Marcello Giovannini

Neurodevelopmental Quotient of Healthy Term Infants at 4 Months and Feeding Practice: The Role of Long-Chain Polyunsaturated Fatty Acids

ABSTRACT: A direct influence of dietary long-chain polyunsaturated fatty acids (LC-PUFA) on the developmental quotient (DQ) of the healthy term infant remains unexplored. To test this hypothesis, we designed a prospective study of three types of diet. Twentynine infants received a LC-PUFA-supplemented formula, 31 received a standard infant formula, and 30 infants were breastfed exclusively. Neurodevelopmental response was measured by the Brunet-Lézine psychomotor development lest at 4 mo. The fatty acid status was also assessed among three diet subgroups (59 subjects) at 4 mo. Formula-fed infants who received LC-PUFA supplementation scored significantly higher (p < 0.01) on the Brunet-Lézine scale than infants who received the standard formula. Breast-fed infants also performed better than those fed the standard formula. Arachidonic acid and docosahexaenoic acid levels in circulating lipids and erythrocyte phospholipids were higher among breast-fed infants and among the group fed the arachidonic- and docosahexaenoic acid-supplemented formula. These findings are suggestive that formula supplementation with one or both of these fatty acids can benefit term infants in neurodevelopmental performance.

Early macronutrient intake and overweight at five years of age.

OBJECTIVE: To examine the influence of the macronutrient intake in early life on the development of overweight in children.DESIGN AND SUBJECTS: An ongoing longitudinal study including 147 randomized healthy children followed up from birth.MEASUREMENTS: Anthropometric parameters were measured at birth, 1 and 5 y of age. Dietary habits at the age of 1 and 5  were assessed by age-adjusted food-frequency questionnaires and 24 h recalls. Parents’ body mass index (BMI) was also recorded.RESULTS: Parental overweight was observed for 51% children. The prevalence of overweight at the age of 5 y was higher in children with than without parental overweight (37.3% vs 8.3%, P<0.0001). Five-year old overweight children had a higher percentage intake of proteins at the age of 1 y than non overweight children (22% vs 20%, P=0.024) and lower intake of carbohydrates (44% vs 47%, P=0.031). Multiple logistic analysis confirmed that protein intake at 1 y of age was associated with overweight at 5 y (P=0.05). In children born from overweight mothers, prevalence of overweight at the age of 5 y tended to be higher in bottle-fed than in breast-fed ones (62.5% vs 23.3%, P=0.08).CONCLUSION: Parental overweight is a major risk factor for childhood overweight in the first years of life, but an early high protein intake may also influence the development of adiposity.

Lower protein content in infant formula reduces BMI and obesity risk at school age: follow-up of a randomized trial

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/m(2)) 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.

A Randomized Prospective Double Blind Controlled Trial on Effects of Long-Term Consumption of Fermented Milk Containing Lactobacillus casei in Pre-School Children With Allergic Asthma and/or Rhinitis

To examine whether long-term consumption of fermented milk containing a specific Lactobacillus casei may improve the health status of preschool children suffering from allergic asthma and/or rhinitis a randomized, prospective, double blind, controlled trial was conducted in 187 children 2–5 y of age. The children received for 12 mo either fermented milk (100 mL) containing Lactobacillus casei (108 cfu/mL) or placebo. The time free from and the number of episodes of asthma/rhinitis after starting intervention were the outcome measures. The number of fever or diarrhea episodes and the change in serum immunoglobulin were further assessed. No statistical difference between intervention and control group occurred in asthmatic children. In children with rhinitis, the annual number of rhinitis episodes was lower in the intervention group, mean difference (95% CI), −1.6 (−3.15 to −0.05); the mean duration of an episode of diarrhea was lower in the intervention group, mean difference −0.81 (−1.52 to −0.10) days. While long-term consumption of fermented milk containing Lactobacillus casei may improve the health status of children with allergic rhinitis no effect was found in asthmatic children.

