Chronic lung disease in very low birthweight infants: A prospective population-based study

A prospective population-based study of chronic lung disease among all very low birthweight infants (birthweight 500-1499 g) born in New Zealand in 1986 is reported. Of 413 of these infants admitted to neonatal units, 355 (86%) survived to 28 days. An additional 50 infants were recorded as liveborn but died in the labour ward or other place of birth. Both observed survival and survival adjusted for birthweight, gestation and gender were significantly (P less than 0.05) better in larger centres. Oxygen requirement was assessed at 28 days of age, 36 weeks equivalent gestation and 84 days of age, when 38.6, 23.1 and 13.8% of infants, respectively, were being treated with oxygen. To examine the joint effects of predictor variables on oxygen requirement at each age, the data were analysed using multiple logistic regression methods. At 28 days, lower birthweight, shorter gestation, respiratory distress syndrome (all P less than 0.0001), and gender and hospital principally caring for the infant (both P less than 0.05) were significantly associated with treatment with oxygen. In comparison with other studies, New Zealand appears to have a relatively high rate of chronic lung disease. We speculate that a contributing factor may be the small size of some regional neonatal units.     

Usefulness of an early neurofunctional assessment in predicting neurodevelopmental outcome in very low birthweight infants

OBJECTIVE: To evaluate whether early neurofunctional assessment may be useful in predicting neurodevelopmental outcome in children of very low birth weight (VLBW). DESIGN: Observational longitudinal study. SETTINGS: Northern Italy. PATIENTS: A total of 250 VLBW children (129 boys, 121 girls) born consecutively 1996-1999. MAIN OUTCOME MEASURES: Neurodevelopment at 36 months of chronological age, classified in accordance with the classification of Tardieu and the International classification of functioning. RESULTS: Of the infants exhibiting normal neurodevelopment (n = 183) or major dysfunction (n = 17) at 3 months of corrected age, 72% and 94% respectively did not change their score during the study. Minor dysfunctions at 3 months of corrected age were transient in 17 (34%) children. After adjustment for neonatal variables, neurodevelopment at 3 months of corrected age remained predictive of dysfunction at 36 months (odds ratio = 4.33, 95% confidence interval 2.05 to 9.12). If the results for the normal and minor dysfunction groups were pooled, the predictive qualities of the 3 month neurofunctional assessment were: sensitivity 0.5, specificity 0.99, positive predictive value 0.94, negative predictive value 0.93. CONCLUSION: Early neurofunctional evaluation may be useful in predicting later neurodevelopmental outcome in VLBW children.     

The long-term neurodevelopmental outcome for very low birthweight (VLBW) infants with 'dystonic' signs at 4 months of age

Abstract  As very low birthweight (VLBW) infants are at a high risk of developmental handicap, it is important to establish predictors of long-term adverse outcome at an early age so that early intervention can be instituted. Longitudinal neurodevelopmental assessments were performed in 107 VLBW infants at 1,4, 8 and 12 months corrected age. Eighteen were diagnosed as 'dystonic' at 4 months of age.
This study compared the outcomes at 4 and 6 years for 15 of the 18 dystonic with 75 of the 89 non-dystonic VLBW infants, respectively. At 9 years of age, nine dystonic and 54 non-dystonic infants were assessed on the Rutter Behaviour Questionnaire. Dystonic children had a lower mean General Cognitive Index (GCI; P= 0.001) and a higher incidence of disability as measured by the Burns Neuro-Sensori-Motor Developmental Assessment Scale (P = 0.0005) and Kitchen disability grading (P = 0.001). Even if the minor neurological aberrations of the premature dystonia syndrome in VLBW infants abate by one year of life, these infants still constitute a high-risk group for subsequent neurodevelopmental disability and therefore require close observation and probably early intervention.     

Neonatal jaundice in 'healthy' very low birthweight infants

The daily bilirubin levels during the first week of life in 94 premature very low birthweight (VLBW, < 1500g) relatively 'healthy' infants were determined. Mean daily bilirubin values peaked on the fourth day of life at 188.1 μmol/l (s.e.m. = 5.3). Twenty-eight infants developed hyperbilirubinaemia (bilirubin > 260 μmol/l), at which time they were exposed to phototherapy. When individual peak bilirubin values were evaluated, the overall peak value was 213.9 μmol/l (s.e.m. = 5.1) occurring at 4.81 days (s.e.m. = 0.11), although the value is most likely an underestimate, since the 28 pre-phototherapy values were not truly peak values. Seventy-six (81%) infants experienced bilirubin levels > 170 μmol/l. The method of delivery apparently had no impact on the bilirubin levels.
All the infants remained well and progressed satisfactorily.'Healthy' VLBW infants experience a much greater incidence and severity of neonatal jaundice than mature infants with the same clinical status.     

