Potential Association of Gut Microbial Metabolism and Circulating mRNA Based on Multiomics Sequencing Analysis in Fetal Growth Restriction.

Objective: Fetal growth restriction (FGR) is a significant contributor to negative pregnancy and postnatal developmental outcomes. Currently, the exact pathological mechanism of FGR remains unknown. This study aims to utilize multiomics sequencing technology to investigate potential relationships among mRNA, gut microbiota, and metabolism in order to establish a theoretical foundation for diagnosing and understanding the molecular mechanisms underlying FGR. Methods: In this study, 11 healthy pregnant women and nine pregnant women with FGR were divided into Control group and FGR group based on the health status. Umbilical cord blood, maternal serum, feces, and placental tissue samples were collected during delivery. RNA sequencing, 16S rRNA sequencing, and metabolomics methods were applied to analyze changes in umbilical cord blood circulating mRNA, fecal microbiota, and metabolites. RT-qPCR, ELISA, or western blot were used to detect the expression of top 5 differential circulating mRNA in neonatal cord blood, maternal serum, or placental tissue samples. Correlation between differential circulating mRNA, microbiota, and metabolites was analyzed by the Spearman coefficient. Results: The top 5 mRNA genes in FGR were altered with the downregulation of TRIM34, DEFA3, DEFA1B, DEFA1, and QPC, and the upregulation of CHPT1, SMOX, FAM83A, GDF15, and NAPG in newborn umbilical cord blood, maternal serum, and placental tissue. The abundance of Bacteroides, Akkermansia, Eubacterium_coprostanoligenes_group, Phascolarctobacterium, Parasutterella, Odoribacter, Lachnospiraceae_UCG_010, and Dielma were significantly enriched in the FGR group. Metabolites such as aspartic acid, methionine, alanine, L-tryptophan, 3-methyl-2-oxovalerate, and ketoleucine showed notable functional alterations. Spearman correlation analysis indicated that metabolites like methionine and alanine, microbiota (Tyzzerella), and circulating mRNA (TRIM34, SMOX, FAM83A, NAPG) might play a role as mediators in the communication between the gut and circulatory system interaction in FGR. Conclusion: Metabolites (METHIONINE, alanine) as well as microbiota (Tyzzerella) and circulating mRNA (TRIM34, SMOX, FAM83A, NAPG) were possible mediators that communicated the interaction between the gut and circulatory systems in FGR.

Association between Intrauterine Microbiome and Risk of Intrauterine Growth Restriction: A Case-Control Study Based on Guangxi Zhuang Birth Cohort in China.

Substantial evidence show that intrauterine growth restriction (IUGR) is linked to both short-term and long-term health consequences. Recent studies have shown that the intrauterine environment harbors a diverse community of microbes. However, the relationship between intrauterine microbiome and IUGR has been rarely studied. In our investigation of 35 neonates with IUGR and 187 neonates without IUGR, we found that the intrauterine microbiome was largely composed of nonpathogenic commensal microbiota from the Proteobacteria, Firmicutes, Actinobacteria, and Bacteroidetes phyla. Carriage of genera Afipia [odds ratio (OR) 0.24; 95% confidence interval (CI) 0.10-0.60], Hydrogenophaga (OR 0.10; 95% CI 0.01-0.76), and Perlucidibaca (OR 0.25; 95% CI 0.10-0.61) were significantly associated with decreased risk of IUGR, while one log10-unit increasing of relative abundance the genera Catenibacterium (OR 2.56; 95% CI 1.09-6.01) and Senegalimassilia (OR 1.78; 95% CI 1.00-3.16), and carriage of Holdemanella (OR 4.07; 95% CI 1.54-10.76), Parvimonas (OR 3.33; 95% CI 1.16-9.57), Sandaracinus (OR 3.27; 95% CI 1.21-8.84), and Streptococcus (OR 3.52; 95% CI 1.13-10.95) were associated with increased risk of IUGR. The present study firstly demonstrated that carriage of Afipia, Hydrogenophaga, and Perlucidibaca in the intrauterine environment is associated with a decreased risk of IUGR, while carriage of Holdemanella, Parvimonas, Sandaracinus, and Streptococcus, and increased relative abundance of Catenibacterium and Senegalimassilia are associated with an increased risk of IUGR. The study provides evidence that the intrauterine microbiome may play a role in the etiology of IUGR.

