Perinatal Antibiotic Exposure Research Articles

Antibiotic therapy and necrotizing enterocolitis

Antibiotic therapy remains a cornerstone of treatment of both medical and surgical presentations of necrotizing enterocolitis (NEC). However, guidelines regarding the administration of antibiotics for the treatment of NEC are lacking and practices vary amongst clinicians. Although the pathogenesis of NEC is unknown, there is consensus that the infant gastrointestinal microbiome contributes to the disease. The presumed connection between dysbiosis and NEC has prompted some to study whether early prophylactic enteral antibiotics can prevent NEC. Yet others have taken an opposing approach, studying whether perinatal antibiotic exposure increases the risk of NEC by inducing a state of dysbiosis. This narrative review summarizes what is known about antibiotics and their association with the infant microbiome and NEC, current antibiotic prescribing practices for infants with medical and surgical NEC, as well as potential strategies to further optimize the use of antibiotics in this population of infants.

Prenatal and Perinatal Antibiotic Exposure and Long-Term Outcome.

Antibiotics are frequently administered during pregnancy. Although necessary to address acute infections, their use facilitates antibiotic resistance. Other associations have also been found with the use of antibiotics, such as perturbations of gut bacteria, delays in microbial maturation, and increased risks of allergic and inflammatory diseases. Little is known about how the prenatal and perinatal administration of antibiotics to mothers affects the clinical outcomes of their offspring. A literature search was conducted of the Cochrane, Embase, and PubMed engines. The retrieved articles were reviewed by two authors and verified for relevance. The primary outcome was the effect of pre- and perinatal maternal antibiotic use on clinical outcomes. Thirty-one relevant studies were included in the meta-analysis. Various aspects are discussed, including infections, allergies, obesity, and psychosocial factors. In animal studies, antibiotic intake during pregnancy has been suggested to cause long-term alterations in immune regulation. In humans, associations have been found between antibiotic intake during pregnancy and different types of infections and an increased risk of pediatric infection-related hospitalization. A dose-dependent positive association between pre- and perinatal antibiotic use and asthma severity has been reported in animal and human studies, while positive associations with atopic dermatitis and eczema were reported by human studies. Multiple associations were identified between antibiotic intake and psychological problems in animal studies; however, relevant data from human studies are limited. However, one study reported a positive association with autism spectrum disorders. Multiple animal and human studies reported a positive association between pre- and perinatal antibiotic use by mothers and diseases in their offspring. Our findings have potentially significant clinical relevance, particularly considering the implications for health during infancy and later in life as well as the related economic burden.

Antibiotic Use During Pregnancy and Childbirth: Prospective Observational Study on Prevalence, Indications, and Prescribing Patterns in a German Tertiary Center.

Introduction Antibiotics are powerful drugs to prevent and treat perinatal infections. Overuse of antibiotics leads to antibiotic resistance, has potential side effects and influences the maternal and neonatal microbiome. Patients and Methods We performed a prospective observational study on the prevalence, indications, and prescribing patterns of antibiotics during pregnancy and childbirth. We included women who had given birth after 23+0 weeks of gestation at a single tertiary center in Germany from January 2020 to March 2021. Descriptive statistics and binomial regression were performed to analyze the factors influencing the prescription of antibiotics. Results We included 522 postpartum women into our study. 337 (64.6%) were exposed to antibiotics during pregnancy and/or childbirth. 115 women received antibiotics during pregnancy, 291 during birth. Most antibiotics during pregnancy were prescribed for urinary tract infections (UTIs) (56.0%). Most prescriptions were issued by obstetrics and gynecology physicians (65.8%), followed by hospitals (16.7%) and family medicine physicians (8.8%). Most antibiotics during childbirth were given for a cesarean section (64.3%), followed by preterm rupture of membranes (41.2%). 95.3% of women who had a preterm birth were exposed to antibiotics. In logistic regression models, lower gestational age at birth, higher maternal body-mass-index and smoking were independently associated with antibiotic use during pregnancy and childbirth. Conclusion We found a high rate of antibiotic exposure during pregnancy and childbirth. Our results imply an urgent need for antibiotic stewardship programs in perinatal medicine as well as further research on the effects of perinatal antibiotic exposure on microbiome development and childhood health.

