Different levels of cardiometabolic indicators in multiple vs. singleton children

Background We aimed to compare cardiometabolic indicators in singletons and multiples at age 7 and explore the birthweight mediation effect. Methods We studied 5431 singletons and 103 sets of multiples from Generation XXI birth cohort. Anthropometric measurements, body composition, and fasting blood samples were obtained. Age- and sex-specific z-scores were calculated (additionally height-specific for blood pressure). Adjusted regression coefficients and respective 95% confidence intervals [β (95%CI)] were computed using path analysis. Results Multiples had lower weight [− 0.419 (− 0.616;-0.223)], height [− 0.404 (− 0.594;-0.213)], BMI [− 0.470 (− 0.705;-0.234)], fat mass index [− 0.359 (− 0.565;-0.152)], waist circumference [− 0.342 (− 0.537;-0.147)], and waist-to-height ratio [− 0.165 (− 0.326;-0.003)] z-scores. These results were explained by the indirect effect via birthweight, which was also negative and significant for all the aforementioned cardiometabolic indicators, while no direct effect was present. There were also significant indirect effects regarding fat-free mass index, glucose, insulin, and blood pressure, though the total effects were not significant, due to the balance between direct and indirect effects. The only significant direct effect was regarding diastolic blood pressure [− 0.165 (− 0.302;-0.028)]. Conclusions At age 7, multiples presented better cardiometabolic indicators explained by lower weight at birth, except for the lower blood pressure which was independent of an effect via birthweight.Generation XXI was funded by Programa Operacional de Saúde – Saúde XXI, Quadro Comunitário de Apoio III and Administração Regional de Saúde Norte (Regional Department of Ministry of Health); FEDER through the Operational Programme Competitiveness and Internationalization and national funding from the Foundation for Science and Technology – FCT (Portuguese Ministry of Science, Technology and Higher Education) (POCI-01- 0145-FEDER-016837), under the project “PathMOB: Risco cardiometabólico na infância: desde o início da vida ao fim da infância” (Ref. FCT PTDC/DTP-EPI/3306/2014), the Unidade de Investigação em Epidemiologia - Instituto de Saúde Pública da Universidade do Porto (EPIUnit) (POCI-01-0145-FEDER-006862; Ref. UID/DTP/04750/2013), and ACS holds a FCT Investigator contract IF/01060/2015; and by the project DOCnet (NORTE-01-0145-FEDER-000003), supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF) and by European Commission [project reference FP7-ENV-2013-603946]

Adiposity rebound and cardiometabolic health in childhood: results from the Generation XXI birth cohort

Background: We aimed to evaluate the association of adiposity rebound (AR) timing on cardiometabolic health in childhood. Methods: Participants were part of the Generation XXI birth cohort, enrolled in 2005/2006 in Porto. All measurements of the child's weight and height performed by health professionals as part of routine healthcare were collected. Individual body mass index (BMI) curves were fitted for 3372 children, using mixed-effects models with smooth spline functions for age and random effects. The AR was categorized into very early (<42 months), early (42-59 months), normal (60-83 months) and late (≥84 months). At age 10 years, cardiometabolic traits were assessed and age- and sex-specific z-scores were generated. Adjusted regression coefficients and 95% confidence intervals [β (95% CI)] were computed. Results: The mean age at AR was 61.9 months (standard deviations 15.7). Compared with children with normal AR, children with very early or early AR had higher z-scores for BMI [β = 0.40 (95% CI: 0.28; 0.53); β = 0.21 (95% CI: 0.12; 0.30)], waist circumference [β = 0.33 (95% CI: 0.23; 0.43); β = 0.18 (95% CI: 0.10; 0.25)], waist-height ratio [β = 0.34 (95% CI: 0.24; 0.44); β = 0.14 (95% CI: 0.07; 0.22)], fat mass index [β = 0.24 (95% CI: 0.15; 0.33); β = 0.14 (95% CI: 0.08; 0.21)], fat-free mass index [β = 0.25 (95% CI: 0.14; 0.35); β = 0.11 (95% CI: 0.03; 0.19)], systolic blood pressure [β = 0.10 (95% CI: 0.01; 0.20); β = 0.08 (95% CI: 0.01; 0.15)], insulin [β = 0.16 (95% CI: 0.04; 0.29); β = 0.10 (95% CI: 0.01; 0.19)], HOMA-IR [β = 0.17 (95% CI: 0.04; 0.29); β = 0.10 (95% CI: 0.03; 0.19)] and C-reactive protein [β = 0.14 (95% CI: 0.02; 0.26); β = 0.10 (95% CI: 0.01; 0.19)]. Children with very early AR also had worse levels of diastolic blood pressure [β = 0.09 (95% CI: 0.02; 0.16)], triglycerides [β = 0.21 (95% CI: 0.08; 0.34)] and high-density lipoprotein cholesterol [β=-0.18 (95% CI: -0.31; -0.04)]. When analysed continuously, each additional month of age at the AR was associated with healthier cardiometabolic traits. Conclusion: The earlier the AR, the worse the cardiometabolic health in late childhood, which was consistently shown across a wide range of outcomes and in the categorical and continuous approach.This work was supported by: Programa Operacional de Saúde—Saúde XXI, Quadro Comunitário de Apoio III and Administração Regional de Saúde Norte (Regional Department of Ministry of Health); FEDER through the Operational Programme Competitiveness and Internationalization and national funding from the Foundation for Science and Technology—FCT (Portuguese Ministry of Science, Technology and Higher Education) (POCI-01–0145-FEDER-016837), under the project ‘PathMOB.: Risco cardiometabólico na infância: desde o início da vida ao fim da infância’ (Ref. FCT PTDC/DTP-EPI/3306/2014) and FCT Investigator contract (info:eu-repo/grantAgreement/FCT/Investigador FCT/IF/01060/2015/CP1319/CT0001/PT) to A.C.S.; Unidade de Investigação em Epidemiologia—Instituto de Saúde Pública da Universidade do Porto (EPIUnit) (POCI-01–0145-FEDER-006862; Ref. info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UID/DTP/04750/2013/PT); Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF): Project DOCnet (NORTE-01–0145-FEDER-000003). C.M. was partially financed by Portuguese funds through FCT within the Projects UIDB/00013/2020 and UIDP/00013/2020

