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.

[Acute onset of floaters, even without flashes, is an urgent ophthalmic warning sign]. / Plotse toename van mouches volantes is een alarmsymptoom, ook zónder lichtflitsen.

Acute onset of floaters is most likely caused by a posterior vitreous detachment (PVD). A PVD can lead to a retinal tear and subsequently to a retinal detachment with permanent vision loss if left untreated. A patient who presents to a primary care physician with acute onset of floaters, in the absence flashes or visual field loss, is often referred to an ophthalmologist without urgency. In the current Dutch general practitioners standard, acute onset or increase of floaters, without flashes or visual loss, is not included as a reason for urgent referral to an ophthalmologist. Patients who present with acute onset of floaters without flashes have a 14-23% risk of having a retinal tear. Risk factors for developing a retinal tear are high myopia, trauma, cataract surgery, or a retinal tear or retinal detachment in the past medical or family history. Patients with acute onset of floaters should be triaged for urgent ophthalmologic assessment.

Maternal vomiting during early pregnancy and cardiovascular risk factors at school age: the Generation R Study.

BACKGROUND: Evidence suggests that low birth weight and fetal exposure to extreme maternal undernutrition is associated with cardiovascular disease in adulthood. Hyperemesis gravidarum, a clinical entity characterized by severe nausea and excess vomiting leading to a suboptimal maternal nutritional status during early pregnancy, is associated with an increased risk of adverse pregnancy outcomes. Several studies also showed that different measures related to hyperemesis gravidarum, such as maternal daily vomiting or severe weight loss, are associated with increased risks of adverse fetal pregnancy outcomes. Not much is known about long-term offspring consequences of maternal hyperemesis gravidarum and related measures during pregnancy. We examined the associations of maternal daily vomiting during early pregnancy, as a measure related to hyperemesis gravidarum, with childhood cardiovascular risk factors. METHODS: In a population-based prospective cohort study from early pregnancy onwards among 4,769 mothers and their children in Rotterdam, the Netherlands, we measured childhood body mass index, total fat mass percentage, android/gynoid fat mass ratio, preperitoneal fat mass area, blood pressure, lipids, and insulin levels. We used multiple regression analyses to assess the associations of maternal vomiting during early pregnancy with childhood cardiovascular outcomes. RESULTS: Compared with the children of mothers without daily vomiting during early pregnancy, the children of mothers with daily vomiting during early pregnancy had a higher childhood total body fat mass (difference 0.12 standard deviation score [SDS]; 95% confidence interval [CI] 0.03-0.20), android/gynoid fat mass ratio (difference 0.13 SDS; 95% CI 0.04-0.23), and preperitoneal fat mass area (difference 0.10 SDS; 95% CI 0-0.20). These associations were not explained by birth characteristics but partly explained by higher infant growth. Maternal daily vomiting during early pregnancy was not associated with childhood blood pressure, lipids, and insulin levels. CONCLUSIONS: Maternal daily vomiting during early pregnancy is associated with higher childhood total body fat mass and abdominal fat mass levels, but not with other cardiovascular risk factors. Further studies are needed to replicate these findings, to explore the underlying mechanisms and to assess the long-term consequences.

Symptoms related to posterior vitreous detachment and the risk of developing retinal tears: a systematic review.

Flashes and floaters are the hallmark symptoms of a posterior vitreous detachment (PVD) which itself is related to an increased risk of the development of retinal tears, retinal detachment and vitreous haemorrhage. The aim of this study is to assess the associations between different symptoms related to PVD and the risk of developing retinal tears. A systematic review of articles written in English, using MEDLINE, Embase (via Embase.com) and the Cochrane Controlled Trials Register (1996-2017) was conducted. Search terms included five elements: PVD, retinal tears, retinal detachment, floaters and flashes. Independent extraction of articles was conducted by two authors using predefined data fields, including study quality indicators. Thirteen studies fulfilled the selection criteria. Analysis of pooled data revealed that presence of isolated flashes was associated with the development of retinal tears in 5.3% of symptomatic eyes [mean 2.9 eyes; 95% CI (2.1, 5.7)].Conversely, floaters alone had a stronger association with retinal tears (16.5% of eyes), as compared to flashes. The association to retinal tears was even greater for those patients reporting both flashes and floaters [mean 17.8 eyes (20.0%); 95% CI (17.4, 18.1)]. Retinal and/or vitreous haemorrhage was also associated with the presence and later development of retinal tears [mean 12.5 eyes (30.0%); 95% CI (11.7, 13.9)]. Patients with more than 10 floaters or a cloud in their vision had a high risk of developing retinal tears (OR19.8, p-value 0.032). In the setting of a PVD, the onset of flashes and floaters, and the presence of retinal and/or vitreous haemorrhage are risk factors for the development of retinal tears. The association is greater when both symptoms are present, and even greater when the patient reports more than 10 floaters, a curtain or a cloud and/or there is a positive finding of a vitreous or retinal haemorrhage. This study supports the necessity of an immediate examination of patients presenting with symptoms related to a PVD, and a follow-up examination might be prudent in a subgroup of these patients.

