Increased surfactant protein-D levels in the airways of preterm neonates with sepsis indicated responses to infectious challenges.

AIM: Sepsis is multifactorial and potentially devastating for preterm neonates. Changes in surfactant protein-D (SP-D), phosphatidylcholine (PC) and PC molecular species during infection may indicate innate immunity or inflammation during sepsis. We aimed to compare these important pulmonary molecules in ventilated neonates without or with sepsis. METHODS: Endotracheal aspirates were collected from preterm neonates born at 23-35 weeks and admitted to the neonatal intensive care unit at the John Radcliffe Hospital, Oxford, UK, from October 2000 to March 2002. Samples were collected at one day to 30 days and analysed for SP-D, total PC and PC molecular species concentrations using enzyme-linked immunosorbent assay and mass spectrometry. RESULTS: We found that 8/54 (14.8%) neonates developed sepsis. SP-D (p < 0.0001), mono- and di-unsaturated PC were significantly increased (p = 0.05), and polyunsaturated PC was significantly decreased (p < 0.01) during sepsis compared to controls. SP-D:PC ratios were significantly increased during sepsis (p < 0.001), and SP-D concentrations were directly related to gestational age in neonates with sepsis (r2  = 0.389, p < 0.01). CONCLUSION: Increased SP-D levels and changes in PC molecular species during sepsis were consistent with direct or indirect pulmonary inflammatory processes. Very preterm neonates we able to mount an acute inflammatory innate immune response to infectious challenges, despite low levels of surfactant proteins at birth.

Changes in hearing threshold between 28 and 42 weeks of age in babies born at under 30 weeks of gestation.

AIM: This study aimed to describe changes in hearing thresholds in babies born below 30 weeks of gestation at 28-42 weeks of postconceptional age, detect differences between gestational ages and explore the prevalence of hearing impairment. METHODS: The threshold of brainstem auditory evoked response (BAER) was obtained longitudinally at 28-42 weeks of postconceptional age in 71 babies born at 23-29 weeks of gestation. RESULTS: The BAER threshold was 28 decibels above normal hearing level (dB nHL) at 28 weeks of postconceptional age and decreased to 13 dB nHL at 39-42 weeks. The threshold was slightly higher in babies born at 23-26 weeks of gestation than in those born at 27-29 weeks at most postconceptional ages studied. From 28 to 36 weeks, the threshold decreased at 0.98 dB/week. At term, BAER threshold elevation (>20 dB nHL) occurred in 12 (16.9%) of the 71 babies. CONCLUSION: The hearing threshold of babies born at 23-29 weeks of gestation decreased from 28 dB at 28 weeks of postconceptional age to 13 dB at 42 weeks. There were no major differences between gestational ages. During the preterm period, the threshold changed at around 1 dB/week. At term, one in six babies had hearing impairment.

Preterm heart in adult life: cardiovascular magnetic resonance reveals distinct differences in left ventricular mass, geometry, and function.

BACKGROUND: Preterm birth leads to an early switch from fetal to postnatal circulation before completion of left ventricular in utero development. In animal studies, this results in an adversely remodeled left ventricle. We determined whether preterm birth is associated with a distinct left ventricular structure and function in humans. METHODS AND RESULTS: A total of 234 individuals 20 to 39 years of age underwent cardiovascular magnetic resonance. One hundred two had been followed prospectively since preterm birth (gestational age=30.3±2.5 week; birth weight=1.3±0.3 kg), and 132 were born at term to uncomplicated pregnancies. Longitudinal and short-axis cine images were used to quantify left ventricular mass, 3-dimensional geometric variation by creation of a unique computational cardiac atlas, and myocardial function. We then determined whether perinatal factors modify these left ventricular parameters. Individuals born preterm had increased left ventricular mass (66.5±10.9 versus 55.4±11.4 g/m(2); P<0.001) with greater prematurity associated with greater mass (r = -0.22, P=0.03). Preterm-born individuals had short left ventricles with small internal diameters and a displaced apex. Ejection fraction was preserved (P>0.99), but both longitudinal systolic (peak strain, strain rate, and velocity, P<0.001) and diastolic (peak strain rate and velocity, P<0.001) function and rotational (apical and basal peak systolic rotation rate, P =0.05 and P =0.006; net twist angle, P=0.02) movement were significantly reduced. A diagnosis of preeclampsia during the pregnancy was associated with further reductions in longitudinal peak systolic strain in the offspring (P=0.02, n=29). CONCLUSIONS: Individuals born preterm have increased left ventricular mass in adult life. Furthermore, they exhibit a unique 3-dimensional left ventricular geometry and significant reductions in systolic and diastolic functional parameters. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01487824.