Weight following birth and childhood dietary intake: A prospective cohort study

Objectives: Unhealthy childhood dietary habits track through life and are independent and modifiable risk factors for disease. Therefore, it is essential to understand the factors involved. We aimed to evaluate the associations of birthweight (BW) and newborn weight change (NWC) during the first 96 h of life and childhood longitudinal weight trajectories with dietary intake at age 4. Methods: As part of the Generation XXI birth cohort (G21), children were recruited in 2005 and 2006 at all public units providing obstetrical and neonatal care in Porto, Portugal. Information was collected by face-to-face interview and abstracted from clinical records. At age 4, weight measurements recorded from birth to current age were abstracted and weight trajectories estimated. Food frequency questionnaires were applied, and three dietary patterns (DPs) were identified: “Energy-dense food (EDF)+Dairy,” “Lower in Healthy Food,” and “Healthier.” Logistic regression models were used to compute the odds ratio (OR) and 95% confidence intervals (CIs) (OR [95% CI]) in a sample of 775 children. Results: Children with higher BW were less frequently in the “EDF+Dairy” DP (0.94 [0.89–0.98] per 100 g increase in BW). Children with higher NWC had lower odds of eating fruit ≥3/d (0.93 [0.87–0.99] per 1% increase in NWC). Children with higher weight during childhood had higher odds of belonging to the “EDF+Dairy” DP (1.90 [1.04–3.47]) and lower odds of eating vegetable soup ≥2/d (0.56 [0.34–0.91]). Children showing catch-up grow in the first year of life had higher odds of eating dairy products ≥3/d (3.76 [1.31–10.80]). Conclusions: The way that children grow during childhood played a major role on dietary intake at age 4

A Multistate Model for Analyzing Transitions Between Body Mass Index Categories During Childhood: The Generation XXI Birth Cohort Study

