A.M. Lammardo

Polyunsaturated fatty acid concentrations in human hindmilk are stable throughout 12-months of lactation and provide a sustained intake to the infant during exclusive breastfeeding: an Italian study

While a wealth of data on the fatty acid composition of mature human milk has been published, limited information is available on the quantities of individual fatty acids supplied to the suckling infant with maternal milk, through the whole first year of life. Our aim was to qualitatively and quantitatively evaluate the fatty acid composition of human milk from Italian mothers, throughout extended lactation with particular emphasis on the long-chain polyunsaturated fatty acids. We have thus measured the total fat content and the concentrations of major fatty acids by quantitative GLC in pooled breast hindmilk collected from all feedings over 24 h at colostrum, 1, 3, 6, 9 and 12 months in ten mothers recruited after delivery of full-term infants. Total saturated fatty acids progressively increase and total monounsaturated progressively decrease as percentage levels, while among long-chain polyunsaturated fatty acids, percentages of arachidonic acid and docosahexaenoic acid decrease from colostrum up to the third month. Hindmilk total lipids (mg/dl) rise more than twofold up to 3 months, and then remain stable. The amounts (mg/dl) of linoleic acid and alpha-linolenic acid progressively increase, following the trend of total fat, while arachidonic and docosahexaenoic concentrations (mg/dl) remain stable throughout the whole nursing period. Assessment of the intakes per kg body weight shows different trends for the individual major long-chain polyunsaturated fatty acids supplied to the infant from hindmilk during exclusive breast-feeding (3 months). This information may be useful for the evaluation of infant intakes during extended lactation.

Free glutamine and glutamic acid increase in human milk through a three-month lactation period.

Background Previous short observational studies on the free amino acid (FAA) content of human milk have shown that glutamine and glutamic acid increase in the first 4 to 6 weeks of life. Methods Changes in human milk content of free amino acids (FAAs) was determined at colostrum, 1 month, and 3 months of lactation in 16 healthy lactating women after delivery of full-term infants. Milk was collected at the end of each feeding (hindmilk) during 24 hours. Results Glutamic acid and taurine were the most abundant FAAs at colostrum. Although taurine remained stable throughout lactation, glutamic acid (the prevalent FAA) and glutamine increased approximately 2.5 and 20 times, respectively, with progressing lactation representing more than 50% of total FAA at 3 months. The content of essential FAA was also stable, so the change in total FAA content was almost entirely due to the changes in glutamic acid and glutamine. Conclusions Breast-fed infants are supplied with progressively increasing amounts of glutamine and glutamic acid throughout lactation. The increasing intake of glutamic acid and glutamine could benefit breast-fed infants with molecules that are likely to protect the enteral mucosa and act as neurotransmitters and as a source of nitrogen.

Earlier smoking habits are associated with higher serum lipids and lower milk fat and polyunsaturated fatty acid content in the first 6 months of lactation

Objective: To investigate the relation between maternal smoking habits, plasma lipids and milk fatty acid (FA) content and composition.Design: Breastfeeding mothers who gave birth to healthy, full-term infants were recruited. Mothers were interviewed on smoking habits, being defined smokers (S) when usually smoking at least five cigarettes per day before pregnancy.Setting: Department of Pediatrics, San Paolo Hospital, Milan, Italy.Subjects: In total, 92 mothers: 61 non-S (NS) and 31 S.Interventions: Pooled hindmilk was collected at the first raise of milk (colostrum stage), 1, 3 and 6 months, and total lipid (TL) content and fatty acid (FA) composition were evaluated. Maternal dietary habits were assessed by a food-frequency questionnaire. Two subsamples (16 NS, 6 S) were investigated after delivery and at 3 months for serum lipids and FA status. At 6 months after delivery, the number of mothers still breastfeeding decreased to 30. Variables were compared using nonparametric tests.Results: In smoking mothers serum levels of triglycerides, cholesterol and low-density lipoproteins were higher, while those of high-density lipoproteins were lower. TL content in breast milk was similar in the two groups just after delivery but higher in milk from NS at 1 month. TL content and FA absolute amounts of linoleic, arachidonic, α-linolenic and docosahexaenoic (DHA) acid in breast milk were lower in S vs NS 1 month after delivery. Also 3 months after delivery, the breast milk of smoking mothers contained less DHA than the breast milk of nonsmoking mothers.Conclusions: Maternal cigarette smoking in early pregnancy is associated with higher plasma lipid levels and lower milk TL and DHA content in the first months of lactation.

