Prophylactic CPAP for Late Preterm Infants Born by C-Section to Reduce NICU Admission

Late preterm infants are at increased risk of respiratory morbidity during the transition from fetal to newborn life. This risk is particularly important among infants born by cesarean section. These infants do not experience some of the physiologic changes associated with labor and vaginal delivery that promote lung fluid clearance and adaptation to air breathing. As a result, respiratory distress is a common reason for neonatal intensive care unit (NICU) admission in this population.

NICU admission may be necessary when an infant requires respiratory support or other intensive care. However, NICU admission also separates infants from their families and may affect early bonding and breastfeeding. Preventing respiratory deterioration before it requires escalation of care could therefore have benefits for both infants and families.

Continuous positive airway pressure (CPAP) is widely used to support newborns who develop respiratory distress. CPAP helps maintain lung expansion and supports breathing without the need for an endotracheal tube. In current practice, CPAP is generally used after signs of respiratory difficulty appear. The PLaNT 2 study evaluates a different approach: providing a brief period of CPAP soon after birth to infants at increased risk, before respiratory distress develops.

Rationale and Preliminary Evidence PLaNT 2 builds on an international, multicenter pilot randomized controlled trial of prophylactic CPAP in spontaneously breathing late preterm infants born by cesarean section. The pilot trial evaluated feasibility, safety, and preliminary evidence of benefit.

A total of 122 infants were enrolled at five centers in the United States, Canada, and Chile, and 115 infants were included in the analysis. No pneumothorax or other serious adverse events were observed in either study group.

The pilot study also showed promising respiratory outcomes. Among the prespecified subgroup of infants born at 35 to 36 weeks of gestation, NICU admission for respiratory reasons occurred in 38% of infants receiving standard care compared with 16% of infants receiving prophylactic CPAP. The need for subsequent respiratory support during the first week was also lower in the prophylactic CPAP group. These findings supported the development of a larger trial focused on infants born at 35 to 36 weeks of gestation.

The pilot was not designed to provide definitive evidence that prophylactic CPAP improves clinical outcomes. PLaNT 2 is designed to answer this question in a larger, international population.

Study Rationale PLaNT 2 is a pragmatic, multicenter, international randomized controlled trial comparing prophylactic CPAP with standard care in late preterm infants born by cesarean section.

The study focuses on infants born at 35 to 36 weeks of gestation because infants born before 35 weeks are routinely admitted to a NICU or special care nursery at many hospitals regardless of their respiratory status. In contrast, infants born at 35 and 36 weeks are not routinely admitted to the NICU. Respiratory problems therefore represent an important and potentially preventable reason for NICU admission in this group.

The intervention is intended to support the infant during the early transition after birth. Rather than waiting for respiratory distress to develop before providing CPAP, the study tests whether a short period of prophylactic CPAP can support lung expansion and respiratory transition before clinically important respiratory problems develop.

The study intervention does not replace standard neonatal care. Infants in either study group may receive CPAP or other respiratory support when clinically indicated. Rescue CPAP is considered part of standard clinical care and is not considered a protocol deviation.

Study Design Families will be approached for informed consent before delivery. Final newborn eligibility will be confirmed after birth.

Because the study evaluates prophylactic CPAP in spontaneously breathing infants, allocation will remain concealed until the clinical team confirms that the infant has established spontaneous breathing within the first 5 minutes after birth. Brief positive-pressure ventilation before spontaneous breathing is established does not by itself make an infant ineligible if spontaneous breathing is subsequently established within this period. Infants who are not spontaneously breathing by 5 minutes will not be randomized and will continue to receive clinically appropriate care.

Participants will be assigned in a 1:1 ratio to prophylactic CPAP or standard care. Randomization will be stratified by participating site and gestational age. Site-specific, sequentially numbered, opaque, sealed envelopes will be used to conceal and implement treatment allocation. Separate envelope sequences will be maintained for the gestational-age strata. For twin pregnancies, one envelope will be used to randomize the pregnancy, and both twins will receive the same study-group assignment.

Infants assigned to the intervention will receive a brief period of prophylactic CPAP beginning shortly after birth. CPAP may be provided at the radiant warmer or while the infant is on the mother's chest when clinically and operationally appropriate. Infants assigned to the control group will receive standard care. Clinical teams in both groups retain full responsibility for the infant's care and may initiate or escalate respiratory support whenever medically indicated.

Assessment of Respiratory Outcomes The primary clinical question is whether prophylactic CPAP lowers NICU admission for respiratory support.

NICU admission practices can differ among hospitals. In addition to recording actual NICU admission, the study therefore includes standardized respiratory assessments after birth. This approach will provide a consistent measure of respiratory status across participating centers.

