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Background: Excessive gestational weight gain seems to be associated with offspring cardio-metabolic risk factors. Little is known about the critical periods of gestational weight gain. We examined the associations of maternal weight gain in different periods of pregnancy with childhood cardio-metabolic risk factors. Methods: In a population-based prospective cohort study from early pregnancy onwards among 5908 mothers and their children, we obtained maternal prepregnancy weight and weight in early, mid and late pregnancy. At the age of 6 years (median: 72.6 months; 95% range: 67.9, 95.8), we measured childhood body mass index (BMI), total body and abdominal fat distribution, blood pressure and blood levels of lipids, insulin and c-peptide. Results: Overall, the associations of maternal prepregnancy weight with childhood outcomes were stronger than the associations of maternal gestational weight gain. Independent from maternal prepregnancy weight and weight gain in other periods, higher weight gain in early pregnancy was associated with higher childhood BMI, total fat mass, android/gynoid fat mass ratio, abdominal subcutaneous fat mass and systolic blood pressure ( P -values<0.05). Independent associations of maternal weight gain in early pregnancy with childhood abdominal preperitoneal fat mass, insulin and c-peptide were of borderline significance. Higher weight gain in mid pregnancy was independently associated with higher childhood BMI, total and abdominal subcutaneous fat mass and systolic blood pressure ( P -values<0.05). The associations for childhood cardio-metabolic outcomes attenuated after adjustment for childhood BMI. Weight gain in late pregnancy was not associated with childhood outcomes. Higher weight gain in early, but not in mid or late pregnancy, was associated with increased risks of childhood overweight and clustering of cardio-metabolic risk factors (odds ratio (OR) 1.19 (95% confidence interval (CI): 1.10, 1.29) and OR 1.20 (95% CI: 1.07, 1.35) per standard deviation increase in early gestational weight gain, respectively). Conclusions: Higher weight gain in early pregnancy is associated with an adverse cardio-metabolic profile in offspring. This association is largely mediated by childhood adiposity.

Background This study aimed to explore socioecological correlates of parental lifestyle patterns during pregnancy, an overlooked topic except for individual socioeconomic factors. Methods We used data from three European mother-offspring cohorts participating in the EndObesity Consortium [EDEN, France, n = 1,962; Generation R, the Netherlands, n = 8,765; and Lifeways, Ireland, n = 932]. In previous principal component analysis, we identified two separate parental lifestyle patterns in pregnancy, characterised by: 1) “high parental smoking, poor-quality maternal diet, and low physical activity”; and 2) “low parental body mass index (BMI) and high gestational weight gain (GWG)”. Applying the socioecological model, we conducted multivariable linear regression analyses on lifestyle pattern scores (outcomes), first including parental socioeconomic and sociodemographic characteristics (block 1), then the urban environment (block 2), and finally psychosocial factors and health-care access (block 3). Results Older parents, those born abroad, or with high SEP had lower scores for the first lifestyle pattern. Conversely, multiparous mothers, those with suboptimal health insurance coverage, or who did not attend parenting preparation sessions followed that pattern more closely. Multiparous mothers, parents with a low SEP, or living in highly deprived areas had lower scores on the second pattern, contrary to those exposed to high population density or living in a neighbourhood with high facility richness. Conclusions Higher SEP, a foreign birthplace, wealthier neighbourhoods, and attendance at antenatal parenting preparation sessions were associated with healthier parental lifestyles during pregnancy. These potential facilitators should be considered for inclusion in tailored family-based health promotion interventions during the perinatal period.

