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Diagnosing placental membrane hypoxic lesions increases the sensitivity of placental examination.

Placental pathologists play a critical role in explaining prenatal and peripartum injury by revealing morphologic findings that both support and extend the clinical findings. There are several hypoxic-ischemic placental lesions that need to be identified by pathology consultation. (1) Unfortunately, it is common for general surgical pathologists not to recognize placental lesions that may have clinical significance, (2) and failure to identify or interpret significant placental lesions are a major cause of failure to explain the etiology of severe injuries in newborns, (3,4) including cerebral palsy. (5) To the list of described villous hypoxic lesions, (1,6-9) 2 placental membrane hypoxic lesions have recently been added and correlated with pregnancy outcome, fetal condition, and other placental features. These 2 new lesions are laminar necrosis (LN), a band of coagulative necrosis present at the choriodecidual interface of the placental membranes, (10,11) and microscopic chorionic pseudocysts (MCPs), which are lakes filled with a homogeneous, granular, eosinophilic material, surrounded by migratory, extravillous trophoblasts of the chorionic layer of the placental membranes (12) (Figure 1). Laminar necrosis was observed in 27% of placentas from mothers with hypertensive disorders (preeclampsia or chronic hypertension) and was linked to other maternal, fetal, neonatal, and placental conditions known to be associated with perinatal hypoxia, and with hypoxia-inducible factor, apoptosis, and oxidative stress playing role in the pathomechanism of LN. (11,13,14) Recently, a lesion of leukocytoclastic necrosis of the decidua basalis, histologically similar to LN and similar to LN associated with preeclampsia, preterm birth, and decreased fetal growth, was described, but this lesion involved the maternal floor. (15) Microscopic chorionic pseudocysts are even more strongly associated with preeclampsia and diabetes mellitus, with their incidence almost mirroring the incidence of preeclampsia throughout gestation, peaking in the early third trimester. Microscopic chorionic pseudocysts are also associated statistically with other placental hypoxic lesions, particularly placental infarction, global hypoxic patterns of placental injury, and LN. (12)

As the practical importance of recognizing LN and MCP has never been compared with the well-known chorionic disc hypoxic lesions, particularly placental infarction and global hypoxic patterns of placental injury, this analysis is intended to retrospectively address this issue from a large database of placental material.

[FIGURE 1 OMITTED]

MATERIALS AND METHODS

This is a retrospective analysis based on consecutive examination of all placenta samples reported by the author from 3 institutions (University of Cincinnati Medical Center, Cincinnati, Ohio; Sheffield Children's National Health Service Trust, Western Bank, Sheffield, United Kingdom; and Canterbury Health Laboratories, Christchurch, New Zealand) on patients pregnant for more than 20 weeks during 1994-2007. Twenty-three selected clinical (maternal and fetal) and 32 gross and microscopic placental features were statistically compared among 4 groups of patients: 168 placentas had at least one hypoxic disc lesion (infarct or global hypoxia) and at least one membrane lesion (MCP or LN; group 1), 750 placentas with at least one hypoxic disc lesion but no hypoxic membrane lesion (group 2), 480 placentas with at least one hypoxic membrane lesion but no hypoxic disc lesion (group 3), and 3192 placentas without hypoxic villous or membrane lesions (group 4). The placentas were submitted for examination at the discretion of obstetricians because of a high-risk pregnancy, fetal distress, the poor condition of the neonate, or for the operative delivery or gross findings of abnormal placenta. Placental examination was performed according to generally accepted criteria; specifically, 2 sections of placental membrane rolls and at least 2 paracentral, full-thickness chorionic disc sections were routinely taken as a part of the placental examination if no gross lesions were identified. All grossly seen lesions were additionally sampled.

