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.

IgG Fc N-glycosylation in Guillain-Barré syndrome treated with immunoglobulins.

Intravenous immunoglobulin (IVIg) is the treatment of choice for Guillain-Barré syndrome (GBS), an immune-mediated peripheral neuropathy causing rapidly progressive limb weakness and respiratory failure. The working mechanism of IVIg in autoimmune diseases has not been elucidated, but previous studies indicate that some anti-inflammatory effects may be mediated by the N-glycosylation of the Fc-portion of IgG. GBS is a model disease to investigate these effects because GBS is an acute and monophasic disorder usually affecting healthy persons, which is treated with a standard course of IVIg, although the clinical response is highly variable. In the current study, the N-glycosylation of the Fc-portion of serum IgG was investigated in patients with GBS before and after treatment with IVIg in relation to clinical course and outcome. Glycoforms of serum IgG1 and IgG2 were determined separately by liquid chromatography mass spectrometry. These IgG subclasses were purified from the serum of 174 GBS patients before and in 150 patients 2 weeks after standard IVIg treatment regimen. Treatment-naive GBS patients compared with age- and sex-matched controls had lower levels of galactosylation of IgG1 and IgG2. IVIg preparations contained relatively high levels of galactosylated and sialylated IgG Fc glycoforms compared with serum IgG in patients. Treatment with IVIg resulted in an increase in serum of the Fc-galactosylation and -sialylation of both IgG1 and IgG2. The extent of normalization in serum IgG Fc glycosylation varied between patients. Multiple logistic regression analysis showed that patients with persistent low IgG galactosylation and sialylation despite IVIg treatment had the most severe forms of GBS and needed ventilator support more often. Kaplan-Meier analysis showed that these patients also needed more time to be able to walk again compared with patients with a normalized IgG Fc glycosylation profile. In conclusion, our results suggest that serum IgG Fc glycosylation in GBS is related to disease severity and clinical recovery after IVIg and may help to develop new measures to monitor the efficacy of treatment.

Parental, fetal, and infant risk factors for preschool overweight: the Generation R Study.

BACKGROUND: Overweight has its origins largely in early life. We aimed to identify the most important parental, fetal, and infant risk factors of preschool overweight. METHODS: In a prospective cohort study, among 3,610 Caucasian preschool children, we assessed the associations of 34 putative parental, fetal, and infant factors with overweight risk. RESULTS: Higher maternal BMI, paternal BMI, and birth weight were associated with higher risk of preschool overweight (odds ratio (OR): 1.23, 95% confidence interval (CI): 1.10, 1.39; OR: 1.35, 95% CI: 1.19, 1.53; and OR: 2.71, 95% CI: 2.27, 3.25, respectively, per SD increase). The same model identified low household income (OR: 1.74, 95% CI: 1.24, 2.45), being female (OR: 1.55, 95% CI: 1.20, 2.01), and experiencing third-trimester accelerated growth (OR: 1.73, 95% CI: 1.24, 2.40) or postnatal accelerated growth (OR: 6.39, 95% CI: 4.54, 8.99) as risk factors for preschool overweight. Higher polyunsaturated fat intake at 14 mo was associated with a lower risk of preschool overweight (OR: 0.77, 95% CI: 0.62, 0.96 per SD). CONCLUSION: Parental anthropometrics and household income, fetal and infant accelerated growth, and infant dietary fat intake are the major risk factors for the development of preschool overweight. Further studies need to explore whether these risk factors could be potential targets for preventive interventions.

Breast-feeding and growth in children until the age of 3 years: the Generation R Study.

Breast-feeding has been suggested to be associated with lower risks of obesity in older children and adults. We assessed whether the duration and exclusiveness of breast-feeding are associated with early postnatal growth rates and the risks of overweight and obesity in preschool children. The present study was embedded in a population-based prospective cohort study from early fetal life onwards, among 5047 children and their mothers in The Netherlands. Compared with children who were breast-fed, those who were never breast-fed had a lower weight at birth (difference 134 (95 % CI - 190, - 77) g). No associations between breast-feeding duration and exclusivity with growth rates before the age of 3 months were observed. Shorter breast-feeding duration was associated with an increased gain in age- and sex-adjusted standard deviation scores for length, weight and BMI (P for trend < 0·05) between 3 and 6 months of age. Similar tendencies were observed for the associations of breast-feeding exclusivity with change in length, weight and BMI. Breast-feeding duration and exclusivity were not consistently associated with the risks of overweight and obesity at the ages of 1, 2 and 3 years. In conclusion, shorter breast-feeding duration and exclusivity during the first 6 months tended to be associated with increased growth rates for length, weight and BMI between the age of 3 and 6 months but not with the risks of overweight and obesity until the age of 3 years.

