Periventricular haemorrhage and leukomalacia in extremely low birthweight infants

Forty (49%) of 82 extremely low birthweight (ELBW, <1000 g) infants had periventricular haemorrhage (PVH). Ten (12%) had germinal layer haemorrhage (GLH) alone, 16 (20%) had intraventricular haemorrhage (IVH) and 14 (17%) had intracerebral haemorrhage (ICH). Almost all the cases of PVH had developed by 4 days of age. Small-for-gestational age infants (12% of study population) had a significantly lower incidence and severity of PVH than appropriate-for-gestational age infants. Of 94 infants born between 23 and 28 weeks gestation, 45 (48%) had PVH. The PVH incidence was 60% in those of 23-26 weeks and 38% in those of 27-28 weeks. The hospital survival rate of ELBW infants was 69% in those without PVH and 43% in those with PVH; 70% in GLH alone; 50% in IVH and 14% in ICH. Three survivors developed post-haemorrhage hydrocephalus of whom two required ventriculoperitoneal shunting. Five survivors developed periventricular leukomalacia (PVL) evidenced by cysts identified between 3 and 7 weeks of age. A significant decrease in the incidence of PVH occurred over the study period (67% in 1982, 38% in 1983 and 33% in 1984). This decrease was seen for ail grades of PVH. The reasons for this decreased incidence are still to be ascertained but this trend suggests that improvements in neonatal intensive care have the potential to improve the neurological outcome of more recent ELBW survivors.     

Periventricular haemorrhage and leukomalacia in extremely low birthweight infants

Forty (49%) of 82 extremely low birthweight (ELBW, less than 1000 g) infants had periventricular haemorrhage (PVH). Ten (12%) had germinal layer haemorrhage (GLH) alone, 16 (20%) had intraventricular haemorrhage (IVH) and 14 (17%) had intracerebral haemorrhage (ICH). Almost all the cases of PVH had developed by 4 days of age. Small-for-gestational age infants (12% of study population) had a significantly lower incidence and severity of PVH than appropriate-for-gestational age infants. Of 94 infants born between 23 and 28 weeks gestation, 45 (48%) had PVH. The PVH incidence was 60% in those of 23-26 weeks and 38% in those of 27-28 weeks. The hospital survival rate of ELBW infants was 69% in those without PVH and 43% in those with PVH; 70% in GLH alone; 50% in IVH and 14% in ICH. Three survivors developed post-haemorrhage hydrocephalus of whom two required ventriculoperitoneal shunting. Five survivors developed periventricular leukomalacia (PVL) evidenced by cysts identified between 3 and 7 weeks of age. A significant decrease in the incidence of PVH occurred over the study period (67% in 1982, 38% in 1983 and 33% in 1984). This decrease was seen for all grades of PVH. The reasons for this decreased incidence are still to be ascertained but this trend suggests that improvements in neonatal intensive care have the potential to improve the neurological outcome of more recent ELBW survivors.     

Risk factors for intraventricular haemorrhage in very low birth weight infants

Objective: In a prospective study at Uludag University Hospital, 120 premature infants with birthweights of 1500 g or less were screened for intraventricular hemorrhage (IVH) using cranial ultrasound. With the purpose of studying the incidence of IVH, the associated risk factors for these neonates were considered.Methods : We studied all the very low birth weight infants admitted in our neonatal unit. We examined the following variables as risk factors for IVH: sex, birth weight, gestational age, Apgar score, mechanichal ventilation, hypercapnia, use of antenatal steroids, tocolytic drugs, vaginalversus cesarean section delivery, and inbornversus outborn status, vasopressor infusion (any vasoactive drug such as dopamine, dobutamine, or epinephrine) not associated with resuscitation, and surfactant administration.Results :The incidence of IVH was 15% (18/120), 50% grade I (9/18), 17% grade II (3/18), 11 % grade III (2/18), and 22% grade IV (4/18). IVH occurred mainly in the first week of life (78%; 14/18). The significant risk factors for IVH were found to be prematurity, outborn status, low 5 minute Apgar score, vaginal delivery, hypercapnia, mechanical ventilation, hypotension, and use of vasopressors on the day of admission. Significant protective factors against IVH included antenatal steroid therapy, cesarean section, magnesium sulfate tocolysis, increasing gestational age, and increasing birth weight.Conclusion: Our results concur with the notion that a tertiary center is the optimal location for delivery of the high risk neonate. Transportation of infantsin utero to a perinatal center specializing in high risk-deliveries results in a decreased incidence of IVH when compared to infants transported postnatally. Aggressive resuscitation, with avoidance of hypercarbia, and rapid restoration of hypovolemia could potentially reduce the incidence of PVH/IVH     

Cognitive and motor function of neurologically impaired extremely low birth weight children

BACKGROUND:

Rates of neurological impairment among extremely low birth weight children (ELBW [<1 kg]) have decreased since 2000; however, their functioning is unexamined.

