Late Fortification Research Articles

Does Early Fortification of Human Milk Decrease Time to Regain Birth Weight as Compared to Late Fortification Among Preterm Infants? - A Randomized Controlled Trial.

To compare the duration required to regain birth weight following early fortification of human milk vs. late fortification among preterm infants. This randomized controlled trial included hemodynamically stable 120 preterm infants (≤32 wk of gestation). The intervention and comparator groups received standard fortification with human milk fortifier when enteral feeds reached 30ml/kg/d (early fortification) and 80ml/kg/d (late fortification) respectively. Neonates in both the groups received feed increments as per standard NICU protocol. Anthropometric measurements (weight, length, and head circumference) at birth and during postnatal follow-up were done following standard precautions and plotted on the sex-specific Fenton growth charts. Primary outcome was the mean duration required to regain birth weight. Secondary outcomes included weight gain velocity, linear growth, increase in head circumference and occurrence of sepsis, feed intolerance and necrotizing enterocolitis. Preterm neonates who received early fortification regained birth weight earlier compared to those in the late fortification group (10.13 ± 2.90 vs. 11.26 ± 3.06, p <0.05). The weight gain velocity, linear growth and increase in head circumference were better in the early fortification group. There was no increased risk of culture proven sepsis, feed intolerance and necrotizing enterocolitis in the early fortification group compared to late fortification. Standard fortification with human milk fortifier when enteral feeds reach 30ml/kg/d helps preterm neonates regain birth weight earlier. Early fortification is well tolerated and safe for the population studied.

A Food Industry Perspective on Folic Fortification

The U.S. Public Health Service (PHS) has recommended that all women of childbearing years, capable of becoming pregnant, consume 400 fig folic acid/d to reduce their risk of having a neural tube defect (NTD)-affected pregnancy. The U.S. Food and Drug Administration subsequently proposed a fo late fortification scheme for cereal grains, which also allowed the continued fortification of breakfast cereals at 0.1 mg per serving. To determine the contribution of ready-to-eat breakfast cereals (RTEC) to folate in takes in women of childbearing years, data were ana lyzed from the U.S. Department of Agriculture’s 1989-1991 Continuing Survey of Food Intakes by In dividuals and 1987-1988 Nationwide Food Consumption Survey. Women consuming RTEC have higher intakes of folate than women reporting no RTEC consumption. Recent reports indicate that most women are unaware of the PHS recommendation to consume more folate, and many health professionals are not advising women of the need to consume adequate folate during the childbearing years. The food industry has been an effective communicator of health and nutrition messages and should be encouraged to raise awareness about the role of folate in NTDs. Better analysis also needs to be conducted to identify women at risk of low folate intakes, so that targeted educational efforts can be made and appropriate vehicles identified for delivering folate to these women.

Human Milk Fortification in Very Preterm Infants in China: A Multicenter Survey.

AimTo investigate the use of human milk fortifier (HMF) for very preterm infants (VPIs) and complications and nutritional status of VPIs due to various breast milk enhancement strategies among the Chinese population.MethodsVPIs with birth weight < 1,800 g and wholly or predominantly breastfed were assigned to the following fortification groups: no HMF, early HMF (adding HMF at an enteral volume of ≤ 80 ml·kg−1·day−1), middle HMF (adding HMF at an enteral volume of 80–100 ml·kg−1·day−1), and late HMF (adding HMF at an enteral volume of ≥100 ml·kg−1·day−1). The growth status and complications for various groups were evaluated.ResultsWe enrolled 985 VPIs, of which 847 VPIs (86.0%) received HMF, whereas 138 VPIs (14.0%) did not. The number of VPIs in the early, middle, and late fortification groups were 89 (9.0%), 252 (25.6%), and 506 (51.4%), respectively. The complete fortification of the early, middle, and late fortification groups was achieved in 13.2 ± 11.0, 13.8 ± 11.7, and 12.3 ± 13.0 days, respectively, without significant differences (p > 0.05). The groups did not exhibit significant differences in the incidence of feeding intolerance, necrotizing enterocolitis (Bell stage ≥ 2), late-onset sepsis, and metabolic bone diseases (p > 0.05). The middle fortification groups exhibited the fastest growth velocity and the least dramatic decrease in the Z-score of weight and length, and the lowest incidence of EUGR (35.7%), whereas the “no HMF” groups exhibited the slowest growth velocity and the largest decline in the Z-score, and the highest incidence of EUGR (61.6%).ConclusionsThe usage rate of HMF was relatively low among Chinese VPIs, fortification often occurred in the late feeding stage, and the time to reach complete fortification was long. Adding HMF and different breast milk enhancement strategies did not increase the incidence of feeding intolerance and necrotizing enterocolitis. The enteral volume of 80–100 ml·kg−1·day−1 with HMF addition led to increased growth in the weight and length and lower EUGR incidence, indicating that the addition of HMF at the specific feeding volume might be the best practice for promoting growth.

