Using Nature to Nurture: Breast Milk Analysis and Fortification to Improve Growth and Neurodevelopmental Outcomes in Preterm Infants

Premature infants are born prior to a critical window of rapid placental nutrient transfer and fetal growth—particularly brain development—that occurs during the third trimester of pregnancy. Subsequently, a large proportion of preterm neonates experience extrauterine growth failure and associated neurodevelopmental impairments. Human milk (maternal or donor breast milk) is the recommended source of enteral nutrition for preterm infants, but requires additional fortification of macronutrient, micronutrient, and energy content to meet the nutritional demands of the preterm infant in attempts at replicating in utero nutrient accretion and growth rates. Traditional standardized fortification practices that add a fixed amount of multicomponent fortifier based on assumed breast milk composition do not take into account the considerable variations in breast milk content or individual neonatal metabolism. Emerging methods of individualized fortification—including targeted and adjusted fortification—show promise in improving postnatal growth and neurodevelopmental outcomes in preterm infants.

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Fenton vs. Intergrowth-21st: Postnatal Growth Assessment and Prediction of Neurodevelopment in Preterm Infants

Nutrients ◽

10.3390/nu13082841 ◽

2021 ◽

Vol 13 (8) ◽

pp. 2841

Author(s):

Miheret Yitayew ◽

Nayef Chahin ◽

Salem Rustom ◽

Leroy R. Thacker ◽

Karen Hendricks-Muñoz

Keyword(s):

Preterm Infants ◽

Gestational Age ◽

Growth Failure ◽

Postnatal Growth ◽

Assessment Tools ◽

Growth Monitoring ◽

Neurodevelopmental Outcomes ◽

Increased Risk ◽

Growth Assessment

Although the survival rate of preterm infants has improved over the years, growth failure and associated impaired neurodevelopmental outcome remains a significant morbidity. Optimal nutrition plays an important role in achieving adequate postnatal growth. Accurate growth monitoring of preterm infants is critical in guiding nutritional protocols. Currently, there is no consensus regarding which growth assessment tool is suitable for monitoring postnatal growth of preterm infants to foster optimal neurodevelopmental outcomes while avoiding future consequences of aggressive nutritional approaches including increased risk for cardiovascular disease and metabolic syndrome. A retrospective single center cohort study was conducted to compare the performance of two growth-assessment tools, Fenton and Intergrowth-21st (IG-21st) in the classification of size at birth, identification of impaired growth and predicting neurodevelopment. A total of 340 infants with mean gestational age of 30 weeks were included. Proportion of agreement between the two tools for identification of small for gestational age (SGA) was high 0.94 (0.87, 0.1) however, agreement for classification of postnatal growth failure at discharge was moderate 0.6 (0.52, 0.69). Growth failure at discharge was less prevalent using IG-21st. There was significant association between weight-based growth failure and poor neurodevelopmental outcomes at 12 and 24 months of age.

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Individualized Target Fortification of Breast Milk: Optimizing Macronutrient Content Using Different Fortifiers and Approaches

Frontiers in Nutrition ◽

10.3389/fnut.2021.652641 ◽

2021 ◽

Vol 8 ◽

Author(s):

Stephanie Fusch ◽

Gerhard Fusch ◽

Efrah I. Yousuf ◽

Markus Rochow ◽

Hon Yiu So ◽

...

Keyword(s):

