Ferdinand Haschke

Does maternal docosahexaenoic acid supplementation during pregnancy and lactation lower BMI in late infancy

Abstract We compared growth of infants whose mothers either did or did not receive docosahexaenoic acid (DHA) supplements during pregnancy and lactation. At 21 weeks gestation, 144 women were enrolled into a randomized, double-blind clinical trial receiving: (1) a basic supplement consisting of vitamins and minerals (BS), or (2) BS plus 4.5 g fructooligosaccharide (BSF), or (3) BSF plus fish oil DHA (200 mg) until the end of the third month of lactation. Infants length, weight and head circumference were measured at birth and at 1, 3 and 21 months. A total of 51 mothers/infants were lost to follow-up by the third month and 24 at 21 months. The two groups not receiving DHA were combined into a control group. Analysis with mixed models adjusted for confounding factors showed a significant time dependent effect for the DHA group on the development of the body mass index (BMI) (P=0.037), and of weight (P=0.046), but no effect on the development of length (P=0.537), or of head circumference (P=0.267). At 21 months, weight of the DHA group was lower by −601 g (95% CI −171; −1030 g) and BMI was lower by −0.76 kg/m2 (95% CI −0.07; −1.46) compared to controls. The results indicate that DHA taken by pregnant and lactating mothers may reduce BMI in late infancy.

Supplementation with 200 mg/Day Docosahexaenoic Acid from Mid-Pregnancy through Lactation Improves the Docosahexaenoic Acid Status of Mothers with a Habitually Low Fish Intake and of Their Infants

Background/Aims: The supply of docosahexaenoic acid (DHA, 22:6ω–3), important for fetal/infant neurodevelopment, depends on the maternal fatty acid (FA) status, which may be marginal in central Europe. Therefore, we investigated the effect of a daily vitamin/mineral supplement with and without 200 mg DHA from mid-pregnancy through lactation on the DHA concentrations in maternal and infant red blood cell phospholipids (RBC%), and in breast milk FA (%). Methods: At 21 weeks’ gestation, 144 women were enrolled into a randomised, double-blind clinical trial receiving daily: (1) a basic vitamin-mineral supplement (Vit/Min group), (2) Vit/Min plus 4.5 g fructo-oligosaccharide (FOS group), or (3) Vit/Min plus 4.5 g FOS plus 200 mg fish oil-derived DHA (DHA-FOS group). FAs were determined by capillary gas-liquid chromatography. Results: While maternal RBC-DHA% at enrolment was not different, at 37 weeks gestation, and 3 months after delivery RBC-DHA% were significantly higher in the DHA-FOS group. The breast milk DHA% was twice as high in the DHA-FOS group (0.50%) than in the two others (0.25 %) (p < 0.001), and the ratio ARA/DHA in the DHA-FOS group was 1.0 ± 0.43, in the others 2.1 ± 0.43 (p < 0.001). The RBC-DHA% of the infants in the DHA-FOS group was also significantly higher, and correlated significantly with maternal RBC-DHA% before and 3 months after delivery. Conclusions: In central Europe, a dose of 200 mg/day DHA from mid-pregnancy through lactation seems appropriate to improve the DHA status of mothers and infants.

Clinical trials prove the safety and efficacy of the probiotic strain Bifidobacterium Bb12 in follow-up formula and growing-up milks

