To investigate the association of low maternal serum isthmin-2 (ISM2) levels in the first trimester with the risk of preeclampsia (PE) and fetal growth restriction (FGR).
Approach:
Study Design: Analyzed samples from 3 prospective pregnancy cohorts, including the POPS study with 4,512 nulliparous patients, measuring 2,904 maternal serum proteins at approximately 12 weeks.
Outcomes Evaluated: Four outcomes were assessed: PE without FGR, FGR without PE, PE with FGR, and a composite of any of the three outcomes.
Statistical Analysis: Compared ISM2 with established placental biomarkers and evaluated its association with uterine artery blood flow.
Functional Studies: Investigated ISM2 expression and function using human trophoblast stem cells and placental organoids.
Key Findings:
Low ISM2 levels at 12 weeks were associated with all four outcomes: PE without FGR, FGR without PE, PE with FGR, and a composite of any of the three outcomes.
ISM2 showed greater discrimination for composite outcomes compared to five established placental biomarkers.
Lower ISM2 at 12 weeks was associated with greater uterine artery resistance at 20 weeks.
In the IMPACT study, lower ISM2 levels were observed in those who experienced PE complicated by preterm birth or FGR.
Limitations:
The study focused on northern European cohorts, requiring validation in other populations.
The reasons for lower ISM2 levels in patients who developed PE or FGR were not determined.
Mechanisms underlying the effects of ISM2 on trophoblast invasion and migration remain unknown.
Conclusion:
Low ISM2 in the first trimester had the strongest association with subsequent PE and/or FGR among the proteins studied.
A nationwide birth cohort found lower odds of short sleep at 1 year among infants breastfed during the first 6 months of life, regardless of formula supplementation.
