| 1. |
- Dzidic, Majda, et al.
(författare)
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Allergy development is associated with consumption of breastmilk with a reduced microbial richness in the first month of life
- 2020
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Ingår i: Pediatric Allergy and Immunology. - : WILEY. - 0905-6157 .- 1399-3038. ; 31, s. 250-257
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Tidskriftsartikel (refereegranskat)abstract
- Background Early colonization with a diverse microbiota seems to play a crucial role for appropriate immune maturation during childhood. Breastmilk microbiota is one important source of microbes for the infant, transferred together with maternal IgA antibodies. We previously observed that allergy development during childhood was associated with aberrant IgA responses to the gut microbiota already at 1 month of age, when the IgA antibodies are predominantly maternally derived in breastfed infants. Objective To determine the microbial composition and IgA-coated bacteria in breastmilk in relation to allergy development in children participating in an intervention trial with pre- and post-natal Lactobacillus reuteri supplementation. Methods A combination of flow cytometric cell sorting and 16S rRNA gene sequencing was used to characterize the bacterial recognition patterns by IgA in breastmilk samples collected one month post-partum from 40 mothers whose children did or did not develop allergic and asthmatic symptoms during the first 7 years of age. Results The milk fed to children developing allergic manifestations had significantly lower bacterial richness, when compared to the milk given to children that remained healthy. Probiotic treatment influenced the breastmilk microbiota composition. However, the proportions of IgA-coated bacteria, the total bacterial load and the patterns of IgA-coating were similar in breastmilk between mothers of healthy children and those developing allergies. Conclusion Consumption of breastmilk with a reduced microbial richness in the first month of life may play an important role in allergy development during childhood.
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| 2. |
- Generó, Magalí Martí, 1983-, et al.
(författare)
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A protocol for characterization of extremely preterm infant gut microbiota in double-blind clinical trials
- 2021
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Ingår i: STAR Protocols. - Cambridge, MA, United States : Cell press. - 2666-1667. ; 2:3
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Tidskriftsartikel (refereegranskat)abstract
- 16S rRNA gene sequencing enables microbial community profiling, but recovering fecal DNA from extremely premature infants is challenging. Here, we describe an optimized protocol for fecal DNA isolation, library preparation for 16S rRNA gene sequencing, taxonomy assignation, and statistical analyses. The protocol is complemented with a quantitative PCR for probiotic L. reuteri identification. This protocol describes how to characterize preterm infant gut microbiota and relate it to probiotic supplementation and clinical outcomes. It is customizable for other clinical trials. For complete details on the use and execution of this protocol, please refer to Martí et al. (2021) and Spreckels et al. (2021).
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| 3. |
- Kindgren, Erik, 1977-
(författare)
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Early Life Environmental Risk Factors and Gut Microbiota in Juvenile Idiopathic Arthritis : - More than a gut feeling
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: The autoimmune disease juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in children, but the cause is not fully established. Only a small percentage (13–18%) of the risk of contracting the disease can be attributed to genetic factors, but environmental factors are believed to be behind most of the risk. An unfavourable composition of gut bacteria has also been suggested as a factor that may increase the risk of developing JIA. Aims: The main aim of this thesis was to study risk factors during fetal life and in the early childhood environment for future onset of JIA. A further aim was to study the composition and importance of the gut microbiota before the onset of JIA. Methods: In the ABIS study, a population-based prospective birth cohort of 17,055 children, data were collected on environmental factors during pregnancy and childhood. We identified 111 individuals with a JIA diagnosis. Environmental factors were mainly analysed using multivariable logistic regression, with adjustment for confounding factors. The microbiome at one year of age was analysed from stool samples by 16S rRNA PCR. Results: Significant associations could be noted between mode of birth, duration of breastfeeding, birth order and exposure to antibiotics or fish early in life with future onset of JIA. These risk factors were found to pose an even higher cumulative risk if several of the factors were present. Carrying a risk allele in combination with being exposed to a specific environmental factor further increased the risk. In addition, several taxa were identified in the gut microbiota at one year that were associated with future onset of JIA. Many of these taxa were associated with one or more of the identified early childhood environmental risk factors. Conclusion: In these studies, it has been demonstrated that children with JIA have, very early in life, already been exposed to negative environmental factors (caesarean section, short-term breastfeeding, being firstborn and being exposed to antibiotics or fish during the first year of life). The effect from these risk factors appears to be to some extent mediated via a changed composition of the gut microbiota. An environmentally induced dysregulation of the microbiome can trigger or accelerate the development of JIA in genetically predisposed children.
