Deborah L O'Connor

Growth and Development of Premature Infants Fed Predominantly Human Milk, Predominantly Premature Infant Formula, or a Combination of Human Milk and Premature Formula

Background In a recent meta-analysis, human milk feeding of low birth-weight (LBW) infants was associated with a 5.2 point improvement in IQ tests. However, in the studies in this meta-analysis, feeding regimens were used (unfortified human milk, term formula) that no longer represent recommended practice. Objective To compare the growth, in-hospital feeding tolerance, morbidity, and development (cognitive, motor, visual, and language) of LBW infants fed different amounts of human milk until term chronologic age (CA) with those of LBW infants fed nutrient-enriched formulas from first enteral feeding. Methods The data in this study were collected in a previous randomized controlled trial assessing the benefit of supplementing nutrient-enriched formulas for LBW infants with arachidonic acid and docosahexaenoic acid. Infants (n = 463, birth weight, 750–1,800 g) were enrolled from nurseries located in Chile, the United Kingdom, and the United States. If human milk was fed before hospital discharge, it was fortified (3,050–3,300 kJ/L, 22–24 kcal/oz). As infants were weaned from human milk, they were fed nutrient-enriched formula with or without arachidonic and docosahexaenoic acids (3,300 kJ/L before term, 3,050 kJ/L thereafter) until 12 months CA. Formula fed infants were given nutrient-enriched formula with or without added arachidonic and docosahexaenoic acids (3,300 kJ/L to term, 3,050 kJ/L thereafter) until 12 months CA. For the purposes of this evaluation, infants were categorized into four mutually exclusive feeding groups: 1) predominantly human milk fed until term CA (PHM-T, n = 43); 2) ≥ 50% energy from human milk before hospital discharge (≥ 50% HM, n = 98); 3) < 50% of energy from human milk before hospital discharge (< 50% HM, n = 203); or 4) predominantly formula fed until term CA (PFF-T, n = 119). Results PFF-T infants weighed approximately 500 g more at term CA than did PHM-T infants. This absolute difference persisted until 6 months CA. PFF-T infants were also longer (1.0–1.5 cm) and had larger head circumferences (0.3–1.1 cm) than both PHM-T and ≥ 50% HM infants at term CA. There was a positive association between duration of human milk feeding and the Bayley Mental Index at 12 months CA (P = 0.032 full and P = 0.073 reduced, statistical models) after controlling for the confounding variables of home environment and maternal intelligence. Infants with chronic lung disease fed ≥ 50% HM until term CA (n = 22) had a mean Bayley Motor Index about 11 points higher at 12 months CA compared with infants PFF-T (n = 24, P = 0.033 full model). Conclusion Our data suggest that, despite a slower early growth rate, human milk fed LBW infants have development at least comparable to that of infants fed nutrient-enriched formula. Exploratory analysis suggests that some subgroups of human milk fed LBW infants may have enhanced development, although this needs to be confirmed in future studies.

Products of the Colonic Microbiota Mediate the Effects of Diet on Colon Cancer Risk

It is estimated that most colon cancers can be attributed to dietary causes. We have hypothesized that diet influences the health of the colonic mucosa through interaction with the microbiota and that it is the milieu interior that regulates mucosal proliferation and therefore cancer risk. To validate this further, we compared colonic contents from healthy 50- to 65-y-old people from populations with high and low risk, specifically low risk Native Africans (cancer incidence <1:100,000; n = 17), high risk African Americans (risk 65:100,000; n = 17), and Caucasian Americans (risk 50:100,000; n = 18). Americans typically consume a high-animal protein and -fat diet, whereas Africans consume a staple diet of maize meal, rich in resistant starch and low in animal products. Following overnight fasting, rapid colonic evacuation was performed with 2 L polyethylene glycol. Total colonic evacuants were analyzed for SCFA, vitamins, nitrogen, and minerals. Total SCFA and butyrate were significantly higher in Native Africans than in both American groups. Colonic folate and biotin content, measured by Lactobacillus rhamnoses and Lactobacillus plantarum ATCC 8014 bioassay, respectively, exceeded normal daily dietary intakes. Compared with Africans, calcium and iron contents were significantly higher in Caucasian Americans and zinc content was significantly higher in African Americans, but nitrogen content did not differ among the 3 groups. In conclusion, the results support our hypothesis that the microbiota mediates the effect diet has on colon cancer risk by their generation of butyrate, folate, and biotin, molecules known to play a key role in the regulation of epithelial proliferation.