Prevalences of overweight and obesity in young children have risen dramatically in the last several decades in most developed countries. Childhood overweight and obesity are known to have immediate and long-term health consequences and are now recognized as important public health concerns. We used a Markov 4-state model with states defined by 4 body mass index (BMI; weight (kg)/height (m)(2)) categories (underweight (2 SDs of BMI z score)) to study the rates of transition to higher or lower BMI categories among children aged 4-10 years. We also used this model to study the relationships between explanatory variables and their transition rates. The participants consisted of 4,887 children from the Generation XXI Birth Cohort Study (Porto, Portugal; 2005-2017) who underwent anthropometric evaluation at age 4 years and in at least 1 of the subsequent follow-up waves (ages 7 and 10 years). Children who were normal weight were more likely to move to higher BMI categories than to lower categories, whereas overweight children had similar rates of transition to the 2 adjacent categories. We evaluated the associations of maternal age and education, type of delivery, sex, and birth weight with childhood overweight and obesity, but we observed statistically significant results only for sex and maternal education with regard to the progressive transitions.L.M.-M. received financial support from the Spanish Ministry of Economy and Competitiveness through project M2017-82379-R, funded by the Agencia Estatal de Investigacion and the European Regional Development Fund. A.C.S. holds an FCT Investigator contract (contract IF/01060/2015) from the Fundacao para a Ciencia e Tecnologia (FCT). The Generation XXI Birth Cohort Study was funded by Programa Operacional de Saude XXI, Quadro Comunitario de Apoio III, and the Administracao Regional de Saude Norte (a regional department of the Portuguese Ministry of Health). The current study was funded by the Fundo Europeu de Desenvolvimento Regional through the Operational Thematic Programme for Competitiveness and Internationalization (COMPETE 2020); by the FCT, Ministerio Portugues da Ciencia, Tecnologia e Ensino Superior (grant POCI-01-0145-FEDER-016837); by the project PathMOB: Risco Cardiometabolico na Infancia: Desde o Inicio da Vida ao Fim da Infancia (grant FCT PTDC/DTP-EPI/3306/2014); by the Unidade de Investigacao em Epidemiologia (EPIUnit), Instituto de Saude Publica da Universidade do Porto (grant POCI-01-0145-FEDER-006862); and by the Fundacao Calouste Gulbenkian (Lisbon, Portugal). This study also resulted from the DOCnet Project (Diabetes and Obesity at the Crossroads Between Oncological and Cardiovascular Diseases-A System Analysis Network Towards Precision Medicine) (grant NORTE-01-0145-FEDER-000003), which is supported by the Programa Operacional da Regiao Norte (NORTE 2020) under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund

Effect of maternal country of birth on breastfeeding practices: results from Portuguese GXXI birth cohort

Background: Maternal country of birth has been associated with perinatal health outcomes but less is known regarding breastfeeding practices in contemporary European settings. This study investigated effect of maternal country of birth on breastfeeding initiation and duration by comparing native Portuguese and migrant mothers. Methods: We analyzed data of 7065 children of the Generation XXI (GXXI) birth cohort recruited at birth (2005-06) and followed-up 4 years later. Logistic regression was used to assess the effect of maternal country of birth on breastfeeding initiation. Kaplan-Meier estimate was used to compare breastfeeding duration by maternal country of birth and length of residence by migrant mothers in Portugal. Results: Breastfeeding initiation and the type of breastfeeding practice were similar for native Portuguese and migrant mothers. The migrants had significantly higher median duration in months of any breastfeeding (Odds Ratio [OR] 6.0, 95% Confidence Interval [CI] 5.4,6.6) and exclusive breastfeeding (OR 4.0, 95% CI 3.8,4.2) than native Portuguese mothers (OR 4.0, 95% CI 3.8,4.2 and OR 3.0, 95% CI 2.9,3.0). Migrant mothers who resided in Portugal for either 5 years (OR 6.0, 95% CI 5.5,6.5 and OR 4.0, 95% CI 3.7,4.3) years had similar duration of any breastfeeding or exclusive breastfeeding, in both cases higher than the native Portuguese mothers. No significant differences were found when world regions were compared. Conclusions: Maternal country of birth does not influence breastfeeding initiation and type of feeding practice. However, migrant mothers have longer breastfeeding duration of either exclusive or any breastfeeding, which was not changed by length of residence in Portugal.GXXI was funded by Programa Operacional de Saude-Saude XXI, Quadro Comunitario de Apoio III and Administracao Regional de Saude Norte (Regional Department of Ministry of Health). It has support from Calouste Gulbenkian Foundation and Portuguese Foundation for Science and Technology. Precisely, EPIUnit-Instituto de Saude Publica da Universidade do Porto (POCI-01-0145-FEDER-006862; Ref. UID/DTP/04750/2013); PhD Grant SFRH/BD/111794/2015 (Carina Rodrigues) as well as the individual grants IF/01060/2015 (Ana Cristina Santos) and SFRH/BSAB/113778/2015 (Henrique Barros), co-funded by the FCT and the POCH/FSE Program

Newborn weight change and childhood cardio-metabolic traits - a prospective cohort study

