A C TA Obstetricia et Gynecologica

AOGS O R I G I N A L R E S E A R C H A R T I C L E

Association between cerebral palsy and microscopically

verified placental infarction in extremely preterm infants
MARIE-THERESE VINNARS1,*, BRIGITTE VOLLMER2,3, JOSEFINE NASIELL1, NIKOS PAPADOGIANNAKIS4
& MAGNUS WESTGREN1
1

Department of Clinical Science, Intervention and Technology, Division of Obstetrics and Gynecology, Karolinska Institute,
Stockholm, 2Department of Womens and Childrens Health, Karolinska Institute, Stockholm, Sweden, 3Clinical
Neurosciences, Faculty of Medicine, University of Southampton, Southampton, UK, and 4Department of Laboratory
Medicine, Division of Pathology, Karolinska Institute, Stockholm, Sweden

Key words
Cerebral palsy, fetal medicine, neurodisability,
neurodevelopmental disability,
neurodevelopmental outcome,
neurodevelopment, placenta and preterm
delivery
Correspondence
Marie-Therese Vinnars, Department of

ldsviks
Obstetrics and Gynecology, Ornsk
o

Hospital, 891 89 Ornskoldsvik, Sweden.

E-mail: marie-therese.vinnars@ki.se
Conflict of interest
The authors have stated explicitly that there
are no conflicts of interest in connection with
this article.
Please cite this article as: Vinnars M-T,
Vollmer B, Nasiell J, Papadogiannakis N,
Westgren M. Association between cerebral
palsy and microscopically verified placental
infarction in extremely preterm infants. Acta
Obstet Gynecol Scand 2015; 94:976982.
Received: 8 November 2014
Accepted: 1 June 2015
DOI: 10.1111/aogs.12688

Abstract
Introduction. Previously, cerebral palsy has been associated with placental
infarctions diagnosed macroscopically by midwifes. However, the risk of misclassification of infarctionsis is high without a histological verification. Therefore, the objective of this study was to study placental histopathology in
relation to developmental outcome at 2.5 years corrected age in a population
born extremely preterm. Material and methods. A prospective cohort study was
carried out at Karolinska University Hospital, Stockholm, Sweden on a population of 139 live born infants delivered <27 gestational weeks during 20042007.
A senior perinatal pathologist, who was blinded to outcome data, evaluated all
placental slides microscopically. Neuromotor and sensory functions of the children were evaluated. Bayley Scales of Infant and Toddler Development-III
(Bayley-III) were used to assess development at corrected age 2.5 years. The
outcome data were evaluated without reference to obstetrical and pathology
data. The primary outcome measure was neurological and developmental status
at 2.5 years of corrected age. This was measured as diagnosis of cerebral palsy,
visual impairment, hearing impairment as well as performance on Bayley-III
scales evaluating cognitive, language and motor functions. Results. Two out of
seven children with placental infarction were diagnosed with cerebral palsy
compared with one child of 51 without placental infarction (p = 0.036). For
developmental outcome according to Bayley-III at 2.5 years no statistically significant associations with placental pathology were found. Conclusion. A possible association between placental infarction, verified by microscopic
examination, and cerebral palsy has been identified in this extremely preterm
population.
Abbreviations:

EXPRESS, Extremely Preterm Infants in Sweden Study; CP,

cerebral palsy.

Introduction
The survival rate of infants born extremely preterm
(<27 weeks of gestation) is >70% in Sweden (1), but neurological and developmental complications are still common among these children (13). Only in a minority of
preterm children who develop cerebral palsy (CP) can a

976

Key Message
Placental infarction, verified by histopathology, might
be associated with a higher risk for cerebral palsy in
infants born at extremely preterm gestational length.

2015 Nordic Federation of Societies of Obstetrics and Gynecology, Acta Obstetricia et Gynecologica Scandinavica 94 (2015) 976982

M.-T. Vinnars et al.

