Protein intake in early infancy has been suggested to be an important risk factor for later obesity, but information on potential mechanisms is very limited.
This study examined the influence of ...protein intake in infancy on serum amino acids, insulin, and the insulin-like growth factor I (IGF-I) axis and its possible relation to growth in the first 2 y of life.
In a multicenter European study, 1138 healthy, formula-fed infants were randomly assigned to receive cow-milk-based infant and follow-on formulas with lower protein (LP; 1.77 and 2.2 g protein/100 kcal) or higher protein (HP; 2.9 and 4.4 g protein/100 kcal) contents for the first year. Biochemical variables were measured at age 6 mo in 339 infants receiving LP formula and 333 infants receiving HP formula and in 237 breastfed infants.
Essential amino acids, especially branched-chain amino acids, IGF-I, and urinary C-peptide:creatinine ratio, were significantly (P < 0.001) higher in the HP group than in the LP group, whereas IGF-binding protein (IGF-BP) 2 was lower and IGF-BP3 did not differ significantly. The median IGF-I total serum concentration was 48.4 ng/mL (25th, 75th percentile: 27.2, 81.8 ng/mL) in the HP group and 34.7 ng/mL (17.7, 57.5 ng/mL) in the LP group; the urine C-peptide:creatinine ratios were 140.6 ng/mg (80.0, 203.8 ng/mg) and 107.3 ng/mg (65.2, 194.7 ng/mg), respectively. Most essential amino acids, IGF-I, C-peptide, and urea increased significantly in both the LP and HP groups compared with the breastfed group. Total IGF-I was significantly associated with growth until 6 mo but not thereafter.
HP intake stimulates the IGF-I axis and insulin release in infancy. IGF-I enhances growth during the first 6 mo of life. This trial was registered at clinicaltrials.gov as NCT00338689.
Since the concept of lasting programming effects on disease risk in human adults by the action of hormones, metabolites, and neurotransmitters during sensitive periods of early development was ...proposed >3 decades ago, ample supporting evidence has evolved from epidemiologic and experimental studies and clinical trials. For example, numerous studies have reported programming effects of infant feeding choices on later obesity. Three meta-analyses of observational studies found that obesity risk at school age was reduced by 15-25% with early breastfeeding compared with formula feeding. We proposed that breastfeeding protects against later obesity by reducing the occurrence of high weight gain in infancy and that one causative factor is the lower protein content of human milk compared with most infant formula (the early protein hypothesis). We are testing this hypothesis in the European Childhood Obesity Project, a double-blind, randomized clinical trial that includes >1000 infants in 5 countries (Belgium, Germany, Italy, Poland, and Spain). We randomly assigned healthy infants who were born at term to receive for the first year infant formula and follow-on formula with higher or lower protein contents, respectively. The follow-up data obtained at age 2 y indicate that feeding formula with reduced protein content normalizes early growth relative to a breastfed reference group and the new World Health Organization growth standard, which may furnish a significant long-term protection against later obesity. We conclude that infant feeding practice has a high potential for long-term health effects, and the results obtained should stimulate the review of recommendations and policies for infant formula composition.
The notion of Palliative Care (PC) in neonatal and perinatal medicine has largely developed in recent decades. Our aim was to systematically review the literature on this topic, summarise the ...evolution of care and, based on the available data, suggest a current standard for this type of care.
Data sources included Medline, the Cochrane Library, CINAHL, and the bibliographies of the papers retrieved. Articles focusing on neonatal/perinatal hospices or PC were included. A qualitative analysis of the content was performed, and data on the lead author, country, year, type of article or design, and direct and indirect subjects were obtained.
Among the 1558 articles retrieved, we did not find a single quantitative empirical study. To study the evolution of the model of care, we ultimately included 101 studies, most of which were from the USA. Fifty of these were comments/reflections, and only 30 were classifiable as clinical studies (half of these were case reports). The analysis revealed a gradual conceptual evolution of the model, which includes the notions of family-centered care, comprehensive care (including bereavement) and early and integrative care (also including the antenatal period). A subset of 27 articles that made special mention of antenatal aspects showed a similar distribution. In this subset, the results of the four descriptive clinical studies showed that, in the context of specific programmes, a significant number of couples (between 37 and 87%) opted for PC and to continue with the pregnancy when the foetus has been diagnosed with a lethal illness.
Despite the interest that PC has aroused in perinatal medicine, there are no evidence-based empirical studies to indicate the best model of care for this clinical setting. The very notion of PC has evolved to encompass perinatal PC, which includes, among other things, the idea of comprehensive care, and early and integrative care initiated antenatally.