Influence of Maternal Gestational Hypertensive Disorders on Microvasculature in School-Age Children: The Generation R Study.

Gestational hypertensive disorders may lead to vascular changes in the offspring. We examined the associations of maternal blood pressure development and hypertensive disorders during pregnancy with microvasculature adaptations in the offspring in childhood. This study was performed as part of the Generation R Study in Rotterdam, the Netherlands (2002-2012), among 3,748 pregnant mothers and their children for whom information was available on maternal blood pressure in different periods of pregnancy and gestational hypertensive disorders. Childhood retinal arteriolar and venular calibers were assessed at the age of 6 years. We found that higher maternal systolic and diastolic blood pressures in early pregnancy were associated with childhood retinal arteriolar narrowing (P < 0.05). Higher maternal systolic blood pressure in late pregnancy, but not in middle pregnancy, was associated with childhood narrower retinal venular caliber (standard deviation score per standardized residual increase in systolic blood pressure: -0.05; 95% confidence interval: -0.08, -0.01). Paternal blood pressure was not associated with childhood retinal vessel calibers. Children of mothers with gestational hypertensive disorders tended to have narrower retinal arteriolar caliber (standard deviation score: -0.13, 95% confidence interval: -0.27, 0.01). Our results suggest that higher maternal blood pressure during pregnancy is associated with persistent microvasculature adaptations in their children. Further studies are needed to replicate these observations.

Longitudinal growth during fetal life and infancy and cardiovascular outcomes at school-age.

OBJECTIVE: Low birth weight is associated with cardiovascular disease. We examined the effects of fetal and infant growth patterns on cardiovascular outcomes in children. METHODS: In a population-based prospective cohort study among 6239 children, we estimated fetal-femur length and weight by 20 and 30 weeks ultrasound, and child length and weight at birth, 0.5, 1, 2 and 6 years. We measured blood pressure (BP), carotid-femoral pulse wave velocity, aortic root diameter, left ventricular mass and fractional shortening at 6 years. We used regression analyses to identify longitudinal growth patterns associated with height-standardized vascular outcomes and body-surface-area-standardized cardiac outcomes. RESULTS: Younger gestational age and lower birth weight were associated with higher BP, smaller aortic root diameter and lower left ventricular mass in childhood (all P values <0.05). Children with decelerated or normal fetal growth followed by accelerated infant growth had higher BP, whereas those with decelerated growth during both fetal life and infancy had a relatively larger left ventricular mass. Longitudinal growth analyses showed that children with increased BP tended to be smaller during third trimester of fetal life, but of normal size during infancy, than children with normal BP. Children with increased aortic root diameter or left ventricular mass tended to be larger during fetal life, but of similar size during infancy. CONCLUSION: Specific fetal and infant growth patterns are associated with different cardiovascular outcomes in children. Further studies are needed to identify the underlying mechanisms and the long-term cardiovascular consequences.

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.

Impact of maternal smoking during pregnancy on microvasculature in childhood. The Generation R Study.

BACKGROUND: Fetal exposure to maternal smoking is associated with an adverse cardiovascular risk profile in later life. Early microvasculature adaptations might be part of the underlying mechanisms for these associations. AIMS: The aim of this study was to examine the influence of maternal smoking during pregnancy on retinal vessel calibers in children. STUDY DESIGN: We performed a population-based prospective cohort study among 3564 school-age children. Maternal smoking patterns during pregnancy were assessed by questionnaires. OUTCOME MEASURES: At the median age of 6.0 years (95% range 5.8, 8.0 years), we measured childhood retinal vessel calibers from retinal photographs. RESULTS: No differences were observed in childhood retinal arteriolar and venular calibers among offspring from mothers who smoked in the first trimester and mothers who continued smoking throughout pregnancy, as compared to mothers who did not smoke during pregnancy. Also, no dose-dependent associations of the number of cigarettes smoked during pregnancy with childhood retinal vessel calibers were present. CONCLUSION: Maternal smoking during pregnancy did not influence childhood retinal arteriolar and venular calibers. The mechanisms linking fetal smoke exposure with cardiovascular risk factors in later life may include other mechanisms than structural microvasculature adaptations.

