Preterm infant growth – with a focus on early nutrition and initial gut microbiota

Preterm birth is a global health challenge. Even though the survival rates of preterm infants have been increasing, these fragile patients face the risks of significant shortand long-term morbidity. Growth failure is a common clinical problem. Successful nutritional management and early enteral feeding result in improved growth and developmental outcomes. The gut microbiota participates in energy harvest and has been linked to health outcomes in term infants. The colonization process and the contribution of common perinatal exposures on preterm gut microbiota composition remain fairly unknown. The aim of this study is to focus on the relationship among early nutrition, early gut microbiota composition and growth in preterm infants. First, early nutritional management and its long-term effects on growth outcomes were studied, and an independent association between first-week energy intake and growth outcomes throughout the first two years of life was detected. Then, the early gut microbiota composition of preterm neonates was compared to that of early-term neonates. The preterm gut microbiota composition was characterized as lower diversity with greater individuality compared to term microbiota composition. The contribution of numerous perinatal exposures on the preterm gut colonization process was studied, and the cause of prematurity was found as the sole significant contributor. Finally, an experimental animal model was developed to investigate whether a fecal microbiota transplant would affect growth and metabolism in germ-free mice. The results revealed impaired growth, increased inflammatory activation, and metabolic changes in mice with a very preterm meconium transplant. In conclusion, early nutritional management, the initial gut microbiota composition and perinatal exposures emerge as potential determinants of preterm infant growth and health and may offer new intervention targets to improve the longterm outcomes of preterm children.Keskoslapsen kasvu – tarkastelussa varhainen ravitsemus ja kehittyvä suolistomikrobisto Ennenaikainen syntymä on maailmanlaajuinen kansanterveysongelma. Vaikka keskosten selviämisennuste on parantunut, ovat he edelleen suuressa riskissä sairastua vakaviin sairauksiin lyhyellä ja pitkällä aikavälillä. Kasvuhäiriö on yleinen kliininen ongelma keskoslasten hoidossa. Onnistunut ravitsemushoito ja aikainen suun kautta toteutettu ravitsemus parantavat sekä kasvua että kehitysennustetta. Suolistomikrobisto osallistuu osaltaan ravinnon hyödyntämiseen, ja sen koostumus on yhdistetty moniin terveysvaikutuksiin täysaikaisilla lapsilla. Keskosen suolistomikrobiston muodostumisesta sekä siihen vaikuttavista raskauden ja synnytyksen aikaisista tekijöistä tiedetään varsin vähän. Tutkimuksen tavoitteena oli tutkia ennenaikaisena syntyneiden lasten ravitsemuksen, suolistomikrobiston ja kasvun välisiä yhteyksiä. Varhaisen ravitsemuksen pitkäaikaisvaikutuksia kasvutuloksiin selvitettiin, ja ensimmäisen elinviikon ravitsemuksen osoitettiin vaikuttavan lapsen kasvuun kahden vuoden korjattuun ikään asti. Keskoslapsen suolistomikrobiston koostumusta verrattiin täysiaikaiseen lapseen, ja vertailussa havaitsimme keskosen mikrobiston olevan yksipuolisempi sekä hyvin yksilöllinen. Erilaisten varhaisten altisteiden vaikutusta suoliston varhaiseen mikrobikolonisaatioon tutkittiin, ja ennenaikaisen syntymän syy oli tutkimuksessa ainoa mikrobiston koostumukseen vaikuttava tekijä. Lopuksi kokeellisessa eläinmallissa tutkittiin ulosteensiirron vaikutusta koe-eläinten kasvuun ja aineenvaihduntaan. Keskosille tyypillinen kasvuhäiriö, tulehdusvaste ja aineenvaihduntahäiriö saatiin siirrettyä erittäin ennenaikaisen keskosten ulosteensiirrolla steriileissä olosuhteissa kasvaneisiin hiiriin. Yhteenvetona varhainen ravitsemus, varhainen suolistomikrobisto ja perinataaliset altisteet näyttäytyvät potentiaalisina keskosen kasvuun ja terveyteen vaikuttavia tekijöitä, ja voivat tarjota uuden terveydellisen interventiokohteen

Spontaneous preterm delivery is reflected in both early neonatal and maternal gut microbiota