OBJECTIVE:

To compare motor and cognitive functioning of ELBW children with neurological impairment, including cerebral palsy and severe hypotonia/hypertonia, between two periods: 1990 to 1999 (n=83) and 2000 to 2005 (n=34).

METHODS:

Measures of function at 20 months corrected age included the Mental and Psychomotor Developmental Indexes of the Bayley Scales of Infant Development and the Gross Motor Functional Classification System as primary outcomes and individual motor function items as secondary outcomes.

RESULTS:

Analysis failed to reveal significant differences for the primary outcomes, although during 2000 to 2005, sitting significantly improved in children with neurological impairment (P=0.003).

CONCLUSION:

Decreases in rates of neurological impairment among ELBW children have been accompanied by a suggestion of improved motor function, although cognitive function has not changed.     

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.     

Extremely low birthweight neonates with protracted ventilation: mortality and 18-month neurodevelopmental outcomes

OBJECTIVE: To compare duration of ventilation to mortality and adverse neurodevelopmental outcomes among extremely low birth weight (ELBW; 501-1000 g) infants. STUDY DESIGN: Retrospective analysis of prospectively collected data from 5364 infants with a birthweight of 501 to 1000 g born at National Institute of Child Health and Human Development (NICHD) Neonatal Research Network centers from 1995 to 1998. The main outcome measures were: survival, duration of mechanical ventilation, and neurodevelopmental outcome. RESULTS: Overall survival was 71%. The median duration of ventilation for survivors was 23 days; 75% were free of mechanical ventilation by 39 days, and 7% were ventilated for > or = 60 days. Of those ventilated for > or = 60 days, 24% survived without impairment. Of those ventilated for > or = 90 days, only 7% survived without impairment. Of those ventilated > or = 120 days, all survivors were impaired. CONCLUSIONS: The prognosis for ELBW with protracted ventilation remains grim. The cohort who remain intubated have diminished survival and high rates of impairment. Parents of these infants should be informed of changes in prognosis as the time of ventilation increases.     

Grades I-II intraventricular hemorrhage in extremely low birth weight infants: effects on neurodevelopment

OBJECTIVE: To quantify the effect of grades I-II intraventricular hemorrhage (IVH) on the neurosensory and cognitive outcomes of extremely low birth weight infants. STUDY DESIGN: Of 706 extremely low birth weight infants without major malformations admitted to our center from 1992 to 2000, 537 survived to 20 months' corrected age (CA) and had cranial ultrasound studies performed, of whom 490 (91%) had complete neurodevelopmental assessments. Infants with severe cranial ultrasound abnormalities or meningitis were excluded, leaving a population of 362 infants, 258 of whom had a normal cranial ultrasound and 104 had an isolated grade I-II IVH. The groups had similar birth weight (808 vs 801 grams) and gestational age (26.5 vs 26.3 weeks). Outcomes of infants with normal cranial ultrasound were compared with those with grades I-II IVH at 20 months' CA. Outcomes included the Bayley Scales of Infant Development Mental Developmental Index (MDI) and major neurosensory abnormality. Logistic regression was used to assess the effect of grades I-II IVH on outcomes while adjusting for other risk factors. RESULTS: Extremely low birth weight infants with grades I-II IVH had a significantly lower mean MDI score than infants with normal cranial ultrasound (74 +/- 16 vs 79 +/- 14, P = .006). They had higher rates of MDI <70 (45% vs 25%; OR, 2.00; 95% CI, 1.20 to 3.30; P = .008), major neurologic abnormality (13% vs 5%; OR, 2.60; 95% CI, 1.06 to 6.36; P = .036), and neurodevelopmental impairment (47% vs 28%; OR, 1.83; 95% CI, 1.11 to 3.03; P = .018) at 20 months' CA, even when adjusting for confounding factors. CONCLUSIONS: Extremely low birth weight infants with grades I-II IVH have poorer neurodevelopmental outcomes at 20 months' CA than infants with normal cranial ultrasound. Advanced radiologic imaging may indicate additional brain injury associated with grade I-II IVH, which could explain these outcomes.     

Baseline serum magnesium concentrations and neurodevelopmental outcomes of extremely low birth weight premature infants

Aim

To test the hypothesis that, in ELBW infants who did not receive antenatal MgSO₄, lower baseline serum Mg is associated with poorer neurodevelopmental outcomes (NDO).

Study design

The study was conducted in two phases: Phase 1 — retrospective, and Phase 2 — prospective.

Subjects

Extremely low birth weight infants.

Outcome measures

Mortality and adverse NDO were assessed in relation to initial serum Mg measured in the first 12 hours of age.

