ARTICLE
Antenatal and Postnatal Growth and 5-Year Cognitive
Outcome in Very Preterm Infants
AUTHORS: Marika Leppänen, MD,a,b Helena Lapinleimu,
MD, PhD,a,c Annika Lind, PhD,d Jaakko Matomäki, MSc,a
Liisa Lehtonen, MD, PhD,a,c Leena Haataja, MD, PhD,c,e and
Päivi Rautava, MD, PhDb,f on behalf of the PIPARI Study
Group
Departments of aPediatrics, bPublic Health, dPsychology, and
ePediatric Neurology, University of Turku, Turku, Finland; and
cPediatrics and fClinical Research Center, Turku University
Hospital, Turku, Finland
KEY WORDS
preterm infants, growth, cognitive development
ABBREVIATIONS
AGA—appropriate for gestational age
BPD—bronchopulmonary dysplasia
CA—corrected age
CI—confidence interval
FSIQ—full-scale IQ
GA—gestational age
HC—head circumference
NEC—necrotizing enterocolitis
SGA—small for gestational age
VLBW—very low birth weight
WHAT’S KNOWN ON THIS SUBJECT: Better postnatal growth,
especially head growth, associates with better cognitive
development in preterm infants. Suboptimal postnatal growth is
more common in infants with poor antenatal growth than in
infants with normal growth.
WHAT THIS STUDY ADDS: Good weight gain and head
circumference growth until 2 years was associated with better
5-year cognitive outcome in non–small for gestational age infants.
Good head circumference growth around term age benefits the
cognitive outcome of small for gestational age infants.
abstract
Drs Leppänen and Lind made substantial contributions to
conception and design, acquired data, analyzed and interpreted
data, and wrote and revised the manuscript; Drs Lapinleimu,
Lehtonen, Haataja, and Rautava made substantial contributions
to conception and design, analyzed and interpreted data, and
wrote and revised the manuscript; Mr Matomäki carried out the
statistical analyses, made substantial contributions to
conception and design and interpretation of data, and wrote and
revised the manuscript; and all authors approved the article to
be published.
www.pediatrics.org/cgi/doi/10.1542/peds.2013-1187
doi:10.1542/peds.2013-1187
Accepted for publication Oct 19, 2013
Address correspondence to Marika Leppänen, MD, Department of
Paediatrics, Turku University Hospital, Kiinamyllynkatu 4-8, PO Box
52, 20521, Turku, Finland. E-mail: marika.leppanen@utu.fi
PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).
Copyright © 2014 by the American Academy of Pediatrics
FINANCIAL DISCLOSURE: The authors have indicated they have
no financial relationships relevant to this article to disclose.
FUNDING: Supported by grants from the Foundation of Pediatric
Research/The South-Western Finnish Foundation of Neonatal
Research, the Päivikki and Sakari Sohlberg Foundation, and
Turku University Hospital.
POTENTIAL CONFLICT OF INTEREST: The authors have indicated
they have no potential conflicts of interest to disclose.
OBJECTIVES: To study how antenatal growth affects cognitive outcome
in very preterm infants and to determine whether there is an association between growth in any particular time period between birth and
5 years of age and cognitive outcome. Small for gestational age (SGA)
and non-SGA infants were analyzed separately, because antenatal
growth may affect postnatal growth.
METHODS: Very low birth weight (,1501 g) infants born between 2001
and 2006 and infants born at ,32 gestational weeks between 2004
and 2006 who were treated at Turku University Hospital (n = 181)
were followed. Weight, length, and head circumference (HC) of the
infants were measured at 9 time points between birth and 5 years.
The growth was determined as a z score change between measurement points. Cognitive development was assessed at 5 years of age
with the Wechsler Preschool and Primary Scales of Intelligence–
Revised. The association between growth and full-scale IQ (FSIQ)
was studied.
RESULTS: Growth in length and height was not associated with 5-year
cognitive outcome. However, weight (r = 0.18, P = .04) and HC growth
(r = 0.25, P = .01) between birth and 2 years of corrected age
correlated to FSIQ in non-SGA children. In SGA children, HC growth
(r = 0.33, P = .03) around term age correlated to FSIQ.
CONCLUSIONS: Cognitive outcome was similar in SGA and non-SGA very
preterm infants. Growth affected cognition positively in both
subgroups, but the critical time period was different. Pediatrics
2014;133:63–70
PEDIATRICS Volume 133, Number 1, January 2014
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Very low birth weight (VLBW) preterm
infants are at risk for cognitive problems1–5 and growth failure.1,6–8 Suboptimal growth at the time of discharge
is still a common phenomenon despite
advances in treatment and nutrition
regimens,9–11 and growth delay, especially in weight8,12,13 and length,8,14,15
usually remains a problem that tends to
ease in childhood1,14,15 and adulthood.7,8,16
Extreme prematurity10,11,17 and being
small for gestational age (SGA)7,15,18–20
are seen as specific risk factors in
this growth lag. Male gender,4,7,16 critical morbidity,6,9,13,21 and of course a
parent’s shortness15,18,22,23 are other
important predictors of later poor growth
in very preterm infants.
