Predisposing Factors to Abnormal First Trimester Placentation and the Impact on Fetal Outcomes

Lindsay Kroener, MD; Erica T. Wang, MD, MAS; Margareta D. Pisarska, MD


Semin Reprod Med. 2016;34(1):027-035. 

In This Article

Abstract and Introduction


Normal placentation during the first trimester sets the stage for the rest of pregnancy and involves a finely orchestrated cellular and molecular interplay of maternal and fetal tissues. The resulting intrauterine environment plays an important role in fetal programming and the future health of the fetus, and is impacted by multiple genetic and epigenetic factors. Abnormalities in placentation and spiral artery invasion can lead to ischemia, placental disease, and adverse obstetrical outcomes including preeclampsia, intrauterine growth restriction, and placental abruption. Although first trimester placentation is affected by multiple factors, preconception environmental influences such as mode of conception, including assisted reproductive technologies which result in fertilization in vitro and intrauterine influences due to sex differences, are emerging as potential significant factors impacting first trimester placentation.


The common thread to many pregnancy-associated pathologies is that their biologic foundation is laid in the first trimester of pregnancy. The process of placentation and trophoblast differentiation occurs throughout the first trimester of pregnancy and requires a complex interplay of multiple factors including maternal immune tolerance, expression of cytokines, growth factors, and autocrine/paracrine/juxtacrine mediators, as well as a receptive decidua that allows for extravillous trophoblast invasion and spiral artery remodeling.[1,2] Abnormal placentation and failure of first trimester trophoblast invasion into the placental bed are at the core of the pathogenesis of preeclampsia[3,4] and placental perfusion-related intrauterine growth restriction (IUGR), both of which contribute significantly to preterm delivery.[5,6] A multitude of factors can impact abnormal placentation leading to adverse fetal outcomes including genetics and epigenetic changes, due to the environment. Specifically, preconception environmental influences due to mode of conception, such as in vitro fertilization (IVF) through assisted reproductive technologies (ART), and intrauterine environmental influences due to fetal sex differences are evolving as significant factors impacting first trimester placentation.

In this review, we will start off by exploring the mechanisms of normal placentation, implications of intrauterine fetal programming, and the impact of genetics and epigenetics on placentation. We will then review the pathophysiology and outcomes of abnormal placentation, including preeclampsia, IUGR, placental abruption, previa, and accreta. Finally, we will focus on two specific environmental influences, mode of conception and ART as well as fetal sex differences, both of which are evolving as potential factors affecting early placentation.