Intrapartum Antibiotics Research Articles

The relationship of prenatal antibiotic exposure and infant antibiotic administration with childhood allergies: a systematic review

BackgroundEarly antibiotic exposure may be contributing to the onset of childhood allergies. The main objective of this study was to conduct a systematic review on the relationship between early life antibiotic exposure and childhood asthma, eczema and hay fever.MethodsPubmed and Embase were searched for studies published between 01-01-2008 and 01-08-2018, examining the effects of (1) prenatal antibiotic exposure and (2) infant antibiotic administration (during the first 2 years of life) on childhood asthma, eczema and hay fever from 0 to 18 years of age. These publications were assessed using the Newcastle Ottawa Scale (NOS) and analysed narratively.Results(1) Prenatal antibiotics: Asthma (12 studies): The majority of studies (9/12) reported significant relationships (range OR 1.13 (1.02–1.24) to OR 3.19 (1.52–6.67)). Three studies reported inconsistent findings. Eczema (3 studies): An overall significant effect was reported in one study and in two other studies only when prenatal antibiotic exposure was prolonged. (2) Infant antibiotics: Asthma (27 studies): 17/27 studies reported overall significant findings (range HR 1.12 (1.08–1.16) to OR 3.21 (1.89–5.45)). Dose-response effects and stronger effects with broad-spectrum antibiotic were often reported. 10/27 studies reported inconsistent findings depending on certain conditions and types of analyses. Of 19 studies addressing reverse causation or confounding by indication at least somewhat, 11 reported overall significant effects. Eczema (15 studies): 6/15 studies reported overall significant effects; 9 studies had either insignificant or inconsistent findings. Hay fever (9 studies): 6/9 reported significant effects, and the other three insignificant or inconsistent findings. General: Multiple and broad-spectrum antibiotics were more strongly associated with allergies. The majority of studies scored a 6 or 7 out of 9 based on the NOS, indicating they generally had a medium risk of bias. Although most studies showed significant findings between early antibiotic exposure and asthma, the actual effects are still unclear as intrapartum antibiotic administration, familial factors and confounding by maternal and child infections were often not addressed.ConclusionsThis review points to a moderate amount of evidence for a relationship between early life antibiotics (especially prenatal) and childhood asthma, some evidence for a relationship with hay fever and less convincing evidence for a relationship with eczema. More studies are still needed addressing intra-partum antibiotics, familial factors, and possible confounding by maternal and childhood infections. Children exposed to multiple, broad-spectrum antibiotics early in life appear to have a greater risk of allergies, especially asthma; these effects should be investigated further.

Immunization with a recombinant BibA surface protein confers immunity and protects mice against group B Streptococcus (GBS) vaginal colonization

Streptococcus agalactiae or group B Streptococcus (GBS) is a Gram-positive bacterium divided into ten distinct serotypes that colonizes the vaginal and rectal tracts of approximately 30% of women worldwide. GBS is the leading cause of invasive infection in newborns, causing sepsis, pneumoniae and meningitis. The main strategy to prevent GSB infection in newborns includes the use of intrapartum antibiotic therapy, which does not prevent late-onset diseases and may select resistant bacterial strains. We still do not have a vaccine formulation specific for this pathogen approved for human use. Conserved surface proteins are potential antigens that could be targets for recognition by antibodies and activation of cell opsonization. We used a serotype V GBS (GBS-V)-derived recombinant surface protein, rBibA, and evaluated the potential protective role of the induced antigen-specific antibodies after parenteral or mucosal immunizations in C57BL/6 mice. In vitro and in vivo assays demonstrated that vaccine formulations containing BibA combined with different adjuvants induced serum IgG and/or secreted IgA antibodies, leading to enhanced opsonophagocytosis of GBS-V cells and reduced invasion of epithelial cells. One BibA-based vaccine formulation adjuvanted with a nontoxic derivative of the heat-labile toxin produced by enterotoxigenic Escherichia coli (ETEC) strains was capable of inducing protection against vaginal colonization and lethal parenteral challenge with GBS-V. Serum collected from vaccinated mice conferred passive protection against vaginal colonization in naïve mice challenged with GBS-V. Taken together, the present data demonstrate that the BibA protein is a promising antigen for development of a vaccine to protect against GBS infection.

Caesarean delivery and the risk of atopic dermatitis in children.

