The human milk endocannabinoidome and neonatal growth in gestational diabetes.

Objective: Endocannabinoids and their N-acyl-ethanolamines (NAEs) and 2monoacyl-glycerols (2-MAGs) congeners are involved in the central and peripheral regulation of energy homeostasis, they are present in human milk and are associated with obesity. Infants exposed in utero to gestational diabetes mellitus (GDM) are more likely to develop obesity. The objective of this cross-sectional study is to compare the profile of eCBome mediators in milk of women with gestational diabetes (GDM+) and without (GDM-) and to assess the association with offspring growth. The hypothesis is that the eCBome of GDM+ human milk is altered and associated with a difference in infant growth. Methods: Circulating eCBome mediators were measured by LC-MS/MS in human milk obtained at 2 months postpartum from GDM+ (n=24) and GDM- (n=29) women. Infant weight and height at 2 months were obtained from the child health record. Z-scores were calculated. Results: Circulating Npalmitoylethanolamine (PEA) was higher in human milk of GDM+ women than in GDM- women (4.9 ± 3.2 vs. 3.3 ± 1.7, p=0.04). Higher levels were also found for several 2monoacyl-glycerols (2-MAGs) (p<0.05). The levels of NAEs (ß=-4.6, p=0.04) and especially non-omega-3 NAEs (B=-5.6, p=0.004) in human milk were negatively correlated with weight-for-age z-score of GDM+ offspring. Conclusion: The profile of eCBome mediators in human milk at 2 months postpartum was different in GDM+ compared to GDM- women and was associated with GDM+ offspring growth at 2 months. Clinical trial registration: ClinicalTrials.gov, identifier (NCT04263675 and NCT02872402).

Antidepressants use during pregnancy and child psychomotor, cognitive and language development at 2 years of age-Results from the 3D Cohort Study.

Introduction: Approximately 5.5% of pregnant women take antidepressants. Studies on prenatal exposure to antidepressants reported no association with child cognition, and inconsistent results with motor function and language development. A limitation has been the failure to adjust for prenatal maternal distress. Objectives: Assess the associations between prenatal exposure to antidepressants and child development at age two, while adjusting for maternal depressive symptoms and stress during pregnancy. Explore indirect effects through birth complications and consider sex-specific associations. Methods: This is an ancillary study of the 3D (Design Develop, Discover) Study initiated during pregnancy. Data on antidepressants were collected through medication logs spanning the entire pregnancy. Depressive symptoms and stress were assessed during pregnancy by self-reported questionnaires, motor and cognitive development with the Bayley Scales of Infant and Toddler Development (BSID-III), and language development with the MacArthur Communicative Development Inventories at age 2. Multiple linear regressions were used to assess the associations between exposure and developmental outcomes. Mediation models were used to assess indirect effects. Interaction terms were introduced to assess sex-specific associations. Results: 1,489 mother-child dyads were included, of whom 61 (4.1%) reported prenatal antidepressant use. Prenatal exposure was negatively associated with motor development (B = -0.91, 95% CI -1.73, -0.09 for fine motor, B = -0.89, 95% CI -1.81, 0.02 for gross motor), but not with cognitive (B = -0.53, 95% CI -1.82, 0.72) and language (B = 4.13, 95% CI -3.72, 11.89) development. Adjusting for maternal prenatal distress only slightly modified these associations. No indirect effect or differential effect according to child sex were found. Conclusion: This study supports evidence of a negative association between prenatal exposure to antidepressants and motor development at age two, after adjusting for maternal distress, but the effect size remains very small, with about only one BSID-III point lower in average.

Enteral supplementation with high-dose docosahexaenoic acid on the risk of bronchopulmonary dysplasia in very preterm infants: a collaborative study protocol for an individual participant data meta-analysis.