SummaryClinical trials to prove the safety and efficacy of follow-up formulas and growing-up milks fortified with Bifidobacterium strain Bb12 (107–108/g formula powder) are summarized in this report. The strain Bb12 was selected because of its excellent survival during intestinal transit and adhesion to enterocytes. Double-blind, randomized, controlled feeding studies with Bb12 in the U.S., China, and Thailand demonstrated normal growth of healthy children between 4 and 36 months of age and catch-up growth in malnourished children. ”Colonization” with Bb12, which indicates survival during intestinal transit, was confirmed when Bb12 was given with milk-based formulas, but was not satisfactory with soy-based formulas. Feeding the milk-based formula with Bb12 resulted in protection from rotavirus infection, fewer periods with hard bowel movements and a lower incidence of diaper rash. Therefore, using follow-up formulas and growing-up milks with Bifidobacterium strain Bb12 is safe and can prevent diseases frequently seen in both industrialized and developing countries.ZusammenfassungKlinische Studien sind notwendig, um die Sicherheit und Wirksamkeit von Folge- und Kleinkindermilch zu beweisen, der Bifidobacterien vom Stamm Bb12 (107–108/Gramm Milchpulver) zugegeben wurden. Dieser Bakterienstamm wurde gewählt, weil er die Darmpassage überleben kann und eine Adhäsionsfähigkeit an Enterozyten besitzt. Randomisierte, kontrollierte Doppelblindstudien in den USA, China und Thailand zeigten, daß gesunde Kinder im Alter zwischen 4 und 36 Monaten bei Ernährung mit einer mit Bb12 versetzten Folgemilch normal wuchsen. Kinder mit Malnutrition zeigten ein Aufholwachstum. Bb12 konnte bei den Kindern im Stuhl nachgewiesen werden, die eine mit Bb12 versetzte Folge- oder Kleinkindermilch auf Kuhmilchbasis erhielten. Bei Ernährung mit Soyamilch, die mit Bb12 versetzt war, war das gastrointestinale Überleben der Bakterien jedoch nicht ausreichend. Die Ernährung mit Folge- oder Kleinkindermilch auf Kuhmilchbasis und Bb12 Zusatz führte zu einer niedrigeren Inzidenz von Rotavirus Infektionen, Obstipation und Windeldermatitis. Es konnte daher in den klinischen Studien einerseits die Sicherheit von Folge- und Kleinkindermilch mit Bb12 gezeigt werden, andererseits tragen diese Nahrungen zur Verhütung einiger Erkrankungen bei, die sowohl in Industrie- als auch in Entwicklungsländern häufig beobachtet werden.

Gastric emptying in healthy newborns fed an intact protein formula, a partially and an extensively hydrolysed formula.

BACKGROUND & AIMSnGastric emptying (GE) is influenced by the type of nutrition. The objective of this study was to compare GE in infants fed an intact protein formula (IPF), a partially hydrolysed formula (PHF), and an extensively hydrolysed formula (EHF).nnnMETHODSnThis was a double-blind, randomized, cross-over study. Following a fasting period of > or = 3 h, 20 healthy newborns were fed IPF, PHF, and EHF containing 50 microl (13)C-octanoic acid (OA). Breath samples were taken before feeding and every 15 min for 4 h thereafter. (13)C-OA breath test was assessed by isotope-ratio mass spectrometry, and GE half-times (t(1/2)) were determined.nnnRESULTSnSeventeen infants with a mean gestational age of 37 wk (range 28-40 wk) and birth weight of 2698 g (range 720-3690 g) completed the study. At study initiation, the mean age was 31 d (range 6 d-13 wk) and the mean weight was 3466 g (range 2100-5700 g). EHF emptied significantly faster than IPF and PHF (medians 46 vs. 55 and 53 min, respectively, Wilcoxon, P<0.05 for both). There was no significant difference between GE of PHF and IPF (Wilcoxon, P=0.2).nnnCONCLUSIONSnEHF may be better tolerated by infants with GE problems.

Urinary D-Lactate Excretion in Infants Receiving Lactobacillus johnsonii with Formula

Background/Aims: Supplementation with certain probiotics can improve gut microbial flora and immune function but should not have adverse effects. This study aimed to assess the risk of D-lactate accumulation and subsequent metabolic acidosis in infants fed on formula containing Lactobacillus johnsonii (La1®). Methods: In the framework of a double-blind, randomized controlled trial enrolling 71 infants aged 4–5 months, morning urine samples were collected before and 4 weeks after being fed formulas with or without La1 (1 × 108/g powder) or being breastfed. Urinary D- and L-lactate concentrations were assayed by enzymatic, fluorimetric methods and excretion was normalized per mol creatinine. Results: At baseline, no significant differences in urinary D-/L-lactate excretion among the formula-fed and breastfed groups were found. After 4 weeks, D-lactate excretion did not differ between the two formula groups, but was higher in both formula groups than in breastfed infants. In all infants receiving La1, urinary D-lactate concentrations remained within the concentration ranges of age-matched healthy infants which had been determined in an earlier study using the same analytical method. Urinary L-lactate also did not vary over time or among groups. Conclusions: Supplementation of La1 to formula did not affect urinary lactate excretion and there is no evidence of an increased risk of lactic acidosis.