Chronic respiratory failure after acquired cytomegalovirus infection in a very low birthweight infant

The case of a female infant who developed chronic respiratory failure after an acquired cytomegalovirus (CMV) infection is presented here. She was a very low birthweight (VLBW) infant and was free from oxygen supplement until 2 months after birth. Interstitial pneumonia occurred at 2 months of age, and her respiratory condition gradually deteriorated. A chest roentgenogram at 4 months revealed hyperinflation and reticular shadow, similar to that of severe chronic lung disease (CLD) in preterm infants. She was mechanically ventilated because of progressive respiratory deterioration, and oxygen dependency continued for 5 months after extubation. There are several previous reports of CMV pneumonia in term neonates or infants. However, there appears to be no published report on the pulmonary sequelae of CMV pneumonia in VLBW infants. The present case seems to indicate that acquired CMV pneumonia in VLBW infants causes chronic respiratory failure even when mechanical ventilation is not administered, and this respiratory failure is very similar to CLD in clinical symptoms and chest roentgenogram.     

Chest radiograph abnormalities in very low birthweight survivors of chronic neonatal lung disease

Objective : To determine whether the neonatal chest radiograph (CXR) at 28 days in very low birthweight (VLBW) infants who develop chronic neonatal lung disease (CNLD) predicts oxygen therapy duration or CXR abnormalities in early childhood. Also, to assess the inter-observer reliability of the radiologists scoring the CXR.
Methodology : Clinically well survivors of CNLD ( n = 46) had neonatal CXR scored (mean age 28.5 days) and compared with current CXR (mean age 40 months). The CXR were scored independently and 'blindly' by two paediatric radiologists using a standardized scoring system (range 0-10).
Results : There was no correlation between neonatal CXR scores and current CXR scores for either radiologist. There was no association between CXR severity scores and duration of oxygen therapy for either neonatal or current CXR. Radiologist A scored the current CXR significantly more abnormal than radiologist B [medians (range): 3 (1-6) vs 1 (0-5), P <0.001] with reasonable correlation ( r = 0.593, P <0.005) but worse than chance agreement (kappa = - 0.034). The median scores for the neonatal CXR were similar [1.5 (0-8) vs 2 (0-8), P = 0.789] and again there was good correlation ( r = 0.760, P <0.0005) although poor individual agreement (kappa = 0.243) between radiologists.
Conclusions : Follow-up CXR abnormalities in VLBW infants with CNLD are usually minor and are not predictive of the duration of oxygen therapy that will be required nor of the CXR appearance in early childhood. Considerable inter-observer variation exists in the interpretation of the CXR in CNLD.     

Audiological evaluation of very low birthweight infants

A population of consecutively surviving very low birthweight (VLBW) infants comprising 41 infants (24 female) birthweight less than 1000 g and 108 infants (63 female) birthweight 1000-1500 g received detailed audiological evaluation. The audiological test battery comprised auditory brainstem evoked response (ABR) prior to hospital discharge, behavioural audiometry and tympanometry at 8-12 months and monitoring as necessary. The ABR results were interpreted with reference to a normative group of 36 full-term infants (birthweight 2.4-4.5 kg). Of the 142 VLBW infants completing audiological evaluation, one (0.7%) had evidence of moderate-severe high frequency sensorineural hearing loss, 83 (58.5%) evidence of conductive dysfunction (18 severe, 42 moderate and 23 mild) and only 58 (40.8%) normal hearing. The 19 infants with severe auditory impairment were more likely to have suffered moderate-severe apnoea, greater than or equal to two courses of mechanical ventilation, prolonged oxygen therapy and recurrent upper respiratory tract infections in the first year of life than infants without severe impairment (P less than 0.05). Because of the incidence of conductive pathology, difficulties occurred when attempting to compare ABR status at 36-42 weeks postmenstrual age with peripheral hearing status at 8-12 months as assessed by visual reinforcement orientation audiometry (VROA) and impedance audiometry. The most useful ABR test parameters as screening measures of peripheral auditory status were Wave I-III-V morphology, wave V threshold levels and wave V absolute latency values when used in combination as a test battery.(ABSTRACT TRUNCATED AT 250 WORDS)     

Distribution of plasma Vitamin E levels in supplemented very low birthweight infants

