Marianne Moore

Positive Screening for Autism in Ex-preterm Infants: Prevalence and Risk Factors

OBJECTIVE. The survival of very low birth weight infants has increased markedly in recent years. Unfortunately, the prevalence of significant and lifelong motor, cognitive, and behavioral dysfunction has remained a major problem confronting these children. The objective of this study was to perform screening tests for early autistic features in children with a history of very low birth weight and to identify risk factors associated with a positive screening result. METHODS. We studied 91 ex-preterm infants ≤ 1500 g at birth. Infants underwent conventional MRI studies at preterm and/or term-adjusted age. We collected pertinent demographic, prenatal, intrapartum, acute postnatal, and short-term outcome data for all infants. Follow-up assessments were performed at a mean age of 21.9 ± 4.7 months, using the Modified Checklist for Autism in Toddlers, the Vineland Adaptive Behavior Scale, and the Child Behavior Checklist. RESULTS. Twenty-six percent of ex-preterm infants had a positive result on the autism screening tool. Abnormal scores correlated highly with internalizing behavioral problems on the Child Behavior Checklist and socialization and communication deficits on the Vineland Scales. Lower birth weight, gestational age, male gender, chorioamnionitis, acute intrapartum hemorrhage, illness severity on admission, and abnormal MRI studies were significantly associated with an abnormal autism screening score. CONCLUSIONS. Early autistic behaviors seem to be an underrecognized feature of very low birth weight infants. The results from this study suggest that early screening for signs of autism may be warranted in this high-risk population followed by definitive autism testing in those with positive screening results.

Fluctuating Pressure-Passivity Is Common in the Cerebral Circulation of Sick Premature Infants

Cerebral blood flow pressure-passivity results when pressure autoregulation is impaired, or overwhelmed, and is thought to underlie cerebrovascular injury in the premature infant. Earlier bedside observations suggested that transient periods of cerebral pressure-passivity occurred in premature infants. However, these transient events cannot be detected reliably by intermittent static measurements of pressure autoregulation. We therefore used continuous bedside recordings of mean arterial pressure (MAP; from an indwelling arterial catheter) and cerebral perfusion [using the near-infrared spectroscopy (NIRS) Hb difference (HbD) signal) to detect cerebral pressure-passivity in the first 5 d after birth in infants with birth weight <1500 g. Because the Hb difference (HbD) signal [HbD = oxyhemoglobin (HbO2) − Hb] correlates with cerebral blood flow (CBF), we used coherence between MAP and HbD to define pressure-passivity. We measured the prevalence of pressure-passivity using a pressure-passive index (PPI), defined as the percentage of 10-min epochs with significant low-frequency coherence between the MAP and HbD signals. Pressure-passivity occurred in 87 of 90 premature infants, with a mean PPI of 20.3%. Cerebral pressure-passivity was significantly associated with low gestational age and birth weight, systemic hypotension, and maternal hemodynamic factors, but not with markers of maternal infection. Future studies using consistent serial brain imaging are needed to define the relationship between PPI and cerebrovascular injury in the sick premature infant.

Impaired Trophic Interactions Between the Cerebellum and the Cerebrum Among Preterm Infants

Background. Advanced neuroimaging techniques have brought increasing recognition of cerebellar injury among premature infants. The developmental relationship between early brain injury and effects on the cerebrum and cerebellum remains unclear. Objectives. To examine whether cerebral parenchymal brain lesions among preterm infants are associated with subsequent decreases in cerebellar volume and, conversely, whether primary cerebellar injury is associated with decreased cerebral brain volumes, with advanced, 3-dimensional, volumetric MRI at term gestational age equivalent. Methods. Total cerebellar volumes and cerebellar gray and myelinated white matter volumes were determined through manual outlining for 74 preterm infants with unilateral periventricular hemorrhagic infarction (14 infants), bilateral diffuse periventricular leukomalacia (20 infants), cerebellar hemorrhage (10 infants), or normal term gestational age equivalent MRI findings (30 infants). Total brain and right/left cerebral and cerebellar hemispheric volumes were calculated. Results. Unilateral cerebral brain injury was associated with significantly decreased volume of the contralateral cerebellar hemisphere. Conversely, unilateral primary cerebellar injury was associated with a contralateral decrease in supratentorial brain volume. Cerebellar gray matter and myelinated white matter volumes were reduced significantly not only among preterm infants with primary cerebellar hemorrhage but also among infants with cerebral parenchymal brain injury. Conclusions. These data suggest strongly that both reduction in contralateral cerebellar volume with unilateral cerebral parenchymal injury and reduction in total cerebellar volume with bilateral cerebral lesions are related to trophic transsynaptic effects. Early-life cerebellar injury may contribute importantly to the high rates of cognitive, behavioral, and motor deficits reported for premature infants.

