Neonatology and the Rights of Families



The Need for Better Premature Infant Follow-up Studies

By Helen Harrison

[Published (in French) in APEP-Info: Revue de l'Association des parents d'enfants prematures du Quebec  Volume 7, No 1 autumn 2000, pp.8-11.]


Relatively few survivors of the NICU have received comprehensive long-term follow-up to determine the outcomes of neonatal treatment. Most existing follow-up studies have been criticized for the small numbers of infants followed, the short duration of follow-up, inconsistencies in reporting and defining disabilities, the absence of control groups, and the many children who are 'lost to follow-up'."  All are factors that have  tended to bias outcome statistics toward optimism. (1- 6)

In 1991, Dr. Gabriel Escobar and his coworkers, conducted a meta-analysis of all English language follow-up studies from the 1960s through the early 1990s (7).  He found 1136 references to very low birthweight outcomes but could identify only 111 studies that met minimum requirements for a scientifically valid sample.

Escobar wrote: "This may seem like a lot of studies -- the total number of births was 20,099 -- but closer inspection revealed that only 7000 or so infants were actually followed for more than 12 months.  This means that, since 1960, on the average, only about 250 such infants were followed annually; [however] in the United States [there are] between 35,000 and 40,000 such births per year."(3)

Escobar also pointed out that many studies do not investigate or list problems that would be of great concern to parents, such as cerebral palsy, and that most studies end too early to diagnose relatively serious problems, such as retardation.

However, the situation Dr. Escobar described in the early 1990s is changing.  There are now several large studies -- all using improved methodology -- that have recently been concluded or are currently being conducted in the US, Canada, UK, Australia and Germany.  New data is beginning to come in from this research showing that prematurity has a far greater impact on behavior, cognition, motor skills, sensory capabilities and later health than has previously been recognized.

For example, a study conducted by the National Institute of Child Health and Human Development (NICHD) of over 1000 extremely low birthweight children has just been published in the journal _Pediatrics_(8).  As infants, they had been treated in 12 major University hospitals in the United States between 1993 and 1994.  They weighed less than 1000 grams at birth and had an average gestational age of 26 weeks. At 18 to 22 months of age, the children were examined by carefully trained evaluators using strictly defined measures of disability.  Every effort was made to assure consistent examination and evaluation standards. Nearly half (49%) of children were found to have one or more major neurodevelopmental abnormality, defined as: cerebral palsy, abnormal neurological findings, blindness, deafness, and/or scores below 70 on the Bayley Scales of Infant Development mental and motor evaluations (a normal score is 100).

The outcome of children born below 26 weeks gestational age was the subject of the recently published EPICure (Extremely Preterm Infants) study from the UK and Eire. Once again, approximately half (49%) of the children had disabilities severe enough to be diagnosed by 30 months of age. (9)

A similarly high incidence of serious abnormality is being found in the preliminary investigations of the TIPP Study (Trial of Indomethacin Prophylaxis in Preterm Infants) -- an international study of the use of indomethacin to prevent intraventricular hemorrhage (10).  The TIPP Study involves over 1000 extremely low birth weight babies treated between 1996 and 1998 in 32 centers in Canada, Australia, the United States, Hong Kong, and New Zealand.  Evaluations of these children (average gestational age of 26 weeks) showed that 47% of the indomethacin treated children had either died or had one or more serious disabilities by 18 months of age and that 46% of the children who were not treated with the drug had similar outcomes.

These large, rigorously conducted studies show a serious handicap rate that is substantially higher than cited in previous studies, raising the following questions: Are outcomes actually worsening?  Or are the new studies, with their superior methodology, simply correcting the biases of earlier studies?

 It may be that both factors are at work. Most studies use standardized tests such as the Bayley Scales of Infant Development which must be revised on a regular basis to reflect the improving development and intelligence scores among the general population -- a phenomenon known as the Flynn effect. (11) The best evidence concerning performance on developmental or IQ tests is obtained by using the average scores of a current control group of fullterm children who are then compared to the preemies (with correction of  premature children's scores for gestational age). (12) Barring a concurrent control group to establish valid "norms," the next best evidence comes from recently revised tests.  In 1993, "norms" for the Bayley Scales of Infant Development (13 ) were revised to reflect improved infant development among fullterm children. Preemies tested using the newly revised norms have lower scores than they would have received on the test only a few years earlier.  As a result, many children who would have scored in the low-normal ranges in the past now fall into the abnormal range and are classified as "disabled." 

