Baby’s First Breath Triggers Life-Saving Changes in the Brain

Summary: A baby’s first breath triggers a signaling system in the brain stem that helps support early breathing. The findings shed light on how problems with this neuropeptide system can increase the risk of SIDS.

Source: University of Virginia

There are few moments in life as precious, as critical and as celebrated as baby’s first breath. New research from the School of Medicine sheds light on the lifelong changes in breathing systems that occur precisely with that first breath – and may offer important insights into Sudden Infant Death Syndrome (SIDS).

A team of researchers led by UVA’s Yingtang Shi, MD; Patrice Guyenet, PhD; and Douglas A. Bayliss, PhD, have discovered a signaling system within the brainstem that activates almost immediately at birth to support early breathing. That first gasp that every parent cherishes appears to trigger this support system.

“Birth is traumatic for the newborn, as the baby has to independently take control over various important body functions, including breathing,” said Bayliss, chairman of UVA’s Department of Pharmacology. “We think that activation of this support system at birth provides an extra safety factor for this critical period.”


The new findings help researchers understand how breathing transitions from a fragile state susceptible to brain-damaging and potentially deadly pauses early in development to a stable and robust physiological system that flawlessly supplies the body with oxygen for the rest of our lives. Before a baby is born, breathing is not required and breathing movements occur only intermittently, so the transition at birth can be a highly vulnerable time.

Bayliss and his colleagues at UVA, working with researchers at the University of Alberta and Harvard University, found that a specific gene is turned on immediately at birth in a cluster of neurons that regulate breathing selectively in mice. This gene produces a peptide neurotransmitter – a chain of amino acids that relays information between neurons. This transmitter, called PACAP, starts to be released by these neurons just as the baby emerges into the world.

The scientists determined that suppressing the peptide in mice caused breathing problems and increased the frequency of apneas, which are potentially dangerous pauses in breathing. These apneas further increased with changes in environmental temperature. These observations suggest that problems with the neuropeptide system may contribute to SIDS.


SIDS, also known as crib death, is the sudden unexplained death of a child less than a year of age. It is the leading cause of infant mortality in Western countries. SIDS is attributed to a combination of genetic and environmental factors, including temperature. UVA’s new research suggest that problems with the neuropeptide system may increase babies’ susceptibility to SIDS and other breathing problems.

This shows a newborn baby
Before a baby is born, breathing is not required and breathing movements occur only intermittently, so the transition at birth can be a highly vulnerable time. Credit: University of Virginia

PACAP is the first signaling molecule shown to be massively and specifically turned on at birth by the breathing network, and it has been linked genetically to SIDS in babies. The causes of SIDS likely are complex, and there may be other important factors to discover, the researchers note.

“These finding raise the interesting possibility that additional birth-related changes may occur in the control systems for breathing and other critical functions,” Bayliss said. “We wonder if this could be a general design principle in which fail-safe support systems are activated at this key transition period, and that understanding those may help us better treat disorders of the newborn.”


The researchers have published their findings in the prestigious scientific journal Nature. The research team consisted of Yingtang Shi, Daniel S. Stornetta, Robert J. Reklow, Alisha Sahu, Yvonne Wabara, Ashley Nguyen, Keyong Li, Yong Zhang, Edward Perez-Reyes, Rachel A. Ross, Bradford B. Lowell, Ruth L. Stornetta, Gregory D. Funk, Patrice G. Guyenet and Douglas A. Bayliss.

Funding: The work was supported by the National Institutes of Health, grants R01 HL108609, R01 HL074011, R01 DK096010, R01 DK075632, K08 DK118201 and T32 HL007374; the Congenital Central Hypoventilation Syndrome Family Foundation; Canadian Institutes of Health Research; and by a Harrison Undergraduate Research Award.

About this neurodevelopment research news

Source: University of Virginia
Contact: Joshua Barney – University of Virginia
Image: The image is credited to University of Virginia

Original Research: Closed access.
A brainstem peptide system activated at birth protects postnatal breathing” by Yingtang Shi, Daniel S. Stornetta, Robert J. Reklow, Alisha Sahu, Yvonne Wabara, Ashley Nguyen, Keyong Li, Yong Zhang, Edward Perez-Reyes, Rachel A. Ross, Bradford B. Lowell, Ruth L. Stornetta, Gregory D. Funk, Patrice G. Guyenet & Douglas A. Bayliss. Nature


A brainstem peptide system activated at birth protects postnatal breathing

Among numerous challenges encountered at the beginning of extrauterine life, the most celebrated is the first breath that initiates a life-sustaining motor activity1. The neural systems that regulate breathing are fragile early in development, and it is not clear how they adjust to support breathing at birth. Here we identify a neuropeptide system that becomes activated immediately after birth and supports breathing. Mice that lack PACAP selectively in neurons of the retrotrapezoid nucleus (RTN) displayed increased apnoeas and blunted CO2-stimulated breathing; re-expression of PACAP in RTN neurons corrected these breathing deficits. Deletion of the PACAP receptor PAC1 from the pre-Bötzinger complex—an RTN target region responsible for generating the respiratory rhythm—phenocopied the breathing deficits observed after RTN deletion of PACAP, and suppressed PACAP-evoked respiratory stimulation in the pre-Bötzinger complex. Notably, a postnatal burst of PACAP expression occurred in RTN neurons precisely at the time of birth, coinciding with exposure to the external environment. Neonatal mice with deletion of PACAP in RTN neurons displayed increased apnoeas that were further exacerbated by changes in ambient temperature. Our findings demonstrate that well-timed PACAP expression by RTN neurons provides an important supplementary respiratory drive immediately after birth and reveal key molecular components of a peptidergic neural circuit that supports breathing at a particularly vulnerable period in life.

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