Effect of long-term transfusion on growth in children with sickle cell anemia: results of the STOP trial

OBJECTIVE: To determine whether long-term transfusion improves growth in children with sickle cell anemia. STUDY DESIGN: In the Stroke Prevention Trial for Sickle Cell Anemia Study, patients were randomized to receive long-term transfusion (CTX) or standard care (STC). Transfusions were administered every 3 to 5 weeks, and hemoglobin S levels were maintained at 30% pretransfusion for an average of 2 years. Serial height and weight measurements (obtained every 3 months), body mass index (BMI) values, and growth z-scores were analyzed. RESULTS: Children in the CTX (n=53) and STC (n=41) groups were similar at baseline. After 24 months, the z-scores for height, weight, and BMI of those receiving CTX had improved significantly, whereas no changes occurred in the STC group. Patients in the CTX group approached normal height-for-age and weight-for-age z-scores. Patients from a large historical control group had significantly lower weight and height growth velocities than patients in the CTX group. CONCLUSIONS: Patients in the Stroke Prevention Trial for Sickle Cell Anemia Study who received CTX had improved height and weight and BMI over a 2-year period. Higher hemoglobin levels resulting from transfusion may improve growth by lowering energy expenditure. In addition to the prevention of vasoocclusive events, CTX results in significant improvement in the growth of children with sickle cell disease.     

Co‐causation of reduced newborn size by maternal undernutrition,infections, and inflammation

More than 20 million babies are born with low birthweight annually. Small newborns have an increased risk for mortality, growth failure, and other adverse outcomes. Numerous antenatal risk factors for small newborn size have been identified, but individual interventions addressing them have not markedly improved the health outcomes of interest. We tested a hypothesis that in low‐income settings, newborn size is influenced jointly by multiple maternal exposures and characterized pathways associating these exposures with newborn size. This was a prospective cohort study of pregnant women and their offspring nested in an intervention trial in rural Malawi. We collected information on maternal and placental characteristics and used regression analyses, structural equation modelling, and random forest models to build pathway maps for direct and indirect associations between these characteristics and newborn weight‐for‐age Z‐score and length‐for‐age Z‐score. We used multiple imputation to infer values for any missing data. Among 1,179 pregnant women and their babies, newborn weight‐for‐age Z‐score was directly predicted by maternal primiparity, body mass index, and plasma alpha‐1‐acid glycoprotein concentration before 20 weeks of gestation, gestational weight gain, duration of pregnancy, placental weight, and newborn length‐for‐age Z‐score (p < .05). The latter 5 variables were interconnected and were predicted by several more distal determinants. In low‐income conditions like rural Malawi, maternal infections, inflammation, nutrition, and certain constitutional factors jointly influence newborn size. Because of this complex network, comprehensive interventions that concurrently address multiple adverse exposures are more likely to increase mean newborn size than focused interventions targeting only maternal nutrition or specific infections.     

Feeding effects on growth during infancy

OBJECTIVE: To examine the effects of formula, other milks, other liquids, cereals, and other solid foods on growth during infancy. STUDY DESIGN: Observational cohort study nested within a large (n=17,046), cluster-randomized trial. We compared growth [weight-for-age, length-for-age, and weight-for-length z scores (WAZ, LAZ, WLZ) and head circumference (HC)] during the intervals 1 to 3, 3 to 6, 6 to 9, and 9 to 12 months, using hierarchical multivariate regression to control for size at the beginning of each interval, maternal education, geographic region, and urban versus rural location. RESULTS: Mixed BF and formula/other milk were associated with significantly higher (versus breast milk only) LAZ at 1 to 3 months (+0.038 and +0.047, respectively). In the 3- to 6-month interval, mixed BF and formula/other milk led to significantly higher WAZ (+0.125 and +0.139) and LAZ (+0.081 and +0.075), whereas cereal intake was associated with large and highly significant reductions in both measures (-0.293 and -0.240) and in HC (-0.291 cm). Mixed BF and formula/other milk continued to have positive albeit smaller associations with WAZ and LAZ in the 6- to 9-month and 9- to 12-month intervals. CONCLUSIONS: Our results confirm the growth-accelerating effects of formula and other milks (versus breast milk) on weight and length gain throughout infancy, with a dose-response gradient and largest associations observed at 3 to 6 months.     

