Research ajog.

org

OBSTETRICS
Fetal growth restriction and risk of
cerebral palsy in singletons born after
at least 35 weeks’ gestation
Eve M. Blair, PhD; Karin B. Nelson, MD

OBJECTIVE: The objective of the study was to improve the under-
standing of etiological paths to cerebral palsy (CP) that include fetal
growth restriction by examining factors associated with growth re-
striction that modify CP risk.
STUDY DESIGN: In a total population of singletons born at or after 35
weeks, there were 493 children with CP and 508 matched controls for
whom appropriateness of fetal growth could be estimated. Fetal
growth was considered markedly restricted if birthweight was more
than 2 SD below optimal for gender, gestation, maternal height, and
parity. We examined maternal blood pressure in pregnancy, smoking,
birth asphyxia, and major birth defects recognized by age 6 years as
potential modifiers of CP risk in growth-restricted births.
RESULTS: More than 80% of term and late preterm markedly growth-
restricted singletons were born following a normotensive pregnancy
and were at statistically significantly increased risk of CP (odds ratio,
4.81; 95% confidence interval, 2.7e8.5), whereas growth-restricted
births following a hypertensive pregnancy were not. Neither a clinical
diagnosis of birth asphyxia nor potentially asphyxiating birth events
occurred more frequently among growth-restricted than among
appropriately grown infants with CP. Major birth defects, particularly
cerebral defects, occurred in an increasing proportion of CP with
increasing growth deficit. The factor most predictive of CP in growth-
restricted singletons was a major birth defect, present in 53% of
markedly growth-restricted neonates with later CP. Defects observed
in CP were similar whether growth restricted or not, except for an
excess of isolated congenital microcephaly in those born growth
restricted. The highest observed CP risk was in infants with both
growth restriction and a major birth defect (8.9% of total CP in this
gestational age group, 0.4% of controls: odds ratio, 30.9; 95% con-
fidence interval, 7.0e136).
CONCLUSION: The risk of CP was increased in antenatally growth-
restricted singletons born at or near term to normotensive mothers.
In growth-restricted singletons, a major birth defect was the dominant
predictor, associated with a 30-fold increase in odds of CP. Identifi-
cation of birth defects in the growth-restricted fetus or neonate may
provide significant prognostic information.
Key words: birth asphyxia, birth defects, pregnancy-induced hyper-
tension, smoking, term and late preterm birth

Cite this article as: Blair EM, Nelson KB. Fetal growth restriction and risk of cerebral palsy in singletons born after at least 35 weeks’ gestation. Am J Obstet Gynecol
2015;212:xx-xx.

S uboptimal fetal growth is associated

with a heightened risk of a range
of adverse outcomes of pregnancy,
cerebral palsy (CP) has been especially
robust.1-8 Defined as a birthweight
greater than 2 SD below optimal, FGR
Much of the literature has considered
FGR as a unitary entity, varying chiefly in
severity and gestational duration at onset.
including antenatal or neonatal death, contributes a larger proportion of CP in The etiology of FGR is known to be varied,
neonatal encephalopathy, perinatal term and late preterm singletons than do however,10 and some reports distinguish
stroke, cerebral palsy, epilepsy, autism, potentially asphyxial birth events or growth deficit arising in normotensive
and schizophrenia. The association of inflammation or a combination of those from that in hypertensive pregnancies.11-13
fetal growth restriction (FGR) with risk factors.9 Pregnancy-induced hypertension
(PIH), which includes preeclampsia, is a
recognized antecedent of growth deficit
From Telethon Kids Institute, University of Western Australia, West Perth, Western Australia (Dr Blair),
and Department of Neurology, Children’s National Medical Center, Washington, DC, and Scientist and an important cause of maternal
Emeritus, National Institute of Neurological Disease and Stroke, Bethesda, MD (Dr Nelson). morbidity and mortality and fetal loss,
Received July 18, 2014; revised Sept. 25, 2014; accepted Oct. 28, 2014. but it is not clear whether PIH is an
E.M.B. and the case-control study were supported by National Health and Medical Research Council important antecedent of CP in FGR
Program grant 353514. births. Maternal smoking is the most
The authors report no conflict of interest. frequent antecedent of FGR in popula-
Presented at the 68th annual meeting of the American Academy of Cerebral Palsy and tion studies,14 but whether it influences
Developmental Medicine, San Diego, CA, Sept. 9-13, 2014. CP risk differently from FGR associated
Corresponding author: Eve Mary Blair, PhD. Eve.Blair@telethonkids.org.au with other antecedents is not known.
0002-9378/$36.00  ª 2015 Elsevier Inc. All rights reserved.  http://dx.doi.org/10.1016/j.ajog.2014.10.1103 Given the paucity of information on
whether differing antecedents of FGR