Early fortification of human milk versus late fortification to promote growth in preterm infants.

Uncertainty exists about the optimal point at which multi-component fortifier should be added to human milk for promoting growth in preterm infants. The most common practice is to start fortification when the infant's daily enteral feed volume reaches 100 mL/kg body weight. Another approach is to commence fortification earlier, in some cases as early as the first enteral feed. Early fortification of human milk could increase nutrient intake and growth rates but may increase the risk of feed intolerance and necrotising enterocolitis (NEC). To assess effects on growth and safety of early fortification of human milk versus late fortification in preterm infants To assess whether effects vary based upon gestational age (≤ 27 weeks; 28 to 31 weeks; ≥ 32 weeks), birth weight (< 1000 g; 1000 to 1499 g; ≥ 1500 g), small or appropriate for gestational age, or type of fortifier (bovine milk-based human milk fortifier (HMF); human milk-based HMF; formula powder) SEARCH METHODS: We used the standard strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 8); OVID MEDLINE (R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Daily and Versions (R) (1946 to 15 August 2019); MEDLINE via PubMed (1 August 2018 to 15 August 2019) for the previous year; and the Cumulative Index to Nursing and Allied Health Literatue (CINAHL) (1981 to 15 August 2019). We searched clinical trials databases and reference lists of included studies. We included randomised controlled trials that compared early versus late fortification of human milk in preterm infants. We defined early fortification as fortification started at < 100 mL/kg/d enteral feed volume or < 7 days postnatal age, and late fortification as fortification started at ≥ 100 mL/kg/d feeds or ≥ 7 days postnatal age. Both review authors assessed trial eligibility and risk of bias and independently extracted data. We analysed treatment effects in individual trials, and we reported risk ratio (RR) for dichotomous data and mean difference (MD) for continuous data, with respective 95% confidence intervals (CIs). We used the GRADE approach to assess the certainty of evidence. We included two trials with a total of 237 infants. All participants were very low birth weight infants (birth weight < 1500 g). Early fortification was started at 20 mL/kg/d enteral feeds in one study and 40 mL/kg/d in the other study. Late fortification was started at 100 mL/kg/d feeds in both studies. One study used bovine milk-based fortifier, and the other used human milk-based fortifier. Meta-analysis showed that early fortification may have little or no effect on growth outcomes including time to regain birth weight (MD -0.06 days, 95% CI -1.32 to 1.20 days), linear growth (MD 0.10 cm/week, 95% CI -0.03 to 0.22 cm/week), or head growth (MD -0.01 cm/week, 95% CI -0.07 to 0.06 cm/week) during the initial hospitalisation period. Early fortification may have little or no effect on the risk of NEC (MD -0.01, 95% CI -0.07 to 0.06). The certainty of evidence was low for these outcomes due to risk of bias (lack of blinding) and imprecision (small sample size). Early fortification may have little or no effect on incidence of surgical NEC, time to reach full enteral feeds, extrauterine growth restriction at discharge, proportion of infants with feed interruption episodes, duration of total parenteral nutrition (TPN), duration of central venous line usage, or incidence of invasive infection, all-cause mortality, and duration of hospital stay. The certainty of evidence was low for these outcomes due to risk of bias (lack of blinding) and imprecision (small sample size). We did not have data for other outcomes such as subsequent weight gain after birth weight is regained, parenteral nutrition-associated liver disease, postdischarge growth, and neurodevelopmental outcomes. Available evidence is insufficient to support or refute early fortification of human milk in preterm infants. Further large trials would be needed to provide data of sufficient quality and precision to inform policy and practice.

