Hammersmith Infant Neurological Examination in infants born at term: Predicting outcomes other than cerebral palsy.

AIM: We explored the ability of the Hammersmith Infant Neurological Examination (HINE) to identify cognitive performance delay at 2 years in a large cohort of infants born at term. METHOD: We conducted a retrospective study of infants born at term at risk of neurodevelopmental impairments assessed using the HINE between 3 and 12 months post-term age and compared them with a cohort of typically developing infants born at term. All infants performed a neurodevelopmental assessment at 2 years of age using the Mental Development Index (MDI) of the Bayley Scales of Infant Development, Second Edition; the presence of cerebral palsy (CP) was also reported. The infants were classified as being cognitively normal/mildly delayed or significantly delayed (MDI < 70). The predictive validity of HINE scores for significantly delayed cognitive performance, in infants with and without CP, was calculated using specific cut-off scores according to age at assessment. RESULTS: A total of 446 at-risk and 235 typically developing infants (345 males, 336 females; mean [SD] gestational age 38.7 weeks [1.4], range 37-43 weeks) were included. Of the at-risk infants, 408 did not have CP at 2 years; 243 had a normal/mild delayed MDI and 165 had an MDI less than 70. Of the at-risk infants, 38 developed CP. HINE scores showed a good sensitivity and specificity, mainly after 3 months, for identifying significantly delayed cognitive performance in infants without CP. In those with CP, the score was associated with their cognitive performance. The comparison group had the highest HINE scores. INTERPRETATION: The HINE provides evidence about the risk of delayed cognitive performance at age 2 years in infants born at term with and without CP.

EXAMEN NEUROLÓGICO INFANTIL DE HAMMERSMITH EN BEBÉS NACIDOS A TÉRMINO: SU USO PARA PREDECIR OTRAS CONDICIONES ADEMÁS DE LA PARÁLISIS CEREBRAL: OBJETIVO: Valoramos la capacidad del examen neurológico infantil de Hammersmith (HINE) para identificar el retraso en el rendimiento cognitivo a los 2 años en una cohorte grande de bebés nacidos a término. MÉTODO: Realizamos un estudio retrospectivo de bebés nacidos a término con riesgo de trastornos del desarrollo neurológico evaluados mediante el HINE entre los 3 y los 12 meses de edad postérmino y los comparamos con una cohorte de bebés nacidos a término con un desarrollo típico. Todos los bebés realizaron una evaluación del desarrollo neurológico a los 2 años de edad utilizando el Índice de Desarrollo Mental (MDI) de las Escalas de Desarrollo Infantil de Bayley, Segunda Edición; también se informó la presencia de parálisis cerebral (PC). Los bebés se clasificaron como cognitivamente normales/levemente con retreaso o significativamente con retraso (MDI < 70). La validez predictiva de las puntuaciones HINE para el rendimiento cognitivo con retraso significativo, en bebés con y sin parálisis cerebral, se calculó utilizando puntuaciones de corte específicas según la edad en la evaluación. RESULTADOS: Se incluyeron un total de 446 lactantes en riesgo y 235 con desarrollo normal (345 varones, 336 mujeres; edad gestacional media [DE] 38,7 semanas [1,4], rango de 37 a 43 semanas). De los lactantes en riesgo, 408 no tenían parálisis cerebral a los 2 años; 243 tenían un MDI con retraso normal/leve y 165 tenían un MDI inferior a 70. De los bebés en riesgo, 38 desarrollaron PC. Las puntuaciones HINE mostraron una buena sensibilidad y especificidad, principalmente después de 3 meses, para identificar un rendimiento cognitivo severo en lactantes sin PC. En aquellos con PC, la puntuación se asoció con su rendimiento cognitivo. El grupo de comparación tuvo las puntuaciones HINE más altas. INTERPRETACIÓN: El HINE proporciona evidencia sobre el riesgo de retraso en el rendimiento cognitivo a los 2 años de edad en bebés nacidos a término con y sin parálisis cerebral.