Utility of Neonatal Ophthalmologic Examination for Detection of Infectious Etiologies for Symmetric Intrauterine Growth Restriction.

OBJECTIVE: To determine the utility of ophthalmologic examination as part of evaluation for infection in infants with intrauterine growth restriction (IUGR). STUDY DESIGN: This is a single-institution retrospective chart review of neonates diagnosed with symmetric IUGR or small for gestational age (SGA) who underwent complete ophthalmologic consultation to assess for intraocular findings suggestive of congenital infection. Data collected included other factors that may cause IUGR, findings of general and ophthalmologic examinations, and results of investigation for intrauterine infection. Cost minimization analysis was also performed. RESULTS: One hundred neonates met the study's inclusion criteria (IUGR, n = 24; SGA, n = 45; IUGR and SGA, n = 31). The mean gestational age at birth was 34.6 ± 3.0 weeks, and the mean birth weight was 1691 ± 530 g; 74% had an identifiable risk factor for IUGR and 84 patients underwent investigation for intrauterine infection. Two of the 73 patients who had urine culture for cytomegalovirus (CMV) were positive (1 of whom had systemic signs of severe congenital infection without eye involvement, the other who had no clinical signs of congenital CMV); evaluations for infection were negative otherwise. No patients had any ophthalmologic signs of congenital infection. CONCLUSIONS: Current literature suggests that routine evaluation of neonates with isolated IUGR for congenital infection may be low-yield and not cost-effective. Our study found that routine ophthalmologic evaluation in newborns with symmetric IUGR who have no systemic signs of intrauterine infection is of little value.

Gut microbiota of newborn piglets with intrauterine growth restriction have lower diversity and different taxonomic abundances.

AIM: Intrauterine growth retardation (IUGR) is a prevalent problem in mammals. The present study was conducted to unveil the alterations in intestinal microbiota in IUGR piglets. METHODS AND RESULTS: We identified the alterations of small intestinal microbiota in IUGR piglets on 7, 21 and 28 days of age using 16S rRNA sequencing. The results showed that IUGR piglets had a decreased alpha diversity of jejunum microbiota at 7 and 21 days of age; had lower abundances of Bacteroidetes and Bacteroides in the jejunum at 7, 21 and 28 days of age, Oscillibacter in the jejunum at 21 days of age, and Firmicutes in the ileum at 21 days of age; whereas they had higher abundances of Proteobacteria and Pasteurella in the ileum at 21 days of age and Escherichia-Shigella in the jejunum at 28 days of age. Correlation analysis showed that Bacteroides, Oscillibacter and Ruminococcaceae_UCG-002 compositions were positively associated with the body weight (BW) of IUGR piglets, nevertheless Proteobacteria and Escherichia-Shigella relative abundances were negatively correlated with the BW of IUGR piglets. Gene function prediction analysis indicated that microbiota-associated carbohydrate metabolism, lipid metabolism, glycan biosynthesis and metabolism, amino acid metabolism, and xenobiotics biodegradation and metabolism were downregulated in the IUGR piglets compared to control piglets. CONCLUSIONS: The present study profiled the intestinal microbiota of newborn piglets with IUGR and the newborn IUGR piglets have lower diversity and different taxonomic abundances. Alterations in the abundances of Bacteroidetes, Bacteroides, Proteobacteria Escherichia-Shigella and Pasteurella may be involved in nutrient digestion and absorption, as well as the potential mechanisms connecting to the growth and development of IUGR in mammals. SIGNIFICANCE AND IMPACT OF THE STUDY: The small intestinal microbiota were highly shaped in the IUGR piglets, which might further mediate the growth and development of IUGR piglets; and the gut microbiota could serve as a potential target for IUGR treatment.

Relation between Helicobacter pylori infection and severe pre-eclampsia complicated by intrauterine growth restriction in a rural area in Egypt.