Body Composition in Preterm Infants Who Are Fed Long-Chain Polyunsaturated Fatty Acids: A Prospective, Randomized, Controlled Trial

The objective of this study was to evaluate growth and body composition of premature infants who were fed formulas with arachidonic acid (ARA; 20:4n6) and docosahexaenoic acid (DHA; 22:6n3) to 1 y of gestation-corrected age (CA). Preterm infants (750–1800 g birth weight and <33 wk gestational age) were assigned within 72 h of first enteral feeding to one of three formulas: control (n = 22), DHA+ARA from fish/fungal oil [DHA+ARA(FF); n = 20], or DHA+ARA from egg/fish oil [DHA+ARA(EF); n = 18]. Human milk feeding was allowed on the basis of the mothers choice. Infants were fed breast milk and/or preterm formulas with or without 0.26% DHA and 0.42% ARA to term CA followed by breast milk or postdischarge preterm formulas with or without 0.16% DHA and 0.42% ARA to 12 mo CA. Body composition was measured by dual-energy x-ray absorptiometry. There were no significant differences among the three study groups at any time point in weight, length, or head circumference. Bone mineral content and bone mineral density did not differ among groups. At 12 mo CA, infants who were fed DHA+ARA-supplemented formulas had significantly greater lean body mass (p < 0.05) and significantly less fat mass (p < 0.05) than infants who were fed the unsupplemented control formula. The DHA+ARA-supplemented formulas supported normal growth and bone mineralization in premature infants who were born at <33 wk gestation. Preterm formulas that had DHA+ARA at the levels and ratios in this study and were fed to 1 y CA led to increased lean body mass and reduced fat mass by 1 y of age.

Growth and Nutrient Intakes of Human Milk–Fed Preterm Infants Provided With Extra Energy and Nutrients After Hospital Discharge

OBJECTIVES. The purpose of this pilot study was to determine whether mixing a multinutrient fortifier to approximately one half of the human milk fed each day for a finite period after discharge improves the nutrient intake and growth of predominantly human milk–fed low birth weight infants. We also assessed the impact of this intervention on the exclusivity of human milk feeding. METHODS. Human milk–fed (≥80% feeding per day) low birth weight (750–1800 g) infants (n = 39) were randomly assigned at hospital discharge to either a control or an intervention group. Infants in the control group were discharged from the hospital on unfortified human milk. Nutrient enrichment of human milk in the intervention group was achieved by mixing approximately one half of the human milk provided each day with a powdered multinutrient human milk fortifier for 12 weeks after discharge. Milk with added nutrients was estimated to contain ∼80 kcal (336 kJ) and 2.2 g protein/100 mL plus other nutrients. Intensive lactation support was provided to both groups. RESULTS. Infants in the intervention group were longer during the study period, and those born ≤1250 g had larger head circumferences than infants in the control group. There was a trend toward infants in the intervention group to be heavier at the end of the intervention compared with those in the control group. Mean protein, zinc, calcium, phosphorus, and vitamins A and D intakes were higher in the intervention group. CONCLUSIONS. Results from this study suggest that adding a multinutrient fortifier to approximately one half of the milk provided to predominantly human milk–fed infants for 12 weeks after hospital discharge may be an effective strategy in addressing early discharge nutrient deficits and poor growth without unduly influencing human milk feeding when intensive lactation support is provided.

Growth and body composition of human milk-fed premature infants provided with extra energy and nutrients early after hospital discharge: 1-year follow-up.

