Head Circumference Gain Research Articles

Formula with large, milk phospholipid-coated lipid droplets in late-moderate preterm infants: a double-blind RCT.

Limited evidence exists on the preferred feeding method when breastfeeding is not possible in late and moderate preterm (LMPT) infants. This RCT evaluates growth, safety, and tolerance of a concept infant formula (IF) with large, milk phospholipid-coated lipid droplets enriched in dairy lipids in LMPT infants with primary objective to demonstrate non-inferiority of daily weight gain from randomization to 3 months corrected age compared to a standard IF. LMPT infants were randomized before or around term equivalent age to either the concept (n = 21) or standard IF (n = 20). Forty-one breastfed (BF) infants served as reference. Due to unintended low recruitment, non-inferiority in daily weight gain could not be demonstrated for the Concept compared to the Control group, but was compared to the BF group. Other outcomes were similar between the formula groups, except for an apparent larger head circumference gain in the Concept group. No apparent differences in growth and body composition outcomes were observed between the Concept and BF reference groups. This small-scale study suggests the concept IF is a safe alternative for parents who choose IF to feed their LMPT infant. Larger trials are needed to better determine impacts on head growth or body composition. In a small group of late and moderate preterm infants, growth from randomization until 3 months corrected age of infants fed with a concept infant formula with large, milk phospholipid-coated lipid droplets was not -significantly different from infants fed a standard infant formula. Infants in the Concept group had non-significant larger gain in head circumference compared to the Control group; larger trials are needed to confirm this finding. Both formulas were well-tolerated, with no differences in adverse events. The concept formula is potentially a safe alternative for parents of moderate to late preterm infants who choose to use formula milk.

Comparison of Paladai Cup Against Nifty Cup Feeding in Preterm Low-Birth-Weight Infants: An Open-Labeled Randomized Controlled Trial.

Background: Neonatal Intuitive Feeding Technology (NIFTY) cup feeding has been found to be feasible in preterm low-birth-weight babies. However, literature on direct comparison of the same with paladai feeding is lacking. Methods: In this open-labeled, randomized controlled trial, preterm infants (<34 weeks/<1800 g) on full oral gastric tube feeding for at least 3 consecutive days, eligible to be given a trial of suck and swallow cup feeding, prior to initiation of direct breastfeeding, were randomized to the two feeding intervention groups: paladai cup and Nifty cup. The primary outcome was the time taken from initiation of oral cup feeds to reaching complete gavage-free cup feeds for at least 24 hours. Secondary outcomes were the ease of use of both instruments, the adverse effects during and within 10 minutes after feeding, and anthropometric parameters (head circumference and weight gain). Results: The median (IQR) time taken from initiation to complete transition to full cup feeding for at least 24 hours was not significantly different [4(3,7) days in Nifty cup group versus 3(2,6) days in paladai cup group, p = 0.25]. Mean ± SD weight gain from intervention to discharge was also similar in both the groups (16 ± 6 g/kg/day in Nifty cup group versus 17 ± 5 g/kg/day in paladai cup group, p = 0.18). Adverse events did not differ (32.9% in group A versus 27.1% in group B, p = 0.580). Nurses did not find any difference in ease of teaching caregivers [median (IQR) Nifty cup group 4(4,5) versus paladai cup group 4(4,5), p = 0.13]. Conclusion: The efficacy and adverse event rates were similar between Nifty cup feeding and paladai cup feeding in preterm infants. Both feeding modalities can be used prior to transition to direct breastfeeding in preterm low-birth-weight infants.

A study of safety and effectiveness of amino-acids based multi-nutrient fortifier in preterm infants

Background: Fortification plays a vital role in supporting the nutritional requirements in the premature infants. Currently in India, fortifiers are either whole protein based or whey protein which are bovine milk- based, which has been associated with increased risk of feed intolerance and necrotizing enterocolitis (NEC), to circumvent this, an amino-acids based fortifier has been made available which provides more proteins (0.35 g/1 g sachet) thereby meeting the nutritional requirements of preterm infants. Aim was to study effect (safety and efficacy) of fortification with the amino-acids based fortifier (HMF-ADVANCE, Analeptik Biologicals) in premature infants admitted in the neonatal intensive care unit (NICU). Methods: A single centre pilot study was conducted on preterm infants with &lt;1800 g birth weight and/or &lt;32 gestational age, amino-acids based fortifier (AABF) was used as the fortification option once the infants reached 100 ml/kg/day feed volume. 1 g of HMF-ADVANCE was mixed in 25 ml of mother’s own milk (MOM) and the fortification was continued till discharge from NICU. Results: A total 100 preterm infants were included for the study, mean gestational age (GA) was 29.38±1.61 weeks, mean birth weight was 1159.90±301.9. Growth outcomes at the end of the study: mean weight gain was 23.73±7.62 g/day, mean head circumference gain was 1.02±0.41 cm/week, mean length gain was 1.01±0.15 cm/week and weight gain velocity were 17.13±2.38 g/kg/day. Blood urea nitrogen (BUN) showed an increasing trend from baseline (before starting fortification: 3.2 mg/dl), 1 week after fortification (6.3 mg/dl) and at the end of study (11.2 mg/dl). AABF was also used in three neonates post NEC. There were no episodes of feed intolerance or necrotising enterocolitis episodes and none of neonates discontinued fortification till discharge from NICU. Conclusions: AABF was well tolerated without any feed intolerance episodes and helped to achieve optimal growth. AABF can be the optimal choice of fortification in low-birth-weight neonates.

