Intrapartum Antibiotic Treatment Research Articles

A common trajectory of gut microbiome development during the first month in healthy neonates with limited inter-individual environmental variations

The early development of the gut microbiome is governed by multiple factors and has significantly long-term effects on later-in-life health. To minimize inter-individual variations in the environment, we determined developmental trajectories of the gut microbiome in 28 healthy neonates during their stay at a postpartum center. Stool samples were collected at three time points: the first-pass meconium within 24 h of life, and at 7 and 28 days of age. Illumina sequencing of the V3–V4 region of 16S rRNA was used to investigate microbiota profiles. We found that there was a distinct microbiota structure at each time point, with a significant shift during the first week. Proteobacteria was most abundant in the first-pass meconium; Firmicutes and Actinobacteria increased with age and were substituted as the major components. Except for a short-term influence of different delivery modes on the microbiota composition, early microbiome development was not remarkably affected by gravidity, maternal intrapartum antibiotic treatment, premature rupture of membranes, or postnatal phototherapy. Hence, our data showed a similar developmental trajectory of the gut microbiome during the first month in healthy neonates when limited in environmental variations. Environmental factors external to the host were crucial in the early microbiome development.

Early Gut Microbiota Profile in Healthy Neonates: Microbiome Analysis of the First-Pass Meconium Using Next-Generation Sequencing Technology.

Gut microbiome development during early life has significant long-term effects on health later in life. The first-pass meconium is not sterile, and it is important to know the initial founder of the subsequent gut microbiome. However, there is limited data on the microbiota profile of the first-pass meconium in healthy neonates. To determine the early gut microbiota profile, we analyzed 39 samples of the first-pass meconium from healthy neonates using 16S rRNA sequencing. Our results showed a similar profile of the microbiota composition in the first-pass meconium samples. Pseudomonas was the most abundant genus in most samples. The evenness of the microbial communities in the first-pass meconium was extremely poor, and the average Shannon diversity index was 1.31. An analysis of the relationship between perinatal characteristics and the meconium microbiome revealed that primigravidae babies had a significantly higher Shannon diversity index (p = 0.041), and the Bacteroidales order was a biomarker for the first-pass meconium of these neonates. The Shannon diversity index was not affected by the mode of delivery, maternal intrapartum antibiotic treatment, prolonged rupture of membranes, or birth weight. Our study extends previous research with further characterization of the gut microbiome in very early life.

Effects of prenatal antibiotic treatment on early infant health: a retrospective study in a rural health facility in Ghana.

Infant mortality remains a major developmental challenge in many low-income countries. Epidemiological evidence suggests that infant acquisition of maternal microbiome is essential for programming of immunity and metabolism. As such, irrational maternal antibiotic use may affect infant health. The aim of the study was to determine the effects of prenatal antibiotic use on early postnatal life (90 days) in a low-income community in Ghana. The study was a retrospective study of 412 mother-baby pair medical records in a low-income community in rural Ghana. During the ninety-day period, the prevalence and relative risk of neonatal sepsis, respiratory disorders, and dermatitis were significantly higher in infants treated prenatally with antibiotics compared to untreated infants. Prenatal antibiotic treatment was not significantly associated with the risk of developing neonatal jaundice and conjunctivitis. However, prenatally antibiotic exposed infants were three times likely to visit the hospital for a non-scheduled/non-review treatment within the first 90 days compared to unexposed babies. Intrapartum antibiotic treatment is associated with poor early infant health. Rationalizing antibiotic use during pregnancy may contribute to reducing infant mortality.

Not Just an Intrapartum Problem: Late-Onset Group B Streptococcus Disease.