INTRODUCTION: Severe bronchopulmonary dysplasia (BPD) is a well-known factor consistently associated with impaired cognitive outcomes. Regarding reported benefits on long-term neurodevelopmental outcomes, the potential adverse effects of high-dose docosahexaenoic acid (DHA) supplementation on this short-term neonatal morbidity need further investigations in infants born very preterm. This study will determine whether high-dose DHA enteral supplementation during the neonatal period is associated with the risk of severe BPD at 36 weeks' postmenstrual age (PMA) compared with control, in contemporary cohorts of preterm infants born at less than 29 weeks of gestation. METHODS AND ANALYSIS: As part of an Australian-Canadian collaboration, we will conduct an individual participant data (IPD) meta-analysis of randomised controlled trials targeting infants born at less than 29 weeks of gestation and evaluating the effect of high-dose DHA enteral supplementation in the neonatal period compared with a control. Primary outcome will be severe grades of BPD (yes/no) at 36 weeks' PMA harmonised according to a recent definition that predicts early childhood morbidities. Other outcomes will be survival without severe BPD, death, BPD severity grades, serious brain injury, severe retinopathy of prematurity, patent ductus arteriosus and necrotising enterocolitis requiring surgery, sepsis, combined neonatal morbidities and growth. Severe BPD will be compared between groups using a multivariate generalised estimating equations log-binomial regression model. Subgroup analyses are planned for gestational age, sex, small-for-gestational age, presence of maternal chorioamnionitis and mode of delivery. ETHICS AND DISSEMINATION: The conduct of each trial was approved by institutional research ethics boards and written informed consent was obtained from participating parents. A collaboration and data sharing agreement will be signed between participating authors and institutions. This IPD meta-analysis will document the role of DHA in nutritional management of BPD. Findings will be disseminated through conferences, media interviews and publications to peer-reviewed journals. PROSPERO REGISTRATION NUMBER: CRD42023431063. TRIAL REGISTRATION NUMBER: NCT05915806.

Absolute prediction of relative changes in contrast sensitivity with aberrations using a single metric of retinal image quality.

Metrics of retinal image quality predict optimal refractive corrections and correlate with visual performance. To date, they do not predict absolutely the relative change in visual performance when aberrations change and therefore need to be a-posteriori rescaled to match relative measurements. Here we demonstrate that a recently proposed metric can be used to predict, in an absolute manner, changes in contrast sensitivity measurements with Sloan letters when aberrations change. Typical aberrations of young and healthy eyes (for a 6 mm pupil diameter) were numerically introduced, and we measured the resulting loss in contrast sensitivity of subjects looking through a 2 mm diameter pupil. Our results suggest that the metric can be used to corroborate measurements of visual performance in clinical practice, thereby potentially improving patient follow-ups.

Docosahexaenoic acid-rich algae oil supplementation in mothers of preterm infants is associated with a modification in breast milk oxylipins profile.

Oxylipins are derived from enzymatic and non-enzymatic oxidation of n-3 and n-6 long-chain polyunsaturated fatty acids. They are known to be involved in inflammatory processes. The aim of this study was to describe the breast milk oxylipin profile following a docosahexaenoic acid (DHA) supplementation of mothers of preterm infants. We examined the oxylipins profile in breast milk collected at day 14 post-delivery, of 40 mothers who delivered before 29 weeks of gestation and who were supplemented with either DHA-rich algae oil (S-DHA) or a placebo (PL). These mothers were selected from the MOBYDIck cohort (NCT02371460 registered on 25/05/2015 in ClinicalTrials.gov) according to the supplementation received (S-DHA vs. PL) and the DHA content quartiles as measured in breast milk (Low vs. High) to generate four study groups. Milk oxylipins, as ng/mL of milk, were analyzed by LC-MS/MS. Ten oxylipins derived from DHA were higher in the S-DHA-High group than the other three groups (P < 0.001). The 18-HEPE, was also higher in the S-DHA-High group (0.11 ± 0.01) compared to the other groups (P = 0.0001). Compared to the PL-Low group, there was a reduction in pro-inflammatory prostaglandins found in the S-DHA-High group with lower levels of prostaglandins PGF2α (0.21 ± 0.45 in the S-DHA-High group vs. 1.87 ± 0.44 in the PL-Low group, P = 0.03) and of PGE2 (0.33 ± 0.26 in the S-DHA-High group vs. 1.28 ± 0.25 in the PL-Low group, P = 0.04).In sum, the DHA supplementation was linked with a predominance of anti-inflammatory oxylipins in breast milk of mothers who delivered very preterm, like 17(S)-HDHA and 18-HEPE, precursors of D and E resolvins respectively. This was also accompanied with a lower level of pro-inflammatory prostaglandins.

Does Growth Velocity Affect Associations between Birth Weight and Neurodevelopment for Infants Born Very Preterm?

