Maternal 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.

Maternal Antibiotic Treatment Dysregulates Goblet Cell Associated Antigen Passages in Neonatal Mice

Abstract Maternal antibiotic treatment (MAT) disrupts the development of the neonatal microbiome, intestinal immune development and increases susceptibility to sepsis in mouse models. Mechanisms by which MAT disrupts neonatal intestinal immune function will facilitate the development of novel strategies to reduce neonatal sepsis risk. Intestinal goblet cell associated antigen passages (GAPs) are portals for physiologic exposure of the immune system to commensal gut bacteria and luminal antigens. GAPs are inhibited by epidermal growth factor receptor (EGFR) signaling, colonic GAPs are closed prior to postnatal day (P) 10 in mice when luminal EGF levels from breast milk are high, then open after P10 when breast milk EGF levels decline. When colonic GAPs are opened inappropriately due to low levels of EGF prior to P10 or dysbiosis of the gut microbiota after weaning, they can facilitate pathological bacterial translocation. Pups of dams treated with ampicillin and neomycin in their drinking water from pup P1–8 had significantly more open GAPs in the small intestine (SI) compared to controls. These data suggest that MAT creates a permissive environment for SI GAPs in the neonatal period which could allow pathologic bacterial translocation. MAT pups weighed significantly less and were significantly hypoglycemic compared to pups from control dams, after weaning MAT pups recover to a normal weight. We hypothesize that MAT pups have reduced intestinal EGFR signaling, leading to stunted growth and irregular opening of GAPs in the SI and colon. These data suggest maternal antibiotic treatment may be a risk factor for sepsis and growth failure in premature neonates.

Fungal infection and neurodevelopmental outcomes at 18-30 months in preterm infants.

Invasive fungal infection (IFI) is associated with significant mortality and morbidity among preterm infants but there has been no population-based study of long-term neurodevelopmental outcomes. The objective of this study was to examine population-based incidence trends as well as mortality, short term in-hospital morbidity and long-term neurodevelopmental outcomes among preterm infants with IFI, non-fungal infections (NFI) and no infections in Canada. We conducted a retrospective cohort study of 8,408 infants born at <29 weeks gestational age (GA), admitted to Canadian Neonatal Network neonatal intensive care units (NICU) from April 2009 to December 2017, and followed up at 18-30 months corrected age (CA) in Canadian Neonatal Follow-Up Network clinics. We compared mortality, long term neurodevelopmental outcomes and short term in-hospital morbidity among 3 groups of infants (IFI, NFI, and no infections). The incidence of IFI was 1.3%, non-IFI 26.9% and no infections 71.7%. IFI incidence varied between 0.93% and 1.94% across the study period with no significant trend over time. Infants of higher gestational age were significantly (p < 0.01) less likely to have IFI. Among infants with IFI, NFI and no infections, the incidence of the significant neurodevelopmental impairment (sNDI) was 44.26%, 21.63% and 14.84% respectively, while mortality was 50%, 25.35% and 22.25% respectively. Even after risk adjustment for confounders (GA, Score for Neonatal Acute Physiology Version II, ruptured membranes >24 h, maternal antibiotic treatment, antenatal steroid use, cesarean section), infants with IFI had significantly higher odds of sNDI than NFI (aOR: 2.19; 95% CI: 1.23, 3.91) or no infections (aOR: 2.97; 95% CI: 1.55, 5.71), and higher odds of mortality than NFI (aOR: 1.55; 95% CI: 1.07, 2.26) or no infections (aOR: 1.45; 95% CI: 0.97, 2.17). Preterm infants with invasive fungal infections have significantly higher incidence of mortality and adverse neurodevelopmental outcomes than those with non-invasive fungal infections and no infections.

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.

Maternal antibiotic treatment during pregnancy attenuates the transport and absorption of maternal antibody IgG through TLR4 and TLR2 receptor.

Maternal antibody IgG, the main antibody in colostrum, plays an important role in neonates protection. Commensal microbiota is closely related to host antibody repertoire. However, there are few reports on how maternal gut microbiota affects maternal antibody IgG transfer. In the present study, we investigated the effects of altering the gut microbiota (treated with antibiotics during pregnancy) on maternal IgG transportation and offspring absorption and explored its underlying mechanisms. Results showed that antibiotic treatment during pregnancy significantly decreased maternal cecal microbial richness (Chao1 and Obesrved species) and diversity (Shannon and Simpson). Plasma metabolome enriched significant changes in the process of bile acid secretion pathway, and the concentration of deoxycholic acid, a secondary metabolite of microorganisms was lowered. Flow cytometry analysis indicated that antibiotic treatment promoted the number of B cells and abated the number of T, DC and M1 cells in intestinal lamina propria of dams. Surprisingly, the serum IgG level in antibiotic treated dams was significantly increased, while IgG contents in colostrum was decreased. Moreover, pregnancy antibiotic treatment in dams was reduced the expression of FcRn, TLR4 and TLR2 in breast of dams and in duodenum and jejunum of neonates. Furthermore, TLR4-/- and TLR2-/- knock-out mice showed a lower FcRn expression in breast of dams and in duodenum and jejunum of neonates. These findings suggest that maternal intestine bacteria may affect the maternal IgG transfer through regulating the breast TLR4 and TLR2 of dams.

