Brain abnormalities seen in late pre-term infants

A study looked into MRI scans of late pre-term infant and found that they have brain abnormalities.

Babies born 32 to 36 weeks into gestation may have smaller brains and other brain abnormalities that could lead to long-term developmental problems, according to a new study published online in the journal Radiology.

Much of the existing knowledge on preterm birth and brain development has been drawn from studies of individuals born very preterm, or less than 32 weeks into gestation at birth.

For the new study, researchers in Australia focused on moderate and late preterm (MLPT) babies -- those born between 32 weeks, zero days, and 36 weeks, six days, into gestation. MLPT babies account for approximately 80 percent of all preterm births and are responsible for much of the rise in the rates of preterm birth over the last 20 years. Despite this, to date there have been no large-scale studies published on brain alterations associated with MLPT birth that may provide insight into brain-behavior relationships in this group of children.

"In those very preterm babies, brain injury from bleeding into the brain or a lack of blood flow, oxygen or nutrition to the brain may explain some of the abnormal brain development that occurs," said the study's lead author, Jennifer M. Walsh,M.B.B.Ch., B.A.O., M.R.C.P.I., from the Royal Women's Hospital in Melbourne, Australia. "However, in some preterm babies, there may be no obvious explanation for why their brain development appears slow compared with babies born on time."

To learn more, the researchers performed magnetic resonance imaging (MRI) exams on 199 MLPT and 50 term-born infants (greater than 37 weeks gestation) between 38 to 44 weeks of gestation. They looked for signs of brain injury and compared the size and maturation of multiple brain structures in the two groups.

While injury rates were similar between the two groups, MLPT birth was associated with smaller brain size at term-equivalent age. In addition, MLPT infants had less developed myelination in one part of the brain and more immature gyral folding compared with term-born controls. Myelination -- the formation of a fatty insulating sheath around some nerve fibers -- and gyral folding -- the folding of the cerebral cortex to increase the brain's surface area -- are important processes in early brain development.

The findings suggest that MLPT birth may disrupt the expected trajectory of brain growth that would normally occur in the last two or so months in utero, according to Dr. Walsh.

"Given that brain growth is very rapid in the last one-third of pregnancy, it is perhaps not surprising that being born during this potentially vulnerable period may disrupt brain development," she said. "Brain growth is very complex, involving not only the neurons with which we think and do things, but also the other brain cells that support the neurons and are vital for normal brain function."

The researchers are hoping to learn in greater depth the impact that moderate to late preterm birth has on the brain, so that they can then begin to try different treatments designed to improve brain function and long-term outcome in these infants.

"Medications, along with early intervention to help parents understand their baby's needs, have been effective in helping very preterm babies catch up to their term-born peers," Dr. Walsh said. "However, whether any of the existing treatments will help babies born between 32 and 36 weeks is unknown, as they have not been studied very much at all."

The researchers plan to follow the infants in the study group through childhood to learn more about the relationship between brain abnormalities and later outcomes. They also are assessing additional MRI information about brain structure and function in these children.

"Understanding what problems they have and what might be causing them is the first step in trying to improve their long-term outcome," Dr. Walsh said.

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Seizures in Infants. What do seizures do to brain cells?

J Neuropathol Exp Neurol. 2014 Apr;73(4):324-34. doi: 10.1097/NEN.0000000000000056.

Correlation between clinical and histologic findings in the human neonatal hippocampus after perinatal asphyxia.

Schiering IA1, de Haan TR, Niermeijer JM, Koelman JH, Majoie CB, Reneman L, Aronica E.

Author information

Abstract

Hypoxic ischemic encephalopathy after perinatal asphyxia is a major cause of mortality and morbidity in infants. Here, we evaluated pathologic changes in the hippocampi of a cohort of 16 deceased full-term asphyxiated infants who died from January 2000 to January 2009. 

Histochemical and immunocytochemical results for glial and neuronal cells were compared between cases with or without seizures and to adult and sudden infant death syndrome cases (n = 3 each). All asphyxiated infants displayed neuronal cell damage and reactive glial changes. Strong aquaporin-4 immunoreactivity was seen on astroglial cells within hippocampi in 50% of cases. 

In patients with seizures, the expression of metabotropic glutamate receptors was increased in glial cells. Cases with seizures displayed increased microglial activation and greater expression of the inflammatory markers interleukin 1β and complement 1q compared with those in cases without seizures. 

All cases with seizures displayed alterations in the blood-brain barrier, as assessed by immunohistochemistry for albumin. These findings confirm the complex cascade of cellular and molecular changes occurring in the human neonatal hippocampus after perinatal asphyxia. These changes may contribute to seizure development leading to secondary brain damage. These data may aid in the development of therapeutic targets for neonatal seizures.

Skin to Skin with Premature Babies - Better Brain Function

Preemies' Brains Reap Long-Term Benefits from Kangaroo Mother Care

Sep. 19, 2012 — Kangaroo Mother Care -- a technique in which a breastfed premature infant remains in skin-to-skin contact with the parent's chest rather than being placed in an incubator -- has lasting positive impact on brain development, revealed Université Laval researchers in the October issue of Acta Paediatrica. 

Very premature infants who benefited from this technique had better brain functioning in adolescence -- comparable to that of adolescents born at term -- than did premature infants placed in incubators.