The samples were fixed in buffered formalin, followed by routine paraffin embedding, cutting, and staining with hematoxylineosin. (1,6,7,9,16) Only cases with at least 3 microscopic chorionic lakes in the membranes were reported as MCP in the placental diagnosis, and LN was reported only in cases in which the lesion involved at least 10% of membrane rolls. Only central or paracentral placental infarctions involving at least 5% of placental parenchyma were included. Specifically, a percentage of infarcted placental tissue was assessed based on gross examination of sliced placental discs. If microscopic placental examination also showed infarction of grossly uninvolved placental parenchyma, the initial percentage was adjusted upward based on the extent of the microscopically infarcted placenta. If placental microscopy confirmed the gross diagnosis of placental infarction and the grossly uninfarcted placenta was indeed free of infarction, the gross estimate was the final estimate. Global (diffuse) placental hypoxia (preuterine, uterine, or postuterine) was histologically diagnosed based on placental maturation (heterogenous or homogenous), excessive syncytial knotting (granular or smudgy chromatin), amount of the extracellular matrix of the chorionic villi (increased or decreased), density of the villous cytotrophoblastic cells (increased or decreased), density of Hofbauer cells (increased or decreased), and villous vascularity (increased or decreased branching of capillaries). Preuterine placental hypoxia features a homogenous placental maturation, increased granular syncytial knotting, decreased extracellular matrix of the chorionic villi, increased density of villous cytotrophoblastic cells, increased density of Hofbauer cells, and increased villous vascularity. Uterine hypoxia differs from preuterine hypoxia only by a heterogeneous, instead of a homogenous, placental maturity. Postuterine hypoxia features a homogenous placental maturity, increased smudgy syncytial knotting, increased extracellular matrix of the chorionic villi, and decreased villous cytotrophoblastic cells, Hofbauer cells, and villous vascularity (Figure 2). (7,8,17-20) Descriptive statistical analysis was performed; Yates [chi square] or single-factor analysis of variance, where appropriate.

[FIGURE 2 OMITTED]

RESULTS

Of the 4590 samples, 419 placentas (9%) showed LN, 183 (4%) showed MCP, and 46 (1%) showed both LN and MCP; 381 placentas (8%) showed villous infarction, 403 (9%) showed features of global placental hypoxia, and 134 (3%) showed both infarctions and features of global placental hypoxia. Placental hypoxic lesions, both membranous and parenchymal, frequently occurred together in same placenta. Altogether, 1398 placentas (30.5% of all placentas) showed histologic hypoxic lesions. Of those, at least one villous hypoxic lesion (infarct or global hypoxia) was seen in 918 placentas (65.7%), whereas 648 placentas (46.3%) showed at least one hypoxic membrane lesion (LN or MCP). Only 168 placentas (12% of placentas with hypoxic lesions) showed at least one villous and one membrane lesion (group 1).

Table 1 depicts maternal and fetal clinical conditions of the studied material. Several maternal clinical factors like preeclampsia (P < .001), chronic hypertension (P < .001), oligohydramnios (P = .02), abnormal cardiotocography (P < .001), induction of labor (P < .001), antepartum bleeding (P = .01), cesarean sections (P < .001), perinatal mortality (P = .05), and fetal growth restriction (P < .001) correlated with hypoxic placental lesions, were mostly in group 1 (hypoxic disc lesions coexisting with hypoxic membrane lesions). Premature rupture of membranes was significantly highest in group 4 (without placental hypoxic lesions). Not surprisingly, the incidence of intrauterine growth restriction was highest in group 1, and the lowest in group 4. Only hypoxic membrane with no chorionic disc lesions was seen in 15% of patients with preeclampsia, 11% with diabetes, and 12% with abnormal antepartum cardiotocography. Only two-thirds of the preeclampsia cases, the most notorious condition known to be associated with "placental insufficiency" and in utero hypoxia, were in groups 1 to 3 (placental hypoxic lesions). Moreover, two-thirds of the cases of perinatal mortality were not associated with morphologic features of placental hypoxia (group 4), where congenital malformations, premature rupture of membranes, and acute chorioamnionitis were most prevalent. Two other common causes of fetal perinatal mortality or morbidity, umbilical cord compromise and congenital anomalies, did not correlate with placental hypoxic lesions; in fact, the trend in this latter group was significantly the reverse.

The placentas (Table 2) tended to be smaller in group 1 (hypoxic disc lesions coexisting with hypoxic membrane lesions), and abnormal coiling of the umbilical cord was more frequent in groups 3 (hypoxic membrane lesions only) and 4 (no placental hypoxic lesions). Retroplacental hematomas were more common in groups 1 and 2 (hypoxic disc lesions), which is not surprising because of their known associations with placental infarctions and preeclampsia. Grossly seen chorionic cysts were most common in group 3. The most common microscopic placental lesion, acute chorioamnionitis, was most frequently observed in group 4, whereas there were no differences in villitis of unknown etiology among the studied groups. In summary, many placental lesions believed to be associated with placental hypoxia were seen more frequently in different constellations in groups 1 to 3. The uterine pattern of placental hypoxia was more commonly statistically significant in group 1, whereas a preuterine pattern was significant in group 2. Apart from intimal cushions, there were no statistically significant differences among the studied groups in the components of the thrombotic vasculopathy complex. Placental edema was more common in group 4.