The purpose of this study was to evaluate the association of Helicobacter pylori (HP) infection with severe pre-eclampsia (PE) complicated by intrauterine growth restriction using rapid stool antigen test in a rural area in Egypt. Maternal stool samples were collected from 50 pregnant women diagnosed with PE-associated intrauterine growth restriction (IUGR) and from 50 women with healthy pregnancies (control) between 34 and 38 weeks of gestation. HP stool antigen (HPSA) was measured using a monoclonal antibody test, which is an immuno-chromatographic assay that uses antibody-coated colloidal gold. A significantly higher percentage of HPSA positive women were found among PE cases complicated by IUGR (76%) compared to healthy pregnancies (32%) (p < .0001). However, in the PE/IUGR group, neonatal weight was not significantly lower in HPSA positive patients compared to HPSA negative patients (p = .08). This led to our conclusion that Helicobacter pylori infection has a possible role in the etiopathogenesis of PE with IUGR with no evident effect on its severity.

Campylobacter coli infection causing second trimester intrauterine growth restriction (IUGR): a case report and review of the literature.

Campylobacter is a gram-negative, microaerophilic, curved rod and a normal resident of the gastrointestinal flora and may be the cause of disease in animals. Transmission to humans occurs by ingestion of contaminated food or by direct contact with infected animals. In the past few decades, an increasing number of reports have implicated the presence of this organism in human abortions as well. An infectious mechanism due to primary placental inflammatory damage followed by secondary damage to the fetus following placental insufficiency and ischemia was suggested. The most common species of Campylobacter are Campylobacter jejuni and Campylobacter coli, which are classically associated with enteritis in humans. We present a rare case of mid-gestation intrauterine growth restriction (IUGR) associated with maternal bacteremia caused by C. coli infection. Our literature review focuses on Campylobacter infections occurring in the second and third trimesters of pregnancy. In all cases, mild maternal symptoms consisting of fever and weakness were presented. However, associated adverse fetal outcome, including abortions, IUGR or preterm labor may occur more frequently than anticipated. Our report strengthens the importance of awareness to this finding and focuses the need to consume properly cooked meat during pregnancy.

Significance of maternal screening for toxoplasmosis, rubella, cytomegalovirus and herpes simplex virus infection in cases of fetal growth restriction.

AIM: The objective of this study was to evaluate the significance of maternal toxoplasmosis, rubella, cytomegalovirus (CMV) and herpes simplex virus (TORCH) screening in cases of fetal growth restriction (FGR). MATERIAL AND METHODS: The medical records of women carrying fetuses with FGR who underwent TORCH screening over a 10-year period were retrospectively reviewed for maternal and congenital TORCH infection. Women carrying fetuses with FGR routinely underwent serologic TORCH tests and systematic ultrasound evaluation for congenital abnormalities. If a congenital CMV infection was suspected, amniotic fluid, placenta or neonatal urine was used for CMV DNA detection by polymerase chain reaction. RESULTS: In 319 patients, no cases of maternal or congenital infection with toxoplasma, rubella, or herpes simplex virus were found. Conversely, six cases (1.8%) were diagnosed with congenital CMV infection, two of which had no structural abnormalities other than FGR. CONCLUSIONS: A complete maternal TORCH screening for cases of FGR appears to be unnecessary. Although a maternal CMV test can be considered, the incidence of congenital CMV infection was found to be low in FGR cases.

Alterations in the Gut Microbiome and Metabolisms in Pregnancies with Fetal Growth Restriction.

Fetuses diagnosed with fetal growth restriction (FGR) are at an elevated risk of stillbirth and adulthood morbidity. Gut dysbiosis has emerged as one of the impacts of placental insufficiency, which is the main cause of FGR. This study aimed to characterize the relationships among the intestinal microbiome, metabolites, and FGR. Characterization was conducted on the gut microbiome, fecal metabolome, and human phenotypes in a cohort of 35 patients with FGR and 35 normal pregnancies (NP). The serum metabolome was analyzed in 19 patients with FGR and 31 normal pregnant women. Multidimensional data was integrated to reveal the links between data sets. A fecal microbiota transplantation mouse model was used to determine the effects of the intestinal microbiome on fetal growth and placental phenotypes. The diversity and composition of the gut microbiota were altered in patients with FGR. A group of microbial species altered in FGR closely correlated with fetal measurements and maternal clinical variables. Fecal and serum metabolism profiles were distinct in FGR patients compared to those in the NP group. Altered metabolites were identified and associated with clinical phenotypes. Integrated multi-omics analysis revealed the interactions among gut microbiota, metabolites, and clinical measurements. Microbiota from FGR gravida transplanted to mice progestationally induced FGR and placental dysfunction, including impaired spiral artery remodeling and insufficient trophoblast cell invasion. Taken together, the integration of microbiome and metabolite profiles from the human cohort indicates that patients with FGR endure gut dysbiosis and metabolic disorders, which contribute to disease pathogenesis. IMPORTANCE Downstream of the primary cause of fetal growth restriction are placental insufficiency and fetal malnutrition. Gut microbiota and metabolites appear to play an important role in the progression of gestation, while dysbiosis induces maternal and fetal complications. Our study elaborates the significant differences in microbiota profiles and metabolome characteristics between women with FGR and normal pregnancies. This is the first attempt so far that reveals the mechanistic links in multi-omics in FGR, providing a novel insight into host-microbe interaction in placenta-derived diseases.

