2.2 Prematurity & Complications of Prematurity

Defining Prematurity

Prematurity is defined by the World Health Organization as birth before 37 completed weeks of gestation. Preterm birth is further stratified by gestational age (GA) at delivery, and the ABHS exam expects fluency with these categories:

Infants are also classified by weight: low birth weight (LBW) under 2500 g, very low birth weight (VLBW) under 1500 g, and extremely low birth weight (ELBW) under 1000 g. Weight and gestational age often but not always align — a growth-restricted term infant can be LBW without being preterm at all.

Antenatal Corticosteroids

A single course of antenatal corticosteroids (betamethasone 12 mg intramuscularly x 2 doses 24 hours apart, or dexamethasone 6 mg intramuscularly x 4 doses 12 hours apart) is recommended for women at risk of preterm birth between 24 0/7 and 34 0/7 weeks, and is considered in select cases as early as 22-23 weeks. Antenatal steroids accelerate fetal lung maturation by inducing surfactant production, and they reduce the incidence and severity of respiratory distress syndrome, intraventricular hemorrhage, necrotizing enterocolitis, and neonatal mortality. Maximum benefit occurs when delivery follows the first dose by 24 hours to 7 days; a single rescue course may be considered if the prior course was given more than 14 days earlier and the patient remains at high risk of delivering within 7 days before 34 weeks.

Respiratory Distress Syndrome (Surfactant Deficiency)

Respiratory distress syndrome (RDS) results from developmental surfactant deficiency in the immature lung. Surfactant, produced by type II pneumocytes, reduces alveolar surface tension and prevents end-expiratory alveolar collapse. RDS incidence rises steeply as gestational age falls, affecting the majority of infants born before 28 weeks. Clinically, RDS presents within minutes to hours of birth with tachypnea, grunting, nasal flaring, intercostal and subcostal retractions, and cyanosis; the classic chest radiograph shows a diffuse "ground-glass" reticulogranular pattern with air bronchograms and low lung volumes. Management includes antenatal steroids for prevention, early continuous positive airway pressure (CPAP), and exogenous surfactant replacement therapy given via endotracheal tube, or less-invasive surfactant administration (LISA), for infants with worsening distress or rising oxygen requirement. Untreated or severe RDS can progress toward bronchopulmonary dysplasia.

Apnea of Prematurity

Apnea of prematurity (AOP) is a pause in breathing lasting 20 seconds or more, or a shorter pause accompanied by bradycardia (below 100 bpm) or oxygen desaturation, in an infant under 37 weeks with no other identifiable cause. It arises from immaturity of central respiratory drive (central apnea), airway obstruction (obstructive apnea), or — most commonly — a mixed pattern. AOP is a diagnosis of exclusion: sepsis, hypoglycemia, anemia, gastroesophageal reflux, seizures, and temperature instability must be considered, especially with new-onset apnea. First-line pharmacologic treatment is caffeine citrate, which reduces apnea frequency, shortens the duration of mechanical ventilation, and, per the landmark Caffeine for Apnea of Prematurity (CAP) trial, reduces the incidence of bronchopulmonary dysplasia and improves neurodevelopmental outcome at 18 months when started early.

Retinopathy of Prematurity (ROP)

Retinopathy of prematurity (ROP) is a proliferative vascular disorder of the developing retina caused by disrupted retinal vascularization, most closely linked to low gestational age, low birth weight, and supplemental oxygen exposure. Screening with dilated indirect ophthalmoscopy is recommended for infants at 30 weeks gestation or less, or 1500 g birth weight or less (plus selected larger or older infants with an unstable clinical course), beginning at 4-6 weeks chronologic age or 31-33 weeks postmenstrual age, whichever is later, with follow-up timed by disease severity until the retina is fully vascularized. ROP is staged 1-5 by severity and classified by zone (I-III, with zone I being most posterior and highest risk) and by the presence of "plus disease" — vascular dilation and tortuosity indicating active disease. Severe disease is treated with laser photocoagulation or intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents to prevent retinal detachment and blindness.

Necrotizing Enterocolitis (NEC)

Necrotizing enterocolitis (NEC) is an acquired gastrointestinal emergency of prematurity involving inflammatory and ischemic bowel necrosis, most common in VLBW infants and typically presenting in the second to third week of life after enteral feeds have begun. Risk factors include prematurity itself, formula feeding (breast milk is protective), bacterial colonization, and bowel ischemia. Presentation includes feeding intolerance, abdominal distension, bloody stools, temperature instability, and apnea or bradycardia. The diagnostic hallmark on abdominal radiograph is pneumatosis intestinalis (gas within the bowel wall), with portal venous gas or pneumoperitoneum (free air, indicating perforation) signaling more advanced disease. Early disease is managed medically with bowel rest, nasogastric decompression, and broad-spectrum antibiotics; perforation or clinical deterioration requires surgery (laparotomy or peritoneal drainage).

Intraventricular Hemorrhage (IVH)

Intraventricular hemorrhage (IVH) originates from the fragile, highly vascular germinal matrix, a structure that involutes by term and is therefore a preterm-specific vulnerability, especially below 32 weeks. IVH is graded by cranial ultrasound using the Papile classification: Grade I (germinal matrix hemorrhage only), Grade II (intraventricular extension without ventricular dilation), Grade III (intraventricular hemorrhage with ventricular dilation), and Grade IV (parenchymal extension, or hemorrhagic venous infarction). Screening head ultrasound is typically performed around 7-14 days of life in infants below about 30-32 weeks, and repeated near term. Higher grades correlate with increased risk of post-hemorrhagic hydrocephalus and adverse neurodevelopmental outcome.

Bronchopulmonary Dysplasia (BPD)

Bronchopulmonary dysplasia (BPD), also called chronic lung disease of prematurity, is defined by a continued oxygen requirement at 28 days of life, and is further graded by respiratory support needs at 36 weeks postmenstrual age for infants born before 32 weeks. It results from a combination of lung immaturity, volutrauma and barotrauma from mechanical ventilation, oxygen toxicity, and inflammation, all of which arrest normal alveolar and vascular development. Prevention strategies include antenatal steroids, early CPAP to minimize invasive ventilation, judicious oxygen titration, caffeine therapy, and vitamin A supplementation; established BPD is managed with a target oxygen saturation range, diuretics or corticosteroids in select cases, and nutritional optimization to support growth.

Patent Ductus Arteriosus (PDA)

Patent ductus arteriosus (PDA) is common in preterm infants because the ductus closes later with decreasing gestational age. A hemodynamically significant PDA causes a left-to-right shunt with pulmonary overcirculation, worsening respiratory distress, feeding intolerance, and risk of BPD. Clinical clues include a continuous machinery murmur, bounding pulses, wide pulse pressure, and a hyperdynamic precordium, though a silent PDA can still be hemodynamically significant in a ventilated preterm infant. Diagnosis is confirmed by echocardiography. First-line medical closure in symptomatic VLBW infants is indomethacin or ibuprofen; refractory or contraindicated cases may require surgical ligation.