COMMENT

Because of unsatisfactory sensitivity (fetal erythroblasts, Table 2) (21) and specificity (meconium, Tables 1 and 2) (22-24) of the placental signs of fetal hypoxia, usually only placental hypoxic lesions are instead diagnosed. (25) Placental oxygen consumption is 4 times higher than fetal oxygen consumption; therefore, the placenta organ is the first affected by hypoxic conditions, followed only later by fetal compromise, in some cases, which was proven in experimental studies for midgestation at least (18) and was confirmed by this study which shows that fetal erythroblastosis is less frequent than purely placental hypoxic lesions (Table 2). In addition, not all cases affected by conditions commonly complicated by placental hypoxia feature placental hypoxic lesions, thus decreasing their specificity. This is due, in part, to histologic placental hypoxic lesions taking at least 2 to 4 hours (1) to 4 days (Tenney-Parker change or infarction) (26) or to develop, with the frequency dependent on gestational age and patients with preterm preeclamptic placentas being more vulnerable. (27,28)

Even such time-honored lesions as placental infarctions have their limitations because they do not infrequently occur in placentas otherwise found to be normal and in otherwise healthy pregnancies, indicating a substantial placental reserve. To increase the specificity of placental infarction diagnoses, only those in the central or paracentral locations that occupy more than 5%, (9) 10%, (23) or 20% (27) of placental parenchyma are regarded as diagnostically significant, particularly if the noninfarcted placental parenchyma shows features of diffuse global hypoxia. In this analysis, the lower end of the spectrum (central or paracentral infarction of >5% of the placental parenchyma) was chosen as the threshold. The real significance of focal hypoxic lesions other than infarction, however, has not been well documented, and the diagnosis is not widely used. (6-9)

Despite identifying and validating several histologic indicators of global maternal hypoperfusion, (25) the features of preuterine, uterine, and postuterine patterns of hypoxic placental injury are probably even less reproducible than focal hypoxic placental lesions because they are largely influenced by determination of placental maturity, and both accelerated and delayed maturity are associated with abnormal pregnancy outcome and poor fetal condition. (29) However, the assessment of placental maturation shows significant interobserver variability (30) and the exact wording of diagnosis may differ significantly even among placental pathologists. We use the terms preuterine, uterine, and postuterine hypoxia, which are probably more adequate than preplacental, uteroplacental, and postplacental hypoxia because the former terms reflect more accurately the pathomechanisms of these types of placental injury than the latter terms do, in line with the original intention of those that introduced those latter terms. (19) In preuterine and uterine placental hypoxia, oxygen is decreased in the intervillous space, whereas in postuterine hypoxia, there is hyperoxemia in the intervillous space, all of which result in hypoxemia in fetal blood (Figure 3). (6,18,19,31-34)

[FIGURE 3 OMITTED]

Based on all the above considerations and because of unsatisfactory sensitivity and specificity of the known and time-honored placental hypoxic lesions, any additional information that can improve the accuracy of the placental consultation should be considered for implementation. Placental lesion multiplicity rather than a single lesion poses a greater risk for fetal growth restriction and neurologic impairment. (4,35) Consequently, this analysis was intended to prove the relevance and usefulness of MCP and LN, which are, as yet, relatively unknown to general pathologists, in diagnosing placental membrane hypoxic lesions. The 2 membrane lesions discussed are easy to appreciate during placental examination. The LN, which is membrane coagulative necrosis (infarction), is a hallmark of acute hypoxia, corresponding to the villous infarction of the chorionic disc. It is easily recognizable, despite concerns expressed by some authors, (13) who doubt whether this lesion can be reliably distinguished from membrane fibrin deposition. Paying attention to the presence of trophoblastic and/or decidual ghost cells, the 2 can be easily distinguished. Microscopic chorionic pseudocysts are also easily recognizable because they stand out clearly on microscopic examination, even on low-power magnification.

