Intra-uterine exposure to selective serotonin reuptake inhibitors (SSRIs), maternal psychopathology, and neurodevelopment at age 2.5years - Results from the prospective cohort SMOK study.

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) are prescribed in 2-8% during pregnancy. Whether prenatal exposure to SSRIs has long-term effects on the children's development is unknown. AIM: The aim of this study was to determine the effect of prenatal exposure to SSRIs on children's cognitive, motor, and behavioral outcomes at 2.5 years, adjusted for maternal depression and anxiety. METHODS: In a prospective, longitudinal cohort-study we included 111 pregnant women treated either or not with an SSRI. We examined cognitive and motor development of their children at 2.5 years, using the Bayley Scale of Infant and Toddler Development, 3rd Edition, and measured emotional and behavioral problems using the parent-rated Child Behavior Checklist (CBCL). Maternal depression and anxiety was determined during pregnancy and at the children's assessment. Differences of normed cognitive, motor, and behavioral scores between SSRI-exposed and non-SSRI-exposed children were tested using multiple linear regression analyses. RESULTS: We examined 102 children. SSRI-exposed children had lower scaled scores on cognition and gross motor development than non-SSRI-exposed children: 9.0 ± 1.4 (mean ± SD) versus 9.9 ± 1.7 [P = 0.004], and 7.9 ± 2.2 versus 9.0 ± 2.5 [P = 0.01], respectively. Differences remained significant after adjusting for maternal depression and anxiety and other confounders in various models (mean difference for cognition 0.8 to 0.9 points, for gross motor 1.1 to 1.2 points). Only after adjusting for severity of maternal anxiety, differences in gross motor scores lost significance. CONCLUSIONS: Prenatal exposure to SSRIs is associated with poorer cognitive and gross motor development of the children at 2.5 years. Effects on gross motor development disappeared after correction for severity of maternal anxiety.

The effect of enteral bolus feeding on regional intestinal oxygen saturation in preterm infants is age-dependent: a longitudinal observational study.

BACKGROUND: The factors that determine the effect of enteral feeding on intestinal perfusion after preterm birth remain largely unknown. We aimed to determine the effect of enteral feeding on intestinal oxygen saturation (rintSO2) in preterm infants and evaluated whether this effect depended on postnatal age (PNA), postmenstrual age (PMA), and/or feeding volumes. We also evaluated whether changes in postprandial rintSO2 affected cerebral oxygen saturation (rcSO2). METHODS: In a longitudinal observational pilot study using near-infrared spectroscopy we measured rintSO2 and rcSO2 continuously for two hours on postnatal Days 2 to 5, 8, 15, 22, 29, and 36. We compared preprandial with postprandial values over time using multi-level analyses. To assess the effect of PNA, PMA, and feeding volumes, we performed Wilcoxon signed-rank tests or logistic regression analyses. To evaluate the effect on rcSO2, we also used logistic regression analyses. RESULTS: We included 29 infants: median (range) gestational age 28.1 weeks (25.1-30.7) and birth weight 1025 g (580-1495). On Day 5, rintSO2 values decreased postprandially: mean (SE) 44% (10) versus 35% (7), P = .01. On Day 29, rintSO2 values increased: 44% (11) versus 54% (7), P = .01. Infants with a PMA ≥ 32 weeks showed a rintSO2 increase after feeding (37% versus 51%, P = .04) whereas infants with a PMA < 32 weeks did not. Feeding volumes were associated with an increased postprandial rintSO2 (per 10 mL/kg: OR 1.63, 95% CI, 1.02-2.59). We did not find an effect on rcSO2 when rintSO2 increased postprandially. CONCLUSIONS: Our study suggests that postprandial rintSO2 increases in preterm infants only from the fifth week after birth, particularly at PMA ≥ 32 weeks when greater volumes of enteral feeding are tolerated. We speculate that at young gestational and postmenstrual ages preterm infants are still unable to increase intestinal oxygen saturation after feeding, which might be essential to meet metabolic demands. TRIAL REGISTRATION: For this prospective longitudinal pilot study we derived patients from a larger observational cohort study: CALIFORNIA-Trial, Dutch Trial Registry NTR4153 .

