Lactoferrin intake from maternal milk during the neonatal hospitalization and early brain development among preterm infants.

BACKGROUND: Lactoferrin is an immuno-modulatory nutrient in human milk that may be neuroprotective. METHODS: In 36 infants born <32 weeks' gestation, we sampled human milk at 14 and 28 days of chronologic age and measured lactoferrin by electrochemiluminescence multiplex immunoassay. Using 3T quantitative brain magnetic resonance imaging scans obtained at term equivalent, we estimated total and regional brain volumes. We compared outcomes between infants exposed to low (bottom tertile, range 0.06-0.13 mg/mL) vs. high (top tertile, range 0.22-0.35 mg/mL) lactoferrin using median regression in models adjusted for gestational age, birth weight z-score, sex, and postmenstrual age. RESULTS: Compared to infants exposed to low lactoferrin, infants exposed to high lactoferrin had 43.9 cc (95% CI: 7.6, 80.4) larger total brain volume, 48.3 cc (95% CI: 12.1, 84.6) larger cortical gray matter, and 3.8 cc (95% CI: 0.7, 7.0) larger deep gray matter volume at term equivalent age. Other regional brain volumes were not statistically different between groups. CONCLUSION: Higher lactoferrin exposure during the neonatal hospitalization was associated with larger total brain and gray matter volumes, suggesting that lactoferrin may have potential as a dietary supplement to enhance brain growth in the neonatal intensive care unit setting. IMPACT: This study suggests that lactoferrin, a whey protein found in human milk, may be beneficial for preterm infant brain development, and therefore has potential as a dietary supplement in the neonatal intensive care unit setting.

Growth Velocities Across Distinct Early Life Windows and Child Cognition: Insights from a Contemporary US Cohort.

OBJECTIVE: To evaluate the relative importance of overall and period-specific postnatal growth and their interaction with fetal growth on cognition in a generally well-nourished population. STUDY DESIGN: We included 1052 children from Project Viva, a prospective cohort in Boston, Massachusetts. Using linear spline mixed-effects models, we modeled length/height and body mass index (BMI) trajectories from birth to 7 years and estimated standardized overall (0-7 years) and period-specific growth velocities ie, early infancy (0-4 months), late infancy (4-15 months), toddlerhood (15-37 months), and early childhood (37-84 months). We investigated associations of growth velocities as well as their interactions with birthweight-for-gestational age on mid-childhood (mean age: 7.9 years) IQ, visual memory and learning, and visual motor ability. RESULTS: Greater overall height velocity was associated with modestly higher design memory score, (adjusted ß [95% CI] 0.19 [-0.01,0.38] P = .057])points per SD increase but lower verbal IQ (-0.88 [-1.76,0.00] P = .051). Greater early infancy height velocity was associated with higher visual motor score (1.92 [0.67,3.18]). Greater overall BMI velocity was associated with lower verbal IQ (-0.71 [-1.52,0.11] P = .090). Greater late infancy BMI velocity was associated with lower verbal IQ (-1.21 [-2.07,-0.34]), design memory score (-0.22 [-0.42,-0.03)], but higher picture memory score (0.22 [0.01,0.43]). Greater early infancy height velocity (-1.5 SD vs 1.5 SD) was associated with higher nonverbal IQ (margins [95% CI] 102.6 [98.9106.3] vs 108.2 [104.9111.6]) among small-for-gestational age infants (P-interaction = 0.04). CONCLUSIONS: Among generally well-nourished children, there might not be clear cognitive gains with faster linear growth except for those with lower birthweight-for-gestational age, revealing the potential importance of early infancy compensatory growth.

Novel metrics to characterize temporal lobe of very preterm infants on term-equivalent brain MRI.

