Maternal vaccination against COVID-19 and neonatal outcomes during Omicron: INTERCOVID-2022 study.

BACKGROUND: In early 2023, when Omicron was the variant of concern, we showed that vaccinating pregnant women decreased the risk for severe COVID-19-related complications and maternal morbidity and mortality. OBJECTIVE: This study aimed to analyze the impact of COVID-19 during pregnancy on newborns and the effects of maternal COVID-19 vaccination on neonatal outcomes when Omicron was the variant of concern. STUDY DESIGN: INTERCOVID-2022 was a large, prospective, observational study, conducted in 40 hospitals across 18 countries, from November 27, 2021 (the day after the World Health Organization declared Omicron the variant of concern) to June 30, 2022, to assess the effect of COVID-19 in pregnancy on maternal and neonatal outcomes and to assess vaccine effectiveness. Women diagnosed with laboratory-confirmed COVID-19 during pregnancy were compared with 2 nondiagnosed, unmatched women recruited concomitantly and consecutively during pregnancy or at delivery. Mother-newborn dyads were followed until hospital discharge. The primary outcomes were a neonatal positive test for COVID-19, severe neonatal morbidity index, severe perinatal morbidity and mortality index, preterm birth, neonatal death, referral to neonatal intensive care unit, and diseases during the neonatal period. Vaccine effectiveness was estimated with adjustment for maternal risk profile. RESULTS: We enrolled 4707 neonates born to 1577 (33.5%) mothers diagnosed with COVID-19 and 3130 (66.5%) nondiagnosed mothers. Among the diagnosed mothers, 642 (40.7%) were not vaccinated, 147 (9.3%) were partially vaccinated, 551 (34.9%) were completely vaccinated, and 237 (15.0%) also had a booster vaccine. Neonates of booster-vaccinated mothers had less than half (relative risk, 0.46; 95% confidence interval, 0.23-0.91) the risk of being diagnosed with COVID-19 when compared with those of unvaccinated mothers; they also had the lowest rates of preterm birth, medically indicated preterm birth, respiratory distress syndrome, and number of days in the neonatal intensive care unit. Newborns of unvaccinated mothers had double the risk for neonatal death (relative risk, 2.06; 95% confidence interval, 1.06-4.00) when compared with those of nondiagnosed mothers. Vaccination was not associated with any congenital malformations. Although all vaccines provided protection against neonatal test positivity, newborns of booster-vaccinated mothers had the highest vaccine effectiveness (64%; 95% confidence interval, 10%-86%). Vaccine effectiveness was not as high for messenger RNA vaccines only. Vaccine effectiveness against moderate or severe neonatal outcomes was much lower, namely 13% in the booster-vaccinated group (all vaccines) and 25% and 28% in the completely and booster-vaccinated groups, respectively (messenger RNA vaccines only). Vaccines were fairly effective in protecting neonates when given to pregnant women ≤100 days (14 weeks) before birth; thereafter, the risk increased and was much higher after 200 days (29 weeks). Finally, none of the neonatal practices studied, including skin-to-skin contact and direct breastfeeding, increased the risk for infecting newborns. CONCLUSION: When Omicron was the variant of concern, newborns of unvaccinated mothers had an increased risk for neonatal death. Neonates of vaccinated mothers had a decreased risk for preterm birth and adverse neonatal outcomes. Because the protective effect of COVID-19 vaccination decreases with time, to ensure that newborns are maximally protected against COVID-19, mothers should receive a vaccine or booster dose no more than 14 weeks before the expected date of delivery.

Conflict between parents, physicians, and healthcare professionals in medical decision-making: How to address it-A systematic review from the ESPGHAN Ethics Committee.

Medical decisions about pediatric gastroenterology pathologies often involve collaboration between the medical team and the family. On occasions, conflict may arise between the individuals involved in decision making (team-family conflict) causing delays in managing a child's health condition. Little is known on the strategies that can be implemented to address such conflicts. Using the systematic review model by McCullough et al., an electronic literature search was conducted using PUBMED databases and SCOPUS. Studies published between 2001 and 2022 were analyzed to identify high-risk families, the barriers and facilitators involved in the team-family conflict and the circumstances in which healthcare professionals can be ethically justified to override parents' medical decisions and to trigger the state intervention. The present review provides recommendations on the more suitable ways to manage team-family conflict and gives a practical approach using a case vignette.

