Term Neurodevelopmental Outcomes Research Articles

Red blood cell transfusions in very and extremely low birthweight infants under restrictive transfusion guidelines: is exogenous erythropoietin necessary?

OBJECTIVETo examine the number and volume of red blood cell transfusions (RBCTs) in very and extremely low birthweight infants under restrictive red blood cell transfusion guidelines without erythropoietin administration, and...

Routine screening cranial ultrasound examinations for the prediction of long term neurodevelopmental outcomes in preterm infants

Routine screening cranial ultrasound examinations for the prediction of long term neurodevelopmental outcomes in preterm infants

Early postnatal dexamethasone treatment and increased incidence of cerebral palsy

OBJECTIVETo study the long term neurodevelopmental outcome of children who participated in a randomised, double blind, placebo controlled study of early postnatal dexamethasone treatment for prevention of chronic lung disease.METHODSThe...

Systemic Candida infection in extremely low birth weight infants: short term morbidity and long term neurodevelopmental outcome.

To describe mortality, morbidity at discharge and neurodevelopmental outcome at 2 years corrected age in extremely low birth weight infants with systemic Candida infection during intensive care stay. We identified all extremely low birth weight (birth weight <1000 g) infants diagnosed with Candida sepsis and/or meningoencephalitis between 1988 and mid-1996 in the tertiary neonatal intensive care centers of Toronto. The outcome of the infected infants at discharge and at 2 years corrected age was compared with a cohort of 470 extremely low birth weight infants born between 1990 and 1994. Forty-six extremely low birth weight infants with systemic Candida infection, mean (+/-SD) gestational age of 24.7 +/- 1.6 weeks and birth weight 699 +/- 135 g, were identified. Case fatality rate was 37% (17 of 46), not significantly different from the control group (35%). Data on 27 infected survivors were available at discharge. All had chronic lung disease compared with 33% in the control cases (P = 0.0001), a high incidence of periventricular leukomalacia (26% vs. 12%, P = 0.06) and an increase in severe retinopathy of prematurity (22% vs. 9%, P = 0.04); 60% had adverse neurologic outcomes at 2 years corrected age compared with 35% in the control group, and 41% vs. 12% had severe disabilities (P = 0.005). Cranial ultrasound examination was the only diagnostic modality in 5 of 13 (38%) cases with central nervous system Candida involvement. All infants with brain parenchymal lesions detected by cranial ultrasound had poor outcome. Early diagnosis and commencement of antifungal treatment favorably affected the outcome. Systemic Candida infection is associated with increased short and long term morbidity in extremely low birth weight infants. Candida infection of the central nervous system has a significant impact on long term neurodevelopmental outcome. Performance of cranial ultrasound examination is recommended as a part of the diagnostic investigation in these infants. Detection of brain parenchymal involvement might provide further information to predict outcome.

Protein supplementation of human milk for promoting growth in preterm infants

For term infants, human milk provides adequate nutrition to facilitate growth, as well as potential beneficial effects on immunity and the maternal-infant emotional state. However, the role of human milk in preterm infants is less well defined as it contains insufficient quantities of some nutrients to meet the estimated needs of the infant. Preterm infants require higher protein intakes than term infants to attain adequate growth rates, and have relatively higher protein turnover rates. Inadequate protein intakes may be partly responsible for low serum albumin and blood urea concentrations in preterm infants. The main objective was to determine if addition of protein to human milk leads to improved growth and neurodevelopmental outcomes without significant adverse effects in preterm infants. The standard search strategy of the Cochrane Neonatal Review Group was used. This includes searches of the Oxford Database of Perinatal Trials, MEDLINE, previous reviews including cross references, abstracts, conferences and symposia proceedings, expert informants, and journal handsearching mainly in the English language. All trials utilizing random or quasi-random allocation to supplementation of human milk with protein or no supplementation in preterm infants who remained in hospital were eligible. Data were extracting using the standard methods of the Cochrane Neonatal Review Group, with separate evaluation of trial quality and data extraction by each author and synthesis of data using relative risk and weighted mean difference. Protein supplementation of human milk results in increases in short term weight gain (WMD 3.6 g/kg/day, 95% CI 2.4 to 4.8 g/kg/day), linear growth (WMD 0.28 cm/week, 95% CI 0.18 to 0.38 cm/week) and head growth (WMD 0.15 cm/week, 95% CI 0.06 to 0.23 cm/week). There are insufficient data to evaluate long term neurodevelopmental and growth outcomes. There are too few infants studied to be certain that adverse effects of protein supplementation are not increased. Blood urea levels are increased (WMD 1.0 mmol/l, 95% CI 0.8 to 1.2 mmol/l). Protein supplementation of human milk in relatively well preterm infants results in increases in short term weight gain, linear and head growth. Urea levels are increased, which may reflect adequate rather than excessive dietary protein intake. Further research should be directed towards the evaluation of specific levels of protein intake in preterm infants and the clinical effects of supplementation with protein, including long term growth and neurodevelopmental outcomes. This may best be done in the context of refinement of available multicomponent fortifier preparations.