BACKGROUND: Preterm birth adversely impacts brain development and contributes to neurodevelopmental impairment; the temporal lobe may be particularly vulnerable to the impact of very preterm (VP) birth. Yet, no prior magnetic resonance imaging (MRI) scoring system incorporated a method to quantify temporal lobe size in VP infants. METHODS: We developed and applied three metrics (temporal lobe length, extra-axial space, and temporal horn width) to quantify temporal lobe structure on term-equivalent brain MRIs obtained from 74 VP and 16 term infants. We compared metrics between VP and term infants and explored associations of each metric with perinatal risk factors. RESULTS: All metrics had excellent reliability (intra-class correlation coefficient 0.62-0.98). VP infants had lower mean temporal lobe length (76.8 mm versus 79.2 mm, p = 0.02); however, the difference attenuated after correction for postmenstrual age. VP infants had larger temporal horn widths compared with term infants (2.6 mm versus 1.8 mm, p < 0.001). Temporal lobe length was positively associated with gestational age, birth weight, and male sex, and negatively associated with the duration of parenteral nutrition. CONCLUSIONS: The proposed metrics are reliable and sensitive in distinguishing differences in temporal lobe development between VP and full-term infants. IMPACT: We developed a novel method for quantifying temporal lobe size among very preterm infants at term equivalent using simple metrics performed on brain MRI. Temporal lobe metrics were reliable, correlated with brain volume from volumetric analysis, and were sensitive in identifying differences in temporal lobe development among preterm compared with term infants, specifically larger temporal horn size in preterm infants. This temporal lobe metric system will enable future work to delineate the perinatal and postnatal factors that impact temporal lobe growth, and better understand the relationship between temporal lobe disturbance and neurodevelopment in very preterm infants.

Systemic Inflammation in the First 2 Weeks after Birth as a Determinant of Physical Growth Outcomes in Hospitalized Infants with Extremely Low Gestational Age.

OBJECTIVE: To examine associations of systemic inflammation with growth outcomes at neonatal intensive care unit discharge or transfer among infants with extremely low gestational ages. STUDY DESIGN: We studied 850 infants at born at 23-27 weeks of gestation. We defined inflammatory protein elevation as the highest quartile of C-reactive protein (CRP), Interleukin (IL)-6, tumor necrosis factor-∝, or IL-8 on postnatal days 1, 7, and 14. We compared z-scores of weight, length, and head circumference at neonatal intensive care unit discharge or transfer between infants with vs without inflammatory protein elevation, adjusting in linear regression for birth size z-score, sex, gestational age, diet, comorbidities, medications, and length of hospitalization. RESULTS: The mean gestational age was 25 weeks (range, 23-27 weeks) and birth weight z-score 0.14 (range, -2.73 to 3.28). Infants with a high CRP on day 7 had lower weights at discharge or transfer (-0.17 z-score; 95% CI, -0.27 to -0.06) than infants without CRP elevation, with similar results on day 14. Infants with CRP elevation on day 14 were also shorter (-0.21 length z-scores; 95% CI, -0.38 to -0.04), and had smaller head circumferences (-0.18 z-scores; 95% CI, -0.33 to -0.04) at discharge or transfer. IL-6 elevation on day 14 was associated with lower weight (-0.12; 95% CI, -0.22 to -0.02); IL-6 elevation on day 7 was associated with shorter length (-0.27; 95% CI, -0.43 to -0.12). Tumor necrosis factor-∝ and IL-8 elevation on day 14 were associated with a lower weight at discharge or transfer. CONCLUSIONS: Postnatal systemic inflammation may contribute to impaired nutrient accretion during a critical period in development in infants with extremely low gestational ages.

Intestinal Inflammation is Significantly Associated With Length Faltering in Preterm Infants at Neonatal Intensive Care Unit Discharge.