Recently there have been attempts
to define the critical growth period
for neurodevelopment in preterm
infants.10,24,25 Prenatal, and even more
often postnatal, growth rates have
been shown to be important for cognitive abilities,10,23 and infants with
both intrauterine and postnatal growth
restriction are especially likely to have
less favorable outcomes.19,23,26,27 Rapid
early weight gain is associated with
improved cognitive outcome in infancy.12 The critical time window for
weight gain might be early, somewhere
between birth and term equivalent
age10,17,25 or between term and 1 year
of age.3 A few studies have found evidence that length gain until 2 years of
age may be associated with neurodevelopment in childhood.14,23,28 If preterm boys lack catch-up growth in
height, this is found to predict impaired
intellectual outcome.1,19
Head growth reflects brain size29 and is
a useful predictor of later neurodevelopment.10 Head growth during the
first weeks25 and months,14 up to 2
years of life,4,14,30–32 has been shown to
be especially important for preterm
infants’ cognitive abilities. Head size
later in childhood has also been associated with cognition.1,12,24
64
To gain a better understanding of the
optimal postnatal growth and its relevance to the cognitive outcome of preterm infants, we need studies with
comprehensive prospective follow-up
of growth with several measurement
points and standardized cognitive testing
in a representative preterm population.
Prenatal growth is an important factor
to take into consideration, which can be
achieved by separately analyzing SGA
and non-SGA preterm infants. There are
just a few studies22,23,26,27 that look
at the association between postnatal
growth patterns and cognition for
these 2 groups separately (Supplemental Table 3). In these studies, the
focus has often been on the catch-up
growth of SGA infants, ignoring the
pattern of postnatal growth for non-SGA
infants, and therefore the results leave
many questions unanswered.22,27 Furthermore, the treatment of preterm
infants has improved in the past decade, including better nutritional support.
Our aim was to assess the relationship between growth and cognition in
a cohort of very preterm infants born
between 2001 and 2006. We wanted
to see whether there is a particular
time window for postnatal growth in
weight, length, or head circumference (HC) between birth and 5 years of
age that affects the cognitive outcome
of preterm infants at 5 years of age,
and if so to see whether the timing
differs in SGA and non-SGA populations.
METHODS
Study Subjects
This study is part of a regional, prospective, and multidisciplinary followup study of very preterm infants:
PIPARI (development and functioning of
VLBW infants from infancy to school
age). There were 274 infants who met
our inclusion criteria; they were born
between 2001 and 2006 with a birth
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weight ,1501 g or between 2004 and
2006 with a gestational age (GA) ,32
weeks (very low GA), treated at Turku
University Hospital, and from Finnishor Swedish-speaking families living
in the catchment area to enable psychological assessment.33 Infants with
severe congenital anomalies or a diagnosed syndrome affecting their development were excluded. Forty-one
(15%) died, 9 (4%) of the families refused to participate, and the number of
later dropouts was 23 (10%). One infant
(0.5%) on long-lasting oral corticosteroid therapy was excluded because of
its potential effects on growth. Regarding the psychological assessment
at 5 years, 2 (1%) infants were tested
too late, and the tests of 17 (6%) infants
were unsuccessful. The final cognitive
outcome was available for 181 infants.
Children without an evaluation of cognitive outcome (dropouts included)
were more likely to have mothers with
lower levels of education (P = .002) and
to have a diagnosis of cerebral palsy
(P = .009) than children with an evaluation of cognitive outcome. No differences were found between these
groups in the incidence of bronchopulmonary dysplasia (BPD), necrotizing
enterocolitis (NEC), sepsis or meningitis, brain pathology, or SGA status.
Nutrition Regimen
We have followed international guidelines in early nutrition, starting parenteral amino acids and lipids on the
first day of life. All infants were given
breast milk at least until discharge.
The breast milk fortification was
started when 150 mL/kg per day was
reached and continued until the infant
reached the weight of 3.5 kg. Solid food
and meat were added at 4 and 5
months of age, respectively. Vitamin D
and iron were supplemented from 2
and 3 weeks of age, respectively. Baby
food was replaced by normal family
food ∼1 year after birth.
ARTICLE
Assessment of Growth
Trained nurses measured the infants in
the hospital and at the follow-up clinic
until 2 years of corrected age (CA), and
thereafter in the well baby clinics. After
birth, weight was measured daily,
crown–heel length twice a month, and
HC weekly until discharge. Weight was
measured to the nearest 0.01 kg with
an infant scale (MeWa GmbH, Schwerin,
Germany) until the age of 2 years of CA
and thereafter to the nearest 0.1 kg.