This analysis confirmed previous reports that both LN (11,13) and MCP (12) are significantly associated statistically with clinical conditions frequently complicated by placental hypoxia and other placental "hypoxic" lesions. Specifically, this study confirmed that placental membrane hypoxic lesions are strongly associated statistically with preeclampsia as well as all its grades (mild; severe; hemolysis, elevated liver enzymes, and low platelets; and eclampsia) and chronic hypertension were highest with coexisting infarction (group 1) and gradually decreased toward group 4, paralleling the trend for abnormal cardiotocography, cesarean section rates, and intrauterine growth restriction. When compared with each other, MCP were found to be associated more frequently than LN with preeclampsia, diabetes mellitus, caesarean section deliveries, marginate placentas, and fetal chorioamnionitis, whereas LN was associated more commonly with macerated and nonmacerated stillbirths, maternal chorioamnionitis, and deep membrane meconium penetration. (36) Both LN and MCP showed even stronger statistical associations with other placental hypoxic lesions than with maternal and fetal status and were particularly associated with decidual arteriolopathy, multinucleated giant cells in decidua basalis, and excessive amount of extravillous trophoblasts in the placental disc (Table 2), just as they are associated with increased amount of migratory trophoblasts in the membranes themselves. (37) Others also found increased amount of immature, proliferating extravillous trophoblasts in the maternal floor in preeclampsia cases. (38) When occurring with infarction, membrane hypoxic lesions were associated with features of global placental hypoxia (preuterine, uterine, and postuterine) in 75% of cases. Moreover, such placental lesions, showing histologic evidence of meconium staining and chorangiosis, were more common with membrane hypoxic lesions occurring without, rather than with, infarctions. On the other hand, of placental thrombotic lesions, only intimal cushioning of chorionic and stem veins was statistically more common with membrane lesions and only when hypoxic membrane lesions and infarctions were occurring together. Multiple luminal vascular abnormalities of chorionic villi, a lesion developing in placentas after fetal death, did not show correlation with placental hypoxic lesions, either villous or membranous, most likely because of the heterogeneous etiology of fetal death. Also, the placental hypoxic lesions did not positively correlate with inflammatory patterns of placental injury, such as acute chorioamnionitis, chronic villitis, or plasmacytic deciduitis, the first one being most common in group 4, with placental infections rarely associated with impaired placental function. (39)

In most placentas (two-thirds) received for examination, there were no histologic features of placental hypoxia either in the membranes or in the chorionic disc because other types of fetal or maternal pathology (malformations, inflammation, thrombophilia, umbilical cord compromise) were more common. In this material, two-thirds of cases of perinatal mortality were associated with congenital anomalies or acute chorioamnionitis but did not feature histologic signs of placental hypoxia. Clinical umbilical cord compromise and histologic fetal thrombotic vasculopathy did not show a correlation with placental hypoxic features either. Finally, it must be stressed again that that the numbers presented in Tables 1 and 2 are only valid if thresholds of 3% MCP, 10% LN, and 5% infarctions are adopted. With adoption of other thresholds, different sensitivities and specificities would have been obtained. As usual, raising the thresholds would increase the specificity of the lesions but would decrease their sensitivity. Thresholds of 5% to 20% in otherwise unremarkable placental parenchyma were adopted for placental infarctions by others. (9,23,27)

In summary, up to now, the placental membrane was a site looked at mainly for features of acute inflammation (chorioamnionitis), meconium, hemosiderin, amnion nodosum, and decidual arteriolopathy. However, being less well vascularized than the placental disc, the membranes are potentially more susceptible for acute hypoxia resulting in LN or a secretory trophoblastic response to chronic hypoxia (MCP). Recording these easily recognizable lesions would leave fewer cases affected by in utero hypoxia undiagnosed and would increase the sensitivity of placental consultation by about 15%. Consequently, findings of LN and MCP should be included in the diagnostic armamentarium of placental hypoxic lesions, not because they are better outcome predictors in general (although in 15% of cases they are), but because placental lesion multiplicity is a risk factor for fetal/neonatal morbidity, (35) having a cumulative negative effect on outcome. (15) Recognition of LN and MCP would add to the relevance and importance of placental consultation, believed to be a "diary of pregnancy."

References

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(2.) Sun CCJ, Revell VO, Belli AJ, Viscardi RM. Discrepancy in pathologic diagnosis of placental lesions. Arch Pathol Lab Med. 2002;126(6):706-709.

(3.) Kraus FT. Introduction: the importance of timely and complete placental and autopsy reports. Semin Diagn Pathol. 2007;24(1):1-4.

(4.) Kraus FT. Clinical syndromes with variable pathologic features. Semin Diagn Pathol. 2007;24(1):43-47.

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(14.) Stanek J, Heil J. Direct evidence of hypoxia by immunohistochemistry in placental membranes with laminar necrosis from patients with severe preeclampsia. Pediatr Dev Pathol. 2006;9(5):406.

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(16.) Langston C, Kaplan C, Macpherson T, et al. Practice guideline for examination of the placenta. Arch Pathol Lab Med. 1997;121(5):449-476.

(17.) Chen CP, Aplin JD. Placental extracellular matrix: gene expression, deposition by placental fibroblasts and the effect of oxygen. Placenta. 2003;24(4):316-325.