OBJECTIVE: To determine how neonatal growth velocity affects the association between birth weight and neurodevelopmental outcomes in infants born preterm. STUDY DESIGN: This study is a secondary analysis of the Maternal Omega-3 Supplementation to Reduce Bronchopulmonary Dysplasia in Very Preterm Infants (MOBYDIck) randomized multicenter trial conducted in breastfed infants born at <29 weeks of gestation, whose mothers were supplemented with docosahexaenoic acid or placebo during the neonatal period. Neurodevelopmental outcomes were assessed at 18-22 months of corrected age using the Bayley-III cognitive and language composite scores. The role of neonatal growth velocity was assessed with causal mediation and linear regression models. Subgroup analyses were stratified by birth weight z-score categories (<25th, ≥25th-≤75th, and >75th percentiles). RESULTS: Neurodevelopmental outcomes were available for 379 children (mean gestational age, 26.7 ± 1.5 weeks). Growth velocity partially mediated the relationships between birth weight and cognitive (ß = -1.1; 95% CI, -2.2 to -0.02; P = .05) and language scores (ß = -2.1; 95% CI, -3.3 to -0.8; P = .002). An increase by 1 g/kg/day in growth velocity was associated with an increase by 1.1 point in the cognitive score (95% CI, -0.03 to 2.1; P = .06) and 1.9 point in the language score (95% CI, 0.7 to 3.1; P = .001), after adjustment for birth weight z-score. For children with birth weight <25th percentile, a 1 g/kg/day increase in growth velocity was associated with an increase by 3.3 points in the cognitive score (95% CI, 0.5 to 6.0; P = .02) and 4.1 points in the language score (95% CI, 1.3 to 7.0; P = .004). CONCLUSIONS: Postnatal growth velocity mediated the relationship between birth weight and neurodevelopmental performance, with larger effects for children with lower birth weight. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT02371460.

Small-for-gestational-age and predictors of HOMA indices, leptin and adiponectin in infancy.

AIM: To assess whether small-for-gestational-age (SGA) - an indicator of poor fetal growth, may affect metabolic health biomarkers in infancy and explore the predictors. METHODS: This was a nested matched (1:2) prospective observational study of 65 SGA (birth weight < 10th percentile) and 130 optimal-for-gestational-age (OGA, birth weight 25th-75th percentiles, control) infants in the 3D birth cohort with subjects recruited in Canada from 1 May 2010 to 31 August 2012. The outcomes included homeostasis model assessment of insulin resistance (HOMA-IR) and beta-cell function (HOMA-ß), circulating leptin and adiponectin concentrations at age 2 years. RESULTS: HOMA-IR, HOMA-ß, leptin and adiponectin concentrations were similar in SGA versus OGA infants. Female sex and accelerated growth in length during mid-infancy (3-12 months) were associated with higher HOMA-IR. Caucasian ethnicity and decelerated growth in weight during late infancy (12-24 months) were associated with lower HOMA-IR. Current BMI was positively associated with circulating adiponectin in SGA infants only (+13.4% [4.0%-23.7%] per BMI z score increment). CONCLUSION: Insulin resistance and secretion, circulating leptin and adiponectin levels were normal in SGA subjects in infancy at age 2 years. The novel observation in SGA-specific positive association between current BMI and circulating adiponectin suggests dysfunctional adiposity-adiponectin negative feedback loop development during infancy in SGA subjects.

Association Between Enteral Supplementation With High-Dose Docosahexaenoic Acid and Risk of Bronchopulmonary Dysplasia in Preterm Infants: A Systematic Review and Meta-analysis.