Probiotics and health: An evidence-based review

The intestinal microbiota is an ecosystem formed by a variety of ecological niches, made of several bacterial species and a very large amount of strains. The microbiota is in close contact with the intestinal mucosa or epithelial interface which is, after the respiratory area, the largest surface of the body, occupying approximately 250-400 m(2). The physiological activities of the microbiota are manifold and are just being unraveled. Based on the observations of the multiple roles played by the microbiota in health and disease, the notion of modifying it with appropriate formulations, i.e. probiotics, is being tested in several settings. This review summarizes the current knowledge on probiotics and discusses both limitations and acquired evidence to support their use in preventive and therapeutic medicine.

Developmental quotient at 24 months and fatty acid composition of diet in early infancy: a follow up study

AIM A follow up study of developmental quotient (DQ) at 24 months of toddlers whose diets in early infancy differed in fatty acid composition, and in whom an association between diet and DQ was observed at 4 months. METHODS 81 toddlers were distributed among three groups according to early type of diet: standard infant formula (SFo, n = 30); long chain polyunsaturated fatty acid (LC-PUFA) enriched formula (LCPFo, n  = 26); human milk (HM, n = 25). DQ at 24 months was assessed by Brunet-Lézine’s psychomotor developmental test. A subgroup (n = 20; SFo 8; LCPFo 6; HM 6) was tested for erythrocyte phosphatidylcholine and phosphatidylethanolamine. RESULTS No DQ differences were found by analysis of variance. Neither DQ nor erythrocyte docosahexaenoic acid at 4 months were predictors of DQ scores at 24 months. Phosphatidylcholine arachidonic and docosahexaenoic acid correlated positively, and phosphatidylcholine linoleic acid and phosphatidylethanolamine eicosapentaenoic acid negatively, with DQ. Multiple regression analysis including these variables explained 52% of interindividual DQ variance. A strong association was found between the erythrocyte phosphatidylcholine arachidonic/linoleic acid ratio and DQ (r= 0.75; p = 0.0001). CONCLUSIONS The diet/DQ association found at 4 months was not predictive of DQ scores at 24 months. Irrespective of dietary or genetic factors, there appears to be a strong correlation between the LC-PUFA composition of the red cell membrane and higher neurodevelopmental performance.

Intrauterine growth restriction is associated with changes in polyunsaturated fatty acid fetal-maternal relationships.

Fetuses with intrauterine growth restriction (IUGR) are at increased risk of death and disease during neonatal, pediatric, and adult life. Postnatal deficits in essential fatty acids have been associated with the neural and vascular complications of premature neonates. We studied whether fetal-maternal fatty acid relationships are already impaired in utero in IUGR fetuses. Fetal (F) and maternal (M) fatty acid profiles were determined in utero in 11 normal [appropriate for gestational age (AGA)] and in 10 IUGR fetuses by fetal blood sampling (FBS) between 19 and 39 wk. Total plasma fatty acid concentrations were significantly higher in M than in F of both AGA (M: 2.03 ± 0.53 mg/mL; F: 0.64 ± 0.29 mg/mL;p < 0.001) and IUGR (M: 2.16 ± 0.59 mg/mL; F: 0.73 ± 0.17 mg/mL;p < 0.001). The F/M ratio was significantly higher for linoleic acid (AGA: 0.36 ± 0.09; IUGR: 0.52 ± 0.12;p < 0.01) and significantly lower for the long-chain polyunsaturated fatty acid docosahexaenoic acid (AGA: 1.94 ± 0.32; IUGR: 1.25 ± 0.19;p < 0.05) and arachidonic acid (AGA: 2.35 ± 0.35%; IUGR: 2.04 ± 0.3%;p < 0.05) in IUGR compared with AGA pregnancies. The differences observed in the relative amounts but not in total plasma concentrations of fatty acid fetal-maternal relationships in pregnancies associated with IUGR could be related to inadequate transplacental supply as well as to a fetal lack of the enzymes necessary for elaboration of these metabolically relevant conditionally essential fatty acids. These differences might have a role in determining the biochemical environment leading to the neural and vascular complications associated with IUGR.

