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Background Fine motor and coordination problems are frequently reported among adolescents born preterm. We aimed to assess performance in hand coordination tasks and to compare concurrent brain activation between adolescents born very preterm and at term at 13 years. Methods A total of 34 right-handed adolescents born very preterm (gestational age less than 32 weeks/birth weight ≤1500 grams) and 37 controls born at term during 2003 to 2006 in Turku University Hospital, Finland, were recruited. At 13 years, finger opposition and diadochokinesis were assessed, and brain functional magnetic resonance imaging data were acquired while the adolescents performed unimanual hand coordination tasks in response to visual cue. Results Adolescents born very preterm performed similar to controls in hand coordination tasks. The very preterm group evoked greater brain activation than the controls in the right precentral gyrus and in the right postcentral gyrus during left-hand finger opposition and in the right postcentral gyrus during left-hand diadochokinesis. Within the very preterm group, lower gestational age was associated with reduced activation in the left superior parietal lobule during right-hand diadochokinesis. Regarding left-hand tasks, lower gestational age was associated with stronger activation in the right cerebellar lobule V and left cerebellar lobule VI during finger opposition and stronger activation in the right superior parietal lobule during diadochokinesis. Conclusions Very preterm birth affected hand coordination-related brain activation. Most of the effects were found for nondominant hand. Clinical performance during the hand coordination tasks was similar in adolescents born very preterm and controls.

Background The objective of this study was to examine how nonverbal skills at age five years relate to visual perception and brain activation during visual perception tasks at age 12 years in very preterm subjects without visual or other neurodevelopmental impairments or major brain pathologies. Methods At age five years, 36 prematurely born (birth weight ≤1500 g or gestational age less than 32 weeks) and 31 term-born control children were assessed with the nonverbal subtests of the Wechsler Preschool and Primary Scale of Intelligence-Revised and the NEPSY-Second Edition. At age 12 years the same children were re-assessed with tasks from the Motor-Free Visual Perception Test, Third Edition, during functional magnetic resonance imaging. Results Test performance at age five years was significantly poorer in the very preterm group than the control subjects, but at age 12 years performance was similar in both groups. In the very preterm group, better nonverbal skills at age five years were significantly associated with stronger neural activation during the visual perception task at age 12 years. No associations between nonverbal skills at age five years and brain activation at age 12 years appeared in the control group. Conclusions The associations between better nonverbal skills and stronger neural activation during visual perception task only observed in the very preterm group may reflect delayed development of the visual perception network and/or prematurity-related neural plasticity. The developmental follow-up of very preterm children should include psychological assessment of nonverbal skills at least until age five years.

OBJECTIVE:To study how the early crying behavior of preterm infants at term, 6 weeks, and 5 months of corrected age is related to later behavioral problems at age 3 and 4 years and parenting stress at 2 and 4 years.METHODS:The study group included 202 live-born, low birth weight infants (birth weight ≤1500 g) born from January 2001 through December 2006 at the Turku University Hospital, Finland. A Baby Day Diary was used to assess the preterm infants’ crying behavior at term, 6 weeks, and 5 months of corrected age. The children’s behavior was assessed using the Child Behavior Check List at 3 and 4 years old, and parenting stress was assessed by using the Parenting Stress Index when the child was 2 and 4 years old.RESULTS:The duration and frequency of crying bouts in infancy was associated with Child Behavior Check List scores at 4 years old and to both mothers’ and fathers’ stress when the child was 2 and 4 years old.CONCLUSIONS:Early excessive crying, especially if lasting up to 5 months of corrected age, is a clinically relevant signal in preterm infants because it may reflect infants’ regulatory problems and/or parenting stress. The crying behavior of preterm infants should be systematically inquired about at well-baby clinics.

