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Centre for Trophoblast Research

 

Ulla Sovio, Francesca Gaccioli, Emma Cook,  Stephen Charnock-Jones, Gordon Smith

Background

The physiological control of human parturition at term is unknown.

Objective

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 studied 2,208 women having first births and performed serial blinded ultrasonography and immunoassay of soluble fms-like tyrosine kinase-1 (sFlt-1) and placenta growth factor (PlGF). We estimated the probability of spontaneous delivery from 37 weeks of gestational age (wkGA) in relation to (i) fetal growth between 20wkGA and 36wkGA, and (ii) the maternal serum sFlt-1:PlGF ratio measured at ∼36wkGA. Data were analyzed using logistic regression and Cox regression.

Results

Fetal size at 36wkGA was not independently associated with the timing of delivery at term. However, there was an inverse relationship between fetal growth between 20wkGA and 36wkGA and the probability of spontaneous labor at 37 to 38 weeks (hazard ratio [95% CI] for a 50 centile increase in abdominal circumference growth velocity = 0.60 [0.47 to 0.78], P=0.0001). This association was weaker at 39 to 40 weeks (0.83 [0.74 to0.93], P=0.0013) and there was no association at 41 weeks and beyond. Very similar associations were observed for estimated fetal weight growth velocity. There was a positive relationship between sFlt-1:PlGF ratio and the probability of spontaneous labor at 37 to 38 weeks (hazard ratio [95% CI] for a 50 centile increase in sFlt-1:PlGF ratio = 3.05 [2.32 to 4.02], P<0.0001). This association was weaker at 39 to 40 weeks (1.46 [1.30 to 1.63], P<0.0001) and there was no association at 41 weeks and beyond. Adjustment for maternal characteristics was without material effect on any of these associations.

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