Research suggests that a drug recently assessed as a potential treatment for fetal growth restriction may cause high blood pressure and raise blood sugar levels in offspring. The study, which urges practitioners to consider both short- and long-term effects when treating people with this pregnancy complication, is published in the American Journal of Physiology-;Heart and Circulatory Physiology. It was chosen as an APSselect article for February.
Fetal (intrauterine) growth restriction is a condition in which an unborn baby is not growing to its full potential in the womb. Babies with fetal growth restriction have a lower-than-average birth weight and much higher risk of being stillborn. The condition is difficult to treat, in part because many medications carry the potential risk of damage to the fetus.
Sildenafil citrate-;a vasodilator most often used as a treatment for erectile dysfunction-;has recently been tested in international clinical trials in severe cases of fetal growth restriction. The results did not show the beneficial effect of fetal weight gain. "The focus of previous studies has been to assess [sildenafil citrate's] effects on the mother, fetus and in some cases, [newborn], but only one study has examined the effects of antenatal [sildenafil citrate] in the long term," researchers of the current study wrote.
To learn more about how sildenafil citrate affects offspring after birth, the researchers studied a mouse model of fetal growth restriction. One group of female mice received daily subcutaneous injections of the drug-;equivalent to a human dose-;during pregnancy ("treated"), while another group was left untreated ("control"). The research team then measured blood pressure, body weight and blood sugar levels of the pups born to both groups. Both males and females born to the treated group had higher blood pressure than those born to the control mice. Body weight did not change in male mice born to treated mothers, but female offspring from the treated group were significantly heavier than those born to the control group. In a test which helps look for evidence of diabetes, females born to treated dams also showed increased blood sugar levels following a sugar challenge, but males were unaffected.
"This study highlights the importance of assessing both the short- and long-term consequences of therapeutics administered during pregnancy," the researchers wrote. Results from animal models of fetal growth restriction may lead to "a more informed choice for the obstetrician and patient on the potential short- and long-term risk vs. benefits of treatments in utero."
Renshall, L. J., et al. (2020) Antenatal sildenafil citrate treatment increases offspring blood pressure in the placental-specific Igf2 knockout mouse model of FGR. Translational Physiology. doi.org/10.1152/ajpheart.00568.2019.