Aim The aim of this study was to analyse the relation between ventricular dilatation at term and neurodevelopmental outcome at 2 years corrected age in infants of very low birthweight (VLBW) or very low gestational age (VLGA). Method A total of 225 VLBW or VLGA infants (121 males, 104 female; mean birthweight 1133g, SD 333g; mean gestational age 29wks, SD 2wks 5d) born in Turku University Hospital were included. Ventricular–brain ratio and the widths of each lateral ventricular horn were determined using ultrasonography, and the volume of the ventricles was measured by magnetic resonance imaging at term. The 2-year outcome measures included scores for the Hammersmith Infant Neurological Examination, the presence of cerebral palsy (CP), the Mental Developmental Index (MDI) of the Bayley Scales of Infant Development (2nd edition), and the presence of severe hearing or vision impairments or any neurodevelopmental impairment (NDI). Results CP was diagnosed in 15 participants (6.7%) and severe hearing deficit in 12 participants (5.3%). No severe vision impairment was found. Mild and severe cognitive delay was found in 24 (10.7%) and 8 (3.6%) of the VLBW or VLGA infants respectively. Isolated ventricular dilatation did not increase the risk for developmental impairments. However, ventricular dilatation with additional brain pathology was significantly associated with CP, MDI score below 70, and NDI. A ventricular–brain ratio above 0.35 was a sensitive measure of developmental impairment. Interpretation Ventricular dilatation at term increases the risk of poor developmental outcome only when associated with other brain pathology. The ventricular–brain ratio is a useful clinical tool for determining the prognosis in VLBW and VLGA infants.

Aim: To study cognitive outcome of premature, very low birth weight (VLBW) infants in relation to parental education and neonatal data. Methods: A regional cohort of 182 VLBW infants born between 2001 and 2006 was followed up. Brain ultrasounds (US) were examined serially until term age and brain magnetic resonance imaging at term age. Neurological status was examined systematically. Cognitive development was assessed using the Mental Developmental Index (MDI) of Bayley Scales at 2 years of corrected age. A total of 192 healthy full-term (FT) controls were assessed with the MDI at 2 years of age. Results: The mean MDI in VLBW infants was 101.7 (SD 15.4), which was lower compared with FT controls (109.8, SD 11.7, p

Objective To study neurodevelopmental outcome at 2 years of corrected age in very-low-birth-weight (VLBW) (⩽ 1500 g) preterm infants with abnormal fetoplacental flow. Methods A total of 258 VLBW infants were born at Turku University Hospital between 2001 and 2006. Of these, 99 had undergone, within 1 week of delivery, antenatal Doppler assessment of blood flow in the umbilical artery (UA), fetal middle cerebral artery (MCA), descending aorta (DAo), aortic isthmus and ductus venosus and were eligible for inclusion in the study. Postnatally brain pathology was assessed by serial ultrasound and magnetic resonance imaging in 86 of the neonates and brain volume was measured in 80. Cognitive development was evaluated at 2 years of corrected age in 83 infants using the Bayley Scales of Infant Development-II. Motor development was assessed using the Hammersmith Infant Neurological Examination. Results On univariate analysis, abnormal pulsatility index (PI) in the UA and an abnormal UA-PI/MCA-PI ratio (P = 0.04 and P = 0.003, respectively) as well as increases in both the DAo-PI and in the DAo-PI/MCA-PI ratio (P = 0.03 and P = 0.02, respectively), were associated with adverse cognitive outcome at 2 years of age. However, when controlling for cerebral volume using multivariate analysis, the association between abnormal antenatal Doppler characteristics and cognitive outcome became statistically non-significant, which indicated the determinant role of the volume reduction. Motor development was not associated with antenatal Doppler indices. Conclusion Abnormal antenatal Doppler indices are associated with adverse cognitive outcome at 2 years in VLBW infants. Our findings suggest that this association may be mediated through brain volume. Copyright © 2010 ISUOG. Published by John Wiley & Sons, Ltd.

