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ISSN: 1476-7058 (print), 1476-4954 (electronic)

J Matern Fetal Neonatal Med, Early Online: 1–7


! 2015 Informa UK Ltd. DOI: 10.3109/14767058.2015.1023709

REVIEW ARTICLE

Placental calcifications: a clue for the identification of high-risk fetuses


in the low-risk pregnant population?
Salvatore Andrea Mastrolia1,2, Adi Yehuda Weintraub2, Yael Sciaky-Tamir2, Dan Tirosh2, Giuseppe Loverro1, and
Reli Hershkovitz2
1
Department of Obstetrics and Gynecology, Azienda Ospedaliera-Universitaria Policlinico di Bari, School of Medicine, University of Bari ‘‘Aldo Moro’’,
Bari, Italy, and 2US Unit, Department of Obstetrics and Gynecology, Soroka University Medical Center, Ben Gurion University of the Negev, Beer
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Sheva, Israel

Abstract Keywords

‘‘What does it mean, Doctor?’’ and ‘‘Is it going to affect my baby in some way?’’. Chorioamnionitis, Grannum grade,
placental histology, pregnancy
outcomes, ultrasound
Those are the most typical questions of pregnant women to obstetricians. Answering is
sometimes easier but placental calcification is not the case, since placental architecture and
disease are two different faces of the same coin and the association between them is not History
completely clear. Placenta can function properly, even in the presence of architectural Received 13 January 2015
alterations, without any fetal consequences. So, remains the question, when does a placental Revised 11 February 2015
For personal use only.

structural anomaly become a sign of increased attention to maternal conditions, fetal Accepted 24 February 2015
development and well-being? The present review will analyze these concepts, with emphasis Published online 19 March 2015
on placental calcification, its pathogenesis, and the state-of-the-art regarding the influence of
this finding on pregnancy outcomes among low-risk pregnant patients.

Introduction of disease of placental injury-associated pregnancy compli-


cations, affecting both the mother and the fetus/neonate. Since
The association between placental architecture and placental
strong parallels exist between placental development and
disease is not completely clear. Understanding the true
structure in mice and humans [2,3], the investigation of
clinical significance of placental calcifications on pregnancy
placental structure and function in mice is a useful tool for
and fetal well-being is a challenging issue for obstetricians.
this purpose.
Even in the presence of architectural alterations, the placenta
Following this principle, Akirav et al. [4] reported in 2005,
may function properly, without any fetal consequences [1].
for the first time, placental calcification deposits in a murine
Identifying the cases where placental structural abnormalities
model. In contrast, the presence of calcification deposits
should raise increased attention to maternal conditions, fetal
in human placentas has been known for more than half
development and well-being may be difficult at times.
a century [5].
The present review will examine these concepts, with
As in humans, placental calcifications in mice are
emphasis on placental calcifications, their pathogenesis, and the
composed of calcium hydroxyapatite crystals [6]. In the
state-of-the-art knowledge regarding the impact of these findings
above-mentioned study, highly echogenic deposits at the
on pregnancy outcomes among low-risk pregnant patients.
implantation site prior to chorio-allantoic placental develop-
Placental calcification: a crosslink between mouse ment were demonstrated [4]. This has not been described in
and human placenta and theories for calcium human pregnancy, most probably due to lack of targeted
crystals deposition ultrasound observations at such an early stage of develop-
ment. Moreover, as gestation advances, mouse placental
Understanding the relationship between placental structure
calcification deposits in the region near the fetal–maternal
and function is a key point in understanding the mechanisms
interface become more rarefied, probably dispersed following
the rapid growth of the chorio-allantoic placenta [4].
Address for correspondence: Salvatore Andrea Mastrolia, Department of The mechanism causing placental calcifications in early
Obstetrics and Gynecology, Azienda Ospedaliera-Universitaria gestation in the mouse is yet unknown. However some clues
Policlinico di Bari, School of Medicine, University of Bari represented by molecules, and structural similarities shared
‘‘Aldo Moro’’, Piazza Giulio Cesare 11, Bari 70123, Italy.
Tel: +390805593583. Fax: +390805592228. E-mail: mastroliasa@ between mouse and human calcified placentas, led to consider
gmail.com and discuss an overlapping of the three known pathways of
2 S. A. Mastrolia et al. J Matern Fetal Neonatal Med, Early Online: 1–7