Objectives: Human milk (HM) is the optimal source of nutrition for premature infants; however, it is unclear whether HM alone is sufficient to meet their elevated nutritional requirements early after hospital discharge. We previously reported that premature infants (750–1800 g birth weight) fed HM containing extra nutrients for 12 weeks after discharge had dietary intakes closer to recommended levels and grew more rapidly than those fed HM alone. The objectives of the present article are to examine the impact of this intervention on bone mineralization, body composition, and HM use up to 1 year. Data are also presented on general developmental level at 18-month corrected age (CA). Patients and Methods: At discharge, predominantly HM-fed infants were randomized to receive for 12 weeks either approximately half of their feedings containing a multinutrient fortifier (intervention, n = 19) or all of their feedings as HM alone (control, n = 20). Results: Intervention infants remained longer (P < 0.001) and had greater whole-body bone mineral content (P = 0.02) until 12-month CA compared with controls. Intervention infants born less than or equal to 1250 g continued to have a larger mean head circumference throughout the first year of life (P < 0.0001). Human milk feeding (mL · kg−1 · day−1) differed between groups at 6- (P = 0.035), but not 12-month CA. No statistically significant differences were found between groups in the mental, motor, or behavior rating scale scores of the Bayley II at 18-month CA. Conclusions: Adding a multinutrient fortifier to HM provided to predominantly HM-fed premature infants early after discharge results in sustained differences in weight, length, and whole-body bone mineral content, and in smaller babies, head circumference for the first year of life.

Folic acid fortification above mandated levels results in a low prevalence of folate inadequacy among Canadians

BACKGROUND Understanding folate intakes after folic acid fortification of the food supply will help to establish dietary and supplement recommendations that balance health benefits and risks. OBJECTIVES The objectives were to estimate the prevalence of folate inadequacy (POFI) and intakes above the Tolerable Upper Intake Level (UL) among Canadians and to estimate the supplemental dose that, with diet, provides reproductive-aged women with 400 μg folic acid/d to prevent neural tube defects. DESIGN Twenty-four-hour recall and supplement (prior 30 d) data from the 2004 Canadian Community Health Survey (n = 35,107) were used to calculate the POFI and intakes above the UL with and without adjustment for fortification overages. POFI was also estimated by risk factors thought to be related to low folate intake. The Software for Intake Distribution Evaluation (SIDE program; Department of Statistics and Center for Agricultural and Rural Development, Iowa State University) was used to estimate usual dietary intakes in all analyses. RESULTS Except for women aged >70 y, POFI was <20% after adjustment for fortification overages. For children aged <14 y, POFI approached zero, even when supplement use was excluded. POFI among adults was unaffected by supplement use, except for women aged >70 y. Only 18% of reproductive-aged women consumed 400 μg folic acid/d from diet and supplements. Modeling showed that supplements containing 325-700 μg folic acid would provide adult women with 400 μg/d but not more than the UL. Diabetes was associated with POFI. CONCLUSIONS Innovative strategies are needed to ensure that the subgroups of Canadians who could still benefit from improved folate intake are targeted. Consideration should be given to removing folic acid from supplements designed for young children and men.

Maternal folate status and lactation.

Folate plays an essential role in DNA, RNA, and protein biosynthesis. For this reason, the physiological need for this vitamin is increased during periods of rapid anabolic activity such as pregnancy and lactation. Although the importance of folate and the consequences of suboptimal folate status during pregnancy, especially during the periconceptional period, are well appreciated, little is known about the value of folate during lactation. The limited number of studies available on folate intake during lactation suggest that many women do not consume an adequate amount of folate and that recommended target intakes may be too low. Although inadequate maternal folate intake does not affect milk folate concentration unless maternal deficiency is severe, potential consequences of suboptimal folate nutrition to both the mother and her future offspring should also be considered.

Nutritional Recommendations for the Late-Preterm Infant and the Preterm Infant after Hospital Discharge

Early nutritional support of preterm infants is critical to life-long health and well being. Numerous studies have demonstrated that preterm infants are at increased risk of mortality and morbidity, including disturbances in brain development. To date, much attention has focused on enhancing the nutritional support of very low and extremely low birth weight infants to improve survival and quality of life. In most countries, preterm infants are sent home before their expected date of term birth for economic or other reasons. It is debatable whether these newborns require special nutritional regimens or discharge formulas. Furthermore, guidelines that specify how to feed very preterm infants after hospital discharge are scarce and conflicting. On the other hand, the late-preterm infant presents a challenge to health care providers immediately after birth when decisions must be made about how and where to care for these newborns. Considering these infants as well babies may place them at a disadvantage. Late-preterm infants have unique and often-unrecognized medical vulnerabilities and nutritional needs that predispose them to greater rates of morbidity and hospital readmissions. Poor or inadequate feeding during hospitalization may be one of the main reasons why late-preterm infants have difficulty gaining weight right after birth. Providing optimal nutritional support to late premature infants may improve survival and quality of life as it does for very preterm infants. In this work, we present a review of the literature and provide separate recommendations for the care and feeding of late-preterm infants and very preterm infants after discharge. We identify gaps in current knowledge as well as priorities for future research.