We previously reported the neurological findings of the Dubowitz neonatal examination in a cohort of 157 low-risk preterms born between 25 and 33 weeks gestational age (GA) and examined at term equivalent age (TEA). Median and range of scores were wider than those found in term-born infants and preterms showed a different neurological behaviour in specific items. However, the cohort number was too small to draw any definitive conclusion about the distribution of findings.We provide normative data from a low-risk cohort of 380 preterm infants; we also assess the findings and their relationship to motor outcome in preterms with major cranial ultrasound (US) abnormality.We assessed, at TEA, 380 low-risk preterms born35 weeks gestation (range 25-34.9, median 29) with normal 2 year motor outcome and 85 preterm infants with major US abnormality.At TEA low-risk preterms had less flexor limb tone, poorer head control but better visual following than term-born infants. For 28/34 of the neurological items the range and median scores were similar across gestational ages. In infants with major US lesions the range and median scores differed from low-risk preterms in 20/34 items; 40% of infants developing a diplegia and 80% developing a tetraplegia had7 items outside the 90th centile; all infants with12 items outside the 90th centile developed a tetraplegia.We provide reference values for the neurological examination of low-risk preterms at TEA. In infants with major US abnormality the number of items outside the 90th centile was an indicator of outcome severity.

Aim: To evaluate the association between infant fussing and crying and developmental outcome in very low birth weight (VLBW) infants. Methods: Hundred and seventeen VLBW infants were followed up to 24 months of corrected age. The duration of fussing and crying and frequency of fuss/cry bouts were measured at term 6 weeks and 5 months of corrected age. Cognitive and motor development was assessed at 24 months of corrected age. Results: The increased duration of combined fuss/cry at term associated with lower psychomotor developmental index (PDI), [regression coefficient (b) =−0.83, p = 0.025]. Crying at term associated negatively with mental developmental index (MDI) (b =−0.91, p = 0.040) and PDI (b =−1.10, p = 0.015). The associations between fuss/cry and PDI, and crying and PDI persisted in multiple regression analysis (b =−0.89, p = 0.030 and b =−1.23, p = 0.018, respectively). Excessive fuss/cry (≥180 min/day) at term associated with lower PDI (p = 0.005) and at 6 weeks with lower MDI (p = 0.024) and PDI (p = 0.012). Increase in the frequency of fuss/cry bouts at 5 months associated with higher PDI in both simple (b = 2.90, p = 0.045) and in multiple regression analysis (b = 3.60, p = 0.019). Conclusions: In VLBW infants, longer duration of fussing and crying in very early infancy, but not at 5 months, is associated with less optimal development at 24 months of age.

OBJECTIVES. The objective of this study was to assess crying behavior during infancy in very preterm infants with or without brain injury.METHODS. A total of 125 very low birth weight infants survived during January 2001 to July 2004 in Turku University Hospital, Finland. They were categorized according to the most pathologic brain finding either in ultrasound or MRI. Baby Day Diary was used to assess crying behavior at term, 6 weeks, and 5 months of corrected age. The behavior of a group of term control infants (n = 49) was assessed at 5 months.RESULTS. Severe brain injuries in very low birth weight infants did not affect the duration of fussing or crying. In very low birth weight infants, brain injuries did not affect the frequency of fussing or crying bouts or the development of circadian rhythm in crying behavior. At 5 months of corrected age, fussing bouts were more frequent in very low birth weight infants compared with term control infants (6.4 per day vs 4.5 per day), and very low birth weight infants were held more (169 minutes [97] vs 130 minutes [69], respectively).CONCLUSIONS. This prospective study using a validated cry diary showed that brain injuries that are related to prematurity do not have major effects on crying behavior or development of circadian rhythm. Prematurity does not increase the duration but increases the frequency of fussing and crying at 5 months of corrected age compared with term control infants. It also seems that prematurity and brain pathology may increase caregiving activity in the form of holding.

Background The predictive value of the combination of neurological examination and brain magnetic resonance imaging (MRI) or cranial ultrasound (cUS) in preterm infants is not known. Aims To study the prognostic value of the combination of neurological examination and brain MRI at term equivalent age (TEA) or serial neonatal cUS in very preterm infants for neurosensory outcome at 2 years of corrected age. Study design A prospective follow-up study. Subjects A total of 216 very preterm infants (birth weight 1132 g [SD 331 g]) born in Turku University Hospital, from 2001 to 2006, were included. Outcome measures The Dubowitz neurologic examination and brain MRI were done at TEA, and serial cUS examinations were performed until TEA. The Hammersmith Infant Neurological Examination (HINE) and neurosensory impairments (NSI) were assessed at 2 years of corrected age. Results Of all infants, 163 (76%) had one or more deviant neurological items at TEA, and 32 (15%) had the HINE total score below the 10th percentile at 2 years of corrected age. A total of 17 (8%) infants had NSI. Neurological examination at TEA improved the negative and positive predictive values of brain MRI for NSI from 99% to 100%, and from 28% to 35%, respectively, and the negative and positive predictive values of cUS from 97% to 100%, and from 61% to 79%, respectively. Conclusions The combination of the Dubowitz neurologic examination and the brain MRI at TEA or serial neonatal cUS provides a valuable clinical tool for predicting long-term neurosensory outcome in preterm infants.

