jaundiced preterm infants is lacking whereas the risk on severe hyperbilirubinemia is high in these infants. Our aim was to define uniform treatment thresholds for jaundiced preterm infants. In this article we present the history and a synopsis of this novel national guideline.

Study Design

A survey on guidelines for hyperbilirubinemia in preterm infants was sent to all Dutch Neonatal Intensive Care Units (NICUs). After comparison with international guidelines, a new consensus-based guideline was developed.

Results

Treatment thresholds of all 10 NICUs were based on Total Serum Bilirubin (TSB) and related to birth weight (n = 9) and gestational age (n = 1). NICUs used age-specific (n = 6) or fixed (n = 4) TSB-thresholds resulting in a large range of thresholds (maximal 170 μmol/L for phototherapy and 125 μmol/L for exchange transfusion). Acidosis, asphyxia, sepsis, active hemolysis and intraventricular hemorrhage were the most frequently used risk factors. Consensus was agreed upon TSB-based treatment thresholds, categorized in 5 birth weight groups and divided in high and low risk infants.

Conclusion

There was no standardized care for jaundiced preterm infants in the Netherlands. In addition to the internationally used guideline for (near) term infants, a novel “consensus based” guideline for preterm infants with a gestational age of less than 35 weeks has been developed and implemented in the Netherlands. This guideline is approved and recommended by the Dutch Society of Pediatrics.