Risk Of Neurodevelopmental Impairment Research Articles

Neurobehavioral assessment as a predictor of neurodevelopmental outcome in preterm infants

Preterm infants are at risk for neurodevelopmental impairment. The Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) is a standardized assessment for the neurobehavioral integrity of the newborn. The use of NNNS as a prognostic tool is still emerging. We hypothesized that the NNNS examination performed at term equivalent can detect neurobehavioral alterations in very low birth weight infants and can help in predicting their neurodevelopmental outcome at 18 months corrected age (CA). This is a prospective study that included preterm infants with birth weight <1500 g and gestational age ≤ 34 weeks. They were evaluated with NNNS at term-equivalent and 12 summary scores were assigned. Infants who had 2 or more NNNS summary scores that were 2 s.d. beyond the mean of the study group were categorized as having abnormal NNNS. Mental Developmental Index (MDI) and Psychomotor Developmental Index (PDI) of Bayley Scales of Infant Development (BSID-II) were determined at 18 months CA. Multiple linear regression models were used to examine the predictivity of the NNNS summary scores for both MDI and PDI. A total of 41 infants were evaluated at term and at 18 months CA. The average MDI was 78±15 and the average PDI was 80 ± 14. Significant neurodevelopmental delay was observed in 50% and 31% of infants with abnormal and normal NNNS, respectively. Using multiple linear regression, NNNS was predictive for both MDI (P=0.011, adjusted R (2)=0.295) and PDI (P=0.002, adjusted R (2)=0.441). Lower MDI was associated with less regulation and more nonoptimal reflexes, whereas lower PDI was associated with less regulation, more nonoptimal reflexes, hypertonicity and handling. NNNS at term-equivalent age can detect neurobehavioral alterations in very low birth weight infants. Individual summary scores showed significant correlation with both the MDI and PDI at 18 months CA.

Fluconazole prophylaxis: can we eliminate invasive Candida infections in the neonatal ICU?

Owing to the high mortality, risk of neurodevelopmental impairment and end-organ involvement with fungal infections in the neonate, prevention of invasive Candida infections in extremely preterm infants should be a priority for each neonatal ICU. Even with prompt or empiric treatment, mortality and neurodevelopmental impairment is high (57%) in infants <1000 g. Multiple studies have been performed with fluconazole prophylaxis, including a recent multicenter randomized controlled trial. All of the studies have demonstrated efficacy and safety with no increase or emergence of fungal resistance. Analysis of these studies demonstrates that fluconazole prophylaxis decreased the incidence of invasive Candida infections in high-risk infants <1000 g by 91% (P = 0.0004) and all infants <1500 g by 85% (P < 0.0001). The mortality rate from all causes was 25% lower (P = 0.029). Furthermore, studies have demonstrated that all Candida-related mortality can be eliminated in an entire neonatal ICU by targeting fluconazole prophylaxis in infants <1000 g. Targeting fluconazole prophylaxis to infants who are either <1000 g or < or =27 weeks is highly effective, safe and inexpensive, and can eliminate these infections as a cause of neurodevelopmental impairment and mortality.

Major Congenital Anomalies Place Extremely Low Birth Weight Infants at Higher Risk for Poor Growth and Developmental Outcomes

Studies of growth and neurodevelopmental impairment in extremely low birth weight infants often exclude infants with major congenital anomalies; thus, there are few outcome data available on these infants. The purpose of this work was to compare growth and neurodevelopmental outcomes of extremely low birth weight infants with major anomalies to extremely low birth weight infants without these findings. It was hypothesized that infants with severe anomalies would have worse growth, neurodevelopmental, and survival outcomes. A retrospective cohort analysis was performed on 5920 extremely low birth weight infants surviving beyond 12 hours of life at 19 neonatal network centers between 1998 and 2001. Infants with significant anomalies were more likely to die before 18 to 22 months' corrected age. A total of 3705 children underwent neurodevelopmental and anthropometric evaluation at 18 to 22 months' corrected age. Statistical significance for unadjusted comparisons was determined by Wilcoxon tests for continuous variables and chi2 or Fisher's exact tests for categorical variables. Regression models were used to compare the outcomes after adjusting for potential confounders. Children with major congenital anomalies were more likely to have Bayley Mental Development Index scores of < or = 70, Psychomotor Development Index scores of < or = 70, neurodevelopmental impairment, moderate-to-severe cerebral palsy, length in the < or = 10th percentile, head circumference in the < or = 10th percentile, more rehospitalizations, and higher rates of early intervention use at 18 to 22 months' corrected age. At 18 to 22 months' corrected age, extremely low birth weight infants born with major anomalies have nearly twice the risk for neurodevelopmental impairment, increased risk of poor growth, and > 3 times greater risk of rehospitalization when compared with extremely low birth weight infants without major anomalies. This information may be valuable for counseling parents regarding the outcomes of these infants and for the facilitation of appropriate support and intervention services.