Is acidemia at birth a risk factor for functional gastrointestinal disorders?

Functional gastrointestinal disorders (FGIDs) are common in early childhood. It has been demonstrated that neonatal acidemia at delivery can lead to significant neonatal morbidity. The primary aim of this study was to evaluate the relationship between acidemia at birth and the development of FGIDs, as regurgitation, colic, and constipation, in term infants. Term newborns born at the Foggia University Hospital, Italy during the year 2020 were included in the study. As per routine clinical practice, a cord blood gas analysis on a blood sample drawn from the umbilical artery (UA) of each infant immediately after birth was performed, and Apgar score was recorded. One year after birth, each infant’s parents were interviewed through a phone call to investigate development of FGIDs, feeding practices, and morbidities. During the study period, 1574 term newborns met the inclusion criteria. The prevalence of infantile colic, regurgitation, and constipation was higher in infants with low UA pH (colic 51.5% vs. 25.4%, p < 0.001; regurgitation 30.6% vs. 15.2%, p < 0.001; constipation 24.6% vs. 16.0%, p = 0.015), with infants having moderate-severe acidemia facing the highest risk for all the examined FGIDs. In binary logistic regression analyses, UA pH and perinatal antibiotic exposure proved to be independently associated with the later diagnosis of each FGID.Conclusion: Newborns with acidemia at birth appear to face a higher risk of FGIDs in infancy. Avoiding low cord blood pH should continue to be the goal for obstetricians, while enhanced long-term surveillance for infants who experienced birth acidemia should be required.What is Known:• Cord blood gas analysis is recommended in all high-risk deliveries, and in some centers, it is performed after all deliveries.• Neonatal acidemia at birth has been linked to adverse outcomes, mainly neurological. Recently, perinatal asphyxia has been reported to increase the risk of developing necrotizing enterocolitis in term infants.What is New:• An association between acidemia at birth and risk of developing FGIDs such as regurgitation and colic during the first year of life had never been described so far.• An increased surveillance of infants with low UA pH at birth may be beneficial and could allow for early detection of any of the reported FGIDs.

Early life dysbiosis drives skin changes associated with increased susceptibility to Atopic Dermatitis

Compromised skin barrier, inflammation, and an altered gut/ skin microbiome (dysbiosis) are major drivers for Atopic Dermatitis (AD). Epidemiological studies indicated a link between perinatal antibiotic exposure, which can induce early life dysbiosis, and the development of AD. However, the mechanistic link between perinatal dysbiosis and AD has not yet been investigated.

Antibiotics at birth and later antibiotic courses: effects on gut microbiota

BackgroundIntrapartum antibiotic prophylaxis (IAP) is widely used, but the evidence of the long-term effects on the gut microbiota and subsequent health of children is limited. Here, we compared the impacts of perinatal antibiotic exposure and later courses of antibiotic courses on gut microbiota.MethodsThis was a prospective, controlled cohort study among 100 vaginally delivered infants with different perinatal antibiotic exposures: control (27), IAP (27), postnatal antibiotics (24), and IAP and postnatal antibiotics (22). At 1 year of age, we performed next-generation sequencing of the bacterial 16S ribosomal RNA gene of fecal samples.ResultsExposure to the perinatal antibiotics had a clear impact on the gut microbiota. The abundance of the Bacteroidetes phylum was significantly higher in the control group, whereas the relative abundance of Escherichia coli was significantly lower in the control group. The impact of the perinatal antibiotics on the gut microbiota composition was greater than exposure to later courses of antibiotics (28% of participants).ConclusionsPerinatal antibiotic exposure had a marked impact on the gut microbiota at the age of 1 year. The timing of the antibiotic exposure appears to be the critical factor for the changes observed in the gut microbiota.ImpactInfants are commonly exposed to IAP and postnatal antibiotics, and later to courses of antibiotics during the first year of life.Perinatal antibiotics have been associated with an altered gut microbiota during the first months of life, whereas the evidence regarding the long-term impact is more limited.Perinatal antibiotic exposure had a marked impact on the infant’s gut microbiota at 1 year of age.Impact of the perinatal antibiotics on the gut microbiota composition was greater than that of the later courses of antibiotics at the age of 1 year.