Hammersmith Infant Neurological Examination for infants born preterm: predicting outcomes other than cerebral palsy.

AIM: We explored the ability of the Hammersmith Infant Neurological Examination (HINE) to identify typical and delayed cognitive performance in a large population of infants born preterm, both with and without cerebral palsy (CP). METHOD: We conducted a retrospective study of infants born preterm who had repeated HINEs between 3 and 12 months corrected age. At 2 years, cognition was assessed using the Mental Development Index (MDI; from the Bayley Scales of Infant Development, Second Edition) and the presence and severity of CP was determined. All children were classified as cognitively typical/mildly delayed or significantly delayed (MDI <70) and CP. The predictive validity of HINE scores for significantly delayed cognitive performance, in children with and without CP, was calculated using specific cut-off scores according to age at assessment. RESULTS: Of 1229 eligible infants (gestational age 25-36wks, mean [SD] 34.9 [2.3]; 646 males, 583 females), 1108 did not develop CP, 891 had an MDI that was typical/mildly delayed, and 217 had an MDI less than 70. Of the 121 infants who developed CP, the MDI was typical in 28, mildly delayed in 27, and less than 70 in 66. HINE scores showed a good sensitivity and specificity, especially after 3 months, for detecting significantly delayed cognitive performance in infants without CP. In those who developed CP, the score was associated with their cognitive level. INTERPRETATION: The HINE provides information about the risk of delayed cognitive performance in infants born preterm with and without CP. What this paper adds The Hammersmith Infant Neurological Examination (HINE) can be used in the first year to identify infants born preterm at risk for delayed cognitive performance. Age-dependent HINE cut-off scores are proposed for detecting increased risk of delayed cognitive performance.

Early psychomotor development of low-risk preterm infants: Influence of gestational age and gender.

BACKGROUND: The influence of gestational age and gender in the neurodevelopment of infants during the first year of age is not yet fully elucidated. AIMS: The purpose of this study was to identify the early occurrence of neurodevelopmental differences, between very preterm, late preterm and term born infants and the possible influence of the gender on the neurodevelopment in early infancy. METHODS: A total of 188 low-risk infants, 69 very preterms, 71 late-preterms, and 48 term infants were assessed at 3, 6, 9, 12 months corrected age using the Hammersmith Infant Neurological Examination (HINE). At two years of age infants performed the Mental Developmental Index (MDI) of the Bayley Scales of Infant Development. RESULTS: The main results indicate that both very preterms and late-preterms showed significant lower global scores than term born infants at each evaluation (p < 0.001) at HINE and namely, at 3 months for the subsections "cranial nerve" and "posture" and at every age for "tone"; no gender differences has been evidenced in neurological performances. At the MDI, very preterms showed significant lower scores (p < 0.01) than both late-preterm and term born infants; gender differences were observed for preterms only (very and late), with best performances for females. CONCLUSIONS: Our results point out the presence of gestational age and gender-dependent differences in the development of infants assessed during the first 2 years of life.

Prognostic value of the qualitative assessments of general movements in late-preterm infants.

BACKGROUND: The quality of general movements (GMs) and its predictive value have never been evaluated in late-preterm (LP) infants. AIMS: To determine the characteristics of GMs and their predictive value for neurodevelopmental outcome in a cohort of infants born between 34 and 36 weeks' gestation. STUDY DESIGN AND SUBJECTS: 574 LP infants were examined using the standard methodological principles of Prechtl's method for assessing GMs both during writhing and fidgety periods. OUTCOME MEASURES: Infants were assessed at 2 years of age with neuromotor and developmental scales. RESULTS: A significant correlation was found between GMs and outcome both at writhing (rs 0.68; p < 0.001) and at fidgety age (rs 0.78; p < 0.001). The assessment at 1 month showed 100% sensitivity and 86% specificity of predicting the development of cerebral palsy (CP), that at 3 months was 100% sensitivity and 97% specificity. CONCLUSIONS: During the fidgety age GMs predict CP with very high sensitivity and specificity. The qualitative assessment of GMs should be employed to help identify LP infants who require early intervention for neurological abnormalities.