We used a probabilistic reversal learning task to examine prediction error-driven belief updating in three clinical groups with psychosis or psychosis-like symptoms. Study 1 compared people with at-risk mental state and first episode psychosis (FEP) to matched controls. Study 2 compared people diagnosed with treatment-resistant schizophrenia (TRS) to matched controls. The design replicated our previous work showing ketamine-related perturbations in how meta-level confidence maintained behavioural policy. We applied the same computational modelling analysis here, in order to compare the pharmacological model to three groups at different stages of psychosis. Accuracy was reduced in FEP, reflecting increased tendencies to shift strategy following probabilistic errors. The TRS group also showed a greater tendency to shift choice strategies though accuracy levels were not significantly reduced. Applying the previously-used computational modelling approach, we observed that only the TRS group showed altered confidence-based modulation of responding, previously observed under ketamine administration. Overall, our behavioural findings demonstrated resemblance between clinical groups (FEP and TRS) and ketamine in terms of a reduction in stabilisation of responding in a noisy environment. The computational analysis suggested that TRS, but not FEP, replicates ketamine effects but we consider the computational findings preliminary given limitations in performance of the model.

Objective To examine whether first trimester fetal growth restriction correlates with cardiovascular outcomes in childhood.Design Population based prospective cohort study.Setting City of Rotterdam, the Netherlands.Participants 1184 children with first trimester fetal crown to rump length measurements, whose mothers had a reliable first day of their last menstrual period and a regular menstrual cycle.Main outcomes measures Body mass index, total and abdominal fat distribution, blood pressure, and blood concentrations of cholesterol, triglycerides, insulin, and C peptide at the median age of 6.0 (90% range 5.7-6.8) years. Clustering of cardiovascular risk factors was defined as having three or more of: high android fat mass; high systolic or diastolic blood pressure; low high density lipoprotein cholesterol or high triglycerides concentrations; and high insulin concentrations.Results One standard deviation score greater first trimester fetal crown to rump length was associated with a lower total fat mass (−0.30%, 95% confidence interval −0.57% to −0.03%), android fat mass (−0.07%, −0.12% to −0.02%), android/gynoid fat mass ratio (−0.53, −0.89 to −0.17), diastolic blood pressure (−0.43, −0.84 to −0.01, mm Hg), total cholesterol (−0.05, −0.10 to 0, mmol/L), low density lipoprotein cholesterol (−0.04, −0.09 to 0, mmol/L), and risk of clustering of cardiovascular risk factors (relative risk 0.81, 0.66 to 1.00) in childhood. Additional adjustment for gestational age and weight at birth changed these effect estimates only slightly. Childhood body mass index fully explained the associations of first trimester fetal crown to rump length with childhood total fat mass. First trimester fetal growth was not associated with other cardiovascular outcomes. Longitudinal growth analyses showed that compared with school age children without clustering of cardiovascular risk factors, those with clustering had a smaller first trimester fetal crown to rump length and lower second and third trimester estimated fetal weight but higher weight growth from the age of 6 months onwards.Conclusions Impaired first trimester fetal growth is associated with an adverse cardiovascular risk profile in school age children. Early fetal life might be a critical period for cardiovascular health in later life.

OBJECTIVE: Data about the consequences of laparoscopic adjustable gastric banding (LAGB) on phospho-calcic and bone metabolism remain scarce. SUBJECTS: We studied a group of 37 obese premenopausal women (age: 24–52 y; mean BMI=43.7 kg/m 2 ) who underwent LAGB. METHODS: Serum calcium, phosphate, alkaline phosphatase, parathormone (PTH), vitamin D 3 , serum C-telopeptides, IGFBP-3 and IGF-1 were measured at baseline, 6, 12, 18 and 24 months after surgery. Body composition, bone mineral content (BMC) and density (BMD) were measured using dual-X-ray absorptiometry (DXA) at baseline, 6, 12 and 24 months after surgery. RESULTS: There was no clinically significant decrease of calcemia; PTH remained stable. Serum telopeptides increased by 100% ( P <0.001) and serum IGFBP-3 decreased by 16% ( P <0.001) during the first 6 months, and then stabilized, whereas IGF-1 remained stable over the 2 y. BMC and BMD decreased, especially at the femoral neck; this decrease was significantly correlated with the decrease of waist and hip circumference. CONCLUSIONS: We concluded that there was no evidence of secondary hyperparathyroidism 24 months after LAGB. The observed bone resorption could be linked to the decrease of IGFBP-3, although this decrease could be attributable to other confounding factors. Serum telopeptides seem to be a reliable marker of bone metabolism after gastric banding. DXA must be interpreted cautiously during major weight loss, because of the artefacts caused by the important variation of fat tissue after LAGB.