Respiratory status will be documented at 30 minutes after birth. At 60 minutes, all randomized infants will undergo a standardized respiratory assessment regardless of their location at that time. This includes infants who remain in the delivery room, are with their parent or in a newborn nursery, are receiving transitional care, or have already been admitted to a NICU.

The 60-minute assessment will document oxygen saturation, supplemental oxygen use, respiratory rate, signs of respiratory distress, and respiratory support. Standardized criteria will be used to determine whether an infant meets predefined criteria for NICU admission for respiratory support, independent of the infant's actual location or the local hospital's admission decision. Actual NICU admission for respiratory support will remain the primary clinically relevant outcome.

Respiratory support and other clinical outcomes will also be followed after the initial transition period. These data will help determine whether any early effect of prophylactic CPAP is associated with differences in subsequent respiratory care.

Family-Centered Outcomes PLaNT 2 also examines outcomes that are important to families. Admission of a newborn to the NICU can result in separation from parents during an important period for bonding and breastfeeding. The study will therefore evaluate parental stress, mother-infant bonding, and exclusive breastfeeding in addition to respiratory outcomes.

Parental stress and mother-infant bonding will be assessed using validated measures. Breastfeeding information will also be collected during the study period. These outcomes will help determine whether differences in respiratory illness and NICU admission are associated with meaningful differences in the experience of infants and their families.

Multicenter and International Design PLaNT 2 is designed as a pragmatic trial so that its findings can apply to routine clinical practice. Participating hospitals represent different patient populations, clinical practices, and health care settings.

CPAP is already commonly used in newborn care, and the intervention relies on equipment and clinical skills that are already available at participating centers. The study tests a new preventive use of an established therapy rather than a new drug or device.

If this approach works, it could lower respiratory complications and unnecessary NICU admissions while allowing more newborns to remain with their families. Because the intervention uses existing technology and clinical expertise, the findings could also be relevant to a wide range of health care settings.

Participants assigned to this arm will receive 20 minutes of prophylactic continuous positive airway pressure (CPAP) at 5 to 6 cm H2O, started within 5 minutes after birth. CPAP may be provided at the radiant warmer or while the infant is on the mother's chest. Participants may receive additional CPAP or other respiratory support if clinically needed.

Other: Prophylactic CPAP

Participants assigned to this arm will receive standard care after birth without prophylactic CPAP. CPAP or other respiratory support may be provided if clinically needed according to usual clinical care.

Other: Standard of Care

Participants assigned to this arm will receive 20 minutes of prophylactic continuous positive airway pressure (CPAP) at 5 to 6 cm H2O, started within 5 minutes after birth. CPAP may be provided at the radiant warmer or while the infant is on the mother's chest. Participants may receive additional CPAP or other respiratory support if clinically needed.

Participants will receive standard care after birth without prophylactic CPAP. CPAP or other respiratory support may be provided if clinically needed according to usual clinical care

Plazo: 60 minutes after birth

At the single assessment at 60 minutes after birth, an infant will be classified as "yes" if they need supplemental oxygen to reach an oxygen saturation greater than 92%, or need CPAP, or need mechanical ventilation. An infant will be classified as "no" if none of these criteria are met. Classification is based on need for respiratory support, regardless of the infant's actual location.

Plazo: 30 minutes and 24 hours after birth

An infant will be classified as "yes" if they need supplemental oxygen to reach an oxygen saturation greater than 92%, or need CPAP, or need mechanical ventilation. An infant will be classified as "no" if none of these criteria are met. Classification is based on need for respiratory support, regardless of the infant's actual location.

Plazo: at hospital discharge (single measurement)

Parents will complete the PSS:NICU at infant hospital discharge to rate stress related to the NICU experience. Items are scored from 1 (not at all stressful) to 5 (extremely stressful). Using Metric 2, responses marked "not experienced" are scored as 1. For each parent, the overall score will be the mean across all PSS:NICU items (range: 1-5; maximum: 5). Mean scores and standard deviations will be reported and compared between the prophylactic CPAP and standard-care groups. Higher scores indicate greater parental stress.

Plazo: at hospital discharge or 30 days whichever comes first (single assessment)

At hospital discharge, the infant will be classified as "Yes" if they received any breast milk, either directly at the breast or as expressed breast milk, including in combination with formula. The infant will be classified as "No" if they received no breast milk. The number and percentage classified as "Yes" and "No" will be reported by study group

Prophylactic CPAP for Late Preterm Infants Born by C-Section to Reduce NICU Admission: A Multicenter Randomized Controlled Trial (PLaNT 2 Study)