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Improved outcomes for very low birthweight infants: evidence from New Zealand national population based data.

OBJECTIVE: To compare the survival and short term morbidity of all New Zealand very low birthweight (VLBW) infants born in two epochs, 1986 and 1998-1999. SETTING: All level III and level II neonatal intensive care units (NICUs) in New Zealand. METHODS: In 1986, data were prospectively collected for a study of retinopathy of prematurity (ROP). In 1998-1999, prospective data were collected by the Australian and New Zealand Neonatal Network (ANZNN). Both cohorts included all VLBW infants born during the calendar year and admitted to a NICU. Data were collected from birth until discharge home or death. RESULTS: More VLBW infants were admitted for care in 1998-1999 (n = 1084, 0.96% of livebirths) than in 1986 (n = 413, 0.78% of livebirths; p < 0.001), including a higher proportion of VLBW infants of < 1000 g birth weight (38% v 32% respectively; p < 0.05). Survival to discharge home increased from 81.8% in 1986 to 90.3% in 1998-1999 (p < 0.001). The 1998-1999 cohort had a higher proportion of infants born in a hospital with a level III NICU (87% v 72% in 1986; p < 0.001) and receiving antenatal corticosteroids (80% v 58% in 1986; p < 0.001). In 1998-1999, the incidence of several morbidities had decreased compared with 1986, including oxygen dependency at 28 days (29% v 39% respectively; p = 0.001) and at 36 weeks postmenstrual age (16% v 23%; p = 0.002), grade 1 intraventricular haemorrhage (IVH) (8% v 24%; p < 0.001), grade 2/3 IVH (5% v 11%; p < 0.001), and stage 3/4 ROP for infants < 1000 g (6% v 13%; p < 0.001). CONCLUSIONS: The outlook for VLBW infants in New Zealand has improved since 1986.

Cerebral Hemorrhage↗

Frequent wheeze at follow up of very preterm infants: which factors are predictive?

OBJECTIVE: To determine if chest radiograph appearance at 28 days or 36 weeks postmenstrual age (PMA) can predict recurrent wheeze or cough at follow up in prematurely born infants more effectively than readily available clinical data. DESIGN: Chest radiographs of infants entered into the UKOS trial, who had had a chest radiograph at 28 days and 36 weeks PMA and completed six months of follow up, were assessed for the presence of fibrosis, interstitial shadows, cystic elements, and hyperinflation. At 6 months of corrected age, the occurrence and frequency of wheeze and cough since discharge were determined using a symptom questionnaire. PATIENTS: A total of 185 infants with a median gestational age of 26 (range 23-28) weeks. RESULTS: Thirty seven infants wheezed more than once a week, compared with the rest of the cohort. These infants had significantly higher chest radiograph scores at 28 days (p = 0.020) and 36 weeks PMA (p = 0.005), with significantly higher scores at 28 days for fibrosis (p = 0.017) and at 36 weeks PMA for fibrosis (p = 0.001) and cystic elements (p = 0.0007). They had also been ventilated for longer (p = 0.013). Forty four infants coughed more than once a week; they did not differ significantly from the rest of the cohort. An abnormal chest radiograph score at 36 weeks PMA had the largest area under the receiver operator characteristic curve with regard to prediction of frequent wheeze. CONCLUSION: An abnormal chest radiograph appearance at 36 weeks PMA predicts frequent wheeze at follow up and appears to be a better predictor than readily available clinical data.

Age Factors↗

Pre-flight testing of preterm infants with neonatal lung disease: a retrospective review.

BACKGROUND: The low oxygen environment during air travel may result in hypoxia in patients with respiratory disease. However, little information exists on the oxygen requirements of infants with respiratory disease planning to fly. A study was undertaken to identify the clinical factors predictive of an in-flight oxygen requirement from a retrospective review of hypoxia challenge tests (inhalation of 14-15% oxygen for 20 minutes) in infants referred for fitness to fly assessment. METHODS: Data from 47 infants (median corrected age 1.4 months) with a history of neonatal lung disease but not receiving supplemental oxygen at the time of hypoxia testing are reported. The neonatal and current clinical information of the infants were analysed in terms of their ability to predict the hypoxia test results. RESULTS: Thirty eight infants (81%) desaturated below 85% and warranted prescription of supplemental in-flight oxygen. Baseline oxygen saturation was >95% in all infants. Age at the time of the hypoxia test, either postmenstrual or corrected, significantly predicted the outcome of the hypoxia test (odds ratio 0.82; 95% confidence intervals 0.62 to 0.95; p = 0.005). Children passing the hypoxia test were significantly older than those requiring in-flight oxygen (median corrected age (10-90th centiles) 12.7 (3.0-43.4) v 0 (-0.9-10.9) months; p < 0.0001). CONCLUSIONS: A high proportion of ex-preterm infants not currently requiring supplemental oxygen referred for fitness-to-fly assessment and less than 12 months corrected age are at a high risk of requiring in-flight oxygen. Referral of this patient group for fitness to fly assessment including a hypoxia test may be indicated.

