JOURNAL OF PATHOLOGY,

MICROBIOLOGY AND IMMUNOLOGY

APMIS 126: 613–620 © 2018 APMIS. Published by John Wiley & Sons Ltd.
DOI 10.1111/apm.12831

Review Article

Abnormalities of placenta implantation

EUMENIA COSTA DA CUNHA CASTRO and EDWINA POPEK

Department of Pathology and Immunology, Texas Children’s Hospital, Pavilion for Women, Baylor College
of Medicine, Houston, TX, USA

da Cunha Castro EC, Popek E. Abnormalities of placenta implantation. APMIS 2018; 126: 613–620.
Implantation abnormalities are a group of disorders encompassing several entities with different degree of severity. This
section will cover the etiopathogenesis, imaging findings, definition, risk factors, and pathology of the abnormally
located and morbidly adherent placenta.
Key words: abnormal placentation; morbidly adherent placenta.
Eumenia Costa da Cunha Castro, Texas Children’s Hospital, Pavilion for Women, Department of Pathology and
Immunology, Baylor College of Medicine, 6621 Fannin St. MC-1195, Houston, Texas, USA. e-mail: ecastro@bcm.edu

Normal implantation is critical for a successful preg-
nancy. Briefly, the implantation in the endometrium
occurs around 6–7 days after the conception and
normally the human blastocyst implants in the upper
portion of the uterus. It starts with apposition of the
blastocyst to the endometrium with subsequent inva-
sion into the endometrium. The trophoblast on the
anchoring villi invades through the endometrium
into the inner 1/3 of myometrium and maternal spi-
ral arteries (Fig. 1: gestational sac) (1). Implantation
abnormalities lead to a group of disorders encom-
passing several entities: placental shape abnormali-
ties, velamentous cord insertion, maternal vascular
malperfusion due to deficient remodeling of the
maternal spiral arteries; abnormally located placen-
tation and morbidly adherent placenta (1, 2). This
section will focus on the abnormally located placen-
tation, which includes placenta previa, low-lying/
marginal placenta and cesarean scar implantation,
and the morbidly adherent placentation (1, 2).
ETIOPATHOGENESIS
Abnormality of decidualization either by trauma or
deficiency of decidua, as in cases of placenta previa
implanting in the lower uterine segment or cesarean
scar, is the common factor in the etiology of abnormal
placentation. The pathogenesis seems to involve an
abnormal interaction between the decidua and the
Received 13 October 2017. Accepted 12 February 2018
invasive extravillous trophoblast, leading to a failure
of maternal tissues to restrain the invading tro-
phoblast (3–6). Multiple hypotheses have been raised
to explain this abnormality. One of them is that anti-
invasive factors, that are antagonist to matrix metallo-
proteinases or are activator of tissue inhibitor of met-
alloproteinases secreted by the decidua, are deficient
in areas of decreased decidualization (7). Another pos-
sibility, is an imbalance in the paracrine/autocrine
regulation between the deficient decidualized endome-
trium and the invasive trophoblasts (8).
RISK FACTORS
Risk factors include any factors that may lead to
damage and scaring of the endometrium. Previous
cesarean delivery or uterine surgery, including prior
dilation and curettage and myomectomies, sponta-
neous or induced abortion, and history of prior
pregnancy with abnormal placentation are the most
important (9–12). In the primigravida, endometrio-
sis and assisted conception have been associated
with abnormal placentation (13, 14). An increased
number of prior cesarean deliveries is also a risk
factor due to the multiple uterine scars (15).
IMAGING
Accurate prenatal diagnosis of abnormal placenta-
tion is paramount for optimal management,

