What medications should not be given to a preterm newborn?

Medications That Should Not Be Given to Preterm Newborns

Sulfonamide antibiotics (including co-trimoxazole/sulfamethoxazole-trimethoprim) should be avoided in premature infants due to the risk of hyperbilirubinemia and kernicterus from bilirubin displacement. 1, 2

Sulfonamides and Co-trimoxazole

Primary contraindication:

• Co-trimoxazole (sulfamethoxazole-trimethoprim) is contraindicated in infants younger than 2 months of age 2
• Sulfonamides should be avoided in premature infants because they can displace bilirubin from albumin-binding sites, leading to hyperbilirubinemia and potential kernicterus 1, 2
• The FDA drug label specifically warns against use in jaundiced, ill, stressed, or premature infants when breastfeeding mothers are taking the medication, due to risk of bilirubin displacement and kernicterus 2

Clinical context:

• Preterm infants have immature hepatic conjugation systems and are already at higher risk for hyperbilirubinemia 3
• Amoxicillin+clavulanic acid is specifically not recommended in women at risk of preterm delivery due to very low risk of necrotizing enterocolitis in the fetus 1

Continuous Opioid Infusions

Morphine and fentanyl for routine mechanical ventilation:

• Routine continuous morphine infusion in mechanically ventilated preterm neonates is not recommended, as it provides no apparent analgesic benefit, does not reduce poor neurologic outcomes (severe IVH, PVL, or death), and may prolong duration of mechanical ventilation 1
• Continuous fentanyl infusions in chronically ventilated preterm infants appear to result in increased ventilator settings and lack demonstrated long-term benefit 1
• These agents should only be used for specific pain management needs, not routinely for all ventilated preterm infants 1

Midazolam for Sedation

In mechanically ventilated preterm infants:

• Routine midazolam use cannot be recommended due to insufficient data demonstrating benefit and concern for increased risk of poor neurologic outcomes 1

Tetracyclines (Doxycycline)

Avoid during late pregnancy and in neonates:

• Tetracyclines should be avoided during the second and third trimesters and at delivery, as they are associated with tooth discoloration and transient suppression of bone growth 1
• Doxycycline should not be the first choice during the first trimester and should be avoided during breastfeeding in long-term treatments 1

Oseltamivir Dosing Caution

Requires adjusted dosing in preterm infants:

• Standard term infant doses of oseltamivir should NOT be used in preterm infants, as they may lead to very high drug concentrations due to immature renal function 1
• Preterm infants require lower weight-based dosing based on postmenstrual age: 1.0 mg/kg per dose twice daily for <38 weeks postmenstrual age; 1.5 mg/kg per dose twice daily for 38-40 weeks; 3.0 mg/kg per dose twice daily for >40 weeks 1
• For extremely preterm infants (<28 weeks), consultation with a pediatric infectious disease physician is recommended 1

Important Clinical Pitfalls

• Always verify gestational age and postmenstrual age before prescribing any medication to ensure appropriate dosing 1
• Monitor for signs of hyperbilirubinemia when any sulfonamide exposure occurs (maternal or direct), particularly in premature, jaundiced, or ill infants 1, 2
• Avoid drugs that displace bilirubin from albumin in any preterm infant with jaundice or at risk for kernicterus 2, 3
• Consider that preterm infants have immature renal and hepatic function, requiring dose adjustments for many medications 1