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| 4. |
- Sahlén Helmer, Charlotte, 1971-
(författare)
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Interaction between preterm infants and their parents : Studies of early interventions in neonatal care
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background Preterm birth negatively affects infant well-being and development. A well-functioning parent-infant interaction can mitigate the risk of preterm birth on infant development. However, parent-infant interaction is often disrupted after preterm birth because of organizational factors in care, infants’ immature interaction cues, and maternal health problems. Different interventions supporting parental-infant interaction exist, but only a few target support for interaction between preterm infants born at gestational week 30-36 and their parents. Thus, an early, feasible and effective intervention that supports the preterm infant and the parents in the neonatal intensive care unit was needed. Aim The overall aim of the thesis was two-fold; first to evaluate the early intervention skin-to-skin contact on mother-infant interaction; and second, to develop a new intervention, the Early Collaborative Intervention (EACI), to explore how mothers’ experience the new intervention, and to study its effects on mother-infant interaction. Methods Study I was a randomized controlled trial with two groups. Families were randomly assigned to either continuous or intermittent skin-to-skin con-tact directly after birth. Mother-infant interaction was video recorded when the infant was four months corrected age during a Still face procedure. The interaction was later scored using two different instruments, the Ains-worth’s Maternal Sensitivity Scales and the Maternal Sensitivity and Responsivity Scale. Furthermore, the dose-response relationship between time in skin-to-skin contact and interaction quality was calculated. Study II had a descriptive design where the rationale, development, frame-work, and practical provision of the EACI program was described. Study III had a qualitative design. Mothers were interviewed about their experiences of the EACI. Data were analyzed with reflexive thematic analysis. Study IV was a randomized controlled trial with two groups. Families were randomly assigned to either the EACI or standard care. The intervention started within three days after birth. Mother-infant interaction was video recorded when the infant was one month corrected age during a bathing session. The interaction was later scored using two different instruments, the Ainsworth’s Maternal Sensitivity Scales, and the Emotional Availability system. Intention to treat and per protocol analysis were calculated as three sessions were considered the minimum required to detect a difference. Results Study I showed no significant differences in maternal interaction behavior between the groups randomized to continuous skin-to-skin contact or intermittent skin-to-skin contact. Dose-response calculations between time in skin-to-skin-contact and interaction quality showed no correlations. In Study II, the theoretical framework of the EACI was based on the attachment theory, the assessment of infant behavior described by Brazelton, and psychoeducational theory. The rationale was to provide tailored early support that improved parent-infant interaction and thereby optimized infant well-being and development. The intervention was developed by a core group in the neonatal intensive care unit at Crown Princess Victoria Children’s Hospital. It was a three-session intervention, provided during an ordinary care procedure with instant provider feedback and hands on guidance during active parental involvement. Two sessions were provided at the hospital, and one after discharge in the home of the family. In Study III two main themes were constructed, “mothers feelings evoked from the Early Collaborative Intervention” and “based on the preterm baby’s behavior”. The mothers experienced the intervention as helpful for their interaction with the infant and for them to see their infant as an individual. The per protocol analysis in Study IV showed that the intervention group had significantly higher mean scores in the Availability, Acceptance and Non-hostility subscales, indicating a more well-functioning interaction. Conclusion Continuous SSC was not superior to intermittent SSC for improving maternal interactive behavior. In contrast, the Early Collaborative Intervention, improved maternal interactive behavior if all three sessions of the intervention were provided. This was also confirmed in the interviews, in which the mothers described the intervention as helpful for their interactive behavior with their preterm infants.
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| 5. |
- Sahlén Helmer, Charlotte, et al.
(författare)
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Mothers experiences of a new early collaborative intervention, the EACI, in the neonatal period : A qualitative study
- 2023
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Ingår i: Journal of Clinical Nursing. - : Wiley. - 0962-1067 .- 1365-2702. ; 32:11-12, s. 2892-2902
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Tidskriftsartikel (refereegranskat)abstract
- Aim To explore mothers experiences of the EArly Collaborative Intervention. Background Preterm birth puts a considerable emotional and psychological burden on parents and families. Parents to moderate and late premature infants have shorter stays at the neonatal intensive care unit and have described a need for support. The EArly Collaborative Intervention was developed to support parents with preterm infants born between gestational Weeks 30 to 36. In this study, mothers experiences of the new intervention were explored. Design A qualitative design guided by a reflexive thematic analysis according to Braun and Clarke. Interviews were individually performed with 23 mothers experienced with the EArly Collaborative Intervention. Data were identified, analysed and reported using reflexive thematic analysis. The COREQ checklist was used preparing the manuscript. Results Two main overarching themes were constructed. The first theme, mothers feelings evoked from the EArly Collaborative Intervention describes the emotions raised by the intervention and how the intervention affected their parental role. Their awareness of the preterm babys behaviour increased, and the intervention helped the parents to communicate around their babys needs. The second theme, based on the preterm babys behavior, describes experiences of the provision and the learning process about their preterm babys needs and communication. The intervention was experienced as helpful both immediately and for future interaction with the baby. Conclusions Mothers found the intervention to be supportive and encouraging. They came to look upon their baby as an individual, and the new knowledge on how to care and interact with their baby affected both their own and their babys well-being. Furthermore, the intervention felt strengthening for their relationship with the other parent. Relevance to Clinical Practice The EArly Collaborative Intervention can support parents abilities as well as their relation to their baby and may thereby contribute to infant development, cognition and well-being.
