Human Milk Banking-Facts and Issues to Resolve

The number of human milk banks is increasing worldwide. Although the beneficial effects of feeding premature infants with their mother’s milk are well documented, less is known about the effects of feeding these infants with pasteurized donor milk. We propose a randomized trial comparing the effects of a 100% human milk-based diet (human milk supplemented with a human milk-derived fortifier) and a diet (partially) based on bovine milk. In theory, human milk has a beneficial effect on various aspects of human physiology, most of which become apparent after infancy. We therefore propose an extensive follow-up program that takes this aspect into consideration. Other issues concerning the practice of human milk banks need to be addressed as well as optimization of the feeding strategies for preterm infants

Optimal Growth of Preterm Infants

The cause of growth restriction in preterm infants is multifactorial, but it has been estimated that about 50% of the variance in early postnatal growth can be attributed to nutrition. Very low birth weight (VLBW) infants who were born small-for-gestational age (SGA) seem to have the highest risk to become growth restricted. Possibly, the intrauterine growth-retarded preterm infant is metabolically different from its appropriately grown counterpart and therefore has different nutritional needs. Neonatal nutrition and the resulting postnatal growth are major determinants in the short- and long-term outcomes of preterm neonates. Although having favorable effects on neurodevelopmental outcome, rapid postnatal weight gain after a period of nutritional restriction is associated with the development of insulin resistance and metabolic syndrome in later life. It seems likely that minimization of postnatal growth failure will decrease the need for catch-up growth and thereby decrease the risk of developing cardiovascular risk factors. Monitoring postnatal growth with current growth charts is complicated. Most growth charts that are currently being used are a reflection of current (nutritional) practices and are not a prescription of how VLBW should grow under optimal conditions. In addition to body weight, other aspects of growth such as lean body mass and length gain should also be taken into account when assessing the quality of postnatal growth. Noninvasive measurements of infant body composition are useful tools in evaluating the success of different nutritional interventions. However, all currently available methods have substantial drawbacks. A relatively new and promising method is air displacement plethysmography. This method still needs to be validated in preterm neonates. In conclusion, neonatal nutrition is a major determinant in the short- and long-term outcomes of preterm neonates. Monitoring postnatal growth is complicated by the lack of prescriptive growth charts and noninvasive measurements to assess the quality of growth. Copyright (C) 2013 S. Karger AG, Base

How Genetic Variants in Children with Familial Hypercholesterolemia Not Only Guide Detection, but Also Treatment

Familial hypercholesterolemia (FH) is a hereditary disorder that causes severely elevated low-density lipoprotein (LDL-C) levels, which leads to an increased risk for premature cardiovascular disease. A variety of genetic variants can cause FH, namely variants in the genes for the LDL receptor (LDLR), apolipoprotein B (APOB), proprotein convertase subtilisin/kexin type 9 (PCSK9), and/or LDL-receptor adaptor protein 1 (LDLRAP1). Variants can exist in a heterozygous form (HeFH) or the more severe homozygous form (HoFH). If affected individuals are diagnosed early (through screening), they benefit tremendously from early initiation of lipid-lowering therapy, such as statins, and cardiovascular imaging to detect possible atherosclerosis. Over the last years, due to intensive research on the genetic basis of LDL-C metabolism, novel, promising therapies have been developed to reduce LDL-C levels and subsequently reduce cardiovascular risk. Results from studies on therapies focused on inhibiting PCSK9, a protein responsible for degradation of the LDLR, are impressive. As the effect of PCSK9 inhibitors (PCSK9-i) is dependent of residual LDLR activity, this medication is less potent in patients without functional LDLR (e.g., null/null variant). Novel therapies that are expected to become available in the near future focused on inhibition of another major regulatory protein in lipid metabolism (angiopoietin-like 3 (ANGPTL3)) might dramatically reduce the frequency of apheresis in children with HoFH, independently of their residual LDLR. At present, another independent risk factor for premature cardiovascular disease, elevated levels of lipoprotein(a) (Lp(a)), cannot be effectively treated with medication. Further understanding of the genetic basis of Lp(a) metabolism, however, offers a possibility for the development of novel therapies

Assessment of intestinal permeability in (premature) neonates by sugar absorption tests

