Rosalie J. Hermos

Maternal thyroid deficiency during pregnancy and subsequent neuropsychological development of the child.

BACKGROUND When thyroid deficiency occurs simultaneously in a pregnant woman and her fetus, the childs neuropsychological development is adversely affected. Whether developmental problems occur when only the mother has hypothyroidism during pregnancy is not known. METHODS In 1996 and 1997, we measured thyrotropin in stored serum samples collected from 25,216 pregnant women between January 1987 and March 1990. We then located 47 women with serum thyrotropin concentrations at or above the 99.7th percentile of the values for all the pregnant women, 15 women with values between the 98th and 99.6th percentiles, inclusive, in combination with low thyroxine levels, and 124 matched women with normal values. Their seven-to-nine-year-old children, none of whom had hypothyroidism as newborns, underwent 15 tests relating to intelligence, attention, language, reading ability, school performance, and visual-motor performance. RESULTS The children of the 62 women with high serum thyrotropin concentrations performed slightly less well on all 15 tests. Their full-scale IQ scores on the Wechsler Intelligence Scale for Children, third edition, averaged 4 points lower than those of the children of the 124 matched control women (P= 0.06); 15 percent had scores of 85 or less, as compared with 5 percent of the matched control children. Of the 62 women with thyroid deficiency, 48 were not treated for the condition during the pregnancy under study. The full-scale IQ scores of their children averaged 7 points lower than those of the 124 matched control children (P=0.005); 19 percent had scores of 85 or less. Eleven years after the pregnancy under study, 64 percent of the untreated women and 4 percent of the matched control women had confirmed hypothyroidism. CONCLUSIONS Undiagnosed hypothyroidism in pregnant women may adversely affect their fetuses; therefore, screening for thyroid deficiency during pregnancy may be warranted.

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%.

Early Minimal Feedings Promote Growth in Critically III Premature Infants

Critically ill premature infants requiring mechanical ventilation and an umbilical artery catheter usually do not receive enteral feedings during the acute phase of their illness. We studied the safety and benefit of early minimal enteral feedings during this time in a prospective, controlled, and randomized study. Twenty-nine infants were randomly assigned to receive only standard intravenous fluid and nutrition (nothing per OS, NPO group; n = 13), or in addition to receive small-volume hypocaloric continuous feedings (1 ml/kg/h), beginning at 24 h of age (early-feeding group; n = 16). Standard enteral feedings were begun in both groups at the resolution of the acute phase of the illness and advanced by protocol. The two groups were of comparable birth weight, gestational age, and Apgar scores. There were no significant differences in the episodes of feeding intolerance. Two infants in the NPO group developed clinical signs of necrotizing enterocolitis. Serum diamine oxidase and somatomedin C were measured weekly until 30-60 days of age and were not different between the two groups. The early-feeding group required fewer days to reach 120 ml/kg/day enteral intake (early-feeding group 10 +/- 3 days, NPO group 13 +/- 4 days; p < 0.05). On day 30 of life the early-feeding group was 223 +/- 125 g above birth weight, while the NPO group was 95 +/- 161 g above birth weight (p < 0.05). The average intake (kcal/kg/day) from day 6 to day 30 was not different between the two groups. We conclude that early minimal feedings in critically ill very-low-birth-weight infants requiring mechanical ventilation are well tolerated and result in reduced time to reach 120 ml/kg/day of enteral feeding and in a greater weight gain by day 30 of life.

Atypical hypothyroidism and the very low birthweight infant.

Results of thyroid screening tests were examined retrospectively on 311,282 infants born in Massachusetts from January 1, 1993 to December 31, 1996. During this period, 118 infants were found to have typical hypothyroidism, characterized by a low thyroxine (T4) and an elevated thyrotropin (TSH) on the initial newborn-screening specimen. Of these, 98 were normal birthweight (NBW, > or = 2,500 g), 9 were low birthweight (LBW, 1,501-2,499 g), and 11 were very low birthweight (VLBW, < or = 1,500 g). Atypical hypothyroidism as defined here is characterized by a low T4 and normal TSH concentration on the initial screening specimen, followed by and elevated TSH level on a repeat blood specimen. This phenomenon occurred in 18 infants, of whom 4 were NBW, 4 were LBW, and 10 were VLBW. The incidence of combined typical and atypical hypothyroidism was: NBW, 1:3051; LBW, 1:1589; VLBW, 1:153, with the highest incidence of atypical hypothyroidism in the VLBW category (48% of cases in this weight category, 56% of all cases of atypical hypothyroidism). In addition, screening programs using a primary TSH screen will miss infants with atypical hypothyroidism. In view of these results, it is suggested that T4 measurements be obtained routinely in all LBW and VLBW infants, with additional routine repeat blood specimens.