Effect of novel human milk oligosaccharides-based human milk fortifier containing lactoferrin, docosahexaenoic acid, and arachidonic acid on the growth of preterm infants with birth weight of 700–1800 g

Background: Premature infants with low birth weight are at risk of growth failure and neurodevelopmental impairment. Human milk oligosaccharides (HMOs) are bioactive components of human milk that may enhance growth and development. The novel HMO-based human milk fortifier (HMoF), which also contains lactoferrin, docosahexaenoic acid (DHA), and arachidonic acid (ARA), can help provide a safer nutritional option for the growth of premature infants. Materials and Methods: We conducted a non-comparative observational study using data from multiple centers that used novel HMO-based HMF (HMoF) in premature infants (n=14) with birth weights of 700–1800 g. The primary outcome of the study was to assess tolerability (in terms of feed tolerance), and secondary outcomes included growth outcomes defined by weight, length, and head circumference during the stay in the NICU and at discharge. Results: A cohort consisting of 14 infants with a mean gestational age of 30.21±2.04 weeks and a birth weight of 1246.36±39.98 g comprised the study. During the study period, incidences of feed interruptions due to feed intolerability were nil, and no infant presented with any signs of adverse effects. The novel HMO-based HMF (HMoF)-fed infant cohort had a mean weight gain of 21.89±5.23 g/day, a mean length gain of 1.01±0.48 cm/week, and mean head circumference gain of 0.89±0.32 cm/week. The mean growth velocity recorded was 16.03±1.73 g/kg/day. Conclusions: Novel HMO-based HMF (HMoF) containing lactoferrin, DHA, and ARA demonstrated acceptable feed tolerance and weight gain without any clinically significant adverse effects. Data indicates that the novel HMoF containing lactoferrin, DHA, and ARA is a safe option for supporting the growth of preterm babies. However, further studies are needed to compare novel HMO-based HMF (HMoF) with standard HMF in a randomized controlled trial.

Growth Assessment of Under-Five Children of Employed and Unemployed Mothers of Etawah District, Uttar Pradesh: A Cross-Sectional Study.

Introduction The under-fiveage group is crucial because the health profile of this age group will have a huge effect on the future development of the nation. Early infancy is marked by several distinct developmental characteristics. Progress in each domain of childhood development is used to track a child's development. Objectives The objectives of the present study were to assess and compare the growth of under-five children of employed and unemployed mothers in the Etawah District of Uttar Pradesh, India. Material and methods A community-based cross-sectional survey was carried out in Etawah district's urban and rural areas between January 2021 and June 2022. A total of 200 mothers with children under the age of five were recruited using the purposive sampling method. To gather pertinent information, a semi-structured, pre-tested, interviewer-administered questionnaire was used. Results In the present study on the comparison of the growth of children among employed and unemployed mothers, it shows that 48 children (50.5%) with a weight between 10.5 and 15 kg were of employed mothers, while 52 children weighing less than 10.5kg were of unemployed mothers (p<0.001). Forty-four children (57.1%) with a chest circumference of more than 48 cm were of employed mothers, while 26 children (78.8%) with a chest circumference of less than 45 cm were of unemployed mothers (p = 0.001). Conclusion The present study indicates that statistically significant differences were found in age-appropriate gain in weight and chest circumference, which was higher among the children of employed mothers in comparison to children ofunemployed mothers. There was no statistically significant difference in age-appropriate gain in height, head circumference, or mid-upper arm circumference among the children of employed mothers and unemployed mothers.

Effect of partially hydrolyzed synbiotic formula milk on weight gain of late preterm and term infants-a multicenter study.

Data on the effectiveness of hydrolyzed infant formula containing both pre- and probiotics (synbiotic formula) on the growth of infants is still scarce. This retrospective study was designed to evaluate the effect of a partially hydrolyzed synbiotic formula on growth parameters and the possible occurrence of major gastrointestinal adverse events or morbidities in infants born via cesarean section (C-section) delivery. C-section-delivered term and late preterm infants who received either partially hydrolyzed synbiotic formula, standard formula, or maternal milk and followed at seven different hospitals from five different regions of Turkey, during a 1-year period with a minimum follow-up duration of 3 months were evaluated retrospectively. All the included infants were evaluated for their growth patterns and any kind of morbidity such as diarrhea, constipation, vomiting, infection, or history of hospitalization. A total of 198 infants (73 in the human milk group, 61 in the standard formula group, and 64 in the partially hydrolyzed synbiotic formula group) reached the final analysis. The groups were similar regarding their demographic and perinatal characteristics. No difference was observed between the three groups regarding gastrointestinal major side effects. Growth velocities of the infants in the human milk and partially hydrolyzed synbiotic formula groups during the first month of life were similar whereas the weight gain of infants in the standard formula group was significantly less than these two groups (p < 0.001). Growth velocities were similar among the three groups between 1st and 3rd months of age. A partially hydrolyzed synbiotic formula provided better weight gain in late-preterm and term infants who were delivered via C-section delivery compared to the standard formula during the first month of life. This weight gain was similar to the infants receiving exclusively human milk. This difference was not observed in length and head circumference gain. No difference was observed in any of the parameters during the 1st-3rd months of age. Specially formulated partially hydrolyzed synbiotic formulas may reverse at least some of the negative impacts of C-section delivery on the infant and help to provide better growth, especially during the early periods of life.

Safety and efficacy of adding postbiotics in infant formula: a systematic review and meta-analysis.

Postbiotics, as emerging products, were added to infant formula, but their safety and efficacy are unclear. To clarify this issue, we wrote this meta-analysis. We searched PubMed, Embase, Web of Science and ProQuest from its establishment to February 2023. The review was registered on PROSPERO database (CRD42022352405). The effects of infant formula with and without postbiotics were compared, and the incidence of serious adverse events (SAEs), digestive symptoms, concentration of stool secretory immunoglobulin A (SIgA), and growth and development indexes were analyzed. Nine randomized controlled trials with 2065 participants were included. The addition of postbiotics to infant formula was found to increase the concentration of stool SIgA (P < 0.05) with very low certainty of evidence, without significantly impacting the incidence of SAEs, infantile colic, flatulence, diarrhea, vomiting, abdominal pain and gastrointestinal disorders, the daily weight gain, the total gain in body length and the daily head circumference gain (all P > 0.05). Adding postbiotics to the formula is safe for infants, which would not increase the incidence of SAEs, infantile colic, flatulence, diarrhea, vomiting, abdominal pain, and gastrointestinal disorders, and could increase the concentration of stool SIgA. IMPACT: Our study provides evidence that the addition of postbiotics to infant formula is safe but not effective. This is the first systematic review and meta-analysis of postbiotics. This study provides strong evidence for the safety of postbiotics and lays a foundation for related clinical trials.