Economic evaluation of a 100% whey-based, partially hydrolysed formula in the prevention of atopic dermatitis among French children

Abstract Objective: A pharmacoeconomic analysis was performed to determine costs, consequences and cost effectiveness of a partially hydrolysed 100% whey-based infant formula, NAN HA, manufactured by Nestlé S.A, Switzerland (PHF-W) and branded under Nidal Excel HA in France, in the prevention of atopic dermatitis (AD) in ‘at risk’ children when compared to standard cows’ milk formula (SF) in France. Methods: A decision-analytic economic model depicting AD treatment pathways, as well as resource utilisation and costs associated with the treatment of AD in healthy yet ‘at risk’ French newborns who cannot be exclusively breastfed was constructed for a 12-month time horizon, including an initial 6 months of intervention with formula consumption. Model inputs were based on the literature, official formularies and expert opinion. The modelled treatment pathways included a dietary management approach (formula change), a medical treatment approach and a combination thereof. The final outcome was the expected cost per avoided case of AD, yielding an incremental cost per avoided case (ICER) of AD when comparing subjects who used PHF-W versus SF. Outcomes were presented from three perspectives: the French Ministry of Health (MOH), the subjects’ family and society as a whole. A secondary analysis also compared PHF-W to extensively hydrolysed formula (EHF) in prevention. Results: The number of avoided AD cases by selecting PHF-W over SF was 13u2009356 cases in a birth cohort of 185u2009298 ‘at risk’ infants. The base case analysis, at 65% reimbursement, yielded expected ICERs of €1343, € –624 (savings) and €719 from the MOH, family and societal perspectives, respectively. From all three perspectives, the highest cost was attributable to formula. In case of a 35% reimbursement rate for PHF-W, the ICER was €615 from the MOH perspective, while the use of PHF-W was cost neutral at 10% reimbursement. PHF-W was cost-saving against EHF (€98–€116 million savings depending on type of EHF), when this latter was used in prevention. One-way and probabilistic sensitivity analyses confirmed the robustness of the model. Conclusion: Under a certain range of assumptions, this analysis based on predictive modelling has established the cost effectiveness of PHF-W in the prevention of AD in infants.

Feeding patterns during the first 2 years and health outcome.

Low-birth-weight infants, in particular those with birth weights <1,500 g, benefit from fortified breast milk. Low protein intake is critical, because it is limiting growth. Long-term health outcomes in small-for-gestational-age infants from developing countries in relation to their early nutrition still need to be evaluated in controlled trials. Term infants both in developing and developed countries also benefit from exclusive breastfeeding: an analysis of a large dataset of surveys from 20 developing countries (168,000 infants and small children from the Demographic Health Survey, United States Agency for International Development) indicates that exclusive breastfeeding until 6 months is associated with significantly higher weight, length, and lower probability of stunting, wasting, and infections. Nine out of 10 infants still receive breast milk between 6 and 12 months and probability of infections tends to be lower if breastfeeding is continued during that age range. Between 12 and 24 months, when stunting and wasting rates are already high, 7 out of 10 infants still receive breast milk. No associations of feeding patterns with disease outcome can be found. Effectiveness trials of complementary feeding strategies in food-insecure countries are urgently needed. Follow-up until 10 years in a developed country now indicates that an infant population at risk for allergic diseases benefits both from breastfeeding and the use of hypoallergenic formula during the first 4 months of life, when compared to cows milk-based formula: both the cumulative incidences of atopic disease and all allergic diseases are significantly lower.