OBJECTIVE: The aim of the study was to assess intestinal inflammatory measures, urinary intestinal fatty acid-binding protein (IFABP), and fecal calprotectin (FC) by gestational age (GA) and postmenstrual age (PMA) and determine the association between intestinal inflammation and growth in preterm infants from birth to hospital discharge. We hypothesized that intestinal inflammation is associated with adverse growth in preterm infants. METHODS: We assayed repeated measures of IFABP and FC in 72 hospitalized preterm infants (<34 weeks' gestation). We calculated weight and length z scores at birth and discharge using the Fenton growth reference. Associations between mean IFABP or FC, growth z scores at discharge, and growth faltering (weight or length z score difference <-0.8 from birth to discharge) were assessed using mixed linear and logistic regression models, adjusted for intrafamilial correlation and potential confounders: GA, sex, birth z score, race/ethnicity, and maternal age. RESULTS: Mean IFABP was greater among infants born at earlier GA and decreased with increasing PMA. Mean FC did not vary by GA or PMA. Higher mean IFABP and FC were associated with lower discharge growth z scores and greater likelihood of growth faltering significant only for mean IFABP and discharge length z score (ß = -0.353, 95% confidence interval [CI]: -0.704 to -0.002) and mean IFABP and length faltering (odds ratio [OR] 1.99, P = 0.018). CONCLUSIONS: Intestinal inflammation, measured by IFABP, was associated with lower length z scores and length faltering at discharge. Interventions to prevent intestinal inflammation may improve linear growth among preterm infants.

Targeting human milk fortification to improve very preterm infant growth and brain development: study protocol for Nourish, a single-center randomized, controlled clinical trial.

BACKGROUND: Human milk is recommended for very preterm infants, but its variable macronutrient content may contribute to undernutrition during a critical period in development. We hypothesize that individually targeted human milk fortification is more effective in meeting macronutrient requirements than the current standard of care. METHODS: We designed a single-center randomized, controlled trial enrolling 130 infants born < 31 completed weeks' gestation. Participants will receive fortified maternal and/or pasteurized donor milk but no formula. For participants in the intervention group, milk will be individually fortified with protein and fat modulars to achieve target levels based on daily point-of-care milk analysis with mid-infrared spectroscopy, in addition to standard fortification. The study diet will continue through 36 weeks' postmenstrual age (PMA). Clinical staff and parents will be masked to study group. Primary outcomes include: 1) body length and lean body mass by air displacement plethysmography at 36 weeks' PMA; 2) quantitative magnetic resonance imaging-based measures of brain size and microstructure at term equivalent age; and 3) Bayley-IV scales at 2 years' corrected age. DISCUSSION: We expect this trial to provide important data regarding the effectiveness of individually targeted human milk fortification in the neonatal intensive care unit (NICU). TRIAL REGISTRATION: NCT03977259 , registered 6 June, 2019.

Early-Life Predictors of Systolic Blood Pressure Trajectories From Infancy to Adolescence: Findings From Project Viva.

Childhood blood pressure (BP) is a strong predictor of later risk of cardiovascular disease. However, few studies have assessed dynamic BP trajectories throughout the early-life period. We investigated the relationship between early-life factors and systolic BP (SBP) from infancy to adolescence using linear spline mixed-effects models among 1,370 children from Project Viva, a Boston, Massachusetts-area cohort recruited in 1999-2002. After adjusting for confounders and child height, we observed higher SBP in children exposed to gestational diabetes mellitus (vs. normoglycemia; age 3 years: ß = 3.16 mm Hg (95% confidence interval (CI): 0.28, 6.04); age 6 years: ß = 1.83 mm Hg (95% CI: 0.06, 3.60)), hypertensive disorders of pregnancy (vs. normal maternal BP; age 6 years: ß = 1.39 mm Hg (95% CI: 0.10, 2.67); age 9 years: ß = 1.84 mm Hg (95% CI: 0.34, 3.34); age 12 years: ß = 1.70 mm Hg (95% CI: 0.48, 2.92)), higher neonatal SBP (per 10-mm Hg increase; age 3 years: ß = 1.26 mm Hg (95% CI: 0.42, 2.09); age 6 years: ß = 1.00 mm Hg (95% CI: 0.49, 1.51); age 9 years: ß = 0.75 mm Hg (95% CI: 0.17, 1.33)), and formula milk in the first 6 months of life (vs. breast milk only; age 12 years: ß = 2.10 mm Hg (95% CI: 0.46, 3.74); age 15 years: ß = 3.52 mm Hg (95% CI: 1.40, 5.64); age 18 years: ß = 4.94 mm Hg (95% CI: 1.88, 7.99)). Our findings provide evidence of programming of offspring SBP trajectories by gestational diabetes, hypertensive disorders of pregnancy, and formula milk intake and of neonatal BP being a potentially useful marker of childhood BP. These factors could be relevant in identifying children who are at risk of developing elevated BP.