Intrapartum Antibiotic Exposure and Body Mass Index in Children.

Intrapartum antibiotic prophylaxis (IAP) reduces a newborn's risk of group B streptococcal infection (GBS) but may lead to an increased childhood body mass index (BMI). This was a retrospective cohort study of infants (n = 223 431) born 2007-2015 in an integrated healthcare system. For vaginal delivery, we compared children exposed to GBS-IAP and to any other type or duration of intrapartum antibiotics to no antibiotic exposure. For cesarean delivery, we compared children exposed to GBS-IAP to those exposed to all other intrapartum antibiotics, including surgical prophylaxis. BMI over 5 years was compared using nonlinear multivariate models with B-spline functions, stratified by delivery mode and adjusted for demographics, maternal factors, breastfeeding, and childhood antibiotic exposure. In vaginal deliveries, GBS-IAP was associated with higher BMI from 0.5 to 5.0 years of age compared to no antibiotics (P < .0001 for all time points, ΔBMI at age 5 years 0.12 kg/m2, 95% confidence interval [CI]: .07-.16 kg/m2). Other antibiotics were associated with higher BMI from 0.3 to 5.0 years of age. In cesarean deliveries, GBS-IAP was associated with increased BMI from 0.7 years to 5.0 years of age (P < .05 for 0.7-0.8 years, P < .0001 for all other time points) compared to other antibiotics (ΔBMI at age 5 years 0.24 kg/m2, 95% CI: .14-.34 kg/m2). Breastfeeding did not modify these associations. GBS-IAP was associated with a small but sustained increase in BMI starting at very early age. This association highlights the need to better understand the effects of perinatal antibiotic exposure on childhood health.

Perinatal Antibiotic Exposure Affects the Transmission between Maternal and Neonatal Microbiota and Is Associated with Early-Onset Sepsis

Intrapartum antibiotic prophylaxis reduces the risk of infection to a mother and neonate, but antibiotic-mediated maternal and neonatal microbiota dysbiosis increases other health risks to newborn infants. We studied the impact of perinatal antibiotic prophylaxis on the microbiota in mothers and newborns with full-term or preterm delivery. Ninety-eight pregnant women and their neonates were divided into the following four groups: full term without antibiotic exposure (FT), full term with antibiotic exposure (FTA), preterm without antibiotic exposure (PT), and preterm with antibiotic exposure (PTA). Bacterial composition was analyzed by sequencing the 16S rRNA gene from maternal vaginal swabs (V) and neonatal meconium (F). The results showed that in maternal vaginal and neonatal meconium microbiota, FT and PT groups had a higher load of Lactobacillus spp. than did the FTA and PTA groups. In addition, whether in the mother or newborn, the dissimilarity in microbiota between FT and PT was the lowest compared to that between other groups. Compared to the FT and PT groups, the dissimilarity in microbial structures between the vagina and meconium decreased in the FTA and PTA groups. The health outcome of infants reveals an association between early-onset sepsis and antibiotic-mediated microbiota dysbiosis. In conclusion, perinatal antibiotic exposure is related to the establishment of gut microbiota and health risks in newborns. Promoting the rational usage of antibiotics with pregnant women will improve neonatal health.IMPORTANCE Perinatal antibiotic prophylaxis is an effective method for preventing group B Streptococcus (GBS) infection in newborns. Antibiotic exposure unbalances women's vaginal microbiota, which is associated with the establishment of the newborn gut microbiota. However, the influence of perinatal antibiotic exposure on neonatal gut microbiota colonization and health outcomes remains unclear. In this study, we found that perinatal antibiotic exposure induced microbiota dysbiosis in a woman's vagina and the neonatal gut, and we highlight a significant decrease in the abundance of Lactobacillus spp. The influence of antibiotic use on the microbiota was greater than that from gestational age. Additionally, full-term newborns without antibiotic exposure had no evidence of early-onset sepsis, whereas in full-term or preterm newborns with antibiotic exposure before birth, at least one infant was diagnosed with early-onset sepsis. These results suggest an association between perinatal antibiotic exposure and microbial dysbiosis in maternal vaginal and neonatal gut environments, which may be related to the occurrence of early-onset sepsis.

