A 9-day-old male neonate was transferred to our NICU in January 2025 for persistent respiratory distress. The infant was born at 34 weeks' gestation via cesarean section due to prenatal ultrasound findings suggestive of OI (bilateral femoral bowing and breech presentation). He was the second child of a father with a confirmed history of OI. Prenatal genetic testing via amniocentesis and whole-exome sequencing identified a heterozygous c.1459G > A (p.Gly487Arg) mutation in the COL1A2 gene, which was inherited from the father (Figure 1).

Examination in the NICU revealed a neonate exhibiting tachypnea (56 breaths per minute), significant tracheal retractions, thoracoabdominal asynchrony, coarse breath sounds with rales bilaterally, and oxygen saturation declining to 85%, necessitating nasal Continuous Positive Airway Pressure (nCPAP) (Figure 4). Notably, bilateral knee valgus deformities and bowing of the lower limbs were observed, consistent with the prenatal diagnosis. The sclerae were not blue.

Laboratory findings were significant for elevated interleukin-6 (44.62 pg/mL), suggesting infection/inflammation, while calcium, phosphate, and ALP levels were within normal limits for gestational age, helping to rule out metabolic bone disease (3). Genetic analysis by Sanger sequencing confirmed the COL1A2 c.1459G > A mutation (Figure 2). Skeletal survey radiographs demonstrated generalized osteopenia, thin cortical bones, and bowing of long bones and clavicles, classic for severe OI (Figure 3) (1).

Our case exemplifies the intricate balance required in managing a neonate with severe OI, where critical care for respiratory compromise must be delivered in the context of extreme skeletal fragility (1, 8). The successful in-hospital course, free of iatrogenic injury, underscores the effectiveness of a vigilant, protocol-driven MDT approach in the controlled NICU environment (4, 5).

Managing the respiratory system in neonates with osteogenesis imperfecta (OI) necessitates specialized approaches that diverge from standard neonatal protocols. Our patient exhibited respiratory distress, weak breathing effort, and a short thorax, with oxygen saturation falling to 85% by the ninth day after birth. Due to the substantial risks invasive procedures pose for OI patients—such as cervical spine injury, odonto-axial dislocation, and fractures of the mandible or teeth during laryngoscopy—we opted against immediate endotracheal intubation. Instead, a carefully titrated, non-invasive strategy was employed. Following a deterioration in his condition and computed tomography (CT) evidence of worsening pneumonia, he was commenced on nasal Continuous Positive Airway Pressure (nCPAP) with the following settings: PEEP 5 cmH₂O, FiO₂ 30%. This intervention successfully stabilized his respiration, thereby avoiding the need for invasive mechanical ventilation. This outcome aligns with literature suggesting noninvasive positive pressure ventilation (NPPV) can manage acute respiratory failure in OI while circumventing intubation-associated complications (9). As he improved, respiratory support was systematically reduced to high-flow nasal cannula (HFNC at 4 L/min, FiO₂ 25%) and was ultimately discontinued on day 18 of life. The pathophysiology of respiratory compromise in these infants involves a combination of intrinsic pulmonary issues from defective type I collagen in the lung matrix and extrinsic restrictive forces caused by thoracic skeletal deformities, such as the short thorax and altered spinal curvature noted in our case (10). The efficacy of this staged, non-invasive protocol highlights the importance of customizing respiratory support for neonatal OI to reduce the considerable dangers posed by invasive airway procedures in this fragile group.

The COL1A2 c.1459G > A (p.Gly487Arg) mutation in our patient is a typical glycine substitution within the triple helix, leading to a structural defect in type I collagen, which explains the severe phenotype (Sillence III) observed (1, 11). The spontaneous fracture that occurred shortly after discharge starkly highlights the transition from the protected hospital setting to the home environment as a period of significant risk (12). This transition represents a critical gap that our current healthcare systems must address more robustly. It mandates not only comprehensive family education on safe handling techniques, recognition of fracture signs, and emergency response but also a seamless handover to community and outpatient services to ensure continuity of care (4). The fracture healing observed in our patient—rapid callus formation followed by remodeling—is a hallmark of OI and has been documented in the perinatal period (7, 13). While this robust healing response is beneficial for fracture union, it can also lead to malalignment if not properly managed. Conservative management with devices like the Pavlik harness is often the mainstay for diaphyseal fractures in infants with OI, providing adequate stability while allowing for this unique biological process (6, 10).

The spontaneous fracture that occurred 16 days after discharge offers a critical insight from our case. This complication highlights the immediate post-discharge phase as a time of significant vulnerability, pointing to a substantial deficiency in existing care continuum models. Our findings indicate that thorough family education—which must incorporate practical training in safe handling, accessible emergency contacts, and explicit instructions for identifying signs of a fracture—forms the foundation for a secure transition home. This component is a cornerstone of patient safety, equivalent in importance to the management provided within the hospital. The parents involved described considerable anxiety, especially concerning techniques for swaddling, carrying, and changing diapers safely. Their experience stresses the necessity of enhanced, direct instruction and reinforcement of these skills prior to discharge.

The principal strengths of this report encompass thorough genetic confirmation, extensive longitudinal imaging that tracks disease progression and fracture healing, and clear reporting on the implementation of a Multidisciplinary Team (MDT) approach from the NICU through the high-risk post-discharge phase. Nevertheless, as a single-case study, the findings possess inherent limitations regarding their generalizability. In comparison to other published accounts of neonatal osteogenesis imperfecta (OI) (2, 4, 12), our work delivers distinctive perspectives on the management of an infant with a confirmed COL1A2 mutation. It particularly stresses the necessity of prolonging the MDT model of care after the patient leaves the hospital. Although the specific interventions described may be established practice, the systematic account of this integrated care pathway and its explicit focus on the risks following discharge offer clinically actionable insights for teams faced with analogous situations.

Looking forward, the long-term management of children with severe OI requires a sustained MDT effort to address progressive skeletal deformities, potential pulmonary complications, and functional limitations (14, 15). While bisphosphonate therapy is often considered after the neonatal period, emerging therapies like mesenchymal stem cell transplantation represent promising future avenues (16). Our experience reinforces that future clinical protocols should specifically address the high-risk post-discharge period through standardized transition pathways, enhanced caregiver training, and closer early follow-up arrangements.