Maternal/fetal mortality and fetal growth restriction: role of nitric oxide and virulence factors in intrauterine infection in rats.

OBJECTIVE: The mechanism of infection-related deaths of pregnant rats and intrauterine growth restriction are not understood. We assessed whether nitric oxide (NO) has differential effects on infection with Escherichia coli Dr/Afa mutants that lack either AfaE or AfaD invasins. STUDY DESIGN: Sprague-Dawley rats were infected intrauterinally with the clinical strain of E coli AfaE(+)D(+) or 1 of its isogenic mutants in the presence or absence of the NO synthesis inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME). Maternal/fetal mortality rates, fetoplacental weight, and infection rates were evaluated. RESULTS: Maternal and/or fetal death was associated with the presence of at least 1 virulence factor (AfaE(+)D(+)>AfaE(+)D(-)>AfaE(-)D(+)) and was increased by L-NAME treatment. The fetal and placental weights were lower than controls and were further reduced by L-NAME treatment. CONCLUSION: These results demonstrate that NO enhanced AfaE- and AfaD-mediated virulence and plays an important role in Dr/Afa(+)E coli gestational tropism.

Intrauterine Growth Restriction Is Associated with Unique Features of the Reproductive Microbiome.

Intrauterine growth restriction (IUGR) is an obstetrical complication with an increased risk of perinatal mortality and morbidity. The uterus, once considered to be a sterile environment, has now been described in recent microbiome studies to harbor diverse commensal placenta microbiota, as well as potentially pathogenic flora known to cause infection. Therefore, in this pilot study, we tested whether IUGR was associated with changes to the reproductive microbiome. The reproductive microbiome was surveyed using 16S sequencing (20 IUGR, 20 controls). Alpha and beta diversity were compared, and differential taxa features associated with IUGR were identified. Microbial screening of the placenta demonstrated a diverse range of flora predominantly including Proteobacteria, Fusobacteria, Firmicutes, and Bacteroidetes. Neither alpha- nor beta-diversity was significantly different by IUGR status. However, at the taxa level, IUGR patients had significantly higher prevalence of Neisseriaceae, mucosal ß-hemolytic bacteria known to uptake iron-bound host proteins including hemoglobin. Moreover, the increase in anaerobic bacteria such as Desulfovibrio reflects the emergence of a hypoxic environment in the IUGR placenta. Further analysis of the reproductive microbiome of IUGR samples showed lower levels of H202-producing Bifidobacterium and Lactobacillus that switch from respiration to fermentation, a less energetic metabolic process, when oxygen levels decrease. Source tracking analysis showed that the placental microbial contents were predominantly contributed from an oral source, as compared to a gut or vaginal source. Our results suggest that the reproductive microbiome profiles may, in the future, constitute potential biomarkers for fetal health during pregnancy, while Neisseriaceae may constitute promising therapeutic targets for IUGR treatment.

Characteristics of the gut microbiota colonization, inflammatory profile, and plasma metabolome in intrauterine growth restricted piglets during the first 12 hours after birth.