Ethical Considerations Within the ESPGHAN Community.

There are limited data on ethical issues related to the daily practice of members of the European Society for Pediatric Gastroenterology Hepatology and Nutrition (ESPGHAN). The role of the ESPGHAN Ethics Committee (EC) is to provide advice on such matters to its members. The present survey aimed to evaluate the current function, and reasons that ESPGHAN members consulted the ECs. One hundred and five participants from 24 different countries answered the questionnaire. Thirty-five point seven percent of the participants used the ESGHAN EC to ask about clinical practice problems and patient-related issues whereas 21.4% ask about human research questions. An important additional finding was that 66.3% of respondents consulted their hospital's EC when they had ethical concerns and 17.4% consulted with other colleagues with expertise. This is the first survey in the ESPGHAN and Europe that analyses ethical issues that are important to members of the National Societies for Pediatric Gastroenterology Hepatology and Nutrition.

Assessment of pregnancy dietary intake and association with maternal and neonatal outcomes.

BACKGROUND: Maternal dietary habits are contributors of maternal and fetal health; however, available data are heterogeneous and not conclusive. METHODS: Nutrient intake during pregnancy was assessed in 503 women with uncomplicated pregnancies, using the validated Food Frequency Questionnaire developed by the European Prospective Investigation into Cancer and Nutrition (EPIC-FFQ). RESULTS: In all, 68% of women had a normal body mass index at the beginning of pregnancy, and 83% of newborns had an appropriate weight for gestational age. Maternal pre-pregnancy body mass index (BMI), gestational weight gain (GWG), and placental weight were independently correlated with birth weight. GWG was not related to the pre-pregnancy BMI. EPIC-FFQ evaluation showed that 30% of women adhered to the European Food Safety Authority (EFSA) ranges for macronutrient intake. In most pregnant women (98.1%), consumption of water was below recommendations. Comparing women with intakes within EFSA ranges for macronutrients with those who did not, no differences were found in BMI, GWG, and neonatal or placental weight. Neither maternal nor neonatal parameters were associated with the maternal dietary profiles. CONCLUSIONS: In our population, maternal pre-pregnancy BMI, GWG, and placental weight are determinants of birth weight percentile, while no association was found with maternal nutrition. Future studies should explore associations through all infancy. IMPACT: Maternal anthropometrics and nutrition status may affect offspring birth weight. In 503 healthy women, maternal pre-pregnancy body mass index (BMI), gestational weight gain (GWG), and placental weight were independently correlated to neonatal birth weight. GWG was not related to the pre-pregnancy BMI. In all, 30% of women respected the EFSA ranges for macronutrients. Neither maternal nor neonatal parameters were associated with maternal dietary profiles considered in this study. Maternal pre-pregnancy BMI, GWG, and placental weight are determinants of neonatal birth weight percentile, while a connection with maternal nutrition profiles was not found.

COVID-19 pandemic in the neonatal intensive care unit: any effect on late-onset sepsis and necrotizing enterocolitis?

The study was aimed at describing potential indirect effects of pandemic-related measures on very-low-birthweight infants in four Italian NICUs. No overall change in late-onset sepsis (LOS) and necrotizing enterocolitis was documented. However, in the NICU where baseline LOS rate was high, a significant reduction in LOS incidence was recorded. Conclusion: COVID-19-related implementation of NICU hygiene policies is likely to reduce the occurrence of LOS in high-risk settings. What is Known: • COVID-19 pandemic has disrupted routine care in Neonatal Intensive Care Units (NICUs), mostly by tightening infection control measures and restricting parental presence in the NICU. • Beyond the described psychological impact of COVID-19 related measures on healthcare workers and NICU families, their consequences in terms of preterm infants' clinical outcomes have not been described in detail yet. What is New: • Strengthened infection-control measures do not seem to have an overall influence on the incidence of necrotising enterocolitis and late-onset sepsis in very-low-birth-weight infants. • However, the implementation of these measures appears to reduce the occurrence of late-onset sepsis in settings where the baseline incidence of the disease is high.

