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.     

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.     

Amplitude-integrated electroencephalography in preterm infants with cystic periventricular leukomalacia

Aim

This study aimed to assess amplitude-integrated electroencephalography (aEEG) findings in preterm infants with cystic periventricular leukomalacia (cPVL) in the early neonatal period.

Methods

We analyzed five infants with cPVL, whose gestational age was between 27 and 30 weeks, and 15 matched control infants. Two-channel (C3-O1 and C4-O2) aEEG was obtained by digital conversion from a conventional electroencephalogram, which was recorded at days 0-5, 6-13, and 21-34 in each infant. We evaluated the averaged two-channel values of several measurements using visual and quantitative analyses.

Results

Infants with cPVL had a significant higher maximal upper-margin amplitude value, with a median of 47.5 μV (range of 42.5-60) compared with the control infants (median, 33.8; range, 23.8-50) in the second visual-analysis record. Infants with cPVL also had a significantly higher mean upper-margin amplitude value, with a median of 18.8 μV (range, 17.7-23.2) compared with the control infants (median, 16.3; range, 10.3-19.0) in the second quantitative-analysis record.

Conclusions

We demonstrated that the upper-margin amplitude of aEEG in infants with cPVL was significantly higher than that in the control infants at 6-13 days after birth.     

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.     

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.     

Amplitude-integrated electroencephalographic activity is suppressed in preterm infants with high scores on illness severity

Background

The neonatal acute physiology score, SNAP-II, reflects the severity of illness in newborns. In term newborns, amplitude integrated EEG (aEEG), is depressed following asphyxia. In preterm infants aEEG is discontinuous, and therefore more difficult to assess compared to term infants.

Aims

Our first aim was to investigate whether assessing aEEG amplitudes by calculating amplitude centiles was consistent with assessment by pattern recognition. Our second aim was to investigate whether the aEEGs of preterm infants were influenced by SNAP-II.

Study Design and Subjects

We recorded aEEGs in 38 infants with a mean gestational age of 29.7 weeks (26.0-31.8 weeks) during the first five days of life. The mean recording time was 130 min. The aEEGs were assessed by pattern recognition, by calculating Burdjalov score, and by calculating the mean values of the 5th, 50th, and 95th centiles of the aEEG amplitudes. Illness severity was determined within the first 24 h.

Results

We assessed 151 recordings and found strong correlations between the 5th and 50th amplitude centiles and the Burdjalov scores (r = 0.71, p < 0.001 and r = 0.47, p < 0.001, respectively). The 5th and 50th amplitude centiles correlated with SNAP-II (r = − 0.34, p < 0.0001 and r = − 0.27, p = 0.001). These correlations were the strongest on the first day of life (r = − 0.55, p = 0.005 and r = − 0.47, p = 0.018, respectively). The 5th and the 50th amplitude centiles were best predicted by gestational age, SNAP-II, and low blood pressure.

Conclusions

Severe illness as measured by the SNAP-II, and low blood pressure had a negative influence on the aEEGs of preterm infants.     

Patterns in sleep-wakefulness in three-month old infants exposed to methadone or buprenorphine

Background

Infants exposed to opioides in-utero frequently demonstrate withdrawal symptoms in the neonatal period and have difficulties with state regulation.

Aim

This study examines sleep-wakefulness-distress patterns as indicators of regulatory mechanisms at 3 months of age.

Participants

A national infant cohort (N = 35) born to women in high-dose maintenance treatment during pregnancy and a comparison group (N = 36) of low-risk infants born in the same period.

Outcome measures

Distributions and frequencies of sleep, wakefulness and distress measured in hours and episodes on sleep charts recorded by the mothers in the two groups.

Results

Women in maintenance treatment were monitored closely during pregnancy to avoid illicit drug use and to be prepared for motherhood. They were also offered residential treatment before pregnancy and after the child was born. There were no statistical differences between the two groups in any of the 10 measures reflecting diurnal and nocturnal rhythmicity at 3 months despite of neonatal abstinence syndrome in 47% of the exposed infants and significant differences in infant characteristics with respect to birth weight, gestational age and maternal characteristics.

Conclusions

Follow-up procedures combining drug monitoring and counseling during pregnancy and in the first months after birth enhance the development of state regulation in terms of sleep-wakefulness patterns.     

Reduced cerebellar diameter in very preterm infants with abnormal general movements

Background

Abnormal General Movements (GMs) early in life are predictive of later neuromotor deficits and are related to white matter abnormalities on magnetic resonance imaging (MRI). However, other structural correlates of abnormal GMs have not been defined.

