Neonatal neurology in extremely and very low birth weight infants: introductory remarks

Survival rates of extremely and very low birth weight infants have been improved dramatically. However, some of the survivors suffer from neurological sequelae. A recent report showed that about 25% of the children with birth weight of less than 1,000 g had some handicaps, including cerebral palsy, mental retardation, and visual disturbance. Therefore, it is very important for pediatric neurologists to assess the neurological symptoms properly in the neonatal period. This symposium was organized to present recent progress in the methods for neurological assessment and to discuss how we should support the development of high risk infants.     

Fosphenytoin in infants of extremely low birth weight

Fosphenytoin, a phosphorylated prodrug of phenytoin, is useful for acute seizures, is given by parenteral administration, and has few cardiac and local irritation adverse effects. There is limited experience in the administration of this new agent to newborns, and concern has been raised regarding the conversion of the prodrug to phenytoin. In two low--birth-weight infants, it was observed that fosphenytoin was converted adequately with varying effects on seizure control.     

Vocal development of infants with very low birth weight

This study describes the vocal development of infants born with very low birth weights (VLBW). Samples of vocalizations were recorded from three groups of infants when they were 8, 12 and 18 months of age: preterm VLBW infants with bronchopulmonary dysplasia (BPD), preterm VLBW infants without BPD, and healthy full-term infants. Infants with BPD produced significantly smaller canonical syllable ratios than the full-term infants throughout the period of study. Premature VLBW infants who did not suffer from BPD produced relatively little canonical babble at 8 months of age, but were performing within the range of the full-term infants at 18 months of age. At 18 months of age, the infants with BPD were reported to have significantly smaller expressive vocabulary sizes than the healthier preterm and full-term infants.     

Characteristic neuropathology of leukomalacia in extremely low birth weight infants

Extremely low birth weight (ELBW) infants with periventricular leukomalacia (PVL) were examined by neuropathological and immunohistochemical methods. Thirteen ELBW infants of 85 infants with PVL, born at 23 to 27 weeks of gestation, showed a widespread type of distribution of PVL from the deep to intermediate white matter. Immunohistochemistry demonstrated glial fibrillary acidic protein (GFAP)-positive astrocytes to be increased in the deep white matter, often spreading to the intermediate white matter, in all cases of PVL. Tumor necrosis factor- (TNF-)-positive cells were found in the deep to intermediate white matter in 69% of PVL cases and appeared earlier, from 23 weeks of gestation, than in controls. β-Amyloid precursor protein (βAPP)-positive axons were found around PVL in the deep to intermediate white matter in 85% of the cases. In age-matched control ELBW infants, GFAP-, TNF--, or βAPP-positive cells were never found. Therefore, in ELBW infants, widespread axonal damage and glial activation with cytokine production occur in the progression of characteristic PVL lesions.     

EEG functional connectivity in term age extremely low birth weight infants

ObjectiveThe hypothesis is tested that electrocortical functional connectivity (quantified by coherence) of extremely low birth weight (ELBW) infants, measured at term post-menstrual age, has regional differences from that of full term infants.Methods128 lead EEG data were collected during sleep from 8 ELBW infants with normal head ultrasound exams and 8 typically developing full term infants. Regional spectral power and coherence were calculated.ResultsNo significant regional differences in EEG power were found between infant groups. However, compared to term infants, ELBW infants had significantly reduced interhemispheric coherence (in frontal polar and parietal regions) and intrahemispheric coherence (between frontal polar and parieto-occipital regions) in the 1–12 Hz band but increased interhemispheric coherence between occipital regions in the 24–50 Hz band.ConclusionsELBW infants at term post-menstrual age manifest regional differences in EEG functional connectivity as compared to term infants.SignificanceDistinctive spatial patterns of electrocortical synchrony are found in ELBW infants. These regional patterns may presage regional alterations in the structure of the cortex.     

Developmental outcome of very low birth weight infants requiring a ventriculo-peritoneal shunt

All infants of less than 1,500 g birth weight who required a ventriculo-peritoneal shunt were followed for developmental problems over the 1st year of life. There were 19 infants; 2 died within the 1st postoperative week. At 1 year of age corrected for prematurity the mean Bayley Mental Developmental Index was 62 +/- 23.0, and the mean Psychomotor Developmental Index was 61 +/- 19. Only 2 infants attained scores greater than 85 on both scales, while an additional 2 infants attained a score of greater than 85 on one scale. It is concluded that ventriculo-peritoneal shunting procedures performed after progressive ventricular enlargement has taken place are not likely to result in normal development of the infant less than 1,500 g birth weight.     

