Early screening for gestational diabetes mellitus: a meta-analysis of randomized controlled trials.

OBJECTIVE: Current evidence is conflicting on whether early screening and treatment for gestational diabetes mellitus improve pregnancy outcomes. Thus, this systematic review and meta-analysis of randomized controlled trials aimed to assess the rate of adverse pregnancy outcomes among participants with early screening and treatment for gestational diabetes mellitus vs those with routine care. DATA SOURCES: A systematic review of the literature was conducted using MEDLINE, Scopus, ClinicalTrials.gov, EMBASE, ScienceDirect, the Cochrane Library at the Central Register of Controlled Trials, and SciELO from inception to November 2021. STUDY ELIGIBILITY CRITERIA: Studies were eligible for inclusion if they described randomized controlled trials comparing early screening with routine care for gestational diabetes mellitus to assess the effects of early screening and treatment on pregnancy outcomes. METHODS: All randomized controlled trials comparing early vs standard screening of gestational diabetes mellitus assessing the effect of early screening (defined as a screening at <20 weeks of gestation) vs routine screening (defined as a screening at ≥20 weeks of gestation) on pregnancy outcomes were included. The primary outcome was defined as large for gestational age, as defined by the trial. The secondary maternal and neonatal outcomes were also evaluated. Subgroup analyses were performed on the basis of screening strategy and methods. RESULTS: After exclusion, 8 randomized clinical trials (1920 participants) of early screening and treatment vs standard care were included. There were a total of 746 participants with early gestational diabetes mellitus. The risk of large for gestational age at birth did not differ between early screening and treatment for gestational diabetes mellitus and routine care among all included trials (8.1 vs 9.0%; relative risk, 0.94; 95% confidence interval, 0.73-1.22). Trials with a protocol of universal screening of participants at their first prenatal visit (>80% screened with HbA1c) and receiving early treatment if the screening test returned positive had a lower risk of large for gestational age (2.3 vs 9.1%; relative risk, 0.29; 95% confidence interval, 0.09-0.90) than those who had routine screening and care. CONCLUSION: Overall, early screening and treatment of gestational diabetes mellitus did not reduce the risk of large for gestational age at birth. However, trials that screened all participants at their first visit and treated early, most for an HbA1c of 5.7% to 6.4%, had a reduced risk of large for gestational age at birth compared with routine care, suggesting a possible benefit of screening all pregnant patients. However, future well-designed trials are needed to confirm these findings.

Thymic stromal lymphopoietin-mediated extramedullary hematopoiesis promotes allergic inflammation.

Extramedullary hematopoiesis (EMH) refers to the differentiation of hematopoietic stem cells (HSCs) into effector cells that occurs in compartments outside of the bone marrow. Previous studies linked pattern-recognition receptor (PRR)-expressing HSCs, EMH, and immune responses to microbial stimuli. However, whether EMH operates in broader immune contexts remains unknown. Here, we demonstrate a previously unrecognized role for thymic stromal lymphopoietin (TSLP) in promoting the population expansion of progenitor cells in the periphery and identify that TSLP-elicited progenitors differentiated into effector cells including macrophages, dendritic cells, and granulocytes and that these cells contributed to type 2 cytokine responses. The frequency of circulating progenitor cells was also increased in allergic patients with a gain-of-function polymorphism in TSLP, suggesting the TSLP-EMH pathway might operate in human disease. These data identify that TSLP-induced EMH contributes to the development of allergic inflammation and indicate that EMH is a conserved mechanism of innate immunity.

Thymic stromal lymphopoietin-elicited basophil responses promote eosinophilic esophagitis.

Eosinophilic esophagitis (EoE) is a food allergy-associated inflammatory disease characterized by esophageal eosinophilia. Current management strategies for EoE are nonspecific, and thus there is a need to identify specific immunological pathways that could be targeted to treat this disease. EoE is associated with polymorphisms in the gene that encodes thymic stromal lymphopoietin (TSLP), a cytokine that promotes allergic inflammation, but how TSLP might contribute to EoE disease pathogenesis has been unclear. Here, we describe a new mouse model of EoE-like disease that developed independently of IgE, but was dependent on TSLP and basophils, as targeting TSLP or basophils during the sensitization phase limited disease. Notably, therapeutic TSLP neutralization or basophil depletion also ameliorated established EoE-like disease. In human subjects with EoE, we observed elevated TSLP expression and exaggerated basophil responses in esophageal biopsies, and a gain-of-function TSLP polymorphism was associated with increased basophil responses in patients with EoE. Together, these data suggest that the TSLP-basophil axis contributes to the pathogenesis of EoE and could be therapeutically targeted to treat this disease.