Group B streptococcal (GBS) infection is a leading cause of neonatal morbidity and mortality globally. While prevention strategies for early onset GBS disease are well established, methods to prevent late-onset GBS disease do not eliminate disease burden, leaving potential for infection, and devastating consequences for affected neonates. Furthermore, the incidence of late-onset GBS has risen in recent years, with preterm infants at the highest risk of infection and death. Meningitis remains the most common and serious complication associated with late onset disease, occurring in 30 percent of cases. The assessment of risk for neonatal GBS infection should not be limited to the birth process or maternal screening results and intrapartum antibiotic prophylaxis treatment status. Horizontal transmission after birth from mothers, caregivers, and community sources has been observed. Late-onset GBS disease and its sequelae remain a significant risk to neonates, and clinicians should be able to recognize the signs and symptoms to provide timely antibiotic therapy. This article discusses of the pathogenesis, risk factors, clinical manifestations, diagnostics, and treatment of neonatal late-onset GBS infection and identifies implications for practicing clinicians.

Molecular Epidemiology of Group B Streptococcus Isolates from Pregnant Women with Premature Rupture of Membranes in Fuzhou, China.

This study investigated the molecular epidemiology of Group B Streptococcus (GBS) in pregnant women with premature rupture of membranes (PROM) in Fuzhou region of China as a source of clinical reference. GBS isolates were obtained from pregnant women with PROM. All isolates were genotyped, serotyped, and tested for drug-resistance and virulence genes using PCR and DNA sequencing. Antibiotic susceptibility testing was performed using the Vitek® 2 automated system. Among the 140 GBS isolates, seventeen sequence types (STs) were identified, of which ST19 (20.0%) was the most prevalent, followed by ST862, ST10, and ST12. Three clonal complexes (CC19, CC10 and CC1) were identified. The predominant serotype was III (45.7%), followed by V (23.6%), Ib (18.6%), Ia (7.1%), and II (3.6%). The prevalence of multidrug resistance was 72.8% (102/140). All isolates were susceptible to penicillin G, ampicillin, quinupristin, linezolid, vancomycin, and tigecycline. The majority of isolates were resistant to erythromycin (70.0%), clindamycin (72.1%), and tetracycline (81.4%), and 28.6% of isolates were resistant to levofloxacin and moxifloxacin. Of the 98 erythromycin-resistant strains, mreA, ermB, mefA, mefE, ermA, and ermTR were detected in 100%, 70.4%, 49.0%, 22.4%, 13.3%, and 9.2%, respectively. No linB was detected among 101 clindamycin-resistant strains. Of the 114 tetracycline-resistant strains, tetM, tetK, tetL and tetO were detected in 52.6%, 61.4%, 7.9%, and 23.7%, respectively. Regarding virulence genes, all strains carried rib and hylB, followed by scpB (98.6%), and bca (80.7%), whereas only one strain carried bac. ST19/III and ST862/III were the most prevalent GBS subtypes. Penicillin G remains a first-line antibiotic for intrapartum antibiotic prophylaxis and treatment of GBS infections. The prevalence of resistance to clindamycin, erythromycin, and tetracycline is high among GBS isolates in the Fuzhou region. ST862 and ST651 are emerging animal origin STs in human infections, and may become potential zoonotic threats.

Early life exposures and development of allergic disease in infants with familial risk: Results from ongoing probiotic intervention trials.

We search revision of risk determinants of the ongoing allergy epidemic. Children numbering 433 born to mothers with allergic disease or sensitisation were selected from the three ongoing probiotic intervention trials for this case-control study. Children who developed atopic eczema or food allergy, had positive skinprick test results or had been prescribed inhaled corticosteroids by the age of 2 years were identified as cases (n=231), while children without allergic manifestations were the healthy controls (n=202). The data on early environmental exposures were collected from prospectively documented study records. The statistical analyses were adjusted for potential confounders. Determinants associated with the increased risk of atopic eczema were lower maternal prepregnancy BMI (aOR 0.15, 95% CI: 0.037-0.54) and maternal intrapartum antibiotic treatment (aOR 2.21, 95% CI 1.20-4.10), the latter also linked to obstructive respiratory symptoms (aOR 3.87, 95% CI 1.07-14.06). The risk of allergic sensitisation was associated with lower maternal prepegnancy BMI (aOR 0.18, 95% CI 0.43-0.79) and intrapartum antibiotic treatment (aOR 2.13, 95% CI 1.07-4.22). Based on our demonstrations, interventions such as personalised diets, can be optimised for specific subgroups and definite risk periods.