Prenatal exposure to persistent organic pollutants and cognition and motor performance in adolescence.

BACKGROUND: Prenatal exposure to persistent organic pollutants (POPs), such as polychlorinated biphenyls (PCBs), was found to be associated with poorer neurological development in children. Knowledge about the effects on outcomes until adolescence is limited. OBJECTIVES: To determine whether prenatal exposure to POPs, particularly hydroxylated PCBs (OH-PCBs), is associated with cognitive and motor development in 13- to 15-year-old children. METHODS: This prospective observational cohort study is part of the Development at Adolescence and Chemical Exposure (DACE)-study, a follow-up of two Dutch birth cohorts. Maternal pregnancy serum levels of PCB-153 and three OH-PCBs were measured, in part of the cohort also nine other PCBs and three OH-PCBs, and in another part five polybrominated diphenyl ethers (PBDEs), dichloroethene (DDE), pentachlorophenol (PCP) and hexabroomcyclododecane (HBCDD). Of the 188 invited adolescents, 101 (53.7%) participated, 55 were boys. Cognition (intelligence, attention, verbal memory) and motor performance (fine motor, ball skills, balance) were assessed. Scores were classified into 'normal' (IQ > 85; scores > P15) and '(sub)clinical' (IQ ≤ 85; scores ≤ P15). We used linear and logistic regression analyses, and adjusted for maternal education, maternal smoking, maternal alcohol use, breast feeding, and age at examination. RESULTS: Several OH-PCBs were associated with more optimal sustained attention and balance. PCB-183 was associated with lower total intelligence (OR: 1.29; 95%CI:0.99-1.68; P = .060), and HBCDD with lower performance intelligence (OR: 3.62; 95%CI:0.97-13.49; P = .056). PCBs, OH-PCBs and PBDEs were negatively associated with verbal memory. CONCLUSIONS: Prenatal background exposure to several POPs can influence neuropsychological outcomes in 13- to 15-year-old Dutch adolescents, although exposure to most compounds does not have clinically relevant consequences at adolescence.

Red Blood Cell Transfusions Affect Intestinal and Cerebral Oxygenation Differently in Preterm Infants with and without Subsequent Necrotizing Enterocolitis.

OBJECTIVE: To assess intestinal and cerebral oxygenation during and after red blood cell (RBC) transfusions in preterms with or without subsequent transfusion-associated necrotizing enterocolitis (TANEC). STUDY DESIGN: In preterms of < 32 weeks' gestational age, we measured intestinal and cerebral regional tissue oxygen saturation (rintSO2, rcSO2) and their variabilities using near-infrared spectroscopy during and after transfusions. We compared eight infants who developed TANEC 6 to 48 hours after RBC transfusions with 16 controls. RESULTS: In TANEC infants, rcSO2 was lower during and after RBC transfusions than in controls, median (interquartile range) 55% (50-62) versus 72% (65-75), p < 0.01. There were no differences regarding rintSO2. Individual rintSO2 and rcSO2 ranges were smaller after transfusions in TANEC infants, 28% (9-36) versus 49% (40-65), p < 0.01, and 17% (14-33) versus 36% (26-57), p = 0.01, as was short-term rintSO2 variability. For each 10% higher rcSO2, the risk of developing TANEC decreased (odds ratio 0.09; 95% confidence interval 0.01-0.63). The smaller the rintSO2 range after transfusion, the higher the risk of developing TANEC. CONCLUSION: In preterm infants lower rcSO2, but not rintSO2, values during and after RBC transfusions are associated with TANEC. Lower rintSO2 and rcSO2 variabilities after RBC transfusions may represent a diminished capacity for vascular adaptation, possibly leading to TANEC.

