Maternal hypertension genes associated with low placental weight and fetal growth inhibition

Hypertension is the most common medical problem encountered during pregnancy, complicating up to 10% of pregnancies. Maternal under nutrition or poor placental function could alter long-lasting body function and physiology, predisposing individuals to cardio-metabolic diseases. Low birth weight (LBW) and fetal growth restriction are associated with the development of cardio-metabolic diseases later in life.

A cohort study by Noriko Sato and team has found that maternal genetic risk of hypertension is associated with reduced placental weight, inhibiting fetal growth and contributing to future cardio-metabolic abnormalities.

Maternal hypertension genes are strongly associated with placental growth and that fetal growth inhibition is induced through the intrauterine environment, it cannot be overlooked that suboptimal intrauterine environment due to reduced placenta growth could generate future hypertension in LBW offspring.

The findings of the study are published in BMC Medicine.

The objective of the study was to evaluate whether hypothesis of BP-increasing genetic variants could affect birth weight by reducing the growth of the placenta, a highly vascular organ, without overtly elevating the maternal BP.

The study was a birth cohort study in the Japanese population possessing time-series fetal growth velocity data as a target and a GWAS summary statistics of BioBank Japan as a base data. They performed polygenic score (PGS) analyses for systolic BP (SBP), diastolic BP, mean arterial pressure, and pulse pressure. A causal mediation analysis was performed to assess the meditation effect of placental weight on birth weight reduced by maternal BP-increasing PGS. Maternal genetic risk score constituted of only "vasculature-related" BP single nucleotide polymorphisms (SNPs) was constructed to examine the involvement of vascular genes in the mediation effect of placental weight. They identified gestational week in which maternal SBP-increasing PGS significantly decreased fetal growth velocity.

The results of the study were

• It was observed that maternal SBP-increasing PGS was negatively associated with offspring birth weight.

• A causal mediation analysis revealed that a large proportion of the total maternal PGS effect on birth weight was mediated by placental weight.

• The placental mediation effect was remarkable when genetic risk score was constituted of "vasculature-related" BP SNPs.

• The inverse association between maternal SBP PGS and fetal growth velocity only became apparent in late gestation.

Sato and team concluded that "Our study suggests that maternal hypertension genes are strongly associated with placental growth and that fetal growth inhibition is induced through the intrauterine environment established by the placenta."

Reference: doi: 10.1186/s12916-021-02131-0