(18.) Kingdom J, Huppertz B, Seaward G, Kaufmann P. Development of the placental villous tree and its consequences for fetal growth. Eur J Obstet Gynecol Reprod Biol. 2000;92(1):35-43.

(19.) Kingdom JC, Kaufmann P. Oxygen and placental villous development: origins of fetal hypoxia. Placenta. 1997;18(8):613-621.

(20.) Stanek J, Eis AL, Myatt L. Nitrotyrosine immunostaining correlates with increased extracellular matrix: evidence of postplacental hypoxia. Placenta. 2001;22(suppl A):S56-S62.

(21.) Bryant C, Beall M, McPhaul L, Fortson W, Ross M. Do placental sections accurately reflect umbilical cord nucleated red blood cell and white blood cell differential counts? J Matern Fetal Neonatal Med. 2006;19(2):105-108.

(22.) Kaspar HG, Abu-Musa A, Hannoun A, et al. The placenta in meconium staining: lesions and early neonatal outcome. Clin Exp Obstet Gynecol. 2000;27(1):63-66.

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(26.) Wallenburg HCS, Hutchinson DL, Schuler HM, Stolte LAM, Janssens J. The pathogenesis of placental infarction, II: an experimental study in the rhesus monkey placenta. Am J Obstet Gynecol. 1973;116(6):841-846.

(27.) Kaplan CG. Fetal and maternal vascular lesions. Semin Diagn Pathol. 2007;24(1):14-22.

(28.) Moldenhauer JS, Stanek J, Warshak C, Khoury J, Sibai B. The frequency and severity of placental findings in women with preeclampsia are gestational age dependent. Am J Obstet Gynecol. 2003;189(4):1173-1177.

(29.) Gilbert Barness E, Debich-Spicer DE. Handbook of Pediatric Autopsy Pathology. Totowa, NJ: Humana Press;2005:117-144.

(30.) Khong TY, Staples A, Bendon RW, et al. Observer reliability in assessing placental maturity by histology. J Clin Pathol. 1995;48(5):420-423.

(31.) Espinoza J, Sebire NJ, McAuliffe F, Krampl E, Nicolaides KH. Placental villous morphology in relation to maternal hypoxia at high altitude. Placenta. 2001;22(6):606-608.

(32.) Kadyrov M, Schmitz C, Black S, Kaufmann P, Huppertz B. Pre-eclampsia and maternal anaemia display reduced apoptosis and opposite invasive phenotypes of extravillous trophoblast. Placenta. 2003;24(5):540-548.

(33.) Mutema G, Stanek J. Numerical criteria for the diagnosis of placental chorangiosis using CD34 immunostaining. Trophoblast Res. 1999;13(1):443-452.

(34.) Mutema G, Stanek J. Increased prevalence of chorangiosis in placentas from multiple gestation. Am J Clin Pathol. 1997;108(3):341.

(35.) Viscardi RM, Sun CC. Placental lesion multiplicity: risk factor for IUGR and neonatal cranial ultrasound abnormalities. Early Hum Dev. 2001;62(1):1-10.

(36.) Stanek J. Acute and chronic placental membrane hypoxic lesions. Virchows Arch. 2009;455(4):315-322.

(37.) Stanek J. Membrane microscopic chorionic pseudocysts are associated with increased amount of placental extravillous trophoblasts. Pathology. 2010; 42(2):125-130.

(38.) Redline RW, Patterson P. Pre-eclampsia is associated with an excess of proliferative immature intermediate trophoblast. Hum Pathol. 1995;26(6):594-600.

(39.) Redline RW. Infections and other inflammatory conditions. Semin Diagn Pathol. 2007;24(1):5-13.

Jerzy Stanek, MD, PhD

Accepted for publication October 7, 2009.

From the Division of Pathology and Laboratory Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.

The author has no relevant financial interest in the products or companies described in this article.

Presented in part at the 21st European Congress of Pathology, European Society of Pathology, Istanbul, Turkey, September 8-13, 2007.