Racial and Ethnic Disparities in the Use of Mother's Milk Feeding for Very Low Birth Weight Infants in Massachusetts.

OBJECTIVE: To examine the extent to which maternal race/ethnicity is associated with mother's milk use among hospitalized very low birth weight (VLBW) infants and maternal receipt of hospital breastfeeding support practices (human milk prenatal education, first milk expression <6 hours after delivery, lactation consultation <24 hours, any skin-to-skin care <1 month). STUDY DESIGN: We studied 1318 mother-VLBW infant pairs in 9 Massachusetts level 3 neonatal intensive care units (NICUs) between January 2015 and November 2017. We estimated associations of maternal race/ethnicity with any and exclusive mother's milk on day 7, on day 28, and at discharge/transfer and hospital practices. We estimated HRs comparing the probability of continued milk use over the hospitalization by race/ethnicity and tested mediation by hospital practices, adjusting for birth weight and gestational age and including hospital and plurality as random effects. RESULTS: Mothers were 48% non-Hispanic white, 21% non-Hispanic black, and 20% Hispanic. Initiation of mother's milk was similar across groups, but infants of Hispanic mothers (hazard ratio [HR], 2.71; 95% CI, 2.05-3.59) and non-Hispanic black mothers (HR, 1.55; 95% CI, 1.17-2.07) stopped receiving milk earlier in the hospitalization compared with infants of non-Hispanic white mothers. Hispanic mothers had lower odds of providing skin-to-skin care at <1 month (OR, 0.61; 95% CI, 0.43-0.87) compared with non-Hispanic whites. CONCLUSIONS: Hispanic and non-Hispanic black mothers were less likely than non-Hispanic white mothers to continue providing milk for their VLBW infants throughout the NICU stay.

Associations of Growth and Body Composition with Brain Size in Preterm Infants.

OBJECTIVE: To assess the association of very preterm infants' brain size at term-equivalent age with physical growth from birth to term and body composition at term. STUDY DESIGN: We studied 62 infants born at <33 weeks of gestation. At birth and term, we measured weight and length and calculated body mass index. At term, infants underwent air displacement plethysmography to determine body composition (fat and fat-free mass) and magnetic resonance imaging to quantify brain size (bifrontal diameter, biparietal diameter, transverse cerebellar distance). We estimated associations of physical growth (Z-score change from birth to term) and body composition with brain size, adjusting for potential confounders using generalized estimating equations. RESULTS: The median gestational age was 29 weeks (range, 24.0-32.9 weeks). Positive gains in weight and body mass index Z-score were associated with increased brain size. Each additional 100 g of fat-free mass at term was associated with larger bifrontal diameter (0.6 mm; 95% CI, 0.2-1.0 mm), biparietal diameter (0.7 mm; 95% CI, 0.3-1.1 mm), and transverse cerebellar distance (0.3 mm; 95% CI, 0.003-0.5 mm). Associations between fat mass and brain metrics were not statistically significant. CONCLUSIONS: Weight and body mass index gain from birth to term, and lean mass-but not fat-at term, were associated with larger brain size. Factors that promote lean mass accrual among preterm infants may also promote brain growth.

Validity of Body Mass Index as a Measure of Adiposity in Infancy.