Placental infarction and cerebral palsy

The study population consists of all surviving infants

delivered between 22+0 and 26+6 gestational weeks in
Stockholm, Sweden between 1 April 2004 and 31 March
2007, and is part of the Extremely Preterm Infants in
Sweden Study (EXPRESS). Multiple pregnancies and cases
where the placentas were not examined were excluded as
were cases where the parents did not give their consent to
participate in the study.
According to clinical practice, in the beginning of the
second trimester an ultrasound examination was performed to determine gestational age. Mothers with a body
mass index of 30 kg/cm2 at first antenatal visit were
defined as obese. The presence of preeclampsia was
recorded and diagnosed, as described previously (18).

72 h. After an initial macroscopic examination, they were

fixed in formalin for approximately 810 days. Thereafter
the membranes and cords were removed and the placentas were weighed and sliced into 0.5- to 1-cm thick
slices, which were examined for any abnormality. Placental weight was regarded as small if it was below the 10th
centile for the actual gestational age (19). At least two or
three pieces of normal placenta, one or two pieces of the
umbilical cord, one or two pieces of the membranes and
pieces from all focally abnormal areas were taken for histological study.
The following pathological variables were assessed: placental abruption, abnormal villous maturation (accelerated or retarded), acute chorioamnionitis (any grade),
fetal thrombosis, placental infarction, placental weight,
decidual arteriopathy, intervillous thrombosis, and
chronic villitis. Data on placental weight were collected
from pathology reports. One senior perinatal pathologist
(N.P.), who was blinded to clinical outcome, reviewed all
original histopathological slides of placental tissue.
Placental abruption was diagnosed histopathologically
by the presence of a retroplacental hematoma and/or clinically. Villous maturation was regarded as accelerated or
retarded in relation to gestational week if more than 50%
of the villous area examined showed those signs. Evaluation of villous maturation included villous size and configuration, layer of trophoblasts and amount, as well as
morphology of blood vessels. Villi close to infarction were
not assessed regarding maturation. Acute chorioamnionitis
was diagnosed histologically and varied from presence of
polymorphonuclear leukocytes at the subchorionic area or
in Langhans fibrinoid and lower third of chorion to an
extensive leukocyte infiltration in the chorion and amnion
with necrosis of amniotic epithelium and micro-abscess
formation. Fetal thrombosis was defined as thrombosis in
the fetal vessels of the placenta or umbilical cord. Placental
infarction was classified as ischemic necrosis of the villi,
including both fresh and older infarctions. Villous necrosis
close to older intervillous thromboses as well as in areas of
extensive intervillous fibrin deposition was not assessed as
infarction. Decidual arteriopathy was defined as fibrinoid
necrosis of the spiral artery wall, lumen thrombosis or
acute atherosis. Intervillous thrombosis (not related to
infarction) included fresh and older lesions. Chronic villitis
was defined as the presence of mononuclear cell infiltrate
in villous stroma, irrespective of the content (2024). Routinely, 3040 high-power fields from macroscopically normal placenta were examined.

Pathological examination

Neurological development

The placentas were routinely sent fresh to the perinatal

pathology section, where they were examined within 48

Neurological and developmental outcome variables at

2.5 years corrected age were neuromotor status (normal

hypoxic event around birth be identified and often the

etiology of the brain injury leading to CP is multifactorial
(46). Impaired placental function may be associated with
an increased risk of developing an adverse neurodevelopmental outcome.
In recent years, several researchers have begun to study
relations between placental pathology and long-term neurodevelopmental outcomes (713). A higher frequency of
chorioamnionitis in those who developed CP has been
noted (14), whereas a comparison of preterm infants
affected by chorioamnionitis or placental underperfusion
found poorer developmental outcome at 2 years of age in
the underperfusion group (10). At 7 years of age the difference was no longer significant, but the sample size was
small. Others have shown that the combination of chorioamnionitis and perfusion defects is associated with adverse
outcome at 24 months (11) and macroscopically diagnosed
placental infarctions have been related to CP (79). However, there is a risk of misclassifying placental infarctions if
the diagnosis is not verified with histology (15) and a previous study on placental histopathology has not shown an
association between placental infarctions and CP (16).
Previous studies have involved small study populations,
selection bias, poorly defined outcome measures and
examination of macroscopic pathology without histological verification of diagnoses (17).
The purpose of this study was to prospectively and
blindly examine associations between placental histopathology and neurological and developmental outcomes at
2.5 years corrected age in a population born extremely
preterm.