Outcome of very low birth weight infants with sonographic enlarged occipital horn

The objective of this study is to compare the neurodevelopmental outcome between very low birth weight infants with and without sonographic disproportionate enlargement of occipital horn. We retrospectively reviewed the brain sonography of all very low birth weight infants born at National Taiwan University Hospital between June 1997 and June 1999. Brain sonography was routinely performed at the age of the third, seventh, twenty-first, and later days as clinically indicated. Intracranial hemorrhage, periventricular leukomalacia, congenital hydrocephalus, and Stage III retinopathy of prematurity were excluded from our study because of the association with neurodevelopmental impairment. Patients with disproportional dilatation of occipital horn more than 15 mm in width were included in the study group, and those with less than 15 mm were in the control group. Both groups received developmental evaluation by the Bayley Scales of Infant Development II at corrected age of 6, 12, 18, and 24 months, respectively. Socioeconomic status and detailed medical history were obtained at assessments. Independent-samples t test was used for comparison. A total of 81 very low birth weight infants were included in this study: 49 infants (female 18, male 31) in the study group and 32 infants (female 23, male 9) in the control group. The mean gestation in these two groups was 30 +/- 2 weeks and 31.1 +/- 2.2 weeks (P = 0.156), and the mean birth body weight was 1290 +/- 269 gm and 1282 +/- 219 gm (P = 0.877), respectively. At corrected age of 24 months, there was no significant difference in muscle tone, neuromotor impairment, hearing impairment, vision, or speech development. Assessment with the mental development index (88.9 +/- 15.6 vs 93 +/- 13.2) (P = 0.238) and the psychomotor development index (93.3 +/- 10.3 vs 89.6 +/- 12.1) (P = 0.149) between these two groups was also comparable. This retrospective analysis suggests that ultrasonographic disproportionate enlargement of the occipital horn in very low birth weight infants does not affect the neuromotor development at corrected ages of 6, 12, 18, and 24 months.     

Neurodevelopment in very low birth weight premature infants with postnatal subependymal cysts

The aim of this study was to investigate the neurodevelopmental outcome in very low birth weight infants with postnatal subependymal cysts. During a 3-year period, postnatal subependymal cysts were diagnosed by serial cranial ultrasound in 21 very low birth weight infants born prior to 33 weeks' gestation. These infants and 116 healthy very low birth weight controls were evaluated with the Bayley Scales of Infant Development at 2 years of age. Preterm infants with postnatal subependymal cysts had a significantly lower Psychomotor Development Index (P = .034) and were more likely than the normal group to have motor developmental delay (Psychomotor Development Index <70) (P = .013). The findings indicate that postnatal subependymal cyst is a significant risk factor for impaired motor development in very low birth weight infants (odds ratio 5.73, 95% confidence interval 1.57-20.97).     

储液囊埋植引流治疗极低体质量早产儿脑室内出血致脑积水的疗效分析

目的 评估储液囊埋植引流治疗极低体质量早产儿脑室内出血致脑积水的疗效分析.方法 回顾性分析2005年1月至2011年6月期间,温州医学院第二附属医院收治的12例出生时体质量＜1 500 g的极低体质量早产儿脑室内出血合并脑积水,进行储液囊埋植引流治疗.储液囊埋植后根据临床表现和影像学检查结果,决定脑脊液引流次数,间歇引流时间和引流量,并观察术后的并发症.若储液囊引流无效者,改行脑室一腹腔分流术.结果 12例脑室出血Ⅲ级8例,Ⅳ级4例,孕龄26 ～ 32周,出生时平均体质量为(1023 ±223)g.埋植Ommaya储液囊时日龄为(17.7±3.1)d,平均体质量为(1 126±236)g.术后1例患儿死于肺部相关并发症,存活的11例患儿中,7例未发现脑室进行性扩大,3例取出储液囊.4例出现脑积水,行脑室一腹腔分流术,并同时取出储液囊.储液囊埋植引流的相关主要并发症(皮肤裂开、脑脊液漏、脑脊液感染、脑室出血)发生率为6/12例(50％),3例出现皮肤切口裂开合并发生脑脊液感染,2例单独出现脑脊液感染,l例术后出现脑室出血.结论 储液囊脑室埋植引流治疗极低体质量早产儿脑室内出血致脑积水具有操作简单、疗效满意、预防或减轻部分患儿脑积水的进一步发展、避免行永久性分流术等优点,但其并发症的发生率相对较高,采用改良的手术方法可降低并发症的发生.     