Fat supplementation of human milk for promoting growth in preterm infants

For term infants, human milk provides adequate nutrition to facilitate growth, as well as potential beneficial effects on immunity and the maternal-infant emotional state. However, the role of human milk in premature infants is less well defined as it contains insufficient quantities of some nutrients to meet the estimated needs of the infant. There are potential short term and long term benefits from human milk, although observational studies have suggested that infants fed formula have a higher rate of growth than infants who are breast fed. The main objective is to determine if addition of supplemental fat to human milk leads to improved growth and neurodevelopmental outcomes without significant adverse effects in preterm infants. The standard search strategy of the Cochrane Neonatal Collaborative Review Group was used. This includes searches of the Oxford Database of Perinatal Trials, MEDLINE, previous reviews including cross references, abstracts, conferences and symposia proceedings, expert informants, journal handsearching mainly in the English language. All trials utilizing random or quasi-random allocation to supplementation of human milk with fat or no supplementation in preterm infants within a hospital were eligible. Data were extracted using the standard methods of the Cochrane Neonatal Collaborative Review Group, with separate evaluation of trial quality and data extraction by each author and synthesis of data using relative risk and weighted mean difference. Results are available for only one small study evaluating the effects of fat supplementation. There are insufficient data to evaluate short term or long term growth outcomes and neurodevelopmental outcomes. There are insufficient data to comment on potential adverse effects. There is insufficient evidence to make recommendations for practice. Further research should evaluate the practice of supplementation of human milk with fat. This may best be done in the context of the development of multicomponent fortifiers. Both short term growth outcomes and long term growth and neurodevelopmental outcomes should be evaluated. Adverse effects should be evaluated.

Multicomponent fortified human milk for promoting growth in preterm infants.

For term infants, human milk provides adequate nutrition to facilitate growth, as well as potential beneficial effects on immunity and the maternal-infant emotional state. However, the role of human milk in premature infants is less well defined as it contains insufficient quantities of some nutrients to meet the estimated needs of the infant. There are potential short term and long term benefits from human milk, although observational studies have suggested that infants fed formula have a higher rate of growth than infants who are breast fed. Commercially-produced multicomponent fortifiers provide additional nutrients to human milk (in the form of protein, calcium, phosphate, and carbohydrate, as well as vitamins and trace minerals). The main objective was to determine if addition of multiple dietary supplements to human milk leads to improved growth, bone metabolism and neurodevelopmental outcomes without significant adverse effects in premature infants. The standard search strategy of the Neonatal Review Group was used. This includes searches of the Oxford Database of Perinatal Trials, MEDLINE, previous reviews including cross references, abstracts, conferences and symposia proceedings, expert informants, journal handsearching mainly in the English language. All trials utilising random or quasi-random allocation to supplementation of human milk with multiple nutrients or no supplementation in premature infants within a nursery setting were eligible. Data were extracted using the standard methods of the Cochrane Collaboration and its Neonatal Review Group, with separate evaluation of trial quality and data extraction by each author and synthesis of data using relative risk and weighted mean difference. Supplementation of human milk with multicomponent fortifiers is associated with short term increases in weight gain, linear and head growth. There is no effect on serum alkaline phosphatase levels. Bone mineral content and nitrogen retention appear to be increased. There are insufficient data to evaluate long term neurodevelopmental and growth outcomes. Adverse effects of fortification do not appear to be significantly increased, although the total number of infants studied and the unavailability of results for some infants randomized and subsequently withdrawn reduces confidence in this conclusion. Blood urea levels are increased and blood pH levels minimally decreased, but the significance of this is uncertain. Multicomponent fortification of human milk is associated with short-term improvements in weight gain, linear and head growth. Despite the absence of evidence of long-term benefit and insufficient evidence to be reassured that there are no deleterious effects, it is unlikely that further studies evaluating fortification of human milk versus no supplementation will be performed. Further research should be directed toward comparisons between different proprietary preparations and evaluating both short-term and long-term outcomes in search of the "optimal" composition of fortifiers.