Cross-sectional observational study protocol: missing microbes in infants born by caesarean section (MiMIC): antenatal antibiotics and mode of delivery

IntroductionThe intestinal microbiome in early life plays a major role in infant health and development. Factors like antibiotic exposure, breast/formula feeding and mode of delivery are known to affect the...

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.

Umbilical Cord Procalcitonin to Detect Early-Onset Sepsis in Newborns: A Promising Biomarker.

Background: Up to 7% of neonates born in high-income countries receive antibiotics for suspected early-onset sepsis (EOS). Culture-proven neonatal sepsis has a prevalence of 0.2%, suggesting considerable overtreatment. We studied the diagnostic accuracy of umbilical cord blood and infant blood procalcitonin (PCT) in diagnosing EOS to improve antibiotic stewardship.Methods: Umbilical cord blood PCT was tested in newborns ≥ 32 weeks of gestation. Groups were defined as following: A) culture-proven or probable EOS (n = 25); B) Possible EOS, based on risk factors for which antibiotics were administered for <72 h (n = 49); C) Risk factor(s) for EOS without need for antibiotic treatment (n = 181); D) Healthy controls (n = 74). Additionally, venous or capillary blood PCT and C-reactive protein (CRP) were tested if blood drawing was necessary for standard care.Results: Between June 2019 and March 2021, 329 newborns were included. Umbilical cord blood PCT was significantly higher in group A than in group C and D. No difference between venous or arterial samples was found. Sensitivity and specificity for cord blood procalcitonin were 83 and 62%, respectively (cut-off 0.1 ng/mL). Antepartum maternal antibiotic administration was associated with decreased PCT levels in both cord blood and infant blood directly postpartum in all groups combined.Conclusion: Umbilical cord blood PCT levels are increased in newborns ≥32 weeks with a proven or probable EOS and low in newborns with risk factors for infection, but PCT seems not a reliable marker after maternal antibiotic treatment. PCT could be useful to distinguish infected from healthy newborns with or without EOS risk factors.

Group B Streptococcus real-time PCR may potentially reduce intrapartum maternal antibiotic treatment.

Protocols for preventing early-onset group B streptococcal (GBS) neonatal infection may result in unnecessary antibiotics administration. Real-time polymerase chain reaction (PCR) can provide a result within 30-60min and has been found to be specific and sensitive for defining intrapartum GBS status. To evaluate whether implementation of GBS fast real-time PCR to all women who require GBS prophylaxis may reduce the use of maternal prophylactic antibiotics. This prospective cohort study included women admitted to a single delivery ward who required prophylactic antibiotics either due to a positive antepartum GBS culture screening performed at 35-37weeks or due to an unknown GBS status with an intrapartum risk factor. All the women were tested by a double vaginal swab (real-time PCR and culture) as soon as it became apparent, they required antibiotic prophylaxis and prior to its administration. Between May 2019 and August 2020, 303 women met eligibility criteria and were enrolled, but four were excluded from the analysis due to failed culture or PCR tests. Of 299 women included in the study, 208 (69.5%) and 180 (60.2%) women, showed no evidence of GBS on intrapartum culture or PCR, respectively. Of 89GBS antepartum carriers, 43 (48.3%) and 32 (35.9%) had negative intrapartum culture and PCR results, respectively. Of the 210 women with risk factors, 165 (78.5%) were culture negative and 148 (70.4%) had a negative PCR. Using intrapartum culture as the gold standard, intrapartum GBS real-time PCR was found to have a sensitivity of 97.8% (95% confidence interval [CI] 92.3, 99.7) and a specificity of 85.6% (95% CI 80.1, 90.1). Compared with antepartum universal culture screening or intrapartum risk-factor assessment, the need for maternal antibiotic treatment may be substantially reduced by implementation of intrapartum GBS real-time PCR, without compromising the sensitivity of GBS detection.

Antibiotics at delivery: do the benefits outweigh the risks?