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influence neurological outcome, we
examined the data of a large population-
based study of births from 1980 to 1995
for a relationship between CP with FGR
and its major known risk factors: PIH,
smoking, acute asphyxial birth, and ma-
jor birth defects. We focused on singleton
births after at least 35 weeks’ gestation
because, although they contribute to 75%
of all CP, their outcomes have received
less attention and because the rates of
term and late preterm CP have not
changed since these data were collected.
M ATERIALS AND M ETHODS
The population-based case-control
study providing the data for this report
was designed to investigate factors asso-
ciated with risk of CP,9,15-17 defined as a
disorder of movement and/or posture
and motor function because of a
nonprogressive interference/lesion or
abnormality of the developing brain.
Persons registered with the Western
Australian Register of Developmental
AnomalieseCerebral Palsy18 were
selected if born between Jan. 1, 1980, and
Dec. 31, 1995, excluding those whose CP
was acquired postneonatally or resulted
in minimal motor impairment.
Controls and perinatal deaths were
selected from the 380,918 births between
1980 and 1995 registered on the
Maternal Child Health Research Data-
base, which links statutory birth and
death registries with statutory pregnancy
and delivery information and includes
more than 99.5% of registered births in
Western Australia. Neonatally surviving
controls not registered as CP were indi-
vidually matched to CP cases for gesta-
tional age (within 1 week), date of birth
(within 12 months), and plurality.
Representative samples of intrapartum
stillbirths and neonatal deaths (live
births dying within 28 days) were
selected by taking 7 and 4 year birth
cohorts, respectively,9 distributed within
the 1980-1995 period.
Information was sought concerning
pregnancy, delivery, neonatal, family,
and maternal obstetric history from
medical records of the hospitals of de-
livery and neonatal care and private ob-
stetricians or general practitioners who
provided antenatal care. These data were
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recorded by trained midwives or
neonatal nurses.16 Analyses of FGR
included singleton births and focused on
children with CP and controls born after
at least 35 weeks’ gestation.
Appropriateness of fetal growth was
assessed with the proportion of optimal
birthweight (POBW). This method
compares the index birthweight with the
median estimated weight of fetuses of
the same gestational age subsequently
live born at term to women without
recorded exposure to common factors
known to affect fetal growth and of the
same height and parity as the index
mother.14,19
Fetal growth was categorized as mild if
POBW was less than 85% (about the
10th percentile of all Western Australian
live births) and marked if POBW was
77.3% or less (2 SD below the median of
the optimally grown population,
approximately the fifth percentile of all
Western Australian live births) or, to
minimize false-negative results, had
been diagnosed neonatally as growth
restricted.
PIH was defined as blood pressure
reaching or exceeding 140/90 mm Hg, a
systolic rise of 20 mm Hg, or a diastolic
rise of 15 mm Hg during pregnancy. As
found with other adverse perinatal out-
comes,20 the presence of proteinuria did
not affect the risk of CP associated with
PIH and was not considered further.
Women were classified as smokers in
pregnancy if they were reported to smoke
after 20 weeks’ gestation; this datum was
missing for about one-third of study
subjects. The number of cigarettes
smoked daily before and after 20 weeks’
gestation was also recorded if available
(83% of smokers). Alcohol and recrea-
tional drug use was noted if recorded, but
gross underreporting is likely.
Data concerning defects present at
birth and recognized at any time before 6
years of age were obtained by linking
with the Western Australian Register
of Developmental AnomalieseBirth
Defects,21 which records up to 10 di-
agnoses of birth defects together with the
age at which each diagnosis was made.
For this analysis birth defects were
categorized hierarchically as cerebral
defects; cardiac defects; other major
ajog.org
defects; and deformational defects and
minor defects (which included cosmetic
defects and those unlikely to affect phys-
ical quality of life). Major defects
excluded exclusively minor defects.
Because CP is defined by motor disorders
not present at birth, it was not considered
a birth defect. Recorded teratogenic ex-
posures and chromosomal or genetic
defects were classified separately.
Sentinel events were defined as intra-
partum events likely to enhance the po-
tential for fetal asphyxia and included
significant intrapartum hemorrhage, cord
prolapse, uterine rupture, a tight nuchal
cord, shoulder dystocia, and maternal
collapse. A clinical diagnosis of birth
asphyxia or hypoxic ischemic encepha-
lopathy in the medical record was noted.
The risks of CP were estimated for
each growth, PIH, and maternal smoking
stratum for singleton births after at least
35 weeks of gestation. Associations were
sought between CP within high-risk
strata for major birth defects, sentinel
events, a clinical diagnosis of birth
asphyxia, and recreational drug use.
Statistical analysis
SAS version 9.3 (SAS Institute, Cary,
NC) was used to generate descriptive
statistics and odds ratios estimated from
a conditional logistic regression, which
effectively adjusts for the matching
variables of gestational duration (within
1 week) and year of birth (within 12
months).
This study was approved by the Prin-
cess Margaret Hospital/King Edward
Memorial Hospital Ethics Committee,
the Confidentiality of Health Informa-
tion Committee of the Western Australia
Department of Health, individual hos-
pital and regional ethics committees, the
University of Sydney Human Research
and Ethics Committee, and the Confi-
dentiality of Health Information
Committee of the Western Australia
Department of Health, whose docu-
ments can be provided on request. All
waived the requirement for individual
patient consent.
R ESULTS
Among the 386,159 infants born in
Western Australia from 1980 through
ajog.org Obstetrics Research