Urinary S-100B Concentrations in Term and Preterm Infants at Risk for Brain Damage

Background: Elevated serum concentrations of S-100B, a 21-kDa protein expressed in astroglial cells, has been used to assess cerebral damage after head trauma, infection, ischemia, and perinatal asphyxia. Objective: As S-100B is eliminated by the kidneys, we investigated the feasibility of measuring S-100B in urine of newborns with severe perinatal asphyxia, and in very low birth weight (VLBW) preterm infants at risk for neurodevelopmental impairment. Methods: We first analyzed urine samples of 8 term or near-term newborns without major medical problems, followed by urine samples of 2 term newborns with severe birth asphyxia, and finally urine samples of 8 VLBW (gestational age 24–28 weeks) infants collected every 4 h for up to 10 days. Results: Urinary S-100B concentrations in 8 term or near-term newborns without major medical problems were consistently <1 µg/l. In 2 term newborns with severe asphyxia (Apgar 0/0/0 and 0/2/4) who subsequently had widespread cerebral damage on magnetic resonance imaging, peak urinary S-100B concentrations on the first day of life were 28.1 and 28.4 µg/l, respectively. In 5/8 VLBW infants, urinary S-100B was >1 µg/l in samples obtained on the first day of life (range 1.2–44.9 µg/l, median 6.8 µg/l). Peak S-100B in urine samples collected during the first 12 h of life were negatively related to gestational age (R_s = –0.882, p = 0.009). Three of the 8 preterm infants had peak urinary concentrations >10 µg/l but neither ultrasound signs of brain damage nor neurodevelopmental delay at 1 year corrected age. Conclusions: The determination of urinary S-100B concentrations might be helpful in term infants with severe asphyxia, while high urinary S-100B concentrations in preterm infants are to be attributed to immaturity.

Neonatal seizures: Have we got the treatment right?

Neonatal seizures: Have we got the treatment right?

Iron Deficiency and Impaired Cognition in Toddlers

Iron deficiency in toddlers is associated with impaired cognition and is an underestimated and undertreated problem. The prevalence of iron deficiency anemia (IDA) during the first year of life has been dramatically reduced in developed countries, mainly due to the increase in breastfeeding and the use of iron-fortified feeding formulae. However, in US and UK children aged 1-2 years, recent studies have shown prevalence rates of >10% and 30% for IDA and iron deficiency, respectively. The daily iron intake in children aged 1-2 years is lower than in any other age group during life. IDA during the first 2 years of life is associated with impaired mental and psychomotor development and these deficits are long lasting, and perhaps irreversible, despite the correction of the anemia. Another compelling reason to prevent iron deficiency in children, especially in children aged 1-2 years, is the proven association of iron deficiency with increased lead absorption. Lead-associated cognitive deficits occur at blood lead levels <10 microg/L, a level once thought to be harmless. The current prevalence rates of iron deficiency and IDA in toddlers, especially among those in the lower socioeconomic groups, are unacceptably high. These young children are doubly at risk for neurodevelopmental impairment, both from the iron deficiency itself as well as from CNS damage caused by the associated increased lead absorption. The current screening and treatment recommendations for IDA in the US and in other developed countries appear to have been unsuccessful in preventing iron deficiency and IDA in a large number of toddlers. Similarly, the associated problem of impaired mental and psychomotor development has not been adequately recognized or addressed in the existing medical literature. The author recommends that, after breastfeeding or an iron-fortified formula is stopped, iron deficiency and IDA be prevented by routine daily supplemental doses of 10mg of elemental iron via iron-fortified vitamins, iron drops, or iron-fortified drinks.