Brainstem auditory response findings in preterm infants after necrotizing enterocolitis.

AIM: To examine brainstem auditory function and detect any abnormality at term in preterm infants after neonatal necrotizing enterocolitis (NEC). METHODS: Brainstem auditory evoked response (BAER) was recorded at 21/sec and 60 dB nHL in 37 preterm infants who had NEC. The data obtained at term equivalent age were analyzed and compared with those in normal term infants. RESULTS: The threshold of BAER in infants after NEC, though slightly elevated, did not differ significantly from that in the controls. The latencies of waves I and III were slightly longer than in the controls, without any statistical significance. However, wave V latency was prolonged and differed significantly from the controls (p < 0.01). I-V interpeak interval was also prolonged (p < 0.05). The data point distribution of wave V latency and I-V interval was higher in the infants after NEC than in the controls. The amplitudes of BAER wave components in the infants after NEC did not differ significantly from those in the controls. CONCLUSION: Preterm infants after NEC have no major abnormality in peripheral auditory function. However, neural conduction in the brainstem auditory pathway is abnormal, suggesting that NEC adversely affects brainstem auditory conduction.

Cochlear function in 1-year-old term infants born with hypoxia-ischaemia or low Apgar scores.

AIM: To examine the influence of perinatal hypoxia-ischaemia (HI) or low Apgar scores on distortion product otoacoustic emissions (DPOAEs) in infants at 1 year and detect any postnatal changes. METHODS: Eighty-eight term infants born with perinatal HI or low Apgar scores alone were recruited at 1 year of age. The ears with type A tympanogram (normal) were studied with DPOAEs at 10 frequencies between 0.5 kHz and 10 kHz. RESULTS: DPOAE pass rates were decreased at all frequencies 1-10 kHz, particularly 1 and 2 kHz in both infants born with HI and those with low Apgar scores (χ(2) = 3.80-15.09, P < 0.05-0.01). Overall pass rates in the two groups were also decreased (X(2) = 10.78 and 12.12, P < 0.01 and 0.01). No marked differences were found between infants born with HI and those with low Apgar score. Compared with those recorded at 1 and 6 months, DPOAE pass rates at 1 year were increased slightly in infants born with HI, but showed no marked changes in those born with low Apgar scores. CONCLUSIONS: DPOAE pass rates, mainly at 1 and 2 kHz, were decreased at 1 year in infants born with perinatal HI and low Apgar scores, suggesting a relative poor cochlear function. Further studies are needed to ascertain the hearing acuity.

Brainstem auditory response findings in late preterm infants in neonatal intensive care unit.

AIM: To examine brainstem auditory function at term in late preterm infants admitted to neonatal intensive care unit (NICU). METHODS: Fifty-two preterm infants, born at 33-36 week gestation, were recruited in an NICU and were studied at term using brainstem auditory evoked response (BAER). RESULTS: Compared with normal term infants, BAER wave V latency in the NICU preterm infants was increased at 51 and 91/sec (p<0.05, 0.05). Intervals of III-V and I-V were increased at all 21, 51 and 91/sec clicks (p<0.05-0.01), which was more significant at higher than lower rates. Interval ratio of III-V/I-III was increased significantly at 51 and 91/sec (p<0.05 and 0.01). Wave I and III latencies and I-III interval did not differ significantly from normal controls at any click rates. All amplitudes of waves I, III and V amplitude tended to be reduced at higher rates, while wave I amplitude was reduced significantly at 91/sec clicks. CONCLUSION: There were BAER abnormalities in the NICU late preterm infants, suggesting compromised brainstem auditory function. Compared with a basically normal BAER in low-risk late preterm infants previously reported, the abnormalities suggest that perinatal problems or complications adversely affect the late preterm auditory brainstem.

