Lack of arachidonic acid (AA) and docosahexaenoic acid (DHA) after extremely preterm birth may contribute to preterm morbidity, including retinopathy of prematurity (ROP).
To determine whether ...enteral supplementation with fatty acids from birth to 40 weeks' postmenstrual age reduces ROP in extremely preterm infants.
The Mega Donna Mega trial, a randomized clinical trial, was a multicenter study performed at 3 university hospitals in Sweden from December 15, 2016, to December 15, 2019. The screening pediatric ophthalmologists were masked to patient groupings. A total of 209 infants born at less than 28 weeks' gestation were tested for eligibility, and 206 infants were included. Efficacy analyses were performed on as-randomized groups on the intention-to-treat population and on the per-protocol population using as-treated groups. Statistical analyses were performed from February to April 2020.
Infants received either supplementation with an enteral oil providing AA (100 mg/kg/d) and DHA (50 mg/kg/d) (AA:DHA group) or no supplementation within 3 days after birth until 40 weeks' postmenstrual age.
The primary outcome was severe ROP (stage 3 and/or type 1). The secondary outcomes were AA and DHA serum levels and rates of other complications of preterm birth.
A total of 101 infants (58 boys 57.4%; mean SD gestational age, 25.5 1.5 weeks) were included in the AA:DHA group, and 105 infants (59 boys 56.2%; mean SD gestational age, 25.5 1.4 weeks) were included in the control group. Treatment with AA and DHA reduced severe ROP compared with the standard of care (16 of 101 15.8% in the AA:DHA group vs 35 of 105 33.3% in the control group; adjusted relative risk, 0.50 95% CI, 0.28-0.91; P = .02). The AA:DHA group had significantly higher fractions of AA and DHA in serum phospholipids compared with controls (overall mean difference in AA:DHA group, 0.82 mol% 95% CI, 0.46-1.18 mol%; P < .001; overall mean difference in control group, 0.13 mol% 95% CI, 0.01-0.24 mol%; P = .03). There were no significant differences between the AA:DHA group and the control group in the rates of bronchopulmonary dysplasia (48 of 101 47.5% vs 48 of 105 45.7%) and of any grade of intraventricular hemorrhage (43 of 101 42.6% vs 42 of 105 40.0%). In the AA:DHA group and control group, respectively, sepsis occurred in 42 of 101 infants (41.6%) and 53 of 105 infants (50.5%), serious adverse events occurred in 26 of 101 infants (25.7%) and 26 of 105 infants (24.8%), and 16 of 101 infants (15.8%) and 13 of 106 infants (12.3%) died.
This study found that, compared with standard of care, enteral AA:DHA supplementation lowered the risk of severe ROP by 50% and showed overall higher serum levels of both AA and DHA. Enteral lipid supplementation with AA:DHA is a novel preventive strategy to decrease severe ROP in extremely preterm infants.
ClinicalTrials.gov Identifier: NCT03201588.
Purpose
Human milk (HM) composition is influenced by factors, like maternal diet and body stores, among other factors. For evaluating the influence of maternal fatty acid (FA) status on milk FA ...composition, the correlation between FA content in HM and in maternal plasma, erythrocytes, and adipose tissue was investigated.
Methods
223 European women who delivered at term, provided HM samples over first four months of lactation. Venous blood and adipose tissue (only from mothers who consented and underwent a C-section delivery) were sampled at delivery. FAs were assessed in plasma, erythrocytes, adipose tissue, and HM. Evolution of HM FAs over lactation and correlations between FA content in milk and tissues and between mother’s blood and cord blood were established.
Results
During lactation, arachidonic acid (ARA) and docosahexaenoic acid (DHA) significantly decreased, while linoleic acid (LA), alpha-linolenic acid (ALA), and eicosapentaenoic acid (EPA) remained stable. Positive correlations were observed between HM and adipose tissue for palmitic, stearic, oleic, and polyunsaturated fatty acids (PUFAs). Correlations were found between milk and plasma for oleic, LA, ARA, ALA, DHA, monounsaturated fatty acids (MUFAs), and PUFAs. No correlation was observed between erythrocytes and HM FAs. LA and ALA were more concentrated in maternal blood than in infant blood, contrary to ARA and DHA, supporting that biomagnification of LCPUFAs may have occurred during pregnancy.