Results

We studied 156 ELBW infants. In phase 1 (n = 102): initial serum Mg (median [IQ range]) was greater in the infants who died compared to those who survived (1.7 [1.5–2.2] mg/dL vs. 1.6 [1.4–1.7] mg/dL, p = 0.034). In phase 2 (n = 54): initial serum Mg was greater in infants who died or had adverse NDO at 9 months when compared to those who survived with better NDO (1.7 [1.55–2.1] mg/dL vs. 1.5 [1.4–1.68] mg/dL, p = 0.008). Using receiver operating characteristic (ROC) curve, increased Mg concentration in the first 12 hours > 1.6 mg/dL was associated with unfavorable outcomes with sensitivity of 73%, specificity of 67%, and odds ratio of 5.5 (CI = 1.2–24.8, p = 0.037).

Conclusions

In a cohort of preterm infants without antenatal exposure to MgSO₄, initial serum Mg concentrations associated positively with poor outcomes. Further studies are needed in ELBW infants with poor NDO to determine whether they have a dysfunctional transport system that prevents Mg from entering into cells, or they have an active process that excretes Mg extracellularly.     

Assisted ventilation and survival of extremely low birthweight infants

Objective : To determine the incremental consumption of ventilator resources associated with the improving survival rate of extremely low birthweight (ELBW, birthweight 500–999 g) infants, from the time assisted ventilation was introduced. Methodology : Cohort study of ELBW infants born in one tertiary perinatal centre (The Royal Women's Hospital, Melbourne). All ELBW infants born from 1971 to 1993 were included in the study. Inhospital survival rates and patient-days of assisted ventilation were the main outcome measures. Discrete eras of relatively stable survival rate and consumption of ventilator resources were identified. These comprised the years 1971–74, 1977–83, 1985–90, and 1992–93. Cost-effectiveness ratios (the incremental consumption of ventilator resources per additional survivor) were calculated between adjacent eras by dividing the increment in the consumption of ventilator resources by the increment in the survival rate. Results : The survival rates rose progressively between eras (6.2, 33.9, 49.1, 68.8%, respectively, as did the consumption of ventilator resources (0.1, 6.6, 16.2, 24.7 patient-days of assisted ventilation per livebirth, respectively). The cost-effectiveness ratio deteriorated initially, increasing from 23.2 to 63.5 additional patient-days of assisted ventilation per additional survivor, but then improved, falling to 43.1 additional patient-days of assisted ventilation per additional survivor in the last era. These changes were even more marked for those of birthweight 750-999 g (20.0, 63.2 to 35.9 additional patient-days of assisted ventilation per additional survivor, respectively). In contrast, the cost-effectiveness ratio was initially worse for those of birthweight 500-749 g, being three-fold higher than for the larger infants, and only improved substantially in the last era (59.8, 58.3 to 44.1 additional patient-days of assisted ventilation per additional survivor, respectively). Conclusions : The initial deterioration in cost-effectiveness ratios between successive eras probably reflected the increased availability of resources for assisted ventilation, without any other major advances in perinatal care. The improvement in cost-effectiveness in the last era reflected, in part, the increased use of antenatal steroid therapy and the introduction of exogenous surfactant to neonatal intensive care.     

Prevalence and aetiology of neurological impairment in extremely low birthweight infants

Objective : To determine the prevalence and perinatal predictors of cerebral palsy, intellectual impairment, visual impairment and deafness in a cohort of extremely low birthweight (ELBW) infants at two years of age.
Methodology : The study population comprised 199 of the 224 (89%) ELBW infants managed at the Mater's Mothers Hospital, Brisbane, between July 1977 and February 1990 and who survived to two years. The prevalence of cerebral palsy, intellectual impairment, blindness and deafness was measured by clinical, psychometric and audiological assessment and the association with 24 risk factors examined.
Results : Cerebral palsy occurred in 20 children (10%). Risk of cerebral palsy was associated with ventricular dilatation, intraventricular haemorrhage, necrotizing enterocolitis and multiple birth, though only ventricular dilatation (OR 4.41; 95% Cl 1.32-14.8) remained significant in the adjusted analysis. Intellectual impairment occurred in 20 children (10%) and was independently associated with ventricular dilatation (OR 15.0; 95% Cl 2.2-102.8), ventilation F _iO₂ >80% (OR 3.4; 95% Cl 1.01-11.5), vaginal delivery (OR 3.5; 95% Cl 1.09-11.4) and male sex (OR 6.1; 95% Cl 1.67-22.3). No perinatal predictor was statistically associated with risk of deafness. Retinopathy of prematurity (OR 36.9; 95% Cl 2.8-495.5) was associated with risk of later visual impairment.
Conclusions : Intellectual impairment was associated with a broad range of perinatal variables. Cerebral palsy was associated with fewer variables, all of which were also associated with intellectual impairment. Neurologic injury was associated with male sex and multiple birth, which are not biological insults themselves, but may be markers of susceptibility to injury.