Variety in placental shape: When does it originate? C.M. Salafia a, * , M. Yampolsky b , A. Shlakhter d , D.H. Mandel a , N. Schwartz c a Placental Analytics, LLC, 93 Colonial Avenue, Larchmont, NY, USA b University of Toronto, Department of Mathematics, Canada c University of Pennsylvania, School of Medicine, Department of Obstetrics, USA d University of Toronto, Rothman School of Management, Canada article info Article history: Accepted 1 December 2011 Keywords: Placenta 3D color Doppler ultrasound Umbilical cord Placental shape abstract Objectives: Observational and empirical evidence suggest that the average placental shape is round with a centrally inserted umbilical cord. Yet variability of shape is common. When in pregnancy do shape and cord insertion variations originate? Materials and methods: Placental measures from published datasets obtained ultrasonographically at 11 e14 weeks and/or at term were correlated. Results: Significant correlations were found between the normalized distance of cord insertion to the margin at 11e14 weeks with the same quantity at delivery (r ¼ 0.509, p < 0.0001). First trimester cord marginality was not correlated with two measures of roundness of the delivered placenta (p ¼ 0.448, and p ¼ 0.812). There was a strong correlation between delivered placental thickness and first trimester cord marginality (r ¼0.368, p ¼ 0.009). There was a significant relationship between the cord marginality at 11e14 weeks and the mean chorionic vascular density at delivery (r ¼0.287, p ¼ 0.015). Placental position in the uterine cavity influences cord marginality at delivery. Modeling suggests that placental growth in the first trimester is non-round. Placental shape at 11e14 weeks is found to be irregular. This irregularity is not correlated with the roundness of the delivered placenta. Both empirically, and in the context of IVF pregnancies, deformation of the vasculogenic zone yields a bi-lobate placental shape. Conclusions: Our findings strongly support the hypothesis that abnormal cord insertion and a multi-lobate shape result from early influences on the placental growth, such as the shape of the vasculogenic zone, or placental position in the uterus, rather than trophotropism later in pregnancy. Ó 2011 Elsevier Ltd. All rights reserved. 1. Introduction While we have provided evidence from observations [1] and empirical modeling [2] that the average placental shape is round with a centrally inserted umbilical cord, variability of shape and- cord insertion is common. Currently, the conventional wisdom regarding how placental shapes are deformed in utero is summa- rized in the concept of “trophotropism”, which, in an over- simplification, can be phrased as “the placenta grows where it can, and does not grow where it cannot”. With the advent of ultrasound in the 1970s (cf. [3]), the term “dynamic placentation” was coined to explain how a placental previa at mid-gestation was not a placental previa at term (so-called “resolved” placenta previa). “Dynamic placentation” did not clearly distinguish between later gestational trophotropism, in which the placental growth actively responds to the local uterine environment [4], and the more passive changes in placental position that would result from differential uterine expansion and/or uterine remodel- ing deforming the anchored placenta [5]. However, gross and histologic examination of cases of “resolved” placenta previa sug- gested that placental “migration”, at least in that context, was accomplished both through “active” differential placental growth with atrophy of more poorly perfused areas and growth in better perfused areas, as well as by the thinning of the lower uterine segment (changing the shape of the placental “foundation” [6]). Thus, from clinical observations, placental shape deviations might in some cases be primarily “active” (due to trophotropism, an active placental response to the local environment), and in others, primarily “passive “(secondary to changing shape of the basal plate due to uterine remodeling) and in others (such as resolving placenta previa), both “active” and “passive” mechanisms of placental shape change might be operative. The putative time of genesis of both abnormal placental shape and abnormal cord insertion (also believed to result from non- uniform placental angiogenetic growth out from the umbilical * Corresponding author. Tel.: þ1 914 834 3764. E-mail address: carolyn.salafia@gmail.com (C.M. Salafia). Contents lists available at SciVerse ScienceDirect Placenta journal homepage: www.elsevier.com/locate/placenta 0143-4004/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.placenta.2011.12.002 Placenta 33 (2012) 164e170