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Research on Prematurity Impacts

Research studies that all of us should have on hand to show the school, the pediatrician, and any other institution or person who deals with our premature children.

By Helen Harrison

See Also: Helen Harrison's Bibliography of the Long Term Effects of Prematurity

"Functional Assessment of a Multicenter Very Low-Birth Weight Cohort at Age 5 Years" Palta, Sadek-Badai, Evans et al. Archives of Pediatric and Adolescent Medicine, 2000;154:23-30.

"This is a multi-center study out of U of  Wisconsin at Madison and U of Iowa (Iowa City).  The participants are more than 400, predominantly Caucasian, very low birth weight preemies (under 1500 grams) born in the late 1980s and early 1990s. The average gestational age is 29 weeks.

This study looks at differences in functional outcomes (mobility, self-care, social) among preemie children who survived before and after the widespread use of steroids and surfactant.

Because the teen studies I am also sending you come from the pre-surfactant era of NICU care, there is always the question of whether or not such studies are still relevant. Most people assume that outcomes have improved in the more recent era, but this large and recent study shows that the CP rate hasn't changed pre- or post-surfactant/steroids (13%), and that functional outcomes such as mobility and social skills appear to have worsened.

Although there is a current 13% CP rate, 30% of VLBW preemies now have seriously subnormal "mobility" -- that is, they score more than 2 standard deviations below the norm on tests of physical functioning.  This is the physical equivalent of retardation -- having an IQ below 70. 51% of VLBW preemies have scores 1 standard deviation below the norm (the physical equivalent of an IQ of 84 or below). That so large a percentage of physically compromised preemies don't have a diagnosis should be of concern (IMHO).

32% of the VLBW children were one standard deviation below the norm in self-care skills, and 39% had subnormal social skills."

"Developmental Coordination Disorder in Extremely Low Birthweight Children( =/<800 grams) at 8.9 Years." Holsti, Grunau, and Whitfield. Pediatric Research, 1999;45:245A, #1443. (The full study has not been published yet to my knowledge.)

"In this study, out of U of British Columbia, Vancouver,  impaired physical functioning that wasn't considered to be cerebral palsy, was referred to as "Developmental Coordination Disorder (DCD)." The 114 children in the study were born between 1982 and 1987.  40 (35%) of the children had either CP and/or subnormal IQ (below 85) and/or sensorineural problems and were *excluded* from the study.  Of the remaining 74 "normal"children, 51% were classified as having DCD.  DCD was defined as being one standard deviation below the norm in tests of fine and large motor skills."

"Prediction of Written Output Ability in Extremely Low Birth Weight (ELBW; =/<800g) Children from Age 4 to 8 Years." Grunau, Whitfield, McConnell et al. Pediatric Research 1999;45:245A, #1440. (The full study has not been published yet to my knowledge)

Also from Vancouver and involving the same children described above, this study reports that difficulties with written work are 8 times more common among "normal" preemies than among fullterm controls.  These problems (at age 8) were predicted by low scores at age 4 1/2 in numerical problem solving, pencil copying, and visual perception.  This study was presented at last year's Society for Pediatric Research meeting in San Francisco.  Sample essays by the preemies and the fullterm children were displayed.  The differences in handwriting, continuity of thought, expression, etc., were striking.

The authors state: "This study highlights continuities in visual-motor perceptual functioning and learning problems....Story writing is a complex activity requiring multifaceted problem-solving in addition to pencil skills."

"Emotional and Behavioral Adjustments of' Normal' Very Low Birth Weight Children Compared to Controls at 7 Years of Age." Kamaya, Moddemann, and Casiro. Pediatric Research. 1996;39:269A #1597. (Not yet published to my knowledge.)

This study, from University of Manitoba in Winnipeg, looked at 48 "non-handicapped" very low birthweight preemies and found they had intellectual, academic, visual-spatial and attentional weaknesses compared to term controls.  Behavior and social competence of these children was rated lower by parents and teachers with significant differences found in somatic complaints, anxiety/depression, social problems, attention problems, and aggressive behavior.

21% of the preemies had scores in the abnormal clinical range on Total Behavior Problems; 19% were in the abnormal range on somatic complaints; 17% were in the abnormal clinical range on attention; 15% were in the abnormal clinical range on "aggression."