Caesarean delivery (C-section) may disrupt maternal-infant microbial transfer and alter immune system development and subsequent risk for atopic dermatitis. Investigate the association between C-section and atopic dermatitis by age four and examine potential sources of bias in the relationship in a large cohort study. Maternal and child information was collected through Kaiser Permanente Northern California's (KPNC) integrated healthcare system. Data sources included electronic medical records, pharmacy databases, state birth records, and prospectively collected breastfeeding surveys. Children were eligible if they were born in a KPNC or contracting hospital between 2005 and 2014 and had continuous enrolment in the KPNC system for at least four years (n=173105). Modified Poisson regression with robust variance estimation was used to estimate the association between C-section and atopic dermatitis overall and when stratified by demographic and labour and delivery characteristics. Although unadjusted analyses showed a positive association between C-section and atopic dermatitis [RR(95%CI): 1.06(1.03, 1.10)], this effect was attenuated towards the null after adjustment [aRR(95%CI): 1.02(0.99, 1.05)]. In stratified analyses, there was evidence that C-section increased atopic dermatitis risk among certain subgroups (eg firstborns, overweight/obese pre-pregnancy BMI), but associations were weak. C-section delivery conditions indicative of the least exposure to maternal microbiome (ie no labour, short interval between membrane rupture and delivery) showed no evidence of association with atopic dermatitis. Estimated associations were not strongly influenced by intrapartum antibiotics, breastfeeding, missing data, or familial factors. Caesarean delivery was not associated with atopic dermatitis by age four in this large US cohort. This association did not appear to be biased by intrapartum antibiotics, breastfeeding behaviour, C-section indication, missing covariates, or familial factors.

Cesarean delivery and the risk of allergic rhinitis in children

BackgroundCesarean delivery (C-section) may influence the infant microbiome and affect immune system development and subsequent risk for allergic rhinitis (AR). ObjectiveTo investigate the association between C-section and AR at ages 6, 8, and 10 years. MethodsData were collected prospectively through Kaiser Permanente Northern Californias (KPNC) integrated healthcare system. Children were eligible if they were born in a KPNC hospital and remained in the KPNC system for minimum 6 years (n = 117,768 age 6; n = 75,115 age 8; n = 40,332 age 10). Risk ratios (RR) for C-section and AR were estimated at each follow-up age and adjusted for important covariates, including intrapartum antibiotics, pre-pregnancy body mass index, maternal allergic morbidities, and breastfeeding. Subanalyses considered information on C-section indication, labor, and membrane rupture. ResultsAfter adjusting for confounders, we did not observe an association between C-section and AR at follow-up ages 6, 8, or 10 years (RR [CI]: 6 years, 0.98 [0.91, 1.04]; 8 years, 1.00 [0.95, 1.07]; 10 years, 1.03 [0.96, 1.10]). In stratified analyses, there was limited evidence that C-section increases the risk of AR in certain subgroups (eg, children of non-atopic mothers, second or higher birth order children), but most estimated risk ratios were consistent with no association. Estimated associations were unaffected by participant attrition, missing data, or intrapartum antibiotics. ConclusionC-section delivery was not associated with AR at follow-up ages of 6, 8, or 10 years in a large contemporary US cohort.

Early-Onset Neonatal Sepsis 2015 to 2017, the Rise of Escherichia coli, and the Need for Novel Prevention Strategies

Early-onset sepsis (EOS) remains a potentially fatal newborn condition. Ongoing surveillance is critical to optimize prevention and treatment strategies. To describe the current incidence, microbiology, morbidity, and mortality of EOS among a cohort of term and preterm infants. This prospective surveillance study included a cohort of infants born at a gestational age (GA) of at least 22 weeks and birth weight of greater than 400 g from 18 centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network from April 1, 2015, to March 31, 2017. Data were analyzed from June 14, 2019, to January 28, 2020. Early-onset sepsis defined by isolation of pathogenic species from blood or cerebrospinal fluid culture within 72 hours of birth and antibiotic treatment for at least 5 days or until death. A total of 235 EOS cases (127 male [54.0%]) were identified among 217 480 newborns (1.08 [95% CI, 0.95-1.23] cases per 1000 live births). Incidence varied significantly by GA and was highest among infants with a GA of 22 to 28 weeks (18.47 [95% CI, 14.57-23.38] cases per 1000). No significant differences in EOS incidence were observed by sex, race, or ethnicity. The most frequent pathogens were Escherichia coli (86 [36.6%]) and group B streptococcus (GBS; 71 [30.2%]). E coli disease primarily occurred among preterm infants (68 of 131 [51.9%]); GBS disease primarily occurred among term infants (54 of 104 [51.9%]), with 24 of 45 GBS cases (53.3%) seen in infants born to mothers with negative GBS screening test results. Intrapartum antibiotics were administered to 162 mothers (68.9%; 110 of 131 [84.0%] preterm and 52 of 104 [50.0%] term), most commonly for suspected chorioamnionitis. Neonatal empirical antibiotic treatment most frequently included ampicillin and gentamicin. All GBS isolates were tested, but only 18 of 81 (22.2%) E coli isolates tested were susceptible to ampicillin; 6 of 77 E coli isolates (7.8%) were resistant to both ampicillin and gentamicin. Nearly all newborns with EOS (220 of 235 [93.6%]) displayed signs of illness within 72 hours of birth. Death occurred in 38 of 131 infected infants with GA of less than 37 weeks (29.0%); no term infants died. Compared with earlier surveillance (2006-2009), the rate of E coli infection increased among very low-birth-weight (401-1500 g) infants (8.68 [95% CI, 6.50-11.60] vs 5.07 [95% CI, 3.93-6.53] per 1000 live births; P = .008). In this study, EOS incidence and associated mortality disproportionately occurred in preterm infants. Contemporary cases have demonstrated the limitations of current GBS prevention strategies. The increase in E coli infections among very low-birth-weight infants warrants continued study. Ampicillin and gentamicin remained effective antibiotics in most cases, but ongoing surveillance should monitor antibiotic susceptibilities of EOS pathogens.