Growth and neurodevelopmental outcome of very low birthweight infants with necrotizing enterocolitis

The aim of the study was to assess the effect of necrotizing enterocolitis (NEC) on neurodevelopmental outcome and growth. Neurodevelopmental outcome of 20 out of 22 suriviving very low birthweight infants (VLBW) diagnosed with NEC between 1992 and 1996 was compared with 40 control infants matched for gestational age and year of admission. Follow‐up studies were performed at 12 and 20 mo of corrected age. The German revision of the Griffiths' scales was used for development assessment. Neurodevelopment was significantly delayed in infants with NEC at 12 mo (median general developmental quotient: 90.0 vs 97.8; p = 0.04) and 20 mo (86.4 vs 97.7; p = 0.004) of age. Somatic growth did not differ between infants with and without NEC. Fifty‐five percent of infants suffering from NEC but only 22.5% of the infants without NEC were severely retarded (developmental quotient &lt; ‐2 SD of a control group of healthy newborns) at 20 mo of corrected age. Conclusion: Preterm infants developing NEC are at risk for neurodevelopmental impairment and need close neurodevelopmental follow‐up for the first years of life.

Growth and neurodevelopmental outcome of very low birthweight infants with necrotizing enterocolitis.

The aim of the study was to assess the effect of necrotizing enterocolitis (NEC) on neurodevelopmental outcome and growth. Neurodevelopmental outcome of 20 out of 22 suriviving very low birthweight infants (VLBW) diagnosed with NEC between 1992 and 1996 was compared with 40 control infants matched for gestational age and year of admission. Follow-up studies were performed at 12 and 20 mo of corrected age. The German revision of the Griffiths' scales was used for development assessment. Neurodevelopment was significantly delayed in infants with NEC at 12 mo (median general developmental quotient: 90.0 vs 97.8; p = 0.04) and 20 mo (86.4 vs 97.7; p = 0.004) of age. Somatic growth did not differ between infants with and without NEC. Fifty-five percent of infants suffering from NEC but only 22.5% of the infants without NEC were severely retarded (developmental quotient < -2 SD of a control group of healthy newborns) at 20 mo of corrected age. Preterm infants developing NEC are at risk for neurodevelopmental impairment and need close neurodevelopmental follow-up for the first years of life.

Visual event-related brain potentials in 4-month-old infants at risk for neurodevelopmental impairments.

The recording of event-related potentials (ERPs) is an electrophysiologic technique that has been used to evaluate the functional maturation of neural pathways responsible for recognition memory systems in infants and children. The purpose of this study was to evaluate ERP correlates of visual recognition memory in 4-month-old infants at risk for later cognitive impairments. We compared ERPs using a test of shape recognition at 4 months of age (adjusted for prematurity) in 16 high-risk, neonatal intensive care unit (NICU) survivors and 16 healthy full-term infants. ERPs were recorded while infants were familiarized with one stimulus (a red cross, 15 trials), then tested with 60 trials of this familiar stimulus and a novel stimulus (a red corkscrew). Both the NICU and control groups' ERPs demonstrated evidence of differential processing of the two stimuli, but the NICU groups' ERP patterns were distinctly different from those of the control group. In the NICU group, the novel stimulus elicited parietal positivity at 1000-1700 ms poststimulus, whereas in the control group the novel stimulus elicited occipital and frontal negativity at 500-1700 ms poststimulus. The ERP pattern demonstrated by the NICU group was atypical as it has not been previously described in healthy infants. The results of the study indicate that the ERP technique can be used to demonstrate altered patterns of neural activity during tasks of visual recognition memory in high-risk infants. We speculate that the atypical ERP patterns described in this study may indicate that patterns of synaptic organization were altered by neonatal events.