Genetic risk score predicts gestational hypertension

With the identification of new genetic variants in pre-eclampsia and gestational hypertension, researchers now have a polygenic risk score (PRS) that may better identify candidates for prophylactic low-dose aspirin in pregnant mothers. ) is created.

There were 18 independent loci significantly associated with hypertension of pregnancy (HDP), 12 of which were novel (i.e., MTHFR-CLCN6, WNT3A, NPR3, PGRand RGL3) — Based on an extended multiancestral genome-wide association study (GWAS) meta-analysis for pre-eclampsia/eclampsia and another GWAS for gestational hypertension only.

From this, a PRS for each outcome was derived, fine-tuned on the UK Biobank dataset, and validated externally. Norwegian Hunt and American nuMoM2b cohortaccording to Pradeep Natarajan, M.D., MMSc, ​​and colleagues at Massachusetts General Hospital and Harvard Medical School in Boston.

The PRS predicted HDP risk in nulliparous women independently of first-trimester risk factors, and the top 10% of highest scorers were found to be at significantly higher risk for pre-eclampsia and hypertension of pregnancy. rice field. Additionally, her high PRS score may expand the range of individuals eligible for prophylactic low-dose aspirin by up to 8.3%, the study authors said. natural medicine.

This may have implications for improving the “moderate” predictive ability of clinical risk factors for HDP, the researchers suggested, citing existing first-pregnancy screening algorithms such as: British Foundation for Fetal Medicine Preeclampsia Model Based on maternal medical history and biomarkers.

“Among the established risk factors for pre-eclampsia, nulliparity carries the greatest population-attributable risk (approximately one-third), with most affected individuals having no overt other than nulliparous.” There are no significant pre-pregnancy risk factors,” said Natarajan’s group.

“Thus, improving pregnancy risk prediction remains an urgent clinical need to optimize HDP prevention,” the authors emphasized. “In contrast to markers that are measured during pregnancy, the PRS can be calculated at any time after birth, including before pregnancy, so it may also be useful for pre-pregnancy counseling and health optimization.”

HDP is known to be associated with maternal stroke, preterm birth requirements, and infant low birth weight. Pregnant women who develop such hypertensive (BP) conditions have also been shown to be at disproportionately high long-term risk of cardiovascular disease and cardiovascular disease. chronic hypertension. Additionally, there is a higher risk of: cognitive decline later life and premature death.

Alarmingly, these blood pressure conditions have become more common over time, with CDC estimates suggesting an increasing prevalence of HDP in maternity hospitals. 13% in 2017 to 16% in 2019.

The United States Task Force on Preventive Services recently proposed expanding routine screening for preeclampsia. Include all HDPs. In its B-grade recommendation, the task force said that all pregnant women should have their blood pressure measured at every prenatal visit to identify and prevent serious health problems associated with hypertension in pregnancy. .

Management of HDP includes close fetal and maternal monitoring, antihypertensive medications, and magnesium sulfate for seizure prevention as needed. Preeclamptic findings can only be treated by delivery, depending on gestational age and whether severe features of preeclampsia are present.

On the other hand, there are currently no HDP prediction tools approved by UK or US guidelines.

Natarajan et al. developed the PRS after performing GWAS studies on discovery and follow-up cohorts using multiancestral meta-analysis.

HDP cases were identified using ICD codes and defined as:

• Pre-eclampsia: New-onset or worsening hypertension after 20 weeks of gestation with proteinuria or other evidence of end-organ dysfunction

• Gestational hypertension: New-onset hypertension without features of preeclampsia

• Eclampsia: progression from pre-eclampsia to maternal seizures

The study included 20,064 pre-eclampsia/eclampsia cases and 703,117 controls, and 11,027 gestational hypertension cases and 412,788 controls.

The authors acknowledged the lack of detailed information such as HDP subtype, preterm vs. term vs. postpartum onset, and presence of fetal growth restriction.

Another limitation of this study was that PRS performance was generally superior in this group, as more than 80% of the GWAS participants were of European descent. This “is consistent with many previously published PRSs and is a well-known challenge in modern genetics,” write Natarajan and co-authors.

“Future studies are needed to confirm whether PRS has the potential to extend existing risk algorithms,” the team added.