The child was usually lying supine
during height measurement up to 2
years of age, after which the child
was standing. HC was measured by
a soft, unstretchable tape, which was
changed regularly. Available data were
collected from hospital records; the
measurements at 5 years of age were
collected by a questionnaire from
nurses in the well baby clinics. SGA
status was defined as a birth weight
,22.0 SD, and non-SGA was between
22.0 and +2.0 SD. In the non-SGA
group, 98% of the infants were classified as appropriate for gestational age
(AGA); 2 infants with birth weight z
scores of +2.2 and +2.6 were included
in this group.
Assessment of Cognitive
Development
A psychologist assessed the cognitive
outcome of the children at 5 years (21
week to 2 months) with a short version
of the Wechsler Preschool and Primary
Scales of Intelligence–Revised.34 This
test is standardized in Finland. The
subtests for information, sentences,
arithmetic, block design, geometric
design, and picture completion were
used, and the full-scale IQ (FSIQ) was
estimated.35 FSIQ was used as a continuous variable (mean 100, SD 15).
Assessment of Brain Pathology
A cranial ultrasound was performed by
the attending neonatologist for all
infants at the ages of 3–5 days and 7–10
days after birth, 1 month after birth,
and monthly until discharge. An MRI
examination of the brain was performed at corrected term age. The
infants were categorized into 3
groups according to the most pathologic brain findings by ultrasound or
MRI.29,36
Statistical Analysis
Growth was assessed using the measures of weight, length, and HC at birth,
36 weeks’ GA (67 days), 40 weeks’ GA
(67 days, term age), 1 month, (67
days), 2 months (67 days), 4 months
(67 days), 1 year (67 days), 2 years
(67 days), and 5 years (62 months).
Age was corrected for prematurity
until 2 years. To determine the particular growth period we evaluated
growth in short periods, in sequential
order, from each age to the following
age points: between 36 weeks’ GA and
term age and between 1 and 2 months.
Growth was also evaluated over longer
periods systematically, from birth and
then from 36 weeks’ GA to all measure
points. We calculated z scores to indicate the number of SDs by which the
measurements differed from the mean
at a specific age. The growth parameters before 40 weeks’ GA were converted to these z scores according to
Finnish growth charts.37–39 These
growth charts are in clinical practice
for growth assessment and based on
live-born infants. We used the World
Health Organization growth curves40
from term to 5 years of age to improve
the comparability and generalizability
of our data. Vermont Oxford Network
definitions were used for neonatal
diagnoses.41 A diagnosis of cerebral
palsy was confirmed by a pediatrician
at the 2-year follow-up visit. Associations
between the categorical predictors and
the continuous response variables
were studied using the Kruskal–Wallis
test. Univariate associations between 2
continuous variables were studied with
Spearman’s correlation coefficient (r).
PEDIATRICS Volume 133, Number 1, January 2014
The association between the background variables (GA, gender, NEC,
BPD, brain pathology, and the mother’s
education) and growth was analyzed.
Associations between the z score
change of growth and FSIQ were
studied by using regression analysis,
controlling for gender, GA, and the
mother’s educational level. A statistically significant result was defined as
P , .05.
RESULTS
The descriptive data including cognitive
outcome and birth growth data are
presented in Table 1 for SGA and nonSGA infants separately. Our cohort
consisted of 33% SGA infants and 67%
non-SGA infants. Most of the SGA infants (68%) had disproportional growth
failure with head sparing, suggesting
that those infants might have had
growth restrictions before birth.
Determinants of Growth
Gender, GA, and brain pathology significantly determined long-term
growth patterns in the whole study
cohort. Girls gained more weight
between birth and 1 year (P = .006)
and 2 years’ CA (P = .007). Higher GA
correlated with better growth before
term equivalent age (weight: r = 0.73,
P , .0001, length: r = 0.56, P , .0001,
HC: r = 0.42, P , .0001) and also up
to 5 years of age (weight: r = 0.55,
P , .0001, length: r = 0.44, P , .0001,
HC: r = 0.25, P = .02). The infants with
a normal brain MRI at term age
gained more weight between
birth and 5 years of age than
did the infants with brain pathology
(P = .02).