Earlier research showed that infants born prior to the 33rd week of pregnancy experienced more cognitive and behavioral problems during childhood and adolescence. Université Laval researchers Cyril Schneider and Réjean Tessier, of the Department of Rehabilitation in the Faculty of Medicine and of the School of Psychology, respectively, and their Colombian colleagues Nathalie Charpak (Kangaroo Foundation) and Juan Ruiz-Peláez (Universidad Javeriana) wanted to determine if Kangaroo Mother Care could prevent these problems. To that end they compared, at age 15, 18 premature infants kept in incubators, 21 premature infants held in Kangaroo contact for an average of 29 days, and 9 term infants.

To assess participants' brain functions, the researchers used transcranial magnetic stimulation. With this non-invasive and painless technique they could activate brain cells in targeted areas, namely the primary motor cortex that controls muscles. By measuring muscle responses to the stimulation, they were able to assess brain functions such as the level of brain excitability and inhibition, cell synchronization, neural conduction speed, and coordination between the two cerebral hemispheres.
The data collected by the researchers indicate that all brain functions of the adolescent Kangaroo group were comparable to those of the term infant group. On the other hand, premature infants placed in incubators significantly deviated from the other two groups 15 years after their birth.

"Thanks to Kangaroo Mother Care, infants benefited from nervous system stimulation -- the sound of the parent's heart and the warmth of their body -- during a critical period for the development of neural connections between the cerebral hemispheres. This promoted immediate and future brain development," suggests neurophysiologist Cyril Schneider.

http://www.sciencedaily.com/releases/2012/09/120919125600.htm

Anxiety in adolescents born preterm or with very low birthweight: a meta-analysis of case–control studies

Anxiety in adolescents born preterm or with very low birthweight: 

a meta-analysis of case-

control studies

 Method  We used a systematic review and meta-analysis. We searched the databases ISI Web of Knowledge, PubMed, PsycNET, Educational Resources Information Center (ERIC), Latin American and Caribbean Literature on the Health Sciences (LILACS), and Virtual Health Library (VHL) with equivalent search expressions (from the databases’ inception to June 2011). Also, we screened reference lists of identified articles. We selected case–control studies of adolescents 11 to 20 years old who were very preterm/VLBW and had a matched reference group born at term with normal birthweight that reported a validated anxiety outcome measure. For data extraction, two authors independently reviewed titles, abstracts, and full articles identified through the searches. Subsequently two authors independently extracted data.

Results  We included six studies with 1519 adolescents (787 very preterm/VLBW, 732 comparisons). The general risk of developing clinically significant anxiety problems was nearly doubled (p<0 .05=".05" 1.15="1.15" 2.27="2.27" 5.5="5.5" 9.9="9.9" 95="95" and="and" comparison="comparison" confidence="confidence" group.="group." group="group" in="in" interval="interval" overall="overall" p="p" population="population" preterm="preterm" prevalences="prevalences" the="the" very="very" were="were">

Interpretation  Those born very preterm/VLBW have an increased risk of developing clinically significant anxiety problems in adolescence.

White-matter abnormalities on term MRI predict cognitive problems in very preterm infants

• Editor's Note:  Here is another reason that before going home, many NICU babies have an MRI and a neurologist's input to help predict outcome.  
• In this study, abnormal white matter predicted mildly low verbal IQ (odds ratio, 6.2), performance IQ (6.0), and full-scale IQ (6.3), and the need for special assistance at school (5.9). 
• 
  

Qualitative Brain MRI at Term and Cognitive 

Outcomes at 9 Years After Very Preterm Birth

1. Sachiko Iwata, MD^a,^b, 
2. Tomohiko Nakamura, MD, PhD^b, 
3. Eriko Hizume, DOT^c,
4. Hideki Kihara, DPT, PhD^c, 
5. Sachio Takashima, MD, PhD^d, 
6. Toyojiro Matsuishi, MD, PhD^a, and 
7. Osuke Iwata, MD^a,^b

+Author Affiliations

1. ^aCentre for Developmental & Cognitive Neuroscience, Department of Paediatrics and Child Health, Kurume University School of Medicine, Kurume, Fukuoka, Japan;
2. Divisions of ^bNeonatology, and
3. ^cRehabilitation, Nagano Children’s Hospital, Nagano, Japan; and
4. ^dYanagawa Institute for Developmental Disabilities, International University of Health and Welfare, Fukuoka, Japan

ABSTRACT

OBJECTIVE: A prospective study was performed to assess the relationship between the appearance of cerebral MRI at term and the cognitive functioning at 9 years old in very preterm born infants.

METHODS: Seventy-six very preterm born infants (birth weight <1500 g or gestational age ≤32 weeks) obtained cerebral MRI at term-equivalent period, which was assessed by using established composite scores for the white and gray matter; cognitive outcomes at 9 years old were assessed in 60 subjects by using Wechsler Intelligence Scale for Children, Third Edition.

RESULTS: Mildly low scores on the different IQ indices (<85) were observed in 23.3% (verbal IQ), 41.7% (performance IQ), and 30.0% (full-scale IQ) of the cohort, whereas moderately low scores (<70) were noted in 3.3% (verbal IQ), 11.7% (performance IQ), and 11.7% (full-scale IQ); cerebral palsy was diagnosed in 10.0%, whereas special assistance at school was required in 56.7%. Abnormal white matter appearances predicted mildly low verbal, performance, and full-scale IQs; moderately low performance and full-scale IQs; cerebral palsy; and the requirement for special assistance at school. Abnormal white matter appearances predicted mild cognitive impairment even after the adjustment for known clinical risk factors. In contrast, abnormal gray matter appearances did not predict any of the outcome measures.

CONCLUSIONS: In a cohort of very preterm born infants, abnormal white matter appearance on term MRI showed consistent associations with cognitive impairments at 9 years old, further supporting the benefit of obtaining term MRI for very preterm born infants.