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.

Early origins of ethnic disparities in cardiovascular risk factors.

BACKGROUND: Not much is known about the ethnic differences in cardiovascular risk factors during childhood in European countries. We examined the ethnic differences in childhood cardiovascular risk factors in the Netherlands. METHODS: In a multi-ethnic population-based prospective cohort study, we measured blood pressure, left ventricular mass, and levels of cholesterol, triglyceride and insulin at the median age of 6.2years. RESULTS: As compared to Dutch children, Cape Verdean and Turkish children had a higher blood pressure, whereas Cape Verdean, Surinamese-Creole and Turkish children had higher total-cholesterol levels (p-values<0.05). Turkish children had higher triglyceride levels, but lower insulin levels than Dutch children (p-values<0.05). As compared to Dutch children, only Turkish children had an increased risk of clustering of cardiovascular risk factors (odds ratio: 2.45 (95% confidence interval 1.18, 3.37)). Parental pre-pregnancy factors explained up to 50% of the ethnic differences in childhood risk factors. In addition to these factors, pregnancy and childhood factors and childhood BMI explained up to 50%, 12.5% and 61.1%, respectively. CONCLUSIONS: Our results suggest that compared to Dutch children, Cape Verdean, Surinamese-Creole and Turkish children have an adverse cardiovascular profile. These differences are largely explained by parental pre-pregnancy factors, pregnancy factors and childhood BMI.

Impact of birth parameters and early life growth patterns on retinal microvascular structure in children: The Generation R Study.

OBJECTIVE: The aim of the study was to examine the associations of birth outcomes and longitudinally measured fetal and infant growth patterns with retinal vessel calibers in childhood. METHODS: In a population-based prospective cohort study among 4122 children, we measured growth characteristics in second and third trimester of pregnancy, at birth, and at 6, 12, 24, 36, 48, and 72 months. At the age of 6 years, we measured retinal arteriolar and venular calibers from digitized retinal photographs. RESULTS: We observed that compared with term-born children, those born preterm had narrower retinal arteriolar caliber [differences -0.46 standard deviation score (95% confidence interval -0.77 to -0.15) and -0.24 standard deviation score (95% confidence interval -0.42 to -0.05) for children born <34 and 34-37 weeks of gestation, respectively]. Children born with a low birth weight (<2500  g) had narrower retinal arteriolar caliber than children with a normal birth weight, but this association was fully explained by gestational age at birth. Accelerated infant growth until 24 months was associated with narrow retinal arteriolar caliber, especially among preterm-born children (P < 0.05). Early growth measures were not associated with retinal venular caliber. CONCLUSION: Preterm birth and accelerated infant growth are associated with narrower retinal arteriolar caliber in childhood. Whether these microvascular adaptations explain the well known associations of fetal and infant characteristics with cardiovascular disease in later life should be further studied.

Retinal microvasculature and cardiovascular health in childhood.

BACKGROUND AND OBJECTIVE: Alterations in retinal microvasculature are associated with increased risk of cardiovascular disease. We examined the associations of retinal vessel caliber with cardiovascular markers in school-age children. METHODS: Among 4007 school-age children (median age of 6.0 years), we measured cardiovascular markers and retinal vessel calibers from digitized retinal photographs. RESULTS: Narrower retinal arteriolar caliber was associated with higher systolic and diastolic blood pressure (-0.20 SD score [SDS] [95% confidence interval (CI) -0.24 to -0.18] and -0.14 SDS [-0.17 to -0.11], respectively, per SDS increase in retinal arteriolar caliber), mean arterial pressure, and pulse pressure, but not with carotid-femoral pulse wave velocity, heart rate, cardiac output, or left ventricular mass. A wider retinal venular caliber was associated with lower systolic blood pressure, mean arterial pressure, and pulse pressure and higher carotid-femoral pulse wave velocity (carotid-femoral pulse wave velocity difference = 0.04 SDS [95% CI 0.01 to 0.07] per SDS increase in retinal venular caliber). Both narrower retinal arteriolar and venular calibers were associated with higher risk of hypertension at the age of 6 years, with the strongest association for retinal arteriolar caliber (odds ratio 1.35 [95% CI 1.21 to 1.45] per SDS decrease in arteriolar caliber). Adjustment for parental and infant sociodemographic factors did not influence the observed associations. CONCLUSIONS: Both retinal arteriolar and venular calibers are associated with blood pressure in school-age children, whereas retinal venular caliber is associated with carotid-femoral pulse wave velocity. Microvascular adaptations in childhood might influence cardiovascular health and disease from childhood onward.