Thyroid function in very low birth weight infants

The purpose of this study was to test the hypothesis that low circulating thyroxine concentrations characteristic of very low birth weight (VLBW) neonates (< 1500 g) are the result of decreased protein binding of thyroid hormones and to elucidate the mechanism(s) responsible and possible significance thereof.

Cortisol in dried blood screening specimens from newborns with raised 17‐hydroxyprogesterone and congenital adrenal hyperplasia

Screening for congenital adrenal hyperplasia (CAH) in newborns has become a routine part of many programmes by measuring levels of 17 α‐hydroxyprogesterone (17‐OHP) in the newborn filter‐paper blood specimen. Unfortunately, raised levels of 17‐OHP, which are largely the consequence of cross‐reacting metabolites, are also found in low birth weight, premature and ill neonates. We speculated that differences in concen_trations of cortisol in the newborn screening specimen would aid in distinguishing between CAH positive and CAH negative infants among those with raised levels of 17‐OHP.

Thyroid peroxidase antibodies in dried blood specimens of newborns.

Previous studies have disclosed that a substantial percentage of infants from mothers with thyroid autoimmunity have antibodies to thyroid peroxidase (TPOAb) at birth. Furthermore, these antibodies have been shown to be of maternal origin. In view of this we thought it would be of interest to determine the prevalence of TPOAb in newborns from an unselected population of women. This was done by retrieving stored dried blood specimens from 240 full-term healthy infants, which had been obtained during 1999 for routine newborn screening. Ten percent of the randomly selected specimens tested TPOAb positive. Thyroid function in the mothers could not be evaluated because all specimens had been tested anonymously. In summary, our results indicate that a significant percentage of newborns were TPOAb positive. It is unclear at this time whether such antibodies reflected maternal thyroid autoimmunity and/or other autoimmune disorders. However, the close association between autoimmune thyroid disease and TPOAb positivity raises the possibility of abnormal thyroid function in some of the mothers.

Problems in the Management of Patients with Infantile Hypothyroidism

There is general agreement that treatment of hypothyroid infants diagnosed by screening has proved to be remarkably effective in preventing the intellectual deficit commonly seen in infantile hypothyroidism of an earlier era. However, not all programs have experienced the same degree of success with respect to neuropsychological outcome among their patients. Both the Toronto and Quebec investigators have reported that children with delayed skeletal maturation had lower global IQ scores than those of the children with normal bone maturation at birth.1, 2

Maternal Thyroid Deficiency During Pregnancy and Subsequent Neuropsychological Development of the Child

When both the fetus and mother have thyroid deficiency, it can be expected that neuropsychological development will be compromised, but it is not clear whether similar problems occur when only the mother is hypothyroid. This study reviewed thyrotropin (TSH) values in stored sera from >25,000 pregnant women. Forty-seven had serum TSH values at or above the 99.7th percentile for all pregnant women, and 15 others had levels between the 98th and 99.6th percentiles as well as a low thyroxine level (below 99.7 nmol/liter). The hypothyroid women were matched with 124 women whose TSH values were normal, and their children underwent 15 tests when they were 7 to 9 years of age. These tests evaluated intelligence, language function, attention, reading ability, visuomotor function, and performance at school. None of the infants in this study had congenital hypothyroidism. The hypothyroid and normothyroid women were comparable demographically and in their pregnancies. Case children performed less well than control children on all of the neuropsychological tests. Full-scale Wechsler IQ scores were an average of 4 points lower in the children of hypothyroid mothers than in the comparison group; 15 and 5 percent, respectively, had scores of 85 or below. IQ scores of the children of the 48 women not treated for hypothyroidism during pregnancy were an average of 7 points lower than those of control children, and 19 percent had scores of 85 or less. When examined 11 years after delivery, 64 percent of untreated women and 4 percent of control women had confirmed hypothyroidism. These findings suggest that it may be worthwhile to routinely screen for hypothyroidism in early pregnancy. Testing at the first prenatal visit and prompt follow-up of those with positive results would permit timely treatment and could prevent adverse neuropsychological effects during early child development. N Engl J Med 1999;341:549–555