Antibiotics administered just before delivery or during the intrapartum period is common globally and recommendations for increased use continue to expand. Before the introduction of maternal screening and treatment for Group B Streptococcus (GBS) colonization to prevent neonatal GBS sepsis in the 1990's, maternal antibiotic treatment at delivery was used rarely, usually for confirmed maternal infections. With maternal screening for GBS, including a 20-25% positivity rate in the United States (US), antibiotic use at delivery increased substantially.(1) Antibiotics at delivery were subsequently recommended for women with prolonged membrane rupture and preterm labor. Recommendations expanded further with evidence that antibiotics reduced post-partum maternal infections associated with cesarean delivery.(2) And now, following a trial in The Gambia that suggested reduced maternal and neonatal infections, several large trials in low- and middle-income countries (LMICs) are evaluating whether widespread azithromycin treatment, not only for women undergoing cesarean delivery, but among all pregnant women, reduces maternal and neonatal morbidity and mortality.(3).

134 Effect of Sow Nutrition on Offspring’s Gut Microbiota

Abstract In mammals, fetal development is programmed by the mother’s metabolism, body condition and health status, and thus by her diet. Besides this nutritional programming, the diet of sows has also an impact on her intestinal microbiota and on colostrum and milk production and composition, which may then modulate the microbiota of piglets. Indeed, colostrum and milk are composed of macronutrients, but contain as well immunoglobulins and immune cells, bioactive molecules such as hormones, growth factors, prebiotic and antimicrobial compounds. The latter two also play a role on the establishment of the gut microbiota. Moreover, the contact of the piglets with the faeces of the sows, at birth and during the lactation period, may all affect the composition of their microbiota. As a proof-of-concept concerning this microbiota modulation, it was shown that maternal antibiotic treatment from 10 days before the estimated farrowing date until 21 days after farrowing, transiently modified both mother fecal and offspring ileal microbiota during the first weeks of life, without effects on offspring’s microbiota on a long-term. There is evidence, although limited, that dietary fibers in the diet of the sows modulate the microbiota and gut homeostasis of the progeny. This has been shown by the use of seaweed extracts, short chain fructo-oligosaccharides, wheat bran, resistant starch, or the inclusion of guar gum and cellulose. For example, wheat bran in the diet of sows modulates the microbiota of the sows and piglets differently. Supplementation of the sow’s diet with probiotics (Bacillus subtilis) also revealed that the development of the intestinal microbiota of piglets is modulated, seen by a reduction in pathogenic communities (i.e. Escherichia coli, Clostridium perfringens) in colon and ileum respectively. In conclusion, to optimize piglet’s gut development through the colonization of the microbiota, the diet of the sow should be taken into account.

Child growth and neurodevelopment after maternal antenatal antibiotic treatment

ObjectiveTo assess whether intermittent preventive treatment of pregnant women (IPTp) with sulfadoxine-pyrimethamine (SP) and azithromycin (AZI) in a malaria-endemic area leads to sustained gains in linear growth and development in...

Maternal Gut Dysbiosis Alters Offspring Microbiota and Social Interactions.

Increasing application of antibiotics changes the gut microbiota composition, leading to dysbiosis of the gut microbiota. Although growing evidence suggests the potential role of gut dysbiosis as the cause of neurodevelopmental disorders and behavioral defects, a broad gap of knowledge remains to be narrowed to better understand the exact mechanisms by which maternal gut dysbiosis alters microbiota development and social interactions of offspring. Here, we showed that maternal gut dysbiosis during gestation is a critical determinant of gut microbiota and social interactions off mouse offspring. Gut microbiota of 2-week-old offspring showed significant changes in response to maternal antibiotic treatment. We even detected distinct effects of maternal oral antibiotics on gut microbiota of 14-week-old offspring. Compared to controls, offspring born to antibiotics-treated mothers displayed reduction in sociability and preference for social novelty, suggesting that the altered offspring social behavior was closely linked to dysbiosis of maternal gut microbiota. Our study opens the possibility to better understand the mechanism of how maternal gut microbiota vertically impairs social interactions of offspring in animal models, providing support to the maternal gut microbiota as a potential mediator between offspring microbiota and behaviors.

How Early-Life Gut Microbiota Alteration Sets Trajectories for Health and Inflammatory Bowel Disease?