Prevalence, antimicrobial susceptibility patterns, serotypes and risk factors for group B streptococcus rectovaginal isolates among pregnant women at Kenyatta National Hospital, Kenya; a cross-sectional study

BackgroundEstimates of Group B Streptococcus (GBS) disease burden, antimicrobial susceptibility, and serotypes in pregnant women are limited for many resource-limited countries including Kenya. These data are required to inform recommendations for prophylaxis and treatment of infections due to GBS.MethodsWe evaluated the prevalence, antimicrobial susceptibility patterns, serotypes, and risk factors associated with rectovaginal GBS colonization among pregnant women receiving antenatal care at Kenyatta National Hospital (KNH) between August and November 2017. Consenting pregnant women between 12 and 40 weeks of gestation were enrolled. Interview-administered questionnaires were used to assess risk factors associated with GBS colonization. An anorectal swab and a lower vaginal swab were collected and cultured on Granada agar for GBS isolation. Positive colonies were tested for antimicrobial susceptibility to penicillin G, ampicillin, vancomycin, and clindamycin using the disk diffusion method. Serotyping was performed by latex agglutination. Logistic regression was used to identify factors associated with GBS colonization.ResultsA total of 292 women were enrolled. Median age was 30 years (Interquartile range {IQR} 26–35) and a median gestational age of 35 weeks (IQR 30–37). Overall GBS was identified in 60/292 (20.5%) of participants. Among the positive isolates, resistance was detected for penicillin G in 42/58 (72.4%) isolates, ampicillin in 32/58 (55.2%) isolates, clindamycin in 14/46 (30.4%) isolates, and vancomycin in 14/58 (24.1%) isolates. All ten GBS serotypes were isolated, and 37/53 (69.8%) of GBS positive participants were colonized by more than one serotype. None of the risk factors was associated with GBS colonization.ConclusionThe prevalence of GBS colonization was high among antenatal women at KNH. In addition, a high proportion of GBS isolates were resistant to commonly prescribed intrapartum antibiotics. Hence, other measures like GBS vaccination is a potentially useful approaches to GBS prevention and control in this population. Screening of pregnant mothers for GBS colonization should be introduced and antimicrobial susceptibility test performed on GBS positive samples to guide antibiotic prophylaxis.

The Role for Intra-Partum Antibiotics in Previously GBS-Colonised Pregnancies, Not So Straightforward After All: A Case Study

Background: Group B Streptococcus (GBS) is the most frequent pathogen involved in early-onset infection in newborn infants. The incidence of early-onset GBS disease (EOGBS) is estimated at 0.4 and 0.57 per 1000 births in the United States of America and the United Kingdom respectively. It is clear that administration of intrapartum antibiotics (IAP) significantly reduces risk of EOGBS (RR 0.17, 95% CI 0.04 to 0.74; number needed to treat to benefit 25, 95% CI 14 to 100), hence institutes such as the Royal College of Obstetrics and Gynecology (RCOG), and American College of Obstetrics and Gynecology (ACOG), have released clinical practice guidelines (CPGs) with the aim to improve the standard of care in GBS screening and IAP for the prevention of EOGBS in neonates. CPGs guide clinicians in their management based on a consensus of care drawn from clinical evidence and offer a standard of care for them to fall back on to guard against medical malpractice litigation. However, deviation from the intended clinical context or the failure to recognize the limits of such guidelines could compromise patient safety. Aim: The aim of this case study is to highlight the role and limitations of clinical practice guidelines in medical practice, through a case of an early onset GBS infection in a neonate that was a result of selectively applying the RCOG and ACOG guidelines outside their intended context. Conclusion: The case illustrates the importance of applying guidelines correctly within the appropriate clinical context but serves also as a reminder for clinicians to understand the limitations of them when accounting for other co-conditions patients often present with in daily medical practice.