Genetic and physiologic correlates of longitudinal immunoreactive trypsinogen decline in infants with cystic fibrosis identified through newborn screening

OBJECTIVES: To characterize the time course and physiologic significance of decline in serum immunoreactive trypsinogen (IRT) levels in infants with cystic fibrosis (CF) by mode of diagnosis and genotype, and to examine IRT heritability. STUDY DESIGN: We studied longitudinal IRT measurements in 317 children with CF. We developed statistical models to describe IRT decline. Pancreatic disease severity (Mild or Severe) was assigned using CF genotype and was confirmed in 47 infants through fat malabsorption studies. RESULTS: Infants with severe disease exhibited IRT decline with non-detectable levels typically seen by 5 years of age. Infants with mild disease exhibited a decline in the first 2 years, asymptomatically approaching a level greater than published norms. IRT and fecal fat were inversely correlated. IRT values in infants with meconium ileus (MI) were significantly lower than newborn-screened infants at birth. The high proportion of shared variation in predicted IRT values among sibling pairs with severe disease suggests that IRT is heritable. CONCLUSIONS: IRT declines characteristically in infants with CF. Lower IRT values in newborns with MI suggest increased pancreatic injury. Furthermore, IRT is heritable among patients with severe disease suggesting genetic modifiers of early CF pancreatic injury. This study demonstrates heritability of a statistically modeled quantitative phenotype.     

Feeding and growth of normal birth weight infants during the first year of life in Shanghai

Aim

This study aimed to explore the relationship between infant feeding practices and growth outcomes in the first 12 months of life.

Design

Investigators completed 262 questionnaires, which included infant feeding patterns, feeding environment, feeding beliefs/attitudes and caregivers' feeding behaviors through on-site face-to-face interviews with the main caregivers of infants at 12 months of age. The infant's weight and length at ages 6 and 12 months were measured.

Setting

The study was conducted in urban Shanghai, China.

Subjects

This study included 262 healthy normal birth weight full-term singleton 6-month-old infants and their main caregivers.

Results

Among 262 infants, 86 (32.82%) infants were overweight [BMI-for-age z scores (BAZ) > + 1] at 12 months. Compared with normal weight infants, the overweight infants had higher birth weights (P = 0.009). Furthermore, the overweight infants gained significantly more weight (P < 0.001) in the first year of life. In normal weight infants, caregivers worried more about infants being “underweight” and “eating less” (P < 0.001) whereas caregivers with overweight infants worried more about infants being “overweight” (P < 0.001). Consequently, the total score of caregivers' over-feeding behaviors was significantly higher in normal weight infants (P = 0.029). However, in overweight infants, the scores of “fed quickly within 10 min” (r = 0.223, P = 0.039) and “feeding was the best way to stop the infant's fussiness” (r = 0.285, P = 0.008) were positively correlated with BAZ.

Conclusions

Overweight in early life is associated with carelessness about excessive appetite and some particular infant feeding behaviors of caregivers in Shanghai.     

Ecological pressures and milk metabolic hormones of ethnic Tibetans living at different altitudes

Background: Very little is known about how milk hormones, shown to influence growth during infancy, may contribute to patterns of altered growth in high altitude living infants.

Aim: This study investigated the association between maternal BMI, the metabolic hormones adiponectin and leptin in human milk and infant weight for age z-scores (WAZ) in Tibetans.

Subjects and methods: A sample of 116 mothers and infants (aged 0–36 months) were recruited from two locations: the Nubri Valley, Nepal (rural; altitude = 2400–3900 m) and Kathmandu, Nepal (urban, 1400 m). Milk samples, anthropometrics, biological data and environmental information were collected on mothers and infants. Milk was analysed for leptin and adiponectin.

Results: Maternal BMI was significantly associated with milk leptin content, but not adiponectin in either group. In the rural high altitude sample, child WAZ declined with age, but no such decline was seen in the urban sample.

Conclusions: Milk leptin and adiponectin were not associated with infant growth in the rural Nubri sample, but were both inversely associated with infant WAZ in the Kathmandu sample. It appears that, in ecologically stressful environments, associations between milk hormones and growth during infancy may not be detectable in cross-sectional studies.