Importance:Immunization of extremely low-birth-weight (ELBW) infants in the neonatal intensive care unit (NICU) is associated with adverse events, including fever and apnea or bradycardia, in the immediate postimmunization period. These adverse events present a diagnostic dilemma for physicians, leading to the potential for immunization delay and sepsis evaluations.

Objective:To compare the incidence of sepsis evaluations, need for increased respiratory support, intubation, seizures, and death among immunized ELBW infants in the 3 days before and after immunization.

Design, Setting, and Participants:In this multicenter retrospective cohort study, we studied 13 926 ELBW infants born at 28 weeks' gestation or less who were discharged from January 1, 2007, through December 31, 2012, from 348 NICUs managed by the Pediatrix Medical Group.

Exposures:At least one immunization between the ages of 53 and 110 days.

Main Outcomes and Measures:Incidence of sepsis evaluations, need for increased respiratory support, intubation, seizures, and death.

Results:Most of the 13 926 infants (91.2%) received 3 or more immunizations. The incidence of sepsis evaluations increased from 5.4 per 1000 patient-days in the preimmunization period to 19.3 per 1000 patient-days in the postimmunization period (adjusted rate ratio [ARR], 3.7; 95% CI, 3.2-4.4). The need for increased respiratory support increased from 6.6 per 1000 patient-days in the preimmunization period to 14.0 per 1000 patient-days in the postimmunization period (ARR, 2.1; 95% CI, 1.9-2.5), and intubation increased from 2.0 per 1000 patient-days to 3.6 per 1000 patient-days (ARR, 1.7; 95% CI, 1.3-2.2). The postimmunization incidence of adverse events was similar across immunization types, including combination vaccines when compared with single-dose vaccines. Infants who were born at 23 to 24 weeks' gestation had a higher risk of sepsis evaluation and intubation after immunization. A prior history of sepsis was associated with higher risk of sepsis evaluation after immunization.

Conclusions and Relevance:All ELBW infants in the NICU had an increased incidence of sepsis evaluations and increased respiratory support and intubation after routine immunization. Our findings provide no evidence to suggest that physicians should not use combination vaccines in ELBW infants. Further studies are needed to determine whether timing or spacing of immunization administrations confers risk for the developing adverse events and whether a prior history of sepsis confers risk for an altered immune response in ELBW infants.

OBJECTIVE: Beneficial effects of breast milk on cognitive skills and behavior ratings have been demonstrated previously in term and very low birth weight infants. Extremely low birth weight infants are known to be at increased risk for developmental and behavior morbidities. The benefits of breast milk that is ingested in the NICU by extremely low birth weight infants on development and behavior have not been evaluated previously.

METHODS: Nutrition data including enteral and parenteral feeds were collected prospectively, and follow-up assessments of 1035 extremely low birth weight infants at 18 months' corrected age were completed at 15 sites that were participants in the National Institute of Child Health and Human Development Neonatal Research Network Glutamine Trial between October 14, 1999, and June 25, 2001. Total volume of breast milk feeds (mL/kg per day) during hospitalization was calculated. Neonatal characteristics and morbidities, interim history, and neurodevelopmental and growth outcomes at 18 to 22 months' corrected age were assessed.