Early fortification of enteral feedings for infants

BACKGROUND:An exclusive human milk diet (EHM) including fortification with a human milk-based fortifier has been shown to decrease the occurrence of necrotizing enterocolitis (NEC) but growth velocity may be less for infants receiving EHM compared to a bovine diet.OBJECTIVE:The objective of this study was to determine if growth is improved by earlier fortification of breast milk for preterm infants supported with a human milk based fortifier.STUDY DESIGN:A multi-center retrospective cohort study of the outcomes of infants of 500– 1250 g birth weight whose breast milk feedings were fortified at >60 mL/kg/day (late) versus <60 mL/kg/day (early) of enteral feeding volume.RESULTS:Median±IQR range for gestational age (27.6±3.4 vs 27.0±2.9 weeks, p = 0.03) and chronic lung disease (CLD: 42.6 vs 27.6%, p = 0.008) were higher, and weight gain (12.9±2.6 vs 13.3±2.6 g/kg/day, p = 0.03) was lower in the late (N = 102) vs the early (N = 292) group. Adjusted multiple linear regression analysis found that early fortification was associated with improved growth velocity for weight (p = 0.007) and head circumference (HC) (p = 0.021) and less negative changes in z-scores for weight (p = 0.022) and HC (p = 0.046) from birth to discharge. Adjusted multiple logistic regression found that early fortification was associated with decreased occurrence of CLD (p = 0.004). No other outcomes, including NEC, were associated with early versus late fortification.CONCLUSION:The study results suggested that early HM fortification appears to positively affect growth for infants whose human milk feedings are fortified with a human milk based fortifier without adverse effects. The incidence of CLD was also reduced in the early fortification group.

Early versus late fortification of breast milk in preterm infants: a systematic review and meta-analysis.

This systematic review and meta-analysis assessed the effects of early fortification (EF) versus late fortification (LF) of breast milk (BM) on growth of preterm infants. Randomized and quasi-randomized controlled trials (RCTs) dealing with the effects of EF versus LF on growth parameters, incidence of adverse events, and duration of hospital stay in preterm infants were included. Data were pooled using the RevMan 5.3 software. Quality of evidence for predefined outcomes was analyzed by GRADE. Available evidence (3 RCTs, 309 preterm infants) showed no statistically significant difference between EF and LF of BM for any of the growth parameters-weight (standardized mean difference (SMD) 0.13; 95% confidence interval (CI) - 0.09, 0.36); length (SMD 0.02; 95% CI - 0.20, 0.25); and head circumference (SMD - 0.10; 95% CI - 0.33, 0.12). Total parenteral nutrition days were similar. Duration of hospital stay was significantly higher with EF (MD 4.29; 95% CI 0.84, 7.75) with a trend of non-significant increase in feed intolerance and necrotizing enterocolitis (NEC).Conclusion: Very low quality evidence did not find any significant difference in growth parameters of preterm infants in association with EF or LF of BM. A significant increase in hospital stay and non-significant increase in feed intolerance and NEC were associated with EF.PROSPERO registration number: CRD42019139235What is Known:• Fortification of breast milk with essential macro- and micronutrients is necessary for optimization of nutrition in preterm infants.• There is no consensus regarding the breast milk feeding volume at which fortification should be initiated.What is New:• Very low quality evidence showed no significant difference between early and late fortification of breast milk on growth parameters of preterm infants.• Early fortification was associated with non-significant increase in feed intolerance and necrotizing enterocolitis and a significant increase in hospital stay.

Early fortification of human milk versus late fortification to promote growth in preterm infants

Early fortification of human milk versus late fortification to promote growth in preterm infants

Does early compared to late fortification of human milk for preterm infants improve clinical outcomes?

