Evaluation of Feeding Intolerance in Premature Infants Using Near Infrared Spectroscopy

Approach Basic study design The study design is a matched-pair case-control cohort, longitudinal.

Study population and assembly of patients Premature infants from 32 to 36 6/7 weeks of postmenstrual age, with feeding tolerance at least of 50ml/kg/day, inpatients at the Brigham and Women's NICU.

Inclusion criteria:

• Premature infants from 32 to 36 6/7 weeks of postmenstrual age, with feeding tolerance at least of 50ml/kg/day which have been diagnosed with food intolerance.
• Control group will be composed with patients from the same population age range tolerating at least 50 ml/Kg/day (Half of the minimum full feeds daily requirement) of Human milk of enteral Formula delivered in bolus, 6 to 8 times per day.
• Written informed consent from parent(s) or guardian.

Exclusion criteria:

• Premature infants with know conditions that could affect the attachment of the sensors in the body areas as Gastroschisis, Omphalocele, Post surgical intestine resection, on peritoneal dialysis, with lacerations in the abdomen and frontal area of the head.
• Infants who have been diagnosed with Necrotizing enterocolitis.
• Infants with current diagnosis of Sepsis and/or Systemic Inflammatory Response Syndrome (SIRS).
• Infants with severe Intra-Ventricular Hemorrhage (Intra-cranial Hemorrhage).
• Infants with Hereditary Spherocytosis, total or partial (hypoplasia) congenital asplenia hypoplasia.

Exposures and their measurement The investigators will use two NIRS devices, the INVOS™ 5100c Cerebral/Somatic Oximeter is a 2 wavelength, diffuse reflectance spectroscopy system employing near infrared light to estimate the percentage of hemoglobin saturated with oxygen in tissue underneath the sensor. An adhesive sensor containing a light source and 2 photodiodes is applied to the skin over the tissue of interest and the returning light is analyzed for oxyhemoglobin and deoxyhemoglobin light absorption. Absorption signals from the photodiode closer to the light source are subtracted from those from the farther photodiode where the returning photons penetrate more deeply in the tissue. This suppresses absorption events originating in the outer layers of tissue that are common to both photodiodes, including the effects of skin pigmentation and subcutaneous tissues. This method of "spatial resolution" also allows estimation of scattering to improve measurement accuracy.

This is a non-invasive device Food and Drug Administration (FDA) approved (FDA 510k #K082327), with an intended use for infants with a weight greater than 2.5 Kg. Given that the target population of this study has weights under the description to use, and being used in cerebral oxygen monitoring, in order to be approved by the Institutional Board Review (IRB) committee. The investigators will catalogue it as non-significant risk device under the Investigational Device Exemption (IDE), 21 CFR 812.

The device has four channels where the light sensors will retrieve the lectures from the splanchnic (left flank), mesenteric (infra-umbilical), muscular (either right or left thigh) and cerebral (forehead) areas. The NIRS sensors Cerebral (IS-C) and Somatic (IS-S) Infant/Neonatal Somatic OxyAlert® will be attached directly to the infant skin in order to obtain the area lecture.

The cases will be diagnosed as feeding intolerant for the attending physician staff and those patients that have been at least with 50ml/Kg/day in their enteral feedings will be approached.

Once the case is attached with the NIRS device, the selection of the matching control will take place, a feeds tolerating infant (at least 50 mL/Kg/day) sharing gestational range age and gender if possible. for The study coordinators will obtain the consent from the parent(s); those families will have the opportunity to speak with the Physician investigator (PI). All the staff members are certified in the CITI program (Collaborative IRB Training Initiative) to ensure and discuss the protocol with the infant's parent(s) or guardian. After the sensors have been attached the data will be recorded the display of the monitor will be turned off, the data will be extracted and analyzed.

Confounders and their measurement The study design will allow to minimize the confounders with restriction (inclusion and exclusion criteria), same at risk population, and matching the cases.

Low perfusion status need to be assessed monitoring vital signs (HR,RR,BP) and pulse-oximetry (SpO2).

Outcomes and their measurement Clinical outcome data will be correlated with tissue oxygen saturation (TOI) from the NIRS device, other outcomes variables include: length of NICU stay, morbidity, mortality, feeding tolerance, advance in the feedings and abdominal sign of intolerance, abdominal distension, gastric residues greater than 50% of the intermittent bolus. Other variables will be recorded, infant perinatal history, level of oxygen requirements, ventilatory support status, morbidities associated, laboratory studies, vital signs and parenteral nutrition status. oxygen saturation by standard pulse oximetry, formula and/or human milk feeding status, and follow them until their discharge from the Hospital, looking for length of stay, development of Necrotizing enterocolitis, and/or Broncho-pulmonary dysplasia. The data will be extracted from their clinical records (EPIC System).