Feeding practices of infants through the first year of life in Italy

Aim: To investigate infant feeding practices through the first year of life in Italy, and to identify factors associated with the duration of breastfeeding and early introduction of solid foods. Methods: Structured phone interviews on feeding practices were conducted with 2450 Italian‐speaking mothers randomly selected among women who delivered a healthy‐term singleton infant in November 1999 in Italy. Interviews were performed 30 d after delivery and when the infants were aged 3, 6, 9 and 12 mo. Type of breastfeeding was classified according to the WHO criteria. Results: Breastfeeding started in 91.1% of infants. At the age of 6 and 12mo, respectively, 46.8% and 11.8% of the infants was still breastfed, 68.4% and 27.7% received formula, and 18.3% and 65.2% were given cows milk. Solids were introduced at the mean age of 4.3 mo (range 1.6–6.5 mo). Introduction of solids occurred before age 3 and 4 mo in 5.6% and 34.2% of infants, respectively. The first solids introduced were fruit (73.1%) and cereals (63.9%). The main factors (negatively) associated with the duration of breastfeeding were pacifier use (p > 0.0001), early introduction of formula (p > 0.0001), lower mothers age (p > 0.01) and early introduction of solids (p= 0.05). Factors (negatively) associated with the introduction of solids foods before the age of 3 mo were mother not having breastfed (p > 0.01), early introduction of formula (p > 0.01), lower infant bodyweight at the age of 1 mo (p= 0.05) and mother smoking (p= 0.05).

Optimizing the use of sapropterin (BH4) in the management of phenylketonuria

Phenylketonuria (PKU) is caused by mutations in the phenylalanine hydroxylase (PAH) gene, leading to deficient conversion of phenylalanine (Phe) to tyrosine and accumulation of toxic levels of Phe. A Phe-restricted diet is essential to reduce blood Phe levels and prevent long-term neurological impairment and other adverse sequelae. This diet is commenced within the first few weeks of life and current recommendations favor lifelong diet therapy. The observation of clinically significant reductions in blood Phe levels in a subset of patients with PKU following oral administration of 6R-tetrahydrobiopterin dihydrochloride (BH(4)), a cofactor of PAH, raises the prospect of oral pharmacotherapy for PKU. An orally active formulation of BH(4) (sapropterin dihydrochloride; Kuvan is now commercially available. Clinical studies suggest that treatment with sapropterin provides better Phe control and increases dietary Phe tolerance, allowing significant relaxation, or even discontinuation, of dietary Phe restriction. Firstly, patients who may respond to this treatment need to be identified. We propose an initial 48-h loading test, followed by a 1-4-week trial of sapropterin and subsequent adjustment of the sapropterin dosage and dietary Phe intake to optimize blood Phe control. Overall, sapropterin represents a major advance in the management of PKU.

Growth patterns of breast fed and formula fed infants in the first 12 months of life: an Italian study

AIM To compare the growth patterns of breast fed and formula fed Italian infants in the first 12 months of life using World Health Organisation (WHO) reference data. METHODS The growth patterns of 73 breast fed infants (36 male, 37 female) and 65 formula fed infants (35 male, 30 female) were compared. Solid foods were introduced with the same weaning schedules from the 5th month in both groups. The weight for age (WA), length for age (LA), and weight for length (WL) z scores (National Center for Health Statistics–WHO data) were calculated at birth, 1, 2, 3, 4, 6, 9, and 12 months. RESULTS Breast fed infants had the highest z scores (WA, WL) at birth. Breast fed groups had significantly higher growth indices at 1 month (WA, LA), 2 months (WA) and 3 months (WA, LA) of age. Compared to breast fed groups, formula fed infants showed significantly higher WA z score changes in the 1–2, 2–3, 3–4, and 4–6 month intervals. LA z score changes were higher for breast fed infants at 0–1 month and for the formula fed infants at 4–6 months. In the 6–12 month interval growth indices progressively increased for the formula fed infants and declined for infants breast fed for longer (12 months). The 0–12 month changes in WA, LA, and WL z scores were positive for formula fed infants and negative for the 12 month breast fed group. Nevertheless, the 12 month breast fed group showed an absolute WA z score just below 0 (mean (SEM) −0.04 (0.26)) at 12 months. CONCLUSION The growth pattern of breast fed and formula fed Italian infants differs in the first 12 months of life. This questions the validity of current reference values for monitoring the growth of breast fed infants. Growth indices in breast fed groups, high at birth and closer than expected to the reference at 12 months, may reflect differences in genetic factors, intrauterine conditions, or both.