From the pages of AllergyWatch

For this edition of From the Pages of AllergyWatch, I have selected reviews relating to childhood allergies and food allergens relating to the theme of this month's Annals of Allergy, Asthma & Immunology. The first article, with comments from Dr Lee, presented data showing that Ara h 2 specific immunoglobulin E (sIgE) has a lower rate of false positivity in children evaluated for peanut allergy. The next article, with comments from Dr Knox, reported that there was no association between intrapartum antibiotic treatment and subsequent development of allergies in childhood.

Maternal Intrapartum Antibiotic Treatment and Gut Microbiota Development in Healthy Term Infants

Objective: The aim of the study was to investigate the impact of intrapartum antibiotic treatment (IAT) on the compositional development of gut microbiota in healthy term infants. Study Design: A case-control study of 24 infants exposed to and 24 matched infants not exposed to IAT was conducted. All subjects were born by vaginal delivery at term and breastfed. None of the infants received antibiotics during the immediate neonatal period. Fecal samples were obtained at the ages of 1 and 6 months. The composition of the intestinal microbiota was assessed by 16S rRNA gene sequencing. Results: IAT was associated with reduced microbial richness but not diversity at 1 month of age. Furthermore, the relative abundances of Clostridiaceae and Erysipelotrichaceae were significantly altered in infants exposed to IAT as compared to nonexposed infants at 1 month of age. The observed deviations in gut microbiota composition between infants exposed and not exposed to IAT diminished by the age of 6 months. Conclusions: IAT is associated with short-term perturbations in the gut microbiota development in healthy term, vaginally delivered, breastfed infants. The composition of the gut microbiota is mostly restored by the age of 6 months.

Differences in maternal group B Streptococcus screening rates in Latin American countries

ObjectiveTo determine rates and results of maternal Group B streptococcus (GBS) screening during pregnancy and identify sociodemographic characteristics associated with GBS screening in Latin American countries. BackgroundGBS is a primary cause of morbidity and mortality in neonates and is prevented by screening pregnant women for GBS before delivery and intrapartum antibiotic treatment. Yet, data regarding national GBS screening practices and the epidemiology of maternal GBS colonization in Latin America are limited. MethodsWe conducted a retrospective observational study using de-identified records of pregnant women in six Latin American countries from a regional database. 460,328 collected from January 1, 2009 through December 31, 2012 met study criteria and were included. Maternal screening rates for GBS were determined, association of demographic variables (ethnicity, age, education level, and civil status) with maternal GBS screening was determined using logistic regression, odds ratios were calculated comparing incidence of adverse neonatal outcomes (sepsis, pneumonia, and meningitis) between countries with high and low rates of GBS screening, maternal GBS colonization prevalence was determined by year and association of demographic variables with maternal GBS colonization was determined using logistic regression. ResultsMaternal GBS screening was less than 15% in each country, except Uruguay which screened greater than 65% of women. The final regression model examining maternal screening rates and demographic variables included the covariates ethnicity, maternal age group, education level and civil status. Countries with lower rates of maternal GBS screening had increased odds of neonatal sepsis [OR 23.3; 95% CI (15.2–35.9)] and pneumonia [OR 19.9; 95% CI (12.1–32.6)]. In Uruguay, GBS prevalence over the study period was 18.5%. Black women, older women and women without a primary education had higher rates of GBS colonization (21.3%, 20.4% and 21.9% respectively). ConclusionsOur study highlights the need for national policy and investments to increase maternal GBS screening and better understand the prevalence of maternal GBS colonization in Latin America. Further research on the burden of neonatal GBS disease within Latin America is needed to inform the introduction of a maternal GBS vaccine, when available.

Antimicrobial susceptibility and serotype distribution of Streptococcus agalactiae rectovaginal colonising isolates from pregnant women at a tertiary hospital in Pretoria, South Africa: An observational descriptive study.

