Efficacy and safety of current treatment options for peripheral retinal haemangioblastomas: a systematic review.

IMPORTANCE: Approximately twenty per cent of Von Hippel-Lindau patients with retinal haemangioblastomas (RH) suffer from visual impairment. Various treatment options are available for peripheral RH. However, management of peripheral RH is complex due to multifocality and bilaterality. OBJECTIVE: To summarize published evidence on efficacy and safety of different interventions for peripheral RH and to provide treatment recommendations for specialists. EVIDENCE REVIEW: Comprehensive searches were performed using Medline, Embase, Web of Science and Google Scholar database on 4 March 2020. English publications that described outcomes related to efficacy or complications in at least two patients with peripheral RH were included. Efficacy and safety were estimated by complete tumour eradication rate, pretherapeutic and treatment-related complication rate. Odds ratios (OR) with 95% confidence intervals (CI) were calculated to calculate the risk estimate of complications between treatment options. FINDINGS: Twenty-seven articles were included in this review describing nine different treatment options for peripheral RH: laser photocoagulation (n = 230), cryotherapy (n = 50), plaque radiotherapy (n = 27), vitreoretinal surgery (n = 88), photodynamic therapy (PDT; n = 14), transpupillary thermotherapy (TTT; n = 10), external beam radiotherapy (n = 3), systemic treatment (n = 7) and intravitreal anti-VEGF (n = 2). Complete tumour eradication was achieved in 86.7% (95% CI: 83.5-89.9%) of all eyes. For the different treatments, this was after laser photocoagulation 89.9% (86.1-93.7%), cryotherapy 70.2% (57.0-83.4%), plaque radiotherapy 96.3% (89.1-100.0%), vitreoretinal surgery (100.0%), PDT 64.3% (38.3-90.3%) and TTT 80.0% (53.8-100.0%). No complete tumour eradication was achieved after systemic therapy, external beam radiotherapy or intravitreal anti-VEGF. Photodynamic therapy and vitreoretinal surgery showed the highest complication rate after treatment compared to the other treatments (OR 10.5 [95% CI: 2.9-38.4]) and (OR 5.9 [95% CI: 3.4-9.9]), respectively. Cases that had pretherapeutic complications showed a higher treatment-related complication rate (OR 14.8 [95% CI: 7.3-30.0]) than cases without complications before treatment. CONCLUSIONS AND RELEVANCE: These findings suggest that laser photocoagulation is the safest and most effective treatment method for peripheral RH up to 1.5 mm in diameter. Vitreoretinal surgery has the highest success rate for complete tumour eradication and may be the most suitable treatment option in the presence of pretherapeutic complications and for larger tumours.

Maternal caffeine intake during pregnancy, early growth, and body fat distribution at school age.

OBJECTIVE: The associations of maternal caffeine intake during pregnancy with offspring growth patterns and body fat and insulin levels at school age were examined. METHODS: In a population-based birth cohort among 7,857 mothers and their children, maternal caffeine intake during pregnancy was assessed by questionnaires. Growth characteristics were measured from birth onward. At 6 years, body fat and insulin levels were measured. RESULTS: Compared to children whose mothers consumed <2 units of caffeine per day during pregnancy (1 unit of caffeine is equivalent to 1 cup of coffee (90 mg caffeine)), those whose mothers consumed ≥6 units of caffeine per day tended to have a lower weight at birth, higher weight gain from birth to 6 years, and higher body mass index from 6 months to 6 years. Both children whose mothers consumed 4-5.9 and ≥6 units of caffeine per day during pregnancy tended to have a higher childhood body mass index and total body fat mass. Only children whose mothers consumed ≥6 units of caffeine per day had a higher android/gynoid fat mass ratio. CONCLUSIONS: These results suggest that high levels of maternal caffeine intake during pregnancy are associated with adverse offspring growth patterns and childhood body fat distribution.

Maternal plasma PUFA concentrations during pregnancy and childhood adiposity: the Generation R Study.

