Phthalates are among the most ubiquitous environmental contaminants and endocrine-disrupting chemicals. Exposure to phthalates and related health effects have been extensively studied over the past four decades. An association between phthalate exposure and allergic diseases has been suggested, although the literature is far from conclusive. This article reviews and evaluates epidemiological (n = 43), animal (n = 49), and cell culture studies (n = 42), published until the end of 2019, on phthalates and allergic diseases, such as asthma, rhinoconjunctivitis, and eczema. In contrast to earlier reviews, emphasis is placed on experimental studies that use concentrations with relevance for human exposure. Epidemiological studies provide support for associations between phthalate exposures and airway, nasal, ocular, and dermal allergic disease outcomes, although the reported significant associations tend to be weak and demonstrate inconsistencies for any given phthalate. Rodent studies support that phthalates may act as adjuvants at levels likely to be relevant for environmental exposures, inducing respiratory and inflammatory effects in the presence of an allergen. Cell culture studies demonstrate that phthalates may alter the functionality of innate and adaptive immune cells. However, due to limitations of the applied exposure methods and models in experimental studies, including the diversity of phthalates, exposure routes, and allergic diseases considered, the support provided to the epidemiological findings is fragmented. Nevertheless, the current evidence points in the direction of concern. Further research is warranted to identify the most critical windows of exposure, the importance of exposure pathways, interactions with social factors, and the effects of co-exposure to phthalates and other environmental contaminants.

Individuals born preterm and at very low birth weight (birth weight ≤ 1500 g) are at an increased risk of perinatal brain injury and neurodevelopmental deficits over the long term. This study examined whether this clinical group has more problems with visual-motor integration, motor coordination, and visual perception compared to term-born controls, and related these findings to cortical surface area and thickness and white matter fractional anisotropy. Forty-seven preterm-born very low birth weight individuals and 56 term-born controls were examined at 18-22 years of age with a combined cognitive, morphometric MRI, and diffusion tensor imaging evaluation in Trondheim, Norway. Visual-motor skills were evaluated with the Beery-Buktenica Developmental Test of Visual-Motor Integration-V (VMI) copying test and its supplemental tests of motor coordination and visual perception. 3D T1-weighted MPRAGE images and diffusion tensor imaging were done at 1.5 T. Cortical reconstruction generated in FreeSurfer and voxelwise maps of fractional anisotropy calculated with Tract-Based Spatial Statistics were used to explore the relationship between MRI findings and cognitive results. Very low birth weight individuals had significantly lower scores on the copying and motor coordination tests compared with controls. In the very low birth weight group, VMI scores showed significant positive relationships with cortical surface area in widespread regions, with reductions of the superior temporal gyrus, insula, and medial occipital lobe in conjunction with the posterior ventral temporal lobe. Visual perception scores also showed positive relationships with cortical thickness in the very low birth weight group, primarily in the lateral occipito-temporo-parietal junction, the superior temporal gyrus, insula, and superior parietal regions. In the very low birth weight group, visual-motor performance correlated positively with fractional anisotropy especially in the corpus callosum, inferior fronto-occipital fasciculus bilaterally, and anterior thalamic radiation bilaterally, driven primarily by an increase in radial diffusivity. VMI scores did not demonstrate a significant relationship to cortical surface area, cortical thickness, or diffusion measures in the control group. Our results indicate that visual-motor integration problems persist into adulthood for very low birth weight individuals, which may be due to structural alterations in several specific gray-white matter networks. Visual-motor deficits appear related to reduced surface area of motor and visual cortices and disturbed connectivity in long association tracts containing visual and motor information. We conjecture that these outcomes may be due to perinatal brain injury or aberrant cortical development secondary to injury or due to very preterm birth.