Breast Milk ◽

Preterm Infants ◽

Significant Proportion ◽

Nutrient Content ◽

Initial Step ◽

Milk Composition ◽

Milk Analysis ◽

Milk Samples ◽

Macronutrient Content ◽

Clinical Scenarios

Background: Native breast milk composition displays significant inter- and intra-individual variation which persists after standard fortification with fixed doses and challenges target fortification. This study aims to analyze the macronutrient composition of different commercially available fortifiers and the effect of different fortification strategies on nutritional intake of preterm infants.Methods: In 103 preterm infants, native breast milk samples were collected from 24-h feeding batches (n = 3,338) and fat, protein and carbohydrate contents were analyzed. Nutrient content was compared for breast milk that had undergone either (i) standard fortification, (ii) targeted fortification, (iii) selective batching according to breast milk composition, or (iv) partial lyophilization. For (i) eight commercially available standard fortifiers were tested. Targeted fortification (ii) involved the addition of single component modulars of either protein, fat or carbohydrates to standard fortified breast milk. Using a mathematical growth model, the combined effect of protein, fat and carbohydrate intake on growth was assessed. The best composition of standard fortifiers as the initial step for target fortification was explored assuming three clinical scenarios for milk analysis.Results: Macronutrient content was highly variable between native breast milk samples, and this variation was still present after standard fortification, however at elevated macronutrient levels. Standard fortification, breast milk batching, as well as partial lyophilization of human milk resulted in deficient and imbalanced enteral intakes in a significant proportion of infants. Target fortification reduced this variation in a, respectively, higher percentage of samples. The effect size was dependent on the number of measurements per week. The optimum composition of standard fortifiers was dependent on the clinical scenario (measurement frequency) for target fortification.Conclusions: To provide precise and accurate intakes of macronutrients, breast milk should be target fortified. Standard fortified breast milk can result in excess above recommended intakes of some macronutrients which limits the efficiency of target fortification. Standard fortifiers with improved composition are needed for target fortification.

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BREAST MILK AND NEURODEVELOPMENTAL OUTCOMES IN EXTREMELY PRETERM INFANTS

Journal of Paediatrics and Child Health ◽

10.1111/jpc.14409_71 ◽

2019 ◽

Vol 55 (S1) ◽

pp. 29-29

Keyword(s):

Breast Milk ◽

Preterm Infants ◽

Neurodevelopmental Outcomes ◽

Extremely Preterm ◽

Extremely Preterm Infants

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Impact of size at birth and postnatal growth on metabolic and neurocognitive outcomes in prematurely born school-age children

Scientific Reports ◽

10.1038/s41598-021-86292-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yoo Jinie Kim ◽

Seung Han Shin ◽

Eun Sun Lee ◽

Young Hwa Jung ◽

Young Ah Lee ◽

...

Keyword(s):

Birth Weight ◽

Preterm Infants ◽

Gestational Age ◽

Growth Velocity ◽

Postnatal Growth ◽

School Age ◽

Z Score ◽

Neurodevelopmental Outcomes ◽

Neurocognitive Outcomes ◽

Size At Birth

AbstractPrematurity, size at birth, and postnatal growth are important factors that determine cardiometabolic and neurodevelopmental outcomes later in life. In the present study, we aimed to investigate the associations between the size at birth and growth velocity after birth with cardiometabolic and neurodevelopmental outcomes in preterm infants. Fifty-six preterm infants born at < 32 weeks of gestation or having a birth weight of < 1500 g were enrolled and categorized into small for gestational age (SGA) and appropriate for gestational age (AGA) groups. Anthropometric and cardiometabolic parameters were assessed at school-age, and the Korean Wechsler Intelligence Scale for Children, fourth edition (K-WISC-IV) was used for assessing the intellectual abilities. The growth velocity was calculated by changes in the weight z-score at each time period. Multivariate analysis was conducted to investigate the associations of growth velocity at different periods with cardiometabolic and neurodevelopmental outcomes. Forty-two (75%) were classified as AGA and 25% as SGA. At school-age, despite the SGA children showing significantly lower body weight, lean mass index, and body mass index, there were no differences in the cardiometabolic parameters between SGA and AGA groups. After adjusting for gestational age, birth weight z-score, weight z-score change from birth to discharge and sex, change in weight z-score beyond 12 months were associated with a higher systolic blood pressure, waist circumference, and insulin resistance. Full-scale intelligent quotient (β = 0.314, p = 0.036) and perceptional reasoning index (β = 0.456, p = 0.003) of K-WISC-IV were positively correlated with postnatal weight gain in the neonatal intensive care unit. Although cardiometabolic outcomes were comparable in preterm SGA and AGA infants, the growth velocity at different time periods resulted in different cardiometabolic and neurocognitive outcomes. Thus, ensuring an optimal growth velocity at early neonatal period could promote good neurocognitive outcomes, while adequate growth after 1 year could prevent adverse cardiometabolic outcomes in preterm infants.

