The association between exposure to antibiotics in the first week of life and later otitis media: The INCA study.

Otitis media (OM) is one of the most common diagnoses in preschool-age children. Its pathophysiology is poorly understood, but is associated with changes in the nasopharyngeal microbiome, immune system, and presence of allergies. These, in turn, can be affected by early-life antibiotic exposure. Therefore, this study aimed to determine if antibiotic treatment in the first week of life in children born at term was associated with acute otitis media (AOM) and otitis media with effusion (OME) in the first 4-6 years of life. METHODS: A prospective birth cohort of 436 term-born infants was followed up at 4-6 years of age. Parents reported (recurrent) AOM and OME through online questionnaires, sent to parents of 418 eligible children. Doctors' diagnoses of AOM and OME were collected after additional informed consent. Multivariate logistic regression analyses were used to study the association between antibiotic exposure and AOM and OME. RESULTS: Of the 436 infants, 151 infants received antibiotics in the first week of life. In total, 341 (82%) questionnaires were collected. The parental-reported prevalence was 45% (155/341) for AOM. Of these 155 children, 33 children also had OME (10% of the total cohort). Doctor's diagnoses were obtained from 308 (74%) children, of which 30% (91/308) had AOM. Of these 91 children, 12 children also had OME and 8 children had OME without a diagnosis of AOM (6% of the total obtained diagnoses). Antibiotic treatment in the first week of life was not significantly associated with parent-reported nor doctor-diagnosed (recurrent) AOM and OME in the first 4-6 years of life in the regression models. CONCLUSION: Antibiotic treatment in the first week of life was not associated with AOM and OME in the first 4-6 years of life in this prospective cohort of Dutch infants. More insight into the pathophysiology of OM is warranted to determine whether antibiotic-induced microbiome changes play a role in the susceptibility to OM.

Microbial effects of prebiotics, probiotics and synbiotics after Caesarean section or exposure to antibiotics in the first week of life: A systematic review.

BACKGROUND AND AIMS: Disruption of the developing microbiota by Caesarean birth or early exposure to antibiotics may impact long-term health outcomes, which can potentially be prevented by nutritional supplements. This systematic review aimed to summarise the evidence regarding the effects of prebiotics, probiotics and synbiotics on the intestinal microbiota composition of term infants born by Caesarean section or exposed to antibiotics in the first week of life. METHODS: A systematic search was performed from inception to August 2022 in Medline and Embase. Two researchers independently performed title and abstract screening (n = 12,230), full-text screening (n = 46) and critical appraisal. We included randomised controlled trials which included term-born infants who were born following Caesarean section or who were exposed to postpartum antibiotics in the first week of life, pre-, pro- or synbiotics were administered <6 weeks after birth and outcome(s) consisted of microbiota analyses. RESULTS: Twelve randomised controlled trials investigating Caesarean born infants and one randomised controlled trial including infants exposed to antibiotics were included. Group sizes varied from 11 to 230 with 1193 infants in total. Probiotic (n = 7) or synbiotic (n = 3) supplementation significantly increased the abundance of the supplemented bacterial species (of the Bifidobacterium and Lactobacillus genus), and there was a decrease in Enterobacteriaceae, especially <4 weeks of age. At phylum level, Actinobacteria (two studies), Proteobacteria (one study) and Firmicutes (one study) increased after probiotic supplementation. In three studies on prebiotics, two studies reported a significant increase in Bifidobacteria and one study found a significant increase in Enterobacteriaceae. DISCUSSION: Prebiotic, probiotic and synbiotic supplements seem to restore dysbiosis after Caesarean section towards a microbial signature of vaginally born infants by increasing the abundance of beneficial bacteria. However, given the variety in study products and study procedures, it is yet too early to advocate specific products in clinical settings.

Clinical outcomes following pre-, pro- and synbiotic supplementation after caesarean birth or antibiotic exposure in the first week of life in term born infants: A systematic review of the literature.