Blood phenylalanine control in phenylketonuria: a survey of 10 European centres

Background:Only limited data are available on the blood phenylalanine (Phe) concentrations achieved in European patients with phenylketonuria (PKU) on a low-Phe diet.Objective:A survey was conducted to compare blood Phe control achieved in diet-treated patients with PKU of different age groups in 10 European centres.Methods:Centres experienced in the management of PKU from Belgium, Denmark, Germany, Italy, The Netherlands, Norway, Poland, Spain, Turkey and the United Kingdom provided retrospective audit data of all patients with PKU treated by diet over a 1-year period. Standard questions were used to collect median data on blood Phe concentrations, percentage of blood Phe concentrations below upper target reference ranges and frequency of blood Phe sampling.Results:Data from 1921 patients on dietary management were included. Blood Phe concentrations were well controlled and comparable across centres in the early years of life. The percentages of blood Phe concentrations meeting each centres local and national target ranges were 88% in children aged up to 1 year, 74% for 1–10 years, 89% for 11–16 years and 65% for adults (>16 years). The frequency of home blood sampling, compared with local and national recommendations for monitoring Phe concentrations, appeared to decline with age (from approximately 100% in infancy to 83% in teenagers and 55% in adults).Conclusions:Although blood Phe control generally deteriorated with age, some improvement was observed in adolescent years across the 10 European centres. The blood Phe control achieved seemed comparable in many of the European centres irrespective of different dietary treatments or national policies.

Body mass index rebound and overweight at 8 years of age in hyperphenylalaninaemic children

Aim: To evaluate whether the age at body mass index (BMI) rebound may be associated with overweight at age 8 y in hyperphenylalaninaemic (HPA) children. Methods: A longitudinal observational study including 97 HPA children born 1984–1993 and detected by the National Neonatal Screening programme. Children were followed up at the same institution and evaluated for dietary intakes and anthropometrical parameters from diagnosis up to the age of 8 y. Outcome measure was overweight at age 8 y, defined according to the International Obesity Task Force. The age at BMI rebound, BMI before and at rebound were considered as potential determinants. Familial overweight, breastfeeding and macronutrients intake at age 1 y were considered as confounders. Results: Mean (95% confidence interval [CI]) age at BMI rebound was 5.0 (4.7–5.3) y. At the age of 8 y, 24.7% (95% CI 16.3–33.1%) of children was overweight. Children overweight at the age of 8y exhibited earlier BMI rebound than non‐overweight children (mean difference [95% CI] —2.1 [‐2.8 to ‐1.4] y) and higher BMI from the age of 1 y (mean difference [95% CI] 1.2 [0.9–2.5] kg/m2) onward. Overweight was more likely in children with, rather than without, parental overweight (41.0% vs 19.8%). After adjustment for confounders, logistic analysis showed that earlier BMI rebound (odds ratio [OR] 2.4, 95% CI 1.2–4.8) and BMI at age 1 y (OR 2.3, 95%CI 1.1–4.98) were independently associated with overweight at the age of 8 y.

Optimising growth in phenylketonuria: Current state of the clinical evidence base

Patients with phenylketonuria (PKU) must follow a strict low-phenylalanine (Phe) diet in order to minimise the potentially disabling neuropsychological sequelae of the disorder. Research in this area has unsurprisingly focussed largely on managing blood Phe concentrations to protect the brain. Protein requirements in dietary management of PKU are met mostly from Phe-free protein substitutes with the intake of natural protein restricted to patient tolerance. Several reports have suggested that growth in early childhood in PKU is sub-optimal, relative to non-PKU control groups or reference populations. We reviewed the literature searching for evidence regarding PKU and growth as well as possible links between dietary management of PKU and growth. The search retrieved only limited evidence on the effect of PKU and its dietary management on growth. Physical development in PKU remains an under-studied aspect of this disorder.

Main issues in micronutrient supplementation in phenylketonuria

For almost all patients with PKU, a low phenylalanine diet is the basis of the treatment despite a widely varying natural protein tolerance. A vitamin and mineral supplement is essential and it is commonly added to a phenylalanine-free (phe-free) source of L-amino acids. In PKU, many phe-free L-amino acid supplements have age-specific vitamin and mineral profiles to meet individual requirements. The main micronutrient sources are chemically derived and their delivery dosage is usually advised in three or more doses throughout the day. Within the EU, the composition of VM (vitamin and mineral) phe-free L-amino acid supplements is governed by the Foods for Special Medical Purposes (FSMP) directive (European Commission Directive number 1999/21/EC and amended by Directive 2006/141/EC). However the micronutrient composition of the majority fails to remain within FSMP micronutrient maximum limits per 100 kcal due to their low energy content and so compositional exceptions to the FSMP directive have to be granted for each supplement. All patients with PKU require an annual nutritional follow-up, until it has been proven that they are not at risk of any vitamin and mineral imbalances. When non-dietary treatments are used to either replace or act as an adjunct to diet therapy, the quality of micronutrient intake should still be considered important and monitored systematically. European guidelines are required about which micronutrients should be measured and the conditions (fasting status) for monitoring.