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Aortic growth arrest after preterm birth: a lasting structural change of the vascular tree

Journal of Developmental Origins of Health and Disease ◽

10.1017/s2040174411000274 ◽

2011 ◽

Vol 2 (4) ◽

pp. 218-225 ◽

Cited By ~ 18

Author(s):

U. Schubert ◽

M. Müller ◽

A.-K. Edstedt Bonamy ◽

H. Abdul-Khaliq ◽

M. Norman

Keyword(s):

Preterm Birth ◽

Carotid Artery ◽

Preterm Infants ◽

Growth Failure ◽

Later Life ◽

Postnatal Growth ◽

Direct Result ◽

Arterial Tree ◽

Very Preterm Infants ◽

Very Preterm

Young people who are born very preterm exhibit a narrower arterial tree as compared with people born at term. We hypothesized that such arterial narrowing occurs as a direct result of premature birth. The aim of this study was to compare aortic and carotid artery growth in infants born preterm and at term. Observational and longitudinal cohort study of 50 infants (21 born very preterm, all appropriate for gestational age, 29 controls born at term) was conducted. Diameters of the upper abdominal aorta and common carotid artery were measured with ultrasonography at three months before term, at term and three months after term-equivalent age. At the first assessment, the aortic end-diastolic diameter (aEDD) was slightly larger in very preterm infants as compared with fetal dimensions. Fetal aortic EDD increased by 2.6 mm during the third trimester, whereas very preterm infants exhibited 0.9 mm increase in aEDD during the same developmental period (P < 0.001 for group difference). During the following 3-month period, aortic growth continued unchanged (+0.9 mm) in very preterm infants, whereas postnatal growth in term controls slowed down to +1.3 mm (P < 0.001 v. fetal aortic growth). At the final examination, aEDD was 22% and carotid artery EDD was 14% narrower in infants born preterm compared with controls, also after adjusting for current weight (P < 0.01). Aortic and carotid artery growth is impaired after very preterm birth, resulting in arterial narrowing. Arterial growth failure may be a generalized vascular phenomenon after preterm birth, with implications for cardiovascular morbidity in later life.

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Germinal Matrix-Intraventricular Hemorrhage: A Tale of Preterm Infants

International Journal of Pediatrics ◽

10.1155/2021/6622598 ◽

2021 ◽

Vol 2021 ◽

pp. 1-14

Author(s):

Walufu Ivan Egesa ◽

Simon Odoch ◽

Richard Justin Odong ◽

Gloria Nakalema ◽

Daniel Asiimwe ◽

...

Keyword(s):

Preterm Infants ◽

Intraventricular Hemorrhage ◽

Very Low Birth Weight ◽

Preterm Neonates ◽

Low Birth Weight Infants ◽

Neurodevelopmental Outcomes ◽

Germinal Matrix ◽

Posthemorrhagic Hydrocephalus ◽

Management Interventions ◽

Incidence Risk

Germinal matrix-intraventricular hemorrhage (GM-IVH) is a common intracranial complication in preterm infants, especially those born before 32 weeks of gestation and very-low-birth-weight infants. Hemorrhage originates in the fragile capillary network of the subependymal germinal matrix of the developing brain and may disrupt the ependymal lining and progress into the lateral cerebral ventricle. GM-IVH is associated with increased mortality and abnormal neurodevelopmental outcomes such as posthemorrhagic hydrocephalus, cerebral palsy, epilepsy, severe cognitive impairment, and visual and hearing impairment. Most affected neonates are asymptomatic, and thus, diagnosis is usually made using real-time transfontanellar ultrasound. The present review provides a synopsis of the pathogenesis, grading, incidence, risk factors, and diagnosis of GM-IVH in preterm neonates. We explore brief literature related to outcomes, management interventions, and pharmacological and nonpharmacological prevention strategies for GM-IVH and posthemorrhagic hydrocephalus.

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