Secondary cystic lesions in the cerebellum in very low birth weight infants

We studied 4 very low birth weight infants with secondary cystic lesions in the cerebellum by serial cranial ultrasound and computed tomography. These infants presented severe respiratory distress, asphyxia at birth and intraventricular hemorrhage. In the neonatal period, cranial ultrasound examination showed significant intraventricular hemorrhage and posthemorrhagic ventricular dilatation with intraparenchymal hemorrhage. However, a cerebellar cyst was not seen in any of the infants. We found evidence of cerebellar hemorrhage by ultrasound in only one patient. Follow-up ultrasound examinations and CT scans showed progressive posthemorrhagic ventriculomegaly in three of the infants and large cystic lesions in the infratentorial area from 3 to 6 months old in all 4 infants. We conclude that the cystic lesions were caused by hemorrhagic and hypoxic-ischemic insults which occurred in very low birth weight infant.     

Use of external drainage for posthemorrhagic hydrocephalus in very low birth weight premature infants

To treat progressive posthemorrhagic hydrocephalus we used early external ventricular drainage (EVD) in 14 premature infants. We think it is important that the catheters in these critically ill infants be inserted in the neonatal intensive care unit, allowing us to keep the infants in an extremely stable environment. Only after prolonged external ventricular drainage (on average 38.4 days) is a ventriculoperitoneal shunt considered, preferably when the child has reached a body weight of 2000 g. There were no infections or other severe drainage-related problems. We report mean daily EVD volumes (which are related to body weight) and EVD duration. The 14 patients included 9 who required permanent shunting. Comparing the mortality, morbidity and follow-up data to at least 3 months of age in this group with similar data for an earlier cohort treated with lumbar punctures and late permanent shunting, we demonstrate the safety of the policy we have recently adopted. Received: 8 January 1997     

Evidence for late developmental deficit in very low birth weight infants surviving intraventricular hemorrhage

88 very low birth weight preterm infants who had been evaluated with neonatal computed tomography scanning and/or echoencephalography were subsequently brought to follow-up. Serial neurodevelopmental testing at 6, 12, and 18 months corrected age demonstrated that even the lesser grades of germinal matrix and intraventricular hemorrhage may be associated with a relatively less favorable neurodevelopmental outcome.     

Parenting stress in families with very low birth weight preterm infants in early infancy

Taking care of a premature infant adds an extra burden to already stressed parents. Previous studies have shown that parental stress occurs during the initial hospitalization. However, there is little information on parental stress over time, and the few existing results are conflicting. In addition, many studies have focused on maternal stress but there is little information about a father's long-term adaptation to stress. The purpose of this study was to examine the degree and type of parenting stress in the families of very low birth weight (VLBW) preterm infants over the first two years of life. We compared parenting stress in families with preterm infants with control families, while also comparing the stress in mothers to that in fathers. Furthermore, we explored the relationship between parenting stress in the preterm group with identified factors that included the infant's age, medical complications, and parents’ perceived feeding issues after they had been discharged from the hospital. This was an exploratory study with a cross sectional design. Participants included a total of 505 mothers from Tainan, Taiwan; 297 with preterm children (239 mothers, 58 fathers) and 208 with full-term children (181 mothers, 27 fathers). Assessments including the Parenting Stress Index, Neonatal Medical Index and Behavior-based Feeding Questionnaire were used to measure parental distress, infants’ medical complications and parents’ perceived feeding issues, respectively. Results of the study, though not statistically significant, indicated the presence of increased parenting stress in parents of preterm infants as compared to parents of full-term infants. 13.1% of mothers with preterm infants demonstrated total stress levels that warranted clinical intervention. We also found that mothers of preterm infants presented different parenting stress patterns than fathers of preterm infants. Fathers of preterm infants tended to have overall higher stress scores than mothers. On the other hand, mothers of preterm infants tended to report more health related difficulties, more depression, higher social isolation and role restriction, and less support from their spouses, than reported by fathers. Moreover, as time went on, parents with preterm infants continued to experience greater parenting stress than those with full-term infants. Understanding the experiences of parents with preterm children is important for health care providers while interviewing parents for information regarding their children and designing intervention programs to improve children's outcomes.     

Umbilical vein interleukin-6 levels in very low birth weight infants developing intraventricular hemorrhage

To assess the relationship between perinatal infection/inflammation as reflected by umbilical vein interleukin-6 (IL-6) levels and the development of periventricular-intraventricular hemorrhage (IVH) in very low birth weight (VLBW) infants, we tested the hypothesis that VLBW infants who develop IVH have higher concentrations of IL-6 in an umbilical vein sample compared to infants without IVH. An inception cohort of 69 VLBW infants was followed from birth until discharge or death to determine the development of IVH by serial neuroultrasounds. Umbilical vein IL-6 levels were measured using commercially available ELISA kit (Endogen Laboratories, Woburn, MA) and compared in IVH and control cohorts. Twenty-two (32%) infants developed IVH, including 18 (82%) with grade I or II and 4 (18%) with grade III or IV. One of these infants also developed periventricular leukomalacia. The umbilical vein IL-6 levels were significantly elevated in infants with IVH with median value of 87 pg/ml (25th percentile value 30 pg/ml and 75th percentile value 310 pg/ml) compared with infants without IVH, with a median value of 0 pg/ml (25th percentile value 0 pm/ml and 75th percentile value 4 pg/ml) (P = 0.007). Umbilical vein IL-6 levels are elevated in neonates who subsequently develop IVH.     