OBJECTIVES: To assess the validity of body mass index (BMI) and age- and sex-standardized BMI z-score (BMIZ) as surrogates for adiposity (body fat percentage [BF%], fat mass, and fat mass index [kg/m2]) at 3 time points in infancy (1, 4, and 7 months) and to assess the extent to which the change in BMIZ represents change in adiposity. STUDY DESIGN: We performed a secondary analysis of 447 full-term infants in a previous trial of maternal vitamin D supplementation during lactation. Study staff measured infant anthropometrics and assessed body composition with dual-energy x-ray absorptiometry at 1, 4, and 7 months of age. We calculated Spearman correlations (rs) among BMI, BMIZ, and adiposity at each time point, and between change in BMIZ and change in adiposity between time points. RESULTS: Infants (N = 447) were 52% male, 38% white, 31% black, and 29% Hispanic. The BMIZ was moderately correlated with BF% (rs = 0.43, 0.55, 0.48 at 1, 4, and 7 months of age, respectively). BMIZ correlated more strongly with fat mass and fat mass index, particularly at 4 and 7 months of age (fat mass rs = 0.72-0.76; fat mass index rs = 0.75-0.79). Changes in BMIZ were moderately correlated with adiposity changes from 1 to 4 months of age (rs = 0.44 with BF% change; rs = 0.53 with fat mass change), but only weakly correlated from 4 to 7 months of age (rs = 0.21 with BF% change; rs = 0.27 with fat mass change). CONCLUSIONS: BMIZ is moderately correlated with adiposity in infancy. Changes in BMIZ are a poor indicator of adiposity changes in later infancy. BMI and BMIZ are limited as surrogates for adiposity and especially adiposity changes in infancy. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00412074.

The impact of preterm birth <37 weeks on parents and families: a cross-sectional study in the 2 years after discharge from the neonatal intensive care unit.

BACKGROUND: Little is known about the quality of life of parents and families of preterm infants after discharge from the neonatal intensive care unit (NICU). Our aims were (1) to describe the impact of preterm birth on parents and families and (2) and to identify potentially modifiable determinants of parent and family impact. METHODS: We surveyed 196 parents of preterm infants <24 months corrected age in 3 specialty clinics (82% response rate). Primary outcomes were: (1) the Impact on Family Scale total score; and (2) the Infant Toddler Quality of Life parent emotion and (3) time limitations scores. Potentially modifiable factors were use of community-based services, financial burdens, and health-related social problems. We estimated associations of potentially modifiable factors with outcomes, adjusting for socio-demographic and infant characteristics using linear regression. RESULTS: Median (inter-quartile range) infant gestational age was 28 (26-31) weeks. Higher Impact on Family scores (indicating worse effects on family functioning) were associated with taking ≥3 unpaid hours/week off from work, increased debt, financial worry, unsafe home environment and social isolation. Lower parent emotion scores (indicating greater impact on the parent) were also associated with social isolation and unpaid time off from work. Lower parent time limitations scores were associated with social isolation, unpaid time off from work, financial worry, and an unsafe home environment. In contrast, higher parent time limitations scores (indicating less impact) were associated with enrollment in early intervention and Medicaid. CONCLUSIONS: Interventions to reduce social isolation, lessen financial burden, improve home safety, and increase enrollment in early intervention and Medicaid all have the potential to lessen the impact of preterm birth on parents and families.

Determinants of physical activity frequency and provider advice during pregnancy.

