US Dept of Agriculture

In our previous studies of the time of initiation of feeding and method of feeding in premature infants, we observed benefits based on a variety of nutritional, metabolic, and gastrointestinal function measures for initiating early feeding (at 4 days) by the intermittent-bolus method. However, we were surprised to find that the more fortified human milk (mother's milk supplemented with protein, minerals, vitamins, and glucose polymers) consumed, the lower the incidence of late-onset sepsis and/or necrotizing enterocolitis (NEC) and the shorter the hospitalization, despite a slower rate of growth. Late-onset sepsis and NEC occurred in 31% and 2%, respectively, of infants fed predominantly fortified human milk compared with 55% and 7%, respectively, in infants fed preterm formula. The benefits for feeding fortified human milk, however, have recently been questioned (Lucas 1996). The benefits with respect to protection from infectious morbidity have not been reported previously.

The purpose of this study in premature infants is to determine the incidence of late-onset sepsis and/or NEC and duration of hospitalization in both a randomized trial of fortified human milk supplemented with either fortified pasteurized donor human milk or preterm formula and in a non-randomized comparison between fortified human milk and preterm formula. In addition, the study is designed to determine the relationship between functional antibody titers in serial milk samples and the incidence of pathogen-specific late-onset sepsis (Staphylococcus epidermidis, Staphylococcus aureus), to determine the long-term sequelae (growth, body composition, health, neurodevelopment) of human milk vs formula feeding in premature infants, and to determine the relationship between stress and milk production in mothers of premature infants.

Other

The use of pasteurized donor human milk (as a supplement if mother's own milk supply is insufficient to meet the infant's needs) has the potential risk of transmission of infection as does all human milk. The milk is to be purchased for use in the study from two Milk Banks (located in Denver and Raleigh) that follow the current strict guidelines for screening donors, screening milk, collection and storage, and pasteurization published by the Human Milk Banking Association of North America (1996). These guidelines have been reviewed and supported by the Centers for Disease Control and Prevention and the Food and Drug Administration (FDA) as well as supported by the American Academy of Pediatrics. The classical Holder pasteurization process (62.5 degree C for 30 minutes) will kill free as well as cell-associated virus for human immunodeficiency virus, human T-cell leukemia virus (HTLV-I and II), and cytomegalovirus (Ruff 1994, Oxtoby 1988). Milk immunoglobulins and other host defense proteins are somewhat resistant to the pasteurization process. Nutritional proteins, carbohydrates, lipids, and minerals are preserved after pasteurization. There are seven Milk Banks in the United States and Canada that currently are dispensing milk that is used in premature nurseries. The Executive Director of The Human Milk Banking Association of North America will serve as consultant to this study to ensure quality control and inform us of any new changes in Milk Banking policies should they arise during this study.

There are psychological stresses that might occur in mothers during completing the questionnaires. One of the co-investigators (CL) will be responsible for meeting with mothers and reviewing the questionnaires with them to reduce their anxiety. The maternal venipunctures may produce some discomfort and a bruise. Approximately 10 ml will be taken no more than every 2 weeks for a total of 16 weeks (80 ml maximum). Trained personnel are responsible for venipunctures.

Dual-energy x-ray absorptiometry (DXA) using a Hologic QDR 2000W system (Hologic Inc., Waltham, MA) will be used to measure total body mineralization. The scanner covers the whole body in about 8 minutes. The low dose (<0.007) allows for use in infants and children. The Hologic QDR-2000W is the newest version bone mineral scanner and is an FDA-approved device for adult use, but should be considered an investigational device, pending final FDA approval for infants. The device is considered "not a significant risk device." Whole body counting of natural 40K in the body will be used to measure total body potassium (TBK) of each subject. The CNRC low-background room is the only US facility designed to monitor TBK in infants. The child will lie in a supine position on a bed for 15 to 30 minutes.

If the infant is transported to the CNRC for the first visit, heart rate and oxygen saturation monitoring will continue as is done in the nursery and the feeding schedule will not be interrupted. Nurses trained in neonatal transport will bring the infants to the CNRC for the first visit.

There are no guaranteed primary benefits to the infant. However, it is expected that this study will enable the partially mother's milk-fed premature infant to continue to receive some of its own mother's milk (rather than reverting to exclusive formula feeding). The work with the mothers potentially will enable them to increase their milk production. The benefits to the mother will be that milk production will be watched more closely and efforts to augment supply may be successful. The follow-up studies will provide accurate estimates of growth which will be communicated with the infant's physician. Parents generally are interested in understanding how their premature infant grows after hospital discharge.