David E. Sesser

Neonatal thyroxine level and perchlorate in drinking water

Environmental contamination of drinking water has been observed for perchlorate, a chemical able to affect thyroid function. This study examines whether that exposure affected the thyroid function of newborns. Neonatal blood thyroxine (T4) levels for days 1 to 4 of life were compared for newborns from the city of Las Vegas, Nevada, which has perchlorate in its drinking water, and those from the city of Reno, Nevada, which does not (detection limit, 4 micrograms/L [ppb]). This study is based on blood T4 analyses from more than 23,000 newborns in these two cities during the period April 1998 through June 1999. No difference was found in the mean blood T4 levels of the newborns from these two cities. Drinking water perchlorate levels measured monthly for Las Vegas ranged during this study period from non-detectable for 8 months to levels of 9 to 15 ppb for 7 months. Temporal differences in mean T4 level were noted in both cities but were unrelated to the perchlorate exposure. This study was sufficiently sensitive to detect the effects of gender, birth weight, and the day of life on which the blood sample was taken on the neonatal T4 level, but it detected no effect from environmental exposures to perchlorate that ranged up to 15 micrograms/L (ppb).

Congenital Hypothyroidism Caused by Excess Prenatal Maternal Iodine Ingestion

We report the cases of 3 infants with congenital hypothyroidism detected with the use of our newborn screening program, with evidence supporting excess maternal iodine ingestion (12.5 mg/d) as the etiology. Levels of whole blood iodine extracted from their newborn screening specimens were 10 times above mean control levels. Excess iodine ingestion from nutritional supplements is often unrecognized.

Neonatal thyroid‐stimulating hormone level and perchlorate in drinking water

BACKGROUND The effect of perchlorate in drinking water on neonatal blood thyroid-stimulating hormone (thyrotropin; TSH) levels was examined for Las Vegas and Reno, Nevada. METHODS The neonatal blood TSH levels in Las Vegas (with up to 15 microg/L (ppb) perchlorate in drinking water) and in Reno (with no perchlorate detected in the drinking water) from December 1998 to October 1999 were analyzed and compared. The study samples were from newborns in their first month of life (excluding the first day of life) with birth weights of 2, 500-4,500 g. A multivariate analysis of logarithmically transformed TSH levels was used to compare the mean TSH levels between Las Vegas and Reno newborns, with age and sex being controlled as potential confounders. RESULTS This study of neonatal TSH levels in the first month of life found no effect from living in the areas with environmental perchlorate exposures of </=15 microg/L (P = 0.97). CONCLUSIONS This study, which was sensitive enough to detect the effects of age and gender on neonatal blood TSH levels, detected no effect from environmental exposures to perchlorate.

Prevalence and Distribution of the c.1436C→T Sequence Variant of Carnitine Palmitoyltransferase 1A among Alaska Native Infants

OBJECTIVES To use genotype analysis to determine the prevalence of the c.1436C→T sequence variant in carnitine palmitoyltransferase 1A (CPT1A) among Alaskan infants, and evaluate the sensitivity of newborn screening by tandem mass spectrometry (MS/MS) to identify homozygous infants. STUDY DESIGN We compared MS/MS and DNA analyses of 2409 newborn blood spots collected over 3 consecutive months. RESULTS Of 2409 infants, 166 (6.9%) were homozygous for the variant, all but one of whom were of Alaska Native race. None of the homozygous infants was identified by MS/MS on the first newborn screen using a C0/C16 + C18 cutoff of 130. Among 633 Alaska Native infants, 165 (26.1%) were homozygous and 218 (34.4%) were heterozygous for the variant. The prevalence was highest in Alaskas northern/western regions (51.2% of 255 infants homozygous; allele frequency, 0.7). CONCLUSIONS The CPT1A c.1436C→T variant is prevalent among some Alaska Native peoples, but newborn screening using current MS/MS cutoffs is not an effective means to identify homozygous infants. The clinical consequences of the partial CPT1A deficiency associated with this variant are unknown. If effects are substantial, revision of newborn screening, including Alaska-specific MS/MS cutoffs and confirmatory genotyping, may be needed.

Transient versus Permanent Congenital Hypothyroidism after the Age of 3 Years in Infants Detected on the First versus Second Newborn Screening Test in Oregon, USA.

Background/Aims: The newborn screening (NBS) program in Oregon, USA, collects two routine specimens in all infants. The aim of our study was to determine the incidence of permanent versus transient congenital hypothyroidism (CH) in infants detected on the first versus second screening test. Methods: Thyroid function was determined in infants after the age of 3 years diagnosed with CH and born in Oregon between 2005 and 2011. Permanent hypothyroidism was defined as a TSH rise >10 mIU/ml after the first year on treatment or a TSH rise >6 mIU/ml with temporary discontinuation of l-thyroxine after the age of 3 years. Results: Of the cases detected on the first test, 72 of 87 (83%) were permanent and 15 of 87 (17%) were transient, while of the cases detected on the second test, 5 of 22 (23%) were permanent and 17 of 22 (77%) were transient (OR 16.3, p < 0.001). There was a female preponderance detected on the first screen versus a male preponderance on the second screen. Blood spot and serum thyroid function tests at diagnosis, before treatment, were not meaningfully different between the two groups. The mean l-thyroxine dose at the age of 3 years was greater on the first screen: 61.2 versus 36.6 μg/day. Conclusions: Infants detected on the second NBS specimen have a higher incidence of transient CH.

SCREENING FOR CONGENITAL HYPOTHYROIDISM: IS FOLLOW-UP OF NEWBORNS WITH LOW T4 AND “NON-ELEVATED” TSH CONCENTRATIONS INDICATED? 525

Most newborn screening programs using a primary T4 screen, with TSH measurement in specimens below a T4 cutoff, choose not to follow-up infants with low T4 and “non-elevated” (typically <25) TSH concentrations. The Northwest Regional Screening Program (NWRSP), which obtains two routine filter paper (FP) specimens in infants born in Oregon and in most infants in Idaho, Alaska, and Nevada, requests a serum specimen in infants with two FP T4 concentrations <3% and in infants with absolute T4< 3ug/dl even when the FP TSH is “not elevated”. To determine the type and frequency of thyroid disorders detected in infants with low T4 and “non-elevated” TSH concentrations, we examined the results of the NWRSP from May 1975 to May 1995. Over this 20 year period, the NWRSP screened 1,747,805 infants. Follow-up of infants with low T4s and“non-elevated” TSHs on screening detected 25 infants with delayed TSH rise (1:67,226), 9 infants with mild hypothyroidism (TSH<25)(1:194,212), 26 infants with hypopituitary hypothyroidism (1:67,223), and 434 infants with TBG deficiency (1:4027). Mean thyroid values were as follows:Table In 1994, this approach led to a recall of 116 infants, including 29 with TBG deficiency and 2 with hypopituitary hypothyroidism. Excluding those with TBG deficiency, the false positive rate was 1:43.5. Newborns who were premature or ill were found with disproportionate frequency among infants with these laboratory values. Thus, the majority of these infants are normal or have TBG deficiency; therefore the psychological harm in creating the “vulnerable” child vs. identifying the rare child with delayed TSH rise, mild hypothyroidism, or hypopituitary hypothyroidism (overall detection rate 1:29, 130) must be evaluated. The NWRSP continues to follow-up infants with low T4 and“non-elevated” TSH levels.