613
 DA CUNHA CASTRO & POPEK
A ensuring that a multidisciplinary team is prepared
B
C the pathological examination of the post-partum
Fig. 1. Placental normal implantational site: (A) Early
implantation site, low power view. Anchoring villi on the
left (arrow) and cytotrophoblast column, which is the
frontrunner of the basal plate, faces the endometrium on
the right (square) (H&E 9 40). (B) High power view of
the interface between the trophoblast cells and the decidua
(square on 1A). The trophoblast (double arrow) invades
up to inner 1/3 of myometrium and the maternal spiral
arteries. The endovascular trophoblast (arrow head) is
noted in the top right corner. Nitabuch fibrinoid is noted
in the interface of the placenta and decidua (arrow) (H&E
9 100). (C) The early relationship between Nitabuch fibri-
noid layer (arrow), invasive trophoblast (double arrow)
and decidua (asterixis) is maintained at the basal plate in
the term placenta (H&E 9 200).
614
for the delivery (12, 16). Transabdominal ultra-
sound is the primary technique used to rule-out
abnormal placentation; however, there are limita-
tions to this technique and false positive results
may occur (17). The addition of color Doppler to
the ultrasonography examination increases the sen-
sitivity for the diagnosis of abnormal placentation
(17). Ultrasound and magnetic resonance imaging
(MRI) appear to have similar sensitivity for the
diagnosis of abnormal placentation. In cases of
posterior accreta, MRI is more useful than the
ultrasound examination (17). By imaging, the diag-
nosis of abnormal placentation is characterized by
the disappearance of the normal subplacental clear
space adjacent to the uteroplacental interface,
extreme thinning of the underlying myometrium,
discontinuity of low signal zone in the gap between
bladder and the uterus, irregularities of the bladder
wall and vascular changes within the placenta.
Useful signs on MRI includes placental bulge with
distorted uterine outline, uterine serosal hypervas-
cularity, dark intraplacental bands of fibrin deposi-
tion extending from the myometrium interface
appearing as low-signal intensity on T2-weighted
images and cervical varicosities (18, 19). However,
in spite of the advance in imaging technique, the
depth of invasion and accurate differential diagno-
sis between accreta, increta and percreta relies on
hysterectomy (20).
TYPES OF ABNORMAL PLACENTATION
Low-lying marginal placenta
Definition
Low-lying placenta is a placenta that ends 2 cm of
the internal cervical os but do not cover it (21).
Most commonly the placenta implantation
occurs in the uterine fundus, followed by implanta-
tion in the anterior wall and posterior wall (22).
Low-lying placentas are most frequently diagnosed
ultrasonographically in the second trimester and
more often, they resolve by the third trimester.
However, when persistent, they are a risk factor for
postpartum hemorrhage (23, 24). Different from
placenta previa, vaginal delivery is possible with
low-lying placentas (25).
Placenta previa
Definition
Placenta previa is defined as a placenta with complete
or partial obstruction of the internal cervical os;
therefore, being “previous” to the delivering fetus.
© 2018 APMIS. Published by John Wiley & Sons Ltd
 PLACENTA IMPLANTATION

Placenta previa is a major cause of third trime-
ster bleeding and has been associated with severe
maternal morbidity including hemorrhage requiring
blood transfusion, disseminated intravascular coag-
ulation and emergency hysterectomy (26). In the
fetus, acute and massive bleeding from placenta
previa has been associated with fetal brain damage
and cerebral palsy (27). There is an increased occur-
rence of placenta previa in women with advanced
maternal age, multiparity, smoking, drug abuse,
prior cesarean delivery, and placenta previa in prior
pregnancy (28, 29). Among those, advanced mater-
nal age and prior cesarean delivery are the main
risk factors and the recent increased incidence of
these factors is likely responsible for temporal
increased incidence of placenta previa (30). Due to
its location in the lower segment of the uterus, a
place that has increased vascularity and decreased
contractility which are predisposing factors for
bleeding, the diagnosis of placenta previa warrants
multidisciplinary management which may some-
times result in a cesarean hysterectomy (16, 31–35).
In cases in which the mother wishes to preserve fer-
tility, more conservative approaches have been
used; however, a 20% failure rate has been
described associated with severe complication (31).
Gross examination of the hysterectomy will show a
placenta implanted in the lower uterine segment

A B

Fig. 2. Placenta previa: (A) Cesarean hysterectomy showing placenta previa with internal os grossly obstructed (arrow).
(B) View of the obliterated cervix underneath the placenta. (C) Microscopic view of the endocervix and the placenta (H&E
9100). Note the blood clot in the endocervix (arrow head).