Safety and efficacy of a probiotic-containing infant formula supplemented with 2'-fucosyllactose: a double-blind randomized controlled trial.

BACKGROUND: Human milk oligosaccharides (HMOs) have important and diverse biological functions in early life. This study tested the safety and efficacy of a starter infant formula containing Limosilactobacillus (L.) reuteri DSM 17938 and supplemented with 2'-fucosyllactose (2'FL). METHODS: Healthy infants < 14 days old (n = 289) were randomly assigned to a bovine milk-based formula containing L. reuteri DSM 17938 at 1 × 107 CFU/g (control group; CG) or the same formula with added 1.0 g/L 2'FL (experimental group; EG) until 6 months of age. A non-randomized breastfed group served as reference (BF; n = 60). The primary endpoint was weight gain through 4 months of age in the formula-fed infants. Secondary endpoints included additional anthropometric measures, gastrointestinal tolerance, stooling characteristics, adverse events (AEs), fecal microbiota and metabolism, and gut immunity and health biomarkers in all feeding groups. RESULTS: Weight gain in EG was non-inferior to CG as shown by a mean difference [95% CI] of 0.26 [-1.26, 1.79] g/day with the lower bound of the 95% CI above the non-inferiority margin (-3 g/day). Anthropometric Z-scores, parent-reported stooling characteristics, gastrointestinal symptoms and associated behaviors, and AEs were comparable between formula groups. Redundancy analysis indicated that the microbiota composition in EG was different from CG at age 2 (p = 0.050) and 3 months (p = 0.052), approaching BF. Similarly, between sample phylogenetic distance (weighted UniFrac) for BF vs EG was smaller than for BF vs CG at 3-month age (p = 0.045). At age 1 month, Clostridioides difficile counts were significantly lower in EG than CG. Bifidobacterium relative abundance in EG tracked towards that in BF. Fecal biomarkers and metabolic profile were comparable between CG and EG. CONCLUSION: L. reuteri-containing infant formula with 2'FL supports age-appropriate growth, is well-tolerated and may play a role in shifting the gut microbial pattern towards that of breastfed infants. TRIAL REGISTRATION: The trial was registered on ClinicalTrials.gov ( NCT03090360 ) on 24/03/2017.

Don't Forget the Bones: Incidence and Risk Factors of Metabolic Bone Disease in a Cohort of Preterm Infants.

Metabolic bone disease of prematurity (MBD) is a condition of reduced bone mineral content (BMC) compared to that expected for gestational age (GA). Preterm birth interrupts the physiological process of calcium (Ca) and phosphorus (P) deposition that occurs mostly in the third trimester of pregnancy, leading to an inadequate bone mineralization during intrauterine life (IUL). After birth, an insufficient intake of Ca and P carries on this alteration, resulting in overt disease. If MBD is often a self-limited condition, in some cases it could hesitate the permanent alteration of bone structures with growth faltering and failure to wean off mechanical ventilation due to excessive chest wall compliance. Despite advances in neonatal intensive care, MBD is still frequent in preterm infants, with an incidence of 16−23% in very-low-birth-weight (VLBW, birth weight <1500 g) and 40−60% in extremely low-birth-weight (ELBW, birth weight <1000 g) infants. Several risk factors are associated with MBD (e.g., malabsorption syndrome, parenteral nutrition (PN), pulmonary bronchodysplasia (BPD), necrotizing enterocolitis (NEC), and some chronic medications). The aim of this study was to evaluate the rate of MBD in a cohort of VLBWI and the role of some risk factors. We enrolled 238 VLBWIs (107 male). 52 subjects were classified as increased risk (G1) and 186 as standard risk (G2) according to serum alkaline phosphatase (ALP) and phosphorus (P) levels. G1 subjects have lower GA (p < 0.01) and BW (p < 0.001). Moreover, they need longer PN support (p < 0.05) and invasive ventilation (p < 0.01). G1 presented a higher rate of BPD (p = 0.026). At linear regression analysis, BW and PN resulted as independent predictor of increased risk (p = 0.001, p = 0.040, respectively). Preventive strategies are fundamental to prevent chronic alteration in bone structures and to reduce the risk of short stature. Screening for MBD based on serum ALP could be helpful in clinical practice to identify subjects at increased risk.

