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Placental Pathology and Perinatal Outcomes
Introduction
The placenta is a remarkable transient organ that serves as the interface between maternal and fetal circulations. Systematic examination of the placenta provides critical insights into the causes of adverse perinatal outcomes, including stillbirth, preterm birth, fetal growth restriction, and neonatal encephalopathy.
Indications for Placental Examination
When to Submit
Maternal indications for placental submission include preeclampsia, eclampsia, HELLP syndrome, gestational diabetes, abruption, fever or chorioamnionitis, autoimmune disease, thrombophilia, and substance use. Fetal and neonatal indications include stillbirth, prematurity (less than 37 weeks), NICU admission, fetal growth restriction, hydrops fetalis, birth asphyxia or low Apgar scores, neonatal seizures, multiple gestation, and congenital anomalies. Placental indications include abnormal appearance, size that is small or large for gestational age, short cord, abnormal cord insertion, and masses or discoloration.
Gross Examination
Standard Protocol
The trimmed placenta (membranes and cord removed) is weighed and compared to gestational age-specific norms. The disc is assessed for shape (round, oval, bilobed, succenturiate lobe), dimensions, and completeness. The fetal surface is evaluated for color, translucency, subchorionic fibrin, and vessels (noting any thrombosis or true knots). The maternal surface is inspected for completeness of cotyledons, adherent blood clot (suggesting possible abruption), infarcts (firm, pale areas), and calcifications. The umbilical cord is measured for length (normal approximately 55-60 cm at term), diameter, number of vessels (two arteries, one vein; single umbilical artery occurs in approximately 1% of cases), insertion site, true knots, and coiling index. The membranes are assessed for color (green suggests meconium, opaque suggests infection), insertion at the disc margin, and completeness.
Cord Insertion Abnormalities
Marginal insertion occurs within 2 cm of the disc edge and is usually benign. Velamentous insertion describes vessels that traverse the membranes before reaching the disc, carrying a risk of vasa previa and vessel rupture. Furcate insertion involves vessels separating before reaching the chorionic plate, which results in increased fragility.
Histologic Examination
Sampling Protocol
A minimum of 2 full-thickness sections of grossly normal parenchyma should be taken. All gross lesions, including infarcts, masses, and areas of discoloration, are sectioned. The umbilical cord is sampled with two sections: one near the insertion and one distally. The membrane roll is prepared by rolling from the rupture site toward the disc margin and sectioning en face. Additional sections are taken as indicated by clinical or gross findings.
Major Pathologic Findings
Maternal Vascular Malperfusion (MVM)
Previously termed "uteroplacental insufficiency" or "maternal vascular underperfusion," MVM is associated with preeclampsia, fetal growth restriction, stillbirth, and placental abruption. Grossly, the placenta is small with infarcts exceeding 5% of the disc and retroplacental hemorrhage. Histologically, the findings include accelerated villous maturation, distal villous hypoplasia, increased syncytial knots, fibrinoid necrosis of decidual vessels (acute atherosis), and mural hypertrophy of decidual arterioles. These changes reflect failed or inadequate spiral artery remodeling by extravillous trophoblast.
Fetal Vascular Malperfusion (FVM)
FVM results from obstruction or reduction of blood flow within the fetal vasculature. It is associated with cord abnormalities such as hypercoiling, true knots, and compression, as well as thrombophilia and fetal cardiac dysfunction. Histologic features include avascular villi (fibrotic, sclerotic villi devoid of capillaries), thrombosis of fetal stem vessels, intimal fibrin cushions, and villous stromal-vascular karyorrhexis. The pattern may be global or segmental, with segmental patterns associated with stem vessel thrombi.
Acute Chorioamnionitis
Acute chorioamnionitis is an ascending infection from the lower genital tract and is the most common cause of preterm premature rupture of membranes and preterm labor. The maternal inflammatory response consists of neutrophils in the chorion and amnion (subchorionitis, chorionitis, chorioamnionitis). The fetal inflammatory response involves neutrophils in the umbilical cord vessels (funisitis, chorionic vasculitis). Staging and grading follow the Amsterdam criteria: stage 1 (early) and stage 2 (advanced); grade 1 (mild) and grade 2 (severe/necrotizing).
