For an extremely preterm infant with bronchopulmonary dysplasia, patent ductus arteriosus, gastro‑oesophageal reflux, and pulmonary hypertension, which step of the supportive‑care cascade corresponds to each of the following medications: vitamin D3 400 IU drops, ferrous sulfate, multivitamin drops, folic‑acid drops, esomeprazole 2.5 mg, domperidone 1 mg/mL, furosemide 2 mg, sildenafil 1 mg, and lactulose 3.3 g/5 mL?

Medication Classification by Treatment Step for Extremely Preterm Infant with BPD, PDA, GERD, and Pulmonary Hypertension

Nutritional Support and Micronutrient Supplementation (Foundational Care)

These medications represent the baseline nutritional support required for all extremely preterm infants with chronic lung disease, addressing increased metabolic demands and preventing deficiencies that impair growth and development.

• Vitamin D3 400 IU drops: Essential micronutrient supplementation for bone health and calcium metabolism in preterm infants with BPD who require increased nutrient intake beyond standard formulas. 1

• Ferrous sulfate: Iron supplementation to prevent anemia of prematurity and support oxygen-carrying capacity, particularly critical in infants with chronic lung disease who have increased oxygen requirements. 1

• Multivitamin drops: Comprehensive vitamin supplementation to meet the extra vitamin and mineral needs of chronically ill infants with BPD, as standard formulas cannot meet these increased requirements. 1

• Folic acid drops 0.3 ml: Specific supplementation for red blood cell production and prevention of megaloblastic anemia, addressing nutrient losses from diuretic therapy and increased metabolic demands. 1

Fluid Management and Cardiac Support (Step 2: Managing Pulmonary Edema and Right Heart Strain)

Diuretic therapy is used cautiously for signs of right heart failure, though routine use is not recommended.

• Furosemide 2 mg: Loop diuretic for managing pulmonary edema and right heart failure in BPD, though the American Thoracic Society recommends against routine use and advises judicious discontinuation given very low quality evidence and lack of long-term benefit. 2, 1 Short-term use (7-8 days) may improve dynamic pulmonary compliance and reduce FiO₂ requirements, but risks include nephrolithiasis, metabolic bone disease, metabolic alkalosis, ototoxicity, and impaired weight gain. 2

• Lactulose 3.3 g/5ml: Osmotic laxative for managing constipation, which is a common side effect of chronic diuretic therapy and can worsen respiratory distress by increasing intra-abdominal pressure. 1

Gastrointestinal Management (Step 3: Addressing Feeding Complications)

Special attention to gastroesophageal reflux is required in infants with BPD due to increased metabolic rates and coordination difficulties.

• Esomeprazole 2.5 mg: Proton pump inhibitor for managing gastroesophageal reflux, which requires special attention in infants with CLDI due to suck-swallowing coordination issues and increased metabolic demands. 1

• Domperidone 1 mg/ml: Prokinetic agent to improve gastric emptying and reduce reflux episodes, supporting adequate nutritional intake in infants with chronic lung disease who require increased caloric density (120 kcal/kg per day initially). 1

Pulmonary Hypertension Management (Step 4: Targeted Vasodilator Therapy)

PAH-targeted therapy should only be initiated after optimizing treatment of underlying respiratory and cardiac disease.

• Sildenafil 1 mg: Oral pulmonary vasodilator (phosphodiesterase-5 inhibitor) dosed at 0.5-2 mg/kg three times daily for symptomatic pulmonary hypertension in BPD after optimization of lung disease management. 1, 3 The American Heart Association recommends this as Class IIa evidence for infants with BPD and PH on optimal treatment of underlying disease, with serial echocardiograms required to monitor response. 1 Sildenafil has become the mainstay of contemporary BPD-PH therapy and can improve oxygenation, though long-term outcome data remain limited. 3, 4

Critical Clinical Context

The presence of patent ductus arteriosus significantly increases the risk of developing BPD-associated pulmonary hypertension. Each additional month of PDA exposure increases the probability of BPD-PH or death (coefficient 0.40, P<0.001), with moderate-to-large PDA conferring an adjusted odds ratio of 4.15 for BPD-PH development. 5 This patient's medication regimen addresses all four major complications (BPD, PDA, GERD, and PH) in a stepwise manner, though the evidence quality for several interventions—particularly routine diuretic use—remains very low. 2

Maintaining oxygen saturations between 92-95% helps keep pulmonary vascular resistance low, decreasing right heart strain and thereby reducing energy requirements, which is why adequate oxygenation support complements this pharmacologic regimen. 1