How does gestational age affect growth and body composition of preterm twins?

BACKGROUND: Twins experience altered growth compared to singletons. The primary aim of this study was to compare growth and body composition (BC) of twin and singleton preterm infants from birth to 3 months according to gestational age (GA). Secondary aims were to evaluate the effect of chorionicity and mode of feeding on twins' BC. METHODS: Anthropometric measurements and BC were performed at term and 3 months in preterm infants (GA < 37 weeks). Infants were categorized as: extremely, very, moderate and late preterm infants. Chorionicity was assigned as monochorionic, dichorionic or multichorionic. Mode of feeding was recorded as any human milk feeding vs formula feeding. RESULTS: Five hundred and seventy-six preterm infants were included (223 twins). Late-preterm twins were lighter and shorter at each study point; fat-free mass (FFM) was lower in these infants at each study point, compared to singletons. No differences were found between twins and singleton on the other category. Multichorionic infants had an FFM deficit compared to monochorionic and dichorionic at term, whereas no differences were found at 3 months. FFM at term was negatively associated with being twin and formula-fed. CONCLUSIONS: Twins and singletons born before 34 weeks' GA showed similar anthropometry and BC. Conversely, twin late-preterm infants showed different growth and BC compared to singletons.

Effect of Target Fortification on Osmolality and Microbiological Safety of Human Milk Over Time.

OBJECTIVES: The fortification of human milk can result in increased osmolality, which may be associated with adverse effects for preterm infants. To evaluate the effect of target fortification on the osmolality and microbiological safety of donor human milk and raw mature milk during the first 72 hours of storage. METHODS: We performed target fortification of 63 pasteurized donor human milk (PDHM) and 54 raw mature milk (RMM) samples in a laminar flow hood. Osmolality (mOsm/kg) was evaluated before fortification (T0), immediately after fortification (T1), at 6 (T2), 24 (T3), 48 (T4), and 72 hours (T5) after fortification. Microbiological analysis was performed at T0, T4, and T5. During the study, all samples were stored at 4°C. RESULTS: Mean osmolality at each study point for PDHM and RMM were, respectively: T0: 291.4 ±â€Š11.0 versus 288.4 ±â€Š5.6 (P = 0.06); T1: 384.8 ±â€Š16.7 versus 398.3 ±â€Š23.7; T2: 393.9 ±â€Š17.7 versus 410.1 ±â€Š27.0; T3: 397.8 ±â€Š17.6 versus 417.9 ±â€Š26.1; T4: 400.0 ±â€Š16.5 versus 420.2 ±â€Š24.9; T5: 399.6 ±â€Š16.5 versus 425.2 ±â€Š25.8 (P < 0.001 from T1 to T5). Microbiological analyses were negative at each study points for PDHM. At T0 16.1% of RMM samples had positive cultures, whereas the bacterial count remained stable thought the study. CONCLUSIONS: PDHM's osmolality increases during the first 6 hours after fortification and remains stable and safe until 72 hours. RMM's osmolality increases during the first 24 hours and remains stable and safe until 72 hours. The storage at 4°C and the manipulation of PDHM and RMM samples in a laminar flow hood seem to be safe and preserve the microbiological safety of fortified pasteurized human milk until 72 hours.

Human milk protein vs. formula protein and their use in preterm infants.

