Much of the body runs on autopilot. Think about your heartbeat, digestive system or blood pressure, or even your fight-or-flight response when you're stressed or in danger. This pilot is called the Autonomic Nervous System (ANS). One of the largest nerves contained in this system is the Vagus Nerve. It's responsible for making sure your body functions smoothly without you having to think about it.

Beginning at conception, a timeline of creation builds the ANS as well as the organs, muscles and other parts of the body it connects to. The authors of this study were able to shed light on what happens when opioids are introduced to this process.

Title: A Review on the Vagus Nerve and Autonomic Nervous System During Fetal Development: Searching for Critical Windows

Published in Frontiers in Neuroscience , September 2021

Summary in plain English :

Synopsis

The autonomic nervous system (ANS) is a vital system in our bodies that controls various functions automatically. It starts working even before we're born, helping in the development of the fetus. One important part of this system is the vagus nerve, which plays a crucial role in many processes, from keeping inflammation in check to producing hormones for energy. It's also the main way our organs communicate with the brain.

This article explores how the ANS, especially the vagus nerve, develops in babies before and after birth. It looks at factors like the baby's characteristics, the mother's lifestyle and health, the health of the placenta, the conditions during birth, and exposure to medications to see how they might affect the vagus nerve's development during these crucial periods.

Understanding this can help doctors and other healthcare professionals create better guidelines for caring for babies, especially to reduce the chances of long-term problems related to the development of the ANS.

The timeline below, provided for reference, shows the main events related to ANS development.

CAN, central autonomic network; fHRV, fetal heart rate variability; FM, fetal movement; GM, general movement; PNS, parasympathetic nervous system.

Findings

The full article (link below) provides a detailed description of development during the 1st, 2nd and 3rd trimesters. There are even important developments during labor and in postnatal life. For the purpose of this summary, focus will be on findings relevant to prenatal opioid exposure. And since many opioid exposed babies are born prematurely, it's important to point out how that may affect the baby as well.

Premature Birth and the Autopilot System: When infants transition from being inside the womb to being born, their bodies need a hormone called cortisol to help with this change. But in cases of premature birth. or when labor doesn't happen naturally, the release of cortisol is significantly reduced. If there's not enough cortisol, it can affect the development of the Central Autonomic Network (CAP). And when cortisol levels are low, it can also lead to problems in controlling inflammation after birth. For example, it could contribute to conditions like necrotizing enterocolitis (NEC), which can harm the cells in certain parts of the brain related to the vagus nerve.

It takes about 37 weeks in the womb for the ANS to fully develop. So, when babies are born too early, they may struggle to handle changes in their body caused by the outside world. Additionally, premature babies often need intense medical care, like help with breathing or various drugs, which can put extra stress on their immature autonomic nervous system. In fact, it seems that even when premature babies catch up to the age when they should have been born, their ANS response is quite low in comparison to full-term babies.

Issues after 40 Weeks: Although premature babies can develop a reasonably healthy autonomic nervous system after 2-3 years, issues with the ANS often persist into later life. These issues can come with problems in regulating the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis, both when they're awake and when they're asleep.

Problems with the ANS during a baby's first year of life can lead to issues with how the heart and blood vessels work. This means it's really important to watch how the ANS develops during the first two years of life to identify babies who might be at risk. If the ANS doesn't mature properly due to things like inflammation, being born prematurely, or being smaller than usual, it can also increase the chances of developing conditions like type 2 diabetes later in life. These conditions, along with others related to metabolism and the immune system, may be linked to how the ANS regulates inflammation.

Additionally, problems with the ANS in newborns can cause issues with the brain and how it functions, and can even lead to conditions like cerebral palsy by the time a child is 2 years old. Since the development of the ANS is connected to the development of the fetal movements, ANS issues can also affect the growth of the central nervous system and behavior. On one hand, fetal movements are linked to the body's fight-or-flight response, which influences how we react to stress. On the other hand, problems with the ANS maturation are linked to changes in how the brain and motor skills develop, which can affect cognitive abilities, language, play, and social skills.

The immaturity of the autonomic nervous system, due to complications that occur before or after birth, such as maternal health issues or difficult births, can affect the overall development of the brain. This, in turn, can influence behavior, the ability to handle stress, and mood regulation. In some cases, it can even lead to serious neurological or psychological problems in infants, adolescents, and adults. Even medical procedures that cause pain during hospital stays can disrupt the regulation of stress and the development of the brain in newborns.

What can be done: Given the potential long-term harm caused by ANS problems, it's crucial to focus on protective measures that support the maturation of the ANS. Breastfeeding, stress reduction during pregnancy, skin-to-skin contact, and social interactions between newborns and parents or caregivers can help babies develop a well-functioning ANS, reduce stress, build resilience, and enhance their brain's adaptability.

Opioid-specific: Overexposure to opioids during pregnancy can harm various fetal systems, including the cardiovascular, respiratory, neurobehavioral, metabolic, and neuroendocrine systems. Early exposure to buprenorphine can lead to higher fetal heart rate variability. Fetuses exposured later in pregnancy (32-36 weeks), display less suppression of motor activity, possibly involving the vagus nerve system. Opioid dependence is also linked to an increased risk of Neonatal Abstinence Syndrome (NAS) and Neonatal Opioid Withdrawal Syndrome (NOWS).

Newborns with NOWS show changes in the levels of various neurotransmitters and hormones, suggesting a potential disruption in vagal and central autonomic pathway activity. Prenatal opioid exposure might program the stress response systems, possibly leading to long-term consequences.

Conclusion

When opioids are involved in building the body’s autopilot system, the opportunity for construction mishaps is high.

Many thanks to the authors of this article: Cerritelli F, Frasch MG, Antonelli MC, Viglione C, Vecchi S, Chiera M and Manzotti A

The full report is accessible here: https://doi.org/10.3389/fnins.2021.721605