Prenatal Methamphetamine Exposure: Effects on Child Development­A Systematic Review.

BACKGROUND: In Germany, the 12-month prevalence of methamphetamine use among persons aged 15 to 34 is 1.9%. An increasing number of newborns are being born after a prenatal methamphetamine exposure (PME). In 2014, in the German state of Saxony, approximately four out of 1000 newborns were affected. METHODS: This systematic review (Prospero registration number CRD42017060536) includes publications that were published between January 1990 and November 2019. The purpose was to determine the effects of PME on the peri- and neonatal condition of the affected children and on their further long-term development. Observational studies with a control group were included in the review and examined for their methodological quality. RESULTS: 31 publications, which dealt with two prospective and six retrospective cohort studies, were included in the review. The studies involved a total of 4446 mother-child pairs with PME, compared with 43 778 pairs without PME. A metaanalysis revealed that PME was associated with, among other findings, lower birth weight (SMD = -0.348; 95% confidence interval [-0.777; 0.081]), shorter body length (SMD= -0.198 [-0.348; -0.047]), and smaller head circumference (SMD= -0.479 [-1.047; 0.089]). Some differences between the groups with and without PME persist into the toddler years. Moreover, children with PME much more commonly display psychological and neurocognitive abnormalities, which are more severe in children growing up in problematic surroundings (discord, violence, poverty, low educational level of the parent or caregiver). A limitation of this review is that not all studies employed an objective or quantitative measure of methamphet - amine use. CONCLUSION: The documented effects of PME on child development necessitate early treatment of the affected expectant mothers, children, and families. Emphasis should be placed on structured and interdisciplinary preventive measures for methamphetamine use.

Targeted and Checkpoint Inhibitor Therapy of Metastatic Malignant Melanoma in Germany, 2000-2016.

Targeted therapies (TT) and immune checkpoint inhibitors (ICI) have become increasingly important in the treatment of metastatic malignant melanoma in recent years. We examined implementation and effectiveness of these new therapies over time in Germany with a focus on regional differences. We analyzed data from 12 clinical cancer registries in 8 federal states in Germany over the period 2000-2016. A total of 3871 patients with malignant melanoma in Union internationale contre le cancer (UICC) stage IV at primary diagnosis (synchronous metastases) or with metachronous metastases were included. We investigated differences in survival of patients treated with new and conventional therapies by log-rank tests for Kaplan-Meier curves. Cox regression models were estimated to adjust therapy effects for demographic, regional, and prognostic factors. New systemic therapies were increasingly applied throughout Germany. TT were most frequently documented in Eastern Germany (East: 11.2%; West: 6.3%), whereas ICI therapies were more frequently used in Western Germany (East: 1.7%; West: 3.9%). TT had a relevant influence on patient survival (hazard ratio (HR) = 0.831; 95%-CI = (0.729; 0.948)). Survival was worse in Eastern Germany (HR = 1.470; 95%-CI = (1.347; 1.604)) relative to Western Germany. Treatment and survival prospects of patients with melanoma differed considerably between Western and Eastern Germany. The differences in regional medication behavior and survival require further exploration.