Association of FGR with risk of CP

TABLE 1 In term and late preterm infants, the
ORs for CP in term and late preterm singleton births odds of CP for those with marked FGR
Variable Factor Nco:Nca OR (95% CI) were increased almost 9-fold compared
Total, n a
Fetal growth 508:493 with infants of appropriate birthweight
AGA 399:325 1 (reference)
for gestational age (AGA) (odds ratio
[OR], 4.16; 95% confidence interval
Mild FGR 82:85 1.21 (0.85e1.73) [CI], 2.5e6.8). For mild FGR there was
Marked FGR 27:83 4.16 (2.5e6.8)b no significant increase in CP risk
Total, na Maternal hypertension 503:477 (Table 1).
AGA N 348:256 1 (reference) Normotensive and hypertensive FGR
Mild FGR N 71:71 1.24 (0.84e1.8) Among markedly FGR singletons, about
Marked FGR N 22:69 4.81 (2.7e8.5)b half of controls and children with CP
born before 35 weeks, but a much larger
AGA Y 47:61 1.56 (1.0e2.4)b
proportion of controls, 81% (22 of 27),
Mild FGR Y 10:11 1.61 (0.65e4.0) CP, 88% (69 of 78), and 71% (34 of 48)
Marked FGR Y 5:9 2.56 (0.78e8.4) perinatal deaths born at or after 35
Total, n a
Maternal smoking 332:331
weeks, experienced normotensive preg-
nancies (Figure 1). Marked FGR in
AGA N 195:161 1 (reference) normotensive gravidae was associated
Mild FGR N 31:25 1.35 (0.63e2.9) with statistically significantly increased
Marked FGR N 13:33 7.82 (2.5e24)b risk of CP, whereas that in hypertensive
gravidae was not (Table 1). In AGA
AGA Y 67:58 1.37 (0.81e2.34)
neonates born of hypertensive pregnan-
Mild FGR Y 22:26 1.11 (0.49e2.5) cies, there was a relatively small elevation
Marked FGR Y 4:28 14.8 (3.3e66)b of CP risk of marginal statistical
Total, na Major birth defect 508:493
significance.
Thus, the large majority of term and
AGA/mild FGR N 465:266 1 (reference) late preterm infants with marked FGR
Marked FGR N 25:39 2.77 (1.5e5.1)b who developed CP were products of
AGA/mild FGR Y 16:144 13.9 (7.5e25.7)b normotensive pregnancies.
Marked FGR Y 2:44 30.9 (7.0e136)b
Maternal smoking
AGA, appropriate birthweight for gestational age; CI, confidence interval; CP, cerebral palsy; FGR, fetal growth restriction; Maternal smoking data were missing for
N, no; Nco:Nca, number of controls: number of CP cases; OR, odds ratio; Y, yes.
a
34.6% of controls, 33.3% of CP, and
Number of subjects with nonmissing data for all stratification variables; b OR differs statistically significantly from unity
(P < .05). 26.3% of perinatal deaths. In those with
Blair. Fetal growth restriction and cerebral palsy. Am J Obstet Gynecol 2014. available data, there was no increase in
CP risk associated with maternal smok-
ing that was not accompanied by marked
FGR (Table 1).
To test the hypothesis that the marked
1995, there were 376,541 singleton growth restricted were so classified on growth restriction in CP births to
births (97.5%) of whom 363,747 the basis of a neonatal diagnosis of smoking mothers resulted from greater
(96.6%) delivered at or after 35 weeks’ growth restriction and did not have a exposure to cigarette smoke, we
gestation. There were 493 singleton birthweight more than 2 SD below their compared the quantities smoked be-
children with CP, 508 matched controls, estimated optimal. Five of the 19 CP thus tween those with marked and those with
and 176 perinatal deaths born at 35 categorized infants were diagnosed as mild or no growth restriction. The
weeks’ gestational age or later and 167 congenitally hydrocephalic. For the mothers of CP births and perinatal
singleton children with CP, 148 matched others, weight was either low relative to deaths with marked growth restriction
controls, and 319 perinatal deaths born length, particularly in CP, or, more did not smoke more than those with
before 35 weeks for whom appropriate- rarely, the length was low relative to the mild or no growth restriction: mean (SE)
ness of growth could be assessed. head circumference. With the exception of the number of cigarettes smoked daily
One quarter of controls (25.9%), of 2 CP infants with marked congenital after 20 weeks’ gestation was 12.2 (1.2) in
22.9% of CP, and 14.9% of perinatal hydrocephaly, all had birthweights below those with a marked restriction and 13.3
deaths who were classified as markedly their estimated optimal. (1.0) in those without. This suggests that

