A 6-hour-old term neonate presents with central cyanosis of the lips, tongue, and mucosa. The pediatrician performs a hyperoxia test by administering 100% inspired oxygen for 10 minutes and measures arterial blood gas. The finding marked **B** in the diagram — NO improvement with the hyperoxia test (pO2 remains <100 mmHg) — is observed. Which of the following is the MOST LIKELY diagnosis in this neonate?

Explanation

## Why Transposition of the great arteries with right-to-left shunt is right The hyperoxia test is a diagnostic tool that distinguishes cardiac from respiratory causes of neonatal cyanosis. A blunted response (pO2 remaining <100 mmHg despite 100% oxygen for 10 minutes) indicates a fixed right-to-left shunt at the cardiac level, which is pathognomonic for cyanotic congenital heart disease (CCHD). Transposition of the great arteries (TGA) is the most common cyanotic CHD presenting in the first hours of life, before ductal closure, and presents with severe cyanosis unresponsive to oxygen. The finding marked **B** — failure of pO2 to rise above 100 mmHg — directly confirms an anatomic right-to-left shunt, diagnostic of CCHD such as TGA. (Nelson 21e Ch 459) ## Why each distractor is wrong - **Meconium aspiration syndrome with pulmonary hypoplasia**: This is a respiratory cause of cyanosis. In respiratory disease, the hyperoxia test shows a ROBUST response, with pO2 rising >250 mmHg because the lungs can oxygenate blood when given high FiO2. The blunted response (finding **B**) rules out respiratory pathology. - **Respiratory distress syndrome due to surfactant deficiency**: RDS is a respiratory cause of cyanosis. Like meconium aspiration, RDS responds to hyperoxia with a significant rise in pO2 (>250 mmHg). The finding **B** (pO2 <100 mmHg despite 100% O2) is incompatible with pure respiratory disease. - **Persistent pulmonary hypertension of the newborn (PPHN) secondary to sepsis**: While PPHN can cause cyanosis and may have a right-to-left shunt component, it is primarily a pulmonary vascular disease and often shows some improvement with hyperoxia and inhaled nitric oxide. The finding **B** — a fixed, blunted response to hyperoxia — is more characteristic of structural CCHD with an obligatory right-to-left shunt (e.g., TGA) than of PPHN, which may show partial response to oxygen and pulmonary vasodilators. **High-Yield:** Hyperoxia test: pO2 >250 mmHg = respiratory cause; pO2 <100 mmHg = CCHD with right-to-left shunt. TGA is the most common cyanotic CHD in the first hours of life. [cite: Nelson 21e Ch 459]