. 2004 Aug;57(8):785–792. doi: 10.1136/jcp.2003.014217

Table 1.

The clinical relevance of placental abnormalities

Disorder	Clinicopathological correlation
Umbilical cord
Short cord (less than 40 cm)	High fetal and neonatal mortality rates and increased frequency of neurological abnormality
Long cord (longer than 70 cm)¹⁹	Maternal factors: systemic diseases, delivery complications, increased maternal age Fetal factors: non-reassuring fetal status, respiratory distress, vertex presentation, cord entanglement, male sex, increased birth weight Gross placental features: increased placental weight, overcoiled cord, true knots, congestion, cord prolapse causing fetal distress
Marginal cord insertion	IUGR, still birth, neonatal death, premature birth, low birth weight
Velamentous insertion	Fetal haemorrhage, fetal death, low birth weight, premature birth, maternal smoking, advanced maternal age
Overcoiling or undercoiling of the cord^9,¹⁰	Fetal demise fetal intolerance to labour, IUGR, chorioamnionitis
True knot	If tight, associated with perinatal mortality of 10% and umbilical vessel thrombosis
Single umbilical artery^20,²¹	Single umbilical artery is associated with fetal malformation chromosome aberration in 25–50%, with IUGR and increased perinatal mortality in normally formed infants
Thrombosis of umbilical cord vessels^12,^13,^22,²³	Thromboembolic spread to placental or fetal vessels. The consequences of cord vessel thrombosis for the fetus may be wide. Severe sequelae such as fetal death, cerebral palsy and IUGR have been described, but delivery of a healthy, live neonate may also occur
Umbilical cord vessel vasculitis and funisitis¹²	Umbilical cord vessel vasculitis and funisitis are associated with cord vessel thrombosis, preterm delivery, amniotic infection, vasospasm of cord vessels
Necrotising funisitis^12,^13,^24,²⁵	It is often associated with premature rupture of the membranes, preterm labour, IUGR, intrauterine death. Usually seen with acute chorioamnionitis. Candida, streptococci, herpes, and syphilis are reported to play a role in the pathogenesis of necrotising funisitis. Mostly associated with chorioamnionitis NOS
Membranes
Acute chorioamnionitis (including “subchorial intervillositis”)^26–³⁴	Strong association with premature rupture of membranes and preterm delivery. Fetal intrauterine infection may occur. Maternal fever and tachycardia are described, but may be asymptotic. Recently, chorioamnionitis has been implicated as a risk factor for periventricular leucomalacia and cerebral palsy
Chronic chorioamnionitis^12,^13,³⁵	Association with premature rupture of membranes, preterm delivery, and prolonged rupture of membranes has been observed. It has been described in herpes virus infection
Amnion epithelial vacuolisation^12,^13,³⁶	Cell degeneration and necrosis of amniotic epithelial cells can be seen in normal and abnormal pregnancies and the evaluation of these alterations might be fairly uncertain because of artefact effects. Small, lipid containing vacuoles in the cytoplasm are the feature, strongly associated with gastroschisis
Pigmented macrophages, meconium staining^12,^13,^32,³⁷	The presence of meconium staining is not necessarily associated with adverse fetal outcome. Meconium staining indicates the danger of meconium aspiration and with other histological signs of fetal distress may underline the diagnosis. Vasospasm of cord vessels and fetal chorionic vessels is reported as a consequence of meconium exposure
Deciduitis, acute deciduitis, chronic decidual necrosis¹³	Acute deciduitis in the decidua capsularis is often associated with ascending infiltrations of the placental membranes, and may be unimportant in isolation. Severe, necrotising, acute deciduitis can be found in placentas with retroplacental haematoma. Chronic deciduitis with scattered infiltration may represent a physiological condition of maternal lymphocyte response
Placenta
Low placental weight, below 10th centile for gestational age^38–⁴⁰	IUGR, pre-eclampsia, increased intervillous fibrin deposition, villitis of unknown origin, and trisomy
High placental weight ^38,³⁹	Maternal diabetes mellitus, maternal or fetal anaemia, fetal hydrops; may also be seen in congenital syphilis, Beckwith-Wiedemann syndrome, congenital nephrotic syndrome
Thin placenta (placenta annulare or placenta membranacea)^38,^41,⁴²	Average thickness less than 2 cm, placenta with large membranous area. Risk of maternal bleeding, placenta praevia, placenta accreta. Often premature delivery occurs. Possibly more frequent in IUGR
Placental haemorrhage