Perinatal maternal antibiotic exposure augments lung injury in offspring in experimental bronchopulmonary dysplasia.

During the newborn period, intestinal commensal bacteria influence pulmonary mucosal immunology via the gut-lung axis. Epidemiological studies have linked perinatal antibiotic exposure in human newborns to an increased risk for bronchopulmonary dysplasia, but whether this effect is mediated by the gut-lung axis is unknown. To explore antibiotic disruption of the newborn gut-lung axis, we studied how perinatal maternal antibiotic exposure influenced lung injury in a hyperoxia-based mouse model of bronchopulmonary dysplasia. We report that disruption of intestinal commensal colonization during the perinatal period promotes a more severe bronchopulmonary dysplasia phenotype characterized by increased mortality and pulmonary fibrosis. Mechanistically, metagenomic shifts were associated with decreased IL-22 expression in bronchoalveolar lavage and were independent of hyperoxia-induced inflammasome activation. Collectively, these results demonstrate a previously unrecognized influence of the gut-lung axis during the development of neonatal lung injury, which could be leveraged to ameliorate the most severe and persistent pulmonary complication of preterm birth.

Impact of Early Life Antibiotic Exposure and Neonatal Hyperoxia on the Murine Microbiome and Lung Injury

Cross talk between the intestinal microbiome and the lung and its role in lung health remains unknown. Perinatal exposure to antibiotics disrupts the neonatal microbiome and may have an impact on the preterm lung. We hypothesized that perinatal antibiotic exposure leads to long-term intestinal dysbiosis and increased alveolar simplification in a murine hyperoxia model. Pregnant C57BL/6 wild type dams and neonatal mice were treated with antibiotics before and/or immediately after delivery. Control mice received phosphate-buffered saline (PBS). Neonatal mice were exposed to 95% oxygen for 4 days or room air. Microbiome analysis was performed using 16S rRNA gene sequencing. Pulmonary alveolarization and vascularization were analyzed at postnatal day (PND) 21. Perinatal antibiotic exposure modified intestinal beta diversity but not alpha diversity in neonatal mice. Neonatal hyperoxia exposure altered intestinal beta diversity and relative abundance of commensal bacteria in antibiotic treated mice. Hyperoxia disrupted pulmonary alveolarization and vascularization at PND 21; however, there were no differences in the degree of lung injury in antibiotic treated mice compared to vehicle treated controls. Our study suggests that exposure to both hyperoxia and antibiotics early in life may cause long-term alterations in the intestinal microbiome, but intestinal dysbiosis may not significantly influence neonatal hyperoxic lung injury.

Exposure to group B Streptococcal antibiotic prophylaxis and early childhood body mass index in a vaginal birth cohort

Purpose: Perinatal antibiotic exposure may be associated with changes in both early infancy gut microbiota and later childhood obesity. Our objective was to evaluate if group B Streptococcus (GBS) antibiotic prophylaxis is associated with higher body mass index (BMI) in early childhood.Materials and methods: This is a retrospective cohort study of mother/child dyads in a single hospital system over a 6-year period. All women with term, singleton, vertex, vaginal deliveries who received no antibiotics or received antibiotics only for GBS prophylaxis and whose children had BMIs available at 2–5 years of age were included. Children were divided into three groups for comparison: children born to GBS positive mothers that received antibiotics solely for GBS prophylaxis, children born to GBS negative women that received no antibiotics (healthy controls), and children born to GBS positive mothers who received no antibiotics. The primary outcome was the earliest available child BMI Z-score at 2–5 years of age. Multivariable linear regression was used to estimate differences in child BMI Z-scores between groups, adjusted for maternal BMI, age, race, parity, tobacco use, and child birthweight.Results: Of 4825 women, 786 (16.3%) were GBS positive and received prophylactic antibiotics, 3916 (81.2%) were GBS negative and received no antibiotics, and 123 (2.5%) were GBS positive but received no antibiotics. Childhood BMI Z-scores were similar between children exposed to intrapartum GBS prophylaxis and healthy controls who were unexposed in both unadjusted (mean (SE), 0.04 (0.04) versus −0.3 (0.02), p = .11) and adjusted (0.01 (0.05) versus −0.04 (0.03), p = .3) models.Conclusions: Exposure to intrapartum antibiotic prophylaxis for GBS was not associated with higher early childhood BMI Z-scores compared to healthy controls.