Prevention of Group B Streptococcal Early-Onset Disease in Newborns

Group B streptococcus (GBS) is the leading cause of newborn infection. The primary risk factor for neonatal GBS early-onset disease (EOD) is maternal colonization of the genitourinary and gastrointestinal tracts. Approximately 50% of women who are colonized with GBS will transmit the bacteria to their newborns. Vertical transmission usually occurs during labor or after rupture of membranes. In the absence of intrapartum antibiotic prophylaxis, 1-2% of those newborns will develop GBS EOD. Other risk factors include gestational age of less than 37 weeks, very low birth weight, prolonged rupture of membranes, intraamniotic infection, young maternal age, and maternal black race. The key obstetric measures necessary for effective prevention of GBS EOD continue to include universal prenatal screening by vaginal-rectal culture, correct specimen collection and processing, appropriate implementation of intrapartum antibiotic prophylaxis, and coordination with pediatric care providers. The American College of Obstetricians and Gynecologists now recommends performing universal GBS screening between 36 0/7 and 37 6/7 weeks of gestation. All women whose vaginal-rectal cultures at 36 0/7-37 6/7 weeks of gestation are positive for GBS should receive appropriate intrapartum antibiotic prophylaxis unless a prelabor cesarean birth is performed in the setting of intact membranes. Although a shorter duration of recommended intrapartum antibiotics is less effective than 4 or more hours of prophylaxis, 2 hours of antibiotic exposure has been shown to reduce GBS vaginal colony counts and decrease the frequency of a clinical neonatal sepsis diagnosis. Obstetric interventions, when necessary, should not be delayed solely to provide 4 hours of antibiotic administration before birth. This Committee Opinion, including Table 1, Box 2, and Figures 1-3, updates and replaces the obstetric components of the CDC 2010 guidelines, "Prevention of Perinatal Group B Streptococcal Disease: Revised Guidelines From CDC, 2010."

Prevention of Group B Streptococcal Early-Onset Disease in Newborns: ACOG Committee Opinion, Number 797.

Group B streptococcus (GBS) is the leading cause of newborn infection. The primary risk factor for neonatal GBS early-onset disease (EOD) is maternal colonization of the genitourinary and gastrointestinal tracts. Approximately 50% of women who are colonized with GBS will transmit the bacteria to their newborns. Vertical transmission usually occurs during labor or after rupture of membranes. In the absence of intrapartum antibiotic prophylaxis, 1-2% of those newborns will develop GBS EOD. Other risk factors include gestational age of less than 37 weeks, very low birth weight, prolonged rupture of membranes, intraamniotic infection, young maternal age, and maternal black race. The key obstetric measures necessary for effective prevention of GBS EOD continue to include universal prenatal screening by vaginal-rectal culture, correct specimen collection and processing, appropriate implementation of intrapartum antibiotic prophylaxis, and coordination with pediatric care providers. The American College of Obstetricians and Gynecologists now recommends performing universal GBS screening between 36 0/7 and 37 6/7 weeks of gestation. All women whose vaginal-rectal cultures at 36 0/7-37 6/7 weeks of gestation are positive for GBS should receive appropriate intrapartum antibiotic prophylaxis unless a prelabor cesarean birth is performed in the setting of intact membranes. Although a shorter duration of recommended intrapartum antibiotics is less effective than 4 or more hours of prophylaxis, 2 hours of antibiotic exposure has been shown to reduce GBS vaginal colony counts and decrease the frequency of a clinical neonatal sepsis diagnosis. Obstetric interventions, when necessary, should not be delayed solely to provide 4 hours of antibiotic administration before birth. This Committee Opinion, including , , and , updates and replaces the obstetric components of the CDC 2010 guidelines, "Prevention of Perinatal Group B Streptococcal Disease: Revised Guidelines From CDC, 2010."

Umbilical cord separation time, predictors and healing complications in newborns with dry care.