Aims

The objective of this study was to explore brain-metrics (linear brain measurements on MRI representative of 3-D brain volumes) at term as a predictor of abnormal GMs at 1 and 3 months' corrected age in preterm infants. It was hypothesized that abnormal GMs would be related to reduced brain-metrics in primary motor areas, namely the cerebellum and parietal lobes.

Study design

Eighty three preterm infants (< 30 weeks' gestational age) were scanned at term-equivalent age. MRI was assessed for white matter abnormality and brain-metrics in six predefined brain regions (i.e. bifrontal, biparietal, lateral ventricles and transverse cerebellar diameters, and inter-hemispheric distance).

Outcome measures

At 1 and 3 months' corrected age infants' GMs were assessed from video-taped footage and rated as normal or abnormal using standardized methodology.

Results

At 1 month, 63% (n = 52) of infants had abnormal GMs with no association between any of the brain-metrics and abnormal GMs. At 3 months, 23% (n = 18) of infants had abnormal GMs (absent fidgety movements n = 18; abnormal fidgety movements n = 0). Reduced bifrontal, biparietal, and cerebellar transverse diameters, along with an increase in lateral ventricle sizes were associated with an increased risk of abnormal GMs at 3 months' corrected age. After controlling for white matter abnormality and grade III/IV intraventricular haemorrhage, only the cerebellar transverse diameter was predictive of abnormal GMs at 3 months.

Conclusions

Reduced cerebellar diameter at term equivalent age is related to abnormal GMs at 3 months' corrected age, independent of white matter abnormality and intraventricular haemorrhage.     

Infant head circumference growth is saltatory and coupled to length growth

Background

Rapid growth rates of head circumference and body size during infancy have been reported to predict developmental pathologies that emerge during childhood.

Aims

This study investigated whether growth in head circumference was concordant with growth in body length.

Subjects

Forty infants (16 males) were followed between the ages of 2 days and 21 months for durations ranging from 4 to 21 months (2616 measurements).

Study design

Longitudinal anthropometric measurements were assessed weekly (n = 12), semi-weekly (n = 24) and daily (n = 4) during home visits. Individual head circumference growth was investigated for the presence of saltatory patterns. Coincident analysis tested the null hypothesis that head growth was randomly coupled to length growth.

Results

Head circumference growth during infancy is saltatory (p < 0.05), characterized by median increments of 0.20 cm (95% confidence interval, 0.10-0.30 cm) in 24-h, separated by intervals of no growth ranging from 1 to 21 days. Daily assessments identified that head growth saltations were coupled to length growth saltations within a median time frame of 2 days (interquartile 0-4, range 1-8 days). Assessed at semi-weekly and weekly intervals, an average 82% (SD 0.13) of head growth saltations was non-randomly concordant with length growth (p ≤ 0.006).

Conclusions

Normal infant head circumference grows by intermittent, episodic saltations that are temporally coupled to growth in total body length by a process of integrated physiology that remains to be described.     

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.     

Early visual assessment in preterm infants with and without brain lesions: correlation with visual and neurodevelopmental outcome at 12 months

Background

Several studies have reported the development of various aspects of visual function in infancy and early childhood in both preterm and term-born infants, but only a few studies have focused on the predictive power of neonatal visual findings in infants with brain lesions.

Aims

To explore visual findings at term age, and at 3 and 12 months corrected age in preterm infants (gestational age < 33 weeks) with and without brain lesions; to compare the assessment at term age and at 12 months; and to assess the relationship between visual findings and neurodevelopmental outcome at 12 months.

Study design

Cranial ultrasound scans (US) were classified in normal, mild or major abnormalities. One-hundred and forty-five infants were assessed with age specific tests for visual function at term age, and at 3 and 12 months. Neurodevelopmental assessment (Griffiths' Scales) was performed at 12 months.

Results

A good correlation was found between early and late visual assessment and neurodevelopment outcome. Of the 121 infants with normal neonatal visual assessment, 119 were also normal at 12 months and 116 had normal developmental quotient. Of the 24 infants with abnormal neonatal visual assessment, 12 were also abnormal at 12 months. All the false positives had normalised by 3 months. Of the 35 infants with major US abnormalities, 20 had normal and 15 abnormal scores on the neonatal assessment. At 1 year 17 had normal and 18 abnormal scores.

Conclusion

A normal visual assessment at term age is a good predictor of normal visual and neurodevelopmental outcome at 12 months. An abnormal visual examination in the neonatal period was a less reliable prognostic indicator, infant should be reassessed at 3 months.     

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.     

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.     

Leptin determination in colostrum and early human milk from mothers of preterm and term infants

Background

Leptin is involved in the regulation of food intake and energy expenditure and is therefore important for growth and brain development. Analytical methods used for leptin measurement in human milk differ widely in the literature and yield varying results.

