PWS study disputes growth hormone link to infant sleep apnea
Data show most babies experience dangerous breathing blocks before therapy
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Most infants with Prader-Willi syndrome (PWS) experience sleep-disordered breathing and obstructive sleep apnea before ever starting growth hormone therapy, a small Belgian study shows.
The findings challenge previous suggestions that growth hormone therapy, a standard treatment for PWS, is what primarily drives the risk of obstructive sleep apnea (OSA), a condition where breathing repeatedly stops and starts due to airway blockages.
Because these vulnerable infants often have trouble waking up or responding properly to breathing distress, they may face a higher risk of sudden death, researchers noted. The study emphasized that individualized sleep monitoring strategies are essential to protect these infants from severe respiratory complications.
“These findings may contribute to a better understanding of early respiratory [breathing] manifestations in PWS and raise important questions about their underlying mechanisms, which are likely multifactorial and remain incompletely understood,” researchers wrote.
How PWS affects sleep and breathing
In addition, because “these infants often have impaired arousal responses and may fail to wake up or respond adequately to respiratory distress,” they may be at a higher risk of sudden death, the researchers wrote. “Given the respiratory vulnerability of these infants, individualized monitoring strategies, comprising PSG [polysomnography] and selective home monitoring, are essential to mitigate respiratory complications.”
PSG is a test that monitors breathing, oxygen levels, brain activity, and other body functions during sleep.
The study, “Polysomnographic findings and brain maturation in infants with Prader-Willi syndrome: a retrospective observational study,” was published in the journal Sleep and Breathing.
Children with PWS, a complex genetic disease, may experience a wide range of symptoms, including slow growth, low muscle tone, excessive hunger, and behavioral problems. PWS also affects areas of the brain involved in sleep and breathing, which can disrupt the signals that control breathing during sleep.
As a result, children with PWS may develop central sleep apnea, in which the brain does not consistently send the right signals to breathe, or sleep-related hypoventilation, meaning slow or shallow breathing during sleep.
Many PWS patients have low levels of growth hormone (GH), which is involved in physical development and other processes. As such, GH therapy, also known as somatropin (sold as Genotropin and Norditropin, with biosimilars available), is commonly used in children with PWS.
However, some studies have suggested the treatment may increase the risk of developing OSA. This is thought to be due to enlargement of the tonsils and adenoids, immune structures located in the back of the throat and nose.
Still, “research on sleep and SDB [sleep-disturbed breathing] in infants with PWS remains limited,” the researchers wrote.
With this in mind, a team of researchers in Belgium retrospectively analyzed data from seven infants, from less than 1 month old to up to 1 year, who were diagnosed with PWS between February 1965 and December 2023 at a single hospital.
Six infants underwent PSG, and the remaining newborn underwent only a sleep electroencephalography (EEG), which records brain activity during sleep, at 2 days old, and died suddenly before the planned PSG could be completed.
These tests were “conducted at various ages, ranging from 2 days to 11 months, all prior to the initiation of GH therapy,” the team wrote.
None of the infants who underwent PSG met the threshold for clinically significant central sleep apnea. Newborns tended to have more central apnea events than older infants, but this difference failed to reach statistical significance.
High rates of sleep apnea detected
In contrast, clinically relevant OSA was detected in four of the six infants with PSG data (66.6%). OSA was classified as mild in half of the cases, and as moderate in the other half.
Two infants with OSA also had paradoxical breathing, an abnormal breathing pattern in which the chest and abdomen move out of sync. This breathing pattern appeared more pronounced in newborns, although the difference did not reach statistical significance.
Oxygen levels also dropped during sleep on several occasions. The median lowest oxygen saturation level, a proxy for blood oxygen levels, was 76%, with individual lows ranging from 68% to 82%.
Brain-wave findings varied. Some infants had age-appropriate EEG patterns, while others showed signs of delayed brain maturation or immature sleep regulation. However, apnea measures and paradoxical breathing were not significantly higher in infants with immature EEG patterns, contrary to expectations.
Overall, these results suggest that OSA and oxygen drops during sleep may occur early in infants with PWS, even before GH therapy begins.
Among the six surviving infants, all later started GH therapy between the ages of 6 months and 2.5 years. Two children later underwent adenotonsillectomy, a surgery to remove the adenoids and tonsils.
“Our findings, together with a review of the literature, highlight the importance of detecting sleep apnea in infants with PWS,” the team wrote. “Future research involving larger, multicenter [studies] and the incorporation of EEG assessments is crucial to deepen our understanding of the interplay between brain dysmaturity and SDB. Such insights will inform early intervention strategies and ultimately improve clinical outcomes.”
