Technical considerations for placental tissue processing and the subsequent impact on genome-wide DNA methylation analysis.

To assess the impact of postnatal processing on placental DNA methylation, array data from flash-frozen placental tissue was compared to perfluorocarbon-immersed and formalin-fixed paraffin-embedded placental tissue. We observed that tissue exposed to perfluorocarbon showed no significant DNA methylation differences when compared to unprocessed tissue, while formalin processing altered the quality and reliability of the data produced on the DNA methylation array platform. Placental DNA methylation allows for the study of gene-environment interactions that influence the fetal environment and development.

Impaired in vivo feto-placental development is associated with neonatal neurobehavioral outcomes.

Background: Fetal growth restriction (FGR) is a risk factor for neurodevelopmental problems, yet remains poorly understood. We sought to examine the relationship between intrauterine development and neonatal neurobehavior in pregnancies diagnosed with antenatal FGR.

Methods: We recruited women with singleton pregnancies diagnosed with FGR and measured placental and fetal brain volumes using MRI.

Comparison of Frequency- and Time-Domain Autoregulation and Vasoreactivity Indices in a Piglet Model of Hypoxia-Ischemia and Hypothermia.

Introduction: The optimal method to detect impairments in cerebrovascular pressure autoregulation in neonates with hypoxic-ischemic encephalopathy (HIE) is unclear. Improving autoregulation monitoring methods would significantly advance neonatal neurocritical care.

Methods: We tested several mathematical algorithms from the frequency and time domains in a piglet model of HIE, hypothermia, and hypotension.

Cerebrospinal Fluid and Parenchymal Brain Development and Growth in the Healthy Fetus.

Objective: The objective of this study was to apply quantitative magnetic resonance imaging to characterize absolute cerebrospinal fluid (CSF) development, as well as its relative development to fetal brain parenchyma in the healthy human fetus.

Design: We created three-dimensional high-resolution reconstructions of the developing brain for healthy fetuses between 18 and 40 weeks' gestation, segmented the parenchymal and CSF spaces, and calculated the volumes for the lateral, third, and fourth ventricles; extra-axial CSF space; and the cerebrum, cerebellum, and brainstem. From these data, we constructed normograms of the resulting volumes according to gestational age and described the relative development of CSF to fetal brain parenchyma.

The Impact of Surgical Patent Ductus Arteriosus Closure on Autonomic Function in Premature Infants.

 Patent ductus arteriosus (PDA) is a common complication of prematurity and a risk factor for poor outcome. Infants undergoing surgical PDA ligation are at highest risk for neurodevelopmental injury. Autonomic dysfunction has been described in premature infants with PDA.

Prenatal evaluation of atelencephaly.

Atelencephaly is a rare lethal congenital brain malformation characterized by underdevelopment of the prosencephalon and is often accompanied by the facial features seen in some cases of holoprosencephaly, such as cyclopia. We report a case of atelencephaly in the fetus with characteristic ultrasound findings. In addition, we report the findings on fetal MRI, which have not been previously described in the literature.

3-D volumetric MRI evaluation of the placenta in fetuses with complex congenital heart disease.

Introduction: Placental insufficiency remains a common cause of perinatal mortality and neurodevelopmental morbidity. Congenital heart disease (CHD) in the fetus and its relationship to placental function is unknown. This study explores placental health and its relationship to neonatal outcomes by comparing placental volumes in healthy pregnancies and pregnancies complicated by CHD using in vivo three-dimensional MRI studies.

Feasibility of noninvasive fetal electrocardiographic monitoring in a clinical setting.

Cardiac rhythm is an essential component of fetal cardiac evaluation. The Monica AN24 is a fetal heart rate monitor that may provide a quick, inexpensive modality for obtaining a noninvasive fetal electrocardiogram (fECG) in a clinical setting. The fECG device has the ability to acquire fECG signals and allow calculation of fetal cardiac time intervals between 16- and 42-week gestational age (GA).

Specialized delivery room planning for fetuses with critical congenital heart disease.

Improvements in fetal echocardiography have increased recognition of fetuses with congenital heart disease (CHD) that require specialized delivery room (DR) care. In this study, care protocols for these low-volume and high-risk deliveries were created. Elements included (1) diagnosis-specific DR care plans and algorithms, (2) a multidisciplinary team with expertise, (3) simulation, (4) checklists, and (5) debriefing.