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 DA CUNHA CASTRO & POPEK

A B

C D

Fig. 3. Basal plate: (A) Normal basal plate: decidua (asterixis), invasive extravillous trophoblast (double arrow) Nitabuch
fibrinoid (open arrow), and villi (arrow) (H&E 9 400). (B) Myometrial fibers adherent to the decidua capsularis is a com-
mon normal finding and not considered accreta (arrow head) (H&E 9 200). (C and D) Occult placenta accreta or micro-
scopic accreta: Myometrial fibers (arrow head) adherent to the basal plate without intervening decidua. The Nitabuch
fibrinoid (open arrow) is present in the interface with the villi (arrow). Invasive trophoblast (double arrow) is noted adja-
cent to the myometrial fibers (H&E 9 400).

obstructing the internal cervical OS (Fig. 2A and
B). Microscopically, placenta is noted adjacent to
endocervical mucosa, and frequently a remote
hematoma is present (Fig. 2C). Placenta previa
may be associated with myometrial fibers adherent
to the basal plate of a delivered placenta, also
known as occult placenta accreta (Fig. 3C and D).
Cesarean scar implantation
Definition
Cesarean scar implantation refers to the placental
implantation within the scar of a prior cesarean
delivery.
The surgical hysterotomy incision does not heal
with complete repair of the myometrium; instead, a
thin fibrous scar is formed holding the myometrial
fibers together. Within the scar, no decidua is noted
leading to morbidly adherent placentas among
other complications. Molecules that enhance
endometrial receptivity during normal implantation,
such as b3 and leukemia-inhibitor factor (LIF),
have been shown to be overexpressed in the site of
abnormal implantation in a cesarean scar site when
compared with the remaining uterine cavity (36).
The placental implantation may occur in a dehis-
cent scar or a well-healed scar (37). When the
implantation occurs in a dehiscent scar, it has worst

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 PLACENTA IMPLANTATION

A B

Fig. 4. Cesarean hysterectomy: (A) Prominent vasculature bulging in the uterine serosa marking the area of the placenta
implantation in the low uterine segment (arrow). The right ovary and fallopian tube are noted on the right side. (B) Fun-
dal sutured hysterotomy on the posterior surface of the uterus. (C) Upon opening, the uterus reveals a placenta implanted
on the anterior wall; a hematoma is present overlying the cervix (arrow). Note the complete obliteration of the internal os.

prognosis, probably due to the thinning of the
myometrium noted in areas of a dehiscent scar
(37). Most often, when diagnosed in the first trime-
ster, cesarean scar pregnancies are treated with
methotrexate or dilation and curettage. Expectant
management is possible but it is usually associated
with increased incidence of hysterectomy due to
placental implantation abnormalities or uterine
rupture (38,39).
Morbidly adherent placenta
Definition
Morbidly adherent placenta is an umbrella term
encompassing similar entities with varying degree
of severity.
Placenta accreta: defined by the placenta attach-
ment onto the myometrium without intervening
decidualized endometrium (2, 20, 40, 41).
Placenta increta: there is placental invasion into
the thinned myometrium and absent decidua.
Placenta percreta: the placental invasion is total
extending through the myometrium to the uterine
serosa and sometimes into adjacent organs, most
frequently the bladder (2, 20, 40, 41).
Myometrial fibers adherent to the basal plate with-
out intervening decidua or “occult placenta accreta”:
Refers to the presence of myometrial fibers in the
basal plate without intervening decidua in the deliv-
ered placenta (Fig. 3). Invasive trophoblast is pre-
sent in varying numbers as is the basal Nitabuch
fibrinoid layer. These cases may represent a