Growth of late preterm infants fed nutrient-enriched formula to 120 days corrected age-A randomized controlled trial.

We aimed to compare the effects of nutrient-enriched formula with standard term formula on rate of body weight gain of late preterm infants appropriately grown for gestational age. A multi-center, randomized, controlled trial. Late preterm infants (34-37 weeks' gestation), with weight appropriate for gestational age (AGA), were randomized to nutrient enriched formula (NEF) with increased calories (22 kcal/30 ml) from protein, added bovine milk fat globule membrane, vitamin D and butyrate or standard term formula 20 kcal/30 ml (STF). Breastfed term infants were enrolled as an observational reference group (BFR). Primary outcome was rate of body weight gain from enrollment to 120 days corrected age (d/CA). Planned sample size was 100 infants per group. Secondary outcomes included body composition, weight, head circumference and length gain, and medically confirmed adverse events to 365 d/CA. The trial was terminated early due to recruitment challenges and sample size was substantially reduced. 40 infants were randomized to NEF (n = 22) and STF (n = 18). 39 infants were enrolled in the BFR group. At 120 d/CA there was no evidence of a difference in weight gain between randomized groups (mean difference 1.77 g/day, 95% CI, -1.63 to 5.18, P = 0.31). Secondary outcomes showed a significant reduction in risk of infectious illness in the NEF group at 120 d/CA [relative risk 0.37 (95% CI, 0.16-0.85), P = 0.02]. We saw no difference in rate of body weight gain between AGA late preterm infants fed NEF compared to STF. Results should be interpreted with caution due to small sample size. The Australia New Zealand Clinical Trials Registry (ACTRN 12618000092291). "mailto:maria.makrides@sahmri.com" maria.makrides@sahmri.com.

Growth and Neurodevelopmental Outcomes of Very Low Birth Weight Infants upto Six Months of Age at a Tertiary Level NICU in Central India: A Prospective Cohort Study

Introduction: The long-term outcomes of Very Low Birth Weight (VLBW) infants are influenced by prematurity, as well as the occurrence of various short-term morbidities, such as Respiratory Distress Syndrome (RDS), sepsis, Necrotising Enterocolitis (NEC), Patent Ductus Arteriosus (PDA), Intraventricular Haemorrhage (IVH), Periventricular Leukomalacia (PVL), Retinopathy Of Prematurity (ROP), and Chronic Lung Disease (CLD). It has been estimated that approximately half of all VLBW infants develop cognitive and behavioural deficits in the future. Therefore, studying VLBW infants and providing longitudinal follow-up after their hospital discharge is increasingly important. This helps in the early diagnosis of neurodevelopmental abnormalities and enables timely intervention for a better quality of life in the future. Aim: To assess the growth and neurodevelopmental outcomes of VLBW infants discharged from the NICU until six months of age. Materials and Methods: A prospective cohort study was conducted in the Neonatal In tensive Crae Unit (NICU) at NSCB Medical College, Jabalpur, Madhya Pradesh, India. The duration of the study was one year and six months, from March 2018 to September 2019. A total of 40 VLBW infants were enrolled and followed-up for six months. The infants were divided into two groups: Group 1 (&lt;32 weeks) and group 2 (&gt;32 weeks). Physical parameters such as weight, length, and head circumference were recorded on admission and at one, three and six months of corrected gestational age. Developmental assessment was performed using the Denver Developmental Screening Test-II (DDST-II) method. The association of risk factors with neurodevelopmental outcomes was also assessed. Data were analysed using Statistical Package for Social Sciences (SPSS) version 20.0, and the Chi-square test, Fisher’s-exact test, and Student’s t-test were used. A p-value less than 0.05 was considered significant. Results: Among the 40 subjects, 12 (30%) were &lt;32 weeks, and 28 (70%) were ≥32 weeks. Overall, parameters were higher in infants ≥32 weeks. Weight and head circumference gain velocity were greater in infants ≥32 weeks during the first three months of life (p&lt;0.05). From three to six months, &lt;32 weeks infants showed a significant increase (p&lt;0.001) in weight and head circumference gain velocity. The length gain velocity in both groups was comparable since birth, and &lt;32 weeks VLBW infants demonstrated good catch-up growth, which was statistically significant (p&lt;0.05). At six months of corrected age, 16 (40%) infants out of the total 40 infants had abnormal neurodevelopmental outcomes. A total of 7 (58.33%) of the &lt;32 weeks VLBW infants and 9 (32.14%) of the ≥32 weeks VLBW infants had Neurodevelopmental Delay (NDD). Hypoglycaemia, shock, hyaline membrane disease, and mechanical ventilation were significantly associated with an increased risk of NDD. Conclusion: The incidence of NDD was significantly higher in infants with lower gestational age, lower birth weight and the presence of associated factors such as hyaline membrane disease, hypoglycaemia, shock, ventilation, and hyperbilirubinaemia. Improved perinatal care, early assessment of development using appropriate tools, and early intervention are necessary to improve the outcomes of these infants.

Omitting routine gastric residual checks may help to accelerate enteral feeds and postnatal growth in stable preterm infants.