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smoking but more strongly in CP (OR,

FIGURE 1 17.9; 95% CI 4e80) than in controls
Proportion of normotensive pregnancies in markedly FGR births (OR, 3; 95% CI, 0.7e12) or perinatal
web 4C=FPO

deaths (OR, 2.5; 95% CI, 0.5e13). Five

Proportion of normotensive pregnancies in controls, CP, and perinatal deaths with fetal growth
restriction born either before 35 weeks or after at least 35 weeks’ gestation.
CP, cerebral palsy; FGR, fetal growth restriction.
Blair. Fetal growth restriction and cerebral palsy. Am J Obstet Gynecol 2014.
the excess of markedly FGR infants born
to smoking mothers of CP births and
perinatal deaths may be attributable to
some characteristic of the woman or her
environment that is associated with
smoking in pregnancy rather than with
smoking itself.
Substance abuse and social disadvan-
tage are possible candidates for a factor
associated with smoking in pregnancy
that raises risk for adverse outcome. In
those with nonmissing data, as antici-
pated, alcohol use was associated with
smoking: in controls (OR, 3.5; 95% CI,
1.8e6.9), CP (OR, 2.0; 95% CI,
1.0e3.9), and perinatal deaths (OR, 3.4;
95% CI, 1.2e9.9). Fetal alcohol syn-
drome was identified in 4 CP cases (and
no controls), 2 of whom were known to
be born to smoking mothers but none of
whom met criteria for either mild or
marked FGR.
Recreational drug use (primarily her-
oin, cocaine, amphetamines, and mari-
juana) was prospectively reported for 8
of 293 controls (2.7%), 16 of 300 CP
(5.3%), and 6 of 122 perinatal deaths
(4.9%) and was also associated with
of seven CP but only 1 of 6 perinatal
deaths born to women who smoked and
were reported to use recreational drugs
were markedly FGR.
Of the total of 28 CP, 4 controls and 10
perinatal deaths who were both mark-
edly FGR and born to mothers known to
smoke, major birth defects were
observed in 18 of the 28 CP but no
control or perinatal death. Excluding 2
CP infants with congenital TORCH
infection (toxoplasmosis, other [hepati-
tis B], rubella [German measles], cyto-
megalovirus, and herpes simplex virus)
(and no reported recreational drug use),
the distribution of the type of defects in
the 4 for whom recreational drug use was
reported was similar to the 12 for whom
it was not, with half of each group sus-
taining a cerebral defect.
FGR and birth asphyxia
For infants born of normotensive preg-
nancies, the proportion of CP associated
with a clinical diagnosis of birth asphyxia
was not higher in markedly FGR infants
(15.6%) than in AGA neonates (22.9%).
Similarly, potentially asphyxiating birth
events occurred less rather than more
frequently during markedly FGR de-
liveries than AGA deliveries (3.0% in
FGR, 10.2% in AGA; Table 2). Thus,
asphyxial birth as identified by either of