BMI, total and abdominal fat distribution, and cardiovascular risk factors in school-age children.

BACKGROUND: More specific total body and abdominal fat mass measures might be stronger associated with cardiovascular risk factors in childhood, than BMI. We examined the independent associations of total and abdominal fat measures with cardiovascular risk factors in school age children. METHODS: We performed a population-based cohort study among 6,523 children. At the age of 6 y, we measured childhood BMI, and general and abdominal fat mass, using dual-energy X-ray absorptiometry, and ultrasound and cardiovascular risk factors. RESULTS: Conditional on BMI, higher fat mass percentage and abdominal fat mass were associated with higher blood pressure, total- and low-density lipoprotein (LDL)-cholesterol, insulin and c-peptide levels, but with lower left ventricular mass and high-density lipoprotein (HDL)-cholesterol (P values < 0.05). These associations differed between underweight, normal weight, overweight, and obese children. Higher childhood adiposity measures were associated with increased odds of cardiovascular risk factors clustering, with the strongest effect for fat mass percentage (odds ratios: 3.01 (95% confidence interval: 2.67, 3.9). CONCLUSION: Our results suggest that general and abdominal fat measures are associated with cardiovascular risk factors in childhood, independent from BMI. These measures may provide additional information for identification of children with an adverse cardiovascular profile.

Influence of maternal angiogenic factors during pregnancy on microvascular structure in school-age children.

Reduced placental growth factor (PlGF) levels and higher soluble fms-like tyrosine kinase (sFlt-1) levels in mothers during pregnancy may have persistent effects on vascular structures in their offspring. We examined whether angiogenic factors during pregnancy also affect childhood retinal microvasculature in a population-based prospective cohort study among 3505 mothers and their children. We measured maternal PlGF and sFlt-1 in the first and second trimester of pregnancy. At the age of 6, we measured childhood retinal arteriolar and venular calibers from digitized retinal photographs. We performed multiple linear regression models, taking maternal and childhood sociodemographic and lifestyle-related characteristics, birth characteristics, and childhood current body mass index and blood pressure into account. We observed that first trimester maternal PlGF and sFlt-1 levels were not associated with childhood retinal arteriolar caliber. Lower second trimester maternal PlGF levels, but not sFlt-1 levels, were associated with narrower childhood retinal arteriolar caliber (difference: -0.09 SD score [95% confidence interval, -0.16 to 0.01], per SD score decrease in PlGF). This association was not explained by maternal and childhood sociodemographic and lifestyle-related characteristics, birth characteristics, or childhood current body mass index and blood pressure. Maternal PlGF and sFlt-1 levels in the first or second trimester were not associated with childhood retinal venular caliber. Our results suggest that lower maternal second trimester PlGF levels affect the microvascular development in the offspring, leading to narrower retinal arteriolar caliber in childhood. Further studies are needed to confirm these findings and to explore the underlying mechanisms and long-term cardiovascular consequences.

Ethnic disparities in general and abdominal adiposity at school age: a multiethnic population-based cohort study in the Netherlands.