Importance: High-dose docosahexaenoic acid (DHA), a long-chain polyunsaturated fatty acid, may affect the risk of bronchopulmonary dysplasia (BPD). However, high-level summative evidence supporting such clinical association in very preterm infants is lacking. Objective: To examine the association between enteral supplementation with high-dose DHA during the neonatal period and the risk of BPD in preterm infants born at less than 29 weeks' gestation. Data Sources: PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials, medRxiv, and ClinicalTrials.gov were searched from inception to August 1, 2022, for eligible articles with no language restrictions. Study Selection: Randomized clinical trials (RCTs) were eligible for inclusion (1) if their interventions involved direct administration of a minimum DHA supplementation of 40 mg/kg/d or breast milk or formula feeding of at least 0.4% of total fatty acids, and (2) if they reported data on either BPD, death, BPD severity, or a combined outcome of BPD and death. Data Extraction and Synthesis: Two investigators completed independent review of titles and abstracts, full text screening, data extraction, and quality assessment using the Cochrane Risk of Bias 2.0. Risk ratios (RRs) with 95% CIs were pooled using random-effect meta-analyses. Main Outcomes and Measures: Primary outcome was BPD using trial-specific definitions, which was further stratified for RCTs that used a more stringent BPD definition based on systematic pulse oximetry assessment at 36 weeks' postmenstrual age. Other outcomes were BPD, death, BPD severity, or combined BPD and death. Results: Among the 2760 studies screened, 4 RCTs were included, which involved 2304 infants (1223 boys [53.1%]; mean [SD] gestational age, 26.5 [1.6] weeks). Enteral supplementation with high-dose DHA was associated with neither BPD (4 studies [n = 2186 infants]; RR, 1.07 [95% CI, 0.86-1.34]; P = .53; I2 = 72%) nor BPD or death (4 studies [n = 2299 infants]; RR, 1.04 [95% CI, 0.91-1.18]; P = .59; I2 = 61%). However, an inverse association with BPD was found in RCTs that used a more stringent BPD definition (2 studies [n = 1686 infants]; RR, 1.20 [95% CI, 1.01-1.42]; P = .04; I2 = 48%). Additionally, DHA was inversely associated with moderate-to-severe BPD (3 studies [n = 1892 infants]; RR, 1.16 [95% CI, 1.04-1.29]; P = .008; I2 = 0%). Conclusions and Relevance: Results of this study showed that enteral supplementation with high-dose DHA in the neonatal period was not associated overall with BPD, but an inverse association was found in the included RCTs that used a more stringent BPD definition. These findings suggest that high-dose DHA supplementation should not be recommended to prevent BPD in very preterm infants.

Gestational Diabetes Mellitus, Human Milk Composition, and Infant Growth.

Background: Gestational diabetes mellitus (GDM) is known to affect human milk composition. Aims of this study were to compare macronutrient and energy content of human milk of women with (GDM+) and without GDM (GDM-), to assess the association between maternal health and human milk macronutrient and energy content and association between human milk macronutrient and energy content and infant growth. Study Design and Methods: Two months after delivery, hindmilk samples were collected. Triglyceride (TG), lactose, and protein content of human milk were measured. An oral glucose tolerance test was performed. Infant weight and length at birth and 2 months were collected. Weight-for-age (WAZ) and weight-for-length z-scores were calculated. Results: Twenty-four GDM+ and 29 GDM- women were included. Protein, lactose, and energy content of human milk were similar between groups. TG concentration was higher in GDM+ than in GDM- women (6.3 ± 2.0 versus 5.3 ± 1.2, p = 0.04). This difference was no longer significant after adjustment for maternal age and infant sex (p = 0.23). Maternal age was associated with TG (r = 0.28, p = 0.04) and lactose (r = -0.30, p = 0.03), while fasting glucose was associated with proteins (r = 0.30, p = 0.03) and tended to be associated with TG (r = 0.27, p = 0.05) and energy (r = 0.24, p = 0.08). TG levels in human milk were associated with weight (ß: 0.26, 95% confidence interval [CI]: 0.02 to 0.50) and WAZ (ß: 0.40, 95% CI: 0.05 to 0.75) at 2 months among children unexposed (GDM-) to GDM, but not among children exposed (GDM+) Conclusions: In conclusion, GDM status, maternal age, and fasting glucose level were associated with human milk composition. Finally, TG in human milk was associated with infant growth among GDM- children but not among GDM+ children. ClinicalTrials.gov NCT02872402.

High doses of enteral docosahexaenoic acid omega-3 supplementation for prevention of bronchopulmonary dysplasia in very preterm infants: a protocol for a systematic review and meta-analysis.

INTRODUCTION: Docosahexaenoic acid (DHA) supplementation in the neonatal period has been proposed to prevent bronchopulmonary dysplasia (BPD) in very preterm infants. We aim to determine the effects of an enteral supplementation with high doses of DHA on the risk for BPD at 36 weeks' postmenstrual age (PMA) in very preterm infants born less than 29 weeks' gestation compared with a control. METHODS AND ANALYSIS: We will conduct a systematic review and meta-analysis of randomised controlled trials (RCTs) searching PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, MedRxiv, ClinicalTrials.gov (up to 1 November 2021) as well as reference lists and citations of included articles and previous reviews. RCTs targeting infants born less than 29 weeks' gestation and evaluating the effect of high doses of DHA enteral supplementation in the neonatal period compared with a control will be eligible. Primary outcome will be BPD defined as the need for oxygen and/or ventilation at 36 weeks' PMA. Two authors will independently screen for inclusion, extract data and assess data quality using the Cochrane instrument (risk-of-bias tool 2.0). We will perform meta-analysis using random effects models. Prespecified subgroup analyses are planned for the infant gestational age and sex, the marine source of DHA, mode of administration and duration of exposure. Sensitivity analysis will be performed according to the accuracy of the BPD definition (ie, physiological definition) and according to the risk of bias of the RCTs. ETHICS AND DISSEMINATION: This protocol for a systematic review and meta-analysis does not require ethics approval, as no primary data are collected. This study will assess the effectiveness of high doses of enteral DHA supplementation on BPD and provide evidence to clinicians and families for decision-making. Findings will be disseminated through conferences, media interviews and publications to peer review journals. PROSPERO REGISTRATION NUMBER: CRD42021286705.