Infants born prematurely have an enhanced intestinal permeability compared to healthy term infants. This enhanced permeability might be a contributing factor in the development of Necrotising Enterocolitis. The assessment of intestinal permeability in premature neonates with sugar absorption tests has been proven to be safe and of minimal burden to the infant. After enteral administration of a test solution containing lactulose and mannitol, the excretion of these sugars is measured in urine, and the ratio is calculated. The lactulose and mannitol concentrations in urine can be measured by the use of a gas chromatograph after pre-purification and derivatisation of the sample. Non-invasive assessment of intestinal permeability can be useful in monitoring the effects of experimental (nutritional) therap

CTCA in children with severe heterozygous familial hypercholesterolaemia: Screening for subclinical atherosclerosis

Familial hypercholesterolemia (FH) is one of the most common genetically inherited disorders in the world. Children with severe heterozygous FH (HeFH), i.e. untreated low-density lipoprotein cholesterol (LDL-C) levels above the 90th percentile for age and sex among FH mutation carriers, can have LDL-C levels that overlap levels of children with homozygous FH (HoFH), but treatment regimen and cardiovascular follow-up to prevent cardiovascular disease are less intensive in children with severe HeFH. In children with HoFH, subclinical atherosclerosis can already be present using computed tomography coronary angiography (CTCA). The question remains whether this is also the case in children with severe HeFH who have a high exposure to elevated LDL-C levels from birth onwards as well. We calculated the cumulative LDL-C exposure (CEtotal [mmol]) in four children with severe HeFH and performed computed tomography coronary angiography (CTCA). These children, aged 13, 14, 15 and 18 years, had CEtotal of 71.3, 97.8, 103.6 and 136.1 mmol, respectively. None of them showed abnormalities on cardiovascular imaging, despite high LDL-C exposure. The results of this study, do not give us an indication to recommend performing CTCA routinely in children with severe HeFH

Medication Use During Pregnancy and Lactation in a Dutch Population

Background: Medication use during pregnancy and lactation can be unavoidable, but knowledge on safety for the fetus or breastfed infant is limited among patients and healthcare providers. Research aim: This study aimed to determine (a) the prevalence of medication use in pregnant and lactating women in a tertiary academic center, (b) the types and safety of these medicines, and (c) the influence of medication use on initiation of breastfeeding. Methods: This study used a cross-sectional survey among women (N = 292) who underwent high-risk or low-risk deliveries. Data about their use of prescribed, over-the-counter, and homeopathic medication during pregnancy were obtained through a structured interview, followed by a questionnaire during lactation. Safety was classified according to the risk classification system from the Dutch Teratological Information Service. Results: Overall, 95.5% of participants used medication. One third of participants used at least one medicine with an unknown risk for the fetus. Teratogenic medication was used by 6.5% of participants, whereas 29.5% used medication with a (suspected) pharmacological effect on the fetus. Lactation was initiated by 258 (88.7%) participants, of which 84.2% used medication while breastfeeding. In 3.8% of participants, this medication was classified unsafe, but none used medication with an unknown risk. One-third of the nonlactating participants decided not to initiate breastfeeding because of medication use. In 70% of participants, this decision was appropriate. Conclusion: The prevalence of overall use of medication in Dutch pregnant and lactating women admitted to a tertiary center was high. There is an urgent need for pharmacometric studies for determination of the safe use of the most frequently used medicines during pregnancy or lactation

Effect of enteral IGF-1 supplementation on feeding tolerance, growth, and gut permeability in enterally fed premature neonates

The gastrointestinal tract of the premature newborn functions suboptimally with regard to digestion, absorption, and feeding tolerance. Human milk contains trophic factors, such as insulin-like growth factor-1 (IGF-1), that are believed to stimulate gut growth and function. The objective of this double blind, randomized, controlled trial was to assess the effects of enteral IGF-1 supplementation on whole body growth measured by weight gain (in grams per kilogram per day), days to regain birth weight, and anthropometrical characteristics, and gut maturation and permeability (measured by sugar absorption tests). The study included 60 premature infants (birth weight 750-1250 g) during the first month of life. Patients received either standard infant formula or standard infant formula supplemented with IGF-1 in a concentration twice that of human colostrum (10 microg/100 mL of formula). Primary endpoints were days to full enteral feeding, days to regain birth weight, and growth rate. Sugar absorption tests were performed weekly to assess the secondary endpoints gut permeability and maturation. None of the primary endpoints differed to statistical significance between groups at any point. However, gut permeability was significantly lower in the IGF-1 supplement group on day 14 compared with the control group. At day 21, lactulose/mannitol excretion ratios were (again) comparable between the groups. Although gut permeability showed a faster decrease in the IGF-1 supplement group, our data do not support IGF-1 supplementation to infant formul