Fetal But Not Maternal Angiotensin Converting Enzyme (ACE)-2 Gene Rs2074192 Polymorphism is Associated with Increased Risk of Being a Small For Gestational Age (SGA) Newborn

Abstract

Background/Aims: The maternal and fetal Renin-Angiotensin-System is involved in the control of pregnancy outcomes such as blood pressure control and gestational age. However, very little is known about the impact of the angiotensin converting enzyme 2 (ACE2) on pregnancy outcome. We thus performed a prospective clinical observational study analyzing the association of maternal and fetal ACE2 gene rs2074192 polymorphism with fetal growth during pregnancy. Methods: 898 singleton pregnant women were prospectively recruited. 739 pregnant women finally participated in the study and were genotyped. 474 women also donated umbilical cord blood for gene analysis of their offspring. All data such as basic demographic information, data from birth records, biochemical and immunological parameters, as well as Doppler ultrasonographic findings during pregnancy were collected. Fetal and maternal ACE2 gene rs2074192 polymorphism was genotyped by DNA sequencing. Results: Our analysis showed that the maternal ACE2 gene rs2074192 polymorphism was not associated with gestational hypertension, gestational diabetes mellitus, anemia, postpartum hemorrhage and fetal growth. However, neonates having rs2074192 T allele were more likely to be born as small for gestational age (SGA) babies. After multivariable logistic regression considering known confounding, we could demonstrate that the neonatal rs2074192 T allele was an independent risk factor for SGA (OR: 22.93, 95%CI: 1.26∼418.77, P< 0.05). Conclusion: This is the first study showing that the babies but not their mothers with ACE2 gene rs2074192 T allele had a high risk for SGA, which contributes to metabolic syndrome and cardiovascular diseases in later life.

Fetal programming and the angiotensin-(1-7) axis: a review of the experimental and clinical data

“…Fetal plasma levels of Ang-(1–7) in the term group were 11-fold higher than Ang II (900 compared with 80 pM) as assessed by separate ELISAs and a similar concentration range for Ang-(1–7) and Ang II was reported for the maternal circulation [109]. Moreover, this group has recently reported that the fetal but not maternal ACE2 polymorphism rs2074192 associated with lower birth weight [113]. We have examined the effects of perinatal programming on future cardiovascular health in a prospective cohort of individuals born preterm with very low birth weight compared with a term-born control cohort and show that alterations in the Ang-(1–7) pathway persist into adolescence and young adulthood.…”

Potential effects of SARS‐CoV‐2 infection during pregnancy on fetuses and newborns are worthy of attention

“…Both human and animal studies have shown that the use of ACE inhibitors in early pregnancy can cause maternal weight loss and decreased blood pressure, uterine blood flow and amniotic fluid production, followed by fetal hypotension or death. The most common adverse effects of ACE inhibitors in the second or third trimester of pregnancy included intrauterine growth retardation, neonatal hypotension, renal failure, oligohydramnios, patent ductus arteriosus and pulmonary hypoplasia 12 Other studies have found that an ACE2 gene polymorphism in pregnant women is associated with recurrent abortion and fetal growth restriction 13,14 . Thus, SARS‐CoV‐2 infection in women is likely to cause adverse reactions similar to those caused by ACE2 inhibitors or ACE2 gene polymorphism in pregnant women and their fetuses.…”

Is highly expressed ACE 2 in pregnant women “a curse” in times of COVID-19 pandemic?

“…Several reports from the literature, have indicated that ACE 2 is highly expressed in the reproductive organs, placenta, uterus and, maternal-fetal interface during pregnancy; which is important for normal fetal growth and also for regulation of the Ang II level. Besides, renal ACE 2 is also upregulated in pregnant women, further in comparison; the placenta shows the highest expression of renal ACE 2 mRNA, followed by kidney and, then the uterus; whereas, the ACE 2 activity is higher in kidney in comparison to placenta and uterus ( Table 1 ) [ [11] , [12] , [13] , [14] ].…”