Maternal smoking during pregnancy and subcutaneous fat mass in early childhood. The Generation R Study.

Maternal smoking during pregnancy increases the risk of obesity in the offspring. Not much is known about the associations with other measures of body composition. We assessed the associations of maternal smoking during pregnancy with the development of subcutaneous fat mass measured as peripheral and central skinfold thickness measurements in early childhood, in a population-based prospective cohort study from early fetal life onward in the city of Rotterdam, The Netherlands. The study was performed in 907 mothers and their children at the ages of 1.5, 6 and 24 months. As compared to non-smoking mothers, mothers who continued smoking during pregnancy were more likely to have a younger age and a lower educational level. Their children had a lower birth weight, higher risk of small size for gestational age and were breastfed for a shorter duration (P-values <0.01). We did not observe differences in peripheral, central and total subcutaneous fat mass between the offspring of non-smoking mothers, mothers who smoked in first trimester only and mothers who continued smoking during pregnancy (P > 0.05). Also, the reported number of cigarettes smoked by mothers in both first and third trimester of pregnancy were not associated with peripheral, central and total subcutaneous fat mass in the offspring at the ages of 1.5, 6 and 24 months. Our findings suggest that fetal exposure to cigarette smoke during pregnancy does not influence subcutaneous fat mass in early childhood. Follow-up studies are needed in children at older ages and to identify associations of maternal smoking during pregnancy with other measures of body composition.

Meningoencephalitis with Streptococcus equi Subspecies equi Leading to a Dural Arteriovenous Fistula.

Invasive infection with Lancefield group C streptococci in humans is extremely rare, with the vast majority of clinical isolates belonging to Streptococcus dysgalactiae subsp. equisimilis. We report a case of meningoencephalitis in a 69-year-old man caused by Streptococcus equi subsp. equi, a microbe that causes strangles in Equus caballus (i.e., the horse). This is only the fourth infection with this subtype of the central nervous system (CNS) reported in humans. The invasiveness of these bacteria, known to be capable of releasing strongly immunogenic exotoxins, is illustrated by white matter lesions that are present in the acute phase. This patient initially recovered well after treatment with antibiotics and glucocorticoids. However, the patient was readmitted 5 months later with multiple intraparenchymatous cerebral haemorrhages. Cerebral angiography confirmed the presence of a suspected superficial dural arteriovenous fistula (DAVF), which is seldom reported after CNS infection. The invasiveness of these bacteria was illustrated by white matter lesions present in the acute phase and the occurrence of a de novo dural arteriovenous fistula in the follow-up period.

Growth in foetal life and infancy is associated with abdominal adiposity at the age of 2 years: the generation R study.

OBJECTIVE: Early weight gain is associated with an increased risk of obesity. It is not known whether rapid weight gain in foetal life and infancy is also associated with increased abdominal adiposity. We examined the associations of foetal and postnatal growth characteristics with abdominal fat mass at the age of 2 years. DESIGN: This study was performed in 481 children participating in a prospective cohort study from early foetal life onward. MEASUREMENTS: Foetal and postnatal growth characteristics in second and third trimester, at birth and at the age of 2 years were related to abdominal fat mass (subcutaneous distance and area, preperitoneal distance and area) measured by ultrasound at the age of 2 years. RESULTS: Foetal and birth weight were not associated with abdominal subcutaneous fat mass. Estimated foetal weight in second trimester of pregnancy was inversely associated with preperitoneal fat area [-3.73% (95% confidence interval -7.23, -0.10)] per standard deviation score increase in weight. Weight gain from birth to the age of 2 years was positively associated with preperitoneal fat mass measures. These associations remained significant after adjustment for age, sex, breastfeeding and body mass index. Positive associations were found between catch-up growth in weight and abdominal fat mass measures. CONCLUSIONS: Our results suggest that rapid growth rates during foetal life and infancy are associated with increased abdominal subcutaneous and preperitoneal fat mass in healthy children. Further studies need to explore whether these associations persist in later life and are related to metabolic syndrome outcomes.

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.

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.

Risk factors and outcomes of maternal obesity and excessive weight gain during pregnancy.