Neurological assessment in infants discharged from a neonatal intensive care unit.

BACKGROUND: Longitudinal motor assessment in infants at different neurodevelopmental risk has not been previously evaluated using structured assessments. AIM: To verify if the Hammersmith Infant Neurological Examination (HINE) is a good tool to predict the neuromotor outcome in infants discharged from a level II-III Neonatal Intensive Care Unit (NICU) METHODS: In this cohort analysis, 1541 infants discharged from our NICU between January of 2002 and the April 2006 were enrolled and assessed using the HINE at 3, 6, 9, 12 months. At two years, these infants were further assessed, and grouped into infants with normal outcome (1150), with mild disability (321) and with cerebral palsy (70), RESULTS: Correlation analysis of Spearman showed a significant (p < 0.0001) and moderate (r(2) = -0.55 to -0.73) negative correlation between HINE scores (3, 6, 9, 12 months) and neurological outcome at two years. Cut-off scores for each assessment' age were provided as predictive value for cerebral palsy. DISCUSSION: This study mainly showed that HINE, as soon as the first months of life, helps in the process of prediction of neurological outcome at two years of age in a heterogeneous population of infants discharged from an NICU.

Longitudinal cognitive assessment in healthy late preterm infants.

BACKGROUND: Longitudinal cognitive development in late preterm (LP) infants has not been previously evaluated, using structured assessments. AIM: To assess longitudinally cognitive development in a population of healthy LP infants from 12 months to preschool age. METHODS: Sixty-two low-risk LP infants (33-36 weeks gestation) with normal or only minor findings on their cranial ultrasound scans were included in the study. They were assessed at 12 and 18 months corrected age using the Bayley Scales of Infant Development II to obtain the mental development index (MDI) and then at preschool age (mean age 62 ± 7 months) using the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-R). RESULTS: The MDI scores obtained at both 12 and 18 months corrected age were within the reported normative range. Using uncorrected ages, their scores were lower at both ages than those obtained using CA (p < 0.01). Full-scale IQ scores within the reported normal range were obtained at 5 years using the WPPSI-R for all but 6 children. Females had significantly higher scores than males (p < 0.001) for the MDI at both 12 and 18 months corrected and uncorrected age. No gender differences were found at preschool age using the WPPSI-R. CONCLUSIONS: Our results suggest that over 90% of the low-risk late preterms reach an MDI and IQ at preschool age within normal range.

Bovine lactoferrin prevents invasive fungal infections in very low birth weight infants: a randomized controlled trial.

BACKGROUND: Lactoferrin is a mammalian milk glycoprotein involved in innate immunity. Recent data show that bovine lactoferrin (bLF) prevents late-onset sepsis in preterm very low birth weight (VLBW) neonates. METHODS: This is a secondary analysis of data from a multicenter randomized controlled trial where preterm VLBW neonates randomly received bLF (100 mg/day; group A1), bLF + Lactobacillus rhamnosus GG (10(6) colony-forming units per day; group A2), or placebo (group B) for 6 weeks. Here we analyze the incidence rates of fungal colonization, invasive fungal infection (IFI), and rate of progression from colonization to infection in all groups. RESULTS: This study included 472 neonates whose clinical, nutritional, and demographical characteristics were similar. Overall, the incidence of fungal colonization was comparable (17.6%, 16.6%, and 18.5% in A1, A2, and B, respectively; P = .89 [A1] and .77 [A2]). In contrast, IFIs were significantly decreased in A1 and A2 (0.7% and 2.0%, respectively) compared with B (7.7%; P = .002 [A1] and .02 [A2]), and this was significantly true both in <1000 g (0.9% [A1] and 5.6% [A2], vs 15.0%) and in 1001 to 1500 g infants (0% and 0% vs 3.7%). The progression rate colonization-infection was significantly lower in the bLF groups: 3.7% (A1) and 12% (A2), vs 41.9%; P < .001 (A1) and P = .02 (A2). No IFI-attributable deaths occurred in the treatment groups, versus 2 in placebo. No adverse effects or intolerances occurred. CONCLUSIONS: Prophylactic oral administration of bLF reduces the incidence of IFI in preterm VLBW neonates. No effect is seen on colonization. The protective effect on IFI is likely due to limitation of ability of fungal colonies to progress toward invasion and systemic disease in colonized infants.