Intrauterine growth restriction (IUGR) predisposes newborns to inflammatory and metabolic disturbance. Disequilibrium of gut microbiota in early life has been implicated in the incidence of inflammation and metabolic diseases in adulthood. This study aimed to investigate the difference in gut microbiota colonization, cytokines and plasma metabolome between IUGR and normal birth weight (NBW) piglets in early life. At birth, reduced (P < 0.05) body, jejunum, and ileum weights, as well as decreased (P < 0.05) small intestinal villi and increased (P < 0.05) ileal crypt depth were observed in IUGR piglets compared with their NBW counterparts. Imbalanced inflammatory and plasma metabolome profile was observed in IUGR piglets. Furthermore, altered metabolites were mainly involved in fatty acid metabolism and inflammatory response. At 12 h after birth and after suckling colostrum, reduced (P < 0.05) postnatal growth and the small intestinal maturation retardation (P < 0.05) continued in IUGR piglets in comparison with those in NBW littermates. Besides, the gut microbiota structure was significantly altered by IUGR. Importantly, the disruption of the inflammatory profile and metabolic status mainly involved the pro-inflammatory cytokines (IL-1ß and IFN-γ) and amino acid metabolism. Moreover, spearman correlation analysis showed that the increased abundance of Escherichia-Shigella and decreased abundance of Clostridium_sensu_stricto_1 in IUGR piglets was closely associated with the alterations of slaughter weight, intestinal morphology, inflammatory cytokines, and plasma metabolites. Collectively, IUGR significantly impairs small intestine structure, modifies gut microbiota colonization, and disturbs inflammatory and metabolic profiles during the first 12 h after birth. The unbalanced gut microbiota mediated by IUGR contributes to the development of inflammation and metabolic diseases.

Flaxseed oil supplementation improves intestinal function and immunity, associated with altered intestinal microbiome and fatty acid profile in pigs with intrauterine growth retardation.

Flaxseed oil (FO), enriched in n-3 polyunsaturated fatty acids (PUFAs), is an important oil source for intestinal development and health. We aimed to study the different effects of FO versus soybean oil (SO) on growth, intestinal health and immune function of neonates with intrauterine growth retardation (IUGR) using a weaned piglet model. Forty pairs of male IUGR and normal birth weight piglets, weaned at 21 ± 1 d, were fed diets containing either 4% FO or SO for 3 weeks consecutively. Growth performance, nutrient digestibility and intestinal function parameters, immunology and microbiota composition were determined. IUGR led to a poor growth rate, nutrient digestibility and abnormal immunology variables, whereas feeding FO diet improved systemic and gut immunity, as indicated by increased plasma concentration of immunoglobulin G and decreased CD3+CD8+ T lymphocytes, and down-regulated intestinal expression of genes (MyD88, NF-κB, TNF-α, IL-10). Although IUGR tended to decrease villous height, feeding FO diet tended to increase the villi-crypt ratio and up-regulated expressions of tight junction genes (Claudin-1 and ZO-1), together with increased mucosa contents of n-3 PUFAs and a lower Σn-6/Σn-3 ratio. Besides, FO diet decreased the abundance of pathogenic bacteria Spirochaetes, and increased phylum Actinobacteria, and genera Blautia and Bifidobacterium in colonic digesta. Our findings indicate that IUGR impairs growth rate, nutrient digestibility, and partly immunology variables, whereas feeding FO-supplemented diet could improve intestinal function and immunity of both IUGR and NBW pigs, associated with the altered gut microbiome and mucosal fatty acid profile.

Managing Q fever during pregnancy: the benefits of long-term cotrimoxazole therapy.

BACKGROUND: Q fever is a zoonosis caused by Coxiella burnetii. During pregnancy, it may result in obstetric complications, such as spontaneous abortion, intrauterine growth retardation, intrauterine fetal death, and premature delivery. Pregnant women are exposed to the risk of chronic Q fever. METHODS: We included 53 pregnant women who received a diagnosis of Q fever. We compared the incidence of obstetric and maternal Q fever complications for women who received long-term cotrimoxazole treatment (n=16) with that for women who did not receive long-term cotrimoxazole treatment (n=37); long-term cotrimoxazole treatment was defined as oral administration of trimethoprim-sulfamethoxazole during at least 5 weeks of pregnancy. RESULTS: Obstetric complications were observed in 81.1% of pregnant women who did not receive long-term cotrimoxazole therapy: 5 (13.5%) women experienced spontaneous abortions, 10 (27%) experienced intrauterine growth retardation, 10 (27%) experienced intrauterine fetal death, and 10 (27%) experienced premature delivery. Oligoamnios was observed in 4 patients (10.8%). Obstetric complications were found to occur significantly more often in patients infected during their first trimester of pregnancy than in those infected later (P=.032). The outcome of the pregnancy was found to depend on placental infection by C. burnetii (P=.013). Long-term cotrimoxazole treatment protected against maternal chronic Q fever (P=.001), placental infection (P=.038), and obstetric complications (P=.009), especially intrauterine fetal death (P=.018), which was found to be related to placental infection (P=.008). CONCLUSIONS: Q fever during pregnancy results in severe obstetric complications, including oligoamnios. Because of its ability to protect against placental infection, intrauterine fetal death, and maternal chronic Q fever, long-term cotrimoxazole treatment should be used to treat pregnant women with Q fever.