| Placental Lesion | Key Histologic Features | Clinical Association | |
|---|---|---|---|
| Maternal vascular malperfusion | Accelerated maturation, distal villous hypoplasia, decidual arteriopathy | Preeclampsia, FGR, abruption | |
| Fetal vascular malperfusion | Avascular villi, stem vessel thrombosis | Cord abnormalities, thrombophilia | |
| Acute chorioamnionitis | Neutrophils in chorion/amnion ± funisitis | Preterm labor, PPROM, neonatal sepsis | |
| Chronic villitis (VUE) | Lymphohistiocytic inflammation of villi | FGR, recurrence risk | |
| Massive perivillous fibrin | Fibrinoid encasing >30% villi | Severe FGR, stillbirth, recurrence | Common organisms include Group B Streptococcus, E. coli, Ureaplasma, and Mycoplasma, and cultures and GBS status should be correlated with histologic findings. |
Chronic Inflammatory Lesions
Chronic villitis (villitis of unknown etiology, or VUE) is a lymphohistiocytic inflammation of villi associated with fetal growth restriction that tends to recur in subsequent pregnancies. Chronic chorioamnionitis is a lymphocytic and histiocytic infiltrate in the chorion associated with preterm birth. Chronic deciduitis, characterized by plasma cells in the decidua, may be physiologic or pathologic depending on extent. It is important to distinguish VUE from infectious villitis caused by CMV, toxoplasmosis, syphilis, or parvovirus B19.
Massive Perivillous Fibrin Deposition and Maternal Floor Infarction
Massive perivillous fibrin deposition (MPFD) involves extensive fibrinoid material encasing more than 30% of villi. Maternal floor infarction (MFI) is a similar process concentrated at the basal plate. Both are associated with severe fetal growth restriction, stillbirth, and recurrence in subsequent pregnancies, and may be related to complement dysregulation or antiphospholipid antibodies. Histologically, villi are entrapped in dense eosinophilic fibrinoid material with trophoblast attenuation.
Placental Findings in Specific Clinical Scenarios
Stillbirth
Placental pathology identifies a cause or contributing factor in 60-70% of stillbirths. Key findings include cord accident (true knot, hypercoiling), massive abruption, fetal vascular malperfusion, severe MVM, infection, and fetomaternal hemorrhage. A systematic approach is essential, encompassing gross examination, histology, clinical-pathologic correlation, and ancillary testing including cultures and karyotype.
Neonatal Encephalopathy
Placental examination contributes to understanding the timing and etiology of brain injury. Sentinel events such as acute abruption, cord prolapse, and uterine rupture may be identified. Chronic pathology including severe MVM, FVM, and chronic villitis suggests chronic in utero compromise. Acute chorioamnionitis with a fetal inflammatory response is associated with neonatal brain injury.
Gestational Trophoblastic Disease
A complete hydatidiform mole shows diffuse villous swelling, trophoblast hyperplasia, and no fetal tissue; it is diploid and androgenetic (46,XX or 46,XY). A partial hydatidiform mole shows focal villous swelling, scalloped villi, focal trophoblast hyperplasia, and fetal tissue is present; it is triploid (69,XXX/XXY/XYY). The distinction is important for surveillance of post-molar gestational trophoblastic neoplasia (persistent elevated hCG).
Clinical Pearls
Maternal vascular malperfusion reflects failed spiral artery remodeling and is the pathologic substrate of preeclampsia, fetal growth restriction, and placental abruption. The Amsterdam Placental Pathology criteria provide a standardized nomenclature for inflammatory, vascular, and other placental lesions that facilitates consistent diagnosis and clinical correlation. Placental examination should be performed in all cases of stillbirth, as pathologic findings identify a cause or contributing factor in the majority of cases. Villitis of unknown etiology (VUE) is a chronic inflammatory process that tends to recur in subsequent pregnancies and is associated with fetal growth restriction.
References
- Khong TY, et al. Sampling and definitions of placental lesions: Amsterdam Placental Workshop Group consensus statement. Arch Pathol Lab Med. 2016;140(7):698-713.
- Redline RW. Classification of placental lesions. Am J Obstet Gynecol. 2015;213(4 Suppl):S21-S28.
- Pinar H, et al. Placental findings in singleton stillbirths. Obstet Gynecol. 2014;123(2 Pt 1):325-336.
- Ernst LM. Placental Pathology (Surgical Pathology Clinics). Elsevier; 2022.