Meta-analysis of elective high frequency ventilation in preterm infants with respiratory distress syndrome

AIMTo summarise the evidence on the efficacy of elective high frequency ventilation compared with conventional ventilation in preterm infants with respiratory distress syndrome.METHODSA search from 1987 onwards was made on...

The fetal circulatory response to chronic placental insufficiency and relation to pregnancy outcome

Chronic fetal growth restriction is associated with both increased perinatal mortality and impaired neurodevelopment. Although it is a much more important cause of fetal neurological damage than intrapartum birth asphyxia, it is more difficult to treat, since the main intervention, timed delivery, carries its own risks. Since it is associated with a range of circulatory changes, which may also cause fetal damage, understanding these may improve management. In this article we review these fetal circulatory changes and assess their significance for predicting perinatal and long term neurodevelopmental outcome. We describe the Doppler assessment techniques, their clinical role in prediction of adverse outcome and the pathogenesis of brain injury in the preterm growth restricted fetus.

Systematic review and meta-analysis of early postnatal dexamethasone for prevention of chronic lung disease

AIMTo review systematically the evidence to determine whether dexamethasone treatment of very low birthweight infants begun within 14 days of age prevents chronic lung disease (CLD) without clinically significant side...

Elective high frequency jet ventilation versus conventional ventilation for respiratory distress syndrome in preterm infants.

This section is under preparation and will be included in the next issue. The objective of this review was to determine whether the elective (commencing soon after initiation of mechanical ventilation) use of high frequency jet ventilation (HFJV), as compared to conventional ventilation (CV) in preterm infants with respiratory distress syndrome (RDS), would decrease the incidence of chronic lung disease (CLD) without adverse effects. Randomized trials from MEDLINE were identified by means of MeSH and text words 'high frequency ventilation', 'high frequency jet ventilation', 'jet ventilation' from the years 1980 to 1997. The EMBASE database, the Oxford Database of Perinatal Trials, the Neonatal Trials Register of the Neonatal Review Group of the Cochrane Collaboration and the Cochrane library were also accessed. Proceedings of recent SPR/APS meetings were hand searched. Information was obtained from experts in the field, and cross references were checked. All randomized controlled trials of elective high frequency jet ventilation versus conventional ventilation in preterm infants born at less than 35 weeks GA or with a birth weight less than 2000 gms with respiratory distress were included in the systematic review. Trials which used HFJV to 'rescue' preterm infants due to severe respiratory distress usually beyond 24 hours, and trials that used HFJV for a mandatory time period and then switched back to CV, were not included in this review. The standard methods of the Neonatal Cochrane Review Group were used, including independent trial assessment and data extraction. Data were analysed using relative risk (RR) and risk difference (RD). From 1/RD the number needed to treat (NNT) for benefits and number needed to harm (NNH) for adverse outcomes were calculated. Overall analysis of the three trials showed that HFJV is associated with a reduction in CLD at 36 weeks postmenstrual age in survivors [RR 0.58 (0.34, 0. 98), RD -0.138 (-0.268, -0.007), NNT 7 (4, 90)]. The use of home oxygen therapy was evaluated in only one study (Keszler 1997) and a lower rate was found in the HFJV group [RR 0.24 (0.07, 0.79), RD -0. 176 (-0.306, -0.047), NNT 5 (3, 21)]. Overall there was a trend towards an increase in the risk of PVL in the HFJV group, which was not significant. Subgroup analyses shows a significant increase in risk of PVL in the trial by Wiswell 1996 [RR 5.0 (1.19, 21.04), RD 0.250 (0.069, 0.431), NNH 4.0 (2.3,14.5)] where a 'low volume strategy' was the standard protocol for HFJV. In the other trial by Keszler 1997, where the intention was to use a 'high volume strategy', there was no significant difference in the incidence of PVL, RR 0.42 (0.14, 1.30). In the overall analysis, there were no significant differences in the incidence of neonatal mortality, IVH all grades or in grades 3 or 4 IVH. In the subgroup where 'low volume strategy' was used there was a non-significant trend toward an increase in risk of IVH all grades and grades 3 or 4 IVH. The overall analysis shows a benefit in pulmonary outcomes in the group electively ventilated with HFJV. Of concern is the significant increase in acute brain injury in one trial which used lower mean airway pressures when ventilating with HFJV. There are as yet no long term pulmonary or neurodevelopmental outcomes from any of the trials. Until further studies ascertain the most appropriate strategy to routinely ventilate premature infants with HFJV safely, ventilation with HFJV cannot be recommended for preterm infants with RDS.

