Association of mid-trimester maternal angiogenic biomarkers with small-for-gestational-age infants in an urban Zambian cohort: a nested case-control study

Int J Gynaecol Obstet. 2022 Jun;157(3):604-612. doi: 10.1002/ijgo.13860. Epub 2021 Aug 25.


Objective: To investigate whether angiogenic biomarker concentrations differ between women who deliver small-for-gestational-age (SGA) infants (<10th centile birth weight for gestational age) compared with controls, because identifying SGA risk early could improve outcomes.

Methods: This case-control study compared serum concentrations of angiogenic biomarkers before 24 weeks of pregnancy from 62 women who delivered SGA infants (cases) and 62 control women from an urban Zambian cohort. Odds of delivering an SGA infant were calculated using conditional logistic regression.

Results: Placental growth factor (PlGF), soluble fms-like tyrosine kinase (sFLT-1) and soluble endoglin (sEng) in controls were 37.74 pg/mL (interquartile range [IQR] 23.12-63.15), 2525.18 pg/mL (IQR 1502.21-4265.54) and 2408.18 pg/mL (IQR 1854.87-3017.94), respectively. SGA cases had higher PlGF (40.50 pg/mL, IQR 22.81-67.94) and sFLT-1 (2613.06 pg/mL, IQR 1720.58-3722.50), and lower sEng (2038.06 pg/mL, IQR 1445.25-3372.26). Participants with sEng concentration below and concomitant sFLT-1 concentration above their respective thresholds (n = 40) had five-fold higher odds of SGA (adjusted odds ratio 4.77, 95% confidence interval 1.61-14.1; P = 0.005).

Conclusion: Biomarker concentrations were similar between cases and controls. Participants with concomitant low sEng and high sFLT-1 had the highest odds of SGA, suggesting that a combination of biomarkers may better for predicting SGA than single biomarkers.

Keywords: Zambia; birth weight; fetal growth; placental angiogenesis; small for gestational age.

MeSH terms

  • Biomarkers
  • Case-Control Studies
  • Endoglin
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Infant, Small for Gestational Age*
  • Placenta Growth Factor
  • Pre-Eclampsia*
  • Pregnancy
  • Zambia


  • Biomarkers
  • Endoglin
  • Placenta Growth Factor