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| 6. |
- van der Heiden, Marieke, et al.
(författare)
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Characterization of the gamma delta T-cell compartment during infancy reveals clear differences between the early neonatal period and 2 years of age
- 2020
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Ingår i: Immunology and Cell Biology. - : Wiley. - 0818-9641 .- 1440-1711. ; 98:1, s. 79-87
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Tidskriftsartikel (refereegranskat)abstract
- gamma delta T cells are unconventional T cells that function on the border of innate and adaptive immunity. They are suggested to play important roles in neonatal and infant immunity, although their phenotype and function are not fully characterized in early childhood. We aimed to investigate gamma delta T cells in relation to age, prematurity and cytomegalovirus (CMV) infection. Therefore, we used flow cytometry to characterize the gamma delta T-cell compartment in cord blood and peripheral blood cells from 14-day-, 2-year- and 5-year-old children, as well as in peripheral blood samples collected at several time points during the first months of life from extremely premature neonates. gamma delta T cells were phenotypically similar at 2 and 5 years of age, whereas cord blood was divergent and showed close proximity to gamma delta T cells from 14-day-old neonates. Interestingly, 2-year-old children and adults showed comparable V delta 2(+) gamma delta T-cell functionality toward both microbial and polyclonal stimulations. Importantly, extreme preterm birth compromised the frequencies of V delta 1(+) cells and affected the functionality of V delta 2(+) gamma delta T cells shortly after birth. In addition, CMV infection was associated with terminal differentiation of the V delta 1(+) compartment at 2 years of age. Our results show an adult-like functionality of the gamma delta T-cell compartment already at 2 years of age. In addition, we demonstrate an altered gamma delta T-cell phenotype early after birth in extremely premature neonates, something which could possible contribute to the enhanced risk for infections in this vulnerable group of children.
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| 7. |
- Wejryd, Erik, 1973-
(författare)
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Probiotics and prebiotics in extremely preterm infants
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Extremely preterm (EPT) infants born before gestational week (gw) 28 and with extremely low birth weight (ELBW, <1,000g) are at risk of gastrointestinal complications such as feeding intolerance and necrotising enterocolitis (NEC). This contributes to suboptimal nutrition and growth restriction, which has been associated with a worse long-time neurodevelopmental outcome. The probiotic bacterium Limosilactobacillus reuteri DSM 17938 has previously been shown to reduce feeding intolerance when given to preterm infants. The effect of this and other probiotics have, however, been insufficiently studied in EPT-ELBW infants. One explanation for the lack of effect in many probiotic prevention studies in ELBW infants may be an extensive treatment with antibiotics. Exclusive breast milk feeding can prevent NEC, but the protective effect is incomplete. The variable content of prebiotic human milk oligosaccharides (HMO) has been suggested to explain this. Aims: To evaluate if oral supplementation with L. reuteri in EPT-ELBW infants improves feeding tolerance, growth rates and neurological development; reduces the prevalence of NEC and sepsis, by having effects on intestinal colonisation, and finally whether mother’s milk HMO composition impacts on NEC, sepsis, and growth. Methods: In total 134 newborn EPT-ELBW infants were randomised to enteral L. reuteri DSM 17938 supplementation or placebo administered from the first three days until gw 35 – 36 in a double-blind trial. Data was collected during intervention and at a standardised follow-up after 2 years. The primary outcome was time to full enteral feeding analysed with an intention to treat analysis. Secondary outcomes were NEC, culture proven sepsis, growth, and neurological development until two years of age. The breast milk content of 15 dominant HMOs in samples from 2 weeks, 4 weeks and in gw 35 – 36 was analysed with high performance anion-ex-change chromatography. L. reuteri-colonisation was determined with quantitative PCR in stool samples at 1, 2, 3 and 4 weeks, at gw 35 – 36 and at 2 years of age. Results: Median time to full enteral feeding was 15 days in both study groups. Probiotics were associated with an improved cranial growth during the first 28 days (-1.2 SD vs -1.7 SD; p<0.01). L. reuteri colonisation rate was 86-98% during the supplementation. After two years, infants supple-mented with L. reuteri had a better Bayley-III language mean score (score 90 vs 83, p<0.05). Low HMO diversity in the mother´s breast milk was associated with NEC development in the infant. Conclusion: L. reuteri did not reduce feeding intolerance in EPT-ELBW infants despite a high colonisation rate. The effect of probiotic supplementation on head growth and language development has not previously been reported and may suggest benefits of regulating the gut microbiota on brain development. A difference in HMO composition in breast milk may be an important factor explaining why exclusively breast milk fed EPT-ELBW infants are partially protected against development of NEC. These studies provide knowledge and guidance for future strategies for feeding and pro-biotic supplementation in EPT-ELBW born children.
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