Background: Caesarean section and early exposure to antibiotics disrupt the developing gastrointestinal microbiome, which is associated with long-term health effects. Objective: The aim of this systematic review was to summarise the impact of prebiotics, probiotics, or synbiotics supplementation on clinical health outcomes of term infants born by caesarean section or exposed to antibiotics in the first week of life. Design: A systematic search was performed in Medline and Embase from inception to August 2021. Title and abstract screening (n = 11,248), full text screening (n = 48), and quality assessment were performed independently by two researchers. Results: Six RCTs studying caesarean born infants were included, group sizes varied between 32-193 with in total 752 children. No studies regarding supplementation after neonatal antibiotic exposure were found. Three studies administered a probiotic, one a prebiotic, one a synbiotic, and one study investigated a prebiotic and synbiotic. Several significant effects were reported at follow-up varying between 10 days and 13 years: a decrease in atopic diseases (n = 2 studies), higher immune response to tetanus and polio vaccinations (n = 2), lower response to influenza vaccination (n = 1), fewer infectious diseases (n = 2), and less infantile colic (n = 1), although results were inconsistent. Conclusions: Supplementation of caesarean-born infants with prebiotics, probiotics, or synbiotics resulted in significant improvements in some health outcomes as well as vaccination responses. Due to the variety of studied products and the paucity of studies, no recommendations can be given yet on the routine application of prebiotics, probiotics, or synbiotics to improve health outcomes after caesarean section or neonatal antibiotic exposure.

Effect of antibiotics in the first week of life on faecal microbiota development.

BACKGROUND: Infants are frequently exposed to antibiotics (AB) in the first week of life for suspected bacterial infections. Little is known about the effect of AB on the developing intestinal microbiota. Therefore, we studied intestinal microbiota development with and without AB exposure in the first week of life in term born infants. METHODS: We analysed the faecal microbiota from birth until 2.5 years of age by 16S rRNA gene amplicon sequencing in a cohort with 56 term born infants, exposed to AB in the first week of life (AB+) (AB for 2-3 days (AB2, n=20), AB for 7 days (AB7, n=36)), compared with 126 healthy controls (AB-). The effects of AB and duration were examined in relation to delivery and feeding mode. RESULTS: AB+ was associated with significantly increased relative abundance of Enterobacteriaceae at 3 weeks and 1 year and a decrease of Bifidobacteriaceae, from 1 week until 3 months of age only in vaginally delivered, but not in C-section born infants. Similar deviations were noted in AB7, but not in AB2. After AB, breastfed infants had lower relative abundance of potentially pathogenic Enterobacteriaceae compared with formula fed infants and recovered 2 weeks faster towards controls. CONCLUSIONS: AB exposure in the first week of life alters faecal microbiota development with deviations in the relative abundance of individual taxa until 1 year of age. These alterations can have long-term health consequences, which emphasises the need for future studies aiming at restoring intestinal microbiota after AB administration.

Neonatal Antibiotics and Food Allergy Are Associated With FGIDs at 4-6 Years of Age.

OBJECTIVES: Antibiotics may contribute to the development of functional gastrointestinal disorders (FGIDs). This study aimed to determine whether antibiotics during the first week of life, infantile colic in the first year of life, gut-associated immune markers at 1 year of age, and allergies at 4-6 years of age in term-born children were associated with a higher prevalence of FGIDs at 4-6 years of age. METHODS: A prospective observational cohort of 436 term-born infants was followed up at the age of 4-6 years; 151 received broad-spectrum antibiotics (AB+), and 285 healthy controls (AB-). Validated Questionnaire On Pediatric Gastrointestinal Symptoms-Rome III and International Study of Asthma and Allergy in Childhood questionnaires were sent to parents of 418 available children. The independent t-test, chi-squared test or non-parametric test and logistic multivariate regression analyses were used. RESULTS: In total, 340 of 418 (81%) questionnaires were completed. Only the presence of functional abdominal pain was significantly higher in AB+ than AB- (4% vs 0.4%, respectively, P  = 0.045). Children with food allergy fulfilled significantly more often the criteria for irritable bowel syndrome (IBS) and abdominal migraine (26% vs 9%, P  = 0.002 and 7% vs 1%, P  = 0.043, respectively) compared to non-allergic children. No differences in FGIDs existed at the age of 4-6 years between children with and without a history of infantile colic. There were significant differences in gut-associated immune markers between children with and without FGIDs. CONCLUSION: Antibiotics during the first week of life resulted in a higher risk for functional abdominal pain at 4-6 years. Furthermore, food allergy was associated with IBS and abdominal migraine at 4-6years.

Early life antibiotics and childhood gastrointestinal disorders: a systematic review.