Growth Patterns
Figure 1 presents the cumulative percentage of SGA infants whose body
growth exceeded 22.0 SD in each
growth measure to describe the catchup growth of these growth-restricted
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TABLE 1 Descriptive Data for the Study Cohort and Their Parents
Multiple birth
GA, wk d/7a
Male
Birth wt, g
Z scorea
Birth length, cm
Z scorea
Birth HC, cm
Z scorea
Antenatal corticosteroidsa
Apgar score at 5 mina
Sepsis or meningitis
BPD
NEC
Brain pathology
Normal
Minor
Major
FSIQ
Cerebral palsy
Length of mother, cm
HC of mother, cm
Length of father, cm
HC of father, cm
a
SGA Children (n = 59)
Non-SGA Children (n = 122)
Mean (min, max) SD or %
Mean (min, max) SD or %
29
30 6/7 (25 5/7, 35 6/7) 2 4/7
51
1090 (400, 1500) 285
23.0 (–5.0, –2.0) 0.8
38 (27, 38) 3.6
22.3 (–7.8, 1.0) 1.6
27 (20, 31) 2.4
21.9 (–5.3, 0.3) 1.2
86
7.2 (2, 10) 1.7
20
10
2
34
28 2/7 (24, 31 6/7) 2 2/7
60
1162 (610, 2025) 308
20.6 (–2.0, 2.6) 0.9
38 (31, 44) 3.2
0.2 (–3.8, 3.7) 1.3
26 (21, 31) 2.5
20.2 (–2.4, 2.8) 1.1
99
6.7 (1, 10) 2.1
15
16
5
29
32
39
99 (42, 133) 17.6
3
166 (153, 181) 5.6
55 (52, 58) 1.5
180 (154, 197) 6.8
58 (54, 63) 1.5
26
36
37
101 (39, 140) 16.9
3
165 (128, 190) 7.2
55 (48, 59) 1.6
181 (161, 198) 6.9
58 (50, 62) 2.0
Statistically significant difference was found between these groups in addition to difference in birth wt z score.
infants. The growth measurements for
SGA and non-SGA children between birth
and 5 years of age are presented in
Supplemental Table 4. Because the
growth of preterm infants might be inconsistent over short time periods, the
percentage of postnatal growth restriction (weight, length, HC ,22.0 SD) is
also presented in Supplemental Table 4.
Growth and Cognitive Outcome
Body growth over a long period, between birth and 5 years of age, did not
associate with cognitive outcome. Postnatal weight gain and growth in HC
between birth and 2 years of CA was
associated with improved cognitive outcome in non-SGA children (see Table 2
for detailed information). Postnatal
growth in length did not correlate to
FSIQ (Table 2). Interestingly, in SGA
infants only good HC growth after 36
weeks’ GA in shorter periods, until 4
months of age (P = .03), was associated
with higher FSIQ at 5 years of age (see
Supplemental Table 5).
When the study infants were studied as
a whole group, only HC growth was
associated with FSIQ between birth and
2 years’ CA. FSIQ at the age of 5 years
increased by 2.5 (95% confidence interval [CI], 0.67–4.33, P = .008) for each
z score increase in the HC between
birth and 1 year of CA, by 3.6 (CI, 0.95–
6.15, P = .007) between term equivalent
age and 1 year of CA, by 2.5 (CI, 0.65–
4.31, P = .008) between birth and
2 years’ CA, and by 3.1 (CI, 0.45–5.70, P =
.02) between term equivalent age and
2 years’ CA after adjustments for GA,
gender, and the mother’s education.
The FSIQ according to the z score
change between birth and 2 years’ CA
(without adjustments) is presented in
Fig 2. The timing of catch-up growth
(.22.0 SD) did not correlate with
cognitive outcome at 5 years of age
(weight, r = 0.05, P = .54; length, r =
0.01, P = .89; HC, r = 0.11, P = .13). We
compared the cognitive outcome at 5
years of age in non-SGA infants who
had catch-down growth (,22.0 SD)
in weight, at 36 weeks’ GA, with non-SGA
infants without catch-down growth,
and we found no difference in cognitive outcome between these groups
(P = .69).
DISCUSSION
FIGURE 1
Growth of SGA infants between birth and 5 years of age. This figure presents the cumulative percentage
of SGA infants whose growth exceeded –20.0 SD in weight (W), length (L), and HC.
66
LEPPÄNEN et al
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We studied the impact of antenatal
(SGA) and postnatal growth on cognition at 5 years of age in a cohort of 181
very preterm infants using comprehensive growth data. Furthermore, we
analyzed whether there is an association between growth during any particular time period between birth and
5 years of age and cognitive outcome at
5 years of age, to discover whether
ARTICLE
TABLE 2 Correlations Between Growth From Birth to 2 Years of CA and 5-y Cognition
Time Period From Birth
To 36 wk GA
To term age
To 1 mo
To 2 mo
To 4 mo
To 1 y
To 2 y
Wt
Length
SGA
Non-SGA
All
SGA
Non-SGA
20.12
20.25
20.14
20.07
20.13
20.003
20.07
0.22*
0.21*
0.12
0.11
0.15
0.18
0.18*
0.08
0.03
0.00
0.01
0.04
0.06
0.04
0.001
20.11
20.10
20.02
20.07
20.12
20.11
0.09
0.05
0.07
0.12
0.16
0.07
0.12
HC
All
SGA
20.16 20.02
20.02 20.02
0.00
0.14
0.04
0.17
0.06
0.13
0.00
0.15
0.03
0.11
Non-SGA
All
0.23*
0.22*
0.18
0.23*
0.28*
0.22*
0.25*
0.13
0.11
0.12
0.16*
0.18*
0.15*
0.15*
In this table are shown correlations (Spearman’s correlation coefficient) according to z score changes in wt, length, HC, and
FSIQ. Correlations are presented separately for SGA, non-SGA, and all study children (both SGA and non-SGA children). Age
was corrected for prematurity.