Relative maturation of peripheral and central regions of the human brainstem from preterm to term and the influence of preterm birth.

Relative maturation of peripheral and central regions of the neonatal brainstem was studied using brainstem auditory evoked responses in 174 healthy preterm infants (gestational age 30-36 wk). From 30- to 42-wk postconceptional age (PCA), I-III and III-V intervals shortened with increasing age. It was difficult to detect any apparent differences in maturational rate between the two intervals. However, III-V/I-III interval ratio decreased with increasing age, indicating that from preterm to term III-V interval shortens more than I-III interval. During term period (37- to 42-wk PCA), I-III interval was similar to term controls, but III-V interval was significantly longer and III-V/I-III interval ratio was significantly greater than controls at 37- to 38-wk PCA and 39-40 wk PCA and was the same as controls at 41-42 wk. Therefore, from 30- to 42-wk PCA maturation of central regions of the brainstem, reflected by III-V interval, is relatively faster than peripheral regions, reflected by I-III interval which seems to be already more mature than III-V interval before 30 wk. Maturation in central regions in preterm infants is relatively delayed at early term, but "catches-up" later, whereas peripheral regions already reach normal level of maturation at early term. Preterm birth slightly delays early maturation of central brainstem regions.

Age-related changes in BAER at different click rates from neonates to adults.

AIM: To characterize age-related changes in brainstem auditory evoked response (BAER) at different click rates from neonates to adults. METHODS: BAER was studied at repetition rates 11-91/sec of clicks in 165 normal neonates and children of various ages and 29 young adults. RESULTS: BAER wave latencies and inter-peak intervals increased linearly with increasing click rate at all ages. The younger was the age, the greater were BAER click rate-dependent changes. At 9 months and younger, the slopes of latency- and interval-rate functions were all significantly greater than in the adults (all p < 0.01). The slopes of wave I latency- and I-III interval-rate functions at 1-2 years and older were similar to those in adults. The slopes of wave III and V latency-rate functions and I-V and III-V interval-rate function at 3-4 years and older did not differ significantly from those in adults. CONCLUSION: BAER is affected by stimulus rate more in younger children than in the older. Adult-like rate-dependent changes are reached at 1-2 years for wave I latency and I-III interval, and 3-4 years for wave III and V latencies and I-V and III-V intervals. Our BAER data at different click rates provide normal references for subjects of various ages.

No close correlation between brainstem auditory function and peripheral auditory threshold in preterm infants at term age.

OBJECTIVE: To determine whether central auditory function in preterm infants correlates with peripheral auditory threshold and whether threshold elevation affects central auditory function. METHODS: Brainstem auditory evoked response (BAER) was recorded at term age using maximum length sequence (MLS) with 91-910/s clicks in 133 preterm infants (gestation 28-36 weeks). The relationship between MLS BAER variables and BAER threshold was analyzed. RESULTS: The latencies and amplitudes of all MLS BAER waves correlated significantly with BAER threshold. However, no correlation was found between MLS BAER interpeak intervals and BAER threshold at any rates. In preterm infants with a threshold >20dB nHL (n=30), MLS BAER wave latencies were all significantly longer than in those with a threshold < or = 20dB nHL (n=103) (P<0.01-0.001). MLS BAER wave amplitudes were significantly smaller than in those 20dB nHL (P<0.05-0.001). However, no interpeak intervals differed significantly between the two groups of infants. V/I amplitude ratio was similar in the two groups. These findings were true of all click rates. Click rate-dependent changes in MLS BAER of the preterm infants with an elevated BAER threshold are generally similar to those with a normal threshold. CONCLUSIONS: Brainstem auditory function does not closely correlate with peripheral auditory threshold at term in preterm infants. Elevation in peripheral threshold due to middle ear disorders does not significantly affect functional status of the auditory brainstem. SIGNIFICANCE: Short term peripheral conductive auditory abnormality does not significantly affect the immature central auditory function.

Sustained depression of brainstem auditory electrophysiology during the first months in term infants after perinatal asphyxia.