Reprints: Jerzy Stanek, MD, PhD, Division of Pathology and Laboratory Medicine, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH 45229-3039 (e-mail: jerzy.stanek@ cchmc.org).
Table 1. Clinical Factors (a-e)

 Group 1 Group 2
 (n = 168) (n = 750)
Feature No. (%) No. (%)

Gestational age (wk) at
 delivery, average [+ or -]

SD 33.1 [+ or -] 4.7 33.3 [+ or -] 5.4
No or poor prenatal care 11 (6.6) 41 (5.5)
Pregnancy-induced hypertension 2 (1.2) 11 (4.7)
Preeclampsia 84 (51.2) 131 (18.9)
Mild 25 (14.9) 38 (25.3)
Severe 44 (26.2) 63 (8.4)
HELLP 13 (7.4) 23 (3.1)
Eclampsia 2 (1.2) 7 (0.9)
Chronic hypertension 10 (5.9) 45 (6.0)
Diabetes mellitus 9 (5.4) 53 (1.2)
Substance abuse 5 (3.0) 49 (6.5)
Premature rupture of membranes 8 (4.8) 79 (10.5)
Multiple gestations 9 (5.4) 69 (1.2)
Oligohydramnios 17 (10.1) 46 (6.1)
Antepartum bleeding 26 (15.5) 92 (12.3)
Abnormal cardiotocographic 36 (21.4) 142 (18.9)
 findings (f)
Meconium-stained amniotic fluid 9 (5.4) 35 (4.7)
Induction of labor 19 (11.3) 58 (7.7)
Umbilical cord compromise (g) 10 (5.9) 30 (4.0)
Cesarean section 76 (45.2) 277 (36.9)
Perinatal mortality 19 (11.3) 108 (14.4)
IUGR 37 (22.0) 93 (12.4)
Congenital anomalies 2 (1.2) 37 (4.9)

 Group 3 Group 4
 (n = 480) (n = 3192)
Feature No. (%) No. (%)

Gestational age (wk) at
 delivery, average [+ or -]

SD 34.7 [+ or -] 5.0 32.8 [+ or -] 6.3
No or poor prenatal care 17 (3.5) 160 (5.0)
Pregnancy-induced hypertension 8 (1.7) 22 (0.7)
Preeclampsia 60 (12.5) 101 (3.8)
Mild 22 (4.6) 46 (1.4)
Severe 31 (6.5) 38 (1.2)
HELLP 5 (1.0) 11 (0.3)
Eclampsia 2 (0.4) 6 (0.2)
Chronic hypertension 12 (2.5) 82 (2.6)
Diabetes mellitus 27 (5.6) 147 (4.6)
Substance abuse 18 (3.7) 156 (4.9)
Premature rupture of membranes 34 (7.1) 487 (15.3)
Multiple gestations 33 (6.9) 380 (11.9)
Oligohydramnios 18 (3.7) 168 (5.2)
Antepartum bleeding 47 (9.8) 296 (9.3)
Abnormal cardiotocographic 57 (11.9) 395 (12.4)
 findings (f)
Meconium-stained amniotic fluid 25 (5.2) 135 (4.2)
Induction of labor 39 (8.1) 141 (4.4)
Umbilical cord compromise (g) 15 (3.1) 151 (4.7)
Cesarean section 172 (35.8) 986 (30.9)
Perinatal mortality 44 (9.2) 425 (13.3)
IUGR 37 (7.7) 205 (6.4)
Congenital anomalies 31 (6.6) 233 (7.3)

Feature F or
 [chi square] (P
Gestational age (wk) at
 delivery, average [+ or -]

SD 14.1 (<.001)
No or poor prenatal care 2 7 (.45)
Pregnancy-induced hypertension 5.6 (.13)
Preeclampsia 587.4 (<.001)
Mild 122.7 (<.001)
Severe 330.9 (<.001)
HELLP 100.0 (<.001)
Eclampsia 8.7 (.03)
Chronic hypertension 25.4 (<.001)
Diabetes mellitus 7.2 (.06)
Substance abuse 5.9 (.12)
Premature rupture of membranes 40.6 (<.001)
Multiple gestations 17.7 (<.001)
Oligohydramnios 9.4 (.02)
Antepartum bleeding 10.8 (.01)
Abnormal cardiotocographic 38.0 (<.001)
 findings (f)
Meconium-stained amniotic fluid 1.0 (.80)
Induction of labor 28.9 (<.001)
Umbilical cord compromise (g) 3.0 (.39)
Cesarean section 23.9 (<.001)
Perinatal mortality 7.6 (.05)
IUGR 71.8 (<.001)
Congenital anomalies 12.7 (.005)

Abbreviations: HELLP, hemolysis, elevated liver enzymes, low
platelets; IUGR, intrauterine growth restriction.

(a) Group 1, placentas with at least 1 hypoxic disc lesion and at
least hypoxic membrane lesion.

(b) Group 2, placentas with at least 1 hypoxic disc lesion but no
hypoxic membrane lesions.

(c) Group 3, placentas with at least 1 hypoxic membrane lesion but
no hypoxic disc lesions.

(d) Group 4, placentas without hypoxic villous or membrane lesions.