Material and methods

2015 Nordic Federation of Societies of Obstetrics and Gynecology, Acta Obstetricia et Gynecologica Scandinavica 94 (2015) 976982

977

Placental infarction and cerebral palsy

or CP), visual function (normal or visual impairment),

hearing (normal or severe impairment), and performance
on the Bayley-III Scales (25) (cognitive, language, and
motor development). Corrected age was the age corrected
for gestation, hence in relation to due date. Delayed
development was assigned when the composite scores
were more than 2 SD below the mean of Swedish children born at term (26), i.e. a composite cognitive score
<83, a composite language score <85, and a composite
motor score <80.
A pediatric neurologist performed a structured examination assessing posture, reflexes, and muscular tone and
CP was diagnosed according to the Bax definition (27).
Information on severe hearing impairment (hearing loss
despite a hearing aid) and severe visual impairment
(blind or only able to see torch light) was gathered to
study neurosensory impairment. The researchers assessing
the children and performing the tests were unaware of
placental pathology data or obstetric history.

Statistical analyses
Data are described as frequencies, percentage (%), means,
and SD. We tested our variables for normality and used
parametric tests for those with normal distributions; t-test
or MannWhitney U-test as appropriate for nonparametric variables. We did not use regression analyses regarding
outcome that was described categorically, because the
material was sparse. For continuous data, we performed a
regression analysis (analysis of covariance) including gestational age (possible confounder), if the data fulfilled the
criteria for this. Associations were considered significant
if p < 0.05. Statistical analyses were performed with STATISTICA 10.0.
The study, which is part of EXPRESS, was approved by
the Regional Research Ethics Board, Lund University
(Dnr 42/2004), and the parents gave informed consent to
data collection and study procedures.

M.-T. Vinnars et al.

(cognitive scales in 50 children, language scales in 49, and

motor scales in 48 children). The assessment was performed at c. 30 months of age (range 2834 months).
Data on CP were available for 58 children. A flow chart
of the study group is shown in Figure 1.
Obstetrical background data are presented in Table 1.
Maternal age ranged from 19 to 43 years. Obesity was
seen in nine (18.8%) women. Data on maternal body
mass index could not be calculated in 15 cases because
data on height and weight at first antenatal visit were
missing. In one case, clinical data regarding abruption
could not be assessed and this case was therefore
excluded from the analysis of this variable. No case had
villitis or retarded villous maturation and only four and
two cases showed features of decidual arteriopathy and

Live-born single birth infants

born in gestational week
22+0 26+6
in Stockholm
April 2004 to March 2007
n = 139
Placenta sent for
pathological
examination
n = 106

Inadequate
quality of
placental tissue
n=1

Alive at
follow up
n = 63

Did not participate

in Bayley-III
assessment
n = 13

Included in the
Bayley-III
assessment
n = 50
Figure 1. Flowchart of the study group.

Results
During the study period, 139 single birth live-born
infants were delivered in gestational weeks 22+0 and up to
26+6 in Stockholm. The placenta had not been examined
in 33 cases and these were excluded along with one case
for which quality of the placental tissue was too poor. In
the excluded cases mean gestational length was
25.3 weeks (SD 1.0) and mean birthweight was 805.4 g
(SD 152.7). In the 105 included cases, the mean gestational length was 24.8 weeks (SD 1.2) and mean birthweight was 742.2 g (SD 159.9) (n = 104).
Of the 105 infants, 63 survived to the age when a Bayley-III assessment was performed in 50 of the children

978

Table 1. Demographic overview of the study group.

Infants alive at 2.5 years
of age (n = 63)
Maternal age (years), mean (SD)
Maternal body mass index (kg/m2),
mean (SD)
Preeclampsia, n (%)
Cesarean section, n (%)
Gestational week, mean (SD)
Male sex, n (%)
Birthweight (g), mean (SD)
Small-for-gestational age, n (%)

31.8 (5.5)
24.8 (5.3)
8 (12.7)
30 (47.6)
25.4 (1.1)
32 (50.1)
790.3 (179.5)
6 (9.5)

2015 Nordic Federation of Societies of Obstetrics and Gynecology, Acta Obstetricia et Gynecologica Scandinavica 94 (2015) 976982

M.-T. Vinnars et al.

