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Maternal IgA protects against the development of necrotizing enterocolitis in preterm infants.

ABSTRACT: Neonates are protected from colonizing bacteria by antibodies secreted into maternal milk. Necrotizing enterocolitis (NEC) is a disease of neonatal preterm infants with high morbidity and mortality that is associated with intestinal inflammation driven by the microbiota1-3. The incidence of NEC is substantially lower in infants fed with maternal milk, although the mechanisms that underlie this benefit are not clear4-6. Here we show that maternal immunoglobulin A (IgA) is an important factor for protection against NEC. Analysis of IgA binding to fecal bacteria from preterm infants indicated that maternal milk was the predominant source of IgA in the first month of life and that a relative decrease in IgA-bound bacteria is associated with the development of NEC. Sequencing of IgA-bound and unbound bacteria revealed that before the onset of disease, NEC was associated with increasing domination by Enterobacteriaceae in the IgA-unbound fraction of the microbiota. Furthermore, we confirmed that IgA is critical for preventing NEC in a mouse model, in which pups that are reared by IgA-deficient mothers are susceptible to disease despite exposure to maternal milk. Our findings show that maternal IgA shapes the host-microbiota relationship of preterm neonates and that IgA in maternal milk is a critical and necessary factor for the prevention of NEC.

SUBMITTER: Gopalakrishna KP

PROVIDER: S-EPMC7424541 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Maternal IgA protects against the development of necrotizing enterocolitis in preterm infants.

Gopalakrishna Kathyayini P KP Macadangdang Benjamin R BR Rogers Matthew B MB Tometich Justin T JT Firek Brian A BA Baker Robyn R Ji Junyi J Burr Ansen H P AHP Ma Congrong C Good Misty M Morowitz Michael J MJ Hand Timothy W TW

Nature medicine 20190617 7

Neonates are protected from colonizing bacteria by antibodies secreted into maternal milk. Necrotizing enterocolitis (NEC) is a disease of neonatal preterm infants with high morbidity and mortality that is associated with intestinal inflammation driven by the microbiota<sup>1-3</sup>. The incidence of NEC is substantially lower in infants fed with maternal milk, although the mechanisms that underlie this benefit are not clear<sup>4-6</sup>. Here we show that maternal immunoglobulin A (IgA) is an ...[more]

PMID: 31209335

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Project description:BackgroundNecrotizing enterocolitis (NEC) is one of the most severe complications in very preterm infants, but there are currently no accepted methods to prevent NEC. Studies have shown that erythropoietin (EPO) has the potential to prevent NEC or improve outcomes of preterm NEC. This study aimed to determine whether recombinant human EPO (rhEPO) could protect against NEC in very preterm infants.MethodsThe study was a prospective randomized clinical trial performed among four NICU centers. A total of 1327 preterm infants with gestational age ≤ 32 weeks were admitted to the centers, and 42 infants were excluded leaving 1285 eligible infants to be randomized to the rhEPO or control group. Infants in the rhEPO group were given 500 IU/kg rhEPO intravenously every other day for 2 weeks, while the control group was given the same volume of saline. The primary outcome was the incidence of NEC in very preterm infants at 36 weeks of corrected gestational age.ResultsA total of 1285 infants were analyzed at 36 weeks of corrected age for the incidence of NEC. rhEPO treatment significantly decreased the incidence of NEC (stage I, II and III) (12.0% vs. 17.1%, p = 0.010), especially confirmed NEC (stage II and III) (3.0% vs. 5.4%, p = 0.027). Meanwhile, rhEPO treatment significantly reduced the number of red blood cells transfusion in the confirmed NEC cases (1.2 ± 0.4 vs. 2.7 ± 1.0, p = 0.004). Subgroup analyses showed that rhEPO treatment significantly decreased the incidence of confirmed NEC at gestational age < 28 weeks (p = 0.019), and the incidence of all stages NEC in preterm infants with hemoglobin < 90 g/l (p = 0.000) and 5 min Apgar score > 5 (p = 0.028).ConclusionRepeated low-dose rhEPO treatment is beneficial against NEC in very preterm infants. Trial registration The protocol was registered retrospectively at ClinicalTrials.gov (NCT03919500) on April 18, 2019. https://clinicaltrials.gov/ct2/show/NCT03919500.

Dataset Information

Maternal IgA protects against the development of necrotizing enterocolitis in preterm infants.

Publications

Maternal IgA protects against the development of necrotizing enterocolitis in preterm infants.

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