The Predictive Value of Amplitude-Integrated Electroencephalography in Preterm Infants for IQ and Other Neuropsychological Outcomes at Early School Age.

BACKGROUND: Amplitude-integrated electroencephalography (aEEG) is used increasingly in neonatal intensive care and seems helpful in predicting outcomes at the age of 2 years. OBJECTIVES: To determine whether early aEEG patterns in preterm infants are equally useful in predicting outcomes at early school age. METHODS: We recorded aEEG in 41 preterms (gestational age 26.0-32.9 weeks) at a median postnatal age of 9.7 h (IQR 7.0-25.3) and in 43 preterms on median day 8 (IQR 7-9). We assessed aEEG by pattern recognition and calculated the means of the aEEG amplitude centiles. At a median of 7.39 years, i.e., early school age, we assessed their motor, cognitive, and behavioral outcomes. RESULTS: Depressed aEEG patterns were not associated with poorer outcomes. Cyclicity directly after birth was associated with a higher total IQ (mean 104 vs. 97, p = 0.05) and higher scores on visual perception (mean percentile 57.1 vs. 40.1, p = 0.049) and visual memory (mean percentile 34.5 vs. 19.1, p = 0.090). We found some associations between the aEEG amplitude centiles and cognitive outcomes, but none for motor or behavioral outcomes. There was an increased risk of abnormal scores on long-term verbal memory in cases of the lower 5th and 50th aEEG amplitude centiles directly after birth. The odds ratios were 0.65 (95% CI 0.42-0.99, p = 0.040) and 0.71 (95% CI 0.52-0.96, p = 0.025), respectively. CONCLUSIONS: In relatively healthy preterm infants the value of aEEG in predicting neuropsychological outcomes at early school age is limited. The presence of cyclicity directly after birth tends to be associated with better cognition.

Functional outcome at school age of children born with gastroschisis.

OBJECTIVE: We aimed to determine motor, cognitive and behavioural outcomes of school aged children born with gastroschisis compared to matched controls. STUDY DESIGN: We compared outcomes of 16 children born with gastroschisis treated at the University Medical Center Groningen, the Netherlands, between 1999 and 2006 with 32 controls matched for gender, gestational age, birth weight, and corrected for small for gestational age (SGA) and parental socioeconomic status (SES). Intelligence, auditory-verbal memory, attention, response inhibition, visual perception, motor skills, visuomotor integration, problem behaviour and executive functioning were evaluated. RESULTS: Median verbal intelligence quotient and global executive functioning scores of children born with gastroschisis were poorer than of controls (95 (inter quartile range (IQR) 88-100) vs. 104 (IQR 98-113), P=0.001, and 29 (IQR 6.8-63.8) vs. 5.0 (IQR 2.8-19.8), P=0.03, respectively). Children with gastroschisis were more often classified as borderline or abnormal than controls regarding response inhibition (odds ratio (OR) 20.4; 95%-confidence interval (95%-CI); 2.4-171.5), selective visual attention (OR 40.4; 95%-CI 5.9-275.4), sustained auditory attention (OR 88.1; 95%-CI 5.8-1342.8), and fine motor skills (50% vs. 0%). Grade retention was more prevalent in gastroschisis children (OR 6.07; 95%-CI 1.42-25.9). These associations persisted after adjustment for SGA and SES. The auditory-verbal memory, visuomotor integration and behavioural problems did not significantly differ from the controls. CONCLUSIONS: Gastroschisis is associated with poorer verbal intelligence, and with an increased risk for poor performance on several aspects of attention, response inhibition and fine motor skills at school age. The follow-up of children born with gastroschisis deserves attention regarding these specific domains, to improve their functional outcomes.

Longitudinal Growth and Neuropsychological Functioning at Age 7 in Moderate and Late Preterms.