Effect of Bifidobacterium breve M-16V supplementation on faecal bifidobacteria in growth restricted very preterm infants - analysis from a randomised trial.

BACKGROUND: Gut development, function and colonisation are impaired in animal models of prematurity with intrauterine growth restriction (IUGR). The effect of Bifidobacterium breve (B. breve) supplementation on faecal bifidobacteria in small for gestational age (SGA: birth weight <10th centile due to IUGR) preterm infants is not known. OBJECTIVE: We compared B. breve M-16V supplementation effect on faecal bifidobacteria in preterm (<33 weeks) SGA versus non-SGA infants in the two arms of our randomised controlled trial. RESULTS: There were no baseline differences in the proportion of detectable B. breve counts between SGA versus non-SGA infants [probiotic: 7 (33%) versus 22 (42%), p = 0.603; placebo: 1 (6%) versus 1 (2%), p = 0.429]. B. breve counts did not differ between SGA and non-SGA infants in response to treatment (p = 0.589), after adjusting for baseline count (p < 0.001) and treatment allocation (p < 0.001). An interaction term between growth status and treatment showed negligible change (p = 0.938). Probiotic treated SGA infants reached full feeds earlier than SGA controls (HR 2.00, 95% CI 1.05-3.82, p = 0.035): Median (IQR): 16 (12-26) versus 19 (11-25) days, after adjustment for age at starting feeds and gestation <28 weeks. CONCLUSION: Response to B. breve M-16V supplementation was not significantly different in preterm (<33 weeks) SGA versus non-SGA infants.

Campylobacter rectus mediates growth restriction in pregnant mice.

BACKGROUND: Recent studies have suggested that subclinical infection may be an important cause of low birth weight. Campylobacters are important human pathogens, causing septicemia and occasionally abortion, premature labor, or severe perinatal infection. The potential role of oral species of Campylobacter in mediating adverse pregnancy outcomes in animal models has not yet been determined. Our objective was to determine the effects of Campylobacter rectus (C. rectus) infection on pregnancy outcomes in a mouse model. METHODS: On embryonic day (E) 7.5, pregnant mice received a subcutaneous, intra-chamber challenge with live C. rectus at concentrations of 0, 10(7) or 10(9) colony forming units (CFU)/ml. They were sacrificed on E 16.5 and fetuses were evaluated for stage of development, weight, and crown-rump length. RESULTS: Dams receiving C. rectus had more fetal resorptions after challenge with 10(7) or 10(9) CFU/ml (24.1% and 30.1%, respectively) than controls (9%). Higher numbers of growth-restricted fetuses were also observed in the C. rectus challenged groups (21%) as compared to controls (2.3%). Fetuses from dams challenged with 10(9) CFU/ml weighed less (0.49 +/- 0.05 g) and had shorter crown-rump lengths (14.69 +/- 0.56 mm) than controls (0.53 +/- 0.04 g; 15.54 +/- 0.63 mm). C. rectus was detected by polymerase chain reaction (PCR) in the placentas from both treated groups and in maternal liver tissues from the 10(9) CFU/ml challenged group. CONCLUSIONS: Remote subcutaneous maternal C. rectus infection increases fetal resorptions and fetal growth restriction in a mouse model. The effects of an oral C. rectus infection on pregnancy remain to be determined.

Placental infection with Chlamydia pneumoniae and intrauterine growth restriction.