BACKGROUND/AIMS: Ethnic differences in obesity prevalence have been reported. We examined ethnic differences in general and abdominal fat distribution in school-age children and the influence of parental prepregnancy, pregnancy, and childhood factors on these differences. METHODS: We performed a multiethnic population-based prospective cohort study among 5,244 children with information about prepregnancy factors, pregnancy, and childhood factors. At the age of 6 years, the BMI, total fat mass, android/gynoid fat mass ratio, and preperitoneal fat mass were assessed via dual-energy X-ray absorptiometry and abdominal ultrasound. RESULTS: The overweight and obesity prevalences among Dutch children were 10.0 and 2.1%, respectively. Higher prevalences were observed among Cape Verdean (21.0 and 10.3%), Dutch Antillean (18.4 and 13.8%), Moroccan (20.6 and 7.7%), Surinamese-Creole (13.4 and 7.7%), Surinamese-Hindustani (12.3 and 6.2%), and Turkish (23.8 and 12.0%) children. In the models adjusted for age and sex only, Moroccan, Surinamese-Hindustani, and Turkish children had a higher total fat mass than Dutch children, whereas Surinamese-Creole children had a lower total fat mass. Compared to Dutch children, the android/gynoid fat mass ratio was higher in Moroccan, Surinamese-Hindustani, and Turkish children, whereas the preperitoneal fat mass was higher among Dutch Antillean, Moroccan, Surinamese-Hindustani, and Turkish children (all p < 0.05). Prepregnancy factors explained up to 73% of these differences. In addition to prepregnancy factors, pregnancy factors explained up to 34% of the differences. Childhood factors did not significantly explain these associations. CONCLUSIONS: All ethnic minority groups had higher risks of overweight and obesity than Dutch children. Moroccan, Surinamese-Hindustani, and Turkish children also had an adverse body fat profile. Prepregnancy and pregnancy might be critical periods for preventive strategies focused on the reduction of ethnic disparities in childhood adiposity.

Fetal and infant growth patterns associated with total and abdominal fat distribution in school-age children.

CONTEXT: Higher infant growth rates are associated with an increased risk of obesity in later life. OBJECTIVE: We examined the associations of longitudinally measured fetal and infant growth patterns with total and abdominal fat distribution in childhood. DESIGN, SETTING, AND PARTICIPANTS: We performed a population-based prospective cohort study among 6464 children. We measured growth characteristics in the second and third trimesters of pregnancy, at birth, and at 6, 12, and 24 months. MAIN OUTCOME MEASURES: Body mass index, fat mass index (body fat mass/height(2)), lean mass index (body lean mass/height(2)), android/gynoid fat ratio measured by dual-energy x-ray absorptiometry, and sc and preperitoneal abdominal fat measured by ultrasound at the median age of 6.0 years (90% range, 5.7-7.4). RESULTS: We observed that weight gain in the second and third trimesters of fetal life and in early, mid, and late infancy were independently and positively associated with childhood body mass index (P < .05). Only infant weight gain was associated with higher fat mass index, android/gynoid fat ratio, and abdominal fat in childhood (P < .05). Children with both fetal and infant growth acceleration had the highest childhood body mass index, fat mass index, and sc abdominal fat, whereas children with fetal growth deceleration and infant growth acceleration had the highest value for android/gynoid fat ratio and the lowest value for lean mass index (P < .05). CONCLUSIONS: Growth in both fetal life and infancy affects childhood body mass index, whereas only infant growth directly affects measured total body and abdominal fat. Fetal growth deceleration followed by infant growth acceleration may lead to an adverse body fat distribution in childhood.

General and abdominal fat outcomes in school-age children associated with infant breastfeeding patterns.

BACKGROUND: Breastfeeding may have a protective effect on the development of obesity in later life. Not much is known about the effects of infant feeding on more-specific fat measures. OBJECTIVE: We examined associations of breastfeeding duration and exclusiveness and age at the introduction of solid foods with general and abdominal fat outcomes in children. DESIGN: We performed a population-based, prospective cohort study in 5063 children. Information about infant feeding was obtained by using questionnaires. At the median age of 6.0 y (95% range: 5.7 y, 6.8 y), we measured childhood anthropometric measures, total fat mass and the android:gynoid fat ratio by using dual-energy X-ray absorptiometry, and preperitoneal abdominal fat by using ultrasound. RESULTS: We observed that, in the models adjusted for child age, sex, and height only, a shorter breastfeeding duration, nonexclusive breastfeeding, and younger age at the introduction of solid foods were associated with higher childhood general and abdominal fat measures (P-trend < 0.05) but not with higher childhood body mass index. The introduction of solid foods at a younger age but not breastfeeding duration or exclusivity was associated with higher risk of overweight or obesity (OR: 2.05; 95% CI: 1.41, 2.90). After adjustment for family-based sociodemographic, maternal lifestyle, and childhood factors, the introduction of solid food between 4 and 4.9 mo of age was associated with higher risks of overweight or obesity, but the overall trend was not significant. CONCLUSIONS: Associations of infant breastfeeding and age at the introduction of solid foods with general and abdominal fat outcomes are explained by sociodemographic and lifestyle-related factors. Whether infant dietary composition affects specific fat outcomes at older ages should be further studied.