calcification (physiological, dystrophic and metastatic calci- feto–placental perfusion (from day 9.5 of mouse gestation
fication) in these models [7–10]. [25]), then high concentrations of calcium may accumulate in
the area of the ectoplacental cone thereby inducing, in mice,
Physiological calcification metastatic calcifications at this site.
In humans, calcium is actively transported across the
In physiological calcification, as observed in teeth and bones,
placenta throughout gestation, making the fetus relatively
osteoblasts produce osteoid matrix providing hydroxyapatite
hypercalcemic [26,27]. This supports the growing fetal
formation in and on collagen fibers. This process, during the
skeleton and is mediated primarily by the fetal parathyroid-
embryonic period, is controlled by a group of molecules
related protein, which greatly increases its concentration
named bone morphogenic proteins (BPMs) that play an
throughout gestation, rather than the maternal parathyroid
important role in fetal development as well [9]. In mice, one
hormone [28]. Calcium binding proteins are thought to buffer
of these proteins, BMP7 (also known as osteogenic protein-1),
the process, preventing disruption of intracellular processes
is highly expressed, adjacent to the implantation site, in the
[29]. The hypothesis that aims to explain metastatic calcifi-
mesometrial region of the decidua, at 7.0–7.5 d gestation in
cations is based on the possibility that, a condition of
presence of extensive calcium deposition [4]. In humans,
abnormal fetal calcium utilization (as proposed in IUGR
BMP7 is expressed in placental cytotrophoblast cells in early
fetuses, showing delayed appearance of ossification sites [30])
pregnancy [7]. The same protein is capable of inducing
can lead to a passive placental diffusion of calcium back to
ectopic bone formation in vivo, in mice [11]. Also, other
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the maternal circulation. This may be creating a calcium-


proteins such as prostate-derived factor (PDF), placenta BMP
enriched environment that promotes the calcium and phos-
(PLAB), and insulin-like growth factor (INSL-4), which are
phate placental precipitation [10].
involved in embryogenesis as well as in bone and cartilage
formation, have been detected in the human placenta [12,13].
Since it is demonstrated that placenta becomes more calcified Mineral content of placental calcifications
as gestational age progresses [10,14,15], it has been Physiological and non-physiological calcifications may be
hypothesized that the expression of these proteins should distinguished by the calcium/phosphate (Ca/P) weight ratio,
increase during pregnancy. Nevertheless, in their study, Poggi which expresses the mineral content of a calcification.
et al. [10] observed that the expression of BMPs remains For example, the Ca/P weight ratio is greater in mature
relatively constant throughout gestation being INSL-4 the
For personal use only.

