Genetic contributions to risk of adverse pregnancy outcomes

Area of Science:

• Genetics and Cardiovascular Health
• Reproductive Medicine
• Maternal-Fetal Medicine

Background:

• Adverse pregnancy outcomes (APOs), including hypertensive disorders of pregnancy (HDP), low birthweight (LBW), and preterm birth (PTB), are linked to cardiovascular risks for mothers and offspring.
• Peripartum cardiomyopathy (PPCM) also carries significant maternal and fetal cardiovascular implications.
• Genetic predisposition plays a crucial role in the development of APOs and PPCM, influencing long-term cardiovascular health.

Purpose of the Study:

• To review the genetic contributions to the risk of adverse pregnancy outcomes (APOs) and peripartum cardiomyopathy (PPCM).
• To explore how genetic discoveries inform understanding of underlying biologic mechanisms and predispositions to cardiovascular disease.

Main Methods:

• Review of recent genome-wide association studies (GWAS) and genetic analyses.
• Identification of genetic loci associated with hypertension, type 2 diabetes, and immune/placental function.
• Comparison of genetic variants in PPCM and dilated cardiomyopathy.

Main Results:

• GWAS have identified genetic loci associated with HDP (e.g., FTO, ZNF831) and gestational diabetes mellitus (GDM) (e.g., CDKAL1, MTNR1B).
• Variants in genes related to immune function and placental health are implicated in PTB and future cardiovascular risks.
• Shared genetic similarities between PPCM and dilated cardiomyopathy suggest common pathophysiologic origins and future heart failure risks.

Conclusions:

• Genetic insights are vital for understanding the mechanisms, risks, and counseling strategies for individuals affected by APOs and PPCM.
• Advances in genetic techniques are uncovering new biologic mechanisms and genetic variants contributing to these conditions.
• Genetic counseling guidelines for PPCM are needed due to identified shared genetic origins with other cardiomyopathies.