PURPOSE OF REVIEW: We review the current available evidence on the metabolic fate of human milk proteins and their potential clinical implications for growth and body composition development vs. those of formula proteins in preterm infants. RECENT FINDINGS: The decreased content of human milk protein in preterm mothers throughout lactation might contribute to the reduced growth reported in exclusively human milk-fed infants compared with that of formula-fed infants. Recent studies have demonstrated that preterm infants are capable of degrading human milk proteins regardless of their degree of prematurity or postnatal age, with limited contribution from milk proteases to protein digestion. The nitrogen balance of fortified human milk-fed preterm infants is higher than that of formula-fed preterm infants. Moreover, the growth of human milk-fed preterm infants appears to be accompanied by fat-free mass deposition. SUMMARY: Provided that adequate protein and energy intakes are delivered, human milk enhances protein use rather than oxidation as well as promotes tissue growth, leading to preferential fat-free mass deposition and contributing to the recovery of the body composition in preterm infants. Human milk feeding should be supported and promoted for all preterm mother-infant pairs.

Macronutrient content of pooled donor human milk before and after Holder pasteurization.

BACKGROUND: Donor human milk (DHM) is the best alternative for preterm infants when their own mother's milk is unavailable. DHM should be pasteurized to guarantee microbiological safety; however, this process can influence the macronutrient content. The aim of this study was to investigate the effect of Holder pasteurization (HoP) on DHM macronutrient content. METHODS: Protein, lactose, lipids (g/100 ml) and energy (kcal/100 ml) of DHM pools were analysed before and after HoP (62.5 °C for 30 min) using mid-infrared spectroscopy (HM analyser Miris AB®). The mean macronutrient content before and after HoP was compared by paired t-test. The percentage decreases (Delta%) were calculated. RESULTS: The change in macronutrient content of 460 pools was determined. Protein, lipids and lactose decreased significantly after HoP (0.88 ± 0.20 vs 0.86 ± 0.20 and 2.91 ± 0.89 vs 2.75 ± 0.84 and 7.19 ± 0.41 vs 7.11 ± 0.48 respectively). The Delta% values were - 2.51 ± 13.12, - 4.79 ± 9.47 and - 0.92 ± 5.92 for protein, lipids and lactose, respectively (p ≤ 0.001). CONCLUSION: This study confirms that the macronutrient content of DHM, especially in terms of lipids and protein, is reduced after HoP. Therefore, in order to perform a tailored fortification of DHM, the clinicians need to be aware of the somewhat diminished nutrient content of DHM.

Safety of Oats in Children with Celiac Disease: A Double-Blind, Randomized, Placebo-Controlled Trial.

OBJECTIVE: To evaluate the long-term validity and safety of pure oats in the treatment of children with celiac disease. STUDY DESIGN: This noninferiority clinical trial used a double-blind, placebo-controlled, crossover design extended over 15 months. Three hundred six children with a biopsy-proven diagnosis of celiac disease on a gluten-free diet for ≥2 years were randomly assigned to eat specifically prepared gluten-free food containing an age-dependent amount (15-40 g) of either placebo or purified nonreactive varieties of oats for 2 consecutive 6-month periods separated by washout standard gluten-free diet for 3 months. Clinical (body mass index, Gastrointestinal Symptoms Rating Scale score), serologic (IgA antitransglutaminase antibodies, and IgA anti-avenin antibodies), and intestinal permeability data were measured at baseline, and after 6, 9, and 15 months. Direct treatment effect was evaluated by a nonparametric approach using medians (95% CI) as summary statistic. RESULTS: After the exclusion of 129 patients who dropped out, the cohort included 177 children (79 in the oats-placebo and 98 in the placebo-oats group; median, 0.004; 95% CI, -0.0002 to 0.0089). Direct treatment effect was not statistically significant for clinical, serologic, and intestinal permeability variables (body mass index: median, -0.5; 95% CI, -0.12 to 0.00; Gastrointestinal Symptoms Rating Scale score: median, 0; 95% CI, -2.5 to 0.00; IgA antitransglutaminase antibodies: median, -0.02; 95% CI, -0.25 to 0.23; IgA anti-avenin antibodies: median, -0.0002; 95% CI, -0.0007 to 0.0003; intestinal permeability test: median, 0.004; 95% CI, -0.0002 to 0.0089). CONCLUSIONS: Pure nonreactive oat products are a safe dietary choice in the treatment of children with celiac disease. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00808301.