bone than in the less organized calcium deposits that are


only one showing an increased expression with advancing associated with metastatic calcifications. The physiological
gestational age. calcification process, in which osteoid mineralizes about 10 d
after its initial secretion, allows the crystal to be well
Dystrophic calcifications organized [31]. In contrast, in metastatic calcifications, a very
rapid mineralization results in a less organized and less
Dystrophic calcification occurs in the site of tissue necrosis,
mature mineral crystal.
where injured or dysfunctional cell membranes allow the
A ratio of 2.00 ± 0.05 is generally observed in human
intracellular passage of extracellular calcium which combines
placental calcifications, resembling the one observed in
with phosphate producing hydroxyapatite crystals [16].
human stones (uroliths, sialoliths) that results from a super-
During early mouse gestation, implantation triggers uterine
saturated environment. The very rapid crystallization that
epithelial cell apoptosis and trophoblast giant cells invade
occurs under these conditions results in less organized, porous
phagocyte epithelial and decidual cells [17,18]. Apoptosis and
small lamellar crystals with a lower Ca/P weight ratio. In
tissue damage caused by trophoblast invasion may conse-
contrast, bone and atherosclerotic lesions typically have Ca/P
quently induce dystrophic calcification [19].
weight ratios that approximate 2.15, the value for stoichio-
In late gestation, a progressive increase in placental
metrically ideal hydroxyapatite.
calcification in the labyrinth is observed in mice. The
The lower Ca/P ratios and porous, lamellar aggregates
labyrinth is the site of maternal–fetal exchange and is
observed in placental calcifications support a non-physio-
considered the murine equivalent of human chorionic villi [3].
logical mechanism of placental calcification that resembles a
It is possible that the normal increase in the calcification of
metastatic process. Ca/P weight ratios in dystrophic calcifi-
the labyrinth in mice and chorionic villi in humans is related
cations have been reported only in calcified necrotic breast
to the normal gestational increase in apoptosis of the
carcinoma [32]. Thus, since there is limited information
trophoblast and stromal tissues of the placenta [20–22],
regarding the mineral composition of dystrophic calcifica-
since apoptotic bodies concentrate calcium and appear to
tions, their involvement in placental structural anomaly
function as nucleating structures for calcium crystal deposits
requires further studies.
formation [19,23].

Diagnosis of placental calcifications


Metastatic calcification
Ultrasound
Metastatic calcification is associated with hydroxyapatite
deposits within unusual sites, arising from a supersaturated Ultrasonographic examination is considered the gold standard
environment in terms of calcium and phosphate concentra- for the diagnosis of placental calcifications due to the fact that
tions [16]. It has been proposed that if active trophoblast placental calcium deposition produces echogenic foci [6,33].
transport of calcium [24] starts before the establishment of the Grannum grading is the recognized sonographic method used
DOI: 10.3109/14767058.2015.1023709 Meaning of placental calcification in low-risk pregnancies 3
Figure 1. Grade 0 placenta showing easily
delineated, relatively straight chorionic plate
and homogeneous texture.
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Figure 2. Grade 1 placenta is characterized by


an undulatory chorionic plate and scattered
echogenic areas.
For personal use only.

to assess placental calcifications and maturity by ultrasound, calcification [35]. As a consequence, even if this system
and it was thought to represent a standard in the evaluation of is considered the gold standard for placental grading,
fetal health in late pregnancy [34]. It is a practical classifi- a Cochrane review recommended to perform future research
cation of placental maturity based on a review of multiple on placental textural assessment in late pregnancy [36].
ultrasound evaluations of placental texture over a 4-year
period. This classification grades placentas from 0 to 3
Correlation between ultrasonographic findings and
according to specific ultrasonic findings at the basal and
placental histology
chorionic plates as well as within the substance of the organ
itself [34]. Following this classification, a grade 0 placenta In most sonographic examinations, evaluation of the placenta
has an easily delineated, relatively straight chorionic plate and is confined only to identification of its site. Detailed
a homogeneous texture (Figure 1). A grade 1 placenta is assessment of placental architecture is performed mainly
characterized by an undulatory chorionic plate and scattered when maternal or fetal disease are suspected and definitive
echogenic areas (Figure 2). Grade 2 is recognized by the diagnosis of placental disease is generally obtained after
presence of small echogenic areas along the basal layer of the delivery, by pathological examination [37]. Unfortunately, the
placenta and comma-like echogenic densities that originate at correlation of antenatal detection of placental disease and
the chorionic plate (Figure 3). A grade 3 placenta is postnatal placental histology is limited. A recent report
characterized by echogenic indentations extending from the by Cooley et al. [37] has aimed to concentrate on such
chorionic plate to the basal layer dividing the placenta into an association. In that prospective study, 1011 low-risk
discrete components, resembling cotyledons (Figure 4). In primigravid patients were included. Placental sonographic
addition, irregular densities that cast acoustic shadows are characteristics were assessed at gestational age of 22–24 and
occasionally present near the chorionic plate. 34–36 weeks. Grannum grade was defined and placental
A shortcoming of the ultrasound is that, despite standar- calcifications were described at 34–36 weeks gestation. After
dized observational conditions, Grannum grading of the delivery, all placentas were evaluated by a clinical patholo-
placenta represents a subjective method to estimate placental gist. The presence of placental calcifications was associated,
4 S. A. Mastrolia et al. J Matern Fetal Neonatal Med, Early Online: 1–7