Placental infarction and cerebral palsy

intervillous thrombosis, respectively. Therefore it was not

possible to analyze those variables.
Cerebral palsy had been diagnosed in three children.
No child in our sample had severe visual or hearing
impairment. The mean Bayley-III composite cognitive
score was 96.0 (SD 8.3), and one child was categorized as
having cognitive delay. The mean Bayley-III composite
language score was 96.5 (SD 14.4), and seven children
(14.3%) were classified as having delayed language development. The mean Bayley-III composite motor score was
101.3 (SD 17.2), with five (10.4%) having delayed motor
development.
Associations between placental pathology and outcome
at 2.5 years are described in Tables 2 and 3. There were no
significant associations between placental pathology and
Bayley-III performance. However, there was a trend for
fetal thrombosis to be related to lower mean Bayley-III
composite cognitive score (p = 0.082) when analyzed with
a t-test. In a regression analysis, including gestational age,
the tendency remained (p = 0.055) (Table 2). The regression coefficient for fetal thrombosis on the composite cognitive score was 2.82 ( 5.71 to 0.067). Of the children
whose placentas showed accelerated villous maturation
(n = 15), none had language composite scores 2 SD below
the mean of the reference population, whereas this was seen
in seven of those without it (n = 34) (p = 0.084). No difference was seen when comparing mean language composite scores between those groups (Table 2).
There was a significant association between placental
infarction and CP (p = 0.036). Two of the seven children
with placental infarction were diagnosed with CP, com-

Table 3. Placental pathology in relation to cerebral palsy.

Cerebral palsy
n
Abruption
Yes
No
Accelerated villous
Yes
No
Chorioamnionitis
Yes
No
Fetal thrombosis
Yes
No
Infarction
Yes
No

p-valuea

n (%)

23
34
maturation
20
38

3 (13.0)
0

0.061

2 (10.0)
1 (2.6)

0.27

39
19

2 (5.1)
1 (5.3)

0.70

10
48

0
3 (6.3)

0.56

7
51

2 (28.6)
1 (2.0)

0.036

Fishers exact test.

pared with only one of the 51 without this. For placental

abruption the result was borderline (p = 0.061), as all
children with abruption had CP (Table 3).
Infants with a low placental weight showed a mean
Bayley-III composite motor score of 92.0 (SD 15.1), compared with children with a normal or heavy placental
weight, whose mean Bayley-III composite motor score
was 103.4 (SD 7.1). There were no differences in mean
Bayley-III composite cognitive or language scores between
children with and without a low placental weight.

Table 2. Placental pathology in relation to developmental outcome.

Bayley-III composite cognitive score
n

Mean (SD)

Adjusted p-value GAa

Abruption
Yes
20
97.3 (9.0)
No
29
95.5 (7.7)
Accelerated villous maturation
Yes
16
94.7 (4.6)
No
34
96.6 (9.5)
Chorioamnionitis
Yes
33
95.5 (8.5)
No
17
97.1 (7.9)
Fetal thrombosis
Yes
9
91.7 (8.7)
No
41
97.0 (8.0)
Infarction
Yes
7
94.3 (6.1)
No
43
96.3 (8.6)

Bayley-III composite language score

n

Mean (SD)

Bayley-III composite motor score

Adjusted p-value GAa

Mean (SD)

Adjusted p-value GAa

0.55

20
28

99.2 (11.2)
95.3 (16.1)

0.45

20
27

100.0 (16.5)
102.4 (18.2)

0.61

0.12

15
34

98.7 (9.3)
95.6 (16.1)

0.97

14
34

100.4 (16.3)
101.6 (17.7)

0.72

0.88

33
16

95.1 (15.4)
99.4 (11.8)

0.60

33
15

103.7 (17.8)
96.0 (14.8)

0.12

0.055

9
40

92.8 (10.8)
97.4 (15.0)

0.30

9
39

95.9 (14.7)
102.5 (17.6)

0.29

0.34

7
42

101.4 (7.4)
95.7 (15.1)

0.53

7
41

98.3 (19.4)
101.8 (17.0)

0.56

GA, gestational age; SD, standard deviation.