* Correlation was statistically significant (P , .05).
there is a particular growth period
significant for brain development. We
found differences in the growth profiles
of SGA and non-SGA infants. In non-SGA
children, good weight gain and growth
in HC between birth and 2 years’ CA was
associated with better cognitive outcome at 5 years of age, but this was
not the case in SGA infants. Consistently, Latal-Hajnal et al26 found that
good weight gain up to 2 years’ CA
was associated with better cognitive
outcome in non-SGA but not in SGA
infants. However, they did not find HC
growth to associate with cognitive
outcome. Hack et al31 also showed
that the HC at 8 months’ CA was associated with cognition for all VLBW
infants (ie, without separating them
into SGA and AGA groups) at 8 to 9
years of age.
We found that good HC growth around
term age was associated with improved
cognition in SGA infants. Similarly, Stathis
et al42 found that poor HC growth between birth and 4 months’ CA was associated with impaired 6-year
cognition in extremely low birth weight
infants. Frisk et al27 showed that cognition was better in the SGA infants
with good postnatal HC growth than in
SGA infants with a small HC at birth and
at 9 months of age. Brandt22 also found
that the SGA infants with HC catch-up
growth until 1 year of age had higher
intelligence scores than those without
HC catch-up growth. After controlling
for gender, GA, and the mother’s education, we found that 5-year FSIQ improved by 2.5 for each z score increase
in HC between term equivalent age and
2 years’ CA.
Our study suggests that the most significant time period for HC growth in
SGA infants is around term age. This
implies that nutrition at home after
discharge from hospital warrants
additional evaluation, especially for
SGA infants. We hypothesized that good
FIGURE 2
Correlation between HC growth and cognitive outcome. The x-axis presents the z score change of HC between birth and 2 years of CA. The y-axis shows the FSIQ.
The horizontal lines at FSIQ 85 and FSIQ 70 mark slightly below normal and significantly below normal, respectively.
PEDIATRICS Volume 133, Number 1, January 2014
67
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growth in weight and length in SGA
infants would be related to better
cognitive outcome, but we did not find
an association between weight and
length growth and cognitive outcomes
in SGA children. In the non-SGA infants,
no single time period for growth was
more significant than any other. Instead, consistent growth in weight and
HC until 2 years’ CA was significant for
good cognitive outcome for non-SGA
infants. This is an important result
because benefits of weight gain in nonSGA infants are also questioned.43 The
relationship between length growth
and cognitive outcome has been controversial10,14,19 in recent publications.
In this study good growth in length was
not associated with better outcome.
The deviation from normal expected
growth was most common at 36 weeks’
GA. At term age, almost all infants, including non-SGA infants, had HCs .2
2.0 SD. The weight and length were .2
2.0 SD in most infants at 1 year of
CA Although SGA infants had catch-up
growth, they remained lighter (z score
mean 20.8 vs 0.0) and shorter (20.4 vs
0.0) and had smaller HCs (20.4 vs 1.0)
than non-SGA infants at 5 years of age.
Postnatal growth restriction at 5 years
of age was rare in our study cohort compared with some earlier studies: 3% vs
15%10 for weight, 3% vs 6%15 for height,
and 1% vs 26%10 for HC.
It must be noted that different studies
report growth in preterm infant populations at different GAs or birth
weights. There is also variation in the
definition of intrauterine growth restriction, because some studies use
a birth weight ,10th percentile and
others ,22.0 SD. In addition, causes
of intrauterine and postnatal growth
restriction vary, as do individual growth
rates and styles.15 Furthermore, some
infants classified as non-SGA at birth
could have been subject to growth restriction in utero and thus had not
achieved their genetic growth potential
before birth. Growth references and
age corrections also vary between
studies, along with the age points and
methods for evaluation of cognitive
outcome. However, because we compared the postnatal growth of SGA and
non-SGA very preterm infants and the
effect of postnatal growth on their
cognitive outcome, we concluded that
the differences between growth charts
used may not be significant. Yet it is
also important to indicate that the
cognitive outcome was described by
the FSIQ and that this global measure is
only 1 aspect of cognitive capacity and
does not describe the neuropsychological profile. One limitation of our
study is the lack of full-term non-SGA
infants for comparison. Measurement
of infants is error-sensitive, and without standardized methods there would
be significant variability between
measurers. At 5 years of age children
were measured by trained nurses at
well baby clinics. The Finnish National
Institute for Health and Welfare has
produced a detailed manual of methods for measuring children correctly,
and the use of these standardized methods is mandatory. Therefore, it is unlikely that the obtained measurements
were not reliable. According to Howe
et al,44 routinely collected length, height,
and weight measures from child health
records are comparable, with no systematic bias, supporting their use in
clinical practice and research.
Cognitive outcome was similar in SGA
and non-SGA preterm born children.
Therefore, we assume that postnatal
growth in this very preterm cohort, for
whom malnourishment was unlikely,
was sufficient for brain development.