The aim of this study was to analyse the relation between ventricular dilatation at term and neurodevelopmental outcome at 2 years corrected age in infants of very low birthweight (VLBW) or very low gestational age (VLGA).A total of 225 VLBW or VLGA infants (121 males, 104 female; mean birthweight 1133 g, SD 333 g; mean gestational age 29 wks, SD 2 wks 5d) born in Turku University Hospital were included. Ventricular-brain ratio and the widths of each lateral ventricular horn were determined using ultrasonography, and the volume of the ventricles was measured by magnetic resonance imaging at term. The 2-year outcome measures included scores for the Hammersmith Infant Neurological Examination, the presence of cerebral palsy (CP), the Mental Developmental Index (MDI) of the Bayley Scales of Infant Development (2nd edition), and the presence of severe hearing or vision impairments or any neurodevelopmental impairment (NDI).CP was diagnosed in 15 participants (6.7%) and severe hearing deficit in 12 participants (5.3%). No severe vision impairment was found. Mild and severe cognitive delay was found in 24 (10.7%) and 8 (3.6%) of the VLBW or VLGA infants respectively. Isolated ventricular dilatation did not increase the risk for developmental impairments. However, ventricular dilatation with additional brain pathology was significantly associated with CP, MDI score below 70, and NDI. A ventricular-brain ratio above 0.35 was a sensitive measure of developmental impairment.Ventricular dilatation at term increases the risk of poor developmental outcome only when associated with other brain pathology. The ventricular-brain ratio is a useful clinical tool for determining the prognosis in VLBW and VLGA infants.

OBJECTIVES. The aim of this study was to assess the relationship among the size of the lateral ventricles, head-circumference measure, and brain volumes. In addition, the association between ventricular dilatation and various brain lesions was defined. PATIENTS AND METHODS. A total of 257 preterm very low birth weight (≤1500 g) infants who met the inclusion criteria were born in Turku University Central Hospital between 2001 and 2006. A total of 209 (84.8%) of 218 survivors participated in the study. The measurements at term included the ventricular brain ratio, the widths of the frontal and occipital horns of the lateral ventricles by ultrasound, total and regional brain volumes by MRI, and head circumference. Brain lesions were defined by ultrasound at 3 to 5, 7 to 10, and 30 days of age monthly until discharge and by MRI and ultrasound at term. RESULTS. An abnormal ventricular brain ratio (>0.35), an increasing number of dilated ventricular horns, and smaller head circumference were significantly associated with smaller total brain tissue volume. The abnormal ventricular brain ratio and the increasing number of dilated ventricular horns in ultrasound associated with larger ventricular volumes in MRI, and a smaller head circumference was associated significantly with reduced regional brain tissue volumes. Brain lesions were more common in infants with ventriculomegaly. CONCLUSIONS. The ventricular brain ratio, widths of the lateral ventricular horns, and head circumference are appropriate measures for the estimation of both total and regional brain tissue volumes. Ventriculomegaly is strongly associated with brain lesions.