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 DA CUNHA CASTRO & POPEK

subclinical form of adherent placenta; however,
they often have delayed placental delivery, manual
removal, or disruption. There is an increased risk
for development of clinical apparent placenta acc-
reta in a subsequent pregnancy (42).
Other histological findings which were signifi-
cantly more frequently seen in morbidly adherent
placentas when compared to controls include basal
chronic villitis, chronic lymphoplasmacytic inflam-
mation in the basal plate, villous agglutination,
remote retromembranous hemorrhage, subchorionic
intervillous thrombi (43, 44), and chorionic villi
extending into myometrial vascular spaces in post-
partum hysterectomies. Morbidly adherent placenta
is a frequent cause of postpartum hemorrhage,
delayed separation or retained placenta, which is
defined clinically as placenta expulsion at least
30 minutes after the delivery of the newborn (16, 45).
A multidisciplinary approach to patients diagnosed
with morbidly adherent placenta in the prenatal per-
iod is desirable and reduces the need for emergency
cesarean hysterectomy (16). Grossly, the hysterec-
tomy shows an enlarged, boggy uterus that when
opened reveals a placenta most often located in the
lower uterine segment (Fig. 4). Dilated tortuous ves-
sels are noted in the uterine serosa, marking the site
of placental implantation. These vessels are seen in
the MRI and are one of the features used in diagnos-
ing morbid adherent placenta (18). In some cases in
which there is total invasion of the myometrium (pla-
centa percreta) one can see the placental tissue pro-
truding through the uterine surface. Microscopically,
there is increased thinning of the myometrium
depending on the severity of the placental tissue
extension into the myometrium (Fig. 5). No or very
patchy decidualized endometrium is seen in between
the invasive trophoblast and the myometrium
(Fig. 5A) in placenta accreta. In most cases, Nita-
buch fibrinoid will be present as well as a variable
amount of invasive trophoblast. In placenta increta
(Fig. 5B), the amount of myometrium is minimal
and the scarce invasive extravillous trophoblasts are
noted extending into the myometrium. In placenta
percreta (Fig. 5C), no myometrium is noted and the
placenta tissue is onto the uterine serosa and some-
times invading adjacent organs, most frequently the
bladder. Trophoblast may be seen extending into the
serosal tissues, fibrinoid layer is minimal. When in
doubt, cytokeratin and vimentin immunohistochemi-
cal stains may be useful in distinguishing decidua
(vimentin positive) from invasive trophoblast (cytok-
eratin positive).

A B

C D

Fig. 5. Microscopic sections of hysterectomies for morbidly adherent placenta: (A) Placenta accreta: Placenta tissue is
noted in contact with the myometrium (arrow head) without intervening decidualized endometrium (H&E 9 100). (B) Pla-
centa increta: There is thinned myometrium (arrow head). Note the presence of villi herniated into vascular space (open
arrow). The small arrow at the bottom of the figure marks the uterine serosal ink (H&E 9100). (C) Placenta percreta: No
myometrial fibers are seen, only the uterine serosa is remaining. The small arrow at the bottom of the figure marks the
uterine serosal ink (H&E 9100). (D) Placenta percreta invading the bladder (arrow highlights bladder musculature). The
villi are devitalized (open arrow).

