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. 2021 Nov;225(5):520.e1-520.e10.
doi: 10.1016/j.ajog.2021.04.232. Epub 2021 Apr 24.

Slowing of fetal growth and elevated maternal serum sFLT1:PlGF are associated with early term spontaneous labor

Ulla Sovio  1 , Francesca Gaccioli  2 , Emma Cook  3 , D Stephen Charnock-Jones  2 , Gordon C S Smith  4
Affiliations

Slowing of fetal growth and elevated maternal serum sFLT1:PlGF are associated with early term spontaneous labor

Ulla Sovio et al. Am J Obstet Gynecol. 2021 Nov.

Abstract

Background: The physiological control of human parturition at term is unknown.

Objective: This study aimed to test the hypothesis that slowing of fetal growth or elevated maternal serum levels of markers of placental hypoxia in late gestation will be associated with earlier term labor.

Study design: We observed 2208 women having first births and performed serial blinded ultrasonography and immunoassay of soluble fms-like tyrosine kinase-1 and placenta growth factor. We estimated the probability of spontaneous delivery from 37 weeks of gestational age concerning (1) fetal growth between 20 and 36 weeks of gestational age and (2) the maternal serum soluble fms-like tyrosine kinase-1-to-placenta growth factor ratio measured at approximately 36 weeks of gestational age. Data were analyzed using logistic regression and Cox regression.

Results: Fetal size at 36 weeks of gestational age was not independently associated with the timing of delivery at term. However, there was an inverse relationship between fetal growth between 20 weeks of gestational age and 36 weeks of gestational age and the probability of spontaneous labor at 37 to 38 weeks' gestation (hazard ratio [95% confidence interval] for a 50 percentile increase in abdominal circumference growth velocity, 0.60 [0.47-0.78]; P=.0001). This association was weaker at 39 to 40 weeks' gestation (0.83 [0.74-0.93]; P=.0013), and there was no association at ≥41 weeks' gestation. Very similar associations were observed for estimated fetal weight growth velocity. There was a positive relationship between soluble fms-like tyrosine kinase-1-to-placenta growth factor ratio and the probability of spontaneous labor at 37 to 38 weeks' gestation (hazard ratio [95% confidence interval] for a 50 percentile increase in soluble fms-like tyrosine kinase-1-to-placenta growth factor ratio, 3.05 [2.32-4.02]; P<.0001). This association was weaker at 39 to 40 weeks' gestation (1.46 [1.30-1.63]; P<.0001), and there was no association at ≥41 weeks' gestation. Adjustment for maternal characteristics was without material effect on any of these associations.

Conclusion: Slowing of fetal growth and biomarkers of placental insufficiency were associated with an increased probability of early onset of spontaneous term labor. We speculated that progressive placental insufficiency may be a physiological phenomenon that occurs with advancing gestational age near and at term and promotes the initiation of labor.

Keywords: fetal growth; fetal stress; placental insufficiency; pregnancy; protein biomarkers; spontaneous labor.

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Figures

Figure 1
Figure 1
Flowchart of the selection of participants for the analysis AC, abdominal circumference; FL, femur length; PlGF, placental growth factor; POP, Pregnancy Outcome Prediction; sFlt-1, soluble fms-like tyrosine kinase-1; wkGA, weeks of gestational age. Sovio et al. Slowing of fetal growth and elevated maternal serum sFLT1:PlGF ratio and early term labor. Am J Obstet Gynecol 2021.
Figure 2
Figure 2
Spontaneous labor <40 weeks by deciles of growth and biomarkers Points are odds and bars are 95% confidence intervals. The dotted red lines in panels A and B represent the predicted odds from logistic regression models with polynomial (linear and quadratic) terms fitted on the percentiles of EFWGV and ACGV, respectively. The line on the figure is fitted to all of the observations and not on the values for the 10 deciles. AC, abdominal circumference; EFW, estimated fetal weight; FL, femur length; GV, growth velocity; PlGF, placental growth factor; sFlt-1, soluble fms-like tyrosine kinase-1; wkGA, weeks of gestational age. Sovio et al. Slowing of fetal growth and elevated maternal serum sFLT1:PlGF ratio and early term labor. Am J Obstet Gynecol 2021.
Figure 3
Figure 3
Smoothed estimated hazard function curves by deciles The blue lines represent decile 1, the black dashed lines represent deciles 2 to 9, and the green lines represent decile 10. AC, abdominal circumference; EFW, estimated fetal weight; FL, femur length; GV, growth velocity; PlGF, placental growth factor; sFlt-1, soluble fms-like tyrosine kinase-1. Sovio et al. Slowing of fetal growth and elevated maternal serum sFLT1:PlGF ratio and early term labor. Am J Obstet Gynecol 2021.
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