Purpose The purpose of this study was to report the long-term outcomes of a continuous series of patients who underwent simultaneous anterior cruciate ligament (ACL) reconstruction and opening wedge high tibial osteotomy (HTO) for varus-related early medial tibio-femoral osteoarthritis. It was hypothesized that this combined surgery sustainably allowed return to sport with efficient clinical and radiological results. Methods From 1995 to 2015, all combined ACL reconstruction (bone-patellar tendon-bone graft) and opening wedge HTO for anterior laxity and early medial arthritis were included. Clinical evaluation at final follow-up used Tegner activity score, Lysholm score, subjective and objective IKDC scores. Radiologic evaluation consisted in full-length, standing, hip-to-ankle X-rays, monopodal weight-bearing X-rays and skyline views. AP laxity assessment used Telos™ at 150 N load. Student’s t test was performed for matched parametric data, Wilcoxon for nonparametric variables and Friedman test was used to compare small cohorts, with p  < 0.05. Results 35 Patients (36 knees) were reviewed with a mean follow-up of 10 ± 5.2 years. The mean age at surgery was 39 ± 9. At final follow-up 28 patients (80%) returned to sport (IKDC ≥ B): 11 patients (31%) returned to sport at the same level and 6 (17%) to competitive sports. Mean subjective IKDC and Lysholm scores were 71.8 ± 14.9 and 82 ± 14.1, respectively. The mean decrease of the Tegner activity level from preinjury state to follow-up was 0.8 ( p  < 0.01). Mean side-to-side difference in anterior tibial translation was 5.1 ± 3.8 mm. Three patients were considered as failures. The mean preoperative mechanical axis was 4.2° ± 2.6° varus and 0.8° ± 2.7° valgus at follow-up. Osteoarthritis progression for medial, lateral, and femoro-patellar compartments was recorded for 12 (33%, p  < 0.05), 6 (17%, p  < 0.001), and 8 (22%, p  < 0.05) knees, respectively. No femoro-tibial osteoarthritis progression was observed in 22 knees (61%). Conclusions Combined ACL reconstruction and opening wedge HTO allowed sustainable stabilization of the knee at 10-year follow-up. However, return to sport at the same level was possible just for one-third of patients, with femoro-tibial osteoarthritis progression in 39% of cases. Level of evidence III.

A state of pathological uncertainty about environmental regularities might represent a key step in the pathway to psychotic illness. Early psychosis can be investigated in healthy volunteers under ketamine, an NMDA receptor antagonist. Here, we explored the effects of ketamine on contingency learning using a placebo-controlled, double-blind, crossover design. During functional magnetic resonance imaging, participants performed an instrumental learning task, in which cue-outcome contingencies were probabilistic and reversed between blocks. Bayesian model comparison indicated that in such an unstable environment, reinforcement learning parameters are downregulated depending on confidence level, an adaptive mechanism that was specifically disrupted by ketamine administration. Drug effects were underpinned by altered neural activity in a fronto-parietal network, which reflected the confidence-based shift to exploitation of learned contingencies. Our findings suggest that an early characteristic of psychosis lies in a persistent doubt that undermines the stabilization of behavioral policy resulting in a failure to exploit regularities in the environment.