Conclusions
These data show that maternal adipose tissue rather than erythrocytes may serve as reservoir of PUFAs and LCPUFAs for human milk. Plasma also supplies PUFAs and LCPUFAs to maternal milk. If both, adipose tissue and plasma PUFAs, are reflection of dietary intake, it is necessary to provide PUFAs and LCPUFAs during pregnancy or even before conception and lactation to ensure availability for mothers and enough supply for the infant via HM.
Aim
Electrolyte balances have not been sufficiently evaluated in extremely preterm infants after early parenteral nutrition. We investigated the risk of early hypophosphatemia and hypokalemia in ...extremely preterm infants born small for gestational age (SGA) who received nutrition as currently recommended.
Methods
This prospective, observational cohort study included all consecutive extremely preterm infants born at 24–27 weeks who received high amino acids and lipid perfusion from birth. We evaluated the electrolyte levels of SGA infants and infants born appropriate for gestational age (AGA) during the first five days of life.
Results
The 12 SGA infants had lower plasma potassium levels from Day One compared to the 36 AGA infants and were more likely to have hypokalemia (58% vs 17%, p = 0.001) and hypophosphatemia (40% vs 9%, p < 0.01) during the five‐day observation period. After adjusting for perinatal factors, SGA remained significantly associated with hypophosphatemia (odds ratio 1.39, confidence intervals 1.07–1.81, p = 0.01).
Conclusion
Extremely preterm infants born SGA who were managed with currently recommended early parenteral nutrition had a high risk of early hypokalemia and hypophosphatemia. Potassium and phosphorus intakes should be set at sufficient levels from birth onwards, especially in SGA infants.
The relationship between human milk oligosaccharides (HMOs) and infant growth and adiposity is not fully understood and comprehensive studies are missing from the current literature.
We screened and ...recruited 370 healthy, pregnant women and their infants from seven European countries. Breastmilk samples were collected using standardized procedures at six time points over 4 months, as were infant parameters. Correlations and associations between HMO area under the curve, anthropometric data, and fat mass at 4 months were tested.
Lacto-N-neotetraose had a negative correlation with the change in length (rs = -0.18, P = 0.02). Sialyllacto-N-tetraose c (LSTc) had a positive correlation with weight for length (rs = 0.19, P = 0.015). Infants at the 25th upper percentile were fed milk higher in 3'-sialyllactose and LSTc (P = 0.017 and P = 0.006, respectively) compared to the lower 25th percentile of the weight-for-length z-score gain over 4 months of lactation. No significant associations between growth and body composition and Lewis or secretor-dependent HMOs like 2'-fucosyllactose were identified.
Changes in the HMO composition of breastmilk during the first 4 months appear to have little influence on infant growth and body composition in this cohort of healthy mothers and infants.
Modest associations exist between individual HMO and infant growth outcomes at least in healthy growing populations. Our study provides a comprehensive investigation of associations between all major HMO and infant growth and adiposity including several time points. Certain groups of HMOs, like the sialylated, may be associated with adiposity during the first months of lactation. HMO may modulate the risk of future metabolic disease. Future population studies need to address the role of specific groups of HMOs in the context of health and disease to understand the long-term impact.
Preterm infants risk deficits of long-chain polyunsaturated fatty acids (LCPUFAs) that may contribute to morbidities and hamper neurodevelopment. We aimed to determine longitudinal serum fatty acid ...profiles in preterm infants and how the profiles are affected by enteral and parenteral lipid sources.
Cohort study analyzing fatty acid data from the Mega Donna Mega study, a randomized control trial with infants born <28 weeks of gestation (n = 204) receiving standard nutrition or daily enteral lipid supplementation with arachidonic acid (AA):docosahexaenoic acid (DHA) (100:50 mg/kg/day). Infants received an intravenous lipid emulsion containing olive oil:soybean oil (4:1). Infants were followed from birth to postmenstrual age 40 weeks. Levels of 31 different fatty acids from serum phospholipids were determined by GC–MS and reported in relative (mol%) and absolute concentration (μmol l−1) units.