Predicting the effects of defocus blur on contrast sensitivity with a model-based metric of retinal image quality.

We measure the effect of defocus blur on contrast sensitivity with Sloan letters in the 0.75-2.00 arc min range of letter gaps. We compare our results with the prediction of the Dalimier and Dainty model [J. Opt. Soc. Am. A25, 2078 (2008)JOAOD60740-323210.1364/JOSAA.25.002078] and propose a new metric of retinal image quality that we define as the model limit for very small letters. The contrast sensitivity is measured for computationally blurred Sloan letters (0, 0.25, and 0.50 diopters for a 3 mm pupil) of different sizes (20/40 to 20/15 visual acuity), and subjects look through a small (2 mm) diaphragm to limit the impact of their own aberration on measurements. Measurements and model predictions, which are normalized by the blur-free condition, weakly depend on letter size and are in good agreement with our metric of retinal image quality. Our metric relates two approaches of modeling visual performance: complete modeling of the optotype classification task and calculation of retinal image quality with a descriptive metric.

Breastfeeding Practices and Associated Factors in Shanghai: A Cross-Sectional Study.

The status of breastfeeding practices remains unsatisfactory across China, but regional differences persist. However, disaggregated data for specific provinces are limited. This representative survey determined the status of breastfeeding and factors associated with breastfeeding practices in Shanghai. The questionnaire was designed in compliance with indicators for assessing infant and young child-feeding practices defined by the World Health Organization and the United Nations Children's Fund (UNICEF). A total of 2665 children aged two years and younger (0-730 days) were investigated, among whom 1677 were aged under six months. The early initiation of breastfeeding (EIBF) rate was 60.3%. Among children aged under six months, 43.4% were exclusively breastfed (EBF). The univariate regression analysis showed that the EBF rate was influenced by multiple factors, including individual, socioeconomic, workplace and employment, and health system. The subsequent multivariate analysis suggested that mothers with a higher rate of EBF shared the following characteristics: intention to breastfeed during pregnancy, breastfeeding knowledge, and higher satisfaction with support through the healthcare system after delivery. The rate of EBF in Shanghai is over 40%, and supporting breastfeeding requires measures at multiple levels, including individual attributes, women's work and employment conditions, breastfeeding knowledge, and health services.

Maternal High-Dose DHA Supplementation and Neurodevelopment at 18-22 Months of Preterm Children.

OBJECTIVES: To determine whether maternal supplementation with high-dose docosahexaenoic acid (DHA) in breastfed, very preterm neonates improves neurodevelopmental outcomes at 18 to 22 months' corrected age (CA). METHODS: Planned follow-up of a randomized, double-blind, placebo-controlled, multicenter trial to compare neurodevelopmental outcomes in breastfed, preterm neonates born before 29 weeks' gestational age (GA). Lactating mothers were randomized to receive either DHA-rich algae oil or a placebo within 72 hours of delivery until 36 weeks' postmenstrual age. Neurodevelopmental outcomes were assessed with the Bayley Scales of Infant and Toddler Development third edition (Bayley-III) at 18 to 22 months' CA. Planned subgroup analyses were conducted for GA (<27 vs ≥27 weeks' gestation) and sex. RESULTS: Among the 528 children enrolled, 457 (86.6%) had outcomes available at 18 to 22 months' CA (DHA, N = 234, placebo, N = 223). The mean differences in Bayley-III between children in the DHA and placebo groups were -0.07 (95% confidence interval [CI] -3.23 to 3.10, P = .97) for cognitive score, 2.36 (95% CI -1.14 to 5.87, P = .19) for language score, and 1.10 (95% CI -2.01 to 4.20, P = .49) for motor score. The association between treatment and the Bayley-III language score was modified by GA at birth (interaction P = .07). Neonates born <27 weeks' gestation exposed to DHA performed better on the Bayley-III language score, compared with the placebo group (mean difference 5.06, 95% CI 0.08-10.03, P = .05). There was no interaction between treatment group and sex. CONCLUSIONS: Maternal DHA supplementation did not improve neurodevelopmental outcomes at 18 to 22 months' CA in breastfed, preterm neonates, but subgroup analyses suggested a potential benefit for language in preterm neonates born before 27 weeks' GA.

