Low Diversity of Human Milk Oligosaccharides is Associated with Necrotising Enterocolitis in Extremely Low Birth Weight Infants
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design and Participants
2.2. Clinical Outcomes
2.3. Purification of Human Milk Oligosaccharides
2.4. Analysis of Human Milk Oligosaccharides
2.5. Statistical Analyses
3. Results
3.1. Description of the Study Population
3.2. Development of the HMOs Over Time
3.3. Clinical Outcomes in Relation to the HMO Levels
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Name | Type | Secreted by | Day 14 n = 78 Median (IQR) | Day 28 n = 71 Median (IQR) | 36th PMW N = 56 Median (IQR) |
---|---|---|---|---|---|
3′-sialyllactose (3SL) | Sialylated | All | 328 (255–395) | 292 (226–336) | 207 (161–280) |
6′-sialyllactose (6SL) | Sialylated | All | 1197 (935–1587) | 821 (602–1019) | 291 (191–488) |
Sialyl-lacto-N-tetraose a (LSTa) | Sialylated | All | 9 (5–14) | 4 (3–8) | 3 (2–5) |
Sialyl-lacto-N-tetraose b (LSTb) | Sialylated | All | 69 (42–127) | 102 (45–142) | 75 (33–108) |
Sialyl-lacto-N-neotetraosec (LSTc) | Sialylated | All | 130 (86–197) | 79 (48–107) | 20 (12–34) |
Disialyl-lacto-N-tetraose (DSLNT) | Sialylated | All | 657 (475–1049) | 669 (394–910) | 389 (206–516) |
2′-fucosyllactose (2FL) | Neutral | Se+ | 5390 (0–7383) | 4720 (0–7072) | 4379 (1964–5840) |
3′-fucosyllactose (3FL) | Neutral | All | 1241 (569–2005) | 1486 (795–2680) | 1803 (1061–3003) |
Lacto-difucotetraose (LDFT) | Neutral | Se+ | 394 (0–685) | 388 (0–717) | 466 (38–645) |
Lacto-N-tetraose (LNT) | Neutral | All | 2294 (1708–3138) | 2205 (1640–2897) | 1529 (1112–2189) |
Lacto-N-neotetraose (LNnT) | Neutral | All | 180 (96–263) | 151 (86–220) | 155 (90–271) |
Lacto-N-fucopentaose I (LNFP I) | Neutral | Se+ | 1163 (0–1852) | 819 (0–1714) | 536 (95–1126) |
Lacto-N-fucopentaose II (LNFP II) | Neutral | Le+ | 401 (147–948) | 384 (152–826) | 324 (177–685) |
Lacto-N-fucopentaose III (LNFP III) | Neutral | All | 362 (261–496) | 402 (301–503) | 423 (320–518) |
Lacto-N-difucohexaose I (LNDH I) | Neutral | Se+ Le+ | 652 (0–1176) | 726 (0–1173) | 454 (0–968) |
Σ analyzed HMO | 15770 (12694–17393) | 14992 (12803–17655) | 11676 (10157–13703) |
No NEC (n = 96) | NEC (n = 10) | p * | |
---|---|---|---|
Gestational age, weeks + days, mean (SD) | 25 + 4 (9 days) | 25 + 1 (9 days) | 0.3 |
Birth weight, g, mean (SD) | 749 (136) | 681 (123) | 0.1 |
Birth weight zscore, mean (SD) | −1.1 (1.2) | −1.4 (1.6) | 0.6 |
Birth length, cm, mean (SD) | 32.7 (2.5) | 32.0 (2.2) | 0.4 |
Birth length z-score, mean (SD) | −1.5 (1.8) | −1.4 (2.0) | 0.9 |
Birth head circumference, cm, mean (SD) | 23.0 (1.5) | 22.8 (1.2) | 0.5 |
Birth head circumference z-score, mean (SD) | −0.8 (0.8) | −0.6 (0.7) | 0.4 |
Small for gestational age, n (%) | 22 (23) | 2 (20) | 0.8 |
Caesarean section, n (%) | 62 (65) | 6 (60) | 0.8 |
Apgar score 5 min, mean (SD) | 6.2 (2.6) | 7.0 (2.4) | 0.3 |
Apgar score 10 min, mean (SD) | 7.8 (1.9) | 8.4 (1.6) | 0.3 |
Male, n (%) | 49 (51) | 9 (90) | <0.01 |
Infants from multiple pregnancy, n (%) | 35 (36) | 4 (40) | 0.8 |
Maternal smoking, n (%) | 2 (2) | 1 (10) | 0.5 |
Maternal preeclampsia, n (%) | 10 (10) | 1 (10) | 1.0 |
Preterm premature rupture of membranes, n (%) | 30 (30) | 4 (40) | 0.6 |
Maternal chorioamnionitis, n (%) | 20 (21) | 3 (30) | 0.6 |
Maternal prepartal antibiotics, n (%) | 51 (53) | 5 (50) | 0.9 |