The prefeed gastric residual check (GRC) when increasing the amounts of feeds given via orogastric and nasogastric tubes as a precaution for necrotizing enterocolitis (NEC) and intestinal intolerance is a routine procedure. However, it is mostly misleading, and recently, there has been a tendency not to check prefeed residuals. We changed our nutrition protocol at the end of 2018 to start minimal enteral feeds (MEFs) and increase feeds without GRCs. We investigated the effects on the incidence of NEC, complications, time to reach full feeds, and growth parameters RESULTS: We compared the results of 60 preterm infants at ≤35 weeks' gestational age (group 1: 2016-2017, cared for with GRC) and 77 preterm infants (group 2: 2019, without routine GRCs). No differences in incidence of NEC and complications were observed. Group 2 started enteral feeds 3 days earlier, reached total feeds 6 days earlier (P < 0.01), and had higher weight (P < 0.01) and head circumference gain (P < 0.01). Extrauterine growth restriction was significantly less for head circumference and also insignificantly less for weight and height. We conclude that starting MEFs earlier and omitting routine GRCs in clinically stable preterm infants accelerate enteral feeds and growth parameters.

Clinical Evaluation of 16-Week Supplementation with 5HMO-Mix in Healthy-Term Human Infants to Determine Tolerability, Safety, and Effect on Growth

Human milk oligosaccharides (HMOs) are complex sugars that occur naturally in human breast milk and provide many beneficial functions. Most formula products lack HMOs or contain only the most abundant HMO, 2′-fucosyllactose; however, benefits of HMOs come from multiple sugars. We therefore developed a mixture of five HMOs (5HMO-Mix) mimicking the natural concentrations of the top five HMOs (5.75 g/L total, comprising 52% 2′-fucosyllactose, 13% 3-fucosyllactose, 26% lacto-N-tetraose, 4% 3′-sialyllactose, and 5% 6′-sialyllactose) representing the groups of neutral, neutral-fucosylated, and sialylated HMOs. We conducted the first multicenter, randomized, controlled, parallel-group clinical study assessing the safety, tolerability, and effect on growth of formula containing the 5HMO-Mix in healthy infants. We enrolled 341 subjects aged ≤14 days; 225 were randomized into groups fed either with infant formula containing 5HMO-Mix (5HMO-Mix) or infant formula without HMOs (IF) for 4 months, with the others exclusively breastfed. There were no differences in weight, length, or head circumference gain between the two formula groups. The 5HMO-Mix was well tolerated, with 5HMO-Mix and breastfed infants producing softer stools at a higher stool frequency than the control formula group. Adverse events were equivalent in all groups. We conclude that the 5HMO-Mix at 5.75 g/L in infant formula is safe and well tolerated by healthy term infants during the first months of life.

Continuous nasogastric milk feeding versus intermittent bolus milk feeding for preterm infants less than 1500 grams.

Milk feedings can be given via nasogastric tube either intermittently, typically over 10 to 20 minutes every two or three hours, or continuously, using an infusion pump. Although the theoretical benefits and risks of each method have been proposed,their effects on clinically important outcomes remain uncertain. OBJECTIVES: To examine the evidence regarding the effectiveness of continuous versus intermittent bolus tube feeding of milk in preterm infants less than 1500 grams. We used the standard search strategy of Cochrane Neonatal to run comprehensive searches in the Cochrane Central Register of Controlled Trials (CENTRAL 2020, Issue 7) in the Cochrane Library; Ovid MEDLINE and Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Daily and Versions; and CINAHL (Cumulative Index to Nursing and Allied Health Literature) on 17 July 2020. We also searched clinical trials databases and the reference lists of retrieved articles for randomised controlled trials (RCTs) and quasi-RCTs. We included RCTs and quasi-RCTs comparing continuous versus intermittent bolus nasogastric milk feeding in preterm infants less than 1500 grams. Two review authors independently assessed all trials for relevance and risk of bias. We used the standard methods of Cochrane Neonatal to extract data. We used the GRADE approach to assess the certainty of evidence. Primary outcomes were: age at full enteral feedings; feeding intolerance; days to regain birth weight; rate of gain in weight, length and head circumference; and risk of necrotising enterocolitis (NEC). We included nine randomised trials (919 infants) in this updated Cochrane Review. One study is awaiting classification. Seven of the nine included trials reported data from infants with a maximum weight of between 1000 grams and 1400 grams. Two of the nine trials included infants weighing up to 1500 grams. Type(s) of milk feeds varied, including human milk (either mother's own milk or pasteurised donor human milk),preterm formula, or mixed feeding regimens. In some instances, preterm formula wasinitially diluted.Earlier studies also used water to initiate feedings. We judged six trials asunclear or high risk of bias for random sequence generation. We judged four trials as unclear for allocation concealment. We judged all trials ashigh risk of bias for blinding of care givers, and seven as unclear or high risk of bias for blinding of outcome assessors. We downgraded the certainty of evidence for imprecision, due to low numbers of participants in the trials, and/or wide 95% confidence intervals, and/or for risk of bias. Continuous compared to intermittent bolus (nasogastric and orogastric tube) milk feeding Babies receiving continuous feeding may reach full enteral feeding almost one day later than babies receiving intermittent feeding (mean difference (MD) 0.84 days, 95% confidence interval (CI) -0.13 to 1.81; 7 studies, 628 infants; low-certainty evidence). It is uncertain if there is any difference between continuous feeding and intermittent feeding in terms of number ofdays of feeding interruptions (MD -3.00 days, 95% CI -9.50 to 3.50; 1 study, 171 infants; very low-certainty evidence). It is uncertain if continuous feeding has any effect on days to regain birth weight (MD -0.38 days, 95% CI -1.16 to 0.41; 6 studies, 610 infants; low-certainty evidence). The certainty of evidence is low and the 95% confidence interval is consistent with possible benefit and possible harm. It is uncertain ifcontinuous feeding has any effect on rate of gain in weight compared with intermittent feeding (standardised mean difference (SMD) 0.09, 95% CI -0.27 to 0.46; 5 studies, 433 infants; very low-certainty evidence). Continuous feeding may result in little to no difference in rate of gain in length compared with intermittent feeding(MD 0.02 cm/week, 95% CI -0.04 to 0.08; 5 studies, 433 infants; low-certainty evidence). Continuous feeding may result in little to no difference in rate of gain in head circumference compared with intermittent feeding (MD 0.01 cm/week, 95% CI -0.03 to 0.05; 5 studies, 433 infants; low-certainty evidence). It is uncertain if continuous feeding has any effect on the risk of NEC compared with intermittent feeding (RR 1.19, 95% CI 0.67 to 2.11; 4 studies, 372 infants; low-certainty evidence). The certainty of evidence is low and the 95% confidence interval is consistent with possible benefit and possible harm. Although babies receiving continuous feeding may reach full enteral feeding slightly later than babies receiving intermittent feeding, the evidence is of low certainty.However, the clinical risks and benefits of continuous and intermittent nasogastric tube milk feeding cannot be reliably discerned from current available randomised trials.Further research is needed to determine if either feeding method is more appropriate for the initiation of feeds. A rigorous methodology should be adopted, defining feeding protocols and feeding intolerance consistently for all infants. Infants should be stratified according to birth weight and gestation, and possibly according to illness.