OBJECTIVE: To determine the association between longitudinal growth measures (height, weight, head circumference, and extent of catch-up growth) and neuropsychological functioning at 7 years in moderately and late preterm children. METHODS: This study was part of a prospective, community-based cohort study. Data on growth were obtained from records on routine assessments in well-child centers until age 4 years and in a research setting at 7 years. Neuropsychological functioning was assessed at age 7 years. We assessed associations of growth with neuropsychological functioning and determined odds ratios for impaired neuropsychological functioning. All analyses were corrected for maternal education. RESULTS: We included 234 children. Median gestational age was 34 weeks (P25-75: 33-35 weeks), and mean birth weight was 2.2 kg (± 0.5 kg). Short stature at all ages was associated with poorer motor, IQ, and attention scores and led to increased risks of impaired motor skills and low IQ. Lower weight at 1 and 4 years was associated with poorer IQ scores. Increased weight gain between age 4 and 7 years was, however, associated with poorer motor, IQ, and attention scores. Decreased head circumference gain in the first year of life was associated with poorer motor and attention scores and led to an increased risk of impaired motor and attention skills. CONCLUSIONS: In moderately and late preterm children, poorer growth in the first 7 years is associated with poorer neuropsychological functioning. Regarding height, short stature was also associated with a higher likelihood of clinically relevant impaired neuropsychological functioning.

The Effect of Maternal Antihypertensive Drugs on the Cerebral, Renal and Splanchnic Tissue Oxygen Extraction of Preterm Neonates.

BACKGROUND: Drugs with antihypertensive action are frequently used in obstetrics for the treatment of preeclampsia (labetalol) and tocolysis (nifedipine) or for neuroprotection (MgSO4), and may affect the hemodynamics of preterm born neonates. OBJECTIVE: The aim of this study was to assess whether maternal antihypertensive drugs affect multisite oxygenation levels of the neonate. METHODS: Eighty preterm neonates of ≤32 weeks of gestational age were monitored using near-infrared spectroscopy. Mean cerebral, renal and splanchnic fractional tissue oxygen extractions (cFTOE, rFTOE and sFTOE) were calculated for the first 5 postnatal days. We determined the effect of various maternal antihypertensive drugs on cFTOE and rFTOE using multilevel analysis, and on sFTOE using Kruskal-Wallis and Mann-Whitney U tests. RESULTS: Eleven infants were exposed to labetalol ± MgSO4, 7 to nifedipine ± MgSO4, 20 to MgSO4 only, and 42 to no maternal antihypertensive drugs. The infants exposed to labetalol ± MgSO4 had a lower cFTOE on days 1 (0.14, p = 0.031), 2 (0.13, p = 0.035) and 4 (0.18, p = 0.046) than nonexposed infants on the corresponding days (0.22, 0.20 and 0.24, respectively). On day 2, cFTOE was also lower in infants exposed to nifedipine ± MgSO4 (0.11, p = 0.028) and to MgSO4 only (0.15, p = 0.047). sFTOE was higher in infants exposed to labetalol ± MgSO4 on days 1 (µ = 0.71) and 2 (µ = 0.82) than in nonexposed infants (µ = 0.26, p = 0.04 and µ = 0.55, p = 0.007, respectively). Maternal antihypertensive drugs did not affect rFTOE. CONCLUSIONS: Low neonatal cFTOE found with maternal antihypertensive drug exposure may relate to either increased cerebral perfusion or neurologic depression induced by the medication, or preferential brain perfusion associated with preeclampsia placental insufficiency. Concomitantly high sFTOE found with labetalol exposure supports the latter, while renal autoregulation may explain rFTOE stability.

Functional outcome at school age of neonatal post-hemorrhagic ventricular dilatation.