Partially Hydrolysed 100% Whey-Based Infant Formula and the Prevention of Atopic Dermatitis: Comparative Pharmacoeconomic Analyses

Clinical trials have demonstrated that the risk of developing atopic dermatitis is reduced when using hydrolysed formulas to feed infants with a documented risk of atopy (i.e. an affected parent and/or sibling)when breastfeeding is not practised. However, little is known about the cost-effectiveness of using hydrolysed formulas. Consequently, economic analyses in 5 European countries (Denmark, France, Germany, Spain and Switzerland) have evaluated the costs and cost-effectiveness of a specific brand of 100% whey-based partially hydrolysed infant formula, NAN-HA® (PHF-W) compared with a cow’s milk standard formula (SF) in the prevention of atopic dermatitis in at-risk children. This review synthesises the findings of these studies. Cost-effectiveness analyses (CEA) used a decision-analytic model to determine treatment pathways, resource utilisation and costs associated with the management of atopic dermatitis in healthy at-risk newborns who were not exclusively breastfed. The model had a 12-month horizon and applied reimbursement rates of 60–100% depending on the country. Outcomes were considered from the perspective of the public healthcare system (e.g. the Ministry of Health; MOH), family and society. The final outcome was the incremental cost-effectiveness ratio per avoided case of atopic dermatitis (ICER) for PHF-W versus SF. A cost-minimisation analysis was also performed to compare PHF-W with extensively hydrolysed formulas (EHF). The base-case CEA produced ICERs per avoided case for PHF-W versus SF of EUR 982–1,343 (MOH perspective), EUR –2,202 to –624 (family perspective) indicating savings, and EUR –1,220 to 719 from the societal perspective. The main costs related to formula (MOH and society) and time loss (family). In the cost-minimisation analysis, PHF-W yielded savings of between EUR 4.3 and 120 million compared with EHF-whey when the latter was used in prevention. In conclusion, PHF-W was cost-effective versus SF in the prevention of atopic dermatitis and cost saving compared with EHF when used in prevention.

Sustainable Clinical Research, Health Economic Aspects and Medical Marketing: Drivers of Product Innovation

Marketing-driven innovation in the field of pediatric nutrition, in particular in the infant formula segment is not sustainable. New benefits of products must be scientifically proven and safety and efficacy of new formulae established in clinical trials. The scientific innovation process of three infant formulae is described. Improvement in protein quality allowed to reduce the protein concentration in whey-based infant formula. Weight gain and BMI of infants fed those formulae corresponds to breastfed infants and is lower than in infants fed traditional formulae with higher protein concentration. A meta-analysis indicates associations between rapid weight gain in infancy and obesity later in life. If infants cannot be exclusively breastfed until 4-6 months of age, feeding low-protein formulae may contribute to positive long-term health outcome with potentially important health economic effects. A partially hydrolyzed whey based formula for prevention of allergic symptoms in children with hereditary risk for allergic diseases was developed more than 25 years ago. The most recent meta-analysis which included 15 randomized clinical trials indicates that the risk of all allergic diseases and atopic dermatitis/eczema is significantly reduced in infants at risk when the partially hydrolyzed formula is fed. The partially hydrolyzed formula had the same protective effect as casein-based high-degree extensively hydrolyzed formula. Because of substantial price differences between the two formulae, feeding the partially hydrolyzed whey formula is cost saving. Hypoallergenic claims can be made in many countries, and international nutrition committees have positively commented the preventive effect of those formulae. Acidified formulae have been widely used during the last decade in replacement feeding programs for infants whose mothers are HIV positive. The formula was innovated by improving whey protein quality and lowering protein concentration. The bacteriostatic properties of the new formula were proven in in vitro tests. Meta-analysis indicated that feeding the formula to immunocompromised infants resulted in growth similar to breastfeeding. The bacteriostatic effects of the acidified formula need to be communicated to health care professionals, but also the risks if replacement feeding is not acceptable, feasible, affordable, sustainable, and safe for mother and infant.

Nestlé’s response to concerns about oral rehydration solution

A Nestle maltodextrin based oral rehydration solution (ORS) has been sold under various trade names in several European countries. In all of these countries and for two decades this product has proved safe and efficacious as an ORS for treatment of diarrhoea and acute gastroenteritis. The product was introduced under the brand name Resorb Junior Plus in Sweden in 2009. In April 2010 Nestle decided to withdraw the product from the Swedish market because of reports of a few unexpected cases of worsening dehydration and hypernatremia during treatment of young children.1 (See also letter from Lidefelt and colleagues.2)nnAfter a meeting between the Nestle Nutrition Institute and Karolinska Hospital, a collaboration was established to find the cause of the unexpected adverse reactions. A review of …