RESULTS: There were 775 (74.9%) infants in the breast milk and 260 (25.1%) infants in the no breast milk group. Infants in the breast milk group were similar to those in the no breast milk group in every neonatal characteristic and morbidity, including number of days of hospitalization. Mean age of first day of breast milk for the breast milk infants was 9.3 +/- 9 days. Infants in the breast milk group began to ingest non-breast milk formula later (22.8 vs 7.3 days) compared with the non-breast milk group. Age at achieving full enteral feeds was similar between the breast milk and non-breast milk groups (29.0 +/- 18 vs 27.4 +/- 15). Energy intakes of 107.5 kg/day and 105.9 kg/day during the hospitalization did not differ between the breast milk and non-breast milk groups, respectively. At discharge, 30.6% of infants in the breast milk group still were receiving breast milk. Mothers in the breast milk group were significantly more likely to be white (42% vs 27%), be married (50% vs 30%), have a college degree (22% vs 6%), and have private health insurance (34% vs 18%) compared with the no breast milk group. Mothers who were black, had a low household income (or = 85, higher mean Bayley Psychomotor Development Index, and higher Bayley Behavior Rating Scale percentile scores for orientation/engagement, motor regulation, and total score. There were no differences in the rates of moderate to severe cerebral palsy or blindness or hearing impairment between the 2 study groups. There were no differences in the mean weight (10.4 kg vs 10.4 kg), length (80.5 cm vs 80.5 cm), or head circumference (46.8 cm vs 46.6 cm) for the breast milk and no breast milk groups, respectively, at 18 months. Multivariate analyses, adjusting for confounders, confirmed a significant independent association of breast milk on all 4 primary outcomes: the mean Bayley (Mental Development Index, Psychomotor Development Index, Behavior Rating Scale, and incidence of rehospitalization). For every 10-mL/kg per day increase in breast milk ingestion, the Mental Development Index increased by 0.53 points, the Psychomotor Development Index increased by 0.63 points, the Behavior Rating Scale percentile score increased by 0.82 points, and the likelihood of rehospitalization decreased by 6%. In an effort to identify a threshold effect of breast milk on Bayley Mental Development Index and Psychomotor Development Index scores and Behavior Rating Scale percentile scores, the mean volume of breast milk per kilogram per day during the hospitalization was calculated, and infants in the breast milk group were divided into quintiles of breast milk ingestion adjusted for confounders. Overall, the differences across the feeding quintiles of Mental Development Index and Psychomotor Development Index were significant. There was a 14.0% difference in Behavior Rating Scale scores between the lowest and highest quintiles. For the outcomes (Mental Development Index, Psychomotor Development Index, Behavior Rating Scale, and Rehospitalization<1 year), only the values for the>80th percentile quintile of breast milk feeding were significantly different from the no breast milk values. In our adjusted regression analyses, every 10 mL/kg per day breast milk contributed 0.53 points to the Bayley Mental Development Index; therefore, the impact of breast milk ingestion during the hospitalization for infants in the highest quintile (110 mL/kg per day) on the Bayley Mental Development Index would be 10 x 0.53, or 5.3 points.

CONCLUSIONS: An increase of 5 points potentially would optimize outcomes and decrease costs by decreasing the number of very low birth weight children who require special education services. The societal implications of a 5-point potential difference (one third of an SD) in IQ are substantial. The potential long-term benefit of receiving breast milk in the NICU for extremely low birth weight infants may be to optimize cognitive potential and reduce the need for early intervention and special education services.

BACKGROUND: Necrotizing enterocolitis (NEC) is a frequent cause of mortality and morbidity in very low birth weight (VLBW) infants. Human milk (HM) feeding has been associated with lower risk of NEC. However, mothers of VLBW infants often experience insufficient milk production, resulting in mixed feedings of HM and formula. Moreover, medical complications often limit the volume of feeding they can be given.

OBJECTIVE: To determine if high proportions of (50% or greater) HM enteral feeding within the first 14 days of life are protective against NEC.

METHOD: This was a prospective cohort study of VLBW infants who were grouped according to the HM proportion of enteral feeding in the first 14 days:<50% (low human milk, LHM, n=46) and>or =50% (high human milk, HHM, n=156). The outcome of interest was development of NEC (Bell stage 2 or 3). Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) and to assess potential confounding due to perinatal risk factors.

RESULT: Two hundred and two infants were studied. Confirmed NEC occurred in 5/46 (10.6%) of the LHM group, as compared with 5/156 (3.2%) of the HHM. Gestational age was the only perinatal factor associated with risk of NEC. After adjustment for gestational age, HHM was associated with a lower risk of NEC ((OR=0.17, 95% CI: 0.04 to 0.68), P=0.01).

CONCLUSION: Enteral feeding containing at least 50% HM in the first 14 days of life was associated with a sixfold decrease in the odds of NEC.

PURPOSE: To determine the influence of breastmilk consumption, as a dose response, in very low-birth-weight (VLBW) infants (<1,500 g) on neurodevelopmental outcomes at 6 and 12 months corrected age, and to determine the influence of selected sociodemographic and infant variables on neurodevelopmental outcomes.

SUBJECTS: VLBW infants (n = 148) who were fed mother's milk or formula by parental choice.

DESIGN: Prospective cohort with longitudinal follow-up at 6 and 12 months corrected age.

METHODS: Self-administered questionnaires given to mothers at study entry, before discharge, and at 3-, 6-, and 12-month follow-up visits. During hospitalization, mothers recorded the 24-hour volume of expressed milk once per week. At each follow-up visit, the volume of a single feeding was assessed by pre- and postbreastfeeding test weights of infants measured on an electronic scale accurate to 1.0 g. The amount of breastfeeding was also assessed by feeding records and mother's report.

MAIN OUTCOME MEASURES: The Bayley Scales of Infant Development (2nd Edition), the Mental Developmental Index (MDI), and the Psychomotor Developmental Index (PDI).