The objective of this study was to explore the umbilical cord separation time, predictors, and healing complications from birth until the newborn was one month old. A quantitative longitudinal observational analytical study by stratified random sample was adopted. Public health system hospitals in southern Spain and at newborns' homes. Between April 2016 and December 2017, the study included 106 neonates born after 35-42 weeks of gestation whose umbilical cord was cured with water and soap and dried later as well as newborns without umbilical canalisation whose mothers enjoyed a low-risk pregnancy. The data collection procedure comprised two blocks: from birth to the time of separation of the umbilical cord and from cord separation to the first month of life of the newborn. Umbilical cord separation time was measured in minutes; socio-demographic and clinical characteristics were measured by means of questionnaires, and the external diameter of the umbilical cord was measured using an electronic stainless-steel calliper and trailing roller. The mean umbilical separation time: 6.61 days (±2.33, IC 95%:6.16-7.05). Incidence of omphalitis was 3.7%; granuloma was 8.6%. Separation time predictors were wetting recurrence, birth weight, intrapartum antibiotics, birth season, and Apgar < 9 (R2 = 0.439 F: 15.361, p <0.01). The findings support the World Health Organization recommendations: dry umbilical cord cares is a safe practice that soon detaches the umbilical cord, taking into account the factors studied that will vary the length of time until the umbilical cord is separated.

Intrapartum antibiotic therapy with cefazolin rather than clindamycin or metronidazole is associated with lower postpartum infectious morbidity among women with chorioamnionitis delivering by cesarean

To investigate whether intrapartum surgical prophylaxis with cefazolin versus clindamycin or metronidazole decreases the risk of postpartum infectious morbidity among women delivering by cesarean receiving a base regimen of ampicillin or penicillin with gentamycin for chorioamnionitis.

Preoperative cefazolin rather than clindamycin or metronidazole is associated with lower postpartum infection among women with chorioamnionitis delivering by cesarean delivery

The optimal antibiotic regimen to prevent maternal postpartum infection among high-risk women treated for chorioamnionitis delivering by cesarean delivery remains to be defined. Emerging data suggest that cefazolin decreases the risk of cesarean surgical site infection. To investigate whether intrapartum antibiotic therapy with cefazolin versus the current standard clindamycin or metronidazole decreases the risk of postpartum infectious morbidity among women delivering by cesarean delivery who were receiving a base regimen of ampicillin or penicillin with gentamicin for chorioamnionitis. A secondary analysis from the Maternal-Fetal Medicine Units Network (MFMU) Cesarean Registry. We included women who delivered by cesarean delivery with presumptive chorioamnionitis (intrapartum fever >100.4°F and receipt of intrapartum antibiotics). All women received a base regimen of penicillin or ampicillin with gentamicin. We compared antibiotic therapy with cefazolin versus clindamycin or metronidazole. The primary outcome was a composite of postpartum maternal infection, including endometritis and surgical site infection. Multivariable logistic regression was used, adjusting for age, parity, race/ethnicity, insurance, body mass index at delivery, tobacco use, pregestational diabetes, American Society of Anesthesiologists classification, trial of labor prior to cesarean delivery, and postpartum antibiotics. Among 1105 women with presumptive chorioamnionitis who delivered by cesarean delivery, 22.0% (n= 244) received cefazolin and 77.9% (n= 861) received clindamycin or metronidazole. Most women were in labor prior to cesarean delivery (93.8%) and received postpartum antibiotics (88.4%). Almost one-tenth (9.5%) were diagnosed with a postpartum infection, most commonly endometritis (80.9%), followed by surgical site infection (20.9%) (not mutually exclusive). Women treated with cefazolin rather than clindamycin or metronidazole had lower odds of postpartum infectious morbidity (adjusted odds ratio, 0.49; 95% confidence interval, 0.26-0.90). This association held when the outcome was restricted to surgical site infection (adjusted odds ratio, 0.11; 95% confidence interval, 0.01-0.92) but not endometritis. Similar results were observed with propensity score analysis. Among women delivering by cesarean delivery who were treated for chorioamnionitis, additional antibiotic therapy with cefazolin decreased the risk of postpartum infection, primarily surgical site infection, compared to the current standard clindamycin or metronidazole.

The relationship of prenatal and infant antibiotic exposure with childhood overweight and obesity: a systematic review.