BACKGROUND: Our aims were to (1) describe the frequency of physical activity and prenatal healthcare provider advice about physical activity during pregnancy and (2) examine determinants and correlates of 3rd trimester physical activity and receipt of physical activity advice. METHODS: We analyzed data from the 2008 Pregnancy Risk Assessment Monitoring System. We studied 2669 women from North Carolina and Colorado with data on physical activity frequency in the 3 months prior to pregnancy and during the 3rd trimester and 1584 women from Oklahoma with data on provider advice regarding physical activity during pregnancy. Respondents reported physical activity, defined as 30 min or more of exercise/physical activity (excluding vocationally related activity), in in these categories: <1 day/week, 1-4 days/week, and ≥5 days/week. We defined adherence to American College of Obstetrics & Gynecology (ACOG) criteria as physical activity ≥5 days/week in the 3rd trimester. We performed logistic regression analyses weighted for sampling and adjusted for socio-demographic factors. RESULTS: Forty-two percent of women in North Carolina and Colorado reported 3rd trimester physical activity <1 day/week, 42% 1-4 days/week, 9% ≥5 days/week; 7% reported being told not to exercise. Seventy-two percent of women in Oklahoma reported receiving physical activity advice from a prenatal care provider. Low activity frequency (<1 day/week) prior to pregnancy was strongly associated with low likelihood of ACOG guideline adherence in the 3rd trimester (aOR 0.10, 95% CU 0.04, 0.30 vs. 1-4 days/week). Underweight women were more likely to adhere to ACOG guidelines than normal weight women (aOR 2.27, 95% CI 1.36, 3.79). Overweight women were more likely to receive physical activity advice (aOR 2.9, 95% CI 1.3, 6.3 vs. normal weight), but obese women were not (aOR 0.65, 95% CI 0.4, 1.2). CONCLUSIONS: Few women meet ACOG guideline criteria for physical activity during pregnancy. Improving physical activity and weight status prior to pregnancy may improve activity levels during pregnancy. Nearly one third did not receive advice about physical activity during prenatal care. Obese women were no more likely to receive advice than their normal weight counterparts, indicating the need for targeted physical activity counseling in this population.

Birth Size, Early Life Weight Gain, and Midchildhood Cardiometabolic Health.

OBJECTIVE: To examine associations of birth size and weight gain during 4 early-life age intervals with midchildhood adiposity and metabolic profile and to evaluate for an interaction between birth size and early-life weight gain. STUDY DESIGN: Using data from 963 participants of Project Viva, a US prebirth cohort, we used multivariable linear regression to examine relations of birth size (tertiles of birthweight-for-gestational-age z-score) and weight gain (body mass index z-score [BMIZ] change) during 4 age intervals (birth-6 months, 6 months-1 year, 1-2 years, 2-3 years) with body composition and metabolic biomarkers during midchildhood (6.6-10.7 years). RESULTS: After accounting for confounders and previous growth, greater BMIZ change during all 4 age intervals corresponded with higher midchildhood adiposity, with larger effect sizes for later (1-2 years and 2-3 years) vs earlier (birth-6 months and 6 months-1 year) time frames. We observed effect modification by birth size for the birth-6 months and 6 months-1 year intervals. Greater birth-6 months BMIZ change was associated with higher overall adiposity (0.40 [95% CI 0.29, 0.51] kg dual x-ray absorptiometry total fat mass per z-score) among children in the highest birth size tertile. Similar associations were observed for central adiposity. Each increment in 6 months-1 year BMIZ change corresponded with 0.55 (0.05, 1.05) units higher homeostatic model assessment of insulin resistance and 2.68 (0.96, 4.40) ng/mL higher leptin among the smallest infants. CONCLUSIONS: BMIZ gain after 1 year is associated with greater midchildhood adiposity regardless of birth size, whereas the long-term influence of weight gain during the first postnatal year may depend on size at birth. Future studies are warranted to validate findings and examine relations with conventional birth size cut-offs.

Weight Status in the First 2 Years of Life and Neurodevelopmental Impairment in Extremely Low Gestational Age Newborns.