Background:Clinical recommendations to limit gestational weight gain (GWG) imply high GWG is causally related to adverse outcomes in mother or offspring, but GWG is the sum of several inter-related complex phenotypes (maternal fat deposition and vascular expansion, placenta, amniotic fluid and fetal growth). Understanding the genetic contribution to GWG could help clarify the potential effect of its different components on maternal and offspring health. Here we explore the genetic contribution to total, early and late GWG.Participants and methods:A genome-wide association study was used to identify maternal and fetal variants contributing to GWG in up to 10 543 mothers and 16 317 offspring of European origin, with replication in 10 660 mothers and 7561 offspring. Additional analyses determined the proportion of variability in GWG from maternal and fetal common genetic variants and the overlap of established genome-wide significant variants for phenotypes relevant to GWG (for example, maternal body mass index (BMI) and glucose, birth weight).Results:Approximately 20% of the variability in GWG was tagged by common maternal genetic variants, and the fetal genome made a surprisingly minor contribution to explain variation in GWG. Variants near the pregnancy-specific beta-1 glycoprotein 5 (PSG5) gene reached genome-wide significance (P=1.71 × 10-8 ) for total GWG in the offspring genome, but did not replicate. Some established variants associated with increased BMI, fasting glucose and type 2 diabetes were associated with lower early, and higher later GWG. Maternal variants related to higher systolic blood pressure were related to lower late GWG. Established maternal and fetal birth weight variants were largely unrelated to GWG.Conclusions:We found a modest contribution of maternal common variants to GWG and some overlap of maternal BMI, glucose and type 2 diabetes variants with GWG. These findings suggest that associations between GWG and later offspring/maternal outcomes may be due to the relationship of maternal BMI and diabetes with GWG.

Mastocytosis is a heterogeneous disease characterized by mast cells accumulation in one or more organs. We have reported that depression is frequent in mastocytosis, but although it was already described, little is known about the prevalence and features of cognitive impairment. Our objective was to describe the prevalence and features of cognitive impairment in a large cohort of patients with this rare disease (n = 57; mean age = 45) and to explore the relations between memory impairment and depression. Objective memory impairment was evaluated using the 3(rd) edition of the Clinical Memory scale of Wechsler. Depression symptoms were evaluated using the Hamilton Depression Rating Scale. Age and education levels were controlled for all patients. Patients with mastocytosis presented high levels of cognitive impairment (memory and/or attention) (n = 22; 38.6%). Cognitive impairment was moderate in 59% of the cases, concerned immediate auditory (41%) and working memory (73%) and was not associated to depression (p≥0.717). In conclusion, immediate auditory memory and attention impairment in mastocytosis are frequent, even in young individuals, and are not consecutive to depression. In mastocytosis, cognitive complaints call for complex neuropsychological assessment. Mild-moderate cognitive impairment and depression constitute two specific but somewhat independent syndromes in mastocytosis. These results suggest differential effects of mast-cell activity in the brain, on systems involved in emotionality and in cognition.

Converging sources of evidence point to a role for inflammation in the development of depression, fatigue and cognitive dysfunction. More precisely, the tryptophan (TRP) catabolism is thought to play a major role in inflammation-induced depression. Mastocytosis is a rare disease in which chronic symptoms, including depression, are related to mast cell accumulation and activation. Our objectives were to study the correlations between neuropsychiatric features and the TRP catabolism pathway in mastocytosis in order to demonstrate mast cells' potential involvement in inflammation-induced depression. Fifty-four patients with mastocytosis and a mean age of 50.1 years were enrolled in the study and compared healthy age-matched controls. Depression and stress were evaluated with the Beck Depression Inventory revised and the Perceived Stress Scale. All patients had measurements of TRP, serotonin (5-HT), kynurenine (KYN), indoleamine 2,3-dioxygenase 1 (IDO1) activity (ratio KYN/TRP), kynurenic acid (KA) and quinolinic acid (QA). Patients displayed significantly lower levels of TRP and 5-HT without hypoalbuminemia or malabsorption, higher IDO1 activity, and higher levels of KA and QA, with an imbalance towards the latter. High perceived stress and high depression scores were associated with low TRP and high IDO1 activity. In conclusion, TRP metabolism is altered in mastocytosis and correlates with perceived stress and depression, demonstrating mast cells' involvement in inflammation pathways linked to depression.