Background: Newborn weight change (NWC) in the first 4 days represents short-term adaptations to external environment. It may be a key developmental period for future cardio-metabolic health, but this has not been explored. We aimed to determine the associations of NWC with childhood cardio-metabolic traits. Methods: As part of Generation XXI birth cohort, children were recruited in 2005/2006 at all public units providing obstetrical and neonatal care in Porto. Birthweight was abstracted from clinical records and postnatal anthropometry was obtained by trained examiners during hospital stay. NWC was calculated as ((minimum weight - birthweight)/birthweight) x 100. At age 4 and 7, children were measured and had a fasting blood sample collected. Fasting glucose, LDL-cholesterol, triglycerides, waist circumference, systolic and diastolic blood pressure were evaluated. This study included 312 children with detailed information on growth in very early life and subsequent cardio-metabolic measures. Path analysis was used to compute adjusted regression coefficients and 95% confidence intervals. Results: NWC was not associated with any cardio-metabolic traits at ages 4 or 7. Strong associations were observed between each cardio-metabolic trait at 4 with the same trait at 7 years. The strongest associations were found for waist circumference [0.725 (0.657; 0.793)] and LDL-cholesterol [0.655 (0.575; 0.735)]. Conclusions: No evidence that NWC is related to childhood cardio-metabolic traits was found, suggesting that NWC should be faced in clinical practice as a short-term phenomenon, with no medium/long term consequences, at least in cardio-metabolic health. Our results show strong tracking correlations in cardio-metabolic traits during childhood.This work was supported by Programa Operacional de Saude - Saude XXI, Quadro Comunitario de Apoio III and Administracao Regional de Saude Norte (Regional Department of Ministry of Health); FEDER through the Operational Programme Competitiveness and Internationalization and national funding from the Foundation for Science and Technology - FCT (Portuguese Ministry of Science, Technology and Higher Education) [POCI-01-0145-FEDER-016837], under the project PathMOB.: Risco cardiometabolico na infancia: desde o inicio da vida ao fim da infancia [Ref. FCT PTDC/DTP-EPI/3306/2014], and FCT Investigator contract [IF/01060/2015] - ACS; Unidade de Investigacao em Epidemiologia - Instituto de Saude Publica da Universidade do Porto (EPIUnit) [POCI-01-0145-FEDER-006862; Ref. UID/DTP/04750/2013]; Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF) - DOCnet (NORTE-01-0145-FEDER-000003); UK Medical Research Council [MC_UU_12013/5] and UK National Institute of Health Research Senior Investigator [NF-SI-0611-10196] - DAL

Peripheral Nerve Regeneration: Current Status and New Strategies Using Polymeric Materials

Experiments concerning peripheral nerve regeneration have been reported since the end of the 19(th) century. The need to implement an effective surgical procedure in terms of functional recovery has resulted in the appearance of several approaches to solve this problem. Nerve autograft was the first approach studied and is still considered the gold standard. Since autografts require donor harvesting, other strategies involving the use of natural materials have also been studied. Nevertheless, the results were not very encouraging and attention has moved towards the use of nerve conduits made from polymers, whose properties can be easily tailored and which allow the nerve conduit to be easily processed into a variety of shapes and forms. Some of these materials are already approved by the US Food and Drug Administration (FDA), as is presented here. Furthermore, polymers with conductive properties have very recently been subject to intensive study in this field, since it is believed that such properties have a positive influence in the regeneration of the new axons. This manuscript intends to give a global view of the mechanisms involved in peripheral nerve regeneration and the main strategies used to recover motor and sensorial function of injured nerves

Bearing My Heart: The Role of Extracellular Matrix on Cardiac Development, Homeostasis, and Injury Response

The extracellular matrix (ECM) is an essential component of the heart that imparts fundamental cellular processes during organ development and homeostasis. Most cardiovascular diseases involve severe remodeling of the ECM, culminating in the formation of fibrotic tissue that is deleterious to organ function. Treatment schemes effective at managing fibrosis and promoting physiological ECM repair are not yet in reach. Of note, the composition of the cardiac ECM changes significantly in a short period after birth, concurrent with the loss of the regenerative capacity of the heart. This highlights the importance of understanding ECM composition and function headed for the development of more efficient therapies. In this review, we explore the impact of ECM alterations, throughout heart ontogeny and disease, on cardiac cells and debate available approaches to deeper insights on cell–ECM interactions, toward the design of new regenerative therapies.This work was funded by the European Regional Development Fund (ERDF) through COMPETE 2020, Portugal 2020, and by the FCT (Fundação para a Ciência e Tecnologia) (POCI-01-0145-FEDER-030985) and by the FCT/Ministério da Ciência, Tecnologia e Inovação in the framework of individual funding (CEECINST/00091/2018) to DN

Maternal smoking: a life course blood pressure determinant?