Figure 3. Grade 2 placenta is recognized by


the presence of small echogenic areas along
the basal layer of the placenta and comma-
like echogenic densities that originate at the
chorionic plate.
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Figure 4. A grade 3 placenta presenting


echogenic indentations extending from the
chorionic plate to the basal layer and dividing
the placenta into discrete components,
resembling cotyledons.
For personal use only.

with a significantly higher incidence of placental infarctions prospective study aiming to provide a quantitative, reprodu-
identified after pathological examination (80% versus 21.5%; cible grading system based on the assessment of placental
p ¼ 0.009: r ¼ 0.115). Of interest, chorioamnionitis occur- calcifications, starting from 2D ultrasound images. Their so-
rence was noted with the increase of Grannum grade [37]. called placentometer, is a software for digital placental
The association between antenatal sonographic diagnosis analysis that was employed on 90 patients, undergoing
of placental calcifications and histologic findings of placental ultrasound examination, to assess fetal biophysical profile at
infarcts raises the importance of the ultrasound on the impact 41 + 5 weeks’ of gestation. Placentas had already been
of impaired placental blood flow. Placental infarcts, resulting evaluated 7 d before and assigned a Grannum grade by the
from chronic vascular placental impairment, are common at same experienced fetal medicine specialist.
term but fetal and neonatal morbidity increases when more This study found a significant correlation between the
than 5% of the placental bed is involved or when the diameter percentage of calcification, defined with the software, and
of the infarcts is larger than 3 cm [1]. Indeed, the association Grannum grades, but had several limitations represented by
between placental infarcts, preeclampsia, and fetal acidosis (1) the small number of participants and (2) the gestational
has been outlined in previous studies [37,38]. The evidence age of the patients, since finding placental calcifications
reported herein suggests that the sonographic detection of before 36 weeks has been associated with bad obstetrical
placental calcifications is correlated with placental and outcomes and is of the highest interest [38].
pregnancy pathologies and this correlation emphasizes the
value of placental antenatal assessment. Placental calcification and pregnancy outcomes
Placental calcifications commonly increase with gestational
Computerized assessment
age, becoming typically apparent after 36 weeks of gestation
In order to increase the objectivity in the diagnosis of [40]. A Grade 3 placental calcification has been described
placental calcifications, Moran et al. [39] designed a in 39.4% of women at term [41], reaching a peak of 54% at
DOI: 10.3109/14767058.2015.1023709 Meaning of placental calcification in low-risk pregnancies 5

