CO2 plays a key role in several critical physiological processes, including:

• Regulating cerebral blood flow
• Maintaining blood pH
• Triggering respiratory drive (the signal that tells the body when and how much to breathe)
• Facilitating oxygen delivery to tissues

Protecting the developing brain remains one of the highest priorities in neonatal intensive care, making the relationship between CO2 and cerebral blood flow especially important. In healthy, full-term infants, the brain can autoregulate its own blood flow. In preterm infants, however, autoregulation is immature,¹ and even small shifts in CO2 can cause harmful changes in cerebral blood flow and pressure, risking injury to the brain.2-5

Maintaining CO2 within safe ranges is therefore critical, as both hypocapnia (low CO2) and hypercapnia (high CO2) — as well as rapid fluctuations — have been shown to carry significant risks for neonates.

Hypercapnia (also called hypercarbia) refers to above-normal CO2 levels. When CO2 levels are elevated, cerebral arteries and arterioles dilate, increasing cerebral blood flow and raising the risk of various types of brain injury.² At the same time, CO2 accumulation can lower an infant’s blood pH, contributing to additional complications.

Several studies have linked hypercapnia to adverse outcomes, including:

• Intraventricular hemorrhage (IVH)^2,3,5
• Bronchopulmonary dysplasia (BPD) in low-weight infants⁶
• Necrotizing enterocolitis (NEC)⁷
• Retinopathy of prematurity (ROP)⁸
• Worse prognosis in infants with congenital diaphragmatic hernia (CDH)⁹
• Respiratory acidosis¹⁰

Hypocapnia (also called hypocarbia) refers to below-normal CO2 levels. Hypocapnia reduces cerebral blood flow, which can increase the risk of neurological injury and other complications. It can also raise a neonate’s blood pH above normal, creating additional risks.

Several studies have linked hypocapnia to adverse outcomes, including:

• Cerebral palsy (CP)¹¹
• Intraventricular hemorrhage (IVH)²
• Periventricular leukomalacia (PVL)¹²
• Cognitive developmental disorder¹³
• Respiratory alkalosis¹⁴

Many premature neonates require some form of respiratory support, such as noninvasive or invasive mechanical ventilation, due to their underdeveloped respiratory systems.¹⁵ The goal is to ensure adequate gas exchange (oxygenation and CO2 removal), while also minimizing ventilator induced lung injury (VILI). Because these infants are extremely fragile, maintaining that delicate balance is both challenging and critical for achieving the best possible outcomes.

To optimize ventilation, it is essential to monitor key gas exchange targets closely. CO2 is a direct reflection of how well ventilation matches metabolic demand, making it one of the most important parameters guiding ventilator management. Continuous CO2 monitoring not only shows whether settings are supporting effective gas exchange and helps clinicians avoid the risks of too-high or too-low CO2, but it also signals when support may be too strong — preventing potential lung overdistention and injury.

Although there is no universal consensus on the optimal pCO2 range for neonates, a recent review of the literature suggests that maintaining a pCO2 level of 37.5-52.5 mmHg is safe and effective in premature infants.⁷

For preterm neonates on noninvasive ventilatory support, a permissive hypercapnia strategy — maintaining PaCO2 levels around 40 – 55 mmHg — is also often used and recommended.¹⁶ This approach may reduce the need for prolonged mechanical ventilation and decrease the risk of ventilator-induced lung injury.

Optimal CO2 targets can vary depending on each infant’s condition and diagnosis. The chart below summarizes recommended CO2 target ranges for neonates, along with suggested interventions to help maintain target levels, or correct values that fall outside the desired range.

With the right approach to CO2 monitoring, care teams can optimize ventilation strategies while safeguarding both brain and lung health. Ongoing visibility can provide care teams with the insights they need to respond early to fluctuations, individualize care strategies, and prevent complications. Several methods are available to monitor CO2 in the NICU, each with unique strengths and limitations:

• Arterial Blood Gas (ABG): ABG tests measure CO2 and other blood gases directly from an arterial sample, providing highly accurate results and insight into acid–base balance. While considered the gold standard, the downsides of ABG tests include that they are invasive (increasing infection risk), provide only intermittent readings, contribute to pain and stimulation, and are a main contributor to blood loss in neonates.
• Capnography (End-tidal CO2): Capnography continuously measures CO2 in exhaled air, offering real-time trends and a waveform that can help identify lung compliance and airway resistance issues. While this technology is noninvasive, it is often infeasible with many patients in the NICU: uncuffed endotracheal tubes, added dead space, ventilation-perfusion (V/Q) mismatch, and low tidal volumes can cause inaccurate readings, and it is incompatible with noninvasive or high-frequency ventilation.
• Transcutaneous CO2 (tcPCO2) Monitoring: Transcutaneous CO2 monitoring is a continuous, noninvasive method where a sensor is placed on the neonate’s skin and gently heated. This heating enhances local perfusion, allowing CO2 from the blood to diffuse through the skin into the sensor, which then accurately estimates arterial CO2 levels. Although factors like poor tissue perfusion may affect accuracy in some patients, it is compatible with both noninvasive and high-frequency ventilation and is a good option for very low birth weight babies in the NICU.