Aerospace Medicine↗

Bowel migration in the normal fetus: US detection.

Ten fetuses underwent ultrasound scanning at 7-10 weeks gestational (postmenstrual) age. In all cases, an echogenic mass measuring 0.5-1.0 cm was demonstrated within the base of the umbilical cord at its insertion into the fetal abdomen. No area with echogenicity characteristic of the small bowel was identified within the lower part of the fetal abdomen. All fetuses were reexamined 4-12 weeks later, at which time the mass in the umbilical cord was no longer seen, and normal fetal bowel was visualized in the lower abdominal cavity of the fetus. This sequence of findings appears to represent the sonographic demonstration of normal fetal bowel migration early in gestation and should not be confused with defects of the abdominal wall such as omphalocele or gastroschisis.

Abdominal Muscles↗

Prediction of neurodevelopmental outcome in the preterm infant: MR-staged myelination compared with cranial US.

In this prospective study, 26 very preterm infants underwent magnetic resonance (MR) imaging of the brain at 44 weeks postmenstrual age (PMA) for staging of myelination. Neurodevelopmental outcome was assessed at 1 year of age. A significant correlation was demonstrated between delayed myelination and neurodevelopmental outcome (Chi 2 = 16.6, P = .01). A significant correlation was also found between ultrasound (US) findings in the neonatal period and outcome at 1 year (Chi 2 = 22.9, P = .03). To establish the criterion with the best predictive value, a multiple regression analysis was performed with periventricular-intraventricular hemorrhage, periventricular leukomalacia (PVL), and the stage of myelination at 44 weeks PMA as independent variables and neurodevelopmental outcome at 1 year of age as a dependent variable. Staging of myelination with MR imaging in the early postnatal period of very preterm infants had predictive value with regard to neurodevelopmental outcome. Detection of PVL with US, however, showed a better correlation with outcome, a result that seems to limit the potential role of MR imaging in this population for this purpose only.

Cerebral Hemorrhage↗

Epithelial lining fluid free IGF-I-to-PAPP-A ratio is associated with bronchopulmonary dysplasia in preterm infants.

Preterm newborns developing retinopathy of prematurity (ROP) and bronchopulmonary dysplasia (BPD) show persistently low levels of insulin-like growth factor-I (IGF-I) in sera. They also present higher free IGF-I concentrations in epithelial lining fluids (ELFs) and lung tissues. Pregnancy-associated plasma protein-A (PAPP-A) is a metalloproteinase that dissociates three binding proteins from the active form of IGF-I, namely free IGF-I. The present study analyzes the ELF concentrations of free IGF-I, PAPP-A, and their ratios in preterm newborns developing or not BPD, defined as O(2) dependence at 36 wk postmenstrual age. Bronchoalveolar lavage fluids of 41 infants (34 without and 7 with BPD) were analyzed on the 2nd and 4th day after birth. Infants developing BPD showed increased ELF free IGF-I and decreased PAPP-A concentrations on both days 2 and 4 compared with newborns without BPD. A nonsignificant trend between these 2 days was observed for free IGF-I (increasing) and PAPP-A (decreasing). On the same days, the free IGF-I-to-PAPP-A ratio was always significantly higher in patients developing BPD. These differences were more significant than those of IGF-I or PAPP-A when individually evaluated. A multivariate analysis confirmed the significance for free IGF-I on day 4, whereas the ratio was confirmed on both days 2 and 4. The same ratio was significantly correlated with some indexes of disease severity, such as hours of oxygen administration, days of hospitalization, and ROP severity scores. Finally, the ratio between ELF free IGF-I and PAPP-A appears to be a useful marker for lung injury of premature newborns.

Bronchoalveolar Lavage Fluid↗

Upper airway muscle activity during nasal occlusion in newborn babies.