Abstract The distribution of plasma Vitamin E (VE) was determined in 25 very low birthweight (VLBW) infants who were supplemented with 100 mg/kg per day of α-tocopherol acetate, given intragastrically. Their mean birthweight was 917 g and mean gestational age was 28 weeks. Mean plasma VE levels after 1 and 6 weeks' supplementation were 2.7 mg/dL (s.e.m. = 1.0) and 6.4 mg/dL (s.e.m. = 1.4), respectively (the difference was not significant). There was wide variability in plasma VE levels in these infants despite being on an identical dose of tocopherol. Plasma VE was < 0.5 mg/dL in 12% of samples, 0.5–3.0 mg/dL in 32%, 3.1–5.0 mg/dL in 18%, and 5.1–20 mg/dL in 38%. Fifteen of the 25 infants had at least one level in the range which has been associated with an increased incidence of septicaemia and necrotizing enterocolitis (> 5.0 mg/dL).
These data suggest that if a policy of VE supplementation for VLBW infants is chosen, monitoring of plasma VE levels appears necessary so that the dosage can be adjusted in order to maintain plasma VE within the optimal range. This study's dosage regimen of supplementing infants with 100 mg/kg per day of VE was associated with a high incidence of elevated plasma VE levels and it is concluded that it is not advisable to use such large doses of VE in the premature newborn.     

Late-onset neutropenia in very low birthweight infants

Aim : To evaluate the incidence and duration of late-onset neutropenia (defined as an absolute neutrophil count (ANC) <1500 mm⁻³ at a postnatal age of >3 wk) in a population of infants with birthweight <2000 g, and to determine whether copper deficiency, a possible cause of both anemia and neutropenia, may be associated with this complication. Methods : Complete blood cell count and differential were assessed in 247 low (LBW) and very low birthweight (VLBW) infants who were discharged after 3 wk of life. In neutropenic infants plasma copper and ceruloplasmin levels were also measured. Results : Late-onset neutropenia was detected in 11 out of 147 VLBW infants (7.5%) and in 7 out of 127 LBW infants (5.5%). A neutrophil count of <1000 mm⁻³ was observed in 14 infants (5.1%). A significantly lower gestational age was found in neutropenic infants compared with non-neutropenic infants. In neutropenic infants ANCs were significantly correlated with hemoglobin and hematocrit. In addition, a significant negative correlation was found between neutrophil and reticulocyte counts. Plasma copper concentration was significantly correlated with birthweight. Oral copper sulfate was administered to infants with plasma copper concentration <50 μg dl⁻¹, and did not seem to affect ANC, hemoglobin, hematocrit or reticulocyte counts.
Conclusion : Late-onset neutropenia appears to be a benign condition that is not associated with any particular complication and does not require specific treatment. Reference ranges after the early neonatal period and during the first few months of life in LBW and VLBW infants should probably be set at lower values.     

Necrotizing enterocolitis in very low birthweight infants: a four-year experience

Fifty (13%) of 375 infants who weighed 1500 g or less at birth had necrotizing enterocolitis (NEC). Haematological changes suggestive of sepsis occurred in 83% and positive bacteriological cultures were found in 38%, the most common organism isolated being Clostridium perfringens. Complications included intestinal perforation in six patients and recurrence of NEC in five, of whom one subsequently developed an intestinal stricture. Five of the eight nursery deaths were secondary to peritonitis and overwhelming sepsis from NEC. In spite of the discontinuation of milk feeds for prolonged periods, satisfactory caloric intake and weight gain were achieved with parenteral nutrition in the survivors. Of the 41 long-term survivors, six (15%) were found to have a disability at 2 years of ago, corrected for prematurity, compared with 48 (20%) of 241 very low birthweight survivors from the same study period who did not have NEC. None had evidence of gastrointestinal dysfunction. Six (15%) children remained below the 10th percentile for both weight and height. This study showed that early diagnosis and therapy for NEC in very tow birthweight infants were associated with a favourable short- and long-term outcome.     

Outcome of very low birthweight infants who required prolonged hospitalization

Abstract Over a 4 year study period, 294 infants with a birthweight ≤ 1500 g survived their initial hospitalization; 103 (35%) were discharged after a gestational age of 40 weeks. The postdischarge infant mortality was significantly higher in those with prolonged initial hospitalization compared with the remaining survivors (6% vs 1%). During the first 2 years, significant infections were found in 66% and rehospitalization in 54% of the children who had prolonged initial hospitalization. At 2 years, 34% were below the 10th centile for weight as were 39% for height; head circumferences were normal. Major disability (27% vs 15%) and developmental delay (13% vs 4%) were significantly more common in survivors with prolonged initial hospitalization compared with the remaining survivors. The study demonstrated the continuing toll of perinatal morbidity among very low birthweight infants who required prolonged hospitalization and emphasized the need for comprehensive medical and social support, not only during their initial hospitalization, but also after discharge.     