Perinatal antibiotics alter preterm infant EEG and neurobehavior in the Family Nurture Intervention trial.

Early exposure to antibiotics has been shown to increase risk for poor neurobehavioral development, particularly with regard to attention deficit disorders. Clinically, electroencephalography (EEG) is increasingly used as a biomarker of these deficits. Less is known about the effects of antibiotics on neurobehavioral and neurophysiological outcomes in preterm infants, a population at particularly high risk for attention deficits and perinatal antibiotic exposure. This study examines the effects of perinatal antibiotic exposure on neonatal EEG and attention deficits as measured by the Child Behavior Checklist in 4- to 5-year-old children who were enrolled in an NICU-based randomized controlled trial comparing Family Nurture Intervention (FNI) to standard care. Antibiotic-exposed infants had increased attention problems and there was a main effect of antibiotic exposure such that exposed infants had higher EEG power. This effect was fourfold greater in infants who received standard NICU care compared to those who received the intervention, suggesting a buffering effect of the intervention. We hypothesize that the relationship between antibiotic exposure and altered neurodevelopment may be due to effects of antibiotics on the microbiome, and that FNI may buffer these adverse consequences.

Perinatal antibiotic exposure alters composition of murine gut microbiota and may influence later responses to peanut antigen

BackgroundAccumulating evidence suggests that the gut microbiota shapes developmental processes within the immune system. Early life antibiotic use is one factor which may contribute to immune dysfunction and the recent surge in allergies by virtue of its effects on gut microbiota.Objective and methodsAs a first step towards determining whether a relationship exists between perinatal antibiotic induced changes in the gut microbiota and the later development of a peanut allergy, we exposed newborn mice to either the broad-spectrum antibiotic vancomycin or to a vehicle for 6 weeks and then used a novel murine model of peanut allergy.ResultsEarly-life treatment with vancomycin resulted in a significant shift in the gut microbiota community characterized by a reduction in the abundance of firmicutes and preponderance of inflammatory proteobacteria. Mice with an antibiotic-altered microbiota, showed a localized allergic-like response characterized by ear swelling and scratching following intra-dermal peanut antigen challenge. Likewise, circulating IgE levels were increased in antibiotic-treated mice, but no evidence of a systemic allergic or anaphylactic-like response was observed. Importantly, we utilized the naturally occurring pro-inflammatory cytokine, tumor necrosis factor-α (TNF-α), rather than the more commonly used cholera toxin, as an adjuvant together with the peanut antigen.ConclusionOur data suggest that early antibiotic exposure promotes a shift in the gut microbiota community that may in turn, influence how mice later respond to a TNF-α + antigen challenge. However, further studies verifying the capacity of microbiota restoration to protect against allergic responses will be needed to confirm a causal role of antibiotic-induced microbiota variations in promoting allergic disease phenotypes.

Reduced Necrotizing Enterocolitis after an Initiative to Promote Breastfeeding and Early Human Milk Administration.

Introduction:We sought to reduce the incidence of necrotizing enterocolitis (NEC) in premature infants (PI) by fostering the postnatal establishment of protective intestinal bacteria through early administration of human milk (HM) and probiotics.Methods:A multidisciplinary team implemented an initiative to support breastfeeding (BF) and provide early postnatal supplemental donor human milk (DHM) and probiotics to PI. Interventions included process improvements in milk preparation, storage, and fortification. PI admitted to our NICU between 2006 and 2015 were monitored for feeding of HM, DHM, and preterm formula (PF), frequency of early feedings, and incidence of NEC.Results:Retrospective review of 2557 cases revealed post-initiative increases in the percentage of PI receiving HM (91.5% to 96.1%), HM within 48 hours of birth (75% to 90.6%), and DHM (17.7% to 71.9%). The percentage of infants receiving feedings on day one increased from 23.9% to 44.6% while the percentage receiving PF within the first 72 hours declined (31.2% to 10.3%). The NEC rate declined from 4.1% to 0.4%. Reduction in NEC occurred despite a simultaneous increase in perinatal antibiotic exposure and the universal but late administration of bovine HM fortifier. The improvement associated with the decrease in NEC included initiation of probiotic administration, a reduction in PF feeding, and improvements in milk preparation, storage, and fortification processes.Conclusions:Early exclusive feedings of HM and avoidance of PF together with probiotics and milkhygiene may decrease NEC in PI. Neither brief perinatal antibiotic exposure nor late introduction of bovine fortifiers appears detrimental in this context.

