What Are the Breathing Complications of Holoprosencephaly?

Many parents worry about whether their baby will have trouble breathing after birth. If you have received a holoprosencephaly (HPE) diagnosis during pregnancy, working with your Maternal-Fetal Medicine (MFM) specialist and a neonatologist to create a clear delivery room plan is one of the most important steps you can take. Babies with HPE can experience breathing difficulties, though the severity depends heavily on their specific facial and brain development. These breathing challenges generally fall into two categories: obstructive issues (where the physical airway is blocked or narrow) and central apnea (where the brain struggles to consistently send the signal to breathe). ^[1][2]

Anatomical and Obstructive Breathing Challenges

Learning about the physical differences associated with HPE can be deeply overwhelming. Because HPE affects how the center of the face and brain develops, many babies are born with differences in their nose, mouth, and throat. ^[3][4] Newborns are “obligate nasal breathers,” meaning they instinctively breathe through their noses rather than their mouths. If the nasal passages are narrow or blocked, it can cause immediate respiratory distress. ^[5]

Common physical causes of airway obstruction in HPE include:

• Nasal stenosis or atresia: The nasal passages may be unusually narrow (such as pyriform aperture stenosis) or completely blocked off at the back of the nose. ^[6][5]
• Severe facial clefts: A cleft lip or palate can change the structure of the airway and complicate breathing, especially during feeding. ^[1] This can also increase the risk of aspiration (inhaling milk or saliva into the lungs), which is why Speech-Language Pathologists (SLPs) or feeding specialists are often involved in evaluating the airway. ^[1]
• Arhinia, Cebocephaly, or Proboscis: In severe cases (often alobar holoprosencephaly), a baby’s face may develop significantly differently. They may be born without a nose (arhinia), with a single central nostril (cebocephaly), or with a tube-like appendage (proboscis). ^[7][1] While this is incredibly difficult to process as an expecting parent, your medical team will guide you through these challenges with compassion and immediate support to secure an open airway. ^[2]

Central Apnea and Autonomic Instability

In addition to physical blockages, the brain malformation itself can affect breathing. HPE involves differences in the forebrain, which can indirectly impact or be associated with changes in the brainstem and hypothalamus—areas that regulate automatic bodily functions. ^[8][1]

This can lead to central apnea, a condition where the brain momentarily pauses or “forgets” to signal the lungs to breathe. ^[1] Instead of struggling against a blocked airway, a baby with central apnea simply stops breathing for brief periods. These neurological differences can also cause broader autonomic instability, meaning the baby might experience sudden fluctuations in their heart rate, body temperature, and respiratory rate. ^[1]

In the Neonatal Intensive Care Unit (NICU), these pauses and fluctuations will trigger monitor alarms. Hearing these alarms and seeing your baby’s color change can be terrifying, but the monitors are there so the nursing staff can step in immediately to gently stimulate your baby or provide oxygen. ^[9]

How Your Care Team Will Help

Because airway management in HPE can be highly complex, a coordinated multidisciplinary team is critical before and immediately following birth. ^[10][1]

• Otolaryngologist (ENT): An ear, nose, and throat specialist will carefully evaluate your baby’s physical airway, often using a small camera (airway endoscopy) to identify exact areas of narrowing. ^[11] If there is a physical blockage, they may recommend specific sleep positioning, specialized tubes to hold the nasal passage open (nasopharyngeal stenting), or non-invasive breathing masks (CPAP). ^[12][13] In some instances, orthodontic or surgical approaches are used to widen the airway. ^[6][14] For the most severe cases of airway obstruction, the team might gently discuss creating an airway in the neck through surgery (tracheostomy). ^[15]
• Pulmonologist and Neonatologist: These lung and newborn specialists will focus on supporting your baby’s overall respiratory health. They will use cardiorespiratory monitoring to watch for central apnea and can provide breathing machines if the baby’s brain needs help maintaining a steady respiratory rhythm. ^[9][13]
• Palliative and Complex Care Teams: Severe cases of HPE, particularly alobar HPE with severe central apnea and significant facial differences, carry a guarded prognosis. ^[16][17] Some intensive interventions may not lead to long-term survival. Palliative care specialists are vital members of the team—not just for end-of-life care, but to help families navigate difficult decisions about which medical interventions truly align with their goals for their baby’s comfort and quality of life. ^[1]