Retroplacental haematoma^12,¹³	Large retroplacental haematomas can cause extensive infarction involving a sufficient proportion of the villous tissue to cause fetal hypoxia or lead to perinatal death. Early separation is called abruptio placentae, and can be lethal if extensive. The AFP concentration may be raised if an old haematoma
Subchorionic haematoma (massive subchorial thrombosis, Breus’s mole)^12,¹³	This is a normal finding when patchy, focal, or diffuse. However, subchorionic thromboses of large size have been reported in association with abortion, premature delivery, and live-born infants also
Placenta praevia	Associated with high risk of third trimester bleeding
Placenta accreta, increta, and percreta	Potentially life threatening clinical conditions, causing uterine rupture and massive postpartum haemorrhage, or leading to caesarean section if prenatally diagnosed. It is often an indication of postpartum hysterectomy because of excessive bleeding. To make the pathological diagnosis of a placenta accreta, examination of the entire uterus is necessary
Placental chorionic villi and intervillous space abnormalities
Syncytial knots^12,¹³	Increased numbers of syncytial knots occur in: pre-eclampsia, hypertension, diabetes mellitus, maternal anaemia, pregnancy at high altitude, thick section (artefact). A correlation between increased syncytial knotting and fetal hypoxia has not been reported. An excessive increase of syncytial knotting may result from reduced fetal perfusion and placental hypoxia or can be the sign of accelerated maturation if the duration of pregnancy was less than 40 weeks
Infarct (acute or old)¹³	No clinical relevance if it is single, marginal, and/or involves less than about 5% of the villous tissue
Extensive placental infarction^12,^13,^31,⁴³	Involving more than 10% of villous tissue: fetal hypoxia, IUGR, stillbirth, pregnancy induced hypertension, abruptio placentae, neurological abnormalities
Nucleated RBC¹³	Raised numbers may occur in many causes of chronic hypoxia, IUGR, stillbirth, acute fetal blood loss, maternal diabetes, and erythroblastosis fetalis
Villous basal membrane thickening¹²	Pre-eclampsia, essential hypertension, diabetes mellitus
VSM deficiency^12,¹³	An increase of VSM is described in pregnancies at high altitude, pre-eclampsia, maternal heart failure, and maternal anaemia. VSM deficiency was reported in pre-eclampsia, materno–fetal rhesus incompatibility, maternal diabetes, low birth weight and stillbirths
Villous stromal fibrosis and sclerosis^12,¹³	Extensive stromal fibrosis occurs in terminal villous deficiency, in IUGR, and in avascular villi as a result of stem vessel thrombosis, and in CMV infection
Villous oedema^12,^13,³¹	Placentas from pregnancies with hydrops fetalis may show a combination of immaturity and oedema. Villous oedema occurs in infections (syphilis, CMV, toxoplasma), in cases of fetal hydrops, and in hydatidiform moles. It is correlated with neurological impairment and cerebral palsy. May be normal if focal
Dysmaturity/immaturity^12,⁴⁴	A failure of villous maturation was found to be associated with fetal hypoxia, IUGR, maternal diabetes, and materno–fetal rhesus incompatibility. Failure of maturation can lead to intrauterine death
Advanced maturation/maturitas praecox^12,¹³	Accelerated maturation can be seen in prematurely delivered placentas in pre-eclampsia. It is considered to be an ischaemic feature
Mesenchymal dysplasia^45,⁴⁶	Associated with Beckwith-Wiedeman syndrome
Perivillous fibrin³², extensive perivillous fibrin deposition	When more than 20–30% of the villous tissue and functional placenta is involved it is associated with IUGR and fetal death. In these cases often 70–80% of the villous population is enveloped by fibrin. The maternal serum AFP values is raised, sometimes extremely so
Maternal floor infarct^12,^13,^39,⁴⁷, Gitter infarct	Massive basal plate perivillous fibrin deposition is termed “maternal floor infarct” and is associated with high mortality and IUGR. Massive perivillous fibrin deposition in a netlike pattern is the “Gitter infarct”. Neither of these is an infarct. Massive perivillous fibrin can recur (18%) and is associated with IUGR and fetal death
Villitis
Acute villitis^12,¹³	Clinical consequences depend on the type of the pathogenic agent. Acute villitis is usually associated with severe maternal infection, preterm delivery and might lead to intrauterine infection and IUD
Chronic villitis: basal, parenchymal, granulomatous, and VUE^12,^13,³²	Chronic villitis: more often of unknown aetiology (VUE) than known. Fetal infections causing chronic villitis: CMV, toxoplasma, connatal syphilis. Chronic villitis is associated with: IUGR and/or stillbirth
	VUE: IUGR, preterm birth, is often recurrent!