OBJECTIVE: The prevalence of overweight and obesity among women of reproductive age is increasing. We aimed to determine risk factors and maternal, fetal and childhood consequences of maternal obesity and excessive gestational weight gain. DESIGN AND METHODS: The study was embedded in a population-based prospective cohort study among 6959 mothers and their children. The study was based in Rotterdam, The Netherlands (2001-2005). RESULTS: Maternal lower educational level, lower household income, multiparity, and FTO risk allel were associated with an increased risk of maternal obesity, whereas maternal European ethnicity, nulliparity, higher total energy intake, and smoking during pregnancy were associated with an increased risk of excessive gestational weight gain (all p-values <0.05). As compared to normal weight, maternal obesity was associated with increased risks of gestational hypertension (OR 6.31 (95% CI 4.30, 9.26)), preeclampsia (OR (3.61, (95% CI 2.04, 6.39)), gestational diabetes (OR 6.28 (95%CI 3.01, 13.06)), caesarean delivery (OR 1.91 (95% CI 1.46, 2.50)), delivering large size for gestational age infants (OR 2.97 (95% CI 2.16, 4.08)), and childhood obesity (OR 5.02 (95% CI:2.97, 8.45)). Weaker associations of excessive gestational weight gain with maternal, fetal and childhood outcomes were observed, with the strongest effects for first trimester weight gain. CONCLUSIONS: Our study shows that maternal obesity and excessive weight gain during pregnancy are associated with socio-demographic, lifestyle, and genetic factors and with increased risks of adverse maternal, fetal and childhood outcomes. As compared to prepregnancy overweight and obesity, excessive gestational weight gain has a limited influence on adverse pregnancy outcomes.

Parental smoking during pregnancy, early growth, and risk of obesity in preschool children: the Generation R Study.

BACKGROUND: Maternal smoking during pregnancy seems to be associated with obesity in offspring. Not much is known about the specific critical exposure periods or underlying mechanisms for this association. OBJECTIVE: We assessed the associations of active maternal and paternal smoking during pregnancy with early growth characteristics and risks of overweight and obesity in preschool children. DESIGN: This study was a population-based, prospective cohort study from early fetal life until the age of 4 y in 5342 mothers and fathers and their children. Growth characteristics [head circumference, length, weight, and body mass index (BMI; in kg/m(2))] and overweight and obesity were repeatedly measured at the ages of 1, 2, 3, and 4 y. RESULTS: In comparison with children from nonsmoking mothers, children from mothers who continued smoking during pregnancy had persistently smaller head circumferences and heights until the age of 4 y, whereas their weights were lower only until the age of 3 mo. This smaller length and normal to higher weight led to an increased BMI [SD score difference: 0.11; 95% CI: 0.02, 0.20; P < 0.05)] and an increased risk of obesity (odds ratio: 1.61; 95% CI: 1.03, 2.53; P < 0.05) at the age of 4 y. In nonsmoking mothers, paternal smoking was not associated with postnatal growth characteristics or risk of obesity in offspring. Maternal smoking during pregnancy was associated with a higher BMI at the age of 4 y in children with a normal birth weight and in those who were small for gestational age at birth. CONCLUSION: Our findings suggest that direct intrauterine exposure to smoke until late pregnancy leads to different height and weight growth adaptations and increased risks of overweight and obesity in preschool children.

Fetal and infant growth and the risk of obesity during early childhood: the Generation R Study.

OBJECTIVE: To examine whether infant growth rates are influenced by fetal growth characteristics and are associated with the risks of overweight and obesity in early childhood. DESIGN: This study was embedded in the Generation R Study, a population-based prospective cohort study from fetal life onward. METHODS: Fetal growth characteristics (femur length (FL) and estimated fetal weight (EFW)) were assessed in the second and third trimesters and at birth (length and weight). Infant peak weight velocity (PWV), peak height velocity (PHV), and body mass index at adiposity peak (BMIAP) were derived for 6267 infants with multiple height and weight measurements. RESULTS: EFW measured during the second trimester was positively associated with PWV and BMIAP during infancy. Subjects with a smaller weight gain between the third trimester and birth had a higher PWV. FL measured during the second trimester was positively associated with PHV. Gradual length gain between the second and third trimesters and between the third trimester and birth were associated with higher PHV. Compared with infants in the lowest quintile, the infants in the highest quintile of PWV had strongly increased risks of overweight/obesity at the age of 4 years (odds ratio (95% confidence interval): 15.01 (9.63, 23.38)). CONCLUSION: Fetal growth characteristics strongly influence infant growth rates. A higher PWV, which generally occurs in the first month after birth, was associated with an increased risk of overweight and obesity at 4 years of age. Longer follow-up studies are necessary to determine how fetal and infant growth patterns affect the risk of disease in later life.