We found that good growth in weight
and HC until 2 years’ CA in non-SGA
children and good HC growth around
term age in SGA infants was associated with better cognitive outcome.
Therefore, our results emphasize the importance of growth evaluation as part
of the developmental follow-up of very
preterm infants. In addition, optimal
postdischarge nutrition might especially benefit SGA infants.
PIPARI STUDY GROUP
In addition to the authors, the PIPARI
study group includes Tuula Äärimaa,
MD, PhD; Mikael Ekblad, MD; Satu
Ekblad, RN; Eeva Ekholm, MD, PhD;
Mira Huhtala, MD; Pentti Kero, MD,
PhD; Riikka Korja, PhD; Harry Kujari,
MD; Hanna Manninen, MD; Jonna
Maunu, MD, PhD; Petriina Munck, PhD;
Pekka Niemi, PhD, professor; Pertti Palo,
MD, PhD; Riitta Parkkola, MD, PhD;
Jorma Piha, MD, professor; Liisi Rautava,
MD, PhD; Hellevi Rikalainen, MD, PhD;
Katriina Saarinen, physiotherapist;
Virva Saunavaara, MSc; Elina Savonlahti, MD; Sirkku Setänen, MD; Matti
Sillanpää, MD, PhD, professor; Suvi
Stolt, PhD; Päivi Tuomikoski-Koiranen,
RN; and Milla Ylijoki, MD, PhD.
REFERENCES
1. Cooke RWI, Foulder-Hughes L. Growth impairment in the very preterm and cognitive
and motor performance at 7 years. Arch
Dis Child. 2003;88(6):482–487
68
2. Larroque B, Ancel PY, Marret S, et al; EPIPAGE
Study Group. Neurodevelopmental disabilities and special care of 5-year-old children
born before 33 weeks of gestation (the
LEPPÄNEN et al
Downloaded from by guest on July 12, 2017
EPIPAGE study): a longitudinal cohort study.
Lancet. 2008;371(9615):813–820
3. Larroque B, Ancel PY, Marchand-Martin L,
et al; Epipage Study Group. Special care
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4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
and school difficulties in 8-year-old very
preterm children: the Epipage cohort
study. PLoS ONE. 2011;6(7):e21361
Saigal S, Doyle LW. An overview of mortality
and sequelae of preterm birth from infancy to adulthood. Lancet. 2008;371(9608):
261–269
Aarnoudse-Moens CSH, Weisglas-Kuperus
N, van Goudoever JB, Oosterlaan J. Metaanalysis of neurobehavioral outcomes in
very preterm and/or very low birth weight
children. Pediatrics. 2009;124(2):717–728
Dusick AM, Poindexter BB, Ehrenkranz RA,
Lemons JA. Growth failure in the preterm
infant: can we catch up? Semin Perinatol.
2003;27(4):302–310
Hack M, Schluchter M, Cartar L, Rahman M,
Cuttler L, Borawski E. Growth of very low
birth weight infants to age 20 years. Pediatrics. 2003;112(1 pt 1). Available at: www.
pediatrics.org/cgi/content/full/112/1/e30
Roberts G, Cheong J, Opie G, et al; Victorian
Infant Collaborative Study Group. Growth of
extremely preterm survivors from birth to
18 years of age compared with term controls. Pediatrics. 2013;131(2). Available at:
www.pediatrics.org/cgi/content/full/131/2/
e439
Clark RH, Thomas P, Peabody J. Extrauterine growth restriction remains a serious
problem in prematurely born neonates.
Pediatrics. 2003;111(5 pt 1):986–990
Franz AR, Pohlandt F, Bode H, et al. Intrauterine, early neonatal, and postdischarge growth and neurodevelopmental
outcome at 5.4 years in extremely preterm
infants after intensive neonatal nutritional
support. Pediatrics. 2009;123(1). Available at:
www.pediatrics.org/cgi/content/full/123/1/e101
Horemuzova E, Söder O, Hagenäs L. Growth
charts for monitoring postnatal growth at
NICU of extreme preterm-born infants. Acta
Paediatr. 2012;101(3):292–299
Kan E, Roberts G, Anderson PJ, Doyle LW;
Victorian Infant Collaborative Study Group.
The association of growth impairment with
neurodevelopmental outcome at eight years
of age in very preterm children. Early Hum
Dev. 2008;84(6):409–416
Ranke MB, Vollmer B, Traunecker R, et al.