Effects of maternal docosahexaenoic acid supplementation on brain development and neurodevelopmental outcomes of breastfed preterm neonates: protocol for a follow-up at preschool age of a randomised clinical trial (MOBYDIckPS).

INTRODUCTION: Docosahexaenoic acid (DHA), an omega-3 fatty acid, is important for brain development with possible implications in neurodevelopmental outcomes. In the two-arm, randomised, double-blind, placebo-controlled Maternal Omega-3 Supplementation to Reduce Bronchopulmonary Dysplasia in Very Preterm Infants trial, very preterm infants (<29 weeks' gestation) were supplemented in high doses of DHA or placebo until they reached 36 weeks' postmenstrual age. We propose a long-term neurodevelopmental follow-up of these children. This protocol details the follow-up at 5 years of age, which aims to (1) confirm our long-term recruitment capacity and (2) determine the spectrum of neurodevelopmental outcomes at preschool age following neonatal DHA supplementation. METHODS AND ANALYSIS: This long-term follow-up involves children (n=194) born to mothers (n=170) randomised to DHA (n=85) or placebo (n=85) from the five sites in Quebec when they will be 5 years' corrected age. The primary outcome measure is related to the long-term recruitment capacity, which we determined as successful if 75% (±10%, 95% CI) of the eligible children consent to the 5-year follow-up study. Interviews with mothers will be conducted to assess various aspects of neurodevelopment at preschool age (executive functions, behavioural problems, global development and health-related quality of life), evaluated with standardised neurodevelopmental questionnaires. In addition, a semistructured interview conducted in a subset of the mothers will be used to determine their acceptability and identify barriers and enablers to their eventual participation to the next phase of the trial. This follow-up study will require approximately 22 months to be completed. ETHICS AND DISSEMINATION: This study was approved by the CHU de Québec-Université Laval Research Ethics Board (MP-20-2022-5926). Mothers will provide informed consent before participating in this study. Findings will be disseminated through peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: NCT02371460.

Use of SMOF lipid emulsion in very preterm infants does not affect the incidence of bronchopulmonary dysplasia-free survival.

BACKGROUND: We aim to assess whether the docosahexaenoic acid (DHA)-containing lipid emulsion (LE) SMOFlipid 20% (Fresenius Kabi Canada Ltd) is associated with bronchopulmonary dysplasia (BPD)-free survival at 36 weeks' postmenstrual age in very preterm infants. METHODS: This cohort study is nested in the MOBYDIck randomized clinical trial (NCT02371460), which investigated the effect of maternal DHA supplementation on BPD-free survival in breastfed very preterm infants born between 23 0/7 and 28 6/7 weeks' gestation in 16 Canadian neonatal intensive care units (2015-2018). Parenteral SMOF-LE was given to the infants according to the sites' routine care protocols. Relative risks (RRs) were estimated using a modified Poisson regression model with generalized estimating equations taking into account recruitment site, multiple birth, DHA supplementation, birth weight, sex, and gestational age. RESULTS: Among 528 infants (mean gestational age, 26.5 weeks [SD, 1.6]), 272 received SMOF-LE. Overall, 56.7% of the infants in the SMOF-LE group and 59.7% infants in the non-SMOF-LE group survived without BPD (adjusted RR, 0.94 [95% CI, 0.77-1.14]; P = 0.51). BPD rates were 39.3% in the SMOF-LE group vs 34.1% in the non-SMOF-LE group (adjusted RR, 1.10 [95% CI, 0.82-1.47]; P = 0.53). Severe BPD rates were 31.8% in the SMOF-LE group vs 28.8% in the non-SMOF-LE group (adjusted P = 0.59). Mortality was not significantly different between the SMOF-LE (6.7%) and non-SMOF-LE groups (9.5%; adjusted P = 0.40). CONCLUSION: In very preterm infants, intravenous DHA-containing SMOF-LE during the neonatal period was not associated with BPD-free survival.