BACKGROUND: Specific knowledge about the functional outcome of preterm born children with post-hemorrhagic ventricular dilatation (PHVD) is lacking. OBJECTIVES: To determine functional outcome at school age in children with post-hemorrhagic ventricular dilatation and to identify whether PHVD characteristics increased the risk for deficits. METHODS: Single-center case-control study. Included were preterm children born between 1996 and 2003 who had PHVD in their neonatal period. The controls were children matched for gestation, gender, and year of birth. At school age, using standardized tests and questionnaires, we assessed intelligence, attention, verbal memory, executive functioning, visual perception, visuomotor integration, motor skills, and behavior. RESULTS: Of 34 children with PHVD 28 survived, three of whom could not be tested at school age (one child's parents declined and two were lost to follow-up). At a mean age of 10years (6-14years) the total and verbal IQs of the remaining 25 children (17 boys, 8 girls) were significantly lower compared to controls (difference in total IQ-14 points, verbal IQ-9 points, P=0.001and P=0.009, respectively). After adjustment for possible confounders, the performance of the PHVD group was poorer on visual perception and attention tests. Selective attention showed a trend toward risk of borderline and abnormal scores (OR 4.03, 95%-CI 0.84-19.2). Within the PHVD group, total IQ was significantly lower (P=0.048) in those who had undergone surgical intervention (n=12). CONCLUSION: At school age, intelligence, attention, and visual perception were more affected in the PHVD group than in the matched controls. Surgical intervention was associated with lower IQ scores.

Associations between developmental trajectories of movement variety and visual attention in fullterm and preterm infants during the first six months postterm.

BACKGROUND: During early infancy major developmental changes, both in the variety of body movements and in visual attention, help the infant to explore its surroundings. Both behaviours depend on a gradual shift from subcortical to cortical functioning. AIMS: First, to determine whether preterms reach mature levels of movement variety (the number of different movement patterns) and visual attention earlier than fullterms. Second, to determine whether individual developmental trajectories of movement variety and visual attention were associated. Finally, we compared the associations of developmental trajectories between fullterm and preterm infants. STUDY DESIGN: In this longitudinal study, 20 fullterm and 9 low-risk preterm infants performed a visual disengagement task every four weeks from six weeks until six months postterm. For each infant we drew up developmental trajectories for movement variety, and for frequencies and latencies of looks. We analyzed the developmental trajectories by means of general linear model (GLM) repeated measures and Monte Carlo analyses. RESULTS: In comparison to fullterms, preterm infants showed a similar increase in movement variety over time (F(4,108)=0.27; partial eta(2)=0.01; P=.90). Visual attention reached mature levels four weeks earlier than movement variety. This effect was stronger in fullterm infants. Neither in fullterm nor in preterm infants did we find an association between the developmental trajectories of movement variety and visual attention. P values ranged from .37 to .99. CONCLUSIONS: During the first 6 months postterm, movement variety and visual attention developed independently. Temporarily, preterm exposure to the extrauterine environment led to shorter latencies of looks but it did not affect developmental trajectories of frequencies of looks and movement variety.

Functional outcomes at age 7 years of moderate preterm and full term children born small for gestational age.

OBJECTIVE: To compare functional outcomes of 7-year-old (school-age) children born small for gestational age (SGA; ie, a birth weight z score ≤ -1 SD), with appropriate for gestational age (AGA) peers, born moderately preterm or full term. STUDY DESIGN: Data were collected as part of the Longitudinal Preterm Outcome Project study, a community-based, prospective cohort study of 336 AGA and 42 SGA born children (median gestational age 35 weeks, range 31-41). Of the SGA children, 32 were moderately preterm, 10 were full term; of the AGA, these numbers were 216 and 120, respectively. At 6.9 years, we assessed intelligence, verbal memory, attention, visuomotor integration, and motor skills and we collected the parent-reported executive functioning. We compared the outcomes of the SGA children with those of their AGA peers. RESULTS: The performance of SGA children was similar to that of their AGA peers, except for attention control which was abnormal more often in SGA children (OR 3.99, 95% CI 1.32-12.12). The IQ of SGA children was 3 points lower, but this difference failed to reach significance. CONCLUSIONS: At school age, children born SGA have a greater risk of abnormal test scores on attention control than children born AGA, independent of gestational age. Their motor and many other cognitive functions are similar. The impact of these outcomes seems limited. Nevertheless, the consequences for school performance deserve attention.

