Further Evidence that an Episode of Premature Labor Is a Pathologic State: Involvement of the Insulin-Like Growth Factor System

Abstract

Introduction: Approximately 47% of women with an episode of preterm labor deliver at term; however, their infants are at greater risk of being small for gestational age and for neurodevelopmental disorders. In these cases, a pathologic insult may disrupt the homeostatic responses sustaining pregnancy. We tested the hypothesis of an involvement of components of the insulin-like growth factor (IGF) system.

Methods: This is a cross-sectional study in which maternal plasma concentrations of pregnancy-associated plasma protease (PAPP)-A, PAPP-A2, insulin-like growth factor-binding protein 1 (IGFBP-1), and IGFBP-4 were determined in the following groups of women: (1) no episodes of preterm labor, term delivery (controls, n = 100); (2) episode of preterm labor, term delivery (n = 50); (3) episode of preterm labor, preterm delivery (n = 100); (4) pregnant women at term not in labor (n = 61); and (5) pregnant women at term in labor (n = 61). Pairwise differences in maternal plasma concentrations of PAPP-A, PAPP-A2, IGFBP-1, and IGFBP-4 among study groups were assessed by fitting linear models on log-transformed data and included adjustment for relevant covariates. Significance of the group coefficient in the linear models was assessed via t-scores, with p < 0.05 deemed a significant result.

Results: Compared to controls, (1) women with an episode of premature labor, regardless of a preterm or a term delivery, had higher mean plasma concentrations of PAPP-A2 and IGFBP-1 (each p < 0.05); (2) women with an episode of premature labor who delivered at term also had a higher mean concentration of PAPP-A (p < 0.05); and (3) acute histologic chorioamnionitis and spontaneous labor at term were not associated with significant changes in these analytes.

Conclusion: An episode of preterm labor involves the IGF system, supporting the view that the premature activation of parturition is a pathologic state, even in those women who delivered at term.

Keywords: Biomarker; Histologic chorioamnionitis; IGFBP-1; IGFBP-4; Intra-amniotic infection/inflammation; PAPP-A; PAPP-A2; Placental pathology; Preterm birth.

Figure 1

Gestational age (weeks) at blood sampling in women without an episode of premature labor who delivered a term neonate (control group), women with an episode of premature labor who delivered at term (PTL_TD group), and women with an episode of premature labor who delivered preterm (PTL_PTD group). Box-and-whisker plots (median, interquartile range, and range) display the distribution of gestational age in each group.

Figure 2

Plasma concentrations of PAPP-A (A), PAPP-A2 (B), IGFBP-1 (C), and IGFBP-4 (D) in women without an episode of premature labor who delivered a term neonate (control group, N=100), women with an episode of premature labor who delivered at term (PTL_TD group, N=50), and women with an episode of premature labor who delivered preterm (PTL_PD group, N=100). Each p value was derived from pairwise comparison between groups by utilizing linear models in which data were log transformed to improve normality. Relevant covariates to adjust for in the analyses were selected by the use of stepwise backward elimination from among the following: gestational age at sampling, sample storage time, body mass index, maternal age, and parity. Box-and-whisker plots (median, interquartile range, and range) display the distribution of analyte values.

Figure 3

Plasma concentrations of PAPP-A (A), PAPP-A2 (B), IGFBP-1 (C), and IGFBP-4 (D) in women without labor (TNL, N=61) and in those with labor at term (TL, N=61). Box-and-whisker plots (median, interquartile range and range) display the distribution of analyte values.