α-Fetoprotein levels in fullterm and very low birthweight infants

Plasma α-fetoprotein (α-FP) levels were determined in fullterm and very low birthweight (VLBW) infants in the first week of life and serially in a cohort of VLBW infants for the first 24 weeks after delivery. A rapid decline in α-FP levels was observed in both the fullterm and VLBW infants initially. Beyond 2 weeks of age, there was a gradual, linear decline until 6 weeks, followed by a more rapid period of decline from 6 to 16 weeks. The decline in the ensuing weeks demonstrated an asymptotic pattern. The half-life of α-FP was 7.5 days in the first week of life in both fullterm and preterm infants, 28.7 days from 2 to 6 weeks of life and 11.9 days from 6 to 16 weeks of life in VLBW Infants.     

Impact of intrauterine growth restriction on neurodevelopmental and growth outcomes in very low birthweight infants

The impact of intrauterine growth restriction (IUGR) in very low birthweight preterm infants weighing ≤ 1250g was determined by comparing longitudinal growth and neurodevelopmental outcome to an adjusted age of 36 months in 52 intrauterine growth restricted children, with 55 birthweight-matched and 56 gestational age-matched children. None of these children had chromosomal anomalies, congenital infections, or major congenital malformations. Gestational ages of intrauterine growth restricted, birthweight- and gestational age-matched infants were 30 (± 3), 26 (± 2), 29 (± 2) weeks; birthweights were 842 (± 232), 872 (± 201) and 1094 (± 142) g, respectively. Intrauterine growth restricted children had fewer complications during initial hospitalization ( p < 0.05), and had lower weights and head circumferences at follow-up ( p > 0.05). No significant differences were present in major neurodevelopmental disabilities between the intrauterine growth restricted and two comparison groups. Persistence of microcephaly was associated with adverse neurodevelopmental outcome.     

Prolonged low-dose indomethacin therapy for patent ductus arteriosus in very low birthweight infants

To determine the efficacy and side-effects of prolonged low-dose indomethacin therapy in very low birthweight (VLBW; <1500 g) infants with a haemodynamically significant patent ductus arteriosus (hsPDA).

Methodology:

Very low birthweight infants admitted over a 16 month period were studied (6 months, retrospectively and 10 months, prospectively). Cross-sectional and M-Mode echocardiograms with pulsed-wave and colour Doppler were performed to assess the significance of ductal patency.

Results:

Forty-one (28%) of 148 VLBW infants were diagnosed to have hsPDA. Indomethacin therapy was successful in 90% after the first course, increasing to 95% after the second course. The recurrence rate after the first course was 3%. Minor and transient complications included oliguria, urea retention, hyponatraemia and thrombocytopenia. Although three infants had focal bowel perforation and the fourth had bowel perforation associated with necrotizing enterocolitis, the incidence of gastrointenstinal pathology was not significantly different from infants without hsPDA and not given indomethacin.

Conclusions:

Very low birthweight infants with hsPDA have a high response rate and low recurrence rate to prolonged lowdose indomethacin therapy. Side-effects were mild and transient. However, it is prudent to be cautious when administering indomethacin in critically ill infants <1000 g with hsPDA who manifest clinical features of bowel ischaemia.     

Transcutaneous bilirubinometry in very low birthweight infants

AIM: To evaluate whether transcutaneous bilirubinometry (TcB) would be a reliable and efficient screening technique for hyperbilirubinaemia in very low birthweight (VLBW, < or =1500 g) infants in an intensive care unit setting. METHODS: TcB measurements (Minolta Airshield Jaundice Meter JM-102, Osaka, Japan) were obtained immediately before or within 10 min following routine blood sampling for plasma bilirubin concentration measurements in 124 VLBW infants not receiving phototherapy. The relationship between the two techniques was analysed by linear regression analysis. A plasma bilirubin > or =150 micromol/l was defined as hyperbilirubinaemia. The sensitivity and specificity of possible TcB cut-off readings to detect hyperbilirubinaemia was evaluated. RESULTS: There was a significant correlation between the measurements of both techniques (p < 0.0001, r = 0.68). In the present study, a TcB cut-off reading of 14 would have reduced the need for plasma bilirubin measurements by 26% without missing true hyperbilirubinaemia. CONCLUSION: The data suggest that TcB will improve VLBW infant care in an intensive care unit setting by reducing the need for invasive bilirubin concentration measurements.     