Cerebral oxygenation is associated with neurodevelopmental outcome of preterm children at age 2 to 3 years.

AIM: The aim of the study was to determine whether regional cerebral tissue oxygen saturation (r(c)SO2) and fractional tissue oxygen extraction (FTOE), using near-infrared spectroscopy, are associated with neurodevelopmental outcome of preterm infants. METHOD: We measured rc SO2 on days 1, 2, 3, 4, 5, 8, and 15 after birth in 83 preterm infants (<32wks gestational age), and calculated FTOE=(SpO2 -r(c)SO2)/SpO2. Cognitive, motor, neurological, and behavioural outcomes were determined at 2 to 3 years using the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III), an age-specific neurological examination, and the Child Behavior Checklist (CBCL) respectively. Multiple linear regression analyses were used to determine whether r(c)SO2 and FTOE contributed to outcome. RESULTS: We followed up 67 infants. The lower quartile (P(25-50)) and highest quartile (P(75-100)) of r(c)SO2 on day 1 were associated with poorer cognitive outcome (p=0.044 and p=0.008 respectively). A lower area under the curve (AUC; over 15d) of r(c)SO2 was associated with poorer cognitive outcome (p=0.014). The lower quartile (P(25-50)) AUC of r(c)SO2 was associated with poorer fine motor outcome (p=0.004). The amount of time r(c)SO2 <50% on day 1 was negatively associated with gross motor outcome (p=0.002). The highest quartile of FTOE on day 1 was associated with poorer total motor outcome (p=0.041). INTERPRETATION: Cerebral oxygen saturation during the first 2 weeks after birth is associated with neurodevelopmental outcome of preterm infants at 2 to 3 years. High and low r(c)SO2 on day 1 were associated with poorer neurodevelopmental outcome.

Early visual attention in preterm and fullterm infants in relation to cognitive and motor outcomes at school age: an exploratory study.

OBJECTIVE: Preterm infants are exposed to the visual environment earlier than fullterm infants, but whether early exposure affects later development is unclear. Our aim was to investigate whether the development of visual disengagement capacity during the first 6 months postterm was associated with cognitive and motor outcomes at school age, and whether associations differed between fullterms and low-risk preterms. METHOD: Seventeen fullterms and ten low-risk preterms were tested in a gaze shifting task every 4 weeks until 6 months postterm. The longitudinal data were converted into single continuous variables by fitting the data with an S-shaped curve (frequencies of looks) or an inverse model (latencies of looks). Neuropsychological test results at school age were converted into composite z scores. We then performed linear regression analyses for each functional domain at school age with the variables measuring infant visual attention as separate predictors and adjusting for maternal level of education and group (fullterms versus preterms). We included an interaction term, visual attention*group, to determine whether predictive relations differed between fullterms and preterms. RESULTS: A slower development of disengagement predicted poorer performance on attention, motor skills, and handwriting, irrespective of fullterm or preterm birth. Predictive relationships differed marginally between fullterms and preterms for inhibitory attentional control (P = 0.054) and comprehensive reading (P = 0.064). CONCLUSION: This exploratory study yielded no indications of a clear advantage or disadvantage of the extra visual exposure in healthy preterm infants. We tentatively conclude that additional visual exposure does not interfere with the ongoing development of neuronal networks during this vulnerable period of brain development.

Motor development in 3-month-old healthy term-born infants is associated with cognitive and behavioural outcomes at early school age.