Fortification of Human Milk With Infant Formula for Very Low Birth Weight Preterm Infants: A Systematic Review

Off-label fortification of expressed human milk (HM) with infant milk formula (IMF) is common in developing countries, though its benefits and safety are unclear. To study the effects of IMF fortification of HM on growth of very low birth weight (VLBW) preterm infants. Systematic review and meta-analysis of randomized and quasi-randomized controlled trials (RCTs). MEDLINE, EMBASE, CINAHL, CENTRAL and other databases were searched for articles published in English language from inception to December 2019, evaluating the effects of HM fortified with IMF as intervention, compared to unfortified HM or HM fortified with human milk fortifier (HMF). Five RCTs including 423 VLBW preterm infants. Feeding with HM fortified with IMF compared to unfortified or HMF-fortified HM. Primary outcome measure was assessment of growth as weight, length and head circumference (HC) gain velocity. Secondary outcome measures were incidences of feed intolerance (FI), necrotizing enterocolitis (NEC), time to reach full feeds, concentration of nutritional biomarkers, duration of hospital-stay and cost of intervention. Of the five studies included in the review, pooled effects regarding weight gain velocity (SMD 0.27 g/day; 95% CI 0.08 to 0.62), length gain (MD 0.07cm/week; 95% CI 0.02 to 0.16) and HC gain (MD 0.05 cm/wk; 95% CI 0.01 to 0.11), were not statistically significant. Sensitivity analysis by pooling studies using unfortified milk as comparator yielded a statistically significant result for all growth parameters. Risk of FI or NEC was comparable. Length of hospitalstay was reduced in the intervention group. A very-low quality evidence suggested that IMF fortification of HM is superior to unfortified milk and may be a safe alternative for HMF for short term growth of VLBW preterm infants.

High versus low medium chain triglyceride content of formula for promoting short-term growth of preterm infants.

In-hospital growth of preterm infants remains a challenge in clinical practice. The high nutrient demands of preterm infants often lead to growth faltering.For preterm infants who cannot be fed maternal or donor breastmilk or may require supplementation, preterm formulas with fat in the form of medium chain triglycerides (MCTs)or long chain triglycerides (LCTs)may be chosen to support nutrient utilization and to improve growth.MCTs are easily accessible to the preterm infant with an immature digestive system, and LCTs are beneficial for central nervoussystem development and visual function. Both have been incorporated into preterm formulas in varying amounts, but their effects on the preterm infant's short-term growth remain unclear. This is an update of a review originally published in 2002, then in 2007. To determine the effects of formula containing high as opposed to low MCTs on early growth in preterm infants fed a diet consisting primarily of formula. SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search Cochrane Central Register of Controlled Trials (CENTRAL; 2020, Issue 8), in the Cochrane Library; Ovid MEDLINE Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily, and Ovid MEDLINE(R); MEDLINE via PubMed for the previous year; and Cumulative Index to Nursing and Allied Health Literature (CINAHL), on 16 September 2020. We also searched clinical trials databases and the reference lists of retrieved articles for randomized controlled trials (RCTs) and quasi-RCTs. We included all randomized and quasi-randomized trials comparing the effects of feeding high versus low MCT formula (for a minimum of five days) on the short-term growth of preterm (< 37 weeks' gestation) infants. We defined high MCT formula as 30% or more by weight, and low MCT formula as less than 30% by weight. The infants must be on full enteral diets, and the allocated formula must be the predominant source of nutrition. The review authors assessed each study's quality and extracted data on growth parameters as well as adverse effects from included studies. All data used in analysis were continuous; therefore, mean differences with 95% confidence intervals were reported. We used the GRADE approach to assess the certainty of evidence. We identified 10 eligible trials(253infants) and extracted relevant growth data from 7 of these trials (136 infants). These studies were found to provide evidence of very low to low certainty. Risk of bias was noted, as few studies described specific methods for random sequence generation, allocation concealment, orblinding.We found no evidence of differences in short-term growth parameters when high and low MCT formulas were compared. As compared to low MCT formula, preterm infants fed high MCT formula showed little to no difference in weight gain velocity (g/kg/d) during the intervention, with a typical mean difference (MD) of -0.21g/kg/d (95% confidence interval (CI) -1.24 to 0.83; 6 studies, 118 infants; low-certainty evidence). The analysis for weight gain (g/d) did not show evidence of differences, with an MD of 0.00 g/d(95% CI -5.93 to 5.93;1 study,18 infants;very low-certainty evidence),finding an average weight gain of 20±5.9 versus 20±6.9 g/d for high and low MCT groups, respectively.We found that length gain showedno difference between low and high MCT formulas, with a typical MD of 0.10cm/week (95% CI -0.09 to 0.29; 3 studies, 61 infants; very low-certainty evidence).Head circumference gain also showed little to no difference during the intervention period, with an MD of-0.04 cm/week (95% CI -0.17 to0.09; 3 studies, 61 infants; low-certainty evidence). Two studies reported skinfold thickness with different measurement definitions, and evidence was insufficient to determine if there was a difference(2studies, 32infants; very low-certainty evidence).There are conflicting data (5studies) as to formula tolerance, with 4 studies reporting narrative results ofno observed clinical difference and 1 study reporting higher incidence of signs ofgastrointestinal intolerancein high MCT formula groups.There is no evidence of effect on the incidence ofnecrotizingenterocolitis(NEC), based on small numbers in two trials.Review authors found no studies addressinglong-term growth parameters or neurodevelopmental outcomes. We found evidence of very low to lowcertainty suggesting no differences among short-term growth data for infants fedlow versushigh MCT formulas. Due to lack of evidence and uncertainty, neither formula type could be concluded to improve short-term growth outcomes or have feweradverse effects. Further studies are necessary because the results from includedstudies are imprecise due to small numbers and do not address important long-term outcomes. Additional research should aim to clarify effects on formula tolerance and on long-term growth and neurodevelopmental outcomes, and should include larger study populations to better evaluate effect on NEC incidence.