OBJECTIVE: To gain further insights into the pathophysiological processes of neuronal impairment in neonatal brainstem after perinatal asphyxia. METHODS: Maximum-length sequence brainstem auditory-evoked response (MLS BAER) was recorded with clicks at 91, 227, 455 and 910/s on days 1, 3, 5, 7, 10, 15 and 30 after birth in 108 term infants who suffered perinatal asphyxia. Wave amplitude variables in the MLS BAER were analysed in detail at 40 dB above BAER threshold in 86 infants who had no peripheral hearing impairment. RESULTS: On day 1 the amplitudes of MLS BAER waves I, III and V were all reduced significantly at all click rates, especially at higher ones (91-910/s, ANOVA P<0.05-0.001). On day 3 these amplitudes were reduced further. On days 5 and 7, the amplitude reduction persisted and did not show any significant further changes. On days 10 and 15 the reduced amplitudes were increased slightly. On day 30 all amplitudes were still reduced significantly (P<0.05-0.0001). During the first month, the reduction of wave amplitudes was more significant for the later MLS BAER components than for the earlier ones, and occurred most significantly at 455 and 910/s clicks. By comparison, the amplitude reduction in conventional BAER was much less significant. CONCLUSIONS: During the first month after perinatal asphyxia the amplitudes of MLS BAER waves were reduced significantly and persistently, which was more significant at higher rates of clicks than at lower rates. The reduction is much more persistent than the increase in wave latencies and intervals we previously reported. SIGNIFICANCE: There is sustained depression of brainstem auditory electrophysiology, indicating neuronal damage of the auditory brainstem, in infants after perinatal asphyxia. This may have important clinical implications.

Brainstem auditory outcomes and correlation with neurodevelopment after perinatal asphyxia.

We used brainstem auditory-evoked responses and neurodevelopmental assessment to detect abnormalities and correlations between such responses and neurodevelopmental outcomes in 78 children (aged 4-12 years) who survived perinatal asphyxia. Twenty children had brainstem auditory-evoked response abnormalities, including increased threshold, reduced wave V amplitude, decreased V/I amplitude ratio, and prolonged I-V interval. Thirty-seven exhibited neurodevelopmental deficits, including cerebral palsy and developmental delay. The remaining 41 exhibited no deficits. Brainstem auditory-evoked response abnormalities were evident in 15 of 37 (40.5%) children with neurodevelopmental deficits, but in only 5 of 41 (12.2%) with no deficits, which differed significantly (chi(2) = 8.2, P < 0.05). The sensitivity, specificity, positive predictive value, and false-negative rate of brainstem auditory-evoked responses to reflect neurodevelopmental outcomes were 40.5%, 87.8%, 75.0%, and 59.5%, respectively. These findings suggest that in children who survive perinatal asphyxia, brainstem auditory impairment occurs more frequently in those with versus those without neurodevelopmental deficits. Brainstem auditory-evoked responses display a moderate correlation with clinically determined neurodevelopmental outcomes. Despite limitations, brainstem auditory-evoked response is valuable for assessing auditory and neurodevelopmental outcomes after perinatal asphyxia.

Orientation and motion-specific visual cortex responses in infants born preterm.

Orientation-specific cortical responses develop earlier in infancy than motion-specific responses. The maturation of orientation-reversal and direction-reversal visual evoked potentials was evaluated in 17 healthy, low risk, preterm infants (born <32 weeks gestation), compared with a group of 26 infants born at term. Both groups were studied at a corrected age of 2-4 months. The age function and magnitude of the orientation-reversal responses was similar in the two groups. Direction-reversal responses across the age range, however, were smaller in the preterm infants, suggesting a delayed maturation of motion processing. Reasons for the vulnerability of motion processing are discussed; the results may reflect anomalies of white matter development in preterm infants that are undetected by ultrasonography.

Sub-optimal function of the auditory brainstem in term infants with transient low Apgar scores.