Higher parenteral lipid administration resulted in lower serum proportion of AA and DHA relative to other fatty acids during the first 13 weeks of life (p < 0.001 for the 25th vs the 75th percentile). The enteral AA:DHA supplement increased the target fatty acids with little impact on other fatty acids. The absolute concentration of total phospholipid fatty acids changed rapidly in the first weeks of life, peaking at day 3, median (Q1-Q3) 4452 (3645–5466) μmol l−1, and was positively correlated to the intake of parenteral lipids. Overall, infants displayed common fatty acid trajectories over the study period. However, remarkable differences in fatty acid patterns were observed depending on whether levels were expressed in relative or absolute units. For example, the relative levels of many LCPUFAs, including DHA and AA, declined rapidly after birth while their absolute concentrations increased in the first week of life. For DHA, absolute levels were significantly higher compared to cord blood from day 1 until postnatal week 16 (p < 0.001). For AA, absolute postnatal levels were lower compared to cord blood from week 4 throughout the study period (p < 0.05).
Our data show that parenteral lipids aggravate the postnatal loss of LCPUFAs seen in preterm infants and that serum AA available for accretion is below that in utero. Further research is needed to establish optimal postnatal fatty acid supplementation and profiles in extremely preterm infants to promote development and long-term health.
ClinicalTrials.gov, identifier: NCT03201588.
Moderately preterm infants account for a large proportion of admissions and bed-days in neonatal units (NU). Management of these infants varies and determinants of length of stay are poorly studied.
...To determine postmenstrual age at hospital discharge for moderately preterm infants and its relation to perinatal risk factors and to organisation of care.
Population-based cohort including 2388 infants, born in 2004-2005 with a gestational age (GA) of 30-34 weeks and admitted to 21 NU reporting to the Swedish perinatal register.
postmenstrual age (PMA) at hospital discharge to home.
Mean PMA at hospital discharge was 36.9 (1.7) weeks. High (> or = 35 years) maternal age, multiple birth, small for gestational age, respiratory distress syndrome, infection, hypoglycaemia and hyperbilirubinaemia were significantly associated with higher PMA at discharge, but could only explain 13% of the variation in PMA at discharge. Mean PMA at discharge differed by up to 2 weeks between hospitals. Infants treated at NUs without fixed discharge criteria had 4.7 days lower PMA at discharge and infants receiving domiciliary care had 9.8 days lower PMA at discharge. Breastfed infants also had lower PMA at discharge (mean 2.7 days lower) than those not breast fed, partly explained by lower morbidity in the breastfed infants.
Perinatal risk factors have small overall impact on length of hospital stay in moderately preterm infants. Organisation of care is probably an important factor. The number of bed-days differs significantly between centres, which may have effects on quality of care and health economy.
Aim: To determine whether growth, feeding tolerance and infectious events of preterm infants is related to the proportion of intake of mother’s own raw milk (maternal milk) versus pooled pasteurized ...banked breast milk (donor milk).
Methods: This is a prospective observational study of 55 premature infants born less than 32 weeks of gestational age admitted to the neonatal intensive care unit at the Children’s Hospital of Toulouse during two 6‐month periods from 2003 to 2005. Enrolled infants were exclusively on enteral feeds with maternal milk ± donor milk.
Results: Mean gestational age was 28.6 weeks (SD 1.5) and mean birth weight 1105 grams (SD 282). During the time of exclusively breast milk feeds, weight gain (g/kg/day) was correlated to the proportion of maternal milk consumed (p = 0.0048, r = 0.4). Necrotizing enterocolitis was inversely correlated to the amount of maternal milk. The amount of maternal milk did not impact on infectious events.
Conclusion: Mother’s own raw milk improves weight gain compared with donor milk in preterm infants. Lactation strategies should be sought that helps mothers to increase their milk production.
Subclinical mastitis (SCM) is an inflammatory state of the lactating mammary gland, which is asymptomatic and may have negative consequences for child growth. The objectives of this study were to: ...(1) test the association between the dietary inflammatory index (DII®) and SCM and (2) assess the differences in nutrient intakes between women without SCM and those with SCM. One hundred and seventy-seven women with available data on human milk (HM) sodium potassium ratio (Na:K) and dietary intake data were included for analysis. Multivariable logistic regression was used to examine the association between nutrient intake and the DII score in relation to SCM. Women without SCM had a lower median DII score (0.60) than women with moderate (1.12) or severe (1.74) SCM (p < 0.01). A one-unit increase in DII was associated with about 41% increased odds of having SCM, adjusting for country and mode of delivery, p = 0.001. Women with SCM had lower mean intakes of several anti-inflammatory nutrients. We show for the first time exploratory evidence that SCM may be associated with a pro-inflammatory diet and women with SCM have lower intakes of several antioxidant and anti-inflammatory nutrients.