Neurological examination of late-preterm infants at term age.

BACKGROUND: Late-preterm infants represent 70% of the whole preterm population. AIMS: To establish the range and frequency distribution of neonatal neurological scores in a large cohort of low risk late-preterm infants and the possible differences with full-term infants. METHODS: Three hundred-seventy-five healthy infants born between 34 and 36 weeks gestational age (GA) without major brain lesions were assessed between 39 and 41 weeks post-menstrual age using the Hammersmith Neonatal Neurologic Assessment and compared to the scores obtained using the same examination in full-term infants. RESULTS: Infants born at 35 and 36 weeks GA had similar median scores in 32 of the 34 items. Infants born at 34 weeks GA had a different profile of scores compared to those born at 35 and 36 weeks, mainly in the tone items. While in infants born at 34 weeks the assessment at term age showed similar median scores to those obtained in full-term infants in 25/34 items, in those born at 35 and 36 GA the number of scores similar to full-term infants increased to 29/34. The main differences involved the tone items, with more marked flexor tone in the limbs and better head control for those born at 35 and 36 weeks. CONCLUSIONS: This data can help as reference data when examining late-preterm infants at term age to see where the individual child stands compared to age matched low risk infants and to identify signs that are outside the reported range in infants with lesions or other risk factors.

The forward parachute reaction and independent walking in infants with brain lesions.

AIM: The aim of this study was to assess the onset of forward parachute reaction (FPR) in infants with brain lesions and its correlation with age of walking. METHOD: FPR was assessed at 6, 9, and 12 months in 140 infants with brain lesions (78 males, 62 females; mean gestational age 31 wks; SD 3.6 wks; mean birthweight 1450 g, SD 252 g). On cranial ultrasound 62 infants had mild and 78 had major abnormalities; 86 developed cerebral palsy. All were followed for 5 years, and the age at which each child achieved independent walking was recorded. Infants who had been born small for gestational age (weight <10th centile) were excluded, as were those who had major congenital malformations, severe postnatal infectious diseases, or metabolic or haematological complications. RESULTS: A complete FPR was present in eight infants at 6 months, in 42 at 9 months, and in 71 at 12 months. At 12 months, 29 infants presented incomplete FPR and 40 presented absent FPR. Seventy-three infants were able to walk independently between the ages of 11 months and 60 months (67 with complete FPR and six with incomplete FPR at 12 mo). A complete FPR at 12 months was a good predictor of independent walking. The age at onset of complete FPR was also a good predictor of age of walking. INTERPRETATION: The late acquisition of a complete FPR appears to be an early sign of a more general delayed maturation of functional abilities.

Early visual assessment in preterm infants with and without brain lesions: correlation with visual and neurodevelopmental outcome at 12 months.

