Thyroid function in very low birth weight infants: effects on neonatal hypothyroidism screening.

OBJECTIVES: To supply normative data for screening thyroxine (T4) and thyrotropin concentrations correlated with birth weight and age at screening of infants with birth weights ranging from 400 to 5500 gm, and to document the effects of screening of very low birth weight (VLBW) infants, because VLBW infants comprise 0.86% of surviving newborn infants and have very low total T4 concentrations with normal or elevated free T4 concentrations as a result of deficient protein binding of thyroid hormones. STUDY DESIGN: Both retrospective and prospective studies were used. We conducted retrospective analyses of screening of T4 and thyrotropin concentrations in 9,324 term, 18,946 low birth weight, and 3,450 VLBW infants in Massachusetts, and a prospective study of T4 and thyrotropin concentrations in 48 VLBW infants at 2 weeks of age. Forty of the infants also had hormone measurements at 4 weeks, 29 at 8 weeks of age, and 24 had analysis of cord blood samples. RESULTS: Median T4 concentrations for each weight group (in 250 gm increments) increased progressively and significantly up to 2500 gm. Of the surviving VLBW infants, 1.5% had screening T4 concentrations that were unmeasurably low (<3.9 nmol/L (0.3 microgram/dl)). The mean T4 concentration varied with age at screening, increasing from cord blood concentrations to a peak at 1 to 3 days of age and thereafter decreasing to a nadir at about 2 weeks in both low birth weight and VLBW infants. In VLBW infants the mean concentrations return to the level of 1 to 3 days by 4 to 8 weeks of age. The incidence of screening thyrotropin concentrations > or = 40 mU/L correlates inversely with weight. The incidence of early, transient hypothyroidism in VLBW infants defined by this thyrotropin concentration was eight times that in term infants. Two infants had late-onset, transient hypothyroidism at 2 and 7 weeks, respectively. CONCLUSIONS: The normative data related to birth weight and age at screening allow proper interpretation of VLBW results for primary T4 and primary thyrotropin screening programs. Screening of the concentrations of T4 and thyrotropin in VLBW increases the number of secondary measurements of T4 in a primary thyrotropin screening program and the number of secondary thyrotropin measurements in a primary T4 screening program by 6% and 9%, respectively. We recommend screening analyses for VLBW infants in the latter part of the first week of life and again at 2 and 4 to 6 weeks of age. This protocol would increase the number of screening analyses by 1.6%.

Screening for congenital hypothyroidism: results of screening one million North American infants.

Pilot programs for screening of newborn infants for congenital hypothyroidism began in North America in 1972. To date, the five oldest programs (Quebec, Pittsburgh, Toronto, Oregon Regional, and New England Regional) have screened 1,046,362 infants. A total of 277 infants with congenital hypothyroidism have been detected and seven have been missed, resulting in a total of 284 affected infants in the screened population and an overall incidence of one in 3,684 live births. Of the affected infants, 246 were determined to have primary hypothyroidism, an incidence of one in 4,254 births. Ten infants with secondary-tertiary hypothyroidism were detected in Quebec, Oregon, and Toronto, an incidence of one in 68,200 births. Of all the infants with primary hypothyroidism who were adequately studied, 63% were determined to have aplastic or hypoplastic glands, 14% normal or enlarged glands, and 23% ectopic thyroid tissue. The estimated minimum incidence of infants with TBG deficiency is one in 8,913 births. Only 8 of the 277 detected infants were suspected clinically to have congenital hypothyroidism prior to the time of confirmation of the diagnosis at 4 to 8 weeks of age. The cost of screening varied from $0.70 to $1.60 per infant, depending on which costs were included in the estimate. Preliminary evidence from Quebec suggests that infants treated in the program have normal developmental testing scores at 18 months of age.