Chronic histiocytic intervillositis, (chronic perivillositis)^48–⁵⁰	Associated with raised maternal serum AFP, recurrent abortion, IUGR, preterm delivery. Malaria infection should be excluded
Abnormalities of the fetal vessels
Fetal chorionic vessel thrombosis and avascular villi; stem vessel thrombosis (single/or multiple); recanalisation of chorionic vessels^8,^31,^32,^51,⁵²	Extensive avascular villi as a result of fetal vessel thrombosis was reported in association with stillbirth, IUGR, maternal and fetal coagulopathy, and fetal thromboembolic disease leading to cerebral palsy
Intimal fibrin cushion^37,⁵³	Neonatal asphyxia, association with disseminated capillary thrombi of fetal vessels. The severity of the fetal consequences depends more on the accompanying vascular lesions, mainly on fetal vessel thrombosis
HEV and haemorrhagic villitis^12,^13,^54–⁵⁶	HEV was reported to be a postmortem artefact and was doubted as being a specific disease entity. HEV was found to be associated with meconium staining and postmaturity. Earlier reports revealed an association with stillbirth, IUGR, neurological disability, maternal hypertension. Can occur in live births, associated with perinatal complications, fetal distress, IUGR. Interlesional relations exist between thrombotic, chronic inflammatory, and chronic vaso-occlusive lesions
Chorangiosis^13,^57,⁵⁸	Perinatal death, congenital malformation, and cerebral palsy were found to be associated with chorangiosis as a response to low grade tissue hypoxia. Although others have supported this observation, it is still unclear how chronic hypoxia results in increased vascularisation. The importance of this alteration needs further investigation
Abnormalities of the maternal vessels¹³
Failure of physiological adaptation of maternal vessels, uteroplacental vessel fibrinoid necrosis,¹² acute atherosis, uteroplacental vessel thrombosis⁵⁹	Uteroplacental or decidual arteriopathy is closely related to pregnancy induced hypertension, maternal essential hypertension, and pre-eclampsia, and results in fetal complications such as IUGR, SGA, and stillbirth. It is associated with APA, SLE, and thrombophilia
Haemorrhages of the placenta
Intervillous haemorrhage and intervillous thrombus	Most often intervillous haemorrhage is related to a maternal vessel lesion and is of maternal origin. Its consequence can be fetal compromise or death depending on the functional placenta parenchyma loss and the rest of the unaffected placenta
Kline’s haemorrhage^12,¹³	In some cases, intervillous haemorrhage and thrombus is a sign of fetal bleeding into the maternal circulation, as described by Kline. Only a few of these alterations lead to a large amount of fetal blood loss and stillbirth or severe anaemia followed by ischaemic lesions of parenchymal organs
Twin placenta, chorionicity	It is important to know the type of twinning because the twin-to-twin transfusion syndrome is associated with diamniotic monochorionic placentas
Angiomas
Angioma of the placenta (chorangioma)^12,^13,⁵⁸	Large lesions often lead to cardiac failure, hydrops, and death of the fetus. Transplacental bleeding and fetomaternal transfusion have been also described, leading to anaemia. Chorangioma was reported to be associated with pre-eclampsia, multiple gestation, premature delivery, fetal thrombocytopenia, and fetal angioma (Kasabach-Merritt syndrome)
Angioma in the cord^60,⁶¹	The lesion can be associated with raised AFP, fetal DIC, and fetal hydrops; fetal death has been described too

AFP, α fetoprotein; APA, anti-phospholipid syndrome; CMV, cytomegalovirus; DIC, disseminated intravascular coagulopathy; HEV, haemorrhagic endovasculitis; IUD, intrauterine death; IUGR, intrauterine growth restriction; NOS, not otherwise specified; RBC, red blood cell; SGA, small for gestational age; SLE, systemic lupus erythematosus; VSM, vasculo–syncytial membrane; VUE, villitis of unknown aetiology.