BACKGROUND: Several studies have reported the development of various aspects of visual function in infancy and early childhood in both preterm and term-born infants, but only a few studies have focused on the predictive power of neonatal visual findings in infants with brain lesions. AIMS: To explore visual findings at term age, and at 3 and 12 months corrected age in preterm infants (gestational age <33 weeks) with and without brain lesions; to compare the assessment at term age and at 12 months; and to assess the relationship between visual findings and neurodevelopmental outcome at 12 months. STUDY DESIGN: Cranial ultrasound scans (US) were classified in normal, mild or major abnormalities. One-hundred and forty-five infants were assessed with age specific tests for visual function at term age, and at 3 and 12 months. Neurodevelopmental assessment (Griffiths' Scales) was performed at 12 months. RESULTS: A good correlation was found between early and late visual assessment and neurodevelopment outcome. Of the 121 infants with normal neonatal visual assessment, 119 were also normal at 12 months and 116 had normal developmental quotient. Of the 24 infants with abnormal neonatal visual assessment, 12 were also abnormal at 12 months. All the false positives had normalised by 3 months. Of the 35 infants with major US abnormalities, 20 had normal and 15 abnormal scores on the neonatal assessment. At 1 year 17 had normal and 18 abnormal scores. CONCLUSION: A normal visual assessment at term age is a good predictor of normal visual and neurodevelopmental outcome at 12 months. An abnormal visual examination in the neonatal period was a less reliable prognostic indicator, infant should be reassessed at 3 months.

Neurodevelopmental outcome at 12 and 18 months in late preterm infants.

BACKGROUND: Late-preterms represent the 70% of the whole preterm population and are reported to be at higher risk for mortality and morbidity than term infants. AIMS: To assess neurodevelopmental outcome in low-risk late-preterm infants at 12 and 18 months corrected age, to compare results of corrected and uncorrected age to those of term-born infants, to analyse the possible influence of gender on outcome. METHODS: Sixty-one healthy infants born between 33 and 36 weeks gestational age without major brain lesions were assessed at 12 and 18 months corrected age using the Bayley II scale. A control group of 60 low-risk term born infants underwent the same assessment. RESULTS: At 12 and 18 months corrected age late preterms showed a mean mental developmental index (MDI) similar to term infants. Comparing the results of the uncorrected age with term infants, the scores were significantly lower at both 12 and 18 months. No gender differences were observed in term-born infants, while male late-preterm infants showed lower MDI than peer females at both ages. CONCLUSIONS: When correcting age for prematurity late-preterms have similar MDI scores to those obtained in term-born infants at 12 and 18 months. In contrast, when using chronological age there is a number of infants with low MDI. As cognitive abnormalities are reported at school age in late preterm infants, our findings raise the question on whether the results obtained using scores uncorrected for age may early identify the infants who will show cognitive difficulties at school age.

Early assessment of visual function in preterm infants: how early is early?

BACKGROUND: Several studies reported on various aspects of visual function at term age and in the first months after birth but less has been reported in preterm infants before they reach termequivalent age. AIMS: To assess the suitability of a battery of tests of visual function for use in infants born at <33weeks gestation (GA) and assessed before 34weeks post-menstrual age (PMA); to evaluate the distribution of the findings according to GA, and to compare the data with those previously published on preterm infants assessed at 35weeks PMA. STUDY DESIGN: Cross-sectional study. SUBJECTS: Sixty-four preterm infants with a GA <33weeks were studied. OUTCOME MEASURES: We used a battery of visual function tests previously validated at 35 and 40weeks PMA in low-risk preterm infants. All the infants in this current study underwent the same assessment before 34weeks PMA. RESULTS: Before 31weeks PMA most infants could not be reliably assessed because of clinical instability, whilst after 31weeks PMA most infants could be assessed and they showed progressive maturation in their responses with PMA. Some items (spontaneous ocular motility, horizontal tracking, tracking a coloured stimulus, and ocular fixation) showed similar results at 32-33weeks PMA to those found in low-risk preterm at 35weeks PMA. Ocular movements to a target and arc tracking were the items with the most immature responses. CONCLUSIONS: Our results provide further evidence that a structured assessment of visual function can be used in clinical routine and for research purposes in infants as young as 31weeks PMA.

Prognostic value of a scorable neurological examination from 3 to 12 months post-term age in very preterm infants: a longitudinal study.

