A study to assess the optimal timing of repeat screening for congenital hypothyroidism in preterm babies concluded that the ideal strategy would involve initial screening at 72 to 120 hours followed by retesting at 1, 2, and 4 weeks, and at term-corrected gestational age or upon discharge from the hospital (J Pediatr 2018; doi.org/10.1016/j.jpeds.2018.09.044).

The common practice of repeat screening once at 2 weeks “will miss a significant number” of infants with delayed thyroid stimulating hormone (TSH) elevation and decompensated permanent congenital hypothyroidism, according to the authors. Moreover, repeat screening only at 4 weeks will lead to delayed diagnosis in babies with decompensated congenital hypothyroidism.

This study examined 13 years of data involving 898,424 babies who were screened for congenital hypothyroidism in the Republic of Ireland. The same AutoDELFIA immunoassay with a cutoff of 8 mU/L for whole blood TSH levels was used throughout the study. Even if their first TSH result was normal, preterm babies underwent weekly screening until they were term-corrected (37 weeks’ gestation) or discharged home.

In all, 586 infants were treated for congenital hypothyroidism, an incidence of 1:1,533 births. Of these babies, 55 were born at <33 weeks’ gestation, 50% (27) of whom had delayed TSH elevations and wouldn’t have been diagnosed when their first screens took place at 72 to 120 hours. Among the 27 infants with delayed TSH elevation, 12 (40.7%) had decompensated hypothyroidism at diagnosis with free thyroxine (FT4) levels <10 pmol/L, while 4 had severe congenital hypothyroidism with FT4 <5.5 pmol/L at diagnosis.

Six of the babies with delayed TSH elevation (22%) have permanent congenital hypothyroidism, and another 12 will be re-evaluated at age 3 years, according to the authors.

If repeat screening had only taken place when these babies were 2 weeks old, 13 (48%) would not have been identified.

The Leptin System Identified as a Key Driver of Type 2 Diabetes Development

A network analysis comparing levels of 27 biomarkers associated with risk for type 2 diabetes highlighted the central role of the leptin system interacting with other biological pathways in the development of this disease many years in advance of an individual’s clinical diagnosis (Diabetes 2018; doi.org/10.2337/db18-0892).

This secondary analysis of a case-control study within the Nurses’ Health Study examined participants who developed diabetes versus those who did not, based on baseline blood samples, biennial and supplemental questionnaires, and a formal diagnosis of diabetes over a 23-year period. In all, the secondary analysis included data from 1,303 new cases of diabetes and 1,627 healthy controls.

The investigators analyzed the biomarker network in cases versus controls for cases diagnosed less than 5 years, between 5 and 10 years, and more than 10 years after blood collection. Among participants who developed diabetes, 311, 491, and 501 were diagnosed <5, 5–10, >10 years after blood collection, respectively.

The 27 biomarkers considered in the study involve inflammation, adipokines, insulin-like growth factor (IGF) axis, endothelial dysfunction, glucose regulation, and body iron stores. The investigators created the correlation network based on pairwise Spearman correlations of these analytes that were statistically different between cases and non-cases using permutation tests.

The overarching network the researchers observed featured “leptin as a highly connected node with differential associations to multiple markers spanning different biologic axes,” including adipose secretion, inflammation, IGF, and glucose regulation. However, the connectedness of biomarker networks varied over the course of diabetes development, with hemoglobin A1C, leptin, and C-peptide networks more prominent in cases diagnosed <5 years, 5–10, and >10 years after blood collection, respectively.

Women With Negative HPV Test Results at Age 55 Safe to Forgo Further Cervical Cancer Screening

Women in developed countries with negative human papillomavirus (HPV) test results at age 55 are at low risk for cervical cancer and likely can forgo screening for this disease for the rest of their lives, a modeling study suggests (Lancet Oncol 2018;19:1569–78). Regular cytology screening up to age 75 may still prevent some cancers, though with declining benefits as women age.

The researchers used a Markov model of cervical cancer natural history and screening as a way to resolve the outstanding question of how long women should continue to be screened for this disease. Different clinical guidelines recommend that screening in high-income settings can be safely stopped anywhere from ages 55 to 70, but all note the low quality of evidence underlying their recommendations.

In their model the authors created an age-structured population of women ages 10 to 100, excluded women who had total hysterectomies, used HPV infection and cancer incidence data from Statistics Canada, and employed a three-stage progressive cervical intraepithelial neoplasia model to incorporate different management and treatment decisions depending on disease stage. Their model also considered 14 oncogenic HPV types and a generic group of other potentially oncogenic HPVs. The authors predicted lifetime risk of cervical cancer if a woman was perfectly adherent to screening guidelines, and if she received screening less often, as is typical.

The authors estimated that without screening or vaccination, 1 in 45 women would be diagnosed with cervical cancer. A woman with a typical screening adherence with cytology testing who stops screening at age 55 would have a 1 in 138 lifetime risk of this disease. This woman’s lifetime risk would drop further if she stopped screening with cytology testing at age 70. A woman who had perfect adherence to recommended cytology screening from age 29 to age 69 would reduce her lifetime risk to 1 in 532.

In contrast, the investigators estimated that a woman with a negative HPV DNA test for the 14 high-risk types who stops undergoing screening at age 55 would have a lifetime risk of cervical cancer of 1 in 1,940. A woman who had never undergone screening would remain at higher risk of cervical cancer for the rest of her life compared to women with typical screening adherence, but “a single negative HPV test still indicated a relatively low remaining risk of cervical cancer after the age of 55 years,” according to the authors.