However, the apparent worsening of outcome may, in part, also be explained by the widespread use of postnatal steroids in the 1990s, a practice that is associated with a significantly increased rate of cerebral palsy, severe retinopathy, and other developmental problems. (8, 14-16)

And, as the authors of these studies point out, the 18 to 30 month data from the NICHD, EPICure and TIPP follow-up disclose only the "tip of the iceberg."  Many cognitive, motor, and behavioral problems cannot be reliably diagnosed until later in childhood.  Usually, the later in childhood that preemies are studied, the more problems are revealed. (3)

Long-term studies of preemies born in the mid to late 1990s will not be available for several years.  However, several large well-conducted studies on preemies born in the 1980s have recently been published.  These studies compare the outcomes of preemies at school age to those of fullterm children from similar socioeconomic backgrounds.

Dr. Michael Whitfield and his colleagues in Vancouver studied 115 extremely premature children who were born weighing less than 800 grams with an average gestational age of 26 weeks. (17) Moderate to severe disability (<85 IQ, non-ambulatory CP, uncorrectable hearing loss or blindness) was present in 27% of the children at eight years of age.  Non-handicapped prematurely born children (those with IQs over 84 and no other serious impairment) were still 3 times more likely than fullterm children to have learning disabilities (47% versus 18%).  The learning problems of the prematurely born children often involved multiple areas of disability, whereas fullterm learning-disabled children usually had only one area of difficulty.  Of the 26% of extremely low birthweight children who were not considered to have learning or other disabilities, 35% were girls and 12% were boys.  (This sexual advantage of prematurely born females is frequently seen in studies of premature survival and outcome.)  But even among these "normal" preemies, behavior problems and problems with fine motor skills (not counted as disabilities in this study) were prevalent.  In addition, the authors commented that the test scores of the group as a whole "grossly understated the complex nature of the individual degree of educational difficulty faced by these children."

In a large, population-based followup study from Germany, children who had been born below 32 weeks gestational age were tested along with control groups of fullterm children, who were used to provide the test "norms."  Of the 264 prematurely born children, almost half (49.6%) had intelligence test scores that were one standard deviation below the average score of their fullterm peers. (18) This is the equivalent of an IQ score below 85 . Twenty-six percent scored 2 or more standard deviations below the fullterm control group, which equates to an IQ of below 70 (retardation).


Compared to their fullterm peers, the prematurely born children had 10 times the rate of sequential processing problems (the ability to repeat numbers and other sequences, an important skill for reading) and 30 times the rate of "simultaneous mental processing problems" (skills necessary for problem solving).

A recent study presented at the American Psychological Association

showed similar results for very low birthweight premature children born in New York State weighing less than 1500 grams. (19) Over 60% of the children (excluding those with severe handicaps) had significantly low achievement and special needs in school.  Over 40% had experienced problems in three or more scholastic areas indicating a "trend toward pervasive dysfunction."

Such studies, which use concurrent control groups and improved forms of assessment, are better able to describe the function of prematurely born children in school and society. However, some of the problems and unusual behavioral characteristics described by parents of school age preemies have not yet been examined in follow-up studies.

I am a parent consultant to the PORT Project (Premature Outcomes Research Team) -- an international group of neonatologists and psychologists looking at school-age outcomes of premature infants born weighing less than 1500 grams, with particular emphasis on those born weighing less than 1000 grams.  We are studying and comparing geographically based cohorts of children from Canada, the United States, the Netherlands, Germany and Jamaica.

To prepare for our 1998 meeting in Amsterdam, I asked the parents on Preemie-Child, an Internet mailing list for parents of school-aged preemies, to tell me what they wanted the physicians of the PORT Project to know about their children I hoped to give the doctors an idea of the concerns that were important to us as parents, as opposed to the sometimes arbitrary categories of impairments used by clinicians. I wanted the doctors to understand how our children's prematurity influences their lives in practical ways.  I wanted to emphasize the actual functioning of the children as opposed to whether or not they fell into some strictly defined category. 