UNLABELLED: AIMS AND STUDY DESIGN: The Hammersmith Infant Neurological Examination proved effective in predicting locomotor function in very preterm infants after 9 months of age. We performed the examination in a cohort of 103 very preterm infants (gestational age below 32 weeks) as early as 3 months' post-term age, and longitudinally at 6, 9 and 12 months. Our aim was to establish the frequency distribution of the optimality scores at each age period, to explore the predictive value of the examination from 3 months onwards as to developmental outcome and locomotor function at 2 years, and to explore its longitudinal consistency. RESULTS: The results showed that this standardized neurological examination can be performed in preterm infants as early as 3 months' post-term age to predict motor outcome at 2 years, and that its high predictive value is consistent across the first year of life due to an effective combination of different items for each age period. CONCLUSIONS: We confirm the high predictive value of this neurological examination in very preterm infants after 9 months and extend it to the assessments performed as early as 3 months post-term. This is of great relevance as in very preterm infants early prediction of motor function is essential for a prompt planning of therapeutic interventions.

Development of the forward parachute reaction and the age of walking in near term infants: a longitudinal observational study.

BACKGROUND: Near term infants are a main part of preterms. They are at higher risk for mortality and morbidity than term infants and could show a quite different development of tone and reflexes from them. The aim of the present study was to describe longitudinally, in a large sample of healthy near term infants, the development of the forward parachute reaction (FPR) and its correlation with the age of acquisition of independent walking. METHODS: The assessment of FPR (as absent, incomplete or complete) was performed at 3, 6, 9, 12 months of corrected age in 484 infants, with a gestational age between 35.0 and 36.9 weeks. The age of acquisition of independent walking was monitored until its appearance. A correlation analysis was done between the age of walking and the acquisition of a complete or incomplete FPR, using the Spearman Rank correlation. The Mann-Withney U test was used to identify significant gestational age differences for the age of FPR appearance. RESULTS: Most of infants had a two-step development pattern. In fact, they showed at first an incomplete and then a complete FPR, which was observed more frequently at 9 months. An incomplete FPR only, without a successive maturation to a complete FPR, was present in the 21% of the whole sample. Infants with a complete FPR walked at a median age of 13 months, whereas those with an incomplete FPR only walked at a median age of 14 months. CONCLUSION: We identified two groups within our sample of near term infants. The first group showed a progressive maturation of FPR, whereas the second one was characterised by the inability to get a complete pattern, within the one year observation's period. Furthermore, we observed a trend toward a delayed acquisition of independent walking in the latter group of infants.

Neuromotor development in infants with cerebral palsy investigated by the Hammersmith Infant Neurological Examination during the first year of age.

BACKGROUND: The Hammersmith Infant Neurological Examination (HINE) is a simple and scorable method for assessing infants between 2 and 24 months of age. AIMS: The purpose of this retrospective study was firstly, to evaluate the neuromotor development of infants with cerebral palsy (CP) by the HINE, during the first year of age; secondly, to correlate the scoring of this neurological tool with levels of the Gross Motor Function Classification System (GMFCS). METHODS: A cohort of 70 infants with a diagnosis of CP at 2 years of age was evaluated by the HINE at 3, 6, 9 and 12 months of corrected age and by GMFCS at 2 years of age. RESULTS: The main results indicate that at 3-6 months, infants with quadriplegia (IV and V levels of GMFCS) and those with severe diplegia (III level) scored below 40, whereas those with mild or moderate diplegia (I-II level) and hemiplegia (I-II level) mainly scored between 40-60. Interestingly, the 26% of infants with hemiplegia scored > or =67 at 12 months. We observed a strong (r=-0.82) and significant (p<0.0001) negative correlation between the scores of the neurological examination and the levels of GMFCS. CONCLUSIONS: Our results point out that the HINE can give additional information about neuromotor development of infants with CP from 3-6 months of age, strictly related to the gross motor functional abilities at 2 years of age.