Regression analysis analysis of covariance, p-values indicate the effect of pathology on outcome. Results are adjusted for gestational age as it is
related to placental pathology.
a

2015 Nordic Federation of Societies of Obstetrics and Gynecology, Acta Obstetricia et Gynecologica Scandinavica 94 (2015) 976982

979

Placental infarction and cerebral palsy

Discussion
This study suggests that there may be relations between
placental pathology and neurodevelopmental outcome in
children born extremely preterm. There was a significant
association between placental infarction and CP; but this
result is uncertain because the number of patients with
unfavorable outcome was limited and this might have
caused a Type 1 error. For developmental outcome some
trends could be observed.
Despite the very small number of children affected, we
found a significant association between placental infarction and CP. Several authors have described associations
between infarction and periventricular leukomalacia (28)
as well as CP (8,9). The studies by Blair et al. (9) and
Nielsen et al. (8) are larger than our study, but they only
included placental infarctions diagnosed macroscopically.
The risk of misclassifying infarctions is high without a
microscopic investigation (15). As far as we know, this is
the first study showing that a suggested relation between
CP and placental infarction can be verified histologically.
However, in contrast to our results, Leviton et al. (16)
did not find an association between CP and placental
infarctions. As their study is larger than ours and as they
could also adjust for gestational age in their analyses, this
could indicate that our result may be a consequence of
the limited number of patients, rather than an actual
association.
According to previous studies, placental abruption
might also be related to CP (6,29). We could only find a
trend towards an association, which might, however, be
explained by lack of power in the present study.
The small sample size is an obvious weakness of this
study, and the fact that only three children were diagnosed with CP calls for caution when drawing any conclusions. Furthermore, trends seen when analyzing the
outcome variables as continuous variables could not be
verified when analyzing them as categorical variables, and
vice versa, indicating a weak, if any, association in this
small material. Unfortunately, we were only able to adjust
for gestational age and most likely other factors do influence the outcome (13).
A strength is that the children were followed up prospectively and that few children dropped out. Usually few
placentas are examined (17), but this was not the case in
this study. Another strength is that the pathologist was
blinded to clinical outcome and performed a uniform
pathological evaluation, which also included a detailed
microscopical examination.
Notably, none of the children with a language composite score more than 2 SD below mean showed accelerated
villous maturation compared with almost a quarter of the
children with normal language development. If this is a

980

M.-T. Vinnars et al.

true finding, and not a consequence of the small material,

it could be speculated whether a hypermatured placenta
is more common in children who mature early and
hence, a marker for a genetic predisposition. Alternatively, accelerated villous maturation might illustrate a
capacity of the placenta to adapt to a suboptimal intrauterine environment, i.e. chronic hypoxia. Previously, we
have shown that accelerated villous maturation is associated with less intrauterine fetal death and better blood
flow in the umbilical artery (30) and inversely associated
with 5-min Apgar score <7 and intraventricular hemorrhage grade 3 (31).
Fetal thrombosis showed a tendency to be related to
lower cognitive function, which is in agreement with a
study by Helderman et al. (13). Previously, fetal thrombotic vasculopathy has been related to neonatal encephalopathy and neurological impairment (13, 32). Also,
Wintermark et al.(33), studying 23 full-term asphyxiated
infants who received therapeutic hypothermia, as well as
Elbers et al. (34), studying a smaller group of placentas
from infants with neonatal stroke, reported several fetal
thromboses in their placental material. This finding is
interesting because in the future fetal thrombosis may be
possible to diagnose prenatally and consequently might
be a candidate for prevention and prenatal therapeutic
interventions. Nevertheless, the result was not significant
and future studies might show that the result is not true.
In spite of the few cases with CP, we were able to show
when verifying placental infarctions histopathologically
that an association with CP was present. The present
findings have to be confirmed in larger cohorts. If these
findings are true, it might be that information on placental pathology should get more attention when evaluating
individual preterm fetuses. Furthermore, an early indicator of increased risk for neurological impairment may be
used as a marker for more intense surveillance and therapeutic interventions may be commenced earlier.

