Nitrate and nitrite are commonly thought of as inert end products of nitric oxide (NO) oxidation, possibly carcinogenic food additives, or well-water contaminants. However, recent studies have shown that nitrate and nitrite play an important role in cardiovascular and gastrointestinal homeostasis through conversion back into NO via a physiological system involving enterosalivary recirculation, bacterial nitrate reductases, and enzyme-catalyzed or acidic reduction of nitrite to NO. The diet is a key source of nitrate in adults; however, infants ingest significantly less nitrate due to low concentrations in breast milk. In the mouth, bacteria convert nitrate to nitrite, which has gastro-protective effects. However, these nitrate-reducing bacteria are relatively inactive in infants. Swallowed nitrite is reduced to NO by acid in the stomach, affecting gastric blood flow, mucus production, and the gastric microbiota. These effects are likely attenuated in the less acidic neonatal stomach. Systemically, nitrite acts as a reservoir of NO bioactivity that can protect against ischemic injury, yet plasma nitrite concentrations are markedly lower in infants than in adults. The physiological importance of the diminished nitrate→nitrite→NO axis in infants and its implications in the etiology and treatment of newborn diseases such as necrotizing enterocolitis and hypoxic/ischemic injury are yet to be determined.

Dietary nitrate and nitrite are sources of gastric NO, which modulates blood flow, mucus production, and microbial flora. However, the intake and importance of these anions in infants is largely unknown. Nitrate and nitrite levels were measured in breast milk of mothers of preterm and term infants, infant formulas, and parenteral nutrition. Nitrite metabolism in breast milk was measured after freeze-thawing, at different temperatures, varying oxygen tensions, and after inhibition of potential nitrite-metabolizing enzymes. Nitrite concentrations averaged 0.07 ± 0.01 μM in milk of mothers of preterm infants, less than that of term infants (0.13 ± 0.02 μM) (P < .01). Nitrate concentrations averaged 13.6 ± 3.7 μM and 12.7 ± 4.9 μM, respectively. Nitrite and nitrate concentrations in infant formulas varied from undetectable to many-fold more than breast milk. Concentrations in parenteral nutrition were equivalent to or lower than those of breast milk. Freeze-thawing decreased nitrite concentration ∼64%, falling with a half-life of 32 minutes at 37°C. The disappearance of nitrite was oxygen-dependent and prevented by ferricyanide and 3 inhibitors of lactoperoxidase. Nitrite concentrations in breast milk decrease with storage and freeze-thawing, a decline likely mediated by lactoperoxidase. Compared to adults, infants ingest relatively little nitrite and nitrate, which may be of importance in the modulation of blood flow and the bacterial flora of the infant GI tract, especially given the protective effects of swallowed nitrite.

Background Plasma nitrite serves as a reservoir of nitric oxide (NO) bioactivity. Because nitrite ingestion is markedly lower in newborns than adults, we hypothesized plasma nitrite levels would be lower in newborns than in adults, and that infants diagnosed with necrotizing enterocolitis (NEC), a disease characterized by ischemia and bacterial invasion of intestinal walls, would have lower levels of circulating nitrite in the days prior to diagnosis. Methods Single blood and urine samples were collected from 9 term infants and 12 adults, 72 preterm infants every 5 d for 3 wk, and from 13 lambs before and after cord occlusion. Results Nitrite fell 50% relative to cord levels in the first day after birth; and within 15 min after cord occlusion in lambs. Urinary nitrite was higher in infants than adults. Plasma and urinary nitrite levels in infants who developed NEC were similar to those of preterm control infants on days 1 and 5, but significantly elevated at 15 and 20 d after birth. Conclusion Plasma nitrite falls dramatically at birth while newborn urinary nitrite levels are significantly greater than adults. Acute NEC is associated with elevated plasma and urinary nitrite levels.

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