Growth and development are similar in
VLBW children born appropriate and small
for gestational age: an interim report on 97
preschool children. J Pediatr Endocrinol
Metab. 2007;20(9):1017–1026
Ramel SE, Demerath EW, Gray HL, Younge N,
Boys C, Georgieff MK. The relationship of
poor linear growth velocity with neonatal
illness and two-year neurodevelopment in
preterm infants. Neonatology. 2012;102(1):
19–24
15. Pierrat V, Marchand-Martin L, Guemas I,
et al; Epipage Study Group. Height at 2 and
5 years of age in children born very preterm: the EPIPAGE study. Arch Dis Child
Fetal Neonatal Ed. 2011;96(5):F348–F354
16. Brandt I, Sticker EJ, Gausche R, Lentze MJ.
Catch-up growth of supine length/height of
very low birth weight, small for gestational
age preterm infants to adulthood. J
Pediatr. 2005;147(5):662–668
17. Ehrenkranz RA, Dusick AM, Vohr BR, Wright
LL, Wrage LA, Poole WK. Growth in the neonatal intensive care unit influences neurodevelopmental and growth outcomes of
extremely low birth weight infants. Pediatrics. 2006;117(4):1253–1261
18. Bocca-Tjeertes IFA, Kerstjens JM, Reijneveld
SA, de Winter AF, Bos AF. Growth and predictors of growth restraint in moderately
preterm children aged 0 to 4 years. Pediatrics. 2011;128(5). Available at: www.pediatrics.org/cgi/content/full/128/5/e1187
19. Lundgren EM, Cnattingius S, Jonsson B,
Tuvemo T. Intellectual and psychological
performance in males born small for gestational age. Horm Res. 2003;59(suppl 1):
139–141
20. De Curtis M, Rigo J. Extrauterine growth
restriction in very-low-birthweight infants.
Acta Paediatr. 2004;93(12):1563–1568
21. Loui A, Tsalikaki E, Maier K, Walch E,
Kamarianakis Y, Obladen M. Growth in high
risk infants ,1500 g birthweight during
the first 5 weeks. Early Hum Dev. 2008;84
(10):645–650
22. Brandt I, Sticker EJ, Lentze MJ. Catch-up
growth of head circumference of very low
birth weight, small for gestational age
preterm infants and mental development
to adulthood. J Pediatr. 2003;142(5):463–
468
23. Casey PH, Whiteside-Mansell L, Barrett K,
Bradley RH, Gargus R. Impact of prenatal
and/or postnatal growth problems in low
birth weight preterm infants on school-age
outcomes: an 8-year longitudinal evaluation. Pediatrics. 2006;118(3):1078–1086
24. Cooke RWI. Are there critical periods for
brain growth in children born preterm?
Arch Dis Child Fetal Neonatal Ed. 2006;91
(1):F17–F20
25. Belfort MB, Rifas-Shiman SL, Sullivan T,
et al. Infant growth before and after term:
effects on neurodevelopment in preterm
infants. Pediatrics. 2011;128(4). Available
at: www.pediatrics.org/cgi/content/full/128/
4/e899
26. Latal-Hajnal B, von Siebenthal K, Kovari H,
Bucher HU, Largo RH. Postnatal growth in
VLBW infants: significant association with
PEDIATRICS Volume 133, Number 1, January 2014
27.
28.
29.
30.
31.
32.
33.
34.
35.
36.
37.
38.
neurodevelopmental outcome. J Pediatr.
2003;143(2):163–170
Frisk V, Amsel R, Whyte HEA. The importance of head growth patterns in predicting the cognitive abilities and literacy skills
of small-for-gestational-age children. Dev
Neuropsychol. 2002;22(3):565–593
Belfort MB, Martin CR, Smith VC, Gillman
MW, McCormick MC. Infant weight gain and
school-age blood pressure and cognition in
former preterm infants. Pediatrics. 2010;
125(6). Available at: www.pediatrics.org/
cgi/content/full/125/6/e1419
Maunu J, Parkkola R, Rikalainen H, Lehtonen
L, Haataja L, Lapinleimu H; PIPARI Group.
Brain and ventricles in very low birth weight
infants at term: a comparison among head
circumference, ultrasound, and magnetic
resonance imaging. Pediatrics. 2009;123(2):
617–626
Cheong J, Hunt LY, Anderson R, et al. Head
growth in preterm infants: correlation with
magnetic resonance imaging and neurodevelopmental outcome. Pediatrics. 2008;
121(6). Available at: www.pediatrics.org/
cgi/content/full/121/6/e1534
Hack M, Breslau N, Weissman B, Aram D,
Klein N, Borawski E. Effect of very low birth
weight and subnormal head size on cognitive abilities at school age. N Engl J Med.
1991;325(4):231–237
Ghods E, Kreissl A, Brandstetter S, Fuiko R,
Widhalm K. Head circumference catch-up
growth among preterm very low birth
weight infants: effect on neurodevelopmental outcome. J Perinat Med. 2011;39(5):
579–586
Leppänen M, Ekholm E, Palo P, et al; PIPARI
Study Group. Abnormal antenatal Doppler
velocimetry and cognitive outcome in verylow-birth-weight infants at 2 years of age.