Elective use of High Frequency Jet Ventilation (HFJV) versus Conventional Ventilation(CV) for Respiratory Distress Syndrome (RDS): Systematic review and Meta-analyses. † 1612

OBJECTIVE: To determine whether the elective (commencing soon after initiation of mechanical ventilation) use of HFJV as compared to CV in ventilated preterm infants with RDS decreases the incidence of chronic lung disease (CLD) without adverse effects. METHODS: Systematic search in accordance with Cochrane reviews. All randomized controlled trials of elective HFJV vs CV in preterm infants <35 weeks GA or <2000 gms with RDS were included. Data analyses were conducted according to the standards of Neonatal Cochrane Review Group using relative risk (RR) and number needed to treat(NNT) or harm (NNH). Preplanned subgroup analyses were trials with surfactant, high volume strategy (HVS), low volume strategy (LVS) and infants of different gestational ages and birth weight. RESULTS: Overall analyses of the three trials included in the meta-analyses1–3, showed that HFJV is associated with a reduction in CLD at 36 weeks post menstrual age (PMA) in survivors [RR 0.58 (0.34, 0.98), NNT 7 (4, 90)]. Home O2, only assessed in one trial3, is reduced [RR 0.24 (0.07,0.79), NNT 5 (3,21)]. For PVL overall RR is 1.24 (0.59, 2.61); in the subgroup where LVS was intended2 the RR is 5.0 (1.19, 21.04), NNH 4.0(2.3,14.5). In the overall analyses there were no significant differences in incidence of IVH all grades and grades 3 or 4, or in neonatal mortality. Subgroup analyses of infants at different gestational age and birthweight could not be performed. CONCLUSIONS: Overall analyses show a benefit in pulmonary outcomes (CLD at 36 wks PMA,2,3 home O2,3) in the group electively ventilated with HFJV. Of concern is the significant increase in PVL in one single centre trial which used LVS. There are as yet no long term pulmonary or neurodevelopmental outcomes from any of the trials. Until further studies ascertain the most appropriate strategy to ventilate preterm infants with HFJV safely, routine use of HFJV cannot be recommended for ventilated preterm infants with RDS.