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 PLACENTA IMPLANTATION
CONCLUSION
The disorders of placental implantation group
include many entities which have in common a
decreased or absent decidualized endometrium
resulting in abnormal implantation and increased
placental adhesion. There is an increase in maternal
and fetal morbidity and mortality associated with
these entities and the treatment most often involves
a cesarean hysterectomy. A multidisciplinary
approach is the best way to reduce morbidity and
mortality.
REFERENCES
1. Norwitz ER. Defective implantation and placentation:
laying the blueprint for pregnancy complications.
Reprod Biomed Online 2006;13:591–9.
2. Vahanian SA, Vintzileos AM. Placental implantation
abnormalities: a modern approach. Curr Opin Obstet
Gynecol 2016;28:477–84.
3. Winship A, Cuman C, Rainczuk K, Dimitriadis E.
Fibulin-5 is upregulated in decidualized human
endometrial stromal cells and promotes primary
human extravillous trophoblast outgrowth. Placenta
2015;36:1405–11.
4. Takahashi H, Ohkuchi A, Kuwata T, Usui R, Baba
Y, Suzuki H, et al. Endogenous and exogenous miR-
520c-3p modulates CD44-mediated extravillous tro-
phoblast invasion. Placenta 2017;50:25–31.
5. Matsumoto H, Sato Y, Horie A, Suginami K, Tani
H, Hattori A, et al. CD9 suppresses human extravil-
lous trophoblast invasion. Placenta 2016;47:105–12.
6. Imakawa K, Bai R, Fujiwara H, Ideta A, Aoyagi Y,
Kusama K. Continuous model of conceptus implanta-
tion to the maternal endometrium. J Endocrinol
2017;233:R53–65.
7. Sharma S, Godbole G, Modi D. Decidual control of
trophoblast invasion. Am J Reprod Immunol
2016;75:341–50.
8. Goh WA, Zalud I. Placenta accreta: diagnosis, man-
agement and the molecular biology of the morbidly
adherent placenta. J Matern Fetal Neonatal Med
2016;29:1795–800.
9. Su HW, Yi YC, Tseng JJ, Chen WC, Chen YF, Kung
HF, et al. Maternal outcome after conservative man-
agement of abnormally invasive placenta. Taiwan J
Obstet Gynecol 2017;56:353–7.
10. Pekar-Zlotin M, Melcer Y, Levinsohn-Tavor O, Tov-
bin J, Vaknin Z, Maymon R. Cesarean scar pregnancy
and morbidly adherent placenta: different or similar?
Isr Med Assoc 2017;19:168–71.
11. Cheng KK, Lee MM. Rising incidence of morbidly
adherent placenta and its association with previous cae-
sarean section: a 15-year analysis in a tertiary hospital
in Hong Kong. Hong Kong Med J 2015;21:511–7.
12. Shamshirsaz AA, Fox KA, Erfani H, Clark SL, Sal-
manian B, Baker BW, et al. Multidisciplinary team
learning in the management of the morbidly adherent
placenta: outcome improvements over time. Am J
Obstet Gynecol 2017;216:612. e1-612.e5.
© 2018 APMIS. Published by John Wiley & Sons Ltd
13. Nur Azurah AG, Wan Zainol Z, Lim PS, Shafiee
MN, Kampan N, Mohsin WS, et al. Factors associ-
ated with placenta praevia in primigravidas and its
pregnancy outcome. Sci World J 2014;270:120.
14. Rombauts L, Motteram C, Berkowitz E, Fernando S.
Risk of placenta praevia is linked to endometrial
thickness in a retrospective cohort study of 4537 sin-
gleton assisted reproduction technology births. Hum
Reprod 2014;29:2787–93.
15. Heller DS. Placenta accreta and percreta. Surg Pathol
Clin 2013;6:181–97.
16. Shamshirsaz AA, Fox KA, Salmanian B, Diaz-Arras-
tia CR, Lee W, Baker BW, et al. Maternal morbidity
in patients with morbidly adherent placenta treated
with and without a standardized multidisciplinary
approach. Am J Obstet Gynecol 2015;212:218. e1-9.
17. Ayati S, Leila L, Pezeshkirad M, Seilanian Toosi F,
Nekooei S, Shakeri MT, et al. Accuracy of color
Doppler ultrasonography and magnetic resonance
imaging in diagnosis of placenta accreta: a survey of
82 cases. Int J Reprod Biomed 2017;15:225–30.
18. Chen X, Shan R, Zhao L, Song Q, Zuo C, Zhang X,
et al. Invasive placenta previa: placental bulge with
distorted uterine outline and uterine serosal hypervas-
cularity at 1.5T MRI – useful features for differentiat-
ing placenta percreta from placenta accreta. Eur
Radiol 2017;8:2.
19. Ishibashi H, Miyamoto M, Shinnmoto H, Murakami
W, Soyama H, Nakatsuka M, et al. Cervical varicosi-
ties may predict placenta accreta in posterior placenta
previa: a magnetic resonance imaging study. Arch
Gynecol Obstet 2017;296:731–6.
20. Jauniaux E, Collins S, Burton GJ. Placenta accreta
spectrum: pathophysiology and evidence-based anat-