Background: In adults, there is increasing evidence for an association between antibiotic use and gastrointestinal (GI) disorders but in children, the evidence is scarce. Objective: Assess the association between exposure to antibiotics in the first 2 years of life in term born children and the presence of chronic GI disorders later in childhood. Design: For this systematic review the MEDLINE, Embase, WHO trial register and Web of Science were systematically searched from inception to 8 June 2020. Title and abstract screening (n=12 219), full-text screening (n=132) as well as the quality assessment with the Newcastle-Ottawa Scale were independently performed by two researchers. Main outcome measures: The association between antibiotics and inflammatory bowel disease (IBD) (n=6), eosinophilic oesophagitis (EoE) (n=5), coeliac disease (CeD) (n=6), infantile colics (n=3), functional constipation (n=2), recurrent abdominal pain, regurgitation, functional diarrhoea and infant dyschezia were examined. Results: Twenty-two studies were included, 11 cohort and 11 case-control studies. A best evidence synthesis showed strong evidence for an association between antibiotic exposure in the first 2 years of life and the presence of IBD, and CeD during childhood. Moderate evidence was found for an association with EoE and no association with functional constipation in the first year of life. There was insufficient evidence for the other studied disorders. Conclusions: The use of antibiotics in early life may increase the risk of GI disorders later in life. Further studies are necessary to unravel the underlying mechanisms and determine potential preventive measures. Meanwhile judicious use of antibiotics in early childhood is highly warranted. PROSPERO registration number: PROSPERO CRD42019132631.

Antibiotic Treatment in the First Week of Life Impacts the Growth Trajectory in the First Year of Life in Term Infants.

OBJECTIVE: Antibiotic treatment in early life appears to increase the risk for childhood overweight and obesity. So far, the association between antibiotics administrated specifically during the first week of life and growth has not been studied. Therefore, we studied the association between growth and antibiotics, given in the first week of life and antibiotic courses later in the first year of life. METHOD: A prospective observational birth cohort of 436 term infants with 151 receiving broad-spectrum antibiotics for suspected neonatal infection (AB+), and 285 healthy controls (AB-) was followed during their first year. Weight, height, and additional antibiotic courses were collected monthly. A generalized-additive-mixed-effects model was used to fit the growth data. Growth curve estimation was controlled for differences in sex, gestational age, delivery mode, exclusive breast-feeding, tobacco exposure, presence of siblings, and additional antibiotic courses. RESULTS: Weight-for-age and length-for-age increase was lower in AB+ compared with AB- (P < 0.0001), resulting in a lower weight and length increase 6.26 kg (standard error [SE] 0.07 kg) and 25.4 cm (SE 0.27 cm) versus 6.47 kg (SE 0.06 kg) and 26.4 cm (SE 0.21 cm) (P < 0.05 and P < 0.005, respectively) in the first year of life. Approximately 30% of the children in both groups received additional antibiotic course(s) in their first year, whereafter additional weight gain of 76 g per course was observed (P = 0.0285). CONCLUSIONS: Decreased growth was observed after antibiotics in the first week of life, whereas increased growth was observed after later antibiotic course(s) in term born infants in the first year of life. Therefore, timing of antibiotics may determine the association with growth.

Parental Presence and Activities in a Dutch Neonatal Intensive Care Unit: An Observational Study.

The presence of parents during a neonatal intensive care unit (NICU) admission is important for the well-being of both infants and their parents. Therefore, the aim of this study was to identify parental presence in terms of frequency, duration, and activities in the NICU in relation to characteristics of both infants and parents. An observational study was performed in a Dutch level III NICU. All infants admitted for more than 24 hours were included. One hundred sixty-two infants were included. For a median duration of 3 to 4 hours a day, at least one of the parents was present. After the first week after birth, 80% of both parents participated in the care of their infant. A vaginal delivery, longer duration of kangaroo care, higher birth weight, bronchopulmonary dysplasia, being a first child, the second and following admission week(s) after birth, and a short driving distance led to a significantly longer duration of presence for both parents. Mothers were present for a significantly longer duration of time than fathers (P = .00). It is recommended that public and employer policies, as well as physical conditions and necessary facilities, in the NICU be examined for their support of parental presence.

Enemas, suppositories and rectal stimulation are not effective in accelerating enteral feeding or meconium evacuation in low-birthweight infants: a systematic review.

Early full enteral feeding in preterm infants decreases morbidity and mortality. Our systematic review covered the effectiveness of rectal stimulation, suppositories and enemas on stooling patterns and feeding tolerance in low-birthweight infants born at up to 32 weeks. It comprised seven studies published between 2007 and 2014 and covered 495 infants. CONCLUSION: Suppositories were ineffective in shortening the time to reach full enteral feeding, and the evidence on enemas was contradictory. Enemas and rectal stimulation did not shorten the time until complete meconium evacuation was reached. Further research into safe, effective interventions to accelerate meconium excretion is needed.