This is one of my best friends, Karen*. She and I met on our first night in college and have been close ever since. We’ve celebrated birthdays, each other’s weddings, and reunions, and in February I visited her in the hospital — traveling from Washington, DC, to Seattle, Washington; that’s how good a friend she is — because she had just given birth only weeks before.
Here, she is pictured with her twin daughters just hours after their birth. They were born at only 34 weeks gestation, six weeks before their due date. It’s quite amazing they even made it this far. You see, Karen was diagnosed with preeclampsia a little over halfway through her pregnancy.
a disorder that occurs only during pregnancy and the postpartum period and affects both the mother and the unborn baby. Affecting at least 5-8% of all pregnancies, it is a rapidly progressive condition characterized by high blood pressure and usually the presence of protein in the urine. Swelling, sudden weight gain, headaches and changes in vision are important symptoms.
Preeclampsia is an extremely serious disorder: globally, preeclampsia and other hypertensive disorders of pregnancy are a leading cause of maternal and infant illness and death. By conservative estimates, 76,000 mothers and 500,000 infants die from these disorders each year.
Karen’s preeclampsia was severe enough that she required 24-hour in-hospital care (antepartum care) for some 40 days prior to her delivery, so as to “keep her pregnant” until the twins were at least 32 weeks. She had to spend Christmas and New Year’s in the hospital away from her husband and son (though Christmas was celebrated in her room!). However, this abundance in caution was worthwhile, given that the twins were born “only” six weeks early.
Because of Karen’s doctors’ expertise in high-risk pregnancy, her twin girls are now happy, healthy 4-month-olds. And because of animal research, her doctors were able to recognize, understand, and monitor the symptoms of her preeclampsia to provide Karen with the best care possible.
Animal models have been relied on to study preeclampsia for decades. As a review by Pennington et al. (2012) states, “Several key aspects of preeclampsia can be studied in vitro …but the nature of the disease limits the utility of cell culture models. Specifically, preeclampsia involves changes in the behavior of fetal trophoblast cells, their interactions with maternal endothelium and the reaction of the maternal system to these vascular changes. Therefore, whole-animal models are needed to recapitulate the complex interactions that underlie preeclampsia” (p.11; emphasis added). A review written by Carter (2007) demonstrates that successful animal models have included:
- Rodents, for understanding placental development;
- Guinea pigs, for the understanding of pregnancy toxemia (the former name for preeclampsia);
- Sheep, for the modeling of toxemia, placental development, fetal physiology and maternal-fetal interactions; and
- Nonhuman primates, for the study of maternal blood pressure, placental structure, and vasculature, as well as trophoblast invasion during pregnancy.
Animal models have also been instrumental in developing the treatments Karen received to manage her preeclampsia long enough for her twins to make it to 36 weeks. During the course of her treatment, Karen received:
- Labetalol, norvasc and hydralazine to treat maternal hypertension. These treatments were tested in rats and baboons, mice, and guinea pigs and rats, respectively.
- Daily iron supplements to increase fetal iron stores. The link between maternal and fetal iron stores was established in rats, guinea pigs, and cats.
- Intravenous magnesium sulfate in 2 different doses to prevent 1) maternal seizure and 2) for fetal neuroprotection. This treatment was tested in nonhuman primates and guinea pigs.
- Steroids to improve fetal lung function before 34 weeks. Nonhuman primates and rats were instrumental in the development of these treatments.
- Multiple daily nonstress tests (NSTs) to monitor fetal oxygen supply via fetal heart rate (FHR) and fetal activity. Experimental studies of hypoxia in animals demonstrated increases in FHR.
- Weekly ultrasound of amniotic fluid levels. The biological effects of ultrasound in animals were first reported in the 1920s, before its use in human therapies.
Each time I see photos of these strong babies (or better yet, snuggle them in person), and each time I hug my best friend Karen and talk to her on the phone, I’ll say a silent “thank you” to the animals who made their health and safety possible.
“While studies in animal models have limitations, utilization of these models allows investigators to directly test whether certain factors found in preeclamptic women can indeed lead to hypertension and other manifestations of preeclampsia. Thus, animal models are useful in advancing our knowledge of preeclampsia and should undoubtedly be of greater use in future studies on mechanisms and the development of specific treatments.” (Granger et al., 2015)
~Amanda M. Dettmer, PhD
*Not her real name.
- Carter, A. M. (2007). Animal models of human placentation–a review. Placenta, 28, S41-S47.
- Granger, J. P., George, E. M., & Roberts, J. M. (2015). Animal Models for Investigating Pathophysiological Mechanisms of Preeclampsia. In Chesley’s Hypertensive Disorders in Pregnancy (Fourth Edition) (pp. 209-220).
- Pennington, K. A., Schlitt, J. M., Jackson, D. L., Schulz, L. C., & Schust, D. J. (2012). Preeclampsia: multiple approaches for a multifactorial disease. Disease models & mechanisms, 5(1), 9-18.