This study aimed to assess the evidence regarding the relationship between early-life antibiotic exposure and childhood overweight/obesity by reviewing observational studies on prenatal antibiotic exposure and systematic reviews on infant antibiotic exposure. A search in Pubmed, Embase and Google Scholar covering the period 1st January till 1st December 2018 led to the identification of five studies on prenatal antibiotic exposure and four systematic reviews on infant antibiotic exposure. Positive trends between prenatal antibiotic exposure and overweight/obesity were reported in all studies; two studies reported a significant overall relationship and the other three reported significant relationships under certain conditions. Effect sizes ranged from odds ratio (OR): 1.04 (0.62-1.74) to relative risk (RR): 1.77 (1.25-2.51). Regarding infant antibiotics, one review concluded there was substantial evidence that infant antibiotic exposure increased the risk of childhood overweight/obesity [pooled effect sizes: RR: 1.21 (1.09-1.33) for overweight and RR: 1.18 (1.12-1.25) for obesity]. Two reviews concluded there was some evidence for a relationship [pooled effect sizes: OR: 1.05 (1.00-1.11) and OR: 1.11 (1.02-1.20)]. The fourth review concluded the studies were too heterogeneous for meta-analyses and the evidence regarding the relationship between infant antibiotic exposure and childhood overweight/obesity was inconclusive. More well-designed studies are needed that include data on intra-partum antibiotics and address important potential confounders (including maternal and childhood infections). This review points to some evidence of a relationship between early-life antibiotic exposure and childhood overweight/obesity; this is especially evident in certain children (i.e. exposed to multiple and broad-spectrum antibiotics, earlier postnatal exposure and male gender) and merits further research.

Early-Onset Neonatal Sepsis

Abstract Despite the great progress made in neonatal and perinatal medicine over the last couple of decades, sepsis remains one of the main causes of morbidity and mortality. Sepsis in pediatric population was defined at the Pediatric Sepsis Consensus Conference in 2005. There is still no consensus on the definition of neonatal sepsis. Neonatal sepsis is a sepsis that occurs in the neonatal period. According to the time of occurrence, neonatal sepsis can be of early onset, when it occurs within the first 72 hours of birth and results from vertical transmission, and of late onset, in which the source of infection is found most often in the environment and occurs after the third day of life. The most common causes of early-onset sepsis are Group B Streptococcus (GBS) and E. coli. Risk factors can be mother-related and newborn-related. Clinical symptoms and signs of sepsis are quite unspecific. The dysfunction of different organs may imitate sepsis. On the other hand, infectious and non-infectious factors may exist simultaneously. The start of the antimicrobial therapy in any newborn with suspected sepsis should not be delayed. Pentoxifylline may have potential benefits in preterm newborns with sepsis. The only proven intervention that has been shown to reduce the risk of early-onset neonatal sepsis is intrapartum intravenous antibiotic administration to prevent GBS infection. It is still a great challenge to discontinue antibiotic treatment in non-infected newborns as soon as possible, because any extended antibiotic use may later be associated with other pathological conditions.

Impact of delivery mode-associated gut microbiota dynamics on health in the first year of life

The early-life microbiome appears to be affected by mode of delivery, but this effect may depend on intrapartum antibiotic exposure. Here, we assess the effect of delivery mode on gut microbiota, independent of intrapartum antibiotics, by postponing routine antibiotic administration to mothers until after cord clamping in 74 vaginally delivered and 46 caesarean section born infants. The microbiota differs between caesarean section born and vaginally delivered infants over the first year of life, showing enrichment of Bifidobacterium spp., and reduction of Enterococcus and Klebsiella spp. in vaginally delivered infants. The microbiota composition at one week of life is associated with the number of respiratory infections over the first year. The taxa driving this association are more abundant in caesarean section born children, providing a possible link between mode of delivery and susceptibility to infectious outcomes.

A Comparison of Pneumococcal Nasopharyngeal Carriage in Very Young Fijian Infants Born by Vaginal or Cesarean Delivery

