Safety of psychotropic medications in pregnancy: an umbrella review.

Weighing risks and benefits of the use of psychotropic medications during pregnancy remains a challenge worldwide. We systematically assessed the strength of associations between psychotropic medication use in pregnant people with mental disorders and various adverse health outcomes in both pregnant people and foetuses. Systematic reviews with meta-analyses of observational studies investigating the association between exposure to psychotropic medication in pregnancy and any adverse health outcomes were included. Credibility was graded into convincing, highly suggestive, suggestive, weak or not significant. Quality of the meta-analyses and of individual studies were assessed with A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2) the Newcastle-Ottawa Scale (NOS), respectively. We considered 21 meta-analyses encompassing 17,290,755 participants (AMSTAR 2 high = 1, low = 12, or critically low = 8). Evidence was suggestive for: (1) preterm birth in pregnant people with either any mental disorder (equivalent odds ratio 1.62 (95% confidence interval 1.24-2.12) or depression (1.65 [1.34-2.02]) receiving antidepressants during any trimester of pregnancy; (2) small for gestational age for pregnant people with depression receiving a SSRI during any trimester of pregnancy (1.50 [1.19-1.90]); and (3) major congenital malformation (1.24 [1.09-1.40]) or cardiac malformations (1.28 [1.11-1.47]) in babies for pregnant people with depression or anxiety receiving paroxetine during first trimester of pregnancy. Additional associations were supported by weak evidence, or were not statistically significant. This umbrella review found no convincing or highly suggestive level of evidence of adverse health outcomes associated with psychotropic medication use in pregnant people with mental disorders.

Gut commensal microvesicles reproduce parent bacterial signals to host immune and enteric nervous systems.

Ingestion of a commensal bacteria, Lactobacillus rhamnosus JB-1, has potent immunoregulatory effects, and changes nerve-dependent colon migrating motor complexes (MMCs), enteric nerve function, and behavior. How these alterations occur is unknown. JB-1 microvesicles (MVs) are enriched for heat shock protein components such as chaperonin 60 heat-shock protein isolated from Escherichia coli (GroEL) and reproduce regulatory and neuronal effects in vitro and in vivo. Ingested labeled MVs were detected in murine Peyer's patch (PP) dendritic cells (DCs) within 18 h. After 3 d, PP and mesenteric lymph node DCs assumed a regulatory phenotype and increased functional regulatory CD4(+)25(+)Foxp3+ T cells. JB-1, MVs, and GroEL similarly induced phenotypic change in cocultured DCs via multiple pathways including C-type lectin receptors specific intercellular adhesion molecule-3 grabbing non-integrin-related 1 and Dectin-1, as well as TLR-2 and -9. JB-1 and MVs also decreased the amplitude of neuronally dependent MMCs in an ex vivo model of peristalsis. Gut epithelial, but not direct neuronal application of, MVs, replicated functional effects of JB-1 on in situ patch-clamped enteric neurons. GroEL and anti-TLR-2 were without effect in this system, suggesting the importance of epithelium neuron signaling and discrimination between pathways for bacteria-neuron and -immune communication. Together these results offer a mechanistic explanation of how Gram-positive commensals and probiotics may influence the host's immune and nervous systems.

A trimodality comparison of volumetric bone imaging technologies. Part I: Short-term precision and validity.