BACKGROUND: Maternal polyunsaturated fatty acid (PUFA) concentrations during pregnancy may have persistent effects on growth and adiposity in the offspring. A suboptimal maternal diet during pregnancy might lead to fetal cardiometabolic adaptations with persistent consequences in the offspring. OBJECTIVE: We examined the associations of maternal PUFA concentrations during pregnancy with childhood general and abdominal fat-distribution measures. DESIGN: In a population-based, prospective cohort study of 4830 mothers and their children, we measured maternal second-trimester plasma n-3 (ω-3) and n-6 (ω-6) PUFA concentrations. At the median age of 6.0 y (95% range: 5.6, 7.9 y), we measured childhood body mass index (BMI), the fat mass percentage, and the android:gynoid fat ratio with the use of dual-energy X-ray absorptiometry and measured the preperitoneal abdominal fat area with the use of ultrasound. Analyses were adjusted for maternal and childhood sociodemographic- and lifestyle-related characteristics. RESULTS: We observed that higher maternal total n-3 PUFA concentrations, and specifically those of eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid, were associated with a lower childhood total-body fat percentage and a lower android:gynoid fat mass ratio (P< 0.05) but not with childhood BMI and the abdominal preperitoneal fat mass area. Higher maternal total n-6 PUFA concentrations, and specifically those of dihomo-γ-linolenic acid, were associated with a higher childhood total-body fat percentage, android:gynoid fat mass ratio, and abdominal preperitoneal fat mass area (P< 0.05) but not with childhood BMI. In line with these findings, a higher maternal n-6:n-3 PUFA ratio was associated with higher childhood total-body and abdominal fat mass. CONCLUSIONS: Lower maternal n-3 PUFA concentrations and higher n-6 PUFA concentrations during pregnancy are associated with higher body fat and abdominal fat in childhood. Additional studies are needed to replicate these observations and to explore the causality, the underlying pathways, and the long-term cardiometabolic consequences.

Body mass index, gestational weight gain and fatty acid concentrations during pregnancy: the Generation R Study.

Obesity during pregnancy may be correlated with an adverse nutritional status affecting pregnancy and offspring outcomes. We examined the associations of prepregnancy body mass index and gestational weight gain with plasma fatty acid concentrations in mid-pregnancy. This study was embedded in a population-based prospective cohort study among 5636 women. We obtained prepregnancy body mass index and maximum weight gain during pregnancy by questionnaires. We measured concentrations of saturated fatty acid (SFA), monounsaturated fatty acid (MUFA), n-3 polyunsaturated fatty acid (n-3 PUFA) and n-6 polyunsaturated fatty acid (n-6 PUFA) at a median gestational age of 20.5 (95% range 17.1-24.9) weeks. We used multivariate linear regression models. As compared to normal weight women, obese women had higher total SFA concentrations [difference: 0.10 standard deviation (SD) (95% Confidence Interval (CI) 0, 0.19)] and lower total n-3 PUFA concentrations [difference: - 0.11 SD (95% CI - 0.20, - 0.02)]. As compared to women with sufficient gestational weight gain, those with excessive gestational weight gain had higher SFA concentrations [difference: 0.16 SD (95% CI 0.08, 0.25)], MUFA concentrations [difference: 0.16 SD (95% CI 0.08, 0.24)] and n-6 PUFA concentrations [difference: 0.12 SD (95% CI 0.04, 0.21)]. These results were not materially affected by adjustment for maternal characteristics. Our results suggest that obesity and excessive weight gain during pregnancy are associated with an adverse fatty acids profile. Further studies are needed to assess causality and direction of the observed associations.

Higher Maternal Plasma n-3 PUFA and Lower n-6 PUFA Concentrations in Pregnancy Are Associated with Lower Childhood Systolic Blood Pressure.

BACKGROUND: Suboptimal maternal diet during pregnancy might lead to fetal cardiovascular adaptations with persistent consequences in the offspring. OBJECTIVE: We assessed the associations of maternal polyunsaturated fatty acid (PUFA) concentrations during pregnancy with childhood blood pressure. METHODS: In a population-based prospective cohort study among 4455 mothers and their children, we measured maternal second-trimester n-3 (ω-3) and n-6 (ω-6) PUFA concentrations in plasma glycerophospholipids and expressed n-3 and n-6 PUFAs as proportions of total PUFAs (wt%). Childhood blood pressure was measured at the median age of 6.0 y (95% range: 5.7-7.9 y). We used linear regression models to assess the associations of maternal PUFA wt% with childhood blood pressure at 6 y. RESULTS: Higher total maternal n-3 PUFA wt% and, specifically, docosahexaenoic acid (DHA; 22:6n-3) wt% were associated with lower childhood systolic blood pressure [differences: -0.28 (95% CI: -0.54, -0.03) and -0.29 mm Hg (95% CI: -0.54, -0.03) per SD increase of total n-3 PUFAs and DHA wt%, respectively], but not with childhood diastolic blood pressure. Total maternal n-6 PUFA wt% was positively associated with childhood systolic blood pressure [differences: 0.36 mm Hg (95% CI: 0.09, 0.62) per SD increase of total n-6 PUFA wt%], but not with childhood diastolic blood pressure. A higher n-6:n-3 PUFA ratio was associated with higher childhood systolic blood pressure (P < 0.05). Pregnancy and childhood characteristics only partly explained the observed associations. CONCLUSIONS: Higher maternal plasma n-3 PUFA and lower n-6 PUFA concentrations during pregnancy are associated with a lower systolic blood pressure in childhood. Further studies are needed to replicate these findings, explore the underlying mechanisms, and examine the long-term cardiovascular consequences.