OBJECTIVES: To assess functional integrity of the auditory brainstem in neonates with transient low Apgar scores. METHODS: Forty-two term infants were studied with brainstem auditory evoked response (BAER) using the maximum length sequence during the first month of life. All had transient low Apgar scores but no clinical signs of hypoxic-ischaemic encephalopathy (HIE). RESULTS: The latencies of BAER waves I and III in these infants were similar to those of age-matched normal controls at all click rates (91/s, 227/s, 455/s and 910/s) during the period studied. Wave V latency was increased at 910/s on day 1 (P<0.01), but did not differ from that in the controls on any other days. I-V interval was increased significantly at 455/s and 910/s on day 1 (P<0.01 and 0.001) and day 3 (P<0.05 and 0.01). On days 5 and 7, BAER wave latencies and intervals were similar to those in the controls. On day 30, all latencies and intervals reached the values in the controls. No abnormalities were seen in BAER wave amplitude variables on any days. CONCLUSIONS: Neonates with transient low Apgar scores but without HIE had a significant increase in I-V interval at very high click rates on the first three days of life. SIGNIFICANCE: Brainstem auditory function is sub-optimal during the first few days in neonates with transient low Apgar scores.

Brainstem auditory evoked responses in very low birthweight infants with chronic lung disease.

UNLABELLED: Very low birthweight (VLBW) infants who had prolonged oxygen dependence due to chronic respiratory problems, typically neonatal chronic lung disease (CLD), are at high risk of neurodevelopmental impairment. To assess the effect of CLD on neonatal auditory function we studied brainstem auditory evoked response (BAER) in VLBW infants who suffered CLD but no other major perinatal complications or problems. At 37-42 week postconceptional age, the latencies of waves I, III and V in CLD infants were all significantly longer than in normal term infants (all p<0.001). The differences between CLD infants and the term controls were greater for the later waves than for the earlier waves. Abnormally prolonged wave latency (>2.5 SD of the mean measurement) was seen in 7 (21.2%) CLD infants for wave I, suggesting peripheral auditory impairment, 8 (24.2%) for wave III and 14 (42.4%) for wave V. I-V interval in CLD infants was significantly longer than in the term controls (p<0.001). Seven (21.2%) infants had abnormally prolonged I-V interval, suggesting brainstem or central auditory impairment. Of these infants, 2 had both prolonged wave latencies and prolonged I-V interval, suggesting both peripheral and central auditory impairment. Similar abnormalities were found in CLD infants when compared with the BAER in birthweight- and age-matched healthy VLBW infants without CLD. CONCLUSION: Neonatal auditory function is impaired, both peripherally and centrally, at term age in VLBW infants who suffer neonatal CLD.

Brain-stem auditory function in very preterm infants with chronic lung disease: delayed neural conduction.

OBJECTIVE: To examine brain-stem auditory function at term in very preterm infants who suffered chronic lung disease (CLD). METHODS: Brain-stem auditory evoked response (BAER) was recorded at term with clicks in 25 very preterm infants with CLD and no concomitant other major perinatal problems. RESULTS: Compared to those in normal term controls, BAER wave V latency and I-V and III-V interpeak intervals in the CLD infants increased significantly (ANOVA P<0.01-0.001). III-V/I-III interval ratio also increased significantly (P<0.01). The latencies of waves I and III did not differ significantly from the controls. However, no abnormalities were found in BAER wave amplitudes. These BAER findings, obtained at 21/s clicks, were also seen at the rates 51 and 91/s, although the increase in III-V interval tended to be more significant. Click rate-dependent changes in BAER variables in the CLD infants were generally similar to the controls, with slight differences. CONCLUSIONS: BAER components, mainly reflecting central auditory function, increased significantly. The increase in wave V latency and I-V interval is due to the increase in III-V interval. SIGNIFICANCE: Neural conduction in the more central portion of the brain-stem auditory pathway is delayed and thus brain-stem auditory function is impaired in CLD infants.

Brainstem auditory evoked response in neonatal neurology.

Over the last three decades, the brainstem auditory evoked response (BAER) has been used to assess functional integrity and development of the auditory system and the brain in conditions that affect the brainstem auditory pathway. As a non-invasive objective test, BAER is particularly suitable in very young or sick infants. It is the major tool to detect hearing impairment in high-risk infants, and a component in universal hearing screening. BAER is also a valuable adjunct to detect neurological impairment in many developmental disorders and functional abnormalities in a range of neurological diseases. The maximum length sequence (MLS) technique has recently been incorporated into neonatal BAER study. Recent results indicate that the MLS has the potential to improve the diagnostic value of BAER in some clinical situations, although the wider utility of this relative new technique remains to be further explored.