TABLE 2
Percentages of exposed controls and CP by growth and PIH
Variable Diagnosis of birth asphyxia Sentinel event Major birth defects
Fetal growth PIH Controls CP Controls CP Controls CP
a
AGA N 0 (0/348) 22.9 (57/249) 4.0 (14/348) 10.2 (26/254) 2.9 (10/348) 34.8a (89/256)
Mild FGR N 0 (0/71) 20.6a (14/68) 5.6 (4/71) 11.3 (8/71) 5.6 (4/71) 42.2a (30/71)
Marked FGR N 0 (0/22) 15.6 (10/64) 9.1 (2/22) 3.0 (2/67) 9.1 (2/22) 55.1a (38/69)
a
AGA Y 2.1 (1/47) 31.0 (18/58) 6.4 (3/47) 8.2 (5/61) 2.1 (1/47) 31.2a (19/61)
Mild FGR Y 0 (0/9) 27a (3/11) 10 (1/10) 9.1 (1/11) 0 (0/10) 36.4a (4/11)
Marked FGR Y 20 (1/5) 44.4a (4/9) 0 (0/5) 0 (0/9) 0 (0/5) 55.6a (5/9)
AGA, appropriate birthweight gestational age; CP, cerebral palsy; FGR, fetal growth restriction; N, no; PIH, pregnancy-induced hypertension; Y, yes.
a
Proportions in excess of 20%.
Blair. Fetal growth restriction and cerebral palsy. Am J Obstet Gynecol 2014.