Can Basic Characteristics Estimate Body Composition in Early Infancy?

OBJECTIVES: Increasing evidence demonstrates that body composition in early life contributes to the programming of health later in life in both full-term and preterm infants. Given the important role of body composition, the increased availability of easy, noninvasive, and accurate techniques for its assessment has been recommended. The aim of the present study was to identify basic characteristics and anthropometric measurements that best correlate with body composition in infants. METHODS: Anthropometric measurements and body composition assessed by air-displacement plethysmography were assessed either at birth or at term-corrected age in 1239 infants (654 full-term, 585 preterm). The associations of sex, GA (gestational age), and weight with FFM (fat-free mass) and FM (fat mass) adjusted by length (g/cm) were investigated by multiple linear regression models. Bland-Altman tests were performed, and an equation for calculating FFM was determined. RESULTS: Preterm infants exhibited increased FM and reduced FFM compared with full-term infants (477.6 ±â€Š204 vs 259.7 ±â€Š147 g and 2583 ±â€Š494 vs 2770 ±â€Š364 g, respectively). GA, male sex, and weight were positively associated with FFM (r = 0.806, P < 0.0001; 6.1 g of average bias). GA and male sex were negatively associated with FM, whereas weight was positively associated with FM (r = 0.641, P < 0.0001; 4.9 g of average bias). CONCLUSIONS: The assessment of body composition represents the criterion standard. When body composition assessment is not feasible, the equation based on sex, GA, and anthropometric measurements can be useful in predicting body composition in both full-term and preterm infants.

Correction to: Clinical evaluation of two different protein content formulas fed to full-term healthy infants: a randomized controlled trial.

Following the publication of the original article [1], it was brought to our attention that the authors' names and surnames were erroneously interchanged.

Maternal views on facilitators of and barriers to breastfeeding preterm infants.

BACKGROUND: The supply of breast milk to preterm infants tends to occur at a lower rate than that recorded among term infants. We aimed to investigate the facilitators of and barriers to breastfeeding during hospital stay according to the experiences of mothers that gave birth to premature infants requiring admission to neonatal intensive care unit. METHODS: A cross-sectional questionnaire survey was conducted. Mothers who had delivered a newborn with a gestational age ≤33 weeks requiring intensive care, entered the study. Basic subjects' characteristics and infant feeding practices were also recorded. RESULTS: A total of 64 mothers were enrolled, leading to a total of 81 infants. At discharge, any breastfeeding was recorded in 66% of infants, with 27% of those infants being exclusively breastfed. Any infant was exclusively fed directly at the breast. Most mothers experienced adequate support during their infant's hospitalization and reported satisfaction with breastfeeding. Almost all mothers felt that feeding their infant human milk was beneficial for the infant's health. Thirty percent of the mothers reported that they had experienced some obstacles to breastfeeding. Specifically, infants born to mothers who experienced difficulties in pumping breast milk (OR = 4.6; CI 1.5-13.9) or in providing an adequate amount of milk to the infant (OR = 3.57; CI 1.1-11.5) were at higher risk of being fed with formula at discharge. CONCLUSIONS: On the basis of the present results, health care professionals should target their efforts to optimize breastfeeding support for mothers of premature infants admitted to level III care, especially by improving breast milk production and endorsing direct breastfeeding.

An infant formula containing dairy lipids increased red blood cell membrane Omega 3 fatty acids in 4 month-old healthy newborns: a randomized controlled trial.

