Expanding the Definition of Long-term
Follow-up to Late Adulthood
Betty Vohr, MDa,b
a
Department of Pediatrics, Alpert Medical School of Brown
University, Providence, Rhode Island; and bWomen and
Infants Hospital, Providence, Rhode Island
Opinions expressed in these commentaries are
those of the author and not necessarily those of the
American Academy of Pediatrics or its Committees.
www.pediatrics.org/cgi/doi/10.1542/peds.2015-0227
DOI: 10.1542/peds.2015-0227
Accepted for publication Jan 22, 2015
Address correspondence to Betty R. Vohr, MD,
Department of Pediatrics, Women and Infants
Hospital, Professor of Pediatrics, Alpert Medical
School of Brown University, 101 Dudley St,
Providence, RI 02905 E-mail: [email protected]
PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online,
1098-4275).
Copyright © 2015 by the American Academy of
Pediatrics
FINANCIAL DISCLOSURE: The author has indicated
she has no financial relationships relevant to this
article to disclose.
FUNDING: No external funding.
POTENTIAL CONFLICT OF INTEREST: The author has
indicated she has no potential conflicts of interest to
disclose.
COMPANION PAPER: A companion to this article can
be found on page e818, online at www.pediatrics.
org/cgi/doi/10.1542/peds.2014-3556.
COMMENTARY
In the United States, NICUs with
training programs for fellows have
follow-up programs for extremely
preterm and very preterm infants who
are considered at greatest risk of
postdischarge neurodevelopmental
morbidity. Late preterm (LPT) births
(34–36 weeks) were for many years
considered low risk, and their
vulnerability was underestimated. Over
the past few decades there has been
a significant increase in the number of
LPT births, related in part to induction
of labor and cesarean delivery births
and to a variety of risk factors.1,2 There
has also been a proliferation in the
number of studies reporting increased
neonatal and postdischarge
morbidities within the LPT population.
The level of physiologic maturation has
been shown to place these infants at
increased risk of a spectrum of medical
problems, including hypothermia,
respiratory disorders, hypoglycemia,
jaundice, immunologic problems,
increased susceptibility to infection,
and feeding problems.3 Vulnerability of
the brain is now also recognized. The
second half of gestation is a critical
period of brain development; and at 34
weeks, the brain weight is 60% of term
brain weight4 and there is a 5-fold
increase in brain volume and brain
maturation, including neurogenesis,
synaptogenesis, and dendritic
arborization between 35 and 41
weeks.5 The interruption of this
process by delivery removes the infant
and the developing brain from the
natural protective environment of the
uterus.6 A number of investigators
have shown that this vulnerability of
LPT infants is associated with an
increased risk of neurologic
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impairments, developmental
disabilities, school failure, behavior,
autism spectrum disorder, and
psychiatric problems that extend to
adolescence and young adult age.7–16
The study in this issue by Heinonen
et al17 addresses the subject of lifelong
brain vulnerability in LPT infants and
builds on their previous finding that
LPT birth is associated with lower
lifetime attained level of education at
56 to 66 years of age.18
The current study is a remarkable
longitudinal investigation that raises
the bar another notch for follow-up
studies. First, the study investigates an
important clinical risk factor, LPT birth,
which currently represents 70% of all
preterm births. Second, the data were
retrieved from well-established
national databases (the Helsinki birth
cohort study with subjects born in
1934 to 1944 and the Statistics Finland
database), which allowed the
investigators to track, identify, link, and
evaluate former LPT infants and term
controls. Third, the duration of followup is extraordinary; the subjects were
senior citizens with a mean age of 68.1
years. Fourth, the assessment used was
the Consortium to Establish a Registry
for Alzheimer’s Disease
Neuropsychological Battery (CERAD),
which provides subscores and
a summary mild cognitive impairment
(MCI) score.
In models adjusted for multiple
confounders, LPT infants scored
significantly lower on word list
recognition (a memory test of delayed
recognition of 10 original words along
with 10 new words) compared with
controls. Consistent with previous
PEDIATRICS Volume 135, number 4, April 2015
work, the investigators reported that
a lower level of educational
attainment was associated with lower
scores on the CERAD scales. Because
a low level of educational attainment
is also a risk factor for MCI, analyses
were done separately comparing
groups with basic low primary or
secondary education versus those
with higher tertiary education. The
basic low-education LPT group had
lower adjusted scores for CERAD
word list recognition, constructional
praxis, clock drawing, Mini-Mental
State Examination, memory total
score, and CERAD total score
compared with term controls,
whereas there were no differences
between former LPT infants with
tertiary education compared with
controls. This finding indicates that,
although LPT infants have an almost
threefold increased risk of MCI
suggestive of early-onset Alzheimer
disease, this outcome is mediated by
a higher level of educational
attainment. Although the increased
risk of age-related MCI in this LPT
population is disturbing, the data
inform us of the potential for effective
intervention. The findings are also an
awakening to the fact that there is
a need to examine not only
neonatal, early childhood, school
age, and young adult effects of risk
factors such as LPT but also lifelong
effects.
As the United States moves in the
direction of electronic health records
and health tracking systems of
population health, analyses linking
prenatal and perinatal factors to longterm outcomes will provide us with
new epidemiologic data and
opportunities to identify relationships
and mechanisms contributing to both
adverse and optimal outcomes and to
PEDIATRICS Volume 135, number 4, April 2015
potential new innovative educational
interventions. Investigators in
Finland and a number of other
European countries appear to have
a head start.
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e1039
Expanding the Definition of Long-term Follow-up to Late Adulthood
Betty Vohr
Pediatrics 2015;135;e1038; originally published online March 2, 2015;
DOI: 10.1542/peds.2015-0227
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PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly
publication, it has been published continuously since 1948. PEDIATRICS is owned, published,
and trademarked by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk
Grove Village, Illinois, 60007. Copyright © 2015 by the American Academy of Pediatrics. All
rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.
Downloaded from by guest on July 28, 2017
Expanding the Definition of Long-term Follow-up to Late Adulthood
Betty Vohr
Pediatrics 2015;135;e1038; originally published online March 2, 2015;
DOI: 10.1542/peds.2015-0227
The online version of this article, along with updated information and services, is
located on the World Wide Web at:
/content/135/4/e1038.full.html
PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly
publication, it has been published continuously since 1948. PEDIATRICS is owned,
published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point
Boulevard, Elk Grove Village, Illinois, 60007. Copyright © 2015 by the American Academy
of Pediatrics. All rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.
Downloaded from by guest on July 28, 2017