Microbial Composition of the Initial Colonization of Newborns.

Early-life interaction with indigenous intestinal microbes is a prerequisite for healthy immune and metabolic maturation. Human infants acquire their gut microbiota predominantly from the mother. A considerable inoculum of microbes is received by the neonate during vaginal delivery. Recent observations suggest that human gut colonization may be initiated prenatally by microbes in amniotic fluid, but the significance of this phenomenon remains unknown. After birth, neonatal gut colonization is guided by human milk factors, which selectively promote the growth of specific microbes, as well as by live microbes present in human milk. Aberrant gut colonization in early life has been associated with an increased risk of noncommunicable diseases in later life. Epidemiological and experimental studies suggest a causal relationship between early-life gut microbiota perturbations and disease risk. Perinatal antibiotic exposure, cesarean section delivery, postnatal antibiotic administration, and formula feeding, which may disrupt intestinal microecology, have been associated with disease development in later life. The modulation of gut microbiota in the perinatal period by pre- and probiotics, for example, may offer a means to reduce the risk of chronic diseases.

Maternal Antibiotic Treatment Impacts Development of the Neonatal Intestinal Microbiome and Antiviral Immunity.

Microbial colonization of the infant gastrointestinal tract (GIT) begins at birth, is shaped by the maternal microbiota, and is profoundly altered by antibiotic treatment. Antibiotic treatment of mothers during pregnancy influences colonization of the GIT microbiota of their infants. The role of the GIT microbiota in regulating adaptive immune function against systemic viral infections during infancy remains undefined. We used a mouse model of perinatal antibiotic exposure to examine the effect of GIT microbial dysbiosis on infant CD8(+) T cell-mediated antiviral immunity. Maternal antibiotic treatment/treated (MAT) during pregnancy and lactation resulted in profound alterations in the composition of the GIT microbiota in mothers and infants. Streptococcus spp. dominated the GIT microbiota of MAT mothers, whereas Enterococcus faecalis predominated within the MAT infant GIT. MAT infant mice subsequently exhibited increased and accelerated mortality following vaccinia virus infection. Ag-specific IFN-γ-producing CD8(+) T cells were reduced in sublethally infected MAT infant mice. MAT CD8(+) T cells from uninfected infant mice also demonstrated a reduced capacity to sustain IFN-γ production following in vitro activation. We additionally determined that control infant mice became more susceptible to infection if they were born in an animal facility using stricter standards of hygiene. These data indicate that undisturbed colonization and progression of the GIT microbiota during infancy are necessary to promote robust adaptive antiviral immune responses.

Perinatal antibiotic exposure of neonates in Canada and associated risk factors: a population-based study

Objective: To describe neonatal antibiotic exposures occurring immediately before and after birth and their associated risk factors.Methods: A retrospective review of the hospital charts of 449 mother–neonate pairs enrolled in the Canadian Healthy Infant Longitudinal Development national birth-cohort study was conducted at two tertiary hospitals and one rural hospital in Manitoba, Canada. The main outcome measures included the following: maternal and neonatal antibiotic use during the perinatal period; indications for antibiotic use, including suspected neonatal sepsis, maternal group B Streptococcus (GBS), premature rupture of membranes and caesarean-section; maternal health status, focusing on gestational hypertension, gestational diabetes, obesity and primigravida pregnancies.Results: During the perinatal period, 45.0% of neonates were exposed to antibiotics. Intravenous penicillin G (17%) and cefazolin (16%) were the most commonly administered intrapartum antibiotics. Colonization with GBS was confirmed in 21.2% of women and treated with antibiotics in 86% of cases. Overweight women and women with hypertension were significantly more likely to receive intrapartum antibiotics for caesarean section or GBS prophylaxis. Antibiotic treatment of the neonate was highest following emergency caesarean section (12%) or unknown maternal GBS status (20%).Conclusions: Neonates in Canada are routinely exposed to antibiotics during the perinatal period.