This evidence-based review aims to answer the following structured clinical question: In preterm infants <37 weeks' gestation (patient), does early fortification of breast milk (intervention) compared to late fortification (control) improve growth outcomes at the time of discharge or affect length of hospital stay (outcome)? MEDLINE, Embase, Maternity and Infant Care Database and Evidence-Based Medicine Reviews were searched for articles published from 2000 onwards that were relevant to the structured clinical question. The National Institute for Health and Care Excellence, National Health and Medical Research Council, Agency for Healthcare Research and Quality, National Institute of Health and Turning Research into Practice databases were also searched, and reference lists of relevant articles were reviewed. A total of 167 articles, after removal of duplicates, were found and screened by title and abstract. Five full-text articles were ultimately included in the review. The results of this review suggest that early fortification is safe and well tolerated. However, earlier fortification has not been shown to have a significant impact on growth outcomes at time of discharge or length of stay. More research is required to determine if early fortification of breast milk may have benefits regarding longer-term growth and neurodevelopmental outcomes.

Hillforts. From Emergence to Present Day

Hillforts. From Emergence to Present Day

Effect of Elemental Sulfur as Fertilizer Ingredient on the Mobilization of Iron from the Iron Pools of a Calcareous Soil Cultivated with Durum Wheat and the Crop’s Iron and Sulfur Nutrition

The granules of conventional fertilizers have been enriched recently with 2% elemental sulfur (S0) via a binding material of organic nature and such fertilizers are suitable for large scale agriculture. In a previous work, we demonstrated that a durum wheat crop that received the enriched fertilization scheme (FBS0-crop) accumulated a higher amount of Fe compared to the durum wheat crop fertilized by the corresponding conventional fertilization scheme (F-crop). In this study, we investigated the effect of S0 on the contingent mobilization of iron from the iron pools of the calcareous field that affiliated the durum wheat crop and the corresponding effect on the crop’s iron nutrition and sulfur nutrition. A sequential extraction of Fe from root zone soil (rhizosoil) was applied and the fluctuations of these fractions during crop development were monitored. The fertilization with FBS0 at sowing affected the iron fractions of the rhizosoil towards iron mobilization, thus providing more iron to the crop, which apart from the iron nutrition fortified the crop’s sulfur nutrition, too. No iron was found as iron attached to carbonates of the rhizosoil. Fluctuations of the iron pool, bound or adsorbed to the organic matter, were exactly the opposite to those of the iron pool associated with the clay particles in both treatments, suggesting iron exchange between the two pools. Replenishment of the F-crop’s Fe content and a deficit in the FBS0-crop’s Fe content in the rhizosoil were found at the end of the cultivation period. Furthermore, the initiation of the fast stem elongation stage (day 125) constituted a turning point. Before day 125, the use of FBS0 increased the iron concentration in the main stems and this was an early fortification effect, followed by an increase in the organic S concentration. Following day 125, the FBS0-crop consisted of plants with higher main stems and less tillers. A late fortification effect was observed in the iron concentration of the main stems and their heads after the stage of complete flowering. Prior to harvesting in the FBS0-crop, all plant parts were heavier, with more iron and organic sulfur accumulated in these plant parts, and the obtained commercial yield of the FBS0-crop was higher by 27.3%.

Is early breast milk fortification more effective in preterm infants?: a clinical trial.

Breast feeding alone does not provide adequate nutrition for growth in preterm infants; therefore, fortifiers are added when over 70-80 cc/kg/day of breast milk is tolerated. As there are few studies comparing early and late breast milk fortification, the following study was conducted. This double-blind clinical trial was performed on 80 preterm infants (gestational age of 28-34 weeks, birth weight <2 kg). The newborns were randomly divided into two groups to receive either early or late fortification. The primary and secondary outcomes were the difference in growth indices and complications (including feeding intolerance, necrotizing enterocolitis (NEC), and septicemia) between the two groups, respectively. Both groups showed increases in growth indices; however, there was no statistically significant difference in increments of growth indices and complications between the two groups. Our findings suggest that early fortification from the first feeding in neonates with exclusive breast feeding did not improve growth in the first 4 weeks in preterm neonates in comparison with late fortification; so early fortification may not be cost effective.