omy for prenatal ultrasound imaging. Am J Obstet
Gynecol 2018;218:75–87.
21. Dashe JS. Toward consistent terminology of placental
location. Semin Perinatol 2013;37:375–9.
22. Zia S. Placental location and pregnancy outcome.
J Turkish German Gynecol Assoc 2013;14:190–3.
23. Heller HT, Mullen KM, Gordon RW, Reiss RE, Ben-
son CB. Outcomes of pregnancies with a low-lying
placenta diagnosed on second-trimester sonography.
J Ultrasound Med 2014;33:691–6.
24. Osmundson SS, Wong AE, Gerber SE. Second-trime-
ster placental location and postpartum hemorrhage.
J Ultrasound Med 2013;32:631–6.
25. Taga A, Sato Y, Sakae C, Satake Y, Emoto I, Mar-
uyama S, et al. Planned vaginal delivery versus
planned cesarean delivery in cases of low-lying pla-
centa. J Matern Fetal Neonatal Med 2017;30:618–22.
26. Faiz AS, Ananth CV. Etiology and risk factors for
placenta previa: an overview and meta-analysis of
observational studies. J Matern Fetal Neonatal Med
2003;13:175–90.
27. Furuta K, Tokunaga S, Furukawa S, Sameshima H.
Acute and massive bleeding from placenta previa and
infants’ brain damage. Early Hum Dev 2014;90:455–8.
28. Pivano A, Alessandrini M, Desbriere R, Agostini A,
Opinel P, d’Ercole C, et al. A score to predict the risk
of emergency caesarean delivery in women with
antepartum bleeding and placenta praevia. Eur J
Obstet Gynecol Reprod Biol 2015;195:173–6.
29. Strong TH Jr, Brar HS. Placenta previa in twin gesta-
tions. J Reprod Med 1989;34:415–6.
619
 DA CUNHA CASTRO & POPEK
30. Palacios-Jaraquemada JM. Caesarean section in cases
of placenta praevia and accreta. Best Pract Res Clin
Obstet Gynaecol 2013;27:221–32.
31. Allahdin S, Voigt S, Htwe TT. Management of pla-
centa praevia and accreta. J Obstet Gynaecol
2011;31:1–6.
32. Camuzcuoglu A, Vural M, Hilali NG, Incebiyik A,
Yuce HH, Kucuk A, et al. Surgical management of 58
patients with placenta praevia percreta. Wien Klin
Wochenschr 2016;128:360–6.
33. Okafori I, Ugwu EO, Obis N, Nwogu-Ikojo EE. Uter-
ine packing in the management of complete placenta
previa. Niger J Med 2014;23:321–4.
34. Kayem G, Keita H. Management of placenta previa
and accreta. J Gynecol Obstet Biol Reprod (Paris)
2014;43:1142–60.
35. Pande B, Shetty A. An audit to review the characteris-
tics and management of placenta praevia at Aberdeen
Maternity Hospital, 2009-2011. J Obstet Gynaecol
2014;34:403–6.
36. Qian ZD, Weng Y, Wang CF, Huang LL, Zhu XM.
Research on the expression of integrin b3 and leukae-
mia inhibitory factor in the decidua of women with
cesarean scar pregnancy. BMC Preg Childbirth
2017;17:84.
37. Kaelin AGTEN A, Cali G, Monteagudo A, Oviedo J,
Ramos J, Timor-Tritsch I. The clinical outcome of
cesarean scar pregnancies implanted “on the scar” ver-
sus “in the niche”. Am J Obstet Gynecol
2017;216:510. e1-510.e6.
620
38. Maheux-Lacroix S, Li F, Bujold E, Nesbitt-Hawes E,
Deans R, Abbott J. Cesarean Scar Pregnancies: a sys-
tematic review of treatment options. J Minim Invasive
Gynecol 2017;24:915–25.
39. Zhang H, Huang J, Wu X, Fan H, Li H, Gao T.
Clinical classification and treatment of cesarean scar
pregnancy. J Obstet Gynaecol Res 2017;43:653–61.
40. Jauniaux E, Collins SL, Jurkovic D, Burton GJ. Acc-
reta placentation: a systematic review of prenatal
ultrasound imaging and grading of villous invasive-
ness. Am J Obstet Gynecol 2016;215:712–21.
41. Cramer SF, Heller DS. Placenta accreta and placenta
increta: an approach to pathogenesis based on the tro-
phoblastic differentiation pathway. Pediatr Dev Pathol
2016;19:320–33.
42. Linn RL, Miller ES, Lim G, Ernst LM. Adherent
basal plate myometrial fibers in the delivered placenta
as a risk factor for development of subsequent pla-
centa accreta. Placenta 2015;36:1419–24.
43. Ernst LM, Linn RL, Minturn L, Miller ES. Placental
pathologic associations with morbidly adherent pla-
centa: potential insights into pathogenesis. Pediatr
Dev Pathol 2017;20:387–93.
44. Heller DS. Do placentas from hysterectomies per-
formed for placenta accreta show adherent muscle? J
Reprod Med 2012;57:459–60.
45. Greenbaum S, Wainstock T, Dukler D, Leron E, Erez
O. Underlying mechanisms of retained placenta: evi-
dence from a population based cohort study. Eur J
Obstet Gynecol Reprod Biol 2017;216:12–7.
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