Primary care clinicians realize the importance of timely and focused prenatal care. What might recent "bench to bedside" progress bring our profession during the next decade that may become even more critical? Here is a preview gleaned from animal studies.
A series of presentations at a recent meeting of the Society for the Study of Reproduction proposed that a mother's health at the time of conception influences significant epigenetic changes in the developing fetus that later manifest as birth defects, obesity, insulin resistance, hypertension, cardiovascular disease, and hepatic steatosis.1 Let's look at 4 studies that frame and try to explain these interesting scientific propositions. There will be much more to follow in the next few years.
EFFECTS OF MATERNAL HEALTH AT CONCEPTION
First, maternal diabetes at the time of conception can adversely affect the pregnancy as early as the 1-cell zygote stage.2 Levels of ATP in diabetic mice oocytes were reduced when compared with those of nondiabetic controls. The oocytes of diabetic mice also had spindle defects and chromosome misalignment during meiosis. As a result, the developing embryos of the mice of diabetic mothers received a dysfunctional complement of mitochondria. From a clinical perspective, Dr Kelle Moley, an author of the study, said, "All of our work suggests there should be a 3- to 4-month preconception period that's included in good maternal health."1
Second, Sinclair and coworkers1,3 looked at the impact of vitamin B12 and methionine levels in female sheep and the effects on their offspring. Obesity, insulin resistance, and hypertension were more likely to develop in the offspring of mothers who were deficient in vitamin B12 and methionine.
Third, a low-protein diet before conception was studied in mice.4 Even if the mothers who had a low-protein diet just before conception were fed a normal diet after, their offspring experienced a higher burden of hypertension and arterial pathology later.
Finally, a high-fat (35%) diet was fed to primates (macaques) who later became pregnant.5 The incidence of both fatty liver disease and elevated triglyceride levels was higher in their offspring.
Commentary by the authors of the studies was informative: "diet, glucose levels in the mother, and vitamin intake, prior to ovulation and conception, can have long-term effects on fetal growth and adolescent and adult disease."1 Furthermore, a similar contribution from the father could not be discounted.1
IMPLICATIONS FOR PRIMARY CARE—AND FOR SOCIETY
Even though all the data came solely from animal research and are very preliminary, the consistent and plausible conclusions should be carefully considered. Society is dealing with an epidemic of diabetes mellitus, hypertension, obesity, and heart disease. To date, prenatal care has focused on folate replacement and the risks of spina bifida and gestational diabetes. The pathological clock may start ticking much earlier, however. The resultant pathology may become permanent and fixed before we know it. It is scary to hypothesize, but the next generation of obese, hypertensive patients with diabetes and heart disease may have been determined as early as the 1-cell zygote stage. Behavior modifications in the parents may need to begin long before the stork starts circling.
1. Fiore K. Mother's health around conception could influence child's disease risk. http://www.medpagetoday.com/obgyn/pregnancy/15188. Accessed July 22, 2009.
2. Wang Q, Ratchford AM, Chi MM, et al. Maternal diabetes causes mitochondrial dysfunction and meiotic defects in murine oocytes. Mol Endocrinol. 2009; 23:1603-1612.
3. Kanakkaparambil R, Singh R, Li D, et al. B-vitamin and homocysteine status determines ovarian response to gonadotropin treatment in sheep. Biol Reprod. 2009;80:743-752.
4. Watkins AJ, Fleming TP. Blastocyst environment and its influence on offspring cardiovascular health: the heart of the matter. J Anat. 2009;215:52-59.
5. Aagaard-Tillery KM, Grove K, Bishop J, et al. Developmental origins of disease and determinants of chromatin structure: maternal diet modifies the primate fetal epigenome. J Mol Endocrinol. 2008;41:91-102.