Streptococcus agalactiae or group B streptococcus (GBS) is a significant cause of neonatal sepsis. Intrapartum antibiotic prophylaxis is recommended for pregnant women identified to be rectovaginally colonised between 34 and 37 weeks' gestational age to decrease the risk of invasive disease in their newborns. An effective multivalent GBS vaccine may prevent a broader scope of GBS-associated diseases, such as GBS early-onset disease, GBS late-onset disease, spontaneous abortion, stillbirth and maternal bacteraemia. Serotype distribution of GBS isolates is essential to determine the efficacy of such a vaccine. To investigate serotype distribution and antimicrobial susceptibility patterns of GBS isolates cultured from rectovaginal specimens during pregnancy. Sixty-nine archived maternal colonising isolates were tested against penicillin, erythromycin, clindamycin, vancomycin and levofloxacin. Minimum inhibitory concentration testing was performed using the ETEST method. Serotyping was performed by the latex agglutination method. The most common serotypes detected were Ia (54%), III (20%), V (16%), II (6%), IV (2%) and Ib (1%). All isolates were fully susceptible to penicillin, vancomycin and levofloxacin. Eight (11%) and 50 (56%) isolates showed intermediate resistance to erythromycin and clindamycin, respectively, and 1 isolate was resistant to erythromycin. The macrolide-lincosamide-streptogramin B (MLSB) phenomenon was noted in 3 (4%) of the isolates. GBS-colonising isolates remain susceptible to penicillin, which remains the drug of choice for intrapartum antibiotic prophylaxis and treatment of invasive disease in newborns. Macrolides should only be used if clinically indicated due to the high prevalence of intermediate resistance. A pentavalent GBS vaccine currently in phase I trials should provide coverage for 97% of the isolates identified in this study.

Chorioamnionitis versus intraamniotic infection among preterm deliveries—is postpartum infectious morbidity different?

Chorioamnionitis can have a highly variable definition with substantial maternal and fetal morbidity, with higher frequencies in preterm births. With the recently updated intraamniotic infection diagnostic criteria by the American College of Obstetricians and Gynecologists, fewer women experiencing preterm delivery may qualify for intrapartum antibiotic treatment, potentially resulting in higher postpartum infectious morbidity. This study aimed to estimate whether the proportion of women delivering preterm who develop postpartum endometritis differs between subjects diagnosed as having clinical chorioamnionitis and those meeting the American College of Obstetricians and Gynecologists' criteria for intraamniotic infection. Secondary analysis was conducted using a randomized controlled trial of antenatal magnesium sulfate for the prevention of cerebral palsy. Subjects were included if they had a clinical diagnosis of chorioamnionitis and maternal temperature of ≥37.8°C and excluded if maternal temperature data were missing. The exposure group included women who met the criteria for intraamniotic infection, defined as a single maternal temperature of ≥39.0°C or maternal temperature of 38.0°C to 38.9°C plus 1 additional clinical risk factor (leukocytosis, purulent cervical drainage, or fetal tachycardia). The primary outcome was postpartum endometritis. The odds of postpartum endometritis were compared between women with intraamniotic infection and women with clinical chorioamnionitis, after adjusting for potential confounders using multivariate logistic regression. Of the original study population, 258 of 2241 (11.8%) subjects met the criteria for chorioamnionitis. Nearly all subjects (98.5%) received antibiotic treatment between randomization and delivery. A total of 144 subjects (55.8%) met the criteria for intraamniotic infection, whereas 114 (44%) only met the criteria for clinical chorioamnionitis. A total of 40 women (15.5%) experienced postpartum endometritis. Women with intraamniotic infection had higher parity (P=.02) and higher maximum maternal temperature (P<.001) and were more likely to have received antibiotic treatment (P=.04). Postpartum endometritis rates were similar between subjects with chorioamnionitis and intraamniotic infection (12% vs 18%; P=.50). After adjustment for potential confounders, the odds of developing postpartum endometritis did not differ between subjects who met the criteria for intraamniotic infection and those who did not (adjusted odds ratio, 1.28; 95% confidence interval, 0.62-2.62). Patients delivering preterm who receive a diagnosis of clinical chorioamnionitis in the intrapartum period seem to have similar odds of developing postpartum endometritis as those meeting the American College of Obstetricians and Gynecologists' criteria for intraamniotic infection, suggesting that this group remains at a high risk for postpartum infectious complications.