Changes in BAER amplitudes after perinatal asphyxia during the neonatal period in term infants.

We recorded serially brainstem auditory evoked response (BAER) during the neonatal period in term infants who suffered perinatal asphyxia. The amplitudes of BAER components was analysed at 40 dB above BAER threshold of each subject who had a threshold

Does peripheral auditory threshold correlate with brainstem auditory function at term in preterm infants?

CONCLUSION: Peripheral auditory threshold does not correlate with brainstem auditory function in preterm infants. Infants with peripheral auditory abnormality seem not to be necessarily more prone to brainstem auditory abnormality than those without the elevation, although further studies are needed in a larger number of subjects. OBJECTIVE: To investigate whether peripheral auditory threshold correlates with brainstem auditory function in preterm infants and shed light on whether preterm infants with threshold elevation are prone to central auditory abnormality. PATIENTS AND METHODS: Brainstem auditory evoked response (BAER) was recorded with clicks at term in preterm infants (gestation 28-36 weeks). Analysis of correlation was made between BAER threshold and various BAER components. BAER data were compared between preterm infants with thresholds < or = 20 dB nHL (n = 113) and those > 20 dB (n = 32). RESULTS: Although BAER threshold correlated significantly with BAER wave latencies and amplitudes, the threshold did not correlate significantly with I-V, I-III and III-V intervals. No significant differences were found between preterm infants with BAER thresholds < or = 20 dB and those > 20 dB in I-V, I-III intervals, although III-V was longer in the infants with thresholds > 20 dB nHL (p < 0.05).

Distortion product otoacoustic emissions in term infants with a low Apgar score.

CONCLUSION: Term infants with a low Apgar score have cochlear impairment, mainly at the frequencies 1-3 kHz. Compared with infants with both a low Apgar score and hypoxic-ischaemic encephalopathy we reported before, the impairment is less severe. OBJECTIVE: To detect any peripheral impairment of cochlear origin in infants with a low Apgar score. SUBJECTS AND METHODS: Fifty-four term infants with a low Apgar score at 1 and/or 5 min but without clinical signs of hypoxic-ischaemic encephalopathy were recruited. Distortion product otoacoustic emissions (DPOAEs) were recorded with the f2 primary tone at 10 frequencies (0.5-10 kHz) on days 3-5 and 1 month after birth. RESULTS: On days 3-5 DPOAE pass rates at most frequencies tended to be decreased, and were significant lower than those in normal term controls at 1, 2, 3, 5, 6 and 10 kHz (chi2=4.49-40.31, p<0.05-0.005). The greatest difference occurred at 1 kHz; 18.5% failed the DPOAE test and this was significantly higher than in the controls (4.3%, chi2=7.65, p<0.01). At 1 month the DPOAE pass rate at most frequencies did not show any significant improvement. The overall failure rate (14.8%) did not differ significantly from that on days 3-5.

Comparison of maturational process of hearing threshold in early life between at-risk and low-risk preterm infants.

AIM: To detect any abnormality in the maturational process of hearing threshold during the early life in at-risk preterm infants. STUDY DESIGN: The threshold of brainstem auditory evoked response was recorded and analyzed longitudinally from 30 to 42weeks of postconceptional age in 357 at-risk infants born at 23-36weeks of gestation. The results were compared with those in 82 low-risk infants born at 30-42weeks at various postconceptional ages. RESULTS: From 31 to 42weeks, the response threshold in the at-risk infants was consistently slightly higher than that in the low-risk infants. No statistically significant difference was found between the two groups of infants at any designated postconceptional ages. The threshold in the at-risk infants born at 23-29weeks of gestation tended to be higher than those born at 30-36weeks at various postconceptional ages, but the difference did not reach statistical significance. There was also no significant difference in the slope of BAER threshold-age function between the at-risk infants, irrespective of gestational ages, and the low-risk infants. CONCLUSION: During the early life, hearing threshold in at-risk preterm, mainly very preterm, infants is marginally elevated, but the maturational process of the threshold is generally similar to that in low-risk infants, without notable abnormality.