Complications of Prematurity
Every immature organ has its own complication and its own clock
Overview: gestational age and the three clocks
Definitions. Preterm birth is delivery before 37 weeks. Late preterm infants are born at 34 0/7–36 6/7 weeks, very preterm infants before 32 weeks, and extremely preterm infants before 28 weeks. Very low birth weight (VLBW) is <1,500 g and extremely low birth weight (ELBW) <1,000 g.
Postmenstrual age (PMA) is gestational age at birth plus chronological age and times BPD, retinal exams, and the resolution of apnea. Corrected age is chronological age minus the weeks born early and is used for growth and developmental milestones until about age 2, whereas vaccines are given on the chronological schedule.
Breathing: apnea of prematurity and BPD
Apnea of prematurity. A respiratory pause of ≥20 seconds, or a shorter pause with bradycardia or desaturation, in an infant born before 34 weeks; it is nearly universal below 28 weeks. It reflects immature brainstem control, with a blunted ventilatory response to CO2, and episodes are central or mixed central-obstructive. It usually begins on days 2–7 and resolves by about 37 weeks PMA, though it can persist to 43–44 weeks in the most immature infants. Periodic breathing (repeated 5–10 second pauses without bradycardia or desaturation) is benign.
Apnea of prematurity is a diagnosis of exclusion. Apnea on the first day, in a term infant, or recurring after a stable period demands evaluation for sepsis/meningitis, hypoglycemia, electrolyte disturbance, anemia, IVH, seizures, temperature instability, and maternal drugs (opioids, magnesium).
Caffeine citrate. This methylxanthine antagonizes adenosine receptors, increasing respiratory drive, CO2 sensitivity, and diaphragm contractility. It is preferred over theophylline because of its long half-life, once-daily dosing, and wide safety margin, and it also lowers rates of BPD and PDA treatment. CPAP or nasal intermittent positive-pressure ventilation is added for persistent apnea; caffeine is usually stopped around 33–34 weeks PMA once the infant is event-free. Apnea of prematurity is not a precursor of SIDS, and home apnea monitors do not prevent SIDS.
Bronchopulmonary dysplasia. BPD is chronic lung disease of very preterm infants, defined by the need for supplemental oxygen or respiratory support at 36 weeks PMA. Volutrauma and barotrauma, oxygen toxicity, and inflammation (chorioamnionitis, sepsis) arrest alveolar and vascular development, leaving fewer, larger alveoli. Prevention bundles antenatal corticosteroids, surfactant, early CPAP instead of intubation, gentle volume-targeted ventilation, caffeine, and avoidance of hyperoxia (saturation targets around 90–95%). Established BPD is managed with oxygen, diuretics, high-calorie nutrition, RSV immunoprophylaxis, and echocardiographic screening for pulmonary hypertension.
Postnatal dexamethasone shortens ventilation, but early or high-dose courses increase cerebral palsy; low-dose courses are reserved for infants still ventilator-dependent after 1–2 weeks.
Patent ductus arteriosus
Why it stays open. The immature ductus constricts poorly in response to oxygen and remains sensitive to circulating PGE2. As pulmonary vascular resistance falls, blood shunts left to right from the aorta into the pulmonary artery. Findings include a continuous "machine" murmur below the left clavicle (often systolic-only early), bounding pulses, a wide pulse pressure with low diastolic pressure, and a hyperdynamic precordium. Pulmonary overflow causes edema and rising oxygen and ventilator needs; systemic steal causes oliguria, feeding intolerance, and NEC.
Management. Echocardiography confirms the ductus and grades its significance. A hemodynamically significant PDA is closed with a COX inhibitor (indomethacin or ibuprofen) or with acetaminophen. Surgical ligation or transcatheter closure is used when drugs fail or are contraindicated.
Avoid NSAIDs with NEC or spontaneous intestinal perforation, active bleeding, thrombocytopenia, or renal failure; they reduce mesenteric, renal, and cerebral blood flow and impair platelet function.
In ductal-dependent congenital heart disease the goal is the opposite: keep the ductus open with prostaglandin E1 (alprostadil).