Neonatal Sepsis

Neonatal sepsis is associated with severe morbidity and mortality in the neonatal period. Clinical manifestations range from subclinical infection to severe local or systemic infection. Neonatal sepsis is divided into three groups as early-onset neonatal sepsis, late-onset neonatal sepsis and very late-onset neonatal sepsis according to the time of the onset. It was observed that the incidence of early-onset neonatal sepsis decreased with intrapartum antibiotic treatment. However, the incidence of late-onset neonatal sepsis has increased with the increase in the survival rate of preterm and very low weight babies. The source of the causative pathogen may be acquisition from the intrauterine origin but may also acquisition from maternal flora, hospital or community. Prematurity, low birth weight, chorioamnionitis, premature prolonged rupture of membranes, resuscitation, low APGAR score, inability to breastfeed, prolonged hospital stay and invasive procedures are among the risk factors. This article reviews current information on the definition, classification, epidemiology, risk factors, pathogenesis, clinical symptoms, diagnostic methods and treatment of neonatal sepsis.

Chorioamnionitis versus intraamniotic infection among preterm deliveries: is postpartum infectious morbidity different?

With new intraamniotic infection (IAI) diagnostic criteria, fewer women experiencing preterm delivery may qualify for intrapartum antibiotic treatment, potentially resulting in higher postpartum infectious morbidity. Thus, the objective of this study was to estimate whether subjects diagnosed with clinical chorioamnionitis have decreased odds of developing endometritis compared to those subjects meeting criteria for IAI.

Impact of maternal intrapartum antibiotics on the initial oral microbiome of neonates

Prior studies have proposed that maternal intrapartum antibiotic exposure shapes the gut microbiota and, subsequently the child's health. However, the effect of maternal intrapartum antibiotic exposure and its influence on the development of the neonatal oral microbiota in early infancy has not yet been reported. The aim of this study was to compare the initial oral microbiota immediately after birth of healthy infants with and without intrapartum antibiotic exposure. Twenty-two newborns of the BaoAn Maternal and Child Care Hospital (Shenzhen, China) were recruited for this study, 11 born to mothers without intrapartum antibiotic exposure (NT group) and 11 to mothers with intrapartum antibiotic prophylaxis with cefamezin (AT group). Oral microbiome profiles were determined by 16S rRNA sequencing based on the V3V4 hyper-variable regions. Phylum Firmicutes was most frequently detected in subjects both groups and a higher frequency was observed in the NT group than the AT group. Phyla Actinobacteria, Bacteroidetes and Proteobacteria were more abundant after intrapartum antibiotics exposure. Genus Lactobacillus belonging to Firmicutes was predominant in the neonates not exposed to antibiotics, while significantly higher percentages of genera Klebsiella, Roseburia, Propionibacterium, Faecalibacterium, Escherichia/Shigella, Corynebacterium, Bifidobacterium, and Bacteroides were noted in AT infants than NT infants. Further function analysis demonstrated that lipopolysaccharide biosynthesis and amino acid-related metabolic function was enriched in the AT group, and carbohydrate metabolism pathways were more abundant in the NT group. These findings revealed distinctions in both taxa and metabolic function of oral microbiota between antibiotics-treated and unexposed groups, which indicated that maternal intrapartum antibiotic treatment is a key regulator of the initial neonatal oral microbiome.

Breast Milk Microbiota Is Shaped by Mode of Delivery and Intrapartum Antibiotic Exposure.