NEURODEVELOPMENTAL OUTCOME OF PREMATURE INFANTS INBORN AT 24, 25, AND 26 WEEKS GESTATION. † 1636

Because of the frequent inaccuracies in assigning gestational ages, most information available about long term neurodevelopmental outcome in extremely immature infants is reported according to birth weight rather than gestational age. Previously, we have reported that poor outcome may not be related to birth weight, with many infants as small as 500 grams at birth being neurodevelopmentally normal. We questioned whether reevaluating extremely immature infants according to gestational age would be more relevant than birth weight. A detailed review of maternal and infant charts was undertaken by a perinatologist and neonatologist to identify inborn infants born at 24, 25 and 26 weeks gestational age from 1/1/90-12/31/94. A total of 134 infants were admitted to the ICN; 39 died before discharge and 95 infants survived to discharge. One infant expired post discharge and 2 were excluded from the study (one congenital anomaly, 1 CNS insult post discharge). Of the remaining 92 infants, 9 are still within the first year of life. Seven infants have been lost and 74/81 infants have been assessed at ≥10 months adjusted age. We report on their outcome at mean adjusted age of 29 months (s.d. ± 16 mos.). We conclude that the rate of neurologic abnormalities is similar in these three very low gestational ages. However, there is a significant association of gestational age and severe developmental delays for infants born between 24 and 26 weeks gestation. Table

SURVIVAL OF INFANTS WITH BIRTH WEIGHT (BW) LESS THAN 501 GRAMS (g).† 1621

Objective: To determine the number and outcome of infants with BW < 501 g at 54 Neonatal Intensive Care Units participating in the Vermont Oxford Neonatal Network. Methods: Pre-defined perinatal and neonatal outcome data were collected on standardized forms for all live births with BW < 501 g during one year (June 1, 1994 - May 31, 1995). Results: There were 391 liveborn infants evaluated of whom 95 were intubated and ventilated, and 296 were not. Ventilated infants, compared to non-ventilated infants, were more likely to have received antenatal steroids (35% vs. 4%, p<0.001), to be delivered by cesarean section (43% vs. 4%, p<0.001), to be more mature(mean gestational age 24 weeks vs. 21 weeks, p<0.001), and to be heavier(mean BW 444 g vs. 370 g, p<0.001). Most deaths (81%) occurred within the first day of life; few infants (1%) died after 28 days. No infant born less than 320 grams or less than 22 weeks survived. Twenty four infants survived to discharge, all of whom were ventilated, and received surfactant. Among survivors, 22 of 24 (92%) received steroids for chronic lung disease. One survivor had grade IV intraventricular hemorrhage (IVH), whereas 17 of 24(71%) had no IVH. The mean hospital stay for survivors was 127 ± 22 days. Conclusions: Some infants with BW < 501 g selected for intubation and ventilation can survive to discharge to home. Further study will be needed to better understand the selection criteria used to offer resuscitation to these extremely low BW infants, and determine the long term neurodevelopmental outcome of the survivors.

Delayed surgery for congenital diaphragmatic hernia: neurodevelopmental outcome in later childhood.

The long term neurodevelopmental outcome was assessed in 23 survivors born with congenital diaphragmatic hernia who had been managed by an elective delay in surgical repair after a period of stabilisation. This cohort was treated in one neonatal surgical unit between 1983 and 1989 by a single team of surgeons and anaesthetists. All children underwent comprehensive neurological, developmental, and anthropometric assessment at a mean age of 56 (range 18-94) months. Two children (9%) had major disability (one with hemiplegia and one with a lower limb monoplegia) and two further children had minor disabilities (one had partial sightedness and squint, the other squint only). The mean developmental quotient (DQ) for the group was 108 (SD 10.8) and none had developmental delay (defined as DQ < 70). Infants who had spent more time in hospital, or had had a longer duration of ventilation, tended to have lower weights and lower occipitofrontal circumference centiles in later childhood. Preoperative stabilisation and delayed surgery for congenital diaphragmatic hernia is not associated with an impaired neurodevelopmental outcome.

Intraventricular haemorrhage.

ABSTRACTNeonatal echoencephalography is performed routinely in all very low birth‐weight neonates in many nurseries throughout the world. The diagnosis of a haemorrhage requires the differentiation of normal echogenic periventricular structures from haemorrhage. A classification of haemorrhage based on size alone is advocated. A separate classification is then used to assess post‐haemorrhagic ventricular dilatation by measurement of “ventricular width”. As the long term neurodevelopmental outcome of the neonate is likely to be more related to the state of the brain parenchyma than the ventricles, the limitations of ultrasound in assessing the parenchyma has resulted in other techniques being investigated to determine if they can better predict subsequent handicap.