Placental Allopregnanolone Levels Rise During Pregnancy

The placenta is the source of more than 200 different hormones that each uniquely contribute to the smooth running of the pregnancy and the fetus' overall health. The placenta carefully calibrates how much of the hormone allopregnanolone (ALLO) it produces during pregnancy.

ALLO, a progesterone derivative, may protect the developing fetal brain in pregnancies compromised by such conditions as high blood pressure. It is known that ALLO is made in the adult brain in response to stress and modulates neuronal excitability. Less is known about how placental ALLO levels evolve during pregnancy and in newborns shortly after birth.

Multi-institutional scientists working with the Children's National Health System (Washington, DC, USA) analyzed cord blood or serum samples collected within the first 36 hours of life for 61 preterm newborns born between 24 to 36 gestational weeks. They compared those preemie samples with samples drawn from 61 newborns carried to term that were matched by race, gender, size for gestational age, delivery method and maternal demographics.

The team used liquid-chromatography-tandem mass spectrometry, a technique that can precisely analyze trace levels of compounds, to compare levels of 27 different steroids, including ALLO and its precursors as well as better-known adrenal gland hormones, such as cortisol and 17-Hydroxyprogesterone. Anna Penn, MD, PhD, a neonatologist/neuroscientist and lead scientists on the study created a model to study how premature loss of ALLO alters orderly brain development. Knowing more about the interplay between ALLO and normal development of the cortex, the outer layer of the cerebrum, is a first step that could lead to strategies to rescue this vital brain region.

Dr. Penn said, “Pregnancies complicated by hypertension tended to correlate with lower ALLO levels, though this finding did not reach statistical significance. This suggests that ongoing placental dysfunction and ALLO loss, not the increase that we expected to be caused by stress, may alter cortical development in these pregnancies and put babies at risk. The cortex is basically the brain's command-and-control center for higher functions. In our model, it develops from the middle of gestation through to the end of gestation. If ALLO levels are disrupted just as these cells are being born, neurons migrating to the cortex are altered and the developing neural network is compromised.” The study was presented at the Pediatric Academic Societies (PAS) 2018 annual meeting held May 5-8, 2018, in Toronto, ON, Canada.

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Children's National Health System