The mode of delivery has been suggested to modulate the bacterial composition of breast milk but the impact of intrapartum antibiotic use on the milk microbiota is currently not known. The aim of this study was to analyze the effects of the mode of the delivery and intrapartum antibiotic administration on the microbial composition of breast milk. Breast milk samples were collected from 84 healthy mothers 1 month after the delivery. In total, 61 mothers had delivered vaginally, 23 of which had received intrapartum antibiotics, 13 women had delivered with non-elective cesarean section, 7 of which had received antibiotics, and 10 mothers had delivered with elective cesarean section without intrapartum antibiotic treatment. Both mode of delivery and intrapartum antibiotic exposure were significantly associated with changes in the milk microbial composition as assessed by analysis of similarities (ANOSIM) test (p = 0.001). The mode of delivery had a more profound effect on the milk microbiota composition as compared to intrapartum antibiotic exposure. Although the clinical significance of breast milk microbiota is currently poorly understood, this study shows that cesarean section delivery has an independent effect on breast milk microbiota composition. The dysbiosis observed in infants born by cesarean section delivery may be aggravated by the aberrant breast milk microbiota.

Prolonged use of antibiotics after birth is associated with increased morbidity in preterm infants with negative cultures

Background: Most preterm infants are exposed to a variable duration of antibiotic therapy after birth despite negative cultures. Data is emerging about the risks of prolonged antibiotics. We sought to assess the association between length of initial antibiotic course and neonatal outcomes in a cohort from a single large perinatal center. Methods: Retrospective cohort study of prospectively collected data on all infants with a birth weight of less than 1250 g hospitalized in our NICU in a 4 year window and who had negative blood and CSF cultures in the first 2 days of life. The primary outcome is a composite of necrotizing enterocolitis (NEC), late onset sepsis (LOS) and death evaluated using multivariable regression analysis. Results: A total of 620 infants less than 1250 g with negative cultures were eligible for study over a 4 year period. The 238 infants with more than 5 days initial antibiotic use were significantly smaller and of lower gestational age than the 382 infants who received up to 5 days of antibiotics. Their mothers had more clinical chorioamnionitis, less maternal hypertension and greater perinatal use of antibiotics. On multivariate analysis, infants who received empiric antibiotics for longer than 5 days had higher rates of neonatal morbidities after adjusting for gestational age, SNAP II, small-for-gestational age status, gender, maternal hypertension, prenatal steroid treatment, clinical chorioamnionitis, intrapartum antibiotic treatment, and multiple births. Composite outcome OR: 1.83 (1.15 to 2.92), LOS OR: 2.02 (1.20 to 3.39), bronchopulmonary dysplasia OR: 1.58 (1.04 to 2.29). Mortality and NEC were not significantly different. Conclusion: More than 5 days of antibiotic treatment in very preterm infants with negative cultures was associated with increased morbidity in our population, and that included BPD. It is of note that patterns of increased morbidity and/or mortality differ between studies. Prospective trials of clinical protocols for starting and stopping antibiotics in the very preterm infants are required.

Sex-specific impact of asthma during pregnancy on infant gut microbiota

Asthma during pregnancy is associated with retardation of fetal growth in a sex-specific manner. Lactobacilli microbes influence infant growth. This study aimed to determine whether lactobacilli and other microbes are reduced in the gut of infants born to an asthmatic mother, and whether this differs by the sex of the infant.Mother-infant pairs (N=1021) from the Canadian Healthy Infant Longitudinal Development full-term cohort were studied. The abundance of infant faecal microbiota at 3–4 months, profiled by gene sequencing, was compared between both women with and without asthma treatment during pregnancy. Infant sex, maternal ethnicity, pre-pregnancy overweight and atopy status, birth mode, breastfeeding status and intrapartum antibiotic treatment were tested as covariates.Independent of birth mode and other covariates, male, Caucasian infants born to women with prenatal asthma harboured fewer lactobacilli in the gut at 3–4 months of age. If asthmatic mothers had pre-pregnancy overweight, the abundance of Lactobacillus in males was further reduced in the infant gut, whereas the microbiota of female infants was enriched with Bacteroidaceae. Similar differences in infant gut microbial composition according to maternal prenatal asthma status were also more evident among women with food or environmental allergies.Gut lactobacilli were less abundant in male infants, but Bacteroidaceae were more abundant in female infants at 3–4 months of age, following maternal asthma during pregnancy.

Maternal intrapartum antibiotic treatment continues to exert a bactericidal effect on the umbilical cord and peripheral venous blood of newborn infants.