Submental electromyorgams (SM EMG) were recorded from 20 preterm babies (gestational age 30 +/- 2 wk, postmenstrual age at study 35 +/- 2 wk) (mean +/- SD) and 3 full-term infants (7-14 days old). SM EMG was evaluated during eupnea and brief experimental airway occlusion. Phasic inspiratory SM EMG was rarely seen during eupnea. SM EMG tended to increase on the first occluded effort, although this increase was not statistically significant in most babies. All infants showed progressive breath-by-breath augmentation of phasic SM EMG during occlusions in rapid-eye-movement (REM) as well as quiet (QS) sleep; phasic increases in SM EMG were similar during REM and QS occlusions in the majority (16/22) of babies. Periods of airway closure were detected during 24 occlusions in 5 infants; phasic SM EMG was reduced on these occasions. The results are consistent with the idea that recruitment of upper airway muscles contributes to the stability of the airway of the preterm human.

Electromyography↗

Interstitial pregnancy treated with local and systemic methotrexate.

We present a case of an intact interstitial pregnancy at 6 postmenstrual weeks and 4 days, which was successfully treated by combined local and systemic methotrexate administration. The embryonic cardiac activity stopped within 1 min after uneventful ultrasound-guided puncture and methotrexate instillation of the chorionic sac. While the beta-hCG serum values returned to normal 59 days after local, and 52 days after systemic treatment, the echogenic lesion has reduced in size by 50%, but is still sonographically detectable 7 months after the procedure. This report shows that medical treatment of interstitial pregnancy may be an effective alternative to the surgical approach.

Adult↗

Essential fatty acids and their long-chain polyunsaturated metabolites in maternal and cord plasma triglycerides during late gestation.

The fatty acid composition of plasma lipids was determined in 41 pairs of mothers and their term infants at time of birth (38-42 postmenstrual weeks) by high-resolution capillary gas-liquid chromatography. Linoleic and alpha-linolenic acids were found at smaller concentrations in cord than in maternal triglycerides, in contrast to strikingly higher proportions of their long-chain polyunsaturated metabolites (LC-PUFA), which indicates a preferential maternofetal transport for certain physiologically important LC-PUFA. While no significant gestational age-dependent changes occurred in maternal plasma triglycerides, the values for most of the fetal long-chain n-3 metabolites increased with the duration of gestation, possibly reflecting an increased transplacental fatty acid passage during late pregnancy or a maturation of desaturation in the fetal liver.

Adult↗

Plasma arginine and urinary nitrate and nitrite excretion in bronchopulmonary dysplasia.

The aim of this prospective study was to determine whether preterm infants with bronchopulmonary dysplasia (BPD) and signs of increased pulmonary artery pressure have a deficiency of plasma arginine (ARG) and systemic nitric oxide (NO) synthesis. Plasma amino acid concentrations, Doppler pulmonary systolic time intervals (ratio of acceleration time and ejection time corrected for heart rate: AT/ET(C)) and urinary nitrate and nitrite concentrations were determined at the 28th day postnatal age and at 36 weeks postmenstrual age in 73 preterm infants less than 30 weeks gestational age. The AT/ET(C) ratios were significantly lower in infants with BPD (n = 32) compared to controls. However, total amino acid concentrations, ARG intake as well as plasma ARG concentrations were not different between groups (median (interquartile-range) micromol/l): control: 58 (42.5-75.5) and 54.5 (42-71) at day 28 and 36 weeks; BPD: 54.5 (31.5-70.5) and 43 (35-62), respectively. Urinary nitrate and nitrite concentrations, were not different between groups at day 28, but significantly higher in infants with BPD at 36 weeks (p = 0.014). In conclusion, plasma ARG concentrations and systemic NO synthesis were not deficient in preterm infants with BPD and signs of elevated pulmonary artery pressure.

Arginine↗

Postnatal changes in pulmonary mechanics and energetics of infants with respiratory distress syndrome following surfactant treatment.