42 weeks [42]. Many textbooks define this finding to be of no and those with a diagnosis of hypertension, diabetes, anemia
clinical significance [43,44]. or placenta previa were excluded from the study. They found
Moreover, data about the association between placental a significant difference between the three groups, in
calcifications and adverse pregnancy outcome are controver- maternal outcomes (including postpartum hemorrhage,
sial. Several studies have focused on the association between maternal transfer to the intensive care unit, placental
placental calcifications detected before 36 weeks gestation abruption) and fetal outcomes (low birth weight, low
and pregnancy outcome, finding an increased incidence Apgar score, neonatal death). After performing a logistic
of intrauterine growth restriction [45–48], low birth weight regression to compare the differences in pregnancy out-
[45,46,48,49], low Apgar score [49], fetal distress [48] and comes among the groups, adjusted for confounders (maternal
pregnancy-induced hypertensive disorders [45,47,50]. In age, body mass index, economic status, marital status, mode
contrast, other studies did not find the same association of delivery, parity) the risks of adverse pregnancy outcomes
[51–53] and suggested that preterm placental calcifications were higher in the group with placental calcifications
have little value in switching the pregnancy label from low detected before 32 weeks than the control group (postpartum
risk to high risk or increasing the level of attention into hemorrhage, OR 3.43; 95% CI, 1.251–9.388; placental
an already high-risk patient. abruption OR 6.52; 95% CI, 1.356–31.382; maternal transfer
The shortcoming of the above-mentioned conclusions to the ICU OR, 9.76; 95% CI, 1.826–52.195; preterm birth
stands in the fact that the majority of studies have small OR, 4.20; 95% CI, 1.775–9.940; low birth weight OR 4.58;
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groups of participants and, in some of them, the effect of 95% CI, 2.201–9.522; low Apgar score OR 6.53;95% CI,
confounders like cigarette smoking, diabetes or hypertension 2.116–20.142; and neonatal death OR 9.04;95% CI, 1.722–
are not considered, increasing the risk for incorrect interpret- 47.411). No significant differences were found between
ation of the results. In addition, many different instruments patients with placental calcifications detected between 32
and study designs were used, drawing a confusing picture and 36 weeks and the control group.
from which extracting any conclusions or recommendations is The evidence presented herein suggests that isolated
hardly possible. In some cases, since they were performed placental calcifications can be associated, in an otherwise
many years ago, ultrasound equipment of poor resolution was low-risk pregnancy, to an increased risk of pregnancy
employed, making the results questionable. maternal complications with conflicting data regarding fetal/
Some more recent considerations have tried to clarify the neonatal outcomes. However, the most recent studies consider
For personal use only.

issue regarding the clinical meaning depicted by placental pregnancy maternal and fetal/neonatal outcomes only with
preterm calcification on pregnancy (maternal and fetal/ regard to Grannum Grade 3 calcifications and do not extend
neonatal) outcome. their analysis to the association between these conditions and
the other Grannum classification grades.
In light of the fact that the pathogenesis for the presence of
Placental calcification and pregnancy outcomes:
placental calcium crystals is not completely clear, an
recent evidences
approach exclusively based on the grading of calcium deposits
In 2005, McKenna et al. [41] studied prospectively 1802 low- is probably not justified.
risk patients at 36 weeks of gestation in order to (1) evaluate
the incidence of Grade 3 calcification using Grannum
Conclusion
classification and (2) investigate the association between a
Grannum Grade 3 placentas and pregnancy outcome. A challenge in modern obstetrics is to unmask high-risk
In their study, 3.8% (n ¼ 68) of patients have developed patients hidden within the low-risk pregnant population. The
Grade 3 placental calcifications at 36 weeks’ gestation. proper assessment of the association between placental
Among them, there was an increased risk for (1) induction of calcifications and pregnancy outcomes can be useful for the
labor due to signs of fetal compromise (RR 4.65; 2.57, 8.44; purpose.
p50.01); (2) delivery of low birth weight neonates below the Literature dealing with this topic is lacking and conflict-
10th percentile for weight at birth (RR 3.13; 1.81, 5.41; ing, but the reports regarding increased risk for adverse
p50.01); and (3) developing preeclampsia at term (RR 4.7; maternal and fetal/neonatal outcomes in presence of preterm
1.87, 11.83; p50.01). In addition, the finding of Grannum placental calcifications cannot be ignored. As a consequence,
Grade 3 placental calcifications was not associated, in this more attention should be paid to patients with preterm
study, with poor fetal/neonatal outcomes including the need placental calcifications and no risk factors for such a finding,
for neonatal resuscitation and admission to NICU [41]. even in pregnancies that are considered to be at low risk for
In another study, Chen et al. [54] evaluated prospectively developing complications.
a cohort of low-risk pregnancies in order to study the Further well-designed studies, with appropriate selection
significance of placental Grade 3 calcifications detected at of inclusion and exclusion criteria and the employment of
different gestational ages. Three groups were created: (1) adequate instrumental settings are needed to give more
patients with placental calcifications diagnosed before 32 convincing answers regarding the clinical significance of
weeks of gestation (n ¼ 63); (2) patients with placental placental calcifications and their impact on pregnancy. In
calcifications diagnosed between 32 and 36 weeks (n ¼ 192); addition, in order to improve the clinical interpretation of
and (3) a control group without placental calcifications placental disease, the task of a better correlation between
established between 28 and 36 weeks (n ¼ 521). Patients antenatal ultrasonographic and postnatal histopathologic
smoking cigarettes or drinking alcohol during pregnancy, placental evaluation should be addressed.
6 S. A. Mastrolia et al. J Matern Fetal Neonatal Med, Early Online: 1–7