Practices in prescribing protein substitutes for PKU in Europe: No uniformity of approach

BACKGROUND There appears little consensus concerning protein requirements in phenylketonuria (PKU). METHODS A questionnaire completed by 63 European and Turkish IMD centres from 18 countries collected data on prescribed total protein intake (natural/intact protein and phenylalanine-free protein substitute [PS]) by age, administration frequency and method, monitoring, and type of protein substitute. Data were analysed by European region using descriptive statistics. RESULTS The amount of total protein (from PS and natural/intact protein) varied according to the European region. Higher median amounts of total protein were prescribed in infants and children in Northern Europe (n=24 centres) (infants <1 year, >2-3g/kg/day; 1-3 years of age, >2-3 g/kg/day; 4-10 years of age, >1.5-2.5 g/kg/day) and Southern Europe (n=10 centres) (infants <1 year, 2.5 g/kg/day, 1-3 years of age, 2 g/kg/day; 4-10 years of age, 1.5-2 g/kg/day), than by Eastern Europe (n=4 centres) (infants <1 year, 2.5 g/kg/day, 1-3 years of age, >2-2.5 g/kg/day; 4-10 years of age, >1.5-2 g/kg/day) and with Western Europe (n=25 centres) giving the least (infants <1 year, >2-2.5 g/kg/day, 1-3 years of age, 1.5-2 g/kg/day; 4-10 years of age, 1-1.5 g/kg/day). Total protein prescription was similar in patients aged >10 years (1-1.5 g/kg/day) and maternal patients (1-1.5 g/kg/day). CONCLUSIONS The amounts of total protein prescribed varied between European countries and appeared to be influenced by geographical region. In PKU, all gave higher than the recommended 2007 WHO/FAO/UNU safe levels of protein intake for the general population.

Diet in phenylketonuria: A snapshot of special dietary costs and reimbursement systems in 10 international centers

BACKGROUND AND AIMS To gather exploratory data on the costs and reimbursement of special dietary foods used in the management of phenylketonuria (PKU) from ten international specialist PKU centers. METHODS Experts from each center provided data on retail costs of the three most frequently used phenylalanine-free protein substitutes and low-protein foods at their center; reimbursement of protein substitutes and low-protein foods; and state monetary benefits provided to PKU patients. RESULTS The mean annual cost of protein substitutes across 4 age groups (2 y, 8 y, 15 y and adults) ranged from €4273 to €21,590 per patient. The cost of low-protein products also differed; the mean cost of low-protein bread varied from €0.04 to €1.60 per 100 kcal. All protein substitutes were either fully reimbursed or covered by health insurance. However, reimbursement for low-protein products varied and state benefits differed between centers. CONCLUSIONS The variation in the cost and reimbursement of diet therapy and the level of additional state benefits for PKU patients demonstrates the large difference in expenditure on and access to PKU dietary products. This highlights the inequality between healthcare systems and access to special dietary products for people with PKU, ultimately leading to patients in some countries receiving better care than others.

Adjusting diet with sapropterin in phenylketonuria: what factors should be considered?

The usual treatment for phenylketonuria (PKU) is a phenylalanine-restricted diet. Following this diet is challenging, and long-term adherence (and hence metabolic control) is commonly poor. Patients with PKU (usually, but not exclusively, with a relatively mild form of the disorder) who are responsive to treatment with pharmacological doses of tetrahydrobiopterin (BH4) have either lower concentrations of blood phenylalanine or improved dietary phenylalanine tolerance. The availability of a registered formulation of BH4 (sapropterin dihydrochloride, Kuvan®) has raised many practical issues and new questions in the dietary management of these patients. Initially, patients and carers must understand clearly the likely benefits (and limitations) of sapropterin therapy. A minority of patients who respond to sapropterin are able to discontinue the phenylalanine-restricted diet completely, while others are able to relax the diet to some extent. Care is required when altering the phenylalanine-restricted diet, as this may have unintended nutritional consequences and must be undertaken with caution. New clinical protocols are required for managing any dietary change while maintaining control of blood phenylalanine, ensuring adequate nutrition and preventing nutritional deficiencies, overweight or obesity. An accurate initial evaluation of pre-sapropterin phenylalanine tolerance is essential, and the desired outcome from treatment with sapropterin (e.g. reduction in blood phenylalanine or relaxation in diet) must also be understood by the patient and carers from the outset. Continuing education and support will be required thereafter, with further adjustment of diet and sapropterin dosage as a young patient grows.