Maternal and fetal vascular lesions of malperfusion in the placentas associated with fetal and neonatal death: Results of a prospective observational study

Document Type



Community Health Sciences; Pathology and Laboratory Medicine


Background: Fetal death, one of the major adverse pregnancy outcomes, is especially common in low and middle-income countries. Placental lesions may play an important role in the etiology of fetal and possibly neonatal death. Prior research relating placental lesions to fetal death causation was often hindered by the lack of agreement on a placental classification scheme. The Amsterdam Consensus statement, published in 2016, focused attention on malperfusions in the maternal and fetal placental circulations.
Objectives: Our purpose was to investigate the relationships of placental maternal vascular (MVM) and fetal vascular malperfusion (FVM) to fetal and neonatal death with a focus on the most important maternal clinical conditions in the pathway to fetal and neonatal death; maternal hypertension, antepartum haemorrhage and decreased fetal growth.
Study design: This was a prospective, observational cohort study conducted at two Asian sites. Data collected included clinical history, gross and histologic evaluation of the placenta, and a number of other investigations to determine cause of death. The placenta was evaluated at both sites using the Amsterdam Consensus framework. We estimated the risk of placental MVM and FVM among fetal and neonatal deaths.
Results: Between July 2018 and January 2020 in India and Pakistan, 814 women with a fetal death, 618 with a preterm live birth and subsequent neonatal death, and 201 term live births, all with a placenta available for study, provided consent. The prevalence of MVM was higher in placentas of fetal deaths (58.4%) and preterm neonatal deaths (31.1%) compared to the term live births (15.4%). Adjusting for site, MVM had a RR of 3.88 (95% CI 2.70-5.59) among fetal deaths vs. term live births and a RR of 2.07 (95% CI 1.41-3.02) for preterm neonatal deaths vs. term live births. Infarcts and distal villous hypoplasia were the most common histological components of MVM. FVM was found less frequently in the placentas of fetal deaths (19.0%) than was MVM (58.4%). However, there were higher frequencies of FVM in fetal death placentas (19.0%) than in placentas from neonatal deaths (8.3%) or in the term live birth placentas (5.0%). Adjusting for site, FVM had a RR of 4.09 (95% CI 2.15-7.75) among fetal deaths vs. term live births and RR 1.77 (95% CI 0.90-3.49) for preterm neonatal deaths vs. term live births. There was a higher incidence of MVM in cases of maternal hypertension (71.4%), SGA (69.9%) and antepartum hemorrhage (59.1%) compared to the incidence of MVM in fetal deaths with none of these conditions (43.3%). There were no significant differences in the occurrence of FVM among the four clinical categories.
Conclusion(s): Histological examination of the placenta, especially for malperfusion disorders, is crucial in elucidating pathways to fetal death and likely for neonatal death in preterm infants. Possibly more important is the potential to focus on placental MVM and FVM during pregnancy as a means to identify fetuses at risk and to reduce the risk of fetal death by early delivery. It is our additional hope that the increased risk of fetal and neonatal death in these pregnancies can be reduced by development of an intervention to reduce the likelihood of developing MVM and/or FVM in the first place.


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Publication (Name of Journal)

American Journal of Obstetrics and Gynecology