Impact of congenital heart disease on fetal brain development and injury.

Purpose Of Review: Advances in cardiac surgical techniques and intensive care have led to improved survival in babies with congenital heart disease (CHD). Although it is true that the majority of children with CHD today survive, many have impaired neurodevelopmental outcome. Although continuing to improve short-term morbidity and mortality are important goals, recent research has focused on defining the impact of CHD on brain development and brain injury in utero.

Magnetic resonance volumetric assessments of brains in fetuses with ventriculomegaly correlated to outcomes.

Objectives: The purpose of this study was to correlate 2-dimensional magnetic resonance (MR) measurements of lateral ventricular width and 3-dimensional measurements of lateral ventricular and supratentorial parenchymal volumes to postnatal outcomes in fetuses with ventriculomegaly.

Methods: A total of 307 fetuses (mean gestational age, 26.0 weeks; range, 15.

The syndrome of perisylvian polymicrogyria with congenital arthrogryposis.

Background: Bilateral perisylvian polymicrogyria (BPP) is a well-recognized malformation of cortical development commonly associated with epilepsy, cognitive impairment, and oromotor apraxia. Reports have suggested the association of BPP with arthrogryposis multiplex congenita. We sought to investigate the clinical, electrophysiological, and neuroradiological features of this combined syndrome to determine if there are unique features that distinguish BPP with arthrogryposis from BPP alone.

Does cerebellar injury in premature infants contribute to the high prevalence of long-term cognitive, learning, and behavioral disability in survivors?

Objective: Although cerebellar hemorrhagic injury is increasingly diagnosed in infants who survive premature birth, its long-term neurodevelopmental impact is poorly defined. We sought to delineate the potential role of cerebellar hemorrhagic injury in the long-term disabilities of survivors of prematurity.

Design: We compared neurodevelopmental outcome in 3 groups of premature infants (N = 86; 35 isolated cerebellar hemorrhagic injury, 35 age-matched controls, 16 cerebellar hemorrhagic injury plus supratentorial parenchymal injury).

Video and CD-ROM as a training tool for performing neurologic examinations of 1-year-old children in a multicenter epidemiologic study.

In lieu of traditional training of examiners to identify cerebral palsy on a neurologic examination at age 1 year, we proposed an alternative approach using a multimedia training video and CD-ROM we developed after a two-step validation process. We hypothesized that use of CD-ROM interactive training will lead to reliable and valid performance of the neurologic examination by both pediatric neurologists and nonpediatric neurologists. All examiners were asked to take one of six interobserver variability tests found on the CD-ROM on two occasions.

Hemodilution elevates cerebral blood flow and oxygen metabolism during cardiopulmonary bypass in piglets.

Background: Hemodilution continues to be widely used during cardiopulmonary bypass (CPB) for both adults and children. Previous studies with nonbypass models have suggested that an increase in cerebral blood flow (CBF) compensates for the reduced oxygen-carrying capacity; however, this increased CBF is achieved by an increase in cardiac output. We hypothesized that even with the fixed-flow perfusion of CPB, CBF would be increased during hemodilution.

The effect of duration of deep hypothermic circulatory arrest in infant heart surgery on late neurodevelopment: the Boston Circulatory Arrest Trial.

Objectives: Despite the technical advantages of total circulatory arrest for vital organ support during infant heart surgery, many centers have moved away from its use because of the demonstrated effects of circulatory arrest of long duration on neurodevelopmental outcomes. Our goal was to determine the functional form of the association between duration of circulatory arrest and risk of neurodevelopmental dysfunction.

Methods: From 1988 to 1992, in a single-center trial, infants with d-transposition of the great arteries underwent the arterial switch operation after random assignment to circulatory arrest or low-flow bypass.

Neurodevelopmental status at eight years in children with dextro-transposition of the great arteries: the Boston Circulatory Arrest Trial.

Objectives: Our goal was to determine which of the two major methods of vital organ support used in infant cardiac surgery, total circulatory arrest and low-flow cardiopulmonary bypass, results in better neurodevelopmental outcomes at school age.

Methods: In a single-center trial, infants with dextrotransposition of the great arteries underwent the arterial switch operation after random assignment to either total circulatory arrest or low-flow cardiopulmonary bypass. Developmental, neurologic, and speech outcomes were assessed at 8 years of age in 155 of 160 eligible children (97%).