OBJECTIVE: To examine the extent to which weight gain and weight status in the first 2 years of life relate to the risk of neurodevelopmental impairment in extremely preterm infants. STUDY DESIGN: In a cohort of 1070 infants born between 23 and 27 weeks' gestation, we examined weight gain from 7-28 days of life (in quartiles) and weight z-score at 12 and 24 months corrected age (in 4 categories: <-2; ≥-2, <-1; ≥1, <1; and ≥1) in relation to these adverse neurodevelopmental outcomes: Bayley-II mental development index <55, Bayley-II psychomotor development index <55, cerebral palsy, Gross Motor Function Classification System ≥1 (cannot walk without assistance), microcephaly. We adjusted for confounders in logistic regression, stratified by sex, and performed separate analyses including the entire sample, and excluding children unable to walk without assistance (motor impairment). RESULTS: Weight gain in the lowest quartile from 7-28 days was not associated with higher risk of adverse outcomes. Children with a 12-month weight z-score <-2 were at increased risk for all adverse outcomes in girls, and for microcephaly and Gross Motor Function Classification System ≥1 in boys. However, excluding children with motor impairment attenuated all associations except that of weight z-score <-2 with microcephaly in girls. Similarly, most associations of low weight z-score at 24 months with adverse outcomes were attenuated with exclusion of children with motor impairment. CONCLUSION: Excluding children who have gross motor impairment appears to eliminate the association of low weight status with neurodevelopmental impairments at 2 years in extremely preterm infants.

Breast Milk Feeding, Brain Development, and Neurocognitive Outcomes: A 7-Year Longitudinal Study in Infants Born at Less Than 30 Weeks' Gestation.

OBJECTIVES: To determine the associations of breast milk intake after birth with neurological outcomes at term equivalent and 7 years of age in very preterm infants STUDY DESIGN: We studied 180 infants born at <30 weeks' gestation or <1250 grams birth weight enrolled in the Victorian Infant Brain Studies cohort from 2001-2003. We calculated the number of days on which infants received >50% of enteral intake as breast milk from 0-28 days of life. Outcomes included brain volumes measured by magnetic resonance imaging at term equivalent and 7 years of age, and cognitive (IQ, reading, mathematics, attention, working memory, language, visual perception) and motor testing at 7 years of age. We adjusted for age, sex, social risk, and neonatal illness in linear regression. RESULTS: A greater number of days on which infants received >50% breast milk was associated with greater deep nuclear gray matter volume at term equivalent age (0.15 cc/d; 95% CI, 0.05-0.25); and with better performance at age 7 years of age on IQ (0.5 points/d; 95% CI, 0.2-0.8), mathematics (0.5; 95% CI, 0.1-0.9), working memory (0.5; 95% CI, 0.1-0.9), and motor function (0.1; 95% CI, 0.0-0.2) tests. No differences in regional brain volumes at 7 years of age in relation to breast milk intake were observed. CONCLUSION: Predominant breast milk feeding in the first 28 days of life was associated with a greater deep nuclear gray matter volume at term equivalent age and better IQ, academic achievement, working memory, and motor function at 7 years of age in very preterm infants.

Human milk intake in preterm infants and neurodevelopment at 18 months corrected age.

BACKGROUND: The effect of human milk intake on neurodevelopment in preterm infants is uncertain. METHODS: We analyzed data from 611 participants in the DHA for Improvement of Neurodevelopmental Outcomes study, enrolled at ≤33 wk gestation from five Australian perinatal centers. The main exposures were (i) average daily human milk intake during the neonatal hospitalization and (ii) total duration of human milk intake before and after discharge. Outcomes were Bayley Scales of Infant Development, 2nd Edition Mental (MDI), and Psychomotor (PDI) Development Indexes. RESULTS: Adjusting for confounders in linear regression, human milk intake was not associated with higher MDI (0.2 points per 25 ml/kg/d; 95% confidence interval (CI): -0.6, 1.0) or PDI (-0.3 points; 95% CI: -1.1, 0.4). Longer duration of human milk intake was also not associated with MDI (0.1 points per month; 95% CI: -0.2, 0.3) or PDI (-0.2 points per month; 95% CI: -0.5, 0.01) scores, except in infants born 29-33 wk gestation (n = 364, MDI 0.3 points higher per additional month, 95% CI: 0.1, 0.6). CONCLUSIONS: We found no associations of human milk intake during the neonatal hospitalization with neurodevelopment at 18 mo corrected age.

Prepregnancy body mass index and risk of preterm birth: association heterogeneity by preterm subgroups.