Inflammatory bowel disease (IBD) is a recurrent chronic inflammatory condition of the intestine without any efficient therapeutic regimens. Gut microbiota, which plays an instrumental role in the development and maturation of the immune system, has been implicated in the pathogenesis of IBD. Emerging evidence has established that early-life events particularly maternal influences and antibiotic treatment are strongly correlated with the health or susceptibility to disease of an individual in later life. Thus, it is proposed that there is a critical period in infancy, during which the environmental exposures bestow a long-term pathophysiological imprint. This notion sheds new light on the development of novel approaches for the treatment, i.e., early interventions, more precisely, the prevention of many uncurable chronic inflammatory diseases like IBD. In this review, we have integrated current evidence to describe the feasibility of the “able-to-be-regulated microbiota,” summarized the underlying mechanisms of the “microbiota-driven immune system education,” explored the optimal intervention time window, and discussed the potential of designing early-probiotic treatment as a new prevention strategy for IBD.

Maternal Antibiotic Treatment Disrupts the Intestinal Microbiota and Intestinal Development in Neonatal Mice.

Maternal antibiotic treatment (MAT) during prenatal and intrapartum periods alters the bacterial composition and diversity of the intestinal microbiota of the offspring. The effect of MAT during pregnancy on the intestinal microbiota and its relationship with intestinal development remain unknown. This study investigated the effects of MAT during pregnancy on intestinal microbiota, injury and inflammation, vascularization, cellular proliferation, and the intestinal barrier in neonatal mice. At timed intervals, we fed pregnant C57BL/6N mice sterile drinking water containing antibiotics (ampicillin, gentamicin, and vancomycin; all 1 mg/ml) from gestational day 15 to delivery. The control dams were fed sterile drinking water. Antibiotic administration was halted immediately after birth. On postnatal day 7, the intestinal microbiota was sampled from the lower gastrointestinal tract and the ileum was harvested for histology, Western blot, and cytokines analyses. MAT significantly reduced the relative abundance of Bacteroidetes and Firmicutes and significantly increased the relative abundance of Proteobacteria in the intestine compared with their abundances in the control group. MAT also significantly increased intestinal injury score and cytokine levels, reduced the number of intestinal goblet cells and proliferating cell nuclear antigen-positive cells, and reduced the expressions of vascular endothelial growth factor and tight junction proteins. Therefore, we proposed that maternal antibiotic exposure during pregnancy disrupts the intestinal microbiota and intestinal development in neonatal mice.

Interactions between maternal fluoxetine exposure, the maternal gut microbiome and fetal neurodevelopment in mice

Selective serotonin reuptake inhibitors (SSRIs) are the most widely used treatment by women experiencing depression during pregnancy. However, the effects of maternal SSRI use on early offspring development remain poorly understood. Recent studies suggest that SSRIs can modify the gut microbiota and interact directly with particular gut bacteria, raising the question of whether the gut microbiome impacts host responses to SSRIs. In this study, we investigate effects of prenatal SSRI exposure on fetal neurodevelopment and further evaluate potential modulatory influences of the maternal gut microbiome. We demonstrate that maternal treatment with the SSRI fluoxetine induces widespread alterations in the fetal brain transcriptome during midgestation, including increases in the expression of genes relevant to synaptic organization and neuronal signaling and decreases in the expression of genes related to DNA replication and mitosis. Notably, maternal fluoxetine treatment from E7.5 to E14.5 has no overt effects on the composition of the maternal gut microbiota. However, maternal pretreatment with antibiotics to deplete the gut microbiome substantially modifies transcriptional responses of the fetal brain to maternal fluoxetine treatment. In particular, maternal fluoxetine treatment elevates localized expression of the opioid binding protein/cell adhesion molecule like gene Opcml in the fetal thalamus and lateral ganglionic eminence, which is prevented by maternal antibiotic treatment. Together, these findings reveal that maternal fluoxetine treatment alters gene expression in the fetal brain through pathways that are impacted, at least in part, by the presence of the maternal gut microbiota.

Maternal antibiotic treatment affects offspring gastric sensing for umami taste and ghrelin regulation in the pig