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 ajog.org
FIGURE 2
Proportion of singleton term and late preterm controls and CP with major
print & web 4C=FPO
birth defects
Proportion of singleton term and late preterm controls and CP with major birth defects by appro-
priateness of intrauterine growth and site of defect.
CP, cerebral palsy.
Blair. Fetal growth restriction and cerebral palsy. Am J Obstet Gynecol 2014.
these criteria did not appear to be the
factor linking growth restriction in
normotensive pregnancy to CP.
Major birth defects recognized by age
6 years
Major birth defects identified by 6 years
occurred in an increasing proportion of
both CP and controls with increasing
growth deficit but in a much higher
proportion of CP (Figure 2), indepen-
dently of the presence of PIH (Table 2).
Figure 2 also shows the increasing pro-
portion, particularly of cerebral defects,
with an increasing growth deficit in CP,
whereas in controls the sole cerebral
defect was seen in an AGA birth.
The proportions with defects were
similar between CP with and without
marked FGR for cardiac defects (w3%)
and male genital defects (w2.3%), lower
in the markedly FGR CP for deforma-
tional defects (1 of 83 [1.2% in FGR] vs
12 of 410 [2.9%]) and higher for cerebral
defects (26 of 83 [31.3%] vs 79 of 410
[19.3%]) and other major defects (12 of
83 [14.5%] vs 33 of 410 [8.1%]).
We accepted registered microcephaly
as a birth defect only if it was diagnosed at
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birth with a head circumference more
than 3 SD below the optimal or a pro-
portion of the optimal head circumfer-
ence at least 0.5 SD below the z-score for
proportion of optimal birth length and
weight. The only individual defect to
occur statistically significantly more
frequently in CP with FGR than without
was congenital microcephaly in the
absence of recognized cerebral structural
defects (9 of 83 [10.8%] in FGR vs 2 of
410 [0.5%]; OR, 30.9, 95% CI, 7.0e136).
Teratogenic exposures, probably
underestimated on the birth defects
register, were reported more often in CP
following marked FGR (8.4% [4
congenital CMV, 1 congenital rubella, 1
valproate, and 1 recreational polydrug
use]) than following mild FGR (4.7% [4
CMV]) or AGA (2.8% [5 CMV, 4
alcohol]). Genetic or chromosomal de-
fects were found more often in CP
following marked FGR (13.25%) and
following mild FGR (11.8%) than
following AGA birth (5.2%). Thus,
recognized teratogenic or genetic factors
preceded 21.7% of CP born markedly
FGR, 16.4% of CP born mildly FGR, and
8.3% of CP born AGA.
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C OMMENT
The major observations of this study are
that at or near term, FGR occurs chiefly
in normotensive pregnancies, that it is in
this group that CP risk is increased, and
that the dominant risk factor for CP in
FGR singletons in this gestational age
group is the presence of major birth
defects.
Others have also observed that much
growth deficit in term and near-term
infants arises in pregnancies uncompli-
cated by PIH.2,11,22,23 In this study and
in 2 other large population-based
studies2,22 with a total of more than a
million births, hypertensive FGR was not
significantly associated with a CP risk.
Despite its relationship with other
adverse outcomes in mother and infant,
hypertensive FGR appears relatively
benign with respect to risk of CP.
Birth asphyxia is often suggested as
the link between poor fetal growth and
CP risk, with the hypothesis that the lack
of energy reserves makes the FGR fetus
especially vulnerable. This hypothesis is
not supported by this and 2 other
population-based studies, which
observed that FGR infants who devel-
oped CP did not have asphyxial births
more often than children with CP who
were AGA.2,24 Stoknes et al24 further
observed that the risk of CP was higher
among FGR infants whose 5 minute
Apgar scores exceeded 3, again suggest-
ing that the additional CP risk with FGR
is not explained by birth asphyxia.
With maternal smoking, the risk of
CP concentrated in markedly FGR in-
fants and was not related to how heavily
gravidae smoked. We cannot identify
the origin of this association, but sus-
picion falls on recreational drug use
prospectively reported by a very small
proportion of women but more often
by women who smoked during their
pregnancy and subsequently bore
markedly growth-restricted infants later
described as CP.25
We observed that the combination of
marked FGR with a major birth defect
was associated with significant increase
in CP risk and that this combina-
tion contributed approximately half
of CP born markedly FGR, with
congenital microcephaly particularly
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Research Obstetrics
being overrepresented.26 Probably no
single factor accounts for the remaining
half.
The etiology of FGR is diverse, and
some of its causes are also potential causes
of unfavorable brain development and
malformations. Infections, malnutrition,
microvascular dysfunction, immunolog-
ical disorders, and many toxins including
alcohol, pesticides, and mycotoxins can
harm both somatic growth and brain and
also cause birth defects. Furthermore,
much remains to be learned about
normal and aberrant biology underlying
somatic and brain growth and
development.
The major strength of this study is that
it is population based, including all CP
not postneonatally acquired, and that
detailed data were collected directly from
the medical records and birth defects
data by linkage with the population-
based birth defects register. The possi-
bility of biased ascertainment of birth
defects remains because children with
CP undergo more frequent and intense
medical examination; however, our
previous study estimated that this bias
was responsible for only 6% of the
increased frequency of noncerebral birth
defects in CP.27
An important limitation of this study
is its inability to include information on
placental structure and function, widely
considered to be key to FGR. The most
common histological lesion of the
placenta in normotensive FGR is chronic
villitis of unknown origin,28 a disorder
many believe to be chiefly immunolog-
ical. Several reports link chronic villitis
with neonatal encephalopathy and cere-
bral palsy.29-32 Our study also does not
include Doppler flow studies or results of
amniocentesis or biophysical profiling
because these were not routinely per-
formed during the years of births in this
study.
Further comments
“[D]ifferent pathophysiologic mecha-
nisms of FGR are probably associated
with different clinical perinatal out-
comes and recurrence risks in subse-
quent pregnancies.”33 The usual clinical
workup for FGR10,34does not attempt
to identify etiological subcategories in
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normotensive FGR, yet these subgroups
may suggest valuable therapeutic or
preventive opportunities. Careful evalu-
ation of the poorly growing fetus for
birth defects, histological examination of
the placenta, and investigation of possible
environmental or genetic influences
would do much to achieve such
identification.
Such information is not only likely to
improve clinical care but also enable a
more informed prognosis for this child
and for future pregnancies of the mother
and contribute to a better understanding
of the important relationship between
aberrant fetal growth and adverse
neurologic outcome.
Implications
Several implications can be derived
from this study. First, most FGR in sin-
gletons at or near term is normotensive,
and marked normotensive growth re-
striction is a risk factor for subsequent
CP. Second, in term and near-term sin-
gletons, growth restriction is associated
with an excess of major birth defects.
Third, the dominant risk factor for CP in
term and near-term singletons is the
presence of a major birth defect, the risk
further increased in the presence of
growth restriction. And finally, detection
of birth defects in the fetus or neonate
with growth restriction may provide
significant prognostic information. -
ACKNOWLEDGMENTS
We thank Linda Watson (Western Australian
Register of Developmental AnomalieseCerebral
Palsy) and Professor Carol Bower (Western
Australian Register of Developmental Anomalies)
for providing access to the data from their
respective registers. This Register is funded by
the Western Australian State Department of
Health.
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Non-infectious risk factors for different types of
cerebral palsy in term-born babies: a population-
based, case-control study. BJOG 2013;120:
724-31.
2. Blair E, Stanley F. Intrauterine growth and
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