Evaluation of an amikacin loading dose for nosocomial infections in very low birthweight infants

AIM: To develop a simplified amikacin dosage regimen for nosocomial infections in preterm infants including a loading dose in order to achieve therapeutic Maximum Serum Concentrations early in the course of therapy. METHODS: Open, non-comparative study during November 2000 to April 2001. The modified amikacin dosing and monitoring protocol included a loading dose of 10 mg/kg in the first week of life, followed by a maintenance regimen of 7.5 mg/kg every 24 h. After the first week of life the corresponding doses were 17 mg/kg (loading) and 15 mg/kg (maintenance). A peak level was measured 30 min after the second dose, a trough level immediately before the third dose. RESULTS: Twenty-five very low birthweight infants (median birthweight 739 g, median gestational age 25 wk) who had 34 episodes of amikacin treatment were included in the analysis. Median amikacin peak and trough values were 37.1 micromol/l and 6.3 micromol/l, respectively. Twenty-nine of all peak levels (85%) and 30 of all trough levels (88%) were within the targeted range of >35 micromol/l and <8.5 micromol/l, respectively. All patients with elevated trough levels were of extremely low birthweight and were born in the 24th week of gestation. Hearing evaluations were performed in 17 of 19 surviving infants at discharge home, all of which gave normal results. CONCLUSION: The new amikacin dosing protocol yielded targeted peak and trough concentrations in a high percentage of very low birthweight infants with nosocomial infection after the first week of life. Our simplified dosage regimen achieved acceptable serum concentrations in all birthweight and gestational age groups, with the exception of extremely low birthweight infants weighing less than 700 g and/or with a gestational age of 24 wk or less. Only limited information can be gained from our data regarding the use of amikacin during the first week of life.     

Perinatal factors, periventricular haemorrhage and mortality in very low birthweight infants

In a population of 225 very low birthweight infants born over a 21 month period the cerebroventricular system was scanned by ultrasound. One third of the infants developed a periventricular haemorrhage; in 41% of infants the haemorrhage was detected before an hour of age and 66% of all haemorrhages occurred within the first 24 hours.
Statistically significant associations with periventricular haemorrhage included vaginal delivery, endotracheal intubation and intravenous sodium bicarbonate when this was administered in the first 24 hours. In a stepwise regression analysis, however, these and other potentially significant variables added little to the total accountable variance. A similar analysis of perinatal factors and mortality revealed that decreasing gestation was the major association with death.     

Psychosocial and psychomotoric development of very low birthweight infants with necrotizing enterocolitis

Twenty-six very low birthweight infants (VLBI) were treated for necrotizing enterocolitis (NEC). We investigated their consecutive health problems and psychosocial development. Method: One to 13 years after onset of NEC, follow-up studies were performed in 12 of the surviving children. Identical follow-up studies were performed in 6 VLBI who had been operated on for diseases other than NEC (control group). We used a detailed interview, a Denver test and a drawing test. Results: Five children of the NEC group had major persistent health problems that impaired their psychomotoric and psychosocial development (including hearing impairment, concomitant strabismus, early onset bronchiai asthma). Nine of 12 VLBI of the NEC group showed signs of reduced social contact, logopaedic problems and minimal partial skill reductions. Conclusion: We found similar results in both children who suffered from NEC and in a small control group of VLBI who had not suffered from NEC, therefore impaired psychomotoric and psychosocial development is probably due to prematurity.     

Severe liver haemorrhage during laparotomy in very low birthweight infants

A review is presented of severe liver haemorrhage as a serious complication in surgery on very low birthweight (VLBW) infants. Clinical data and pathological findings, as well as the outcome of the treatment, of five VLBW infants (<1000 g) who experienced liver haemorrhage during surgical exploration for necrotizing enterocolitis or spontaneous intestinal perforation were reviewed retrospectively. At the time of surgery, all infants had signs and symptoms of impending sepsis. The bleeding was predominantly "spontaneous" without obvious iatrogenic liver damage. In three infants, severe liver haemorrhage could be stabilized by early liver tamponade using absorbable thrombostatic sponges and polyglactin mesh. Conclusion: Intraoperative liver haemorrhage potentially life-threatening complication of surgery in preterm infants, which is not frequently investigated. Immediate perihepatic liver packing may be used to achieve adequate bleeding control.