Effect of Maternal Docosahexaenoic Acid Supplementation on Very Preterm Infant Growth: Secondary Outcome of a Randomized Clinical Trial.

INTRODUCTION: The aim of the study was to determine the effect of a maternal docosahexaenoic acid (DHA) supplementation during lactation, compared with a placebo, on the neonatal growth profile of breastfed very preterm infants. METHODS: Preterm infants' growth profile, growth velocity from birth to 36 weeks' postmenstrual age (PMA), and growth at 36 weeks' PMA were pre-specified secondary outcomes of a randomized placebo-controlled trial conducted in 16 Canadian neonatal intensive care units (2015-2018). Lactating mothers who delivered before 29 weeks' gestation were given 1.2 g of DHA daily or a placebo within 72 h of delivery and up to 36 weeks' PMA. Analyses were performed using a linear regression model with generalized estimating equations. RESULTS: 461 mothers and their 528 infants (DHA, N = 273; placebo, N = 255) were included with mean gestational age of 26.5 weeks (standard deviation [SD] = 1.6); 275 (52.1%) were males; mean birth weight was 895 g (SD = 240). DHA interaction with sex was significant on weight profile (interaction p < 0.001), weight velocity (interaction p = 0.05), and weight at 36 weeks' PMA (interaction p = 0.02). Females in the DHA group gained more weight compared to the placebo group (mean difference [MD], 52.6 g [95% confidence interval [CI]: 24.5-80.8], p < 0.001). Weight velocity was significantly higher in females of the DHA group (MD, 3.4 g/kg/day [95% CI: 0.6-6.2], p = 0.02). At 36 weeks' PMA, the weight of males in the DHA group was significantly smaller (MD, -88.9 g [95% CI: -166.2 to -11.6], p = 0.02). CONCLUSION: DHA positively affected female infants' neonatal weight profile and velocity and negatively affected male infants' weight at 36 weeks' PMA.

Determinants of Healthy Diet Among Children Exposed and Unexposed to Gestational Diabetes.

OBJECTIVES: To evaluate the association between individual and environmental determinants of diet quality with diet quality of children exposed to gestational diabetes mellitus (GDM+) and unexposed (GDM-); to study the association between mother and child vegetables and fruit (VF) intakes. DESIGN: Cross-sectional study. PARTICIPANTS: One hundred forty-two children (104 GDM+; 38 GDM-) aged 6.2 ± 2.5 years. VARIABLES: Canadian Healthy Eating Index 2007 (HEI-C) and VF were obtained with 2 24-hour dietary recall questionnaires in children. Maternal VF was obtained by a validated food frequency questionnaire, and weight and height were measured. Sociodemographic determinants were obtained by questionnaires. ANALYSIS: Linear regression models were used to evaluate the association between individual and environmental determinants and the HEI-C score with interaction for GDM status. RESULTS: Family meals were associated with HEI-C among GDM- but not GDM+ children (ß = 9.97, P = 0.01 and ß = -0.41, P = 0.84, respectively; P for interaction = 0.02). Children's age (ß = -1.45; 95% confidence interval, -2.19 to -0.72; P < 0.001) was a determinant of HEI-C among all children. Maternal VF intakes were positively associated with children's VF intake (r = 0.30, P < 0.001, r2 = 0.09), with association of larger variance among GDM- children (r = 0.38, r2 = 0.14, P = 0.02) than GDM+ children (r = 0.23, r2 = 0.05, P = 0.02). CONCLUSIONS: The food environment at home was associated differently with the diet quality of GDM+ and GDM- children. Whether targeting family meals and maternal diet quality is a good strategy to improve children's diet quality among GDM+ children needs to be further investigated.

Breast-feeding, rapid growth in the first year of life and excess weight at the age of 2 years: the 3D Cohort Study.