In vivo peripheral quantitative computed tomography (pQCT) and peripheral magnetic resonance imaging (pMRI) modalities can measure apparent bone microstructure at resolutions 200 µm or higher. However, validity and in vivo test-retest reproducibility of apparent bone microstructure have yet to be determined on 1.0 T pMRI (196 µm) and pQCT (200 µm). This study examined 67 women with a mean age of 74±9 yr and body mass index of 27.65±5.74 kg/m2, demonstrating validity for trabecular separation from pMRI, cortical thickness, and bone volume fraction from pQCT images compared with high-resolution pQCT (hr-pQCT), with slopes close to unity. However, because of partial volume effects, cortical and trabecular thickness of bone derived from pMRI and pQCT images matched hr-pQCT more only when values were small. Short-term reproducibility of bone outcomes was highest for bone volume fraction (BV/TV) and densitometric variables and lowest for trabecular outcomes measuring microstructure. Measurements at the tibia for pQCT images were more precise than at the radius. In part I of this 3-part series focused on trimodality comparisons of precision and validity, it is shown that pQCT images can yield valid and reproducible apparent bone structural outcomes, but because of longer scan time and potential for more motion, the pMRI protocol examined here remains limited in achieving reliable values.

A Trimodality Comparison of Volumetric Bone Imaging Technologies. Part III: SD, SEE, LSC Association With Fragility Fractures.

Part II of this 3-part series demonstrated 1-yr precision, standard error of the estimate, and 1-yr least significant change for volumetric bone outcomes determined using peripheral (p) quantitative computed tomography (QCT) and peripheral magnetic resonance imaging (pMRI) modalities in vivo. However, no clinically relevant outcomes have been linked to these measures of change. This study examined 97 women with mean age of 75 ± 9 yr and body mass index of 26.84 ± 4.77 kg/m(2), demonstrating a lack of association between fragility fractures and standard deviation, least significant change and standard error of the estimate-based unit differences in volumetric bone outcomes derived from both pMRI and pQCT. Only cortical volumetric bone mineral density and cortical thickness derived from high-resolution pQCT images were associated with an increased odds for fractures. The same measures obtained by pQCT erred toward significance. Despite the smaller 1-yr and short-term precision error for measures at the tibia vs the radius, the associations with fractures observed at the radius were larger than at the tibia for high-resolution pQCT. Unit differences in cortical thickness and cortical volumetric bone mineral density able to yield a 50% increase in odds for fractures were quantified here and suggested as a reference for future power computations.

A Trimodality Comparison of Volumetric Bone Imaging Technologies. Part II: 1-Yr Change, Long-Term Precision, and Least Significant Change.

The previous article in this 3-part series demonstrated short-term precision and validity for volumetric bone outcome quantification using in vivo peripheral (p) quantitative computed tomography (pQCT) and magnetic resonance imaging (MRI) modalities at resolutions 200 µm or higher. However, 1-yr precision error and clinically significant references are yet to be reported for these modalities. This study examined 59 women with mean age of 75 ± 9 yr and body mass index of 26.84 ± 4.77 kg/m², demonstrating the lowest 1-yr precision error, standard errors of the estimate, and least significant change values for high-resolution (hr) pQCT followed by pQCT, and 1.0-T pMRI for all volumetric bone outcomes except trabecular number. Like short-term precision, 1-yr statistics for trabecular separation were similar across modalities. Excluding individuals with a previous history of fragility fractures, or who were current users of antiresorptives reduced 1-yr change for bone outcomes derived from pQCT and pMR images, but not hr-pQCT images. In Part II of this 3-part series focused on trimodality comparisons of 1-yr changes, hr-pQCT was recommended to be the prime candidate for quantifying change where smaller effect sizes are expected, but pQCT was identified as a feasible alternative for studies expecting larger changes.

Acquired myelinated retinal nerve fiber layer in a child with neurofibromatosis 1-related optic pathway glioma.

Myelinated retinal nerve fiber layer (RNFL) is a rare structural anomaly that occurs from abnormal myelination extending anterior to the lamina cribrosa. Clinically, myelinated RNFL is characterized as a gray-white lesion with feathered, well-demarcated borders obscuring the retinal vasculature. Myelinated RNFL is typically congenital, benign, and asymptomatic. It is most commonly noted as an incidental finding on ophthalmic examination. However, cases of acquired myelinated RNFL have been reported. We report the case of a patient with neurofibromatosis type 1 and optic pathway glioma with unilateral acquired myelinated RNFL.