Independent risk factors for a small placenta and a small‐for‐gestational‐age infant at 35–41 weeks of gestation: An association with circulating angiogenesis‐related factor levels at 19–31 weeks of gestation

Aim Our aim was to investigate the effects of angiogenesis‐related factor levels at 19–25 and 26–31 weeks of gestation (WG) on the later occurrence of a small‐for‐gestational‐age (SGA) placenta (small placenta) or an SGA infant delivered at 35–41 WG. Methods We measured plasma levels of soluble fms‐like tyrosine kinase 1 (sFlt‐1) and placental growth factor (PlGF), and the serum level of soluble endoglin (sEng) in 679 pregnant women with blood sampling at both 19–25 and 26–31 WG in a prospective study. A small placenta and an SGA infant were defined as <10th percentile, respectively. Multivariate logistic regression analyses were performed using maternal factors, a high mean pulsatility index (high mPI) of the uterine artery in the second trimester, and angiogenesis‐related factor levels. Results Regarding the occurrence of a small placenta, low PlGF at 19–25 WG (adjusted odds ratio [95% confidence interval]: 2.4 [1.01–5.7]) and a high mPI (2.5 [1.4–4.3]) were independent risk factors. Moreover, low PlGF at 26–31 WG (3.3 [1.5–7.0]) was also an independent risk factor after adjusting for the effect of mPI. Concerning the occurrence of an SGA infant, a high mPI (2.8 [1.6–5.2]) and high sEng at 26–31 WG (2.3 [1.2–4.5]) were independent risk factors. Conclusion Low levels of PlGF at 19–25 and 26–31 WG were independent risk factors for a small placenta at ≥35 WG; and a high sEng at 26–31 WG was an independent risk factor for an SGA infant at ≥35 WG.