To evaluate the association between infant fussing and crying and developmental outcome in very low birth weight (VLBW) infants.Hundred and seventeen VLBW infants were followed up to 24 months of corrected age. The duration of fussing and crying and frequency of fuss/cry bouts were measured at term 6 weeks and 5 months of corrected age. Cognitive and motor development was assessed at 24 months of corrected age.The increased duration of combined fuss/cry at term associated with lower psychomotor developmental index (PDI), [regression coefficient (b)=-0.83, p=0.025]. Crying at term associated negatively with mental developmental index (MDI) (b=-0.91, p=0.040) and PDI (b=-1.10, p=0.015). The associations between fuss/cry and PDI, and crying and PDI persisted in multiple regression analysis (b=-0.89, p=0.030 and b=-1.23, p=0.018, respectively). Excessive fuss/cry (or=180 min/day) at term associated with lower PDI (p=0.005) and at 6 weeks with lower MDI (p=0.024) and PDI (p=0.012). Increase in the frequency of fuss/cry bouts at 5 months associated with higher PDI in both simple (b=2.90, p=0.045) and in multiple regression analysis (b=3.60, p=0.019).In VLBW infants, longer duration of fussing and crying in very early infancy, but not at 5 months, is associated with less optimal development at 24 months of age.

The aim of this study was to evaluate associations between infant crying, holding and mother-infant interaction.The study groups included 30 firstborn Finnish preterm infants (1501 g or32 weeks), and their 36 full-term controls. Caregiver's holding and infant's crying behavior was assessed using Baby Day Diary at 5 months of corrected age. The quality of mother-infant interaction was assessed using PC-ERA at 6 and 12 months of corrected age.The results showed that longer duration of holding in home environment was associated with better quality of mother-infant interaction at 6 and 12 months of corrected age in preterm infants. Preterm infants cried more often and were held more than full-term infants. The frequency of crying was associated with the duration of holding in preterm infants. Mother-infant interaction was comparable between the groups of preterm and full-term infants.Our results underline the importance of caregiver's physical closeness for the quality of the mother-infant interaction in preterm infants. Prematurity itself does not necessary affect the quality of mother-infants interaction in a non-risk population.

To evaluate the association between histologic inflammation of placenta and brain findings in ultrasound examinations and regional brain volumes in magnetic resonance imaging in very-low-birth-weight (VLBW) or in very preterm infants.VLBW or very preterm infants (n = 121) were categorized into 3 groups according to the most pathologic brain finding on ultrasound examinations until term. The brain magnetic resonance imaging performed at term was analyzed for regional brain volumes. The placentas were analyzed for histologic inflammatory findings.Histologic chorioamnionitis on the fetal side correlated to brain lesions in univariate but not in multivariate analyses. Low gestational age was the only significant risk factor for brain lesions in multivariate analysis (P.0001). Histologic chorioamnionitis was not associated with brain volumes in multivariate analyses. Female sex, low gestational age, and low birth weight z score correlated to smaller volumes in total brain tissue (P = .001, P = .0002, P.0001, respectively) and cerebellum (P = .047, P = .003, P = .001, respectively). In addition, low gestational age and low-birth-weight z score correlated to a smaller combined volume of basal ganglia and thalami (P = .0002).Placental inflammation does not appear to correlate to brain lesions or smaller regional brain volumes in VLBW or in very preterm infants at term age.

Objective To determine the correlation between fetoplacental blood flow and brain injury and volumes in very low birth weight (VLBW) infants. Study design Antenatal blood flow from the umbilical artery (UA), middle cerebral artery (MCA), and descending aorta was determined in 70 VLBW infants. The directions of the total diastolic flow of the aortic isthmus and the end-diastolic flow of ductus venosus also were measured. Serial brain ultrasound examinations and MRI at term were performed to assess brain abnormalities. On the basis of brain imaging findings, the newborn infants were classified as normal (n = 14), intermediate brain pathology (n = 31), and major pathology (n = 25) groups. Results Abnormalities in fetoplacental blood flow were not related to anatomic brain lesions. However, an abnormal UA/MCA pulsatility index ratio was associated with reduced total brain volume (mean, 360 mL; SD, 32.5 mL) and reduced cerebral volume (344 mL; SD, 28.4 mL) compared with infants with normal UA/MCA pulsatility index ratio (mean, 405 mL; SD, 51.3 mL, P = .01, and mean, 368 mL; SD, 52.3 mL, P = .012), respectively. Conclusions Redistribution of fetal blood flow in VLBW infants is associated with reduced brain volume at term age. Neurodevelopmental follow-up of this cohort will clarify the significance of these blood flow changes on development.