Pneumococcal nasopharyngeal carriage is a prerequisite for pneumococcal disease. The main transmission route is from toddlers, who commonly carry pneumococci. However, neonatal pneumococcal disease case reports suggest that vertical pneumococcal transmission may also occur. To describe and compare pneumococcal nasopharyngeal carriage and density by infant mode of delivery in young Fijian infants. Annual cross-sectional surveys were performed in Suva, Fiji, before the introduction of 10-valent pneumococcal conjugate vaccine (PCV10), from September 14 to December 20, 2012, and after PCV10 was introduced, from July 11 to November 19, 2013; July 15 to December 9, 2014; and August 13 to November 19, 2015. Caregivers of 2006 infants aged 5 to 8 weeks participated in the surveys. Statistical analysis was performed from May 24, 2018, to August 12, 2019. Caregivers provided data on infant mode of delivery and demographics via interviewer-led survey. Pneumococci in swab samples were detected and quantified by lytA quantitative polymerase chain reaction with molecular serotyping by microarray. Pneumococci were categorized as PCV10 or non-PCV10 serotypes. Of the 2006 infants (976 girls and 1030 boys; mean [SD] age, 6.1 [0.02] weeks]), 1742 (86.8%) were born vaginally and 264 were born by cesarean delivery. Infants delivered vaginally, compared with those born by cesarean delivery, had a higher prevalence of overall pneumococcal nasopharyngeal carriage (470 of 1722 [27.3%; 95% CI, 25.2%-29.4%] vs 47 of 260 [18.1%; 95% CI, 13.6%-23.3%]; P = .002), PCV10 carriage (113 of 1698 [6.7%; 95% CI, 5.5%-7.9%] vs 8 of 256 [3.1%; 95% CI, 1.4%-6.1%]; P = .03), and non-PCV10 carriage (355 of 1698 [20.9%; 95% CI, 19.0%-22.9%] vs 38 of 256 [14.8%; 95% CI, 10.7%-19.8%]; P = .02), and had higher median densities of overall pneumococci (4.9 log10 genome equivalents [GE]/mL [interquartile range, 4.8-5.0 log10 GE/mL] vs 4.5 log10 GE/mL [interquartile range, 4.1-4.6 log10 GE/mL]; P = .01) and non-PCV10 pneumococci (4.9 log10 GE/mL [interquartile range, 4.7-5.0 log10 GE/mL] vs 4.4 log10 GE/mL [interquartile range, 4.0-4.7 log10 GE/mL]; P = .01). Vaginal delivery was associated with overall (adjusted odds ratio, 1.57 [95% CI, 1.10-2.23]; P = .01) and non-PCV10 (adjusted odds ratio, 1.49 [95% CI, 1.01-2.20]; P = .04]) pneumococcal nasopharyngeal carriage. Vaginal delivery was not associated with PCV10 carriage (adjusted odds ratio, 1.67 [95% CI, 0.80-3.51]; P = .17). After adjustment, vaginal delivery was not associated with density. Pneumococcal nasopharyngeal carriage prevalence and density were higher in infants delivered vaginally compared with those delivered by cesarean birth. After adjustment, vaginal delivery was associated with pneumococcal carriage. Differences in carriage by mode of delivery may be due to differential exposure to the vaginal microbiota during delivery and the effect of intrapartum antibiotics during cesarean delivery on the infant microbiome. Our findings also raise the hypothesis that vertical transmission may contribute to pneumococcal acquisition.

Clinical and Microbiological Characteristics of Group B Streptococcus from Pregnant Women and Diseased Infants in Intrapartum Antibiotic Prophylaxis Era in Taiwan

Group B Streptococcus (GBS) is one of the most important pathogens for neonates. This study included 69 invasive GBS diseases in neonates, including 7 early-onset disease (EOD), 55 late-onset disease, and 7 very-late-onset disease from 2013 to 2017. A significant reduction of EOD after the deployment of intrapartum antibiotic prophylaxis (IAP) in 2012 was observed. A previously-recognized hypervirulent clone GBS III ST17, accounting for 68% of the overall infections and 71% of the meningitis, was identified among the 69 cases. A novel GBS Ia ST890 emerged, becoming the fourth most common clone. Overall 96% of the invasive GBS infections were caused by serotypes Ia, Ib, and III. We collected 300 GBS isolates from vagina of the healthy pregnant women in 2014 and 2017. The serotype distribution of the maternal colonization isolates was VI (35%), III (21%), V (15%), Ib (13%) and Ia (11%) in 2014, and VI (32%), III (22%), V (16%), Ia (16%), and Ib (8%) in 2017. The most common sequence types were ST1 (32%), ST12 (22%), and ST23 (15%). Serotype diversity of maternal colonization strains did not change between 2014 and 2017. The study provides useful information in surveillance of GBS disease in the era of IAP.

Effect of In-Utero Antibiotic Exposure on Childhood Outcomes: Methods and Baseline Data of the Fetal Antibiotic EXposure (FAX) Cohort Study.