AIM: To determine whether motor development at 3 months of age is associated with cognitive, motor, and behavioural outcomes in healthy children at early school age. METHOD: In this cohort study, we included 74 term-born, healthy children (44 males, 30 females; median gestational age 40.1 wks, range 38.0-42.6 wks). From video recordings (median 12.9 wks, range 9.3-18.6 wks), we assessed the quality of fidgety movements, and calculated a motor optimality score. At school age (median 5 y 11 mo, range 5 y 8 mo-7 y 6 mo), we performed detailed cognitive, motor, and behavioural assessments. We examined whether aspects of motor development were associated with functional outcomes. RESULTS: An age-adequate motor repertoire, in particular the presence of antigravity, midline leg, and manipulation movements, was related to poorer cognition, whereas variable finger postures was related to better cognition. Children with a monotonous concurrent motor repertoire had better ball skills but experienced more behavioural problems. The presence of antigravity movements tended to be associated with abnormal recognition (odds ratio [OR] 4.4, 95% confidence interval [CI], 0.9-21; R(2) =0.17; p=0.070), where the absence of variable finger postures was associated with borderline and abnormal visual-spatial perception (OR 20, 95% CI, 1.7-238; R(2) =0.39; p=0.018). INTERPRETATION: Detailed aspects of motor development at 3 months of age are associated with cognition and behaviour, but not with motor outcome, in healthy children at early school age. Our findings suggest that early motor development may be the basis for later cognitive and behavioural performance. Since the associations were only moderate, possible environmental influences should be acknowledged.

Functional outcome at school age of preterm-born children treated with high-dose dexamethasone.

BACKGROUND: Postnatal dexamethasone (DXM) treatment is associated with adverse motor outcome. It is largely unknown as to what extent functional outcome at school age is affected. AIMS: Our first aim was to determine motor, cognitive, and behavioural outcome at school age of preterm-born children treated with high-dose DXM for pulmonary problems. Our second aim was to identify DXM-related risk factors for adverse outcome. STUDY DESIGN: In this cohort study, we included 53 very preterm-born children treated with DXM (starting dose 0.5mg/kg/d) after the first week of life. At the median age of 9 years, we performed a detailed neuropsychological assessment. RESULTS: Compared to the norm population, DXM-treated children scored worse on the Movement-ABC (abnormal fine motor, ball skills and balance: 59%, 47% and 30%, respectively). They more often had total (36%), verbal (32%) and performance IQs (55%) below 85 (P<.001, P=.002, P<.001, respectively). On each of the remaining measures, DXM-treated children scored worse than the norm population, except for verbal long-term memory and verbal recognition memory. DXM-related risk factors were associated with poorer performance. CONCLUSIONS: At school age, multiple domains of functional outcome were affected in DXM-treated children. Risk factors related to the use of DXM should be considered as serious potentiaters of adverse outcome in children treated with high-dose DXM.

Development of fine motor skills in preterm infants.

Fine motor skills are related to functioning in daily life and at school. We reviewed the status of knowledge, in preterm children, on the development of fine motor skills, the relation with gross motor skills, and risk factors for impaired fine motor skills. We searched the past 15 years in PubMed, using ['motor skills' or 'fine motor function' and 'preterm infant'] as the search string. Impaired gross and fine motor skills are among the most frequently occurring problems encountered by preterm children who do not develop cerebral palsy. The prevalence is around 40% for mild to moderate impairment and 20% for moderate impairment. Fine motor skill scores on the Movement Assessment Battery for Children are about 0.62 of a standard deviation lower compared with term children. Risk factors for fine motor impairments include moderately preterm birth (odds ratio [OR] 2.0) and, among very preterm children (<32 wk gestation), intra-uterine growth restriction (ORs 2-3), inflammatory conditions (late-onset sepsis and necrotizing enterocolitis, ORs 3-5), and dexamethasone therapy for bronchopulmonary dysplasia (OR 2.7). A better understanding of factors that play a role in the development of and recovery from brain injury could guide future intervention attempts aimed at improving fine motor skills of preterm children.

Visuospatial and visuomotor deficits in preterm children: the involvement of cerebellar dysfunctioning.