Ultrasound Obstet Gynecol. 2010;36(2):178–
185
Wechsler D. Wechslerin Älykkyystestistö
Esikouluikäisille, Käsikirja. Helsinki, Finland:
Psykologien Kustannus Oy; 1995
Lind AK, Korkman M, Lehtonen L, et al;
PIPARI Study Group. Cognitive and neuropsychological outcomes at 5 years of age in
preterm children born in the 2000s. Dev
Med Child Neurol. 2011;53(3):256–262
Maunu J, Kirjavainen J, Korja R, et al; PIPARI
Study Group. Relation of prematurity and
brain injury to crying behavior in infancy.
Pediatrics. 2006;118(1). Available at: www.
pediatrics.org/cgi/content/full/118/1/e57
Sorva R, Perheentupa J, Tolppanen EM. A
novel format for a growth chart. Acta
Paediatr Scand. 1984;73(4):527–529
Sorva R, Lankinen S, Tolppanen EM, Perheentupa
J. Variation of growth in height and weight
69
Downloaded from by guest on July 12, 2017
of children. II. After infancy. Acta Paediatr
Scand. 1990;79(5):498–506
39. Pihkala J, Hakala T, Voutilainen P, Raivio K.
Characteristics of recent fetal growth
curves in Finland [in Finnish]. Duodecim.
1989;105(18):1540–1546
40. Child growth standards. Geneva, Switzerland:
World Health Organization. Available at:
www.who.int/childgrowth/standards/en/
41. Manual of Operation for Infants Born in
2012. Vermont Oxford Network Database.
Vermont Oxford Network; 2012:1–51. Available at: http://www.vtoxford.org/. Accessed
January 2012
42. Stathis SL, O’Callaghan M, Harvey J, Rogers
Y. Head circumference in ELBW babies is associated with learning difficulties and cognition but not ADHD in the school-aged child.
Dev Med Child Neurol. 1999;41(6):375–380
43. Beyerlein A, Ness AR, Streuling I, HaddersAlgra M, von Kries R. Early rapid growth:
no association with later cognitive functions in children born not small for gestational age. Am J Clin Nutr. 2010;92(3):
585–593
44. Howe LD, Tilling K, Lawlor DA. Accuracy of
height and weight data from child health
records. Arch Dis Child. 2009;94(12):950–
954
BITS, BOTS, AND PEOPLE: When I get an email asking me to claim money from
a bank account in Nigeria or make contact with a long lost relative currently
living in Bulgaria, I am fairly confident these are fake, and probably automatically
generated. They are deleted without much thought. When a news organization
reports that Twitter erupted over events someplace, I am less sure how to interpret the news. It would appear that social media sites are easily manipulated.
As discussed in The New York Times (August 11, 2013), robotic programs, or
“bots”, have become increasingly sophisticated and have been used to discredit
political opponents, shape news stories, influence buying habits, and even find
love. Bots for social media, often called socialbots, can be programmed to tweet
and retweet. They have oddities, specific histories, matching accounts on multiple
social media sites, and sleep cycles, making them hard to detect as non-human.
Amazingly, some researchers estimate that only 35 percent of the average Twitter
user’s followers are real people.
Approximately half of all Internet traffic already comes from nonhuman sources
like bots. Computer scientists in Brazil recently revealed that a popular journalist
on Twitter was actually a bot they had created. While that does not sound terrible,
a respected ranking site classified the make-believe journalist as having more
online “influence” than Oprah Winfrey. Others have stolen Twitter hashtags of
political opponents and flooded the internet with inappropriate messages –
forcing Twitter, per protocol, to shut down the hashtag. The effect was to silence
the opponents.
Dating sites are not immune to the effects of bots. When a large on-line dating
company bought a smaller service, they redesigned the site. The result was a sharp
decline in the number of bots, but also members using the site. Evidently, the bots,
which had automatically liked postings and had sent flirtatious emails, made the
site seem safe and full of love – if only robotic love.
Now when I read or hear anything about social media, I take what I hear with a grain
(or more) of salt and ask myself, how likely is this real or generated automatically?
Noted by WVR, MD
70
LEPPÄNEN et al
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Antenatal and Postnatal Growth and 5-Year Cognitive Outcome in Very
Preterm Infants
Marika Leppänen, Helena Lapinleimu, Annika Lind, Jaakko Matomäki, Liisa
Lehtonen, Leena Haataja and Päivi Rautava
Pediatrics 2014;133;63; originally published online December 16, 2013;
DOI: 10.1542/peds.2013-1187
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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 © 2014 by the American Academy of Pediatrics. All
rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.
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Antenatal and Postnatal Growth and 5-Year Cognitive Outcome in Very
Preterm Infants
Marika Leppänen, Helena Lapinleimu, Annika Lind, Jaakko Matomäki, Liisa
Lehtonen, Leena Haataja and Päivi Rautava
Pediatrics 2014;133;63; originally published online December 16, 2013;
DOI: 10.1542/peds.2013-1187
The online version of this article, along with updated information and services, is
located on the World Wide Web at:
/content/133/1/63.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 © 2014 by the American Academy
of Pediatrics. All rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.
Downloaded from by guest on July 12, 2017