PRINCIPAL RESULTS: After controlling for specific sociodemographic and infant variables, this study of VLBW infants showed no statistically significant effect of predominantly breastfeeding compared with predominantly formula feeding on neurodevelopmental outcomes to 12 months corrected age. The most significant predictor of MDI scores at 6 and 12 months corrected age was birth weight, in which higher birth weights predicted higher MDI scores.

CONCLUSIONS: Despite the lack of statistically significant differences, the findings suggest a small but consistent advantage in developmental scores in infants who were fed their mother's milk compared with those who were predominantly formula fed. Supporting parents to breastfeed preterm infants may maximize the potential advantages of early nutrition in the neurodevelopmental outcome of VLBW infants.

Eighty-four depressed pregnant women were recruited during the second trimester of pregnancy and randomly assigned to a massage therapy group, a progressive muscle relaxation group or a control group that received standard prenatal care alone. These groups were compared to each other and to a non-depressed group at the end of pregnancy. The massage therapy group participants received two 20 min therapy sessions by their significant others each week for 16 weeks of pregnancy, starting during the second trimester. The relaxation group provided themselves with progressive muscle relaxation sessions on the same time schedule. Immediately after the massage therapy sessions on the first and last days of the 16-week period the women reported lower levels of anxiety and depressed mood and less leg and back pain. By the end of the study the massage group had higher dopamine and serotonin levels and lower levels of cortisol and norepinephrine. These changes may have contributed to the reduced fetal activity and the better neonatal outcome for the massage group (i.e. lesser incidence of prematurity and low birthweight), as well as their better performance on the Brazelton Neonatal Behavior Assessment. The data suggest that depressed pregnant women and their offspring can benefit from massage therapy.

BACKGROUND: We previously reported beneficial effects of breast milk ingestion by infants with extremely low birth weight in the NICU on developmental outcomes at 18 months' corrected age. The objective of this study was to determine whether these effects of breast milk in infants with extremely low birth weight persisted at 30 months' corrected age.

METHODS: Nutrition data, including enteral and parenteral feeds, were prospectively collected, and 30 months' corrected age follow-up assessments were completed on 773 infants with extremely low birth weight who participated in the National Institute of Child Health and Human Development Neonatal Research Network Glutamine Trial. A total of 593 ingested some breast milk during the neonatal hospitalization, and 180 ingested none. Neonatal feeding characteristics and morbidities and 30-month interim history, neurodevelopmental outcomes, and growth parameters were analyzed. Children were divided into quintiles of breast milk volume to evaluate the effects of volume of human milk ingested during the NICU hospitalization.

RESULTS: At 30 months, increased ingestion of breast milk was associated with higher Bayley Mental Developmental Index scores, higher Bayley behavior score percentiles for emotional regulation, and fewer rehospitalizations between discharge and 30 months. There were no differences in growth parameters or cerebral palsy. For every 10 mL/kg per day increase in breast milk, the Mental Developmental Index increased by 0.59 points, the Psychomotor Developmental Index by 0.56 points, and the total behavior percentile score by 0.99 points, and the risk of rehospitalization between discharge and 30 months decreased by 5%.

CONCLUSIONS: Beneficial effects of ingestion of breast milk in the NICU persist at 30 months' corrected age in this vulnerable extremely low birth weight population. Continued efforts must be made to offer breast milk to all extremely low birth weight infants both in the NICU and after discharge.

It has been shown that milk derived from mothers with term infants is not optimal for premature babies. There is also concern about the effect of heat sterilizing breast milk. At Baragwanath Hospital, the majority of mothers remain with and care for their premature babies. Over many years, pooled pasteurized breast milk has been fed to these babies before direct breast feeding is instituted. A study was done to compare feeding pooled pasteurized breast milk and untreated own mother's milk to very low birth weight babies. There was a significantly more rapid weight gain both in terms of regaining birth weight and, from this point, to reaching a weight of 1,800 g when using untreated own mother's milk. This occurred in spite of the fact that there was little difference, especially in terms of energy content, between the two types of breast milk. This was due to the fact that the pooled pasteurized milk was also largely obtained from mothers of premature babies. It is suggested from our data that slower weight gain in the group receiving the pooled pasteurized milk could be due to the pasteurization, which probably destroys heat-labile milk lipase.

Pregnant women diagnosed with major depression were given 12 weeks of twice per week massage therapy by their significant other or only standard treatment as a control group. The massage therapy group women versus the control group women not only had reduced depression by the end of the therapy period, but they also had reduced depression and cortisol levels during the postpartum period. Their newborns were also less likely to be born prematurely and low birthweight, and they had lower cortisol levels and performed better on the Brazelton Neonatal Behavioral Assessment habituation, orientation and motor scales.