Maternal Antioxidant Levels in Pregnancy and Risk of Preeclampsia and Small for Gestational Age Birth: A Systematic Review and Meta-Analysis.

BACKGROUND: Oxidative stress in preeclampsia and small for gestational age (SGA) birth suggests antioxidant supplementation could prevent these conditions. However, it remains unclear whether maternal antioxidant levels are systematically lower in these pregnancies. OBJECTIVE: To conduct a systematic review of the association between maternal antioxidant levels during pregnancy and preeclampsia or SGA. METHODS: We searched PubMed, Embase, and several other databases from 1970-2013 for observational studies that measured maternal blood levels of non-enzymatic antioxidants (vitamins A, C, E, and carotenoids) during pregnancy or within 72 hours of delivery. The entire review process was done in duplicate. Study quality was assessed using the Newcastle-Ottawa Scale and additional questions. We pooled the standardized mean difference (SMD) across studies, stratified by outcome and pregnancy trimester, and investigated heterogeneity using meta-regression. RESULTS: We reviewed 1,882 unique citations and 64 studies were included. Most studies were small with important risk of bias. Among studies that addressed preeclampsia (n = 58) and SGA (n = 9), 16% and 66%, respectively, measured levels prior to diagnosis. The SMDs for vitamins A, C, and E were significantly negative for overall preeclampsia, but not for mild or severe preeclampsia subtypes. Significant heterogeneity was observed in all meta-analyses and most could not be explained. Evidence for lower carotenoid antioxidants in preeclampsia and SGA was limited and inconclusive. Publication bias appears likely. CONCLUSIONS: Small, low-quality studies limit conclusions that can be drawn from the available literature. Observational studies inconsistently show that vitamins C and E or other antioxidants are lower in women who develop preeclampsia or SGA. Reverse causality remains a possible explanation for associations observed. New clinical trials are not warranted in light of this evidence; however, additional rigorous observational studies measuring antioxidant levels before clinical detection of preeclampsia and SGA may clarify whether levels are altered at a causally-relevant time of pregnancy.

A focus on the optical properties of the regenerated newt lens.

Lens regeneration studies in the adult newt suggest that molecular aspects of lens regeneration are complete within 5 weeks of lentectomy. However, very little is known about the optical properties of the regenerated lens. In an aquatic environment, the lens accounts for almost all of the refractive power of the eye, and thus, a fully functional lens is critical. We compared the optical properties of 9- and 26-week regenerated lenses in the red spotted newt, Notophthalmus viridescens, with the original lenses removed from the same eyes. At 9 weeks, the regenerated lenses are smaller than the original lenses and are histologically immature, with a lower density of lens proteins. The 9 week lenses have greater light transmission, but significantly reduced focal length and refractive index than the original lenses. This suggests that following 9 weeks of regeneration, the lenses have not recovered the functionality of the original lens. By 26 weeks, the transmission of light in the more mature lens is reduced, but the optical parameters of the lens have recovered enough to allow functional vision.

De novo germline and postzygotic mutations in AKT3, PIK3R2 and PIK3CA cause a spectrum of related megalencephaly syndromes.

Megalencephaly-capillary malformation (MCAP) and megalencephaly-polymicrogyria-polydactyly-hydrocephalus (MPPH) syndromes are sporadic overgrowth disorders associated with markedly enlarged brain size and other recognizable features. We performed exome sequencing in 3 families with MCAP or MPPH, and our initial observations were confirmed in exomes from 7 individuals with MCAP and 174 control individuals, as well as in 40 additional subjects with megalencephaly, using a combination of Sanger sequencing, restriction enzyme assays and targeted deep sequencing. We identified de novo germline or postzygotic mutations in three core components of the phosphatidylinositol 3-kinase (PI3K)-AKT pathway. These include 2 mutations in AKT3, 1 recurrent mutation in PIK3R2 in 11 unrelated families with MPPH and 15 mostly postzygotic mutations in PIK3CA in 23 individuals with MCAP and 1 with MPPH. Our data highlight the central role of PI3K-AKT signaling in vascular, limb and brain development and emphasize the power of massively parallel sequencing in a challenging context of phenotypic and genetic heterogeneity combined with postzygotic mosaicism.

Recovery of function following regeneration of the damaged retina in the adult newt, Notophthalmus viridescens.

The red-spotted newt, Notophthalmus viridescens, is one of few adult vertebrate organisms that has retained the remarkable ability to regenerate a complete retina following injury or removal. The aim of this study was to develop a non-invasive method to monitor recovery of components within the retinal circuitry, in vivo, following surgical removal (retinectomy) of the adult newt retina. A novel and reproducible protocol was established for full-field electroretinography in the intact newt retina. Electroretinograms (ERGs) were measured at the corneal surface. The effects of dilation and external body temperature on the ERG amplitudes were measured as well as the reproducibility in recording ERGs in the same animal over time. Retinectomies were conducted on 15 newts, and the a- and b-wave amplitudes were measured prior to retinectomy and at various timepoints after retinectomy. Surgical removal of the retina resulted in an initial loss of ERG a- and b-waves, representing loss of photoreceptor cells and cells of the inner nuclear layer. The ERG amplitudes recovered to baseline levels by 15 weeks post-retinectomy, indicative of subsequent restoration of retinal function after regeneration.