Abstract
ObjectiveThe (pro)renin receptor [(P)RR] has been recognized as a multifunctional receptor. The purpose of this study was to assess the association between plasma soluble (P)RR [s(P)RR] concentration in human cord blood (i.e., neonatal blood at birth) and small for gestational age (SGA) birth.MethodsParticipants were women with a singleton pregnancy who delivered at the National Center for Child Health and Development between January 2010 and December 2011. Inclusion criteria were availability of maternal pre-pregnancy and paternal body mass index, and the absence of structural anomalies in neonates. s(P)RR concentration in cord blood was measured in 621 neonates. The 621 pairs of mothers and neonates were categorized into four groups based on quartiles of s(P)RR concentrations in cord blood. SGA was defined as a birth weight below the 10th percentile for gestational age. Logistic regression analysis was performed to assess the association between cord plasma s(P)RR concentration (quartiles) and incidence of SGA births.ResultsAmong 621 neonates, 55 (8.9%) were diagnosed as SGA (SGA group) and 566 (91.1%) were not (non-SGA group). Average s(P)RR concentration in cord blood was 66.1±12.6 ng/ml (mean±standard deviation). There were 155 pairs in the first plasma s(P)RR concentration quartile (Q1: <58.2 ng/ml), 153 pairs in the second quartile (Q2: 58.2–65.1 ng/ml), 157 pairs in the third quartile (Q3: 65.1–73.1 ng/ml) and 156 pairs in the fourth quartile (Q4: >73.1 ng/ml). The distribution of SGA births was 18 (11.6%) in Q1, 14 (9.2%) in Q2, 16 (10.2%) in Q3 and 7 (4.5%) in Q4, respectively. The odds ratio of SGA births was 0.24 (95% confidence interval: 0.08–0.71) for the fourth quartile compared to the first quartile in multivariate models. The P-value for trend was also significant (P = 0.020).ConclusionHigh s(P)RR concentration is associated with a lower SGA birth likelihood.
Highlights
Therenin receptor [(P)RR] was initially thought to contribute to the renin-angiotensin system (RAS) [1]
A birth weight below the 10th percentile for gestational age was classified as small for gestational age (SGA)
S(P)RR concentration in cord blood was lower in the SGA group than in the non-SGA group (62.9 ng/ml vs. 66.6 ng/ml, p = 0.049)
Summary
The (pro)renin receptor [(P)RR] was initially thought to contribute to the renin-angiotensin system (RAS) [1]. Recent studies have revealed (P)RR to be a multifunctional receptor. In addition to regulating the RAS, (P)RR is closely associated with the vacuolar-type H+-ATPase (V-ATPase), which is important for the maintenance of intracellular pH [2,3], and Wnt signaling, an important component of embryonic development [4,5,6]. While in vitro studies have revealed a role for (P)RR in fetal development, no studies have addressed the association between (P)RR and fetal development in vivo. We developed an s(P)RR enzyme-linked immunosorbent assay (ELISA) kit [8] that allows s(P)RR quantitation in clinical settings
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