In-hospital Growth of Very Low Birth Weight Preterm Infants: Comparative Effectiveness of 2 Human Milk Fortifiers.

Amidst a high prevalence of prematurity, limited research on the growth of very low birth weight (VLBW) preterm infants and the availability of a reformulated fortifier c(RF), the study aimed to compare in-hospital growth of such infants receiving exclusively human milk fortified with either of 2 different formulations in a tertiary South African hospital. In a prospective comparative effectiveness design, intakes and growth of VLBW infants on the Original Fortifier (OF; 2016-2017) were compared with those receiving RF (2017-2018). Daily intake was calculated using published composition of preterm and mature milk with fortifier (OF: 0.2 g protein, 3.5kcal/g powder; RF: 0.4 g protein, 4.4 kcal/g powder). Change in z scores from start to end of fortification for weight (WFAZ), length (LFAZ), and head circumference (HCFAZ) for age was the primary outcome. Additionally, weight gain velocity (g · kg-1 · day-1) and gain in length and head circumference (HC) (cm/week) were calculated. Fifty-eight infants (52% girls; gestational age: 30 ± 2 weeks; birth weight: 1215 ± 187 g) received OF for 16 days and 59 infants (56% girls; gestational age: 29 ± 2 weeks; birth weight 1202 ± 167 g) received RF for 15 days. Protein intake of RF (3.7 ± 0.4 g · kg-1 · day-1) was significantly higher (P < 0.001) than of OF (3.4 ± 0.2 g · kg-1 · day-1). Protein-to-energy ratio of RF (2.6 ± 0.2 g/100 kcal) was significantly higher (P < 0.001) than of OF (2.3 ± 0.1 g/100 kcal). In both groups, WFAZ and LFAZ decreased; HCFAZ improved slightly. No significant differences (P > 0.05) were noted between the 2 groups for change in z scores, weight gain velocity, length or HC gain. Despite a modest increase in protein intake and protein-to-energy ratio, the growth of VLBW infants on RF was not better than on OF during their hospital stay.

Vitamin D Status of Very Low Birth Weight Neonates at Baseline and Follow-up after Daily Intake of 800 IU Vitamin D.

Vitamin D deficiency (VDD) is rampant in neonates. Recommendations for supplementation are variable. An observational study was done on less than 32 weeks of very low birth weight neonates to find prevalence of VDD (<20 ng/ml) at baseline; at 38 ± 2 weeks post-menstrual age (PMA) after daily intake of 800 IU vitamin D (vit D). Secondary objectives were to find determinants of VDD, to compare growth in deficient; vit D sufficient (VDS) neonates; to find vit D toxicity. Of 83 neonates, 81 (97.6%) were VDD at baseline and 5 (6%) at 38 ± 2 weeks PMA. Determinants for VDD at baseline were inadequate maternal sun exposure (p < 0.001) and vit D supplementation (p = 0.007). Factors for VDD at 38 ± 2 weeks PMA were male gender (p = 0.049), morbidities (p = 0.006), ventilation >24 h (<0.001), sepsis (p = 0.032), caffeine (p ≤ 0.001) and missed supplements (p < 0.001). Weight and length gain of VDD to VDS neonates were (6.70 ± 2.40 to 8.96 ± 2.21 g/day); (0.82 ± 0.34 to 1.08 ± 0.37 cm/week), respectively (p < 0.001). Head circumference gain (cm/week) of VDS; VDD neonates was 0.58 ± 0.09; 0.54 ± 0.06 (p = 0.054), respectively. No neonates developed vit D toxicity. In preterm VLBW neonates, the prevalence of VDD was 97.6% but decreased by >90% at 38 ± 2 weeks with a daily intake of 800 IU vit D. Inadequate maternal vit D intake and sun exposure determined low baseline vit D status of neonates. Male gender, morbidities, ventilation, sepsis, caffeine, missed vitamin D supplements were determinants of poor vit D status at follow-up. Weight gain and length increments were more in the VDS group.

Individualized versus standard diet fortification for growth and development in preterm infants receiving human milk.

