Utility of Repeat Testing for Congenital Hypothyroidism in Infants with Very Low Birth Weight.

OBJECTIVE: To assess for possible missed hypothyroidism in infants of very low birth weight (VLBW) whose initial newborn screening (NBS) was within normal reference range. STUDY DESIGN: We analyzed serum thyroid-stimulating hormone (TSH) obtained at 36 weeks of corrected gestational age or at hospital discharge if earlier (retest TSH) in infants with VLBW in the neonatal intensive care unit to determine the prevalence and factors associated with retest TSH ≥5 mU/L, a concentration requiring close follow-up for hypothyroidism. Utility of alternative cut-offs for NBS TSH also was assessed. RESULTS: A total of 398 infants, median gestational age 29 (range 22-36) weeks, birth weight 1138 (470-1498) g, were included in this study. Retest TSH was obtained at 49.5 (12-137) days after birth. Median retest TSH was 3.1 (0.5-27.9) mU/L. Seventy-three (18.3%) of the cohort had retest TSH ≥5 mU/L. Adjusting NBS cut-off to ≥15 or ≥10 mU/L identified <50% of infants with TSH ≥5 mU/L, resulting in 6% false positives and >70% false negatives. Multiple regression modeling indicated that 35% of variance in retest TSH value was explained by NBS TSH concentration, birth weight, and gestational age, all P < .01. CONCLUSIONS: Retesting for hypothyroidism at 36 weeks of corrected gestational age in infants with VLBL and normal NBS could identify infants who require ongoing surveillance until thyroid function has been definitively ascertained. Adjusting NBS TSH cutoffs is not a valid option for identifying potential hypothyroidism in infants with VLBW because of lack of sensitivity and unacceptable false-positive and false-negative rates.

Progression of Vasculopathy in Young Individuals with Turner Syndrome.

Vasculopathy has been identified in young individuals with Turner syndrome (TS). No studies in young individuals with TS have investigated whether this vasculopathy progresses over time. The objective of this study is to describe the changes in vasculopathy over time in a cohort of young individuals with TS. Repeat ultrasound and SphygmoCor CPV® (AtCor Medical) measurements of carotid thickness and peripheral arterial stiffness were performed. Vascular measurements were compared at baseline and follow-up. Follow-up measurements were also compared to historical lean (L) and obese (O) age-, race-, and sex-matched non-TS controls. Thirty-five individuals with TS were studied at a mean age of 19.4 years (range, 13.9-27.5). Mean time to follow-up was 7.2 years (range, 7.1-7.8). Carotid intima media thickness increased by 0.03 ± 0.07 mm (p < 0.01) over time, but was less than L and O controls at follow-up. Pulse wave velocity carotid-femoral increased by 0.51 ± 0.86 m/s (p < 0.01) over time, but was similar to L and less than O controls at follow-up. Augmentation index (AIx) remained unchanged (p = 0.09) over time, but was significantly higher at follow-up than both control groups (p < 0.01 for both). There were no identified differences between 45,X and other TS genotypes. We demonstrate evidence of vascular thickening and stiffening over 7 years in a cohort of young individuals with TS, as well as a persistently increased augmentation index compared to L and O non-TS controls. It is unclear whether the increase in vascular structure and function are related to normal aging or if TS is a risk factor. Higher body mass index seems to be a risk factor. Early estrogen replacement and longer exposure to growth hormone therapy need to be further explored as potential protective factors.

Drosophila muller f elements maintain a distinct set of genomic properties over 40 million years of evolution.

The Muller F element (4.2 Mb, ~80 protein-coding genes) is an unusual autosome of Drosophila melanogaster; it is mostly heterochromatic with a low recombination rate. To investigate how these properties impact the evolution of repeats and genes, we manually improved the sequence and annotated the genes on the D. erecta, D. mojavensis, and D. grimshawi F elements and euchromatic domains from the Muller D element. We find that F elements have greater transposon density (25-50%) than euchromatic reference regions (3-11%). Among the F elements, D. grimshawi has the lowest transposon density (particularly DINE-1: 2% vs. 11-27%). F element genes have larger coding spans, more coding exons, larger introns, and lower codon bias. Comparison of the Effective Number of Codons with the Codon Adaptation Index shows that, in contrast to the other species, codon bias in D. grimshawi F element genes can be attributed primarily to selection instead of mutational biases, suggesting that density and types of transposons affect the degree of local heterochromatin formation. F element genes have lower estimated DNA melting temperatures than D element genes, potentially facilitating transcription through heterochromatin. Most F element genes (~90%) have remained on that element, but the F element has smaller syntenic blocks than genome averages (3.4-3.6 vs. 8.4-8.8 genes per block), indicating greater rates of inversion despite lower rates of recombination. Overall, the F element has maintained characteristics that are distinct from other autosomes in the Drosophila lineage, illuminating the constraints imposed by a heterochromatic milieu.