Hypothyroxinemia in Mechanically Ventilated Term Infants Is Associated With Increased Use of Rescue Therapies

Abstract

Although common in preterm infants, transient hypothyroxinemia (TH) has not been investigated extensively in ill term infants. The objectives of this study were to investigate serum thyroxine (T4) and thyroid-stimulating hormone (TSH) in sick term infants and to determine whether there is any association between measures of thyroid function and short-term outcome in term infants who receive mechanical ventilation. The investigation consisted of both a prospective observational study and a retrospective cohort study. In the prospective study, T4 and TSH were measured after birth in a group of sick term infants (n = 38) and compared with a group of well term infants (n = 18). Infants in the sick group received mechanical ventilation or continuous positive airway pressure and/or had neonatal seizures. Illness severity was quantified using the Score for Neonatal Acute Physiology. The retrospective cohort study included term infants who required mechanical ventilation and were born over a 5-year period (n = 347). Routine T4 screening was collected on the fifth day of life. TH was diagnosed in infants with a T4 <10%, with a TSH <25 microIU/mL. Clinical outcomes in infants with TH were compared with infants without TH. In the prospective study, infants in the sick group had lower T4 on the fifth day of life as compared with infants in the well group (11.7 +/- 4.9 vs 18.9 +/- 5.4 microg/dL), and 34% of infants in the sick group had a T4 <10th percentile compared with 6% of infants in the well group. T4 on day of life 5 was inversely correlated with Score for Neonatal Acute Physiology (R = -0.52). In the retrospective study, 21% of mechanically ventilated infants developed TH and were given statistically more inhaled nitric oxide, high-frequency ventilation, vasopressors, and pharmacologic paralysis when compared with infants without TH. Moreover, infants with TH were statistically more likely to die or require transfer to an extracorporeal membrane oxygenation center compared with infants without TH. Our data show that, similar to preterm infants, ill term infants develop TH. Term infants with TH required more intensive rescue interventions, including inhaled nitric oxide and transfer to an extracorporeal membrane oxygenation center. However, whether T4 levels are a marker or a mediator of clinical outcome remains to be determined.