Prenatal steroids, n (%) | 94 (81) | 10 (100) | 0.2 |
Received surfactant, n (%) | 78 (81) | 9 (90) | 0.4 |
Antibiotics during first week, n (%) | 95 (99) | 10 (100) | 1.0 |
Antibiotics during second week, n (%) | 76 (79) | 10 (100) | 0.2 |
Probiotic supplementation, n (%) | 50 (52) | 5 (50) | 1.0 |
Patent ductus arteriosus treated, n (%) | 70 (73) | 7 (70) | 1.0 |
Secreted by | NEC (n = 9) Median (IQR) | No NEC (n = 80) Median (IQR) | p * | |||
---|---|---|---|---|---|---|
3SL | All | 318 | (231–376) | 321 | (254–395) | 0.8 |
6SL | All | 1437 | (1220–1635) | 1159 | (919–1585) | 0.2 |
LSTa | All | 9 | (7–17) | 10 | (5–14) | 0.6 |
LSTb | All | 49 | (29–144) | 68 | (42–128) | 0.4 |
LSTc | All | 138 | (103–196) | 130 | (85–198) | 0.7 |
DSLNT | All | 572 | (401–1193) | 674 | (498–1038) | 0.4 |
2FL | Se+ | 6331 | (0–8026) | 5390 | (3374–7223) | 0.9 |
3FL | All | 675 | (436–3004) | 1255 | (575–1841) | 0.6 |
LDFT | Se+ | 45 | (0–651) | 410 | (28–686) | 0.2 |
LNT | All | 3507 | (1277–4320) | 2294 | (1710–2990) | 0.7 |
LNnT | All | 129 | (90–208) | 187 | (111–273) | 0.2 |
LNFP I | Se+ | 797 | (0–3903) | 1165 | (441–1789) | 0.5 |
LNFP II | Le+ | 124 | (0–1996) | 413 | (191–880) | 0.6 |
LNFP III | All | 363 | (332–437) | 351 | (267–526) | 0.8 |
LNDH I | Se+ Le+ | 0 | (0–213) | 882 | (0–1279) | <0.01 |
Σ analyzed HMO | 15889 | (11623–18311) | 15770 | (13405–17274) | 0.8 |
Secretedby | Sepsis (n = 32) Median (IQR) | No Sepsis (n = 57) Median (IQR) | p * | |||
---|---|---|---|---|---|---|
3-SL | All | 283 | (236–336) | 331 | (268–399) | 0.2 |
6-SL | All | 1313 | (1088–1647) | 1142 | (876–1503) | <0.05 |
LSTa | All | 7 | (4–12) | 11 | (7–14) | 0.1 |
LSTb | All | 62 | (34–154) | 72 | (42–114) | 0.5 |
LSTc | All | 134 | (102–174) | 127 | (79–199) | 0.8 |
DSLNT | All | 622 | (426–941) | 644 | (502–1093) | 0.2 |
2FL | Se+ | 4829 | (0–7674) | 5944 | (3429–7467) | 0.3 |
3FL | All | 1367 | (595–2983) | 1227 | (524–1833) | 0.4 |
LDFT | Se+ | 386 | (0–664) | 404 | (22–690) | 0.7 |
LNT | All | 2459 | (1481–3630) | 2194 | (1768–2710) | 0.5 |
LNnT | All | 202 | (100–273) | 177 | (110–257) | 0.9 |
LNFP I | Se+ | 957 | (0–1625) | 1490 | (475–2042) | 0.2 |
LNFP II | Le+ | 494 | (171–1348) | 372 | (123–749) | 0.3 |
LNFP III | All | 363 | (269–468) | 351 | (255–531) | 0.8 |
LNDH I | Se+ Le+ | 632 | (0–1194) | 821 | (0–1231) | 0.5 |
Σ analyzed HMO | 15723 | (13137–17176) | 15972 | (13008–17512) | 0.8 |
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Wejryd, E.; Martí, M.; Marchini, G.; Werme, A.; Jonsson, B.; Landberg, E.; Abrahamsson, T.R. Low Diversity of Human Milk Oligosaccharides is Associated with Necrotising Enterocolitis in Extremely Low Birth Weight Infants. Nutrients 2018, 10, 1556. https://doi.org/10.3390/nu10101556
Wejryd E, Martí M, Marchini G, Werme A, Jonsson B, Landberg E, Abrahamsson TR. Low Diversity of Human Milk Oligosaccharides is Associated with Necrotising Enterocolitis in Extremely Low Birth Weight Infants. Nutrients. 2018; 10(10):1556. https://doi.org/10.3390/nu10101556
Chicago/Turabian StyleWejryd, Erik, Magalí Martí, Giovanna Marchini, Anna Werme, Baldvin Jonsson, Eva Landberg, and Thomas R. Abrahamsson. 2018. "Low Diversity of Human Milk Oligosaccharides is Associated with Necrotising Enterocolitis in Extremely Low Birth Weight Infants" Nutrients 10, no. 10: 1556. https://doi.org/10.3390/nu10101556