There is a relationship between thyroid function tests (TFT) and cardiac function. Children who undergo cardiac bypass surgery have deranged TFTs and treatment with T3 improves myocardial function [7,8]. On comparison of children (beyond neonatal period) with septic shock versus those with sepsis but no shock, researchers have reported lower thyroid hormone levels among the former [2,9]. Septic shock may just reflect greater severity of sickness, as the above authors did not adjust for the level of sickness to determine whether TFTs have an independent relationship with shock. In view of the proven association of lower levels of thyroid hormones and septic shock in older children, paucity of data in preterm infants, and the uncertainty whether deranged TFTs are associated with hypotension independent of the level of sickness, we planned this study.

We conducted a cross-sectional study in a level III Neonatal Intensive Care Unit (NICU) in northern India, after Ethics Committee approval. Written informed consent was obtained from parents.

We recruited inborn premature neonates (30-35 weeks of gestation) diagnosed to have sepsis, based on clinical sepsis associated either with a positive body fluid culture, or C-reactive protein value >10 mg/L, or a chest X-ray suggestive of pneumonia. Subjects were excluded if they had maternal thyroid disorder; intake of drugs that could affect TFTs; or anticipated life expectancy <12 hours. We enrolled two groups: those with sepsis and fluid-resistant hypotensive shock (Group A) and those with sepsis but no shock (Group B). Shock was defined as systolic blood pressure (BP) less than the lower bound of the 95% CI by Zubrow’s charts after receiving two normal saline boluses of 10 ml/kg each. For those with an arterial cannula, we used the invasive BP and for others we used non-invasive BP records.

In Group B, absence of shock was defined as both systolic and diastolic BP above the lower bound of the 95% CI’s; no oliguria (urine output <1 mL/kg/h); no prolongation of capillary refill time (>3 seconds); and no narrowing of pulse pressure (<20 mm Hg) in the preceding 6 hours, data for which was obtained from the patient’s records. Subjects in group B were individually matched (1:1) with subjects in group A for gestation (± 1 week) and chronological age. They included the first eligible subject after the corresponding case in group A had been enrolled. We defined subjects in Group A according to BP as this objective measure reflects decompensated shock. Group B was defined to exclude all signs of hypoperfusion and shock so that there was a clear demarcation between groups. We recorded baseline demographics, morbidity profile, and clinical features of hypoperfusion. We assayed serum T3, T4 and TSH in all subjects by immuno-radiometric assays before the administration of inotropes. Hemolyzed and lipemic samples were not assayed. We calculated the SNAPPE-II over a 12-hour period after enrolment.

We followed up all subjects until death or discharge from the NICU. We compared the groups for TSH, T3 and T4 values. We determined the independent predictors of group membership as mentioned below, and determined the independent predictors of the risk of dying.

To detect a difference in mean TSH level of 2.3 mIU/ml assuming a 1:1 ratio of the groups; standard deviation of 3.5 mIU/ml; 5% alpha error and 20% beta error [10], 36 subjects were required per group. Data regarding the standard deviation of the difference in TSH values between matched neonates are not available in the literature, hence we could not calculate sample size for matched groups.

Statistical analysis: Statistical tests for related groups were used as the groups were matched. Categorical variables were compared by McNemar’s test. Numerical variables were compared by paired Student’s t-test and Wilcoxan signed rank sum test. Since derangement of TFTs is associated with the degree of sickness, we determined whether the TFTs were associated with septic shock after adjusting for level of sickness. We performed univariate followed by multivariate conditional logistic regression analysis to estimate the adjusted odds ratio (OR) of belonging to group A, for the following variables: SNAPPE-II, T3, T4 and TSH values. We also performed multivariate logistic regression to estimate the adjusted OR of dying, for the following covariates: gestational age, baseline mean BP, SNAPPE-II score, and T3, T4 and TSH values.

Of 4794 livebirths, 255 babies in the gestational age group 30-35 weeks developed sepsis. 58 of them developed septic shock of which 10 were missed, 5 refused consent and 7 excluded for other exclusion criteria; leaving 36 cases for enrollment in Group A. An equal number of matched subjects were selected in Group B. All subjects in Group A had at least one abnormal perfusion parameter (urine output <1 mL/kg/h, capillary refill time >3 seconds or pulse pressure <20 mm Hg) in addition to low BP. Twenty-six, 30 and 13 subjects in Group A had oliguria, delayed capillary refill and/or narrow pulse pressure, respectively, with several having >1 abnormal parameter (Table I).

TABLE I Comparison of Clinical Characteristics Between Septic Preterm Neonates With (Group A) 
and Without (Group B) Shock (N=72)

Contributors: SD: planned the study, analyzed the data and wrote the manuscript; SS: recruited patients and collected the data; AB: performed the thyroid hormone assays; SV: helped with data collection and data analysis; PK: supervised the study, supervised the data analysis and finalized the manuscript.

Funding: None; Competing interest: None stated.