- More than one-third of resuscitated infants born alive at 21 weeks' gestational age survived to hospital discharge in a single-center study.
- Among 22 infants born alive, resuscitation was attempted on 17, with six surviving to discharge from the NICU.
- Long-term outcome data were not available, and ethical questions regarding previable resuscitation remain.
More than a third of resuscitated infants born alive at 21 weeks' gestational age -- an age previously believed to be previable -- survived to discharge, a single-center, retrospective case series showed.
Among 22 infants born alive, resuscitation was attempted in 17. Of these, six survived to discharge from the neonatal intensive care unit (NICU) and one remained hospitalized, while 10 died, reported Patrick McNamara, MBBCh, MSc, of the University of Iowa in Iowa City, and colleagues.
Five infants who survived had early cardiorespiratory instability treated with vasoactive medications and/or inhaled nitric oxide. Three had no or grade 1 intraventricular hemorrhage (IVH), two had grade 2 IVH, and two had grade 3 (severe) IVH, though none of the infants required neurosurgical intervention. The six infants who survived to discharge received low-flow supplemental oxygen, and none required tracheostomy, the researchers noted in JAMA Network Open.
"The fact survival is possible at 21 weeks gestation, and more so with minimal morbidity in some cases, will be surprising to some clinicians," McNamara and co-author Rachael Hyland, MD, also of the University of Iowa, told MedPage Today in an email. "In addition, the ethics of resuscitation at this gestation will also be questioned by other experts, given the fact that adverse neurodevelopmental outcome occurs in many extremely preterm infants (even greater than 22 weeks' gestation) in some centers."
The case series was small and the results apply to the approach at their center, so it is hard to draw meaningful broad conclusions, acknowledged McNamara and Hyland. "Nevertheless, our findings are hypothesis generating and clearly show that some infants born at this gestation can survive."
With advances in medical care and evolving experience, the earliest gestational age at which neonatal resuscitation is offered continues to decrease, McNamara and colleagues noted.
"The latest U.S. cohort data, collected from 2013 to 2018 and again from 2020 to 2022, report survival rates of 30% to 35% for infants born at 22 weeks' gestational age receiving resuscitation, improved from 23% survival in a similar population from 2006 to 2011," the researchers wrote. "There is considerable variability in survival at this gestational age, however, with reported survival as low as zero and as high as 83% within international and single-center cohorts."
"Resuscitation at less than 22 weeks' gestational age has been historically rare," they added, "but in some centers, resuscitation at 21 weeks is now offered in selected cases."
In an accompanying editorial, Steven McElroy, MD, of UC Davis Children's Hospital in Sacramento, noted that this case series has generated both enthusiasm as well as concern, as questions like "what exactly does viability mean?" as well as "whether survival is enough" remain.
Bioethics is an important consideration, he pointed out. "While the autonomy of the patient born at 21 weeks is critical, we must also consider nonmaleficence and beneficence," he wrote. "Given the data we have, are we acting on the best behalf of these infants?"
All discharged patients in the study were followed up with serial developmental assessments, but findings were limited due to the early chronological age of the survivors; only four were older than 6 months corrected age at the time of the study's completion.
One survivor was older than 2 years corrected age, and their developmental assessment findings were normal, McNamara and colleagues reported. The other three who were older than 6 months corrected age were "delayed in their milestones but progressing." Two were diagnosed with spastic-type cerebral palsy, one had mild to moderate hearing loss, and one had visual defects requiring glasses.
Overall, three of the six survivors to discharge required rehospitalization for reasons including respiratory viral illness, inadequate weight gain, gastrostomy tube placement, and a supraglottoplasty for laryngomalacia.
"Despite these concerns, there is room for cautious optimism," McElroy said. "Our field is constantly pushing the limits of who we can help and finding better and more efficient ways to do it."
The study included all infants born alive at a gestational age of 21 weeks 0 to 6 days from January 2010 to February 2025. Live birth was defined as any evidence of activity or heart rate present, and resuscitation was broadly defined as any attempt to revive or stimulate.
There were 22 infants born alive at 21 weeks' gestational age, and an additional 230 fetuses were classified as stillbirths at 21 weeks during the period. Seventeen of the 22 liveborn infants were resuscitated (8 female and 9 male) and included in the analysis. Median age was 21 weeks and 5 days.
Over the course of the study period, rates of resuscitation and NICU admission increased. From 2010 to 2019, six infants were born alive, with resuscitation attempted in three. However, none of these infants survived. From 2020 to February 2025, 16 infants were born alive, with resuscitation attempted in 14, six of whom survived to discharge.
Survivors were less likely to be part of a multiple gestation (one of seven vs six of 10 who died), and were more likely to have received a complete course of antenatal steroids (three of seven vs none of 10).
Limitations of the study included its small numbers and single-center experience. All infants in the cohort were born vaginally, and results do not apply to other obstetric delivery practices, McNamara and colleagues noted.
The research team further pointed to ethical questions regarding previable resuscitation, which they noted are "complex and beyond the scope of this study."
"We suggest that consideration of resuscitation at 21 weeks is ethically permissible in experienced centers of excellence when there is shared decision-making between families and clinicians," they wrote.
McNamara and colleagues stressed the need for long-term outcome data.
Disclosures
Neither McNamara nor Hyland reported any relevant disclosures. A co-author of the study reported receiving grant support from the NIH outside the submitted work.
McElroy did not report any relevant disclosures.
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