BACKGROUND: Postnatal alterations in pulmonary mechanics, energetics and functional residual capacity (FRC) describe the structural maturation of the preterm respiratory system. OBJECTIVE: To evaluate longitudinal changes in pulmonary function in infants with respiratory distress syndrome (RDS) treated with oxygen, positive pressure ventilation and synthetic surfactant (Exosurf). METHODS: Serial pulmonary function tests were performed in surfactant-treated infants [mean +/- SD birth weight (BW) = 1,112 +/- 276 g, gestational age (GA) = 29 +/- 3 weeks] at postnatal ages: <3 days, 1, 2, 3, 4 and 6-8 weeks until term postmenstrual age (PMA). Tidal volume, pulmonary compliance (C(L)), pulmonary resistance (R(T)) and flow-resistive work were analyzed following simultaneous measurements of airflow and transpulmonary pressure signals. Serial FRC measurements were made in a randomly selected group. RESULTS: Prior to 28 weeks' PMA, C(L) was unchanged irrespective of GA. At age 1 week the likelihood ratio (LR) for bronchopulmonary dysplasia (BPD) based on C(L), R(T) and GA was predicted to be >90% for those with BW <750 g (LR >100) as compared to <10% probability (LR = 0.3) for infants >1,500 g. Significant linear increase in C(L) to PMA was evident >28 weeks' PMA (r = 0.86, p < 0.01) at 0.17 ml/cm H2O/kg/week. By term PMA, mean C(L) was 2.60 +/- 0.07 ml/cm H2O. Improvements in FRC of preterm infants with RDS who recovered occur at a more rapid rate ( approximately 25 ml/kg) compared to those who developed BPD ( approximately 20 ml/kg). CONCLUSIONS: Slow but incremental postnatal pulmonary improvement, minimal <28 weeks' PMA, were comparable for all infants. Along with diminished FRC, these changes reflect persistent deleterious effects of positive pressure ventilation, alveolar hyperoxia and unrecognized pulmonary overdistension.

Continuous Positive Airway Pressure↗

Outcome of extremely preterm infants randomized at birth to different PaCO2 targets during the first seven days of life.

BACKGROUND: Ventilation with higher PaCO(2) goals may reduce lung injury and bronchopulmonary dysplasia (BPD). The effect may be enhanced by using a higher PaCO(2) goal than in previous trials. OBJECTIVE: To determine the clinical benefits and safety of higher PaCO(2) goals for ventilated preterm infants. STUDY DESIGN: Preterm infants with a gestational age between 23 and 28 completed weeks receiving mechanical ventilation within 6 h of birth were randomized to be managed with either a PaCO(2) target between 55 and 65 mm Hg (7.3- 8.7 kPa, minimal ventilation) or 35 and 45 mm Hg (4.7- 6.0 kPa, routine ventilation) for the first 7 days of life. The primary outcome measure was BPD, defined as need for mechanical ventilation or supplemental oxygen at 36 weeks postmenstrual age, or death. The neurodevelopmental status was assessed at 18-22 months corrected age. RESULTS: The trial was stopped early after enrolling 31% of the projected sample size. Enrolled infants had a median birth weight of 640 g. BPD or death occurred in 21/33 (64%) infants after minimal ventilation and 19/32 (59%) infants after routine ventilation. Minimal ventilation was associated with trends towards higher mortality and higher incidence of neurodevelopmental impairment, and a significantly increased combined outcome of mental impairment or death (p < 0.05). CONCLUSION: Minimal ventilation as performed in this study did not improve clinical outcome, and may have been associated with a worse neurodevelopmental outcome.

Algorithms↗

Platelet serotonin uptake and effects of vitamin B6-treatment in premenstrual tension.

The platelet serotonin uptake kinetics was studied in 19 women with premenstrual tension syndrome (PMS) and 19 age-matched symptom-free controls during the pre- and postmenstrual phases. Both groups exhibited stable Vmax and Km values at the two phases of the menstrual cycle. There were no differences between the two groups regarding the level of Vmax and Km, respectively. The effect of season (p less than 0.001), with lowered values of Vmax during spring compared to corresponding values during the later half of the year, was identical in both groups. A tendency to lowered Vmax values in the follicular phase in women with PMS during spring may indicate that women with PMS are more vulnerable to developing depressive episodes during this period than symptom-free women. The blood platelet count in whole blood was decreased in the luteal phase in the control group but remained stable in the PMS group. The effect of vitamin B6 on clinical symptoms and the platelet serotonin uptake during the luteal phase was investigated in a double-blind crossover design. Vitamin B6 treatment did not significantly improve the PMS symptoms. There was no effect of treatment on Km. Vmax increased significantly in response to treatment (F = 9.6; p less than 0.001) in both groups, but there was no significant difference between placebo and vitamin B6.

Adult↗

Development of arachnoid villi and granulations in man.

The superior sagittal sinus and confluens sinuum of 27 fetuses and newborns ranging from postmenstrual intervals of 26-54 weeks were studied by scanning electron microscopy and histology. 26-week specimens showed oval depressions in the final portions of tributary veins to the sinus. Histologically there were arachnoid tissue clusters within the dural wall. The walls of the depressions were more irregular by the 30th week. Arachnoid villi were apparent by the 35th week and granulations were observed after the 39th weeks. The granulations increased in complexity as development proceeded.