The preterm brain: IVH and PVL
Germinal matrix hemorrhage. The subependymal germinal matrix is a richly vascular region of fragile capillaries that involutes by about 32–34 weeks. Infants born before 32 weeks or under 1,500 g have pressure-passive cerebral blood flow, so swings in blood pressure or CO2 rupture these vessels. Most bleeds occur within the first 72 hours, and many are clinically silent; large ones cause a bulging fontanelle, falling hematocrit, apnea, seizures, or shock. Very preterm infants therefore get a screening cranial ultrasound through the anterior fontanelle in the first week or two, repeated near term-equivalent age. Antenatal steroids and delayed cord clamping reduce IVH, and antenatal magnesium sulfate before 32 weeks reduces cerebral palsy.
Grading and sequelae. Papile grade I is confined to the germinal matrix, II extends into the ventricle without dilation, III distends the ventricle, and IV is a periventricular hemorrhagic (venous) infarction. Posthemorrhagic hydrocephalus is followed with serial ultrasound and head circumference, temporized with taps or a reservoir, and treated with a ventriculoperitoneal shunt; grade IV infarction produces contralateral spastic hemiparesis.
Periventricular leukomalacia. Hypoperfusion in the periventricular watershed plus inflammation (chorioamnionitis, sepsis) kills vulnerable preoligodendrocytes. The resulting spastic diplegia affects legs more than arms because the leg corticospinal fibers run closest to the ventricles.
| Feature | IVH | PVL |
|---|---|---|
| Lesion | Hemorrhage from germinal matrix capillaries | Ischemic/inflammatory white-matter necrosis |
| Timing | First 72 hours | Cysts visible after 2–6 weeks |
| Detection | Early screening head ultrasound | Later ultrasound; term-equivalent MRI |
| Main sequelae | Posthemorrhagic hydrocephalus; hemiparesis after grade IV | Spastic diplegia, visual and cognitive deficits |
Eyes, blood, and temperature
Retinopathy of prematurity. Retinal vessels normally reach the periphery near term. After preterm birth, relative hyperoxia suppresses VEGF and halts vessel growth (phase 1); the avascular peripheral retina then becomes hypoxic, VEGF surges, and abnormal neovascularization with fibrosis can cause traction retinal detachment (phase 2). Risk rises with lower gestational age and birth weight, high or fluctuating oxygen, sepsis, and poor weight gain.
- WhoBirth weight ≤1,500 g or gestational age ≤30 weeks, plus larger infants with an unstable course.
- WhenFirst dilated exam at 31 weeks PMA or 4 weeks of age, whichever is later; repeat until the retina is mature.
- TreatLaser photoablation of the avascular retina or intravitreal anti-VEGF (bevacizumab, ranibizumab), which needs extended follow-up for late reactivation.
- Follow upLifelong risk of myopia, strabismus, amblyopia, and retinal detachment.
Anemia of prematurity. A normocytic, hyporegenerative anemia with low reticulocytes and inappropriately low erythropoietin. Hemoglobin falls to about 7–9 g/dL within the first 1–2 months, earlier and deeper than the term physiologic nadir of 9–11 g/dL at 8–12 weeks. Phlebotomy, short red-cell life span, and rapid growth add to it. Prevention and treatment include delayed cord clamping, fewer blood draws, iron 2 mg/kg/day by 1 month of age in human milk-fed infants, and restrictive transfusion thresholds; erythropoietin is not routinely used.
Thermoregulation. Preterm infants have a high surface area-to-mass ratio, thin permeable skin with large evaporative losses, little brown fat or glycogen, and no shivering. Delivery rooms are kept at 23–25 °C; infants under 32 weeks go under a radiant warmer in a polyethylene wrap without drying, with a hat, then into a humidified servo-controlled incubator or skin-to-skin care. The target is 36.5–37.5 °C, because cold stress causes hypoglycemia, metabolic acidosis, apnea, and higher mortality.
Late preterm infants and follow-up
Not small term babies. Infants born at 34–36 weeks have more hypothermia, hypoglycemia, poor feeding with dehydration, hyperbilirubinemia, respiratory distress, apnea, and readmission than term infants. They should stay at least 48 hours, pass a car-seat tolerance screen, feed successfully before discharge, and be seen within 48 hours afterward.