OBJECTIVE: To assess relationships between breast-feeding, rapid growth in the first year of life and overweight/obesity status at the age of 2 years. DESIGN: As part of an observational, longitudinal study beginning in early pregnancy, multivariable logistic regressions were used to assess associations between breast-feeding duration (total and exclusive) and rapid weight gain (RWG) between birth and 1 year of age, and to determine predictors of overweight/obesity status at the age of 2 years. SETTING: Nine hospitals located in the province of Quebec, Canada. PARTICIPANTS: A sample of 1599 term infants who participated in the 3D Cohort Study. RESULTS: Children having RWG in the first year and those having excess weight at the age of 2 years accounted for 28 % and < 10 %, respectively. In multivariable models, children breastfed < 6 months and from 6 months to < 1 year were, respectively, 2·5 times (OR 2·45; 95 % CI 1·76, 3·41) and 1·8 times (OR 1·78; 95 % CI 1·29, 2·45) more likely to show RWG up to 1 year of age compared to children breastfed ≥ 1 year. Children exclusively breastfed < 3 months had significantly greater odds of RWG in the first year (OR 1·94; 95 % CI 1·25, 3·04) compared to children exclusively breastfed for ≥ 6 months. Associations between breast-feeding duration (total or exclusive) and excess weight at the age of 2 years were not detected. RWG in the first year was found to be the main predictor of excess weight at the age of 2 years (OR 6·98; 95 % CI 4·35, 11·47). CONCLUSIONS: The potential beneficial effects of breast-feeding on rate of growth in the first year of life suggest that interventions promoting breast-feeding are relevant for obesity prevention early in life.

Large-for-Gestational-Age, Leptin, and Adiponectin in Infancy.

CONTEXT: Fetal overgrowth "programs" an elevated risk of obesity and type 2 diabetes in adulthood. Plausibly, adipokines may be involved in programming metabolic health. OBJECTIVE: This work aimed to evaluate whether large-for-gestational-age (LGA), an indicator of fetal overgrowth, is associated with altered circulating leptin and adiponectin levels in infancy, and assess the determinants. METHODS: In the Canadian 3D birth cohort, we studied 70 LGA (birth weight > 90th percentile) and 140 optimal-for-gestational-age (OGA, 25th-75th percentiles) infants matched by maternal ethnicity, smoking, and gestational age at delivery. The primary outcomes were fasting leptin, and total and high-molecular-weight (HMW) adiponectin concentrations at age 2 years. RESULTS: LGA infants had higher body mass index (BMI) than OGA infants. However, there were no significant differences in leptin, and total and HMW adiponectin concentrations. Leptin concentrations were positively associated with female sex, weight (z score) gain 0 to 24 months, current BMI, and the sum of triceps and subscapular skinfold thickness, and negatively associated with maternal age and White ethnicity. Female sex was associated with lower total and HMW adiponectin concentrations. Weight (z score) gain 0 to 24 months and current BMI were positively correlated with total and HMW adiponectin concentrations in LGA infants only. CONCLUSION: This study is the first to demonstrate that LGA does not matter for circulating leptin and adiponectin concentrations in infancy, and there may be LGA-specific positive associations between weight gain or current BMI and adiponectin concentrations in infancy, suggesting dysfunction in establishing the adiposity-adiponectin negative feedback loop in LGA individuals.

Docosahexaenoic acid-rich algae oil supplementation on breast milk fatty acid profile of mothers who delivered prematurely: a randomized clinical trial.

Preterm infants are deficient in long-chain polyunsaturated fatty acids, especially docosahexaenoic acid (DHA), a fatty acid (FA) associated with an increase in bronchopulmonary dysplasia (BPD). In two previous randomized control trials, DHA supplementation did not reduce the risk of BPD. We examined the breast milk FA profile, collected 14 days after birth, of mothers who delivered before 29 weeks of gestation and who were supplemented with DHA-rich algae oil or a placebo within 72 h after birth as part of the MOBYDIck trial. Milk FA were analyzed by gas chromatography. The total amount of FA (mg/mL) was similar in both groups but the supplementation increased DHA (expressed as % of total FA, mean ± SD, treatment vs placebo, 0.95 ± 0.44% vs 0.34 ± 0.20%; P < 0.0001), n-6 docosapentaenoic acid (DPA) (0.275 ± 0.14% vs 0.04 ± 0.04%; P < 0.0001) and eicosapentaenoic acid (0.08 ± 0.08% vs 0.07 ± 0.07%; P < 0.0001) while decreasing n-3 DPA (0.16 ± 0.05% vs 0.17 ± 0.06%; P < 0.05). Supplementation changed the ratio of DHA to arachidonic acid (1.76 ± 1.55% vs 0.60 ± 0.31%; P < 0.0001) and n-6 to n-3 FA (0.21 ± 0.06% vs 0.17 ± 0.04%; P < 0.0001). DHA-rich algae supplementation successfully increased the DHA content of breast milk but also included secondary changes that are closely involved with inflammation and may contribute to changing clinical outcomes.