Declaration of interest vascular calcification by apoptotic bodies. Circ Res 2000;87:


1055–62.
The authors declare no conflicts of interest. The authors alone 24. Lafond J, Goyer-O’Reilly I, Laramée M, Simoneau L. Hormonal
are responsible for the content and writng of this article. regulation and implication of cell signaling in calcium transfer by
placenta. Endocrine 2001;14:285–94.
25. Phoon CK, Aristizabal O, Turnbull DH. 40 MHz Doppler
References characterization of umbilical and dorsal aortic blood flow in the
early mouse embryo. Ultrasound Med Biol 2000;26:1275–83.
1. Fox H. The pathology of the placenta. Philadelphia (PA): WB 26. Husain SM, Mughal MZ. Mineral transport across the placenta.
Saunders; 1997. Arch Dis Child 1992;67:874–8.
2. Sapin V, Blanchon L, Serre AF, et al. Use of transgenic mice model 27. Pitkin RM. Calcium metabolism in pregnancy and the perinatal
for understanding the placentation: towards clinical applications in period: a review. Am J Obstet Gynecol 1985;151:99–109.
human obstetrical pathologies? Transgenic Res 2001;10:377–98. 28. Hosking DJ. Calcium homeostasis in pregnancy. Clin Endocrinol
3. Rossant J, Cross JC. Placental development: lessons from mouse (Oxf) 1996;45:1–6.
mutants. Nat Rev Genet 2001;2:538–48. 29. Tuan RS. Ca2+-binding protein of the human placenta.
4. Akirav C, Lu Y, Mu J, et al. Ultrasonic detection and developmental Characterization, immunohistochemical localization and func-
changes in calcification of the placenta during normal pregnancy in tional involvement in Ca2+ transport. Biochem J 1985;227:
mice. Placenta 2005;26:129–37. 317–26.
5. Frank M, Sodin-Semrl S, Rozman B, et al. Effects of low- 30. Zilianti M, Fernandez S, Azuaga A, et al. Ultrasound evaluation
molecular-weight heparin on adhesion and vesiculation of phospho- of the distal femoral epiphyseal ossification center as a screening
lipid membranes: a possible mechanism for the treatment of test for intrauterine growth retardation. Obstet Gynecol 1987;70:
J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by HINARI on 07/09/15

hypercoagulability in antiphospholipid syndrome. Ann N Y Acad 361–4.