Acknowledgments
We acknowledge the important contribution by Karel
Marsal and the EXPRESS group.

Funding
This study was funded by the Swedish Research Council.
References
1. Fellman V, Hellstrom-Westas L, Norman M, Westgren M,
Kallen K, Lagercrantz H, et al. One-year survival of
extremely preterm infants after active perinatal care in
Sweden. JAMA. 2009;301:222533.

2015 Nordic Federation of Societies of Obstetrics and Gynecology, Acta Obstetricia et Gynecologica Scandinavica 94 (2015) 976982

M.-T. Vinnars et al.

2. Marlow N, Wolke D, Bracewell MA, Samara M, EPICure

Study Group. Neurologic and developmental disability at
six years of age after extremely preterm birth. N Engl J
Med. 2005;352:919.
3. Moore T, Hennessy EM, Myles J, Johnson SJ, Draper ES,
Costeloe KL, et al. Neurological and developmental
outcome in extremely preterm children born in England
in 1995 and 2006: the EPICure studies. BMJ. 2012;345:
e7961.
4. Fleiss B, Gressens P. Tertiary mechanisms of brain damage:
a new hope for treatment of cerebral palsy? Lancet Neurol.
2012;11:55666.
5. Gilbert WM, Jacoby BN, Xing G, Danielsen B, Smith LH.
Adverse obstetric events are associated with significant risk
of cerebral palsy. Am J Obstet Gynecol. 2010;203:328 e15.
6. Nelson KB. Causative factors in cerebral palsy. Clin Obstet
Gynecol. 2008;51:74962.
7. Adams-Chapman I, Vaucher YE, Bejar RF, Benirschke K,
Baergen RN, Moore TR. Maternal floor infarction of the
placenta: association with central nervous system injury
and adverse neurodevelopmental outcome. J Perinatol.
2002;22:23641.
8. Nielsen LF, Schendel D, Grove J, Hvidtjorn D, Jacobsson
B, Josiassen T, et al. Asphyxia-related risk factors and their
timing in spastic cerebral palsy. BJOG. 2008;115:151828.
9. Blair E, de Groot J, Nelson KB. Placental infarction
identified by macroscopic examination and risk of cerebral
palsy in infants at 35 weeks of gestational age and over.
Am J Obstet Gynecol. 2011;205:124 e17.
10. van Vliet EO, de Kieviet JF, van der Voorn JP, Been JV,
Oosterlaan J, van Elburg RM. Placental pathology and
long-term neurodevelopment of very preterm infants. Am
J Obstet Gynecol. 2012;206:489 e17.
11. Kaukola T, Herva R, Perhomaa M, Paakko E, Kingsmore
S, Vainionpaa L, et al. Population cohort associating
chorioamnionitis, cord inflammatory cytokines and
neurologic outcome in very preterm, extremely low birth
weight infants. Pediatr Res. 2006;59:47883.
12. Redline RW, Minich N, Taylor HG, Hack M. Placental
lesions as predictors of cerebral palsy and abnormal
neurocognitive function at school age in extremely low
birth weight infants (<1 kg). Pediatr Dev Pathol.
2007;10:28292.
13. Helderman JB, OShea TM, Kuban KC, Allred EN, Hecht
JL, Dammann O, et al. Antenatal antecedents of cognitive
impairment at 24 months in extremely low gestational age
newborns. Pediatrics. 2012;129:494502.
14. Murphy DJ, Sellers S, MacKenzie IZ, Yudkin PL, Johnson
AM. Casecontrol study of antenatal and intrapartum risk
factors for cerebral palsy in very preterm singleton babies.
Lancet. 1995;346:144954.
15. Becroft DM, Thompson JM, Mitchell EA. Placental
infarcts, intervillous fibrin plaques, and intervillous
thrombi: incidences, cooccurrences, and epidemiological
associations. Pediatr Dev Pathol. 2004;7:2634.