Cerebellar Hemorrhage in the Preterm Infant: Ultrasonographic Findings and Risk Factors

Cerebellar hemorrhage (CBH) in premature infants is increasingly diagnosed secondary to improved neuroimaging techniques and survival of very small preterm infants. Information is limited, however, on the incidence, topography, and risk factors for CBH in the preterm infant. Objectives. To define the incidence of CBH in preterm infants diagnosed by neonatal cranial ultrasound (US), describe the sonographic features of CBH, and identify maternal and perinatal risk factors associated with this lesion. Methods. A systematic electronic database search identified preterm infants born 1998–2002 with US diagnosis of CBH. For 35 cases of CBH we double-matched (according to gestational age, gender, and year of birth) 70 preterm controls with normal cranial USs and performed detailed medical-record reviews for both patients and controls. Results. Unilateral CBH was seen in 25 patients (71%), vermian hemorrhage was seen in 7 (20%), and combined bihemispheric and vermian hemorrhage was seen in 3 (9%). Isolated CBH occurred in 8 patients (23%); the remaining infants had associated supratentorial lesions. The incidence of CBH in preterm infants weighing <750 g at birth showed significant increase over the study period. Univariate analyses identified maternal, intrapartum, and early postnatal hemodynamic risk factors; multivariate regressions indicated that emergent caesarian section, patent ductus arteriosus, and lower 5-day minimum pH independently increased the odds of CBH. Neonatal mortality and morbidity were significantly higher among patients with CBH compared with preterm controls. Conclusions. CBH is an important complication of extreme preterm birth and has been underrecognized in surviving preterm infants. Predictors of CBH seem to be multifactorial and include combined maternal, intrapartum, and early postnatal factors.

Cerebral Hemodynamic Changes During Intensive Care of Preterm Infants

OBJECTIVES. The objectives of this study were to examine the circulatory changes experienced by the immature systemic and cerebral circulations during routine events in the critical care of preterm infants and to identify clinical factors that are associated with greater hemodynamic-oxygenation changes during these events. METHODS. We studied 82 infants who weighed <1500 g at birth and required intensive care management and continuous blood pressure monitoring from an umbilical arterial catheter. Continuous recording of cerebral and systemic hemodynamic and oxygenation changes was performed. We studied 6 distinct types of caregiving events during 10-minute epochs: (1) quiet baseline periods; (2) minor manipulation; (3) diaper changes; (4) endotracheal tube suctioning; (5) endotracheal tube repositioning; and (6) complex events. Each event was matched with a preceding baseline. We examined the effect of specific clinical factors and cranial ultrasound abnormalities on the systemic and cerebral hemodynamic oxygenation changes that were associated with the various event types. RESULTS. There were highly significant differences in hemodynamics and oxygenation between events overall and baseline epochs. The magnitude of these circulatory changes was greatest during endotracheal tube repositioning and complex caregiving events. Lower gestational age, higher illness severity, chorioamnionitis, low Apgar scores, and need for pressor-inotropes all were associated with circulatory changes of significantly lower magnitude. Cerebral hemodynamic changes were associated with early parenchymal ultrasound abnormalities. CONCLUSIONS. Routine caregiving procedures in critically ill preterm infants are associated with major circulatory fluctuations that are clinically underappreciated and underdetected by current bedside monitoring. Our data underscore the importance of continuous cerebral hemodynamic monitoring in critically ill preterm infants.

Current Definitions of Hypotension Do Not Predict Abnormal Cranial Ultrasound Findings in Preterm Infants

OBJECTIVE. Hypotension is a commonly treated complication of prematurity, although definitions and management guidelines vary widely. Our goal was to examine the relationship between current definitions of hypotension and early abnormal cranial ultrasound findings. METHODS. We prospectively measured mean arterial pressure in 84 infants who were ≤30 weeks’ gestational age and had umbilical arterial catheters in the first 3 days of life. Sequential 5-minute epochs of continuous mean arterial pressure recordings were assigned a mean value and a coefficient of variation. We applied to our data 3 definitions of hypotension in current clinical use and derived a hypotensive index for each definition. We examined the association between these definitions of hypotension and abnormal cranial ultrasound findings between days 5 and 10. In addition, we evaluated the effect of illness severity (Score for Neonatal Acute Physiology II) on cranial ultrasound findings. RESULTS. Acquired lesions as shown on cranial ultrasound, present in 34 (40%) infants, were not predicted by any of the standard definitions of hypotension or by mean arterial pressure variability. With hypotension defined as mean arterial pressure < 10th percentile (<33 mmHg) for our overall cohort, mean value for mean arterial pressure and hypotensive index predicted abnormal ultrasound findings but only in infants who were ≥27 weeks’ gestational age and those with lower illness severity scores. CONCLUSIONS. Hypotension as diagnosed by currently applied thresholds for preterm infants is not associated with brain injury on early cranial ultrasounds. Blood pressure management directed at these population-based thresholds alone may not prevent brain injury in this vulnerable population.

Occurrence of Hyaline Membrane Disease (HMD) in Infants ≥ 34 Weeks Gestation Is Not Explained by Carrier State for Surfactant Protein-B (SP-B) Mutation 121ins2

Occurrence of Hyaline Membrane Disease (HMD) in Infants ≥ 34 Weeks Gestation Is Not Explained by Carrier State for Surfactant Protein-B (SP-B) Mutation 121ins2

Clinical Markers of Barotrauma and Oxygen Toxicity and Inter-Hospital Variation in Rates of Chronic Lung Disease Among Surviving Very Low Birth Weight Infants

Clinical Markers of Barotrauma and Oxygen Toxicity and Inter-Hospital Variation in Rates of Chronic Lung Disease Among Surviving Very Low Birth Weight Infants