Sci 2009;1173:874–86. 31. Skinner HC. Mineral composition of bone. In: Albright G, Brand R,
6. Varma VA, Kim KM. Placental calcification: ultrastructural and X- eds. The scientific basis of orthopedics. New York (NY): Appleton
ray microanalytic studies. Scan Electron Microsc 1985;(Pt 4): and Lange; 1988:1122–6.
1567–72. 32. Ortega-Pérez G, Pardo-Garcı́a R, Ramia-Angel JM, et al. Recurrent
7. Martinovic S, Latin V, Suchanek E, et al. Osteogenic protein-1 is infiltrating ductal carcinoma and dystrophic calcifications after
produced by human fetal trophoblasts in vivo and regulates the breast-conserving therapy. Breast J 2000;6:267–68.
synthesis of chorionic gonadotropin and progesterone by tropho- 33. Al-Zuhair AG, Ibrahim ME, Mughal S. Calcium deposition on the
blasts in vitro. Eur J Clin Chem Clin Biochem 1996;34:103–9. maternal surface of the human placenta: a scanning electron
8. Ying Y, Zhao GQ. Detection of multiple bone morphogenetic microscopic study. Arch Gynecol 1984;234:167–72.
protein messenger ribonucleic acids and their signal transducer, 34. Grannum PA, Berkowitz RL, Hobbins JC. The ultrasonic changes
Smad1, during mouse decidualization. Biol Reprod 2000;63: in the maturing placenta and their relation to fetal pulmonic
1781–6. maturity. Am J Obstet Gynecol 1979;133:915–22.
For personal use only.