Association between mechanical ventilation and neurodevelopmental disorders in a nationwide cohort of extremely low birth weight infants

Mechanical ventilation for preterm infants independently contributes to poor neurodevelopmental performance. However, few studies have investigated the association between the duration of mechanical ventilation and the risk for various developmental disorders in extremely low birth weight (ELBW) (<1000 g) infants. Using a large nationwide database, we did a 10-year retrospective follow-up study to explore the effect of mechanical ventilation on the incidence of cerebral palsy (CP), autism spectrum disorder (ASD), intellectual disability (ID), and attention-deficit/hyperactivity disorder (ADHD) in ELBW infants born between 1998 and 2001. Seven hundred twenty-eight ELBW infants without diagnoses of brain insults or focal brain lesions in the initial hospital stay were identified and divided into three groups (days on ventilator: ≦2, 3–14, ≧15 days). After adjusting for demographic and medical factors, the infants in the ≧15 days group had higher risks for CP (adjusted hazard ratio: 2.66; 95% confidence interval: 1.50–4.59; p < 0.001) and ADHD (adjusted hazard ratio: 1.95; 95% confidence interval: 1.02–3.76; p < 0.05), than did infants in the ≦2 days group. The risk for ASD or ID was not significantly different between the three groups. We conclude that mechanical ventilation for ≧15 days increased the risk for CP and ADHD in ELBW infants even without significant neonatal brain damage. Developing a brain-protective respiratory support strategy in response to real-time cerebral hemodynamic and oxygenation changes has the potential to improve neurodevelopmental outcomes in ELBW infants.     

Nutritional state,maturational delay on electroencephalogram,and developmental outcome in extremely low birth weight infants

The aim of this study is to clarify the relation among developmental outcome, nutritional state during the neonatal period, maturational electroencephalographic changes. Thirteen extremely low birth weight infants who completed 6- or 9-year follow-up were a subject of this study. Undernutrition was defined as enteral feeding below 100 mL/kg/day at 3 weeks of age. Dysmature patterns were defined as the persistence of EEG patterns 2 weeks or more immature for post-conceptional age. IQ was examined at 6 and 9 years of age. Body height and weight, and head circumference at 6 years of age were stratified by the percentile grades. Full and verbal IQ was significantly lower in infants with undernutrition than those with normal nutrition. Among infants with undernutrition, those with persistent dysmature patterns tended to have lower full and performance IQ than those without persistent dysmature patterns. Head circumference was 50 percentile or larger in all infants with normal nutrition, whereas it was below 50 percentile in six of eight infants with undernutrition. Extremely low birth weight infants with undernutrition had worse neurodevelopmental outcome at 6 or 9 years of age than those with normal nutrition. Among infants with undernutrition, developmental outcome was relatively worse in those with persistent dysmature patterns than those without.     

Cognitive outcomes for extremely preterm/extremely low birth weight children in kindergarten

Our objectives were to examine cognitive outcomes for extremely preterm/extremely low birth weight (EPT/ELBW, gestational age <28 weeks and/or birth weight <1000 g) children in kindergarten and the associations of these outcomes with neonatal factors, early childhood neurodevelopmental impairment, and socioeconomic status (SES). The sample comprised a hospital-based 2001-2003 birth cohort of 148 EPT/ELBW children (mean birth weight 818 g; mean gestational age 26 weeks) and a comparison group of 111 term-born normal birth weight (NBW) classmate controls. Controlling for background factors, the EPT/ELBW group had pervasive deficits relative to the NBW group on a comprehensive test battery, with rates of cognitive deficits that were 3 to 6 times higher in the EPT/ELBW group. Deficits on a measure of response inhibition were found in 48% versus 10%, odds ratio (95% confidence interval) = 7.32 (3.32, 16.16), p < .001. Deficits on measures of executive function and motor and perceptual-motor abilities were found even when controlling for acquired verbal knowledge. Neonatal risk factors, early neurodevelopmental impairment, and lower SES were associated with higher rates of deficits within the EPT/ELBW group. The findings document both global and selective cognitive deficits in EPT/ELBW children at school entry and justify efforts at early identification and intervention.