(e) Descriptive statistics: F, 1-tailed Fisher exact test;
[chi square], Yates chi-square; P, probability.

(f) Abnormal findings on a nonstress test or a contraction stress
test or abnormal findings on an intrapartum cardiotocography
(prolonged bradycardia or prolonged tachycardia or decreased fetal
heart rate variability or late decelerations).

(g) Variable decelerations, encirclement, true knot, or prolapse.

Table 2. Placental Factors (a-e)

 Group 1 Group 2
 (n = 168) (n = 750)
Feature No. (%) No. (%)

Placental weight (g, 344.5 [+ or -] 153.6 368.4 [+ or -] 368.6
 average [+ or -] SD)
Abnormal coiling of
 umbilical cord, Total
 No. (No. hypocoiled,
 No. hypercoiled; %) 2 (0, 2; 1.2) 17 (2, 15; 2.3)
Battledore placenta 21 (12.5) 50 (6.7)
Velamentous insertion 1 (0.6) 12 (1.6)
 of umbilical cord
Other umbilical cord 11 (6.5) 50 (6.7)
 pathology (f)
Marginate or vallate 20 (11.9) 68 (9.1)
 placenta
Gross chorionic cysts 3 (1.8) 11 (1.5)
Succenturiate lobe 6 (3.6) 3 (0.4)
Acute chorioamnionitis 24 (14.3) 203 (27.1)
Chronic villitis of 14 (8.3) 51 (6.8)
 unknown etiology
Amnion nodosum 6 (3.6) 9 (1.2)
Hypertrophic decidual 79 (47.0) 200 (26.7)
 arteriolopathy
Atherosis of spiral 40 (23.8) 80 (10.7)
 arterioles
Nonmarginal infarction 92 (54.8) 423 (56.4)
 (>5% of placental
 disc)
Intervillous thrombus 29 (17.3) 81 (10.8)
 (thrombi)
Retroplacental hematoma 19 (11.3) 80 (10.7)
Perivillous fibrin
 deposition (>20% of 19 (11.3) 95 (12.7)
 placental disc)
Multinucleated
 trophoblastic giant 43 (25.6) 56 (7.5)
 cells in decidua
 basalis
Erythroblastosis of 16 (9.5) 43 (5.7)
 fetal blood
Excessive amount of 29 (17.3) 25 (3.3)
 extravillous
 trophoblasts
Meconium macrophages 38 (22.6) 215 (28.7)

Features of global 120 (71.4) 428 (57.1)
 hypoxia (Figure 3)
Preuterine 33 (27.5) 228 (53.3)
Uterine 59 (49.2) 122 (28.5)
Postuterine 28 (23.3) 78 (18.2)
Chorangiosis 29 (17.3) 126 (16.8)
Laminar necrosis of 110 (65.5) 0
 membranes
Microscopic chorionic 65 (38.7) 0
 cysts of membranes
Thrombi in fetal 5 (3.0) 20 (2.7)
 vessels
Clusters of avascular 5 (3.0) 31 (4.1)
 chorionic villi
Intimal cushions of 8 (4.8) 13 (1.7)
 stem or chorionic
 veins
Multiple luminal
 vascular 16 (9.5) 67 (8.9)
 abnormalities of
 chorionic villi
Edema 3 (1.8) 39 (5.2)

 Group 3 Group 4
 (n = 480) (n = 3192)
Feature No. (%) No. (%)

Placental weight (g, 401.8 [+ or -] 167.7 387.7 [+ or -] 191.3
 average [+ or -] SD)
Abnormal coiling of
 umbilical cord, Total
 No. (No. hypocoiled,
 No. hypercoiled; %) 19 (9, 10; 4.0) 58 (19, 39; 1.8)
Battledore placenta 48 (10.0) 278 (8.7)
Velamentous insertion 5 (1.0) 103 (3.2)
 of umbilical cord
Other umbilical cord 35 (7.3) 300 (9.4)
 pathology (f)
Marginate or vallate 59 (12.3) 274 (8.6)
 placenta
Gross chorionic cysts 23 (4.8) 75 (2.3)
Succenturiate lobe 10 (2.1) 73 (2.3)
Acute chorioamnionitis 120 (25.0) 1373 (43.0)
Chronic villitis of 45 (9.4) 233 (7.3)
 unknown etiology
Amnion nodosum 12 (2.5) 85 (2.7)
Hypertrophic decidual 89 (18.5) 316 (9.9)
 arteriolopath y
Atherosis of spiral 17 (3.5) 48 (1.5)
 arterioles
Nonmarginal infarction 0 0
 (>5% of placental
 disc)
Intervillous thrombus 43 (9.0) 257 (8.0)
 (thrombi)
Retroplacental hematoma 23 (4.8) 156 (4.9)
Perivillous fibrin
 deposition (>20% of 32 (6.7) 181 (5.7)
 placental disc)
Multinucleated
 trophoblastic giant 38 (7.9) 92 (2.9)
 cells in decidua
 basalis
Erythroblastosis of 18 (3.7) 75 (2.3)
 fetal blood
Excessive amount of 12 (2.5) 15 (0.5)
 extravillous
 trophoblasts
Meconium macrophages 181 (37.7) 853 (26.7)

