Breast milk is a complex liquid with immune-competent cells and soluble proteins that provide immunity to the infant and affect the maturation of the infant’s immune system. Exosomes are nanovesicles (30–100 nm) with an endosome-derived limiting membrane secreted by a diverse range of cell types. Because exosomes carry immunorelevant structures, they are suggested to participate in directing the immune response. We hypothesized that human breast milk contain exosomes, which may be important for the development of the infant’s immune system. We isolated vesicles from the human colostrum and mature breast milk by ultracentrifugations and/or immuno-isolation on paramagnetic beads. We found that the vesicles displayed a typical exosome-like size and morphology as analyzed by electron microscopy. Furthermore, they floated at a density between 1.10 and 1.18 g/ml in a sucrose gradient, corresponding to the known density of exosomes. In addition, MHC classes I and II, CD63, CD81, and CD86 were detected on the vesicles by flow cytometry. Western blot and mass spectrometry further confirmed the presence of several exosome-associated molecules. Functional analysis revealed that the vesicle preparation inhibited anti-CD3-induced IL-2 and IFN-γ production from allogeneic and autologous PBMC. In addition, an increased number of Foxp3+CD4+CD25+ T regulatory cells were observed in PBMC incubated with milk vesicle preparations. We conclude that human breast milk contains exosomes with the capacity to influence immune responses.

PROACTIVE APPROACH TO resuscitation and intensive care of extremely preterm infants (Ͻ27 gestational weeks) has increased survival and lowered the gestational age of viability. 1-4 There are concerns that increased survival may come at the cost of later neurodevelopmental disability among survivors. Approximately 25% of extremely preterm infants born in the 1990s had a major disability at preschool age, such as impaired mental development, cerebral palsy (CP), blindness, or deafness. 5,6 More recent studies report decreasing, 7,8 unchanged, 2 or increasing rates of neurodevelopmental disability 9-11 at preschool age compared with previous decades. The most immature infants, ie, those born before 25 weeks Author Affiliations and Members of the EXPRESS Group appear at the end of this article.

OBJECTIVETo perform comparative analyses of obstetric and perinatal outcomes between type 1 diabetic pregnancies and the general obstetric population in Sweden between 1991 and 2003.RESEARCH DESIGN AND METHODSThis was a population-based study. Data were obtained from the Medical Birth Registry, covering >98% of all pregnancies in Sweden. A total of 5,089 type 1 diabetic pregnancies and 1,260,207 control pregnancies were included. Odds ratios (ORs) were adjusted for group differences in maternal age, parity, BMI, chronic hypertensive disease, smoking habits, and ethnicity.RESULTSIn type 1 diabetes, preeclampsia was significantly more frequent (OR 4.47 [3.77–5.31]) as was delivery by cesarean section (5.31 [4.97–5.69]) compared with results for the general population. Stillbirth (3.34 [2.46–4.55]), perinatal mortality (3.29 [2.50–4.33]), and major malformations (2.50 [2.13–2.94]) were more common in type 1 diabetic than in control pregnancies. The risk of very preterm birth (<32 gestational weeks) was also higher among type 1 diabetic women (3.08 [2.45–3.87]). The incidence of fetal macrosomia (birth weight ≥2 SD above the mean) was increased in the diabetic group (11.45 [10.61–12.36]).CONCLUSIONSType 1 diabetes in pregnancy is still associated with considerably increased rates of adverse obstetric and perinatal outcomes. The eightfold increased risk for fetal macrosomia in type 1 diabetic pregnancies is unexpected and warrants further investigation.

BackgroundSub-Saharan Africa is facing rapidly increasing prevalences of cardiovascular disease, obesity, diabetes and hypertension. Previous and ongoing undernutrition among pregnant women may contribute to this development as suggested by epidemiological studies from high income countries linking undernutrition in fetal life with increased burden of non-communicable diseases in later life. We undertook to study the risks for hypertension, glucose intolerance and overweight forty years after fetal exposure to famine afflicted Biafra during the Nigerian civil war (1967–1970).Methods and FindingsCohort study performed in June 27–July 31, 2009 in Enugu, Nigeria. Adults (n = 1,339) born before (1965–67), during (1968–January 1970), or after (1971–73) the years of famine were included. Blood pressure (BP), random plasma glucose (p-glucose) and anthropometrics, as well as prevalence of hypertension (BP>140/90 mmHg), impaired glucose tolerance (IGT; p-glucose 7.8–11.0 mmol/l), diabetes (DM; p-glucose ≥11.1 mmol/l), or overweight (BMI>25 kg/m2) were compared between the three groups. Fetal-infant exposure to famine was associated with elevated systolic (+7 mmHg; p<0.001) and diastolic (+5 mmHg; p<0.001) BP, increased p-glucose (+0.3 mmol/L; p<0.05) and waist circumference (+3cm, p<0.001), increased risk of systolic hypertension (adjusted OR 2.87; 95% CI 1.90–4.34), IGT (OR 1.65; 95% CI 1.02–2.69) and overweight (OR 1.41; 95% CI 1.03–1.93) as compared to people born after the famine. Limitations of this study include the lack of birth weight data and the inability to separate effects of fetal and infant famine.ConclusionsFetal and infant undernutrition is associated with significantly increased risk of hypertension and impaired glucose tolerance in 40-year-old Nigerians. Prevention of undernutrition during pregnancy and in infancy should therefore be given high priority in health, education, and economic agendas.

Background-Survivors of preterm birth constitute a new generation of young adults, but little is known about their long-term health. We investigated the association between gestational age (GA) and risk of high blood pressure (HBP) in young Swedish men and whether GA modified the risk of HBP; ie, whether HBP was related to being born small for gestational age (SGA

Background-Low birthweight (LBW) has been associated with an increased incidence of adult cardiovascular disease.Endothelial dysfunction and loss of arterial elasticity are early markers of hypertension and atherosclerosis. We studied the prevalence of these markers in 44 healthy, prepubertal (age 9Ϯ1.3 years) children, 22 with LBW for age. Methods and Results-Endothelial function in skin was tested with the local application of acetylcholine (inducing endothelium-dependent vasodilation) and nitroglycerin (endothelium-independent vasodilation), and local perfusion changes were measured with the laser Doppler method. The elastic properties of the abdominal aorta and common carotid artery were measured with an ultrasonic vessel-wall tracking system. Endothelium-dependent vasodilation was lower in children with LBW (88Ϯ33 perfusion units [PU]) than in normal-birthweight controls (133Ϯ34 PU, PϽ0.001).There was no difference in aortic or carotid elasticity between the 2 groups, but a negative correlation was found between birthweight and stiffness of the carotid artery wall (rϭϪ0.45, PϽ0.01). Endothelium-independent vasodilation and blood pressure were similar in the 2 groups. Conclusions-Schoolchildren with a history of LBW show impaired endothelial function and a trend toward increased carotid stiffness. These findings may be early expressions of vascular compromise, contributing to susceptibility to disease in adult life.

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