For example, many of our children have learning problems that may not fit the definition of "learning disability" used by a particular school system or a particular follow-up study.  Many of our children have significant motor problems that don't meet the criteria of CP used by some follow-up clinics and physicians.  Some of our children display unusual patterns of behavior that don't quite fit the definition of hyperactivity, or of attention deficit disorder, or of autism.  Nevertheless, these problems (alone or in combination) can present significant challenges for adjustment at school, later employment, or independent living.

The Preemie-Child parents described a variety of problems in their children who were age 4 or older, many of whom had been dismissed as from infant follow-up as "normal" or as having only minor problems.  These problems included:

1) Social dysfunction and isolation; low self-esteem.

2) Behavioral problems -- general immaturities; poor impulse control; stereotypic and/or self-injurious behavior such as rocking, hair pulling; intense need for order and routine; sleep disorders.

3) "Sensory integration disorders" -- exaggerated startling and fear responses to loud or high-pitched sounds; extreme aversions to certain tastes and textures; "tactile defensiveness" -- for example, not liking to be touched, excessive sensitivity to labels in clothing and seams in socks, aversions to walking barefoot on sand or grass, etc.

4) Abnormal reactions to pain.   Many children were relatively insensitive to the pain of illness and injury  -- one mother told how her son would put his hand on a burning light bulb with no reaction; another told of her daughter's lack of pain response to a burst appendix.  However, the children were often terrified of painless medical procedures or of anything to do with medicine -- others were frightened by white coats or ads on television mentioning "doctors" or "hospitals."

5) Abnormal fear responses, such as the inability to recognize or respond appropriately to life-threatening situations (one mother described how her young child repeatedly tried to jump overboard from a ferry).  But, at the same time, these "fearless" children may have peculiar and strange phobias (another mother described how her child would shriek in fear and burst into tears at the sight of a housefly).

6) Gross and fine motor problems serious enough to interfere with the child's daily life, but which never received a diagnosis of cerebral palsy.

7) Speech problems -- verbal apraxia, slow speech, stuttering, or raspy or inaudible voices due to vocal cord damage caused by intubation or possibly as a result of nerve damage from PDA surgery.

8) Growth problems.


9) Learning problems, especially with math, handwriting, copying, and spelling (although some children were quite good at memorizing).

10) Eating and digestive disorders; frequent gagging and vomiting; "oral aversion," intestinal problems, especially constipation.

11) Dental problems -- poor tooth enamel, oddly shaped or discolored teeth, "iatrogenic cleft palate" -- a groove in the roof of the mouth caused by the ventilator tube.

12) Vision problems (ROP and /or eye muscle imbalances) that worsen in later life requiring more surgery or which lead to progressive vision loss.

The members of the PORT Project on hearing of the issues described by the Preemie-Child parents suggested that I forget about the second edition of my book for a while and just write about school-age preemie behavior based on the parents' quotes!

And there are times that I am tempted to do just that.  One of the major challenges in rewriting _The Premature Baby Book_ is trying to figure out how to present this new, not-very-optimistic data to new parents in ways that won't be totally overwhelming.  (The information in the first edition in 1983 was disturbing enough to some parents!)  So it is a constant tug of war between presenting the information with total honesty and trying to preserve what's left of the sanity of new preemie parents.

As follow-up becomes more reliable, more responsible, and more uniformly conducted, I suspect we will be seeing many studies similar to the ones I have described above.  With new MRI techniques and brain assessments I think the biological basis for many of the problems described by the school-age outcome studies (and by the Preemie-Child parents) will become evident.  

This new data is, as one neonatologist recently put it, "sobering."  Although it confirms what many "veteran" parents have long suspected, it is not information that most new parents want to hear.  Fortunately, we, who are veteran parents, can also reassure new parents of premature babies that many preemies, despite the obstacles of their early births, can have happy and successful lives.

I have just had the privilege of spending part of my summer with 6 teen and young adult preemies -- two of whom were micropreemies.  Paul, age 20, born at 25 weeks gestation, is now blind and in a wheelchair.  He is a bright, charming young man who looks forward to a university degree and a career in political science. Jody, born at 26 weeks and 750 grams, is now 23. She coped with serious learning problems from the beginning, but has recently graduated from college. She hopes to become an educational counselor, specializing in helping children, who, like herself, are trying to overcome the challenges of prematurity.  My own 25 year old son has hydrocephalus and cerebral palsy.  He is retarded, autistic and vision impaired.  Nevertheless he has become an accomplished rock musician -- a talent that gives him a great deal of pleasure.