Features of global 0 0
 hypoxia (Figure 3)
Preuterine 0 0
Uterine 0 0
Postuterine 0 0
Chorangiosis 97 (20.2) 379 (11.9)
Laminar necrosis of 356 (74.2) NA
 membranes
Microscopic chorionic 165 (34.3) NA
 cysts of membranes
Thrombi in fetal 9 (1.9) 96 (3.0)
 vessels
Clusters of avascular 17 (3.5) 100 (3.1)
 chorionic villi
Intimal cushions of 14 (2.9) 51 (1.6)
 stem or chorionic
 veins
Multiple luminal
 vascular 36 (7.5) 297 (9.3)

 abnormalities of
 chorionic villi
Edema 10 (2.1) 187 (5.9)

Feature F or
 [chi square] (P)

Placental weight (g, 6.2 (<.001)
 average [+ or -] SD)
Abnormal coiling of
 umbilical cord, Total
 No. (No. hypocoiled,
 No. hypercoiled; %) 8.7 (.03)
Battledore placenta 7.1 (.07)
Velamentous insertion 13.0 (.005)
 of umbilical cord
Other umbilical cord 7.3 (.06)
 pathology (f)
Marginate or vallate 7.7 (.05)
 placenta
Gross chorionic cysts 12.9 (.005)
Succenturiate lobe 11.6 (.009)
Acute chorioamnionitis 144.7 (<.001)
Chronic villitis of 3.1 (.37)
 unknown etiology
Amnion nodosum 5.4 (.14)
Hypertrophic decidual 282.4 (<.001)
 arteriolopathy
Atherosis of spiral 300.1 (<.001)
 arterioles
Nonmarginal infarction NA
 (>5% of placental
 disc)
Intervillous thrombus 19.3(<.001)
 (thrombi)
Retroplacental hematoma 43.1 (<.001)
Perivillous fibrin
 deposition (>20% of 47.9 (<.001)
 placental disc)
Multinucleated
 trophoblastic giant 192.9 (<.001)
 cells in decidua
 basalis
Erythroblastosis of 40.4 (<.001)
 fetal blood
Excessive amount of 264.9 (<.001)
 extravillous
 trophoblasts
Meconium macrophages 26.7 (<.001)

Features of global NA
 hypoxia (Figure 3)
Preuterine NA
Uterine NA
Postuterine NA
Chorangiosis 32.7 (<.001)
Laminar necrosis of NA
 membranes
Microscopic chorionic NA
 cysts of membranes
Thrombi in fetal 1.6 (.66)
 vessels
Clusters of avascular 1.6 (.66)
 chorionic villi
Intimal cushions of 9.6 (.02)
 stem or chorionic
 veins
Multiple luminal
 vascular 1.4 (.69)
 abnormalities of
 chorionic villi
Edema 14.8 (.002)

Abbreviation: NA, not applicable.

(a) Group 1, placentas with [greater than or equal to] 1 hypoxic disc
lesion and [greater than or equal to] 1 hypoxic membrane lesion.

(b) Group 2, placentas with [greater than or equal to] 1 hypoxic disc
lesion but no hypoxic membrane lesions.

(c) Group 3, placentas with [greater than or equal to] 1 hypoxic
membrane lesion but no hypoxic disc lesions.

(d) Group 4, placentas without hypoxic villous or membrane lesions.

(e) Descriptive statistics: F, 1-tailed Fisher exact test;
[chi square], Yates chi-square; P, probability.

(f) Other pathology includes umbilical cords that are too long, too
short, or too thin or that have strictures, massive edema, aneurysm,
varix, hematoma, vessels unprotected by Wharton jelly, chorda,
ulcers, barber pole funisitis, amniotic band, meconium toxicity, or
furcate insertion.
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Author:Stanek, Jerzy
Publication:Archives of Pathology & Laboratory Medicine
Date:Jul 1, 2010
Words:5554
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