DOI: 10.1177/03331024261492308 ISSN: 0333-1024

Association between migraine and angiogenic biomarkers in women with suspected or confirmed hypertensive disorders of pregnancy

Linda Al-Hassany, Noor R.A. Bruijn, Langeza Saleh, Rugina I. Neümañ, Britt W.H. van der Arend, Anna C.M. Kluivers, Gisela M. Terwindt, Willy Visser, A.H. Jan Danser, Antoinette MaassenVanDenBrink
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Aim

Migraine is associated with increased odds of hypertensive disorders of pregnancy (HDP). Elevated soluble Fms-like tyrosine kinase-1 (sFlt-1), decreased placental growth factor (PlGF), and upregulated sFlt-1/PlGF ratios are biomarkers of preeclampsia-related complications. Our primary objective was to examine the effect of migraine on sFlt-1, PlGF, and their ratio within subgroups of women with different HDP diagnoses. Our secondary objective was to evaluate the interrelationship between migraine and these biomarkers in the overall cohort with suspected or confirmed HDP.

Methods

We evaluated pregnant women with suspected or confirmed HDP in whom sFlt-1, PlGF and their ratio were measured during index pregnancy. Migraine diagnoses before/during index pregnancy were retrospectively assessed according to ICHD-3 criteria. Both, descriptive and adjusted analyses were performed, comparing women with and without migraine. For the latter analyses, linear regression analyses were conducted for the log-transformed sFlt-1 levels, PlGF levels and their ratio, while adjusting for gestational age, maternal age, and smoking status.

Results

Among 234 women (mean age 32 years, SD = 5), 91 had (a history of) migraine. No significant association between migraine and the log-transformed biomarkers was observed in women with and without migraine across HDP groups, also when adjusting for confounding factors (adjusted estimates of the sFlt-1/PlGF ratio: β  = −0.2 [95% CI: −1.0–0.6] for women with preeclampsia or hemolysis, elevated liver enzyme levels, and low platelet levels syndrome, β  = -0.8 [95% CI: −2.0–0.4] for gestational hypertension, and β  = −0.1 [95% CI: −0.7–0.4] for those without HDP). Secondary analyses showed that, when pooling the overall study population, women with migraine had lower sFlt-1 levels and sFlt-1/PlGF ratios compared to women without migraine. Adjusted analyses in the overall study population instead showed that migraine was not associated with significant changes in log sFlt-1 levels ( β  = −0.2 [95% CI: −0.5–0.04]), but rather with higher log PlGFs levels ( β  = 0.3 [95% CI: 0.03–0.6]) and lower log sFlt-1/PlGF ratios ( β  = −0.5 [95% CI: −1.0 – −0.08]).

Conclusions

Results of this study do not support enhanced angiogenic imbalance by migraine status within HDP groups. As a consequence, interpretation of sFlt-1 and PlGF might not require modification according to migraine status within different HDP diagnoses. The findings observed in the overall cohort require cautious interpretation; whether migraine influences magnitude of angiogenic dysregulation warrants prospective investigation.

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