BackgroundThe widespread use of antepartum and intrapartum antibiotics has raised concerns about the possible disruption of the child’s gut microbiota and effects on the maturation from the infant to the adult microbiome. The Fetal Antibiotic EXposure (FAX) study provides a cohort to examine the association between in-utero exposure to antibiotics and adverse childhood outcomes including body weight, atopic diseases, and autism spectrum disorders and to investigate the role of other potential factors mitigating or moderating the risk for adverse outcomes.ObjectiveThe aim of this paper was to describe the methods, cohort characteristics, and retention of infants included in the study cohort.MethodsFor this retrospective cohort study, we included children born in Kaiser Permanente Southern California (KPSC) hospitals between January 1, 2007, and December 31, 2015, within 22 to 44 completed weeks of gestation with KPSC insurance coverage during the first year of life. Follow-up data collection was performed through electronic medical records.ResultsThe study cohort was comprised 223,431 children of which 65.7% (146,720/223,431) were exposed to antibiotics in-utero: 19.0% (42,511/223,431) were exposed during the antepartum period, 30.0% (66,896/223,431) during the intrapartum period, and 16.7% (37,313/223,431) exposed during both the antepartum and intrapartum periods.During their first year of life, children had a median of 5 weight and height measurements; the frequency of weight and height measurements declined to a median of 3 in their second year of life and 2 for 3 to 5 years of age. The 5-year retention of children in the health plan was over 80% with the highest retention for Hispanic children.ConclusionsThis cohort of children will provide a unique opportunity to address key questions regarding the long-term sequelae of in-utero exposure to antibiotics using real-world data. The high retention and multiple medical visits over time allow us to model the trajectories of body mass index over time.International Registered Report Identifier (IRRID)DERR1-10.2196/12065

Impact of intrapartum and postnatal antibiotics on the gut microbiome and emergence of antimicrobial resistance in infants

Altogether, 20–30% of women receive intrapartum antibiotic prophylaxis (IAP) to prevent sepsis in infants and 2–5% of newborn infants receive antibiotics due to suspected sepsis. Caesarean section has a long-term impact on the intestinal microbiome but the effects of perinatal antibiotics on gut microbiome in vaginally delivered infants are not well known. We compared the impact of IAP, postnatal antibiotics, or their combination on the gut microbiome and emergence of antimicrobial resistance in a controlled study of 149 newborn infants recruited within 24 hours after birth. We collected 659 fecal samples, including 426 daily samples from infants before discharge from the hospital and 111 follow-up samples at six months. Penicillin was mostly used for IAP and the combination of penicillin and aminoglycoside for postnatal treatment. Postnatal antibiotic groups received Lactobacillus reuteri probiotic. Newborn gut colonization differed in both IAP and postnatal antibiotics groups as compared to that in control group. The effect size of IAP was comparable to that caused by postnatal antibiotics. The observed differences were still present at six months and not prevented by lactobacilli consumption. Given the present clinical results, the impact of perinatal antibiotics on the subsequent health of newborn infants should be further evaluated.

Outcome of Late-onset Neonatal Sepsis at a Tertiary Hospital in Oman.

ObjectivesWe sought to determine the prevalence, pattern of causative organisms, and mortality of newborns with culture-proven late-onset sepsis (LOS) and to determine and compare the risk factors linked to late-onset gram-positive and late-onset gram-negative sepsis in Sultan Qaboos University Hospital (SQUH).MethodsWe conducted a cross-sectional retrospective study of data obtained between 1 January 2007 and 31 December 2014 (eight years) from infants in the neonatal intensive care unit (NICU) at SQUH. Infants born in SQUH (inborn) and other institutions (outborn) with positive blood cultures were included in the study.ResultsThe total number of live births and admissions during the study period were 26 289 and 3559, respectively. The total number of infants identified with LOS were 125 of whom 69 (55.2%) were gram-positive, 52 (41.6%) were gram-negative, and four (3.2%) were due to Candida species (spp.). The majority of infants (n = 113, 90.4%) were inborn; 69 (55.2%) were males and 56 (44.8%) were females. The prevalence of LOS among inborn admissions was 4.3 per 1000 live births. Most infections occurred in very low birth weight infants (n = 81, 64.8%). Eleven (8.8%) infants died due to gram-negative sepsis. Klebsiella pneumoniae followed by Pseudomonas aeruginosa were the leading cause of death. Maternal intrapartum antibiotics were the only independent risk factor correlating with gram-negative organisms in multivariate analysis (p = 0.003).ConclusionsLOS poses a burden in the NICU, which could be due to the increasing survival of premature babies. The main contributing organisms to LOS are gram-positive bacteria. Klebsiella spp. is a major cause of mortality in LOS. The use of intrapartum antibiotic prophylaxis in mothers might explain the positive correlation of maternal antibiotics as a risk factor with gram-negative infections.