Review Question - QID 217666

This patient with tachypnea, increased work of breathing (subcostal retractions and tracheal tugging), decreased oxygen saturation, diffusely decreased breath sounds, and a chest radiograph showing bilateral diffuse reticulogranular opacities and air bronchograms most likely has neonatal respiratory distress syndrome (NRDS). NRDS is caused by immature pulmonary surfactant and is associated with a decreased lecithin-to-sphingomyelin ratio (<2:1).

NRDS is the most common form of respiratory failure in preterm infants and results from surfactant deficiency. Surfactant deficiency causes decreased lung compliance and atelectasis, which manifests clinically as tachypnea, increased work of breathing, and cyanosis. Risk factors associated with NRDS include male sex, preterm delivery, and maternal diabetes. Maternal diabetes and hyperglycemia lead to hyperinsulinemia in both the mother and fetus. In turn, insulin antagonizes the action of cortisol, which then leads to decreased production of surfactant. Immature surfactant production can be quantified by the lecithin-to-sphingomyelin ratio; a value <1.5:1 suggests immature surfactant production, while a value >2:1 indicates mature surfactant production. Diagnosis of NRDS is based primarily on clinical history and presentation, as well as chest radiography. NRDS will manifest with bilateral atelectasis, air bronchograms, and “ground glass” (reticulogranular opacities) on chest radiographs. The treatment of NRDS includes supportive care with mechanical ventilation and surfactant replacement. Prophylaxis against NRDS includes the pretreatment of mothers at high risk of preterm birth (< 34 weeks of gestation) with corticosteroids (e.g., betamethasone) and achieving glycemic control in patients with gestational diabetes.

Atar et al. reviewed the molecular mechanisms underpinning the relationship between maternal diabetes and the production of neonatal surfactant. The authors found that hyperglycemia and consequent hyperinsulinemia can downregulate cortisol-mediated surfactant lipid and protein synthesis. They recommended further research on ways to improve glycemic control in patients with gestational diabetes.

Figure/Illustration A show a chest radiograph of a neonate with respiratory distress syndrome. Characteristic findings of NRDS are highlighted including bilateral diffuse reticulogranular densities (red arrows), air bronchograms (blue circles), and a bell-shaped thorax (green trapezoid).

Incorrect Answers:
Answer 1: Episodes of apnea lasting longer than 20 seconds describe apnea of prematurity (AOP). AOP is caused by immature respiratory control and manifests in preterm and low birth weight neonates with episodes of apnea accompanied by hypoxemia. However, AOP usually manifests 2-3 days after birth and would not be expected to have a chest radiograph showing ground-glass opacities.

Answer 2: Green-stained amniotic fluid is associated with meconium aspiration syndrome (MAS). MAS is associated with post-term births, maternal diabetes, and maternal infection, and causes respiratory distress immediately after birth. Chest radiograph generally shows increased lung volumes, pleural effusion, and asymmetric, patchy opacities.

Answer 3: A hamartomatous pulmonary lesion describes a congenital pulmonary airway malformation (CPAM), a developmental malformation of the lower respiratory tract. Although CPAM is usually asymptomatic at birth, a minority of patients can present with tachypnea, increased work of breathing, and cyanosis due to air trapping in cysts. On chest radiograph, CPAM is characterized by air-filled cysts.

Answer 5: Prominent precordial impulse and a narrowly split S2 would be associated with persistent pulmonary hypertension of the newborn (PPHN). PPHN is characterized by elevated pulmonary vascular resistance and is associated with MAS, prolonged premature rupture of membranes, and maternal infection. Symptoms usually manifest within 24 hours of birth and include respiratory distress, low APGAR scores, and a cardiac exam consistent with pulmonary hypertension. Chest radiographs in patients with PPHN usually show clear lung fields with decreased vascular markings and a normal-sized heart.

Bullet Summary:
Gestational diabetes is often complicated by respiratory distress syndrome due to an insulin-mediated decrease in surfactant production with a decreased lecithin-to-sphingomyelin ratio.