There is accumulating evidence that early protein intake is related with weight gain in childhood. However, the evidence is mostly limited to the first year of life, whereas the ...high-weight-gain-velocity period extends up to about 2 years of age. We aimed to investigate whether protein intake during the second year of life is associated with higher weight gain and obesity risk later in childhood. We conducted a systematic review with searches in both PubMed
/MEDLINE
and the Cochrane Central Register of Controlled Trials. Ten studies that assessed a total of 46,170 children were identified. We found moderate-quality evidence of an association of protein intake during the second year of life with fat mass at 2 years and at 7 years. Effects on other outcomes such as body mass index (BMI), obesity risk, or adiposity rebound onset were inconclusive due to both heterogeneity and low evidence. We conclude that higher protein intakes during the second year of life are likely to increase fatness in childhood, but there is limited evidence regarding the association with other outcomes such as body mass index or change in adiposity rebound onset. Further well-designed and adequately powered clinical trials are needed since this issue has considerable public health relevance.
This article reviews the role of protein intake on metabolic programming early in life. The observations that breastfeeding in infancy reduces the risk of being overweight and obese later in life and ...the differences in the protein content between formula milk and human milk have generated the early protein hypothesis. The present review focuses on a mechanistic approach to programmed adiposity and the growth and development of other organs by protein intake in infancy, which may be mediated by branched-chain amino acids, insulin, and insulin-like growth factor 1 via the mammalian target of rapamycin. Observational studies and clinical trials have shown that lowering the protein content in infant and follow-on formulas may reduce the risk of becoming obese later in life. The recent body of evidence is currently being translated into new policies. Therefore, the evolution of European regulatory laws and recommendations by expert panels on the protein content of infant and follow-on formulas are also reviewed. Research gaps, such as the critical window for programming adiposity by protein intake, testing formulas with modified amino acids, and the long-term consequences of differences in protein intake on organ functionality among well-nourished infants, have been identified.
Since iron plays an important role in several physiological processes, its deficiency but also overload may harm the development of children. The aim was to assess the effect of iron-fortified milk ...on the iron biochemical status and the neurodevelopment of children at 12 months of age.
Randomized controlled trial conducted in 133 Spanish children, allocated in two groups to receive formula milk fortified with 1.2 or 0.4 mg/100 mL of iron between 6 and 12 months of age. Psychomotor (PDI) and Mental (MDI) Development Index were assessed by the Bayley Scales before and after the intervention. Maternal obstetrical and psychosocial variables were recorded. The biochemical iron status of children was measured and data about breastfeeding, anthropometry and infections during the first year of life were registered.
Children fortified with 1.2 mg/100 mL of iron, compared with 0.4 mg/100 mL, showed higher serum ferritin (21.5 vs 19.1 μg/L) and lower percentage of both iron deficiency (1.1 to 5.9% vs 3.8 to 16.7%, respectively, from 6 to 12 months) and iron deficiency anemia (4.3 to 1.1% vs 0 to 4.2%, respectively, from 6 to 12 months) at the end of the intervention. No significant differences were found on neurodevelopment from 6 to 12 months between children who received high dose of Fe compared with those who received low dose.
Despite differences on the iron status were observed, there were no effects on neurodevelopment of well-nourished children in a developed country after iron supplementation with doses within dietary recommendations. Follow-up studies are needed to test for long-term neurodevelopmental improvement.
Retrospectively registered in ClinicalTrials.gov with the ID: NCT02690675.
To assess the effects of pharmacological interventions in patients with idiopathic hypercalciuria.
We performed a search of multiple databases, trial registries, grey literature and conference ...proceedings up to October 2019. We included randomized and quasi-randomized controlled trials that examined any pharmacological intervention for preventing complications of idiopathic hypercalciuria (given for at least four months and six of follow-up). The primary outcomes were stone-free patients, urinary symptoms and severe adverse events.
We included five RCTs (n=446 patients, all adults, 4 in individuals with kidney stones and 1 in postmenopausal women with osteoporosis). Diuretics were likely to increase the number of stone-free patients (RR 1.61, 95% CI 1.33–1.96, moderate quality of evidence (QoE)); 274 more stone-free patients/1000 patients treated (95% CI: 148–432) and produced a slight decrease in the stone formation rate (mean difference −0.18, 95% CI −0.30 to −0.06, low QoE); 180 fewer stones/year/1000 patients treated (95% CI: 300 r to 60). No data on urinary symptoms were reported. The association between diuretic use and severe adverse events was uncertain (RR 5.00, 95% CI 0.60–41.88, very low QoE); 4 more severe adverse events/1000 patients treated (95% CI: 0 fewer to 39 more).
The addition of diuretics to a normal or modified diet probably reduces the number of stone recurrences and may decrease the stone formation rate. It is uncertain whether diuretics increase the occurrence of severe adverse events. There were no studies investigating other outcomes or in children.
Evaluar los efectos de intervenciones farmacológicas en pacientes con hipercalciuria idiopática.
Realizamos una búsqueda en múltiples bases de datos, registros de ensayos, literatura gris y actas de congresos hasta octubre de 2019. Incluimos ensayos clínicos aleatorizados y cuasialeatorizados que examinaban cualquier intervención farmacológica para prevenir las complicaciones de la hipercalciuria idiopática (mínimo 4 meses de intervención y 6 meses de seguimiento). Los outcomes primarios fueron pacientes libres de cálculos, síntomas urinarios y efectos adversos graves.