9. Ducy P, Karsenty G. The family of bone morphogenetic proteins. 35. Moran M, Ryan J, Higgins M, et al. Poor agreement between
Kidney Int 2000;57:2207–14. operators on grading of the placenta. J Obstet Gynaecol 2011;31:
10. Poggi SH, Bostrom KI, Demer LL, et al. Placental calcification: 24–8.
a metastatic process? Placenta 2001;22:591–6. 36. Bricker L, Neilson JP, Dowswell T. Routine ultrasound in late
11. Franceschi RT, Wang D, Krebsbach PH, Rutherford RB. Gene pregnancy (after 24 weeks’ gestation). Cochrane Database Syst Rev
therapy for bone formation: in vitro and in vivo osteogenic activity 2008;(4):CD001451.
of an adenovirus expressing BMP7. J Cell Biochem 2000;78: 37. Cooley SM, Reidy FR, Mooney EE, McAuliffe FM. Antenatal
476–86. suspicion of ischemic placental disease and coexistence of maternal
12. Paralkar VM, Vail AL, Grasser WA, et al. Cloning and character- and fetal placental disease: analysis of over 500 cases. Am J Obstet
ization of a novel member of the transforming growth factor-beta/ Gynecol 2011;205:576.e1–6.
bone morphogenetic protein family. J Biol Chem 1998;273: 38. Cooley SM, Donnelly JC, Walsh T, et al. The impact of
13760–7. ultrasonographic placental architecture on antenatal course, labor
13. Laurent A, Rouillac C, Delezoide AL, et al. Insulin-like 4 (INSL4) and delivery in a low-risk primigravid population. J Matern Fetal
gene expression in human embryonic and trophoblastic tissues. Mol Neonatal Med 2011;24:493–7.
Reprod Dev 1998;51:123–9. 39. Moran M, Higgins M, Zombori G, et al. Computerized assessment
14. Haney AF, Trought WS. The sonolucent placenta in high-risk of placental calcification post-ultrasound: a novel software tool.
obstetrics. Obstet Gynecol 1980;55:38–41. Ultrasound Obstet Gynecol 2013;41:545–9.
15. Frank H, Kaufmann P. Nonvillous parts and trophoblast invasion. 40. Harris RD, Alexander RD. Ultrasound of the placenta and umbilical
In: Benirschke K, Kaufmann P, eds. Pathology of the human cord. In: Callen P, ed. Ultrasonography in obstetrics and gyne-
placenta. New York (NY): Springer-Verlag; 2000:171–2. cology. Philadelphia (PA): Saunders WB; 2000:602–4.
16. Anderson HC. Calcific diseases. A concept. Arch Pathol Lab Med 41. McKenna D, Tharmaratnam S, Mahsud S, Dornan J. Ultrasonic
1983;107:341–8. evidence of placental calcification at 36 weeks’ gestation:
17. Parr EL, Tung HN, Parr MB. Apoptosis as the mode of uterine maternal and fetal outcomes. Acta Obstet Gynecol Scand 2005;
epithelial cell death during embryo implantation in mice and rats. 84:7–10.
Biol Reprod 1987;36:211–25. 42. Moya F, Grannum P, Pinto K, et al. Ultrasound assessment of the
18. Bevilacqua EM, Abrahamsohn PA. Trophoblast invasion during postmature pregnancy. Obstet Gynecol 1985;65:319–22.
implantation of the mouse embryo. Arch Biol Med Exp (Santiago) 43. Spirt BA, Gorden LP. Sonography of the placenta. In: Fleischer AC,
1989;22:107–18. Manning FA, Jeanty P, Romero R, eds. Sonography in obstetrics
19. Kim KM. Apoptosis and calcification. Scanning Microsc 1995;9: and gynecology principles and practice. New York (NY): McGraw-
1137–75; discussion 75–8.
Hill; 2001:195–7.
20. Halperin R, Peller S, Rotschild M, et al. Placental apoptosis in 44. Nolan RL. The placenta, membranes, umbilical cord, and amniotic
normal and abnormal pregnancies. Gynecol Obstet Invest 2000;50:
fluid. In: Sauerbrei EE, Nguyen KT, Nolan RL, eds. A practical
84–7.
guide to ultrasound in obstetrics and gynecology. Philadelphia
21. Axt R, Meyberg R, Mink D, et al. Immunohistochemical detection
(PA): Lippincot-Raven; 1998:438–9.
of apoptosis in the human term and post-term placenta. Clin Exp
45. Baeza Valenzuela A, Garcı́a Méndez A. Premature aging of the
Obstet Gynecol 1999;26:56–9.
placenta. Ultrasonic diagnosis. Ginecol Obstet Mex 1995;63:
22. Mu J, Kanzaki T, Tomimatsu T, et al. Expression of apoptosis in
287–92.
placentae from mice lacking the prostaglandin F receptor. Placenta
46. Patterson RM, Hayashi RH, Cavazos D. Ultrasonographically
2002;23:215–23.
observed early placental maturation and perinatal outcome. Am J
23. Proudfoot D, Skepper JN, Hegyi L, et al. Apoptosis regulates
Obstet Gynecol 1983;147:773–7.
human vascular calcification in vitro: evidence for initiation of
DOI: 10.3109/14767058.2015.1023709 Meaning of placental calcification in low-risk pregnancies 7
47. Hills D, Irwin GA, Tuck S, Baim R. Distribution of placental grade 51. Hill LM, Breckle R, Ragozzino MW, et al. Grade 3 placentation:
in high-risk gravidas. AJR Am J Roentgenol 1984;143:1011–13. incidence and neonatal outcome. Obstet Gynecol 1983;61:728–32.
48. Chitlange SM, Hazari KT, Joshi JV, et al. Ultrasonographically 52. Vosmar MB, Jongsma HW, van Dongen PW. The value of
observed preterm grade III placenta and perinatal outcome. Int J ultrasonic placental grading: no correlation with intrauterine
Gynaecol Obstet 1990;31:325–8. growth retardation or with maternal smoking. J Perinat Med
49. Proud J, Grant AM. Third trimester placental grading by ultrason- 1989;17:137–43.
ography as a test of fetal wellbeing. Br Med J (Clin Res Ed) 1987; 53. Miller JM, Brown HL, Kissling GA, Gabert HA. The relationship
294:1641–4. of placental grade to fetal size and growth at term. Am J Perinatol
50. Kazzi GM, Gross TL, Rosen MG, Jaatoul-Kazzi NY. The 1988;5:19–21.
relationship of placental grade, fetal lung maturity, and neonatal 54. Chen KH, Chen LR, Lee YH. Exploring the relationship between
outcome in normal and complicated pregnancies. Am J Obstet preterm placental calcification and adverse maternal and fetal
Gynecol 1984;148:54–8. outcome. Ultrasound Obstet Gynecol 2011;37:328–34.
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