Effect of macronutrient intake during the second trimester on glucose metabolism later in pregnancy

BACKGROUND Dietary intake is known to influence glucose metabolism, but there is little consensus on the optimal distribution of macronutrient intakes during pregnancy to prevent gestational diabetes (GDM). OBJECTIVE We aimed to investigate whether macronutrient intake distribution during the second trimester of pregnancy was associated with glucose metabolism later in pregnancy. DESIGN Women with singleton pregnancies and without preexisting type 1 or type 2 diabetes were included. Participants underwent a 3-h oral-glucose-tolerance test at 30 wk (95% CI: 25, 33 wk) gestation and were asked to recall their second-trimester dietary intake by using a validated food-frequency questionnaire. RESULTS Of the 205 participants, 47 (22.9%) had a diagnosis of GDM. A higher intake of saturated fat (β ± SEE: 0.059 ± 0.021; P = 0.005) and trans fat (0.381 ± 0.145; P = 0.009) as a percentage of energy and of added sugar (0.017 ± 0.007; P = 0.02) and a lower intake of vegetable and fruit fiber (-0.026 ± 0.012; P = 0.03) were individually associated with increased fasting glucose after multiple adjustment. In participants with a family history of type 2 diabetes, a higher vegetable and fruit fiber intake was associated with reduced insulin resistance (-0.100 ± 0.029; P = 0.0008) and increased insulin sensitivity (0.029 ± 0.012; P = 0.01), after similar adjustment. An increased risk (OR per 1-SD change) of GDM was associated with lower carbohydrate (0.60; 95% CI: 0.40, 0.90) and higher total fat (1.61; 95% CI: 1.06, 2.44) intakes as a percentage of energy, after similar adjustment. CONCLUSIONS Macronutrient intake during the second trimester of pregnancy was associated with a risk of abnormal glucose metabolism later in pregnancy. This finding supports the need for continued work to determine optimal prenatal nutritional strategies to prevent GDM. This trial is registered at clinicaltrials.gov as NCT01405547.

Field Testing of the 2006 World Health Organization Growth Charts From Birth to 2 Years: Assessment of Hospital Undernutrition and Overnutrition Rates and the Usefulness of BMI

BACKGROUND The World Health Organization (WHO) recently released a growth standard, a first attempt at describing how children should grow in an ideal environment. These charts introduce body mass index (BMI)-for-age percentiles for children younger than 2 years. Adopting the WHO standard may affect the number of children screened to require follow-up; hence, field testing needs to be completed in a tertiary care center where the incidence of suboptimal nutrition is high. The objectives of this study were to quantify differences between the new WHO and 2000 Centers for Disease Control and Prevention (CDC) growth charts for children younger than 2 years. The interchangeability of the WHO weight-for-length and WHO BMI percentiles was also assessed. METHODS Percentile scores were computed for children younger than 2 years (n = 547) admitted to a pediatric tertiary health care center in Toronto, Canada. RESULTS The WHO standard identified more children younger than 2 years as at risk of overweight/obesity compared with the CDC reference (21.0% vs 16.6%, >or=85th weight-for-length percentile) and fewer children as wasted (18.6% vs 23.0%, <5th weight-for-length percentile). The WHO BMI-for-age and WHO weight-for-length percentiles were highly correlated (r2 = 0.83) but not interchangeable. For approximately 9% of all children, and approximately 16% of those aged <or=6 months, BMI-for-age and weight-for-length percentiles differed by >25 percentile points. CONCLUSIONS These data describe for the first time the magnitude of differences in the number of children screened as undernourished (4.4% decrease) or overnourished (4.4% increase) with adoption of the WHO standard in a tertiary care setting. Furthermore, the WHOs BMI-for-age and weight-for-length percentiles for children younger than 2 years are correlated but are not interchangeable.