Arachnoid↗

Blood transfusion in late anemia of prematurity: effect on oxygen consumption, heart rate, and weight gain in otherwise healthy infants.

BACKGROUND: In premature infants there is no universally accepted definition of anemia requiring transfusion. We designed the present investigation to study the effects of red blood cell transfusion (based on simple transfusion rules) on weight gain, energy metabolism, and heart rate in otherwise healthy preterm infants. PATIENTS AND METHODS: We measured oxygen consumption (VO2), respiratory quotient (RQ) and energy expenditure (EE) by 4-hour indirect calorimetry, and assessed weight gain over 7 days and heart rate in 12 infants with late anemia of prematurity before and after red blood cell transfusion (10 ml/kg). At the time of transfusion, postmenstrual age was 38 +/- 1 weeks (mean +/- SEM), body weight 2.14 +/- 0.13 kg, and hemoglobin concentration 7.7 +/- 0.3 g/dl (range: 5.5-9.2). RESULTS: Red blood cell transfusion increased the hemoglobin concentration by 3.8 +/- 0.5 g/dl, but had no significant effect on weight gain (15.4 +/- 2.4 vs. 13.8 +/- 1.8 g/kg/day), VO2 (8.7 +/- 0.3 vs. 8.7 +/- 0.3 ml/kg/min), minimal VO2 (7.2 +/- 0.3 vs. 7.7 +/- 0.4 ml/kg/min), RQ (0.96 +/- 0.02 vs. 0.95 +/- 0.02), EE (50 +/- 2 vs. 51 +/- 2 kcal/kg/day), and heart rate (160 +/- 3 vs. 158 +/- 3 min-1). CONCLUSION: We conclude that oxygen supply and energy metabolism were not compromised in the anemic preterm infants at the time of red blood cell transfusion.

Anemia, Neonatal↗

Plasma renin activity and its postnatal development in preterm infants. Preliminary report.

Immunoassayable plasma renin activity (PRA) was measured in 16 healthy preterm infants of different gestational ages. A total of 52 measurements have been performed between the second week of life and the date of the expected term. PRA was found markedly increased in preterm infants and a highly significative negative correlation with postmenstrual age was proved.

Female↗

Zinc balances in preterm infants.

Zinc balances were studied in three groups of preterm babies. The first group received bank human milk of 25% concentration, the second group bank human milk enriched with 1 g/100 ml of lactalbumin hydrolysate, and the third group an industrial formula in which 40% of the fats were replaced with medium chain triglycerides (MCT). Zn intakes (microgram/kg/day) were, respectively, 796 +/- 136 (group 1), 689 +/- 231 (group 2), and 252 +/- 67 (group 3). In all 3 groups, fecal Zn excretion was very high: range; 6,862-635 micrograms/kg/day (group 1), 3,022-194 micrograms/kg/day (group 2), and 304-27 micrograms/kg/day (group 3), respectively. Zn retentions were mostly negative for groups 1 and 2 (7/8 and 18/23, respectively), and mostly positive (12/14), for group 3. Zn absorption was found to be related to fecal fat (p less than 0.001) in all groups, and in group 1 and 2 to fecal N (p less than 0.001) and Zn intake (p less than 0.02). Positive zinc balances were obtained when fat and nitrogen absorption exceeded 90%. This was achieved at 280 days of postmenstrual age in preterm babies fed bank human milk, but much sooner in preterm babies fed with MCT.

Diet↗

Effects of birthweight status and gestational age on the quality of general movements in preterm newborns.

It is hypothesised that individual differences in nervous system functioning, undetected by a neurological examination, are reflected in the quality of spontaneous movements of preterm newborns. Given this hypothesis it is expected that a short pregnancy duration and IUGR will be related to an abnormal movement quality. These expectations were confirmed in a group of 37 small-for-gestational-age and appropriate-for-gestational-age preterm newborns with gestational ages ranging from 27 to 34 weeks without serious perinatal complications and for whom no overt neurological abnormalities could be detected based on the evaluation of elicited responses and tonus at the postmenstrual age of 35 weeks. The quality of general movements was adversely affected by both IUGR and a pregnancy duration below 32 weeks. Newborns with an abnormal movement quality also had significantly lower obstetrical optimality scores. Previous research has shown these scores to be related to the neurological condition of the newborn. We conclude that observations of movement quality, being neither intrusive nor time consuming, may constitute a useful addition to the neurological assessment of preterm newborns without serious perinatal complications.

Birth Weight↗