Human milk as compared to formula reduces morbidity in preterm infants but requires fortification to meet their nutritional needs and to reduce the risk of extrauterine growth failure. Standard fortification methods are not individualized to the infant and assume that breast milk is uniform in nutritional content. Strategies for individualizing fortification are available; however it is not known whether these are safe, or if they improve outcomes in preterm infants. To determine whether individualizing fortification of breast milk feeds in response to infant blood urea nitrogen (adjustable fortification) or to breast milk macronutrient content as measured with a milk analyzer (targeted fortification) reduces mortality and morbidity and promotes growth and development compared to standard, non-individualized fortification for preterm infants receiving human milk at < 37 weeks' gestation or at birth weight < 2500 grams. We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 9), in the Cochrane Library; Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Daily and Versions(R); and the Cumulative Index to Nursing and Allied Health Literature (CINAHL), on September 20, 2019. We also searched clinical trials databases and the reference lists of retrieved articles for pertinent randomized controlled trials (RCTs) and quasi-randomized trials. We considered randomized, quasi-randomized, and cluster-randomized controlled trials of preterm infants fed exclusively breast milk that compared a standard non-individualized fortification strategy to individualized fortification using a targeted or adjustable strategy. We considered studies that examined any use of fortification in eligible infants for a minimum duration of two weeks, initiated at any time during enteral feeding, and providing any regimen of human milk feeding. Data were collected using the standard methods of Cochrane Neonatal. Two review authors evaluated the quality of the studies and extracted data. We reported analyses of continuous data using mean differences (MDs), and dichotomous data using risk ratios (RRs). We used the GRADE approach to assess the certainty of evidence. Data were extracted from seven RCTs, resulting in eight publications (521 total participants were enrolled among these studies), with duration of study interventions ranging from two to seven weeks. As compared to standard non-individualized fortification, individualized (targeted or adjustable) fortification of enteral feeds probably increased weight gain during the intervention (typical mean difference [MD] 1.88 g/kg/d, 95% confidence interval [CI] 1.26 to 2.50; 6 studies, 345 participants), may have increased length gain during the intervention (typical MD 0.43 mm/d, 95% CI 0.32 to 0.53; 5 studies, 242 participants), and may have increased head circumference gain during the intervention (typical MD 0.14 mm/d, 95% CI 0.06 to 0.23; 5 studies, 242 participants). Compared to standard non-individualized fortification, targeted fortification probably increased weight gain during the intervention (typical MD 1.87 g/kg/d, 95% CI 1.15 to 2.58; 4 studies, 269 participants) and may have increased length gain during the intervention (typical MD 0.45 mm/d, 95% CI 0.32 to 0.57; 3 studies, 166 participants). Adjustable fortification probably increased weight gain during the intervention (typical MD 2.86 g/kg/d, 95% CI 1.69 to 4.03; 3 studies, 96 participants), probably increased gain in length during the intervention (typical MD 0.54 mm/d, 95% CI 0.38 to 0.7; 3 studies, 96 participants), and increased gain in head circumference during the intervention (typical MD 0.36 mm/d, 95% CI 0.21 to 0.5; 3 studies, 96 participants). We are uncertain whether there are differences between individualized versus standard fortification strategies in the incidence of in-hospital mortality, bronchopulmonary dysplasia, necrotizing enterocolitis, culture-proven late-onset bacterial sepsis, retinopathy of prematurity, osteopenia, length of hospital stay, or post-hospital discharge growth. No study reported severe neurodevelopmental disability as an outcome. One study that was published after our literature search was completed is awaiting classification. We found moderate- to low-certainty evidence suggesting that individualized (either targeted or adjustable) fortification of enteral feeds in very low birth weight infants increases growth velocity of weight, length, and head circumference during the intervention compared with standard non-individualized fortification. Evidence showing important in-hospital and post-discharge clinical outcomes was sparse and of very low certainty, precluding inferences regarding safety or clinical benefits beyond short-term growth.

Comparison of different protein concentrations of human milk fortifier for promoting growth and neurological development in preterm infants.

Human milk alone may provide inadequate amounts of protein to meet the growth requirements of preterm infants because of restrictions in the amount of fluid they can tolerate. It has become common practice to feed preterm infants with breast milk fortified with protein and other nutrients but there is debate about the optimal concentration of protein in commercially available fortifiers. To compare the effects of different protein concentrations in human milk fortifier, fed to preterm infants, on growth and neurodevelopment. We used the standard search strategy of Cochrane Neonatal to search CENTRAL (2019, Issue 8), Ovid MEDLINE and CINAHL on 15 August 2019. We also searched clinical trials databases and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. We included all published and unpublished randomised, quasi-randomised and cluster-randomised trials comparing two different concentrations of protein in human milk fortifier. We included preterm infants (less than 37 weeks' gestational age). Participants may have been exclusively fed human milk or have been supplemented with formula. The concentration of protein was classified as low (< 1g protein/100 mL expressed breast milk (EBM)), moderate (≥ 1g to < 1.4g protein/100 mL EBM) or high (≥ 1.4g protein/100 mL EBM). We excluded trials that compared two protein concentrations that fell within the same category. We undertook data collection and analyses using the standard methods of Cochrane Neonatal. Two review authors independently evaluated trials. Primary outcomes included growth, neurodevelopmental outcome and mortality. Data were synthesised using risk ratios (RR), risk differences and mean differences (MD), with 95% confidence intervals (CI). We used the GRADE approach to assess the certainty of the evidence. We identified nine trials involving 861 infants. There is one trial awaiting classification, and nine ongoing trials. The trials were mostly conducted in infants born < 32 weeks' gestational age or < 1500 g birthweight, or both. All used a fortifier derived from bovine milk. Two trials fed infants exclusively with mother's own milk, three trials gave supplementary feeds with donor human milk and four trials supplemented with preterm infant formula. Overall, trials were small but generally at low or unclear risk of bias. High versus moderate protein concentration of human milk fortifier There was moderate certainty evidence that a high protein concentration likely increased in-hospital weight gain compared to moderate concentration of human milk fortifier (MD 0.66 g/kg/day, 95% CI 0.51 to 0.82; trials = 6, participants = 606). The evidence was very uncertain about the effect of high versus moderate protein concentration on length gain (MD 0.01 cm/week, 95% CI -0.01 to 0.03; trials = 5, participants = 547; very low certainty evidence) and head circumference gain (MD 0.00 cm/week, 95% CI -0.01 to 0.02; trials = 5, participants = 549; very low certainty evidence). Only one trial reported neonatal mortality, with no deaths in either group (participants = 45). Moderate versus low protein concentration of human milk fortifier A moderate versus low protein concentration fortifier may increase weight gain (MD 2.08 g/kg/day, 95% CI 0.38 to 3.77; trials = 2, participants = 176; very low certainty evidence) with little to no effect on head circumference gain (MD 0.13 cm/week, 95% CI 0.00 to 0.26; I² = 85%; trials = 3, participants = 217; very low certainty evidence), but the evidence is very uncertain. There was low certainty evidence that a moderate protein concentration may increase length gain (MD 0.09 cm/week, 95% CI 0.05 to 0.14; trials = 3, participants = 217). Only one trial reported mortality and found no difference between groups (RR 0.48, 95% CI 0.05 to 5.17; participants = 112). No trials reported long term growth or neurodevelopmental outcomes including cerebral palsy and developmental delay. Feeding preterm infants with a human milk fortifier containing high amounts of protein (≥ 1.4g/100 mL EBM) compared with a fortifier containing moderate protein concentration (≥ 1 g to < 1.4 g/100 mL EBM) results in small increases in weight gain during the neonatal admission. There may also be small increases in weight and length gain when infants are fed a fortifier containing moderate versus low protein concentration (< 1 g protein/100 mL EBM). The certainty of this evidence is very low to moderate; therefore, results may change when the findings of ongoing studies are available. There is insufficient evidence to assess the impact of protein concentration on adverse effects or long term outcomes such as neurodevelopment. Further trials are needed to determine whether modest increases in weight gain observed with higher protein concentration fortifiers are associated with benefits or harms to long term growth and neurodevelopment.

