Heart rate variability may predict risk of disease in premature infants
Measuring variability of heart rate may identify premature infants at risk of developing necrotizing enterocolitis, a serious inflammatory condition that can lead to death, according to Penn State College of Medicine researchers.
Necrotizing enterocolitis, or NEC, may lead to destruction of the intestinal wall and vital organ failure. It affects 6 to 10 percent of premature infants within the first two weeks of life.
“NEC is currently diagnosed by a combination of laboratory and radiology tests, usually done when the disease is already significant,” said Kim Doheny, director of clinical research in newborn medicine and assistant professor of pediatrics. “Since NEC progresses so rapidly and the symptoms develop suddenly, a non-invasive biomarker that allows early detection of patients at risk is required as a matter of urgency.”
Heart rate fluctuates in the intervals between beats, and contributors to this fluctuation are measured through mathematical analysis. One of these contributors is the parasympathetic nervous system - the system that controls digestive responses and regulates the organs during rest - represented through measurement of high-frequency energy distribution. The researchers studied 70 infants born at 28 to 35 weeks within the first five to eight days of life. The babies were stable with no sign of illness.
The researchers then measured heart rate variability in the infants to test whether measuring the high-frequency component of heart rate variability may be used as a way to predict an infant’s NEC risk before disease onset. They reported the results in Neurogastroenterology & Motility.
Of the 70 infants studied, nine who later developed NEC had decreased high frequency in the heart rate variability, suggesting reduced parasympathetic nervous system activity. Of all the infants with a decreased high-frequency heart rate variability, 50 percent developed the disease. In contrast, 98 percent of those with a higher high-frequency value did not get the disease.
What Is Necrotizing Enterocolitis?
Necrotizing enterocolitis (NEC) is inflammation and death of intestinal tissue. It may involve just the lining of the intestine or the entire thickness of the intestine. In severe cases, the intestine may even perforate (a hole develops in the wall of the intestine). If this happens, the bacteria normally found only in the intestine can leak into the abdomen and cause widespread infection. This is considered a medical emergency.
NEC is most common in premature infants. It usually develops within two weeks of birth. Up to 80 percent of cases occur in premature babies, according to Children’s Hospital Cleveland Clinic. (CHCC). Around 10 percent of infants who weigh less than 3 pounds and 5 ounces develop NEC, states the Boston Children’s Hospital. (BCH)
NEC is a very dangerous disease that can progress quickly. Immediate medical attention is strongly urged if your baby shows possible symptoms.
What Causes Necrotizing Enterocolitis?
The exact cause of NEC is not clear. However, there are several theories. A lack of oxygen during a difficult delivery may result in your baby developing this condition. Other theories involve issues related to the baby’s prematurity; for instance, incomplete development in the intestines may lead to NEC.
The Texas Pediatric Surgical Associates believe that the lactose present in baby formula may lead to NEC. Because premature babies cannot completely digest this substance, the remainder might allow bacteria to grow, leading to the disease.
Having too many red blood cells and receiving blood transfusions are also risk factors.
This disease may spread between infants. This is suggested by the fact that several cases often occur in the same nursery. If another infant in your baby’s nursery develops the condition, your baby may be at risk.
“This shows that measuring high-frequency variability during this early critical window of postnatal development has value for identifying NEC risk at a time when symptoms are not evident and interventions to improve the parasympathetic nervous system activity can be given,” said researcher R. Alberto Travagli, professor of neural and behavioral sciences. “This relatively simple, economical, and non-invasive method offers the opportunity to monitor at-risk infants more closely and to test the efficacy of emerging treatments.”
As many as 50% of all premature infants manifest feeding intolerance during their hospital course, but less than one fourth of those infants develop necrotizing enterocolitis (NEC). As with all neonatal care, the risks and benefits of various clinical approaches to NEC must be considered carefully.
Patients with mild (Bell stage II) NEC require GI rest to facilitate resolution of the intestinal inflammatory process. These babies are traditionally kept on a diet of nothing by mouth (NPO) for 7-10 days, making parenteral hyperalimentation necessary. Many of these babies have difficult intravenous (IV) access. Therefore, the need for prolonged parenteral nutrition frequently requires placing central venous catheters, which have attendant risks and complications that include thromboembolic events and nosocomial infections.
Cessation of feeding and initiation of broad-spectrum antibiotics in every baby with feeding intolerance impedes proper nutrition and exposes the baby to unnecessary antibacterials that may predispose to fungemia. On the other hand, failure to intervene appropriately for the baby with early NEC may exacerbate the disease and worsen the outcome. Clearly, managing this population requires a high degree of clinical suspicion for possible untoward events, tempered by cautious watching and waiting.
Placement of a peripheral arterial line may be helpful at the beginning of the patient’s treatment to facilitate serial arterial blood sampling and invasive monitoring.
Placement of a central venous catheter for administration of pressors, fluids, antibiotics, and blood products is prudent because severely affected patients often have complications that include sepsis, shock, and disseminated intravascular coagulation (DIC).
If the baby is rapidly deteriorating, with apnea and/or signs of impending circulatory and respiratory collapse, airway control and initiation of mechanical ventilation is indicated.
The researchers say future investigations should include a larger sample that also includes measurement of inflammation at the time heart rate variability is measured.
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Other researchers are Charles Palmer, professor of pediatrics; Kirsteen Browning, assistant professor of neural and behavioral sciences; Puneet Jairath, neonatal fellow, newborn medicine; Duanping Liao, professor of public health sciences; and Fan He, research coordinator.
Children’s Miracle Network, Johnson & Johnson Health Behaviors and Quality of Life, and the National Institutes of Health funded this research.
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Matt Solovey
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