Impact of perinatal antibiotic exposure on the infant gut microbiota at one year of age

Background Disruption of the infant gut microbiota has been linked to long-term health outcomes, including obesity and allergic disease [1]. Antibiotics can significantly alter the microbiota [2], but evidence is scarce for the long-term effect of antibiotic exposure during the perinatal period (shortly before or after delivery). Our research aimed to determine the impact of infant and maternal perinatal antibiotic exposure on the infant gut microbiota at 1 year of age.

A retrospective chart review to identify perinatal factors associated with food allergies

BackgroundGut flora are important immunomodulators that may be disrupted in individuals with atopic conditions. Probiotic bacteria have been suggested as therapeutic modalities to mitigate or prevent food allergic manifestations. We wished to investigate whether perinatal factors known to disrupt gut flora increase the risk of IgE-mediated food allergies.MethodsBirth records obtained from 192 healthy children and 99 children diagnosed with food allergies were reviewed retrospectively. Data pertaining to delivery method, perinatal antibiotic exposure, neonatal nursery environment, and maternal variables were recorded. Logistic regression analysis was used to assess the association between variables of interest and subsequent food allergy diagnosis.ResultsRetrospective investigation did not find perinatal antibiotics, NICU admission, or cesarean section to be associated with increased risk of food allergy diagnosis. However, associations between food allergy diagnosis and male gender (66 vs. 33; p=0.02) were apparent in this cohort. Additionally, increasing maternal age at delivery was significantly associated with food allergy diagnosis during childhood (OR, 1.05; 95% CI, 1.017 to 1.105; p=0.005).ConclusionsGut flora are potent immunomodulators, but their overall contribution to immune maturation remains to be elucidated. Additional understanding of the interplay between immunologic, genetic, and environmental factors underlying food allergy development need to be clarified before probiotic therapeutic interventions can routinely be recommended for prevention or mitigation of food allergies. Such interventions may be well-suited in male infants and in infants born to older mothers.

Late-onset neonatal infections: incidences and pathogens in the era of antenatal antibiotics

Widespread use of intrapartum antimicrobial prophylaxis has significantly reduced the incidence of early-onset neonatal infection (EONI); however, little is known about the effects of increased maternal exposure to antibiotics on late-onset neonatal infection (LONI). This study aims to evaluate LONI epidemiology in our region after the application of French recommendations and to determine whether LONI-causing organisms and their antibiotic susceptibility are influenced by peripartum antibiotic exposure. We performed a prospective epidemiologic study of 139 confirmed and possible cases of bacterial LONI in patients treated with antibiotics for at least 5 days of the 22,458 infants born in our region in the year 2007. The overall incidence of LONI caused by all pathogens, Group B streptococcus (GBS) and Escherichia coli (E. coli) were 6.19, 0.36 and 2.72, respectively, per 1,000 live births. Our findings revealed three major types of LONI: E. coli-induced urinary tract infection (UTI) among term infants, coagulase negative Staphylococcus septicemia affecting preterm infants, and GBS infections with severe clinical presentation. Univariable analysis revealed that maternal antibiotic exposure was significantly associated with the risk of amoxicillin-resistant E. coli infection (p = 0.01). Postnatal antibiotic exposure was associated with an increased risk of E. coli LONI (p = 0.048). This link persisted upon multivariable analysis; however, no additional risk factors were identified for LONI caused by antibiotic-resistant E. coli. Our findings confirm that despite the benefits of antenatal antibiotics, this treatment can increase the risk of antibiotic-resistant cases of LONI. National and international surveillance of LONI epidemiology is essential to assess benefits and potential negative consequences of perinatal antibiotic exposure.