BackgroundScarce is knowledge on the process regulating the development of acid secretion, orexigenic signaling, and chemosensing in the stomach of young pigs. Changes of early microbial encounters by suckling pigs can interact with the gut maturation, by the induction of different molecular signaling. Our goal was to assess if the age of offspring and the maternal environment, influenced by sow antibiotic treatment peripartum, could affect gastric morphology and the expression of genes involved in the control of hydrochloric secretion, feed intake, taste, and inflammation in offspring stomach.Methods84 pigs from sows fed a diet with amoxicillin (on –d10 to +d21 from farrowing, ANT) or without (CON) were sacrificed at d14, d21, d28 (weaning) or d42. Samples of oxyntic (OXY), pyloric (PY) and cardiac mucosae close to OXY were collected and parietal and enteroendocrine cells (EECs) were counted. Relative gene expression of a set of 11 key genes (ATP4A, SSTR2, GAST, GHRL, MBOAT4, PCSK1, GNAT1, TAS1R1, TAS1R3, IL8 and TNF) was assessed by qRT-PCR. In addition, 40 offspring obtained from the same ANT and CON sows were offered a normal or a fat-enriched diet for 4 weeks between 140 and 169 d of age, and then OXY and PY were sampled.ResultsThe number of parietal and EECs increased with age (P < 0.001). ATP4A increased with age (within suckling, P = 0.043, post-weaning vs. suckling, P < 0.001), SSTR2 increased only after weaning (P < 0.001). In OXY, GHRL increased during suckling (P = 0.012), and post-weaning as a trend (P = 0.088). MBOAT4 tended to increase during suckling (P = 0.062). TAS1R1 increased from suckling to post-weaning period (P =0.001) and was lower in ANT offspring (P = 0.013). GNAT1 in PY was higher in ANT offspring (P = 0.041). Antibiotic treatment of sows peripartum increased expression of GHRL and MBOAT4 in OXY of growing-finishing offspring aged 5 months.ConclusionsData show that sensing for umami taste and ghrelin regulation can be affected by maternal environment, but the development of acid secretion, orexigenic signaling and taste perception in the stomach are mostly developmentally controlled.

Maternal antibiotic exposure disrupts microbiota and exacerbates hyperoxia-induced lung injury in neonatal mice.

Perinatal antibiotic treatment alters intestinal microbiota and augments hyperoxia-induced lung injury in mice offspring. The effect of maternal antibiotic treatment (MAT) during pregnancy on the lung microbiota and its relationship with lung injury remains unknown. We fed timed-pregnant C57BL/6N mice sterile drinking water containing antibiotics from gestational day 15 to delivery. Neonatal mice were reared in either room air (RA) or hyperoxia (85% O2) from postnatal days 1 to 7. Four study groups were obtained: control + RA, control + O2, MAT + RA, and MAT + O2. On postnatal day 7, lung and intestinal microbiota were sampled from the left lung and lower gastrointestinal tract. The right lung was harvested for histology and cytokine analysis. MAT during pregnancy significantly reduced the total number of commensal bacteria in the intestine and birth body weight of newborn mice compared with control newborn mice. Neonatal hyperoxia exposure impaired alveolarization and angiogenesis, which was exacerbated by MAT. Neonatal hyperoxia altered the composition and diversity of intestinal and lung microbiota and MAT further exacerbated neonatal hyperoxia-induced intestinal and lung dysbiosis. MAT during pregnancy exacerbates hyperoxia-induced lung injury probably through the modulation of intestinal and lung microbiota in neonatal mice. MAT during pregnancy reduced the total number of commensal bacteria in the intestine. Neonatal hyperoxia altered the composition and diversity of intestinal and lung microbiota. MAT exacerbated neonatal hyperoxia-induced intestinal and lung dysbiosis. Neonatal hyperoxia exposure impaired alveolarization and angiogenesis, which was exacerbated by MAT. Avoiding and carefully using antibiotics during pregnancy is a potential therapeutic target for preventing lung injury in hyperoxia-exposed infants.

Lethal Neonatal Respiratory Failure by Perinatal Transmission of Ureaplasma Parvum after Maternal PPROM.

A primiparous pregnant woman was admitted due to preterm premature rupture of membranes (PPROM) at 27+0 week of gestational age (WGA). Conventional vaginal microbiological analysis had no pathological finding. Management decisions based on national guidelines included antenatal corticoids, tocolytics and antibiotics. Unstoppable efforts of preterm labor in 28+0 WGA and supposed amniotic infection syndrome necessitated emergency cesarean section. The preterm infant underwent NICU therapy, developed an early-onset neonatal sepsis and therapy-refractory pulmonary insufficiency with consecutive right heart failure, resulting in death on the 36th day of life. Microbiota analyses by 16Sr DNA sequencing was performed from maternal vaginal swabs and from neonatal pharyngeal swabs. Maternal antibiotic treatment resulted in depletion of physiological vaginal colonization with Lactobacillus crispatus. Ureaplasma parvum became the dominant vaginal microorganism at delivery and was detected in high relative abundance in the neonatal specimen. Progressive radiological air-space changes and interstitial pathologies associated with Ureaplasma infection (bronchopulmonary dysplasia type III) were seen early at the 3rd and distinctly from 14th day of life. This clearly demonstrates the need of vaginal colonization diagnostics in PPROM patients and awareness of the consecutive risks in the preterm. Vaginal microbiome analysis may allow individualized and targeted maternal and fetal diagnostic, prophylactic and therapeutic strategies to identify, protect and treat the high-risk neonates after PPROM.