Incluimos 5 RCT (n=446 pacientes, todos adultos, 4 en individuos con cálculos renales y uno en mujeres posmenopáusicas con osteoporosis). Los diuréticos aumentaban probablemente el número de pacientes libres de cálculos (RR 1,61; IC 95%: 1,33 a 1,96, moderada calidad de evidencia QoE); 274 más pacientes libres de cálculos/1.000 pacientes tratados (IC 95%: 148 a 432) y producían una ligera disminución en la tasa de formación de cálculos (diferencia media −0,18; IC 95%: −0,30 a −0,06, baja QoE); 180 menos cálculos/año/1.000 pacientes tratados (IC 95%: 300 a 60). No se informaron datos sobre síntomas urinarios. La asociación entre el uso de diuréticos y los efectos adversos graves fue incierta (RR 5,00; IC 95%: 0,60 a 41,88, muy baja QoE); 4 efectos adversos severos más/1.000 pacientes tratados (IC 95%: 0 a 39).
Los diuréticos añadidos a una dieta normal o modificada probablemente reducen la aparición de cálculos y pueden disminuir su tasa de formación. Es incierto si los diuréticos incrementan la ocurrencia de efectos adversos graves. No se encontraron estudios que investigaran otros outcomes o realizados en niños.
Background: Early nutrition is recognized as a target for the effective prevention of childhood obesity. Protein intake was associated with more rapid weight gain during infancy—a known risk factor ...for later obesity.Objective: We tested whether the reduction of protein in infant formula reduces body mass index (BMI; in kg/m2) and the prevalence of obesity at 6 y of age.Design: The Childhood Obesity Project was conducted as a European multicenter, double-blind, randomized clinical trial that enrolled healthy infants born between October 2002 and July 2004. Formula-fed infants (n = 1090) were randomly assigned to receive higher protein (HP)– or lower protein (LP)–content formula (within recommended amounts) in the first year of life; breastfed infants (n = 588) were enrolled as an observational reference group. We measured the weight and height of 448 (41%) formula-fed children at 6 y of age. BMI was the primary outcome.Results: HP children had a significantly higher BMI (by 0.51; 95% CI: 0.13, 0.90; P = 0.009) at 6 y of age. The risk of becoming obese in the HP group was 2.43 (95% CI: 1.12, 5.27; P = 0.024) times that in the LP group. There was a tendency for a higher weight in HP children (0.67 kg; 95% CI: −0.04, 1.39 kg; P = 0.064) but no difference in height between the intervention groups. Anthropometric measurements were similar in the LP and breastfed groups.Conclusions: Infant formula with a lower protein content reduces BMI and obesity risk at school age. Avoidance of infant foods that provide excessive protein intakes could contribute to a reduction in childhood obesity. This trial was registered at clinicaltrials.gov as NCT00338689.
The primary aim of the Obemat2.0 trial was to evaluate the efficacy of a multicomponent motivational program for the treatment of childhood obesity, coordinated between primary care and hospital ...specialized services, compared to the usual intervention performed in primary care. This was a cluster randomized clinical trial conducted in Spain, with two intervention arms: motivational intervention group vs. usual care group (as control), including 167 participants in each. The motivational intervention consisted of motivational interviewing, educational materials, use of an eHealth physical activity monitor and three group-based sessions. The primary outcome was body mass index (BMI) z score increments before and after the 12 (+3) months of intervention. Secondary outcomes (pre-post intervention) were: adherence to treatment, waist circumference (cm), fat mass index (z score), fat free mass index (z score), total body water (kg), bone mineral density (z score), blood lipids profile, glucose metabolism, and psychosocial problems. Other assessments (pre and post-intervention) were: sociodemographic information, physical activity, sedentary activity, neuropsychological testing, perception of body image, quality of the diet, food frequency consumption and foods available at home. The results of this clinical trial could open a window of opportunity to support professionals at the primary care to treat childhood obesity. The clinicaltrials.gov identifier was NCT02889406.
Abstract Maternal smoking during pregnancy is one of the most modifiable causes of morbidity and mortality for both pregnant women and their fetuses. The long-term effects of prenatal exposure to ...smoke on child behavior and development have been the subject of more extensive research than have the short-term effects. Therefore, the aim of this work is to examine the effects of smoke exposure during pregnancy on neonatal behavior, including in our study a group of mothers exposed to secondhand smoke. The behavior of 282 healthy full-term newborns was assessed using the Neonatal Behavior Assessment Scale (NBAS) at 48–72 h of life. Sixty-two mothers smoked during pregnancy (no mother smoked more than 15 cig/day) and 17 were exposed to secondhand smoke. After adjusting for socio-demographic and obstetric factors, both newborns whose mothers smoked and those whose mothers were exposed to secondhand smoke showed significantly lower scores in the habituation cluster than non-smoking mothers. Exposure to secondhand smoke was also related to lower motor system cluster scores as well as some supplementary items and the newborns of smoking mothers showed significantly lower scores in the state regulation cluster and in some items of the state organization cluster than the newborns of non-smoking mothers. We conclude that active and passive smoking during pregnancy affects several aspects of neurobehavioral development, regardless of socio-demographic, obstetric and pediatric factors.
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