BACKGROUND: To evaluate the association between prepregnancy body mass index (BMI) is associated with early vs. late and medically-induced vs. spontaneous preterm birth (PTB) subtypes. METHODS: Using data from the Boston Birth Cohort, we examined associations of prepregnancy BMI with 189 early (<34 completed weeks) and 277 late (34-36 completed weeks) medically-induced PTBs and 320 early and 610 late spontaneous PTBs vs. 3281 term births (37-44 weeks) in multinomial regression. To assess for mediation by important pregnancy complications, we performed sequential models with and without hypertensive disorders of pregnancy, chorioamnionitis, and gestational diabetes. RESULTS: Prevalence of prepregnancy obesity (BMI ≥ 30.0 kg/m2) was 28% among mothers with medically-induced PTBs, 18% among mothers with spontaneous PTBs, and 18% among mothers with term births (p = <0.001). After adjustment for demographic and known risk factors for PTB, prepregnancy obesity was associated with higher odds of both early [OR 1.78 (1.19, 2.66)] and late [OR 1.49 (1.09, 2.04)] medically-induced PTB. These effect estimates were attenuated with inclusion of hypertensive disorders of pregnancy and gestational diabetes. For spontaneous deliveries, prepregnancy obesity was associated with decreased odds of PTB (0.76 [0.58, 0.98]) and underweight was nearly associated with increased odds of PTB (1.46 [0.99, 2.16]). CONCLUSION: Prepregnancy obesity is associated with higher risk of medically-induced, but not spontaneous PTB. Hypertensive disorders of pregnancy and gestational diabetes appear to partially explain the association between prepregnancy obesity and early and late medically-induced PTB.

Deciphering macronutrient information about human milk.

Clinicians caring for small, vulnerable newborns increasingly have access to specific nutritional information about human milk through point-of-care analyzers and labeled products. It is critical for clinicians to recognize that there is considerable variability in how human milk nutritional data are derived and reported, which impacts the interpretation of nutritional values, comparison of nutritional data between products, and ultimately the ability to deliver optimal nutritional care. This article distills key issues that will enable clinicians to interpret human milk nutritional labels/analysis more effectively, ultimately allowing them to make better decisions about dietary strategies. We aim to empower clinicians to ask questions about milk sampling techniques, reported nutrient values, analysis techniques, and milk bank pooling practices. This knowledge can put human milk nutrient values in context, improve clinical care, and help to drive more rigorous research for exploring the impact of human milk feeding on infant outcomes.

Association between type of feeding at hospital discharge and nutritional status of Brazilian very preterm infants: a multicenter study.

OBJECTIVES: To examine trends over time in diet and size of very preterm infants, and associations of diet with size at hospital discharge/transfer. METHODS: The authors studied 4062 surviving very preterm infants born < 32 weeks' gestational age and < 1500 g between January 2012 and December 2020 from 12 Brazilian Neonatal Intensive Care Units. Diet type at discharge/transfer was classified as exclusive human milk, exclusive formula, or mixed. Outcomes were weight and head circumference at hospital discharge and the change in each from birth to discharge. The authors used linear regression to estimate adjusted associations of diet type with infant size, overall, and stratified by fetal growth category (small vs. appropriate for gestational age). The authors also examined trends in diet and infant size at discharge over the years. RESULTS: Infants' mean gestational age at birth was 29.3 weeks, and the mean birth weight was 1136 g. Diet at discharge/transfer was exclusive human milk for 22 %, mixed for 62 %, and exclusive formula for 16 %. Infant size in weight and head circumference were substantially below the growth chart reference for all diets. Infants fed human milk and mixed diets were lighter and had smaller heads at discharge/transfer than infants fed formula only (weight z: -2.0, -1.8, and -1.5; head z: -1.3, -1.2 and -1.1 for exclusive human milk, mixed and exclusive formula respectively). CONCLUSION: Results suggest high human milk use but gaps in nutrient delivery among hospitalized Brazilian very preterm infants, with little evidence of improvement over time.