"Visual-Motor, Visual-Perceptual, and Fine Motor Outcomes in Very-Low-Birthweight Children at 5 Years. Goyen, Lui, and Woods. Developmental Medicine and Child Neurology. 1998;40:76-81.

This study, from Westmead Hospital in NSW, Australia, of  83 "normal" preemies showed that 71% had below average fine motor skills. Twenty-three percent of these "normal" children were considered impaired or seriously impaired by these problems.

"Neuropsychological  Analysis of the Visuomotor Problems in Children born Preterm at < or = 32 weeks of gestation: A Five Year Prospective Follow-up." Luoma, Herrgard, and Martikainen. Developmental Medicine and Child Neurology 1998;40:21-30.

This study, from Kuopio University Hospital in Finland, of 46 "normal" preemies showed that they achieved lower scores in visuospatial and sensorimotor functions compared to term born controls.

"They had most difficulty with drawing direction of lines and in integrating two or more forms.  They also had problems with 3-dimensional constructions as well as visual perception of rotated shapes or slopes of lines."

"Short-term Memory and Language Outcomes After Extreme Prematurity at Birth" Briscoe, Gathercole and Marlow. Journal of Speech, Language and Hearing Research. 1998:41:654-66. University of Bristol, England.

From the University of Bristol. 26 children born before 32 weeks gestation were compared with 26 fullterm children on short-term memory and language skills.  The preterm children scored more poorly across the full range of measures. 1/3 of the children showed large deficits and were classified as "at risk" for persisting language difficulties.

"Psychological Findings in Preterm Children Related to Neurologic Status and Magnetic Resonance Imaging." Olsen, Vainionpaa, Paakko et al. Pediatrics.1998;102:329-36.
"Magnetic Resonance Imaging of Periventricular Leukomalacia and its Clinical Correlation in Children." Olsen, Paakko, Vainionpaa et al. Annals of Neurology 1997;41:754-61.

People often ask what an MRI can show about problems of prematurity.  These two studies that come from University of Oulu, Finland, and involve 42 "normal" children born <32 weeks and/or 1750 grams compared with term controls.  They show the following:

32% of the LBW and VLBW children showed signs of PVL

10% had CP, and all with CP had signs of PVL

31% of the preemies had "minor neurologic dysfunction" which showed up on such tests as "deviations in tongue movements," "heel walking," "Fogs test results (don't know what this is), and finger opposition as well as behavioral disturbances. 25% of these children had evidence of PVL on MRI

However signs of PVL were also seen in 25% of preemie children considered normal.

No signs of PVL or CP were seen in control children who were born at term.

Children with PVL did worse on tests involving "heel walking" and on the "Fogs test"

Children who performed poorly on tests of visuoperceptual and spatial abilities often had signs of PVL, especially posterior ventricular enlargement.

Children who showed signs of "minor neurologic abnormalities" were likely to have attention problems (whether or not they had abnormal scans).  They also had the most trouble at school.

Although MRI abnormalities are often related to learning and behavior problems, the authors conclude that a thorough neurological examination is superior to MRI.  They recommend closer follow-up for children with minor neurological disorders.

The studies found that although MRI findings were often related to future problems they did not always predict learning and behavior problems. The authors suggested that thorough tests of neurological functioning were probably more useful.

"Cerebral MRI of Very Low Birth Weight Children at 6 Years of Age Compared with the Findings at One Year" Skranes, Nilsen, Smevik et al. Pediatric Radiology. 1998;28:471-5.
"Cerebral Magnetic Resonance Imaging and Mental and Motor Function of Very Low Birth Weight Children at Six Years of Age." Skranes, Vik, Nilsen et al. Neuropediatrics. 1997;28:149-54.

In the next two studies researchers from University Hospital of Trondheim, Norway show that certain types of MRI abnormalities, which are extremely common even in "normal" preemies, are closely related to certain types of learning problems.

These two studies involve a one year geographical cohort of very low birth weight (VLBW, born weighing less than 1500 grams) children at age 6.  Of 31 VLBW non-disabled survivors, 27 were examined by MRI at age one and 20 of these were reexamined at age 6 and given various motor, IQ, and psychological/educational tests.

At age one 21 of the 27 infants (78%) had abnormal myelination on MRI. Myelination refers to the insulation of the nerve fibers with a fatty substance known as myelin.  Myelin helps conduct nerve impulses.  Many preemies show "delayed myelination," and there is always the question with this finding of whether it reflects a true delay in myelination or whether it is an indication of permanent brain damage.