Preterm birth (gestational age < 37 weeks) with very low birth weight (VLBW, birth weight ≤ 1500 g) is associated with lifelong cognitive deficits, including in executive function, and persistent alterations in cortical and subcortical structures. However, it remains unclear whether “catch-up” growth is possible in the preterm/VLBW brain. Longitudinal structural MRI was conducted with children born preterm with VLBW (n = 41) and term-born peers participating in the Norwegian Mother and Child Cohort Study (MoBa) (n = 128) at two timepoints in early school age (mean ages 8.0 and 9.3 years). Images were analyzed with the FreeSurfer 5.3.0 longitudinal stream to assess differences in development of cortical thickness, surface area, and brain structure volumes, as well as associations with executive function development (NEPSY Statue and WMS-III Spatial Span scores) and perinatal health markers. No longitudinal group × time effects in cortical thickness, surface area, or subcortical volumes were seen, indicating similar brain growth trajectories in the groups over an approximately 16-month period in middle childhood. Higher IQ scores within the VLBW group were associated with greater surface area in left parieto-occipital and inferior temporal regions. Among VLBW preterm-born children, cortical surface area was smaller across the cortical mantle, and cortical thickness was thicker occipitally and frontally and thinner in lateral parietal and posterior temporal areas. Smaller volumes of corpus callosum, right globus pallidus, and right thalamus persisted in the VLBW group from timepoint 1 to 2. VLBW children had on average IQ 1 SD below term-born MoBa peers and significantly worse scores on WMS-III Spatial Span. Executive function scores did not show differential associations with morphometry between groups cross-sectionally or longitudinally. This study investigated divergent or “catch-up” growth in terms of cortical thickness, surface area, and volumes of subcortical gray matter structures and corpus callosum in children born preterm/VLBW and did not find group × time interactions. Greater surface area at mean age 9.3 in left parieto-occipital and inferior temporal cortex was associated with higher IQ in the VLBW group. These results suggest that preterm VLBW children may have altered cognitive networks, yet have structural growth trajectories that appear generally similar to their term-born peers in this early school age window.

Preterm birth and very low birth weight (VLBW, ≤1500 g) are worldwide problems that burden survivors with lifelong cognitive, psychological, and physical challenges. In this multimodal structural magnetic resonance imaging (MRI) and diffusion MRI (dMRI) study, we investigated differences in subcortical brain volumes and white matter tract properties in children born preterm with VLBW compared to term-born controls (mean age=8 years). Subcortical brain structure volumes and cortical thickness estimates were obtained, and fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) were generated for 18 white matter tracts. We also assessed structural relationships between white matter tracts and cortical thickness of the tract endpoints. Compared to controls, the VLBW group had reduced volumes of thalamus, globus pallidus, corpus callosum, cerebral white matter, ventral diencephalon, and brain stem, while the ventricular system was larger in VLBW subjects, after controlling for age, sex, IQ, and estimated total intracranial volume. For the dMRI parameters, group differences were not significant at the whole-tract level, though pointwise analysis found shorter segments affected in forceps minor and left superior longitudinal fasciculus - temporal bundle. IQ did not correlate with subcortical volumes or dMRI measures in the VLBW group. While the deviations in subcortical volumes were substantial, there were few differences in dMRI measures between the two groups, which may reflect the influence of advances in perinatal care on white matter development.

Public health measures necessary to counteract the coronavirus disease 2019 (COVID-19) pandemic have resulted in dramatic changes in the physical and social environments within which children grow and develop. As our understanding of the pathways for viral exposure and associated health outcomes in children evolves, it is critical to consider how changes in the social, cultural, economic, and physical environments resulting from the pandemic could affect the development of children. This review article considers the environments and settings that create the backdrop for children's health in the United States during the COVID-19 pandemic, including current threats to child development that stem from: A) change in exposures to environmental contaminants such as heavy metals, pesticides, disinfectants, air pollution and the built environment; B) changes in food environments resulting from adverse economic repercussion of the pandemic and limited reach of existing safety nets; C) limited access to children's educational and developmental resources; D) changes in the social environments at the individual and household levels, and their interplay with family stressors and mental health; E) social injustice and racism. The environmental changes due to COVID-19 are overlaid onto existing environmental and social disparities. This results in disproportionate effects among children in low-income settings and among populations experiencing the effects of structural racism. This article draws attention to many environments that should be considered in current and future policy responses to protect children's health amid pandemics.