As parents, we must acknowledge the results of this new research, but not be overwhelmed by it.  Instead, we can use the information to "validate" our own observations of our children and to help us cope realistically with the difficulties of preemie parenthood.  We can use it to educate our children's educators who are often unaware of the learning challenges of prematurely born children.  We can cite these studies to advocate for better medical and educational research into the problems of prematurity and for informed ethical decision-making for parents of the most extremely preterm newborns.  Above all, we can use this information to get the special medical, educational, and social services we need to support our families and help our preemies achieve their full potential.


1.  Aylward GP et al. Who goes and who stays: Subject loss in a multicenter, longitudinal follow-up study. _Developmental and Behavioral Pediatrics_.1985;6:3-8.

2.  Collin MF et al. Emerging developmental sequelae in the 'normal' extremely low birth weight infant. _Pediatrics_. 1991;88:115-120.

3.  Escobar GJ. Prognosis of surviving very low birthweight infants: Still in the dark. _British Journal of Obstetrics and Gynaecology_. 1992;99:1-3.

4. Gross SJ et al. Impact of a matched term control group on interpretation of developmental performance in preterm infants. _Pediatrics_. 1992;90:681-687.

5. Tin W et al. Outcome of very preterm birth: children reviewed with ease at 2 years differ from those followed up with difficulty. _Archives of Disease in Childhood_. 1998;79:F83-87.

6. Wariyar UK and Richmond S.  Morbidity and preterm delivery: The importance of 100% follow-up. _The Lancet_. 1989:1(8634), 387-388.

7. Escobar GJ et al. Outcome among children surviving very low birth-weight infants: A meta-analysis. _Archives of Disease in Childhood_.1992;66:203-211.

8.  Vohr BR et al. Neurodevelopmental and functional outcomes of extremely low birth weight infants in the National Institute of Child Health and Human Development National Research Network, 1993-1994. _Pediatrics_ 2000;105:1216-1226.

9.  Wood NS et al. Neurologic and developmental disability after extremely preterm birth.  _The New England Journal of Medicine_ 2000;343:378-384.

10.  Schmidt BK et al. International randomized placebo-controlled trial of indomethacin prophylaxis in preterm infants (TIPP) _Society for Pediatric Research_ 2000;47:431A, #2547.  Presented at the Society for Pediatric Research Meeting in Boston, May 16, 2000.

11. Flynn JR. The mean IQ of Americans: Massive gain 1932 to 1978. _Psychological Bulletin_ 1984;95:29-51.

12.  Wolke D et al. The cognitive outcome of very preterm infants may be poorer than often reported: an empirical investigation of how methodological issues make a big difference. _European Journal of Pediatrics_1994;153:906-915.

13.  Bayley N.  _Bayley Scales of Infant Development-II_  San Antonio, TX: Psychological Corporation; 1993.

14.  Jobe A. Glucocorticoids in Perinatal Care: Misguided Rockets? _J Peds_2000;137:1-3.

15.  Finer NN et al. Postnatal steroids: Short-term gain, long-term pain?

 _J Peds_ 2000;137:9-13.

16.  Vohr BR et al. Effects of Neonatal Interventions on Retinopathy of Prematurity (ROP) in Extremely Low Birth Weight (ELBW) Survivors <1000 Grams.

 _Pediatric Research_ 2000;47:327A #1932.

17. Whitfield MF et al. Extremely premature (<800 g) schoolchildren: multiple areas of hidden disability. _Archives of Disease in Childhood_1997;77:F85-F90.

18.  Wolke D and Meyer R. Cognitive status, language attainment, and prereading skills of 6-year-old very preterm children and their peers: the Bavarian Longitudinal Study. _Developmental Medicine and Child Neurology_1999;41:94-109.

19.   Barlow JR and Lewandowski L.  Ten-year longitudinal study of preterm infants: Outcomes and predictors. Presented at the 108th Annual Convention of the American Psychological Association at Washington, DC, August 8, 2000.

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