One of the more consistent findings in follow-up studies of preterm children is a deficit in visuospatial and visuomotor skills. Impairment of the dorsal visual stream and basal ganglia damage have been hypothesized to underlie this deficit. However, given recent findings of impaired cerebellar development in preterm children without lesions to this structure, and the involvement of the cerebellum in visuospatial and visuomotor functioning, we argue the cerebellum should be included in models relating impaired development of brain networks to visuospatial and visuomotor deficits in this population. Here, we review the current literature on impaired cerebellar development in preterm children, and suggest possible underlying mechanisms.

Volume expansion does not alter cerebral tissue oxygen extraction in preterm infants with clinical signs of poor perfusion.

BACKGROUND: Preterm infants with signs of poor perfusion are often treated with volume expansion, although evidence regarding its effect on cerebral perfusion is lacking. Moreover, the effect is questionable in preterm infants with an adequate cerebrovascular autoregulation (CAR). A useful measure to assess perfusion is cerebral fractional tissue oxygen extraction (cFTOE). OBJECTIVES: To assess the effect of volume expansion on cFTOE in preterm infants with signs of poor perfusion. METHODS: In this observational study, we assessed cFTOE using near-infrared spectroscopy in preterm infants with signs of poor perfusion before, during and 1 h after volume expansion treatment. Simultaneously, we measured mean arterial blood pressure (MABP). We tested the effect of volume expansion on both cFTOE and MABP, using multi-level analyses. We intended to define a subgroup that responded to volume expansion with an increase in blood pressure and a decrease in cFTOE, suggesting absent CAR. RESULTS: In 14 preterm infants, with a median gestational age of 26.7 weeks (25.0-28.7 weeks) and a median birth weight of 836 g (615-1,290 g), we found a small increase in MABP during (1.4 ± 1.4 mm Hg, p = 0.003) and after (1.8 ± 1.7 mm Hg, p = 0.001) volume expansion, but no change in cFTOE during (-0.19 ± 0.1% p = 0.44) or after (-0.53 ± 0.1% p = 0.34) volume expansion. We were unable to define a subgroup lacking CAR. CONCLUSIONS: Cerebral perfusion, as assessed by cFTOE, does not improve in preterm infants with signs of poor perfusion following volume expansion. In these infants, either CAR is present or volume expansion is inadequate to affect cFTOE.

Motor and cognitive outcome at school age of children with surgically treated intestinal obstructions in the neonatal period.

BACKGROUND: The motor and cognitive outcome at school age of newborn children with surgically treated intestinal obstructions is unknown. Physiological stress and anesthesia may potentially be harmful in the period of early brain development in newborn infants. OBJECTIVE: To determine motor and cognitive outcome at school age in children with surgically treated intestinal obstructions as newborns, and to identify clinical risk factors for adverse outcome. STUDY DESIGN: Cohort study of infants born between 1995 and 2002 with atresia, stenosis, or intestinal malrotation. At 6 to 13years we assessed their motor functions, intelligence, attention, visual perception, visuomotor integration, and verbal memory. RESULTS: Of 44 children three (7%) died. Twenty-seven survivors (66%) were included for follow-up (median gestational age 36.7weeks, birth weight 3000g). Motor outcome was abnormal (<5th percentile) in 22% of the children, which was significantly more than in the norm population (P<0.01). Scores on selective attention were abnormal in 15% of the children (P<0.01). Other cognitive functions were not affected. Lower birth weight and intestinal perforation were risk factors for poorer motor outcome (R(2)=53.0%), intrauterine growth restriction was a risk factor for poorer selective attention (R(2)=36.6%). CONCLUSIONS: Children treated surgically for intestinal obstructions in the neonatal period had an increased risk for poor motor functioning and selective attention at school age. Low birth weight, intrauterine growth restriction and intestinal perforation were risk factors for adverse outcome. We recommend to closely follow the motor and attentional development of these children.