Scientists do a lot of stuff to cells in culture and rodents in plastic boxes, but ultimately we often want to better understand the human condition. It's always exciting for me, as a medical doctor, to see the sorts of translational studies that bring concepts from bench to bedside, so to speak.
TanYa M. Gwathmey1, Mark C. Chappell1, Patricia A. Nixon2, Lisa K. Washburn3
1Hypertension and Vascular Research, Wake Forest School of Medicine, Winston-Salem, NC,2Health and Exercise Science, Wake Forest School of Medicine, Winston-Salem, NC,3Dept of Pediatrics, Wake Forest School of Medicine, Winston-Salem, NC
Peri- and neo-natologists have know for many years that term delivery is preceded by a burst of cortisol from the fetal adrenal glands. This surge of steroid produces an increase in surfactant production by the fetal lungs, making them ready for postnatal life. It may also help drive kidney maturation for the external world.
In the 1980s betamethasone, a pharmacologic glucocorticoid similar to cortisol, became standard treatment for preterm labor. Women who presented advanced in labor might not receive it, because it would not get to the fetus in time. Those who would likely keep the critter in utero for another day or two got the shot.
Full-term is 37-38 weeks of estimated gestational age (EGA), based on the time from the last menstrual cycle (depending on which classification system you use). Nephrogenesis is not complete in the human fetus until 36 weeks EGA, so anything done in pregnancy prior to that time may have a substantial impact on future kidney structure and function.
The present study examined measures of kidney function in 14-year-old African American girls with or without prenatal exposure to betamethasone. First question: why girls? Turns out the sample of boys in this cohort is insufficient for these sorts of comparisons. The girls were classified in 3 groups: Full term; Preterm without betamethasone; and Preterm with betamethasone. Both preterm groups had similar degrees of prematurity, averaging 28 weeks EGA. All of these kids are fairly similar in many ways, and all have "normal" blood pressure; however, the preterm girls, both with and without betamethasone, trend higher within the normal range (reported at an earlier meeting).
A number of markers of kidney health were presented in the current poster:
- 8-isoprostane, a marker of oxidative stress
- Angiotensinogen, the precursor of angiotensin
- Angiotensin II
Premature girls showed higher levels of urinary angiotensinogen, angiotensin II, and microalbuminuria, with trends to higher levels with betamethasone exposure. Betamethasone exposure increased 8-isoprostane in the urine over full-term girls; preterm subjects without betamethasone exposure had levels intermediate to the other groups.
Obviously these results are not the startling, clear-cut, "eureka" differences that we are used to seeing in studies of models. The numbers are fairly low, with only 10-20 subjects per group. People are less enthusiastic about controlling other variables than our animal or cellular subjects. We do not yet have information on physical activity, body habitus, perinatal exposure to other drugs, and a million other variables that may affect renal health.
We also do not have a non-African-American control group. Blacks in this country have a disproportionate risk of prematurity as well as hypertension and chronic kidney disease. While these studies suggest that being born early and getting betamethasone are both bad for African American kidneys, we do not know if these factors are different for the white population.
Now, don't get me wrong. Betamethasone treatment has improved respiratory issues (along with administration of surfactant at birth), and a long-term risk of hypertension and kidney disease beats dying at birth of prematurity and respiratory distress. It is important that we recognize effects of these agents so we can come up with strategies to mitigate their consequences.
As always, further study is in order. And these investigators are on the case.