Most of the abnormal or "delayed" myelination in these children was located in the "central occipital white matter" and or in the "centrum semiovale" (it may help to get a map of the brain to get an idea precisely where these structures are located but they are in the area of the ventricles).

12 of the 27 (44%) of the "non-disabled" infants, at age one, had irregular and dilated ventricles.  Ventricular malformation and enlargement usually indicates that parts of the surrounding brain tissue have died and that the ventricles have enlarged to fill in the spaces.  This condition is sometimes referred to as "hydrocephalus ex vacuo."  It is an indication of PVL (periventricular leukomalacia).  Only an estimated 30% of PVL is found on NICU ultrasound scans, so children who left the NICU with a clean bill of neurological health have often suffered undetected PVL (more about this when I review the study by Stewart et al).

Only two of the "non-disabled" VLBW preemies had normal scans at age 1.

At age 6, 20 of the 27 children were reexamined by MRI and other special tests to try to determine whether the abnormalities seen at age 1 had persisted and if so, what they meant.

Most of the children with abnormal MRIs at age 1 continued to have abnormal MRIs at age 6.

Children who had abnormal myelination in the central occipital white matter *combined with* abnormal myelination in the centrum semiovale and/or ventricular enlargement now showed signs of "gliosis" -- or scarring related to tissue death and loss in glial cells of the brain. Glial cells are (I think) the cells that give support and structure to the neurons.  Gliosis is another indicator of PVL. 12 out of 13 children with these findings showed continued signs of PVL at age 6.

Abnormalities in the central occipital white matter alone had normalized in two children and persisted as delayed myelination in 3 children at age 6.

All the children with ventricular dilation (enlargement) at age 1 still had it at age 6.

In all, 12 of 20 (60%) of these non-disabled preemies had signs of gliosis (aka PVL).

The 20 children were then tested for IQ, motor, and perceptual functioning.

Gliosis in the centrum semiovale was related to lower scores on gross motor skills and locomotion.  Additional gliosis in the central occipital white matter was related to both fine motor and gross motor impairments.  The authors speculate that damage has occurred to both motor and visual pathways in these regions affecting eye-hand coordination and balance.

Overall presence of MRI abnormality was not related to lower IQ, however there was a significant relationship between gliosis [PVL] in both the centrum semiovale and the central occipital white matter and low scores on the performance part of the IQ test, as well as on tests of picture completion and the Block design test.  The authors state: "This may indicate visual and spatial perceptual problems, caused by damage to posterior visual pathways and occipito-thalamic tracts (get out your brain maps!)  dealing with visuo-motor integration."

"Executive Function of Children with Extremely Low Birthweight:  A Case Control Study" Harvey, O'Callaghan and Mohay. Developmental Medicine and Child Neurology. 1999;41:292-7.

The studies by Skranes and others indicate that *most* VLBW preemies have suffered white matter damage [PVL].  Recent research (not included in the packet) shows that white matter loss [PVL] can negatively affect gray matter development.  Gray matter is what makes up the frontal lobe, and the frontal lobe handles much of what is referred to as "executive function" -- such
abilities as planning, sequencing, and inhibition of impulsive behavior.

This study from Mater Children's Hospital in South Brisbane, Australia, tested 30 ELBW (<1000 g at birth) preemies at age 4 to 5 and compared their abilities with 30 fullterm children of the same age.  The preemies scored significantly lower than their peers on all executive tasks.

"Behavioural Adjustments in School of Very Low Birthweight Children" Sykes, Hoy, Bill et al. Journal of Child Psychology and Psychiatry. 1997;38:315-25.

Not surprisingly, problems with "executive function" have consequences for school adjustment.  This study out of Queens University in Belfast, Northern Ireland, looked at a cohort of 243 prematurely born VLBW (<1500 g) children at age 7-8.  The children, both male and female, were rated by their teachers as expressing more behavioral and school adjustment problems that controls. Environmental factors such as high social class played no role in ameliorating these problems. The authors speculate that the problem behaviors "reflect a failure in self-regulatory [executive, or frontal lobe] functions."

Helen Harrison is the well known author of The Premature Baby Book, often referred to as the "Bible of Prematurity" by older preemie parents. These observations are excerted with permission from posts to the prematurity parents support internet mailing lists on prematurity: Preemie-child and Preemie-L.

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