Kangaroo Mother Care –Differences and Quantitative Benefits in Different Subgroups of Low Birth Weight Babies

Objectives: To determine the effectiveness of Kangaroo Mother Care in subgroups of LBW babies-Preterm AGA, Preterm SGA and Term SGA, To assess any differences in benefits of KMC in relation to duration in the subgroups, To assess weight gain difference in NICU and at home at first follow up visit and up to 40 weeks of follow up to Preterm AGA, Preterm SGA and till gain of 2500g in Term SGA babies. Study design: Prospective observational study. Setting: NICU in a large teaching institute, department of pediatrics, Mahatma Gandhi Memorial Hospital, North Telangana. Subjects and Methods: 240 neonates with birth weight &lt;2500g, hemodynamically stable. Intervention: The subjects are classified into three subgroups-based on gestational age (by new Ballard’s score) and by weight (Lubchenco’ s charts) into Preterm Appropriate for gestational age (PT AGA) (102), Preterm Small for Gestational Age (PT SGA) (88) and Term Small for Gestational age (T SGA) (50). Further categorized into &lt;=32 wks,33-34wks,35- 36wks,&gt;=37wks.KMC was given to all subgroups at hospital and home with mean duration of 9+2hrs at hospital and 5+2hrs at home. Outcome Measures: Growth measured by average daily weight gain, mean weight gain, (weight was measured by electronic weighing scale (seca), head circumference (measured by non-stretchable and non-metallic tape) and total length (measured by infant meter) in follow up to 40 weeks of corrected gestational age in Preterm and up to gain of 2500g in Term SGA were assessed with KMC. Results: Better weight gain was noticed in all the 3 subgroups of LBW neonates with KMC at hospital and home. In spite of lower duration of KMC at home PT AGA (33-34 weeks) subgroup has the highest weight gain (24.5+5.5g/day, p=0.003), highest head circumference gain (0.70+0.5cm/week, p=0.002), highest length gain (0.90+0.6cm/week, p &lt;0.008). The time taken to reach full feeds and the time to reach initiation of direct breastfeeds were comparable in all subgroups but attained much earlier in PT AGA (33-34wks) and PT AGA (35-36wks). Duration of hospital stay is least in PT AGA with mean of 12.68 ± 6.37 days.KMC significantly reduced the incidence of apnea in all subgroups of LBW babies. All babies were on exclusive breastfeeds at the end of the study (98%). Conclusion: We conclude by this present study that KMC improves growth in all sub groups of LBW infants. KMC has significantly reduced the incidence of co mortifies like apnea, hypothermia, hypoglycemia in all the subgroups of LBW babies. KMC is cost effective, easily accessible and acceptable not only to mothers but also by majority of the family members

Effect of 100% human milk-derived fortifier on growth of premature infants with birth weight of 1000–1500 g

Background: Preterm birth has the highest risk of perinatal morbidity and mortality. Nutrition plays a key role in the growth and development of a preterm infant. Fortification of expressed breast milk is followed to provide an optimal nutrition and a faster catch up growth. The new 100% human milk-derived fortifier (HMDF) can help in providing a safe nutritional option for a premature infant. Objective: The objective of the study was to assess the feed tolerance and impact of a new 100% HMDF on growth outcomes of preterm infants. Materials and Methods: In a single-center study, exclusively human milk-fed preterm infants (1000–1500 g birth weight) were chosen to receive human milk fortified with a new 100% HMDF. The fortifier was initiated when the enteral feed volume reached 100 ml/kg/day and was administered until discharge. The primary outcome of the study was to assess feed tolerance and the secondary endpoints included growth parameters. Results: The cohort study comprised 13 infants with a mean gestational age of 31.64±2.2 weeks and birth weight of 1314.62±110.1 g. During the study period, feed interruptions were nil and none of the infants showed any adverse events of clinical significance. Growth outcomes recorded at the end of the study period showed a mean weight gain of 25.97±7.7 g/day, mean length gain of 0.32±0.23 cm/week, and mean head circumference gain of 0.39±0.20 cm/week. The mean weight growth velocity of the infants was 18.37±5.1 g/kg/day. Conclusion: Preterm infants who received a new 100% HMDF demonstrated feed tolerance and weight gain without any clinically significant record of adverse events. The findings indicate that the new HMDF is a safe option for providing an exclusive human milk-based diet. However, a study with a larger study population may be required to reinforce the findings of this study.