Aims

To compare different preparation methods for the analysis of leptin in human milk and to investigate the leptin levels in colostrum and mature human milk from mothers of preterm or term infants.

Methods

Mothers delivering a preterm (n = 37) or a term infant (n = 40) were recruited for a prospective study and were ask to collect breast milk on the 3rd and 28th day of lactation. Leptin, protein and fat concentrations were analysed. Clinical data of mother and child were recorded prospectively.

Results

Skim milk was most appropriate for leptin analysis. Human milk leptin concentrations did not differ between preterm and term human milk. In term milk, leptin concentration on day 28 was lower than on day 3 (p < 0.05). Milk leptin levels on the 3rd and 28th day were positively correlated with mothers' body mass index, but not with fat content in milk.

Conclusion

Skim milk was the most stabile preparation for leptin analysis. Preterm and term human milk contain leptin in equal concentrations. Human milk leptin depends on mothers' body mass index.     

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.     

Hypothalamic-pituitary-adrenal (HPA) axis function in 3-month old infants with prenatal selective serotonin reuptake inhibitor (SSRI) antidepressant exposure

Background

Prenatal exposure to stress and selective serotonin reuptake inhibitors (SSRIs) alter hypothalamic-pituitary-adrenal (HPA) stress reactivity in offspring, however, the effects of combined exposure to HPA activity in human infants is unknown.

Objective

To examine HPA basal levels and stress responsiveness in 3-month olds with prenatal exposure to SSRIs.

Methods

Salivary cortisol levels in infants of SSRI treated mothers (n = 31, mean exposure 230.2 ± 72.2 days) were compared with non-SSRI exposed (n = 45) infants in response to a challenge (infant-controlled habituation task) and under basal conditions in the late afternoon/early evening. Mode of feeding, to account for possible postnatal drug exposure via breast milk, as well as measures of pre and postnatal maternal mood, were included as covariates.

Results

Lower post-stress cortisol levels were observed in non-SSRI exposed/non-breastfed infants compared with non-SSRI exposed infants who were breastfed at 3 months of age. Stress reactivity patterns among SSRI exposed infants did not differ with mode of feeding. The cortisol reactivity slope (CRS) was significantly lower among non-SSRI exposed non-breastfed infants compared with non-SSRI exposed breastfed infants. Early evening basal cortisol levels were lower in SSRI exposed infants than in non-SSRI exposed infants, controlling for maternal mood and mode of feeding. Postnatal SSRI exposure (infant SSRI drug levels) via breast milk was not associated with stress or basal cortisol levels. Total cortisol, reflected by the AUC measure, did not differ significantly between exposure groups.

Conclusions

Prenatal SSRI exposure altered HPA stress response patterns and reduced early evening basal cortisol levels. Stress challenge HPA response differences only became apparent when the moderating effect of method of feeding was accounted for. These findings suggest an early “programming” effect of antenatal maternal mood, prenatal SSRI exposure and postnatal maternal care giving on the HPA system.     

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.     

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.     

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.     

Maternal vitamin B-12 and folate status during pregnancy and excessive infant crying

Background

The etiology of excessive infant crying is largely unknown. We hypothesize that excessive infant crying may have an early nutritional origin during fetal development.

Aims

This study is the first to explore whether (1) maternal vitamin B-12 and folate status during pregnancy are associated with excessive infant crying, and (2) whether and how maternal psychological well-being during pregnancy affects these associations.

Study design

Women were approached around the 12th pregnancy week to complete a questionnaire (n = 8266) and to donate a blood sample (n = 4389); vitamin B-12 and folate concentrations were determined in serum. Infant crying behavior was measured through a postpartum questionnaire (± 3 months; n = 5218).

Subjects

Pregnant women living in Amsterdam and their newborn child.

Outcome measures

Excessive infant crying, defined as crying ≥ 3 h/day on average in the past week.

Results

Multiple logistic regression analysis was performed for 2921 (vitamin B-12) and 2622 (folate) women.Vitamin B-12 concentration (categorized into quintiles) was associated with excessive infant crying after adjustment for maternal age, parity, ethnicity, education, maternal smoking and psychological problems (OR[95%CI]: Q1 = 3.31[1.48-7.41]; Q2 = 2.50[1.08-5.77]; Q3 = 2.59[1.12-6.00]; Q4 = 2.77[1.20-6.40]; Q5 = reference). Stratified analysis suggested a stronger association among women with high levels of psychological problems during pregnancy. Folate concentration was not associated with excessive infant crying.

Conclusions

First evidence is provided for an early nutritional origin in excessive infant crying. A low maternal vitamin B-12 status during pregnancy could, in theory, affect infant crying behavior through two potential mechanisms: the methionine-homocysteine metabolism and/or the maturation of the sleep-wake rhythm.