Introduction: Exposure to maternal smoking early in life may affect blood pressure (BP) control mechanisms. We examined the association between maternal smoking (before conception, during pregnancy, and 4 years after delivery) and BP in preschool children. Methods: We evaluated 4295 of Generation XXI children, recruited at birth in 2005–2006 and reevaluated at the age of 4. At birth, information was collected by face-to-face interview and additionally abstracted from clinical records. At 4-year follow-up, interviews were performed and children’s BP measured. Linear regression models were fitted to estimate the association between maternal smoking and children’s BP. Results: Children of smoking mothers presented significantly higher BP levels. After adjustment for maternal education, gestational hypertensive disorders, and child’s body mass index, children exposed during pregnancy to maternal smoking presented a higher systolic BP (SBP) z-score (β = 0.08, 95% confidence interval [CI] 0.04 to 0.14). In crude models, maternal smoking was associated with higher SBP z-score at every assessed period. However, after adjustment, an attenuation of the association estimates occurred (β = 0.08, 95% CI 0.03 to 0.13 before conception; β = 0.07, 95%CI 0.02 to 0.12; β = 0.04, 95%CI −0.02 to 0.10; and β = 0.06, 95%CI 0.00 to 0.13 for the first, second, and third pregnancy trimesters, respectively; and β = 0.07, 95%CI 0.02 to 0.12 for current maternal smoking). No significant association was observed for diastolic BP z-score levels. Conclusion: Maternal smoking before, during, and after pregnancy was independently associated with systolic BP z-score in preschool children. This study provides additional evidence to the public health relevance of maternal smoking cessation programs if early cardiovascular health of children is envisaged. Implications: Using observational longitudinal data from the birth cohort Generation XXI, this study showed that exposure to maternal smoking—before pregnancy, during pregnancy, and 4 years after delivery—was associated with a systolic BP-raising effect in children at the age of 4. The findings of this study add an important insight into the need to support maternal smoke-free environments in order to provide long-term cardiovascular benefit, starting as early as possible in life.Generation XXI has been funded by the Operational Health Programme XXI Health, Community support framework III (co-funded by Feder), Administração Regional de Saúde do Norte, Fundação Calouste Gulbenkian and Fundação para a Ciência e Tecnologia (SFRH/BSAB/113778/2015; PD/BD/105824/2014; PD/BD/105827/2014; F-COMP-01-0124-FEDER-011008; FCT—PTDC/SAU-ESA/105033/2008). Also, the Portuguese Foundation for Science and Technology funds the Epidemiology Research Unit of the Institute of Public Health of the University of Porto (UID/DTP/04750/2013). This article is a result of the project DOCnet (NORTE-01-0145-FEDER-000003), supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF)

A new approach to estimating weight change and its reference intervals during the first 96 hours of life

AIM: We aimed to apply a novel model to estimate weight change and its reference intervals during the first 96 h of life and the time of weight nadir. METHODS: This study involved 1288 full-term singletons, from the Generation XXI birth cohort. Recruitment occurred between 2005 and 2006 in all five public units providing obstetrical and neonatal care in Porto, Portugal. Birthweight was abstracted from clinical records, and the subsequent newborn anthropometrics were obtained by trained examiners. Longitudinal models to estimate postnatal weight were tested and the weight ratio was calculated as the weight during 96 h of life divided by birthweight. RESULTS: The chosen model was (weight(t)~ 3241.442 + (-9.378) × t + 0.119 × t(2) + 0.000 × t(3) + b0i + b1i × t, where t represented the newborn infant's age in hours and bi represented the random coefficients. The curve inflection point (nadir) was achieved at 52.3 h of life, corresponding to a loss of 218 g and a weight ratio of 0.933. We estimated that at six, 12, 24 and 36 h of life the mean weight ratio and 10th-90th percentiles were 0.978 (0.968-0.988), 0.968 (0.953-0.983), 0.951 (0.928-0.974) and 0.939 (0.909-0.969), respectively. CONCLUSION: .This model allows a more accurate estimate of newborn weight change and its reference intervals, and estimated the nadir at 52.3 h of life, corresponding to a weight ratio of 0.933