BACKGROUND: When breastfeeding is not possible, infants are fed formulas (IF) in which lipids are usually of plant origin. However, the use of dairy fat in combination with plant oils enables a lipid profile closer to breast milk in terms of fatty acid (FA) composition, triglyceride structure, polar lipids and cholesterol contents. The objective of this study was to determine the effect of an IF containing a mix of dairy fat and plant oils on Omega-3 FA content in red blood cells (RBC). METHODS: This study was a monocentric, double-blind, controlled, randomized trial. Healthy term infants were fed formulas containing a mix of dairy fat and plant oils (D), plant oils (P) or plant oils supplemented with ARA and DHA (PDHA). Breastfed infants were enrolled as a reference group (BF). FA in RBC phosphatidylethanolamine was evaluated after 4 months and FA in whole blood were evaluated at enrollment and after 4 months by gas chromatography. Differences between groups were assessed using an analysis of covariance with sex and gestational age as covariates. RESULTS: Seventy IF-fed and nineteen BF infants completed the protocol. At 4 months, RBC total Omega-3 FA levels in infants fed formula D were significantly higher than in group P and similar to those in groups PDHA and BF. RBC DHA levels in group D were also higher than in group P but lower than in groups PDHA and BF. RBC n-3 DPA levels in group D were higher than in groups P, PDHA and BF. A decrease in proportions of Omega-3 FA in whole blood was observed in all groups. CONCLUSIONS: A formula containing a mix of dairy lipids and plant oils increased the endogenous conversion of Omega-3 long-chain FA from precursor, leading to higher total Omega-3, DPA and DHA status in RBC than a plant oil-based formula. Modifying lipid quality in IF by adding dairy lipids should be considered as an interesting method to improve Omega-3 FA status. TRIAL REGISTRATION: Identifier NCT01611649 , retrospectively registered on May 25, 2012.

No effect of adding dairy lipids or long chain polyunsaturated fatty acids on formula tolerance and growth in full term infants: a randomized controlled trial.

BACKGROUND: When breastfeeding is not possible, infants are fed formulas in which lipids are usually of plant origin. However, the use of dairy fat in combination with plant oils enables a lipid profile in formula closer to breast milk in terms of fatty acid composition, triglyceride structure and cholesterol content. The objectives of this study were to investigate the impact on growth and gastrointestinal tolerance of a formula containing a mix of dairy lipids and plant oils in healthy infants. METHODS: This study was a monocentric, double-blind, controlled, randomized trial. Healthy term infants aged less than 3 weeks whose mothers did not breastfeed were randomly allocated to formula containing either: a mix of plant oils and dairy fat (D), only plant oils (P) or plant oils supplemented with long-chain polyunsaturated fatty acids (PDHA). Breastfed infants were included in a reference group (BF). Anthropometric parameters and body composition were measured after 2 and 4 months. Gastrointestinal tolerance was evaluated during 2 day-periods after 1 and 3 months thanks to descriptive parameters reported by parents. Nonrandomized BF infants were not included in the statistical analysis. RESULTS: Eighty eight formula-fed and 29 BF infants were enrolled. Gains of weight, recumbent length, cranial circumference and fat mass were similar between the 3 formula-fed groups at 2 and 4 months and close to those of BF. Z-scores for weight, recumbent length and cranial circumference in all groups were within normal ranges for growth standards. No significant differences were noted among the 3 formula groups in gastrointestinal parameters (stool frequency/consistency/color), occurrence of gastrointestinal symptoms (abdominal pain, flatulence, regurgitation) or infant's behavior. CONCLUSIONS: A formula containing a mix of dairy lipids and plant oils enables a normal growth in healthy newborns. This formula is well tolerated and does not lead to abnormal gastrointestinal symptoms. Consequently, reintroduction of dairy lipids could represent an interesting strategy to improve lipid quality in infant formulas. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT01611649 , retrospectively registered on May 25, 2012.

Clinical evaluation of two different protein content formulas fed to full-term healthy infants: a randomized controlled trial.