AbstractBackgroundAberrant gut microbiota composition in preterm neonates is linked to adverse health consequences. Little is known about the impact of perinatal factors or maternal gut microbiota on initial preterm gut colonization.MethodsFecal samples were collected from 55 preterm neonates (ResultsPreterm neonates exhibited significantly lower gut microbiota alpha diversity and distinct beta diversity clustering compared to term neonates. Spontaneous preterm birth was associated with distinct initial gut microbiota beta diversity as compared to iatrogenic delivery. Gestational age or delivery mode had no impact on the preterm gut microbiota composition. The cause of preterm delivery was also reflected in the maternal gut microbiota composition. The contribution of maternal gut microbiota to initial preterm gut colonization was more pronounced after spontaneous delivery than iatrogenic delivery and not dependent on delivery mode.ConclusionsThe initial preterm gut microbiota is distinct from term microbiota. Spontaneous preterm birth is reflected in the early neonatal and maternal gut microbiota. Transmission of gut microbes from mother to neonate is determined by spontaneous preterm delivery, but not by mode of birth.ImpactThe initial gut microbiota in preterm neonates is distinct from those born full term. Spontaneous preterm birth is associated with changes in the gut microbiota composition of both preterm neonates and their mothers. The contribution of the maternal gut microbiota to initial neonatal gut colonization was more pronounced after spontaneous preterm delivery as compared to iatrogenic preterm delivery and not dependent on delivery mode.Our study provides new evidence regarding the early gut colonization patterns in preterm infants.Altered preterm gut microbiota has been linked to adverse health consequences and may provide a target for early intervention.</p

Preterm infant meconium microbiota transplant induces growth failure, inflammatory activation, and metabolic disturbances in germ-free mice

Preterm birth may result in adverse health outcomes. Very preterm infants typically exhibit postnatal growth restriction, metabolic disturbances, and exaggerated inflammatory responses. We investigated the differences in the meconium microbiota composition between very preterm (37 weeks) human neonates by 16S rRNA gene sequencing. Human meconium microbiota transplants to germ-free mice were conducted to investigate whether the meconium microbiota is causally related to the preterm infant phenotype in an experimental model. Our results indicate that very preterm birth is associated with a distinct meconium microbiota composition. Fecal microbiota transplant of very preterm infant meconium results in impaired growth, altered intestinal immune function, and metabolic parameters as compared to term infant meconium transplants in germ-free mice. This finding suggests that measures aiming to minimize the long-term adverse consequences of very preterm birth should be commenced during pregnancy or directly after birth.</p

The Effect of Early Nutrition on Growth in Extremely Low Gestational Age Infants

Objective: Extremely preterm birth is associated with high risk of extra-uterine growth retardation. We investigated whether nutritional management during the first seven days of life affects growth patterns until the corrected age of two years in extremely preterm infants. Methods: A retrospective study of 78 extremely preterm (<28 weeks of gestation) neonates was conducted. Data regarding parenteral and enteral intake of energy, protein, lipids and glucose during the first seven days of life were collected from patient records. The outcome measures included weight, height and head circumference with Z-scores at term-equivalent age and the corrected ages of one and two years. Analyses were performed with hierarchical linear mixed models. Results: Intake of energy during the first seven days of life was statistically significantly associated with weight, length and head circumference until the corrected age of two years after adjusting for potential confounding factors. Similar statistically significant associations were observed with lipid intake and weight and length but not with head circumference. Early intake of protein or glucose was not associated with growth parameters during the first two years of life. Conclusions: Energy intake during the first seven days of life tends to program the growth pattern throughout infancy. On the macronutrient level, early lipid intake was associated with subsequent growth, whereas early intake of protein or glucose was not. These results provide support for aggressive early nutritional management of extremely preterm infants.Siirretty Doriast

Preterm infant meconium microbiota transplant induces growth failure, inflammatory activation, and metabolic disturbances in germ-free mice

Preterm birth may result in adverse health outcomes. Very preterm infants typically exhibit postnatal growth restriction, metabolic disturbances, and exaggerated inflammatory responses. We investigated the differences in the meconium microbiota composition between very preterm (37 weeks) human neonates by 16S rRNA gene sequencing. Human meconium microbiota transplants to germ-free mice were conducted to investigate whether the meconium microbiota is causally related to the preterm infant phenotype in an experimental model. Our results indicate that very preterm birth is associated with a distinct meconium microbiota composition. Fecal microbiota transplant of very preterm infant meconium results in impaired growth, altered intestinal immune function, and metabolic parameters as compared to term infant meconium transplants in germ-free mice. This finding suggests that measures aiming to minimize the long-term adverse consequences of very preterm birth should be commenced during pregnancy or directly after birth.Peer reviewe

The preterm gut microbiota and administration routes of different probiotics : a randomized controlled trial

Peer reviewe

Spontaneous preterm delivery is reflected in both early neonatal and maternal gut microbiota

Aberrant gut microbiota composition in preterm neonates is linked to adverse health consequences. Little is known about the impact of perinatal factors or maternal gut microbiota on initial preterm gut colonization.The study was funded by the Finnish Society for Pediatric Research and Juho Vainio Foundation. Open access funding provided by University of Turku (UTU) including Turku University Central Hospital.Peer reviewe