Placental infarction and cerebral palsy

16. Leviton A, Allred EN, Kuban KC, Hecht JL, Onderdonk

AB, OShea TM, et al. Microbiologic and histologic
characteristics of the extremely preterm infants placenta
predict white matter damage and later cerebral palsy. the
ELGAN study. Pediatr Res. 2010;67:95101.
17. Nelson KB, Blair E. The placenta and neurologic and
psychiatric outcomes in the child: study design matters.
Placenta. 2011;32:6235.
18. Vinnars MT, Nasiell J, Ghazi S, Westgren M,
Papadogiannakis N. The severity of clinical manifestations
in preeclampsia correlates with the amount of placental
infarction. Acta Obstet Gynecol Scand. 2011;90(1):
1925.
19. Pinar H, Sung CJ, Oyer CE, Singer DB. Reference values
for singleton and twin placental weights. Pediatr Pathol
Lab Med. 1996;16:9017.
20. Cox P, Marton T. Pathological assessment of intrauterine
growth restriction. Best Pract Res Clin Obstet Gynaecol.
2009;23:75164.
21. Faye-Petersen J. Handbook of Placental Pathology. 2nd
edn. Abingdon: Taylor and Francis, 2006.
22. Oyelese Y, Ananth CV. Placental abruption. Obstet
Gynecol. 2006;108:100516.
23. Redline RW. Placental pathology: a systematic approach
with clinical correlations. Placenta. 2008;29 Suppl. A:S86
91.
24. Roberts DJ, Post MD. The placenta in pre-eclampsia and
intrauterine growth restriction. J Clin Pathol.
2008;61:125460.
25. Bayley N. Bayley Scales of Infant and Toddler
Development, 3rd edn. San Antonio, TX: The Psycological
Corporation, 2006.
26. Serenius F, Kallen K, Blennow M, Ewald U, Fellman V,
Holmstrom G, et al. Neurodevelopmental outcome in
extremely preterm infants at 2.5 years after active perinatal
care in Sweden. JAMA. 2013;309:181020.
27. Bax M, Goldstein M, Rosenbaum P, Leviton A, Paneth N,
Dan B, et al. Proposed definition and classification of
cerebral palsy, April 2005. Dev Med Child Neurol.
2005;47:5716.
28. Kumazaki K, Nakayama M, Sumida Y, Ozono K,
Mushiake S, Suehara N, et al. Placental features in preterm
infants with periventricular leukomalacia. Pediatrics.
2002;109:6505.
29. Tronnes H, Wilcox AJ, Lie RT, Markestad T, Moster D.
Risk of cerebral palsy in relation to pregnancy disorders
and preterm birth: a national cohort study. Dev Med
Child Neurol. 2014;56:77985.
30. Vinnars MT, Nasiell J, Holmstrom G, Norman M,
Westgren M, Papadogiannakis N. Association between
placental pathology and neonatal outcome in preeclampsia:
a large cohort study. Hypertens Pregnancy. 2014;33:145
58.
31. Vinnars MT, Papadogiannakis N, Nasiell J, Holmstr
om G,
Westgren M. Placental pathology in relation to stillbirth

2015 Nordic Federation of Societies of Obstetrics and Gynecology, Acta Obstetricia et Gynecologica Scandinavica 94 (2015) 976982

981

Placental infarction and cerebral palsy

and neonatal outcome in an extremely preterm

population: a prospective cohort study. Acta Obstet
Gynecol Scand. 2015;94:58490.
32. McDonald DG, Kelehan P, McMenamin JB, Gorman WA,
Madden D, Tobbia IN, et al. Placental fetal thrombotic
vasculopathy is associated with neonatal encephalopathy.
Hum Pathol. 2004;35:87580.

982

M.-T. Vinnars et al.

33. Wintermark P, Boyd T, Gregas MC, Labrecque M, Hansen

A. Placental pathology in asphyxiated newborns meeting
the criteria for therapeutic hypothermia. Am J Obstet
Gynecol. 2010;203:579 e19.
34. Elbers J, Viero S, MacGregor D, DeVeber G, Moore AM.
Placental pathology in neonatal stroke. Pediatrics.
2011;127:e7229.

2015 Nordic Federation of Societies of Obstetrics and Gynecology, Acta Obstetricia et Gynecologica Scandinavica 94 (2015) 976982