BACKGROUND: A high early protein intake is associated with rapid postnatal weight gain and altered body composition. We aimed to evaluate the safety of a low-protein formula in healthy full-term infants. METHODS: A randomized controlled trial was conducted. A total of 118 infants were randomized to receive two different protein content formulas (formula A or formula B (protein content: 1.2 vs. 1.7 g/100 mL, respectively)) for the first 4 months of life. Anthropometry and body composition by air displacement plethysmography were assessed at enrolment and at two and 4 months. The reference group comprised 50 healthy, exclusively breastfed, full-term infants. RESULTS: Weight gain (g/day) throughout the study was similar between the formula groups (32.5 ± 6.1 vs. 32.8 ± 6.8) and in the reference group (30.4 ± 5.4). The formula groups showed similar body composition but a different fat-free mass content from breastfed infants at two and 4 months. However, the formula A group showed a fat-free mass increase more similar to that of the breastfed infants. The occurrence of gastrointestinal symptoms or adverse events was similar between the formula groups. CONCLUSIONS: Feeding a low-protein content formula appears to be safe and to promote adequate growth, although determination of the long-term effect on body composition requires further study. TRIAL REGISTRATION: The present study was retrospectively registered in ClinicalTrials.gov (trial number: NCT03035721 on January 18, 2017).

Is targeted fortification of human breast milk an optimal nutrition strategy for preterm infants? An interventional study.

BACKGROUND: Fortifying human milk contributes to the prevention of postnatal growth failure in preterm infants. Because of the natural variability of human milk, targeted fortification of human milk has been advocated. However, data regarding the efficacy and safety of prolonged targeted fortification are scarce. We aimed to assess the safety of targeted fortification of human milk in preterm infants compared with standard fortification, as well as the effects on infant growth. METHODS: We conducted an interventional study during hospital stay in healthy very low birth weight preterm infants who were exclusively fed human milk. Pools of human milk collected for 24 h were analysed using mid-infrared transmission spectroscopy. Targeted fortification of human milk was performed by adding macronutrients to native human milk to obtain optimal ratios of fat (4.4 g), carbohydrates (8.8 g), and protein (3 g) per 100 ml. The intervention period lasted 4-7 weeks. Weekly weight and daily growth rates were compared with those of a standardized fortification group of very low birth weight preterm infants who received standard fortified human milk (n = 10). The osmolality as well as the metabolic and gastrointestinal tolerance were monitored. Intergroup differences were evaluated using the Mann-Whitney U-test. RESULTS: A total of 10 preterm infants (birth weight 1223 ± 195 g; gestational age 29.1 ± 1.03 weeks) were enrolled and 118 samples of pooled milk were analysed. On average, 1.4 ± 0.1 g of protein, 2.3 ± 0.5 g of carbohydrate, and 0.3 ± 0.1 g of fat per 100 ml were added to the milk. Osmolality values after target fortification were within recommended limits (376 ± 66 mOsml/kg). Weekly weight gain (205.5 g; 95 % CI 177-233 vs 155 g; 95 % CI 132-178; p = 0.025) and daily growth rates (15.7 g/kg/day; 95 % CI 14.5-16.9 vs 12.3 g/kg/day; 95 % CI 10.7-13.9; p = 0.005) were higher in infants receiving target fortification than in infants receiving standardized fortification. The infants receiving targeted fortified milk consumed similar volumes as infants in the standardized fortification group (148 ± 4.5 vs 146 ± 4 ml/kg/day). No signs of either gastrointestinal or metabolic intolerance were observed. CONCLUSIONS: Target fortification appears to promote growth in very low birth weight preterm infants without any detrimental effects. Trial registration NCT02716337.

Body composition in late preterm infants according to percentile at birth.

BACKGROUND: The data on body composition of late preterm infants, evaluated according to percentile at birth, are scarce. The study aimed to investigate body composition of late preterm infants, according to percentile at birth, and to compare their body composition with that of term newborns. METHODS: A total of 122 (99 appropriate and 23 small for gestational age (SGA)) late preterm infants underwent growth and body composition assessment using an air displacement plethysmography system on the fifth day of life and at term. The reference group was composed of 42 healthy, term, breast-fed infants. RESULTS: At birth, appropriate and SGA late preterm infants had lower fat mass and fat-free mass indexes than term newborns. The fat mass and fat-free mass content increased significantly throughout the study, irrespective of percentile at birth. At term, fat mass index, but not fat-free mass index, was higher in both appropriate and SGA late preterm infants than in term newborns. CONCLUSION: Late preterm infants, irrespective of their percentile at birth, show postnatal growth characterized by predominant fat mass accretion. The potential long-term health clinical implications of these findings need to be further elucidated.