It is unclear whether maternal intrapartum antibiotic treatment (IAT) continues to exert a bactericidal effect on common pathogens in neonates. We studied the in vitro bactericidal effect of IAT on the cord and peripheral venous blood of newborn infants. Umbilical cord and peripheral venous blood from newborn infants born at Kaplan Medical Center, Israel, from April to October 2014 were studied for serum bactericidal titres against Group B Streptococcus (GBS) and Escherichia coli (E. coli) strains. We studied 60 samples of umbilical cord blood and 18 samples of peripheral venous blood from 60 newborn infants whose mothers received IAT. The controls were 10 samples of cord blood from mothers without IAT. Cord blood exerted a bactericidal effect against 98% of GBS isolates but only 8% of E.coli isolates. Peripheral blood exerted a bactericidal effect against GBS in 94% of cases, but not against E. coli. No bactericidal effect was seen in the blood from the controls. We found a continued bactericidal effect of umbilical cord blood and neonatal peripheral blood from newborn infants of IAT-treated mothers, mainly against GBS, but rarely against E. Coli. These findings may assist clinicians treating at-risk infants exposed to IAT.

Adverse events in women and children who have received intrapartum antibiotic prophylaxis treatment: a systematic review

BackgroundAdverse events from intrapartum antibiotic prophylaxis (IAP) are poorly documented yet essential to inform clinical practice for neonatal group B Streptococcus (GBS) disease prevention. In this systematic review, we appraised and synthesised the evidence on the adverse events of IAP in the mother and/or her child.MethodsWe searched MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, Cochrane, and Science Citation Index from date of inception until October 16th 2016. Reference lists of included studies and relevant systematic reviews were hand-searched. We included primary studies in English that reported any adverse events from intrapartum antibiotics for any prophylactic purpose compared to controls. The search was not restricted to prophylaxis for GBS but excluded women with symptoms of infection or undergoing caesarean section. Two reviewers assessed the methodological quality of studies, using the Cochrane Risk of Bias tool, and the Risk of Bias Assessment Tool for Nonrandomised Studies. Results were synthesised narratively and displayed in text and tables.ResultsFrom 2364 unique records, 30 studies were included. Despite a wide range of adverse events reported in 17 observational studies and 13 randomised controlled trials (RCTs), the evidence was inconsistent and at high risk of bias. Only one RCT investigated the long-term effects of IAP reporting potentially serious outcomes such as cerebral palsy; however, it had limited applicability and unclear biological plausibility. Seven observational studies showed that IAP for maternal GBS colonisation alters the infant microbiome. However, study populations were not followed through to clinical outcomes, therefore clinical significance is unknown. There was also observational evidence for increased antimicrobial resistance, however studies were at high or unclear risk of bias.ConclusionsThe evidence base to determine the frequency of adverse events from intrapartum antibiotic prophylaxis for neonatal GBS disease prevention is limited. As RCTs may not be possible, large, better quality, and longitudinal observational studies across countries with widespread IAP could fill this gap.Trial registrationCRD42016037195.

Antibiotic treatment at delivery shapes the initial oral microbiome in neonates

Oral microorganisms are important determinants of health and disease. The source of the initial neonatal microbiome and the factors dictating initial human oral microbiota development are unknown. This study aimed to investigate this in placental, oral and gut microbiome profiles from 36 overweight or obese mother-baby dyads as determined by 16S rRNA sequencing. Expression of five antibiotic resistance genes of the β-lactamase class was analysed in the infant oral microbiota samples by QPCR. The neonatal oral microbiota was 65.35% of maternal oral, 3.09% of placental, 31.56% of unknown and 0% of maternal gut origin. Two distinct neonatal oral microbiota profiles were observed: one strongly resembling the maternal oral microbiota and one with less similarity. Maternal exposure to intrapartum antibiotics explained the segregation of the profiles. Families belonging to Proteobacteria were abundant after antibiotics exposure while the families Streptococcaceae, Gemellaceae and Lactobacillales dominated in unexposed neonates. 26% of exposed neonates expressed the Vim-1 antibiotic resistance gene. These findings indicate that maternal intrapartum antibiotic treatment is a key regulator of the initial neonatal oral microbiome.