Abstract
Objective
Maternal immune activation has been proposed as a mechanism for adverse pregnancy outcomes, yet the mechanisms and effects of timing remain unclear. Immune disruption in early gestation may be particularly detrimental as this is an important period for placental development, which has been associated with the pathology of adverse obstetric outcomes. To increase our understanding of risk factors for adverse obstetric outcomes, we aim to investigate the association between multiple inflammatory and angiogenic markers during early pregnancy and adverse pregnancy outcomes in a large population-based cohort.
Design
Prospective population-based pregnancy cohort study (n = 7513).
Setting
Rotterdam, the Netherlands.
Population
Pregnant women in Rotterdam between April 2002 and January 2006.
Methods
Serum inflammatory markers (high-sensitivity (HS)-C-reactive protein (CRP), interleukin (IL)-1β, IL-6, IL-17a, IL-23, interferon (IFN)-γ) and angiogenic factors (sFlt-1 and PlGF) were analysed in repeated measures around 13–20 weeks gestation. A cytokine index was created using principal component analysis.
Main Outcome Measures
Hypertensive disorders of pregnancy, spontaneous preterm birth and small for gestational age at birth.
Results
HS-CRP, but not the cytokine index, was associated with increased risk of spontaneous preterm birth after multiple testing correction. We found no association of HS-CRP or the cytokine index with hypertensive disorders of pregnancy and small for gestational age at birth after multiple testing correction. Inflammatory and angiogenic factors were associated with each other, yet effect sizes were small.
Conclusions
We found no strong evidence of a link between early gestation typical inflammatory marker levels and the risk of adverse pregnancy outcomes.
Maternal immune activation has been proposed as a mechanism for adverse pregnancy outcomes, yet the mechanisms and effects of timing remain unclear. Immune disruption in early gestation may be particularly detrimental as this is an important period for placental development, which has been associated with the pathology of adverse obstetric outcomes. To increase our understanding of risk factors for adverse obstetric outcomes, we aim to investigate the association between multiple inflammatory and angiogenic markers during early pregnancy and adverse pregnancy outcomes in a large population-based cohort.
Design
Prospective population-based pregnancy cohort study (n = 7513).
Setting
Rotterdam, the Netherlands.
Population
Pregnant women in Rotterdam between April 2002 and January 2006.
Methods
Serum inflammatory markers (high-sensitivity (HS)-C-reactive protein (CRP), interleukin (IL)-1β, IL-6, IL-17a, IL-23, interferon (IFN)-γ) and angiogenic factors (sFlt-1 and PlGF) were analysed in repeated measures around 13–20 weeks gestation. A cytokine index was created using principal component analysis.
Main Outcome Measures
Hypertensive disorders of pregnancy, spontaneous preterm birth and small for gestational age at birth.
Results
HS-CRP, but not the cytokine index, was associated with increased risk of spontaneous preterm birth after multiple testing correction. We found no association of HS-CRP or the cytokine index with hypertensive disorders of pregnancy and small for gestational age at birth after multiple testing correction. Inflammatory and angiogenic factors were associated with each other, yet effect sizes were small.
Conclusions
We found no strong evidence of a link between early gestation typical inflammatory marker levels and the risk of adverse pregnancy outcomes.
| Original language | English |
|---|---|
| Number of pages | 12 |
| Journal | BJOG: An International Journal of Obstetrics and Gynaecology |
| DOIs | |
| Publication status | E-pub ahead of print - 2 May 2025 |
Keywords
- CRP
- Cytokines
- Maternal immune activation
- Pre-eclampsia
- Preterm birth