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Releases Packard
Children's News
Children's Fund
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How Sex Hormones Affect the Fetal BrainBY MEREDITH ALEXANDER KUNZ WINTER 2006 -- Throughout pregnancy, a mother's placenta surrounds her baby with life-giving nutrients and hormones that help the fetus develop into a healthy newborn. Infants born prematurely, however, lose the full benefit of this organ and can face serious complications. Many spend months in the neonatal intensive care unit (NICU), building strength in their lungs and learning how to suck and swallow.
But long after they have graduated from the NICU, extremely premature babies can face another challenge. For reasons not fully understood, those born before 28 weeks gestation are at high risk for neurological difficulties, often causing them to lag behind their peers in brain development well into childhood. Packard neonatologist Anna Penn, MD, PhD, wants to understand why. In concert with fellow faculty members in Stanford's Neuroscience Institute, she is using her background in developmental biology to find ways to nurture brain development in preemies. Their work spans fields as diverse as neurosurgery, computer science, maternal-fetal medicine, and biology. "Stanford is a terrific place to do this work, because I can draw upon the strengths in basic science programs such as neuroscience and developmental biology, as well as the clinical expertise in neonatology at Packard Children's," Penn says. The Role of Sex Steroids
Penn and her colleagues are taking a new approach to preemies' developmental problems by focusing on the sex steroids estrogen and progesterone, produced in high levels by the mother's placenta. So far, Penn says, few researchers have investigated the potentially vital role these steroidal hormones play in brain development outside of sexual regions in the brain. For example, while scientists already know that estrogens have an important impact on the adult brain -- research has shown that estrogens can prevent damage from aging and stroke and even slow the onset of Alzheimer's -- no one is certain about their effects on a baby's neurons. Could it be that losing placental sex steroids harms the preemie's brain development? To answer this question, Penn's research is focusing on two portions of the brain, the cerebellum and the hippocampus. "From 24 weeks to birth, these are the areas of the brain that are still generating new neurons," she says. To uncover how these hormones affect brain development, Penn is using a mouse model to examine how many neurons are made, how many survive, and the location of specific hormone receptors at different stages of development. A Customized CocktailPenn's ultimate goal is to create a means of replacing lacking hormones for premature babies with a "cocktail" of drugs customized to a baby's gestational age and specific needs.
"Development is an ongoing process, and you have to tailor the timing and type of hormones you're giving to the physiological stage of the preemie," says Penn. The exact cocktail would be "monitored and modified as the infant is developing, to maximize its neurological potential," she explains. The course of treatment could last months, "during the period in which the baby would have been in utero," Penn says. Such therapy could help preemies make up for lost time in the womb, Penn and her collaborators hope. For a generation of premature babies, this treatment would offer the chance for them to catch up to other kids developmentally, no longer trailing behind after coming into the world early.
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