BACKGROUND: The concept that low birth weight infants are more predisposed to coronary artery disease (CAD) in adulthood has been studied extensively. Although many infectious agents have been associated with intrauterine growth restriction (IUGR), Chlamydia pneumoniae an organism implicated in CAD has not been investigated. It was our aim to assess whether C. pneumoniae DNA is present in placental tissue and whether its detection is associated with IUGR. METHODS: Fifty-nine pregnant women were studied: 32 women had an uncomplicated pregnancy with no antenatal or post-natal evidence of IUGR. Twenty-seven women had pregnancies with ultrasonographically demonstrated IUGR, defined as foetal abdominal circumference measuring less than 2 S.D.s from the mean for gestational age. At the time of delivery, maternal blood and placental tissue samples were obtained. Placental samples were taken from four sites centrally and peripherally on the maternal and foetal side of the placentas and tested by nested polymerase chain reaction for C. pneumoniae DNA. IgG antibodies to C. pneumoniae were measured using microimmunfluorescence. RESULTS: C. pneumoniae DNA was detected in 44% of the placental tissue but there was no difference in the prevalence of bacterial DNA between the control and the low birth weight group (P=0.58). Additionally C. pneumoniae seropositivity did not differ between the index and control groups (78 vs. 70%, P=0.44). CONCLUSIONS: C. pneumoniae is present in placental tissue. Its presence however does not correlate with IUGR. Similarly, maternal C. pneumoniae seropositivity is not related to low birth weight. Thus C. pneumoniae infection is unlikely to play a role in the pathogenesis of IUGR.

The human microbiome and the great obstetrical syndromes: a new frontier in maternal-fetal medicine.

The emergence of the concept of the microbiome, together with the development of molecular-based techniques, particularly polymerase chain reaction (PCR) amplification using the 16S ribosomal RNA (rRNA) gene, has dramatically increased the detection of microorganisms, the number of known species, and the understanding of bacterial communities that are relevant to maternal-fetal medicine in health and disease. Culture-independent methods enable characterization of the microbiomes of the reproductive tract of pregnant and nonpregnant women, and have increased our understanding of the role of the uterine microbiome in adverse obstetric outcomes. While bacterial ascent from the vaginal tract is recognized as the primary cause of intrauterine infection, the microbiomes of the gastrointestinal, oral, and respiratory tracts are shown to be involved by means of hematogenous spread. The transmission of maternal microbiomes to the neonate, by vaginal delivery or cesarean section, is shown to affect health from birth to adulthood.

Prevention of Intrauterine Growth Restriction and Preterm Birth with Presumptive Antibiotic Treatment of Pregnant Women: A Literature Review.

Intrauterine growth restriction and preterm birth (PTB) account for a large share of global child mortality, morbidity and developmental loss. Of the numerous risk factors for these conditions, maternal infections have been most consistently identified. Our aim was to study if presumptive antibiotic treatment of pregnant women before any signs of the onset of labor would promote fetal growth and reduce the incidence of PTB or low birthweight (LBW). In a systematic literature search, we identified 14 clinical trials of sufficient quality. Eight trials concluded that there was a positive effect on one or both of the conditions, and others found no such association. The trials reporting an effect were typically conducted in Sub-Saharan Africa (6 trials) and with broadest spectrum antibiotics, whereas data from India (2) suggested no intervention effect and trials in the US (5) or Europe (1) yielded both positive and negative findings. We conclude that appropriately chosen presumptive antimicrobial treatment of pregnant women, targeting infections in the reproductive tract but also other maternal infections such as malaria, other parasitic diseases, skin infections, and periodontitis, can in selected contexts promote fetal growth and reduce the incidence of PTB and LBW.

Foetal intrauterine growth restrictions with Helicobacter pylori infection.

BACKGROUND: Helicobacter pylori infection has been associated with growth restriction in young children. AIM: To determine whether there is an association between H. pylori infection and intrauterine growth restriction. METHODS: Four hundred and forty-eight consecutive pregnant women (aged 15-44 years), attending for routine examinations in the third trimester, were enrolled. Clinical, demographic and previous obstetric data, as well as smoking history, were collected. At delivery, the weight, height, gender and status of the neonate were recorded; intrauterine growth restriction was defined if the birth weight was below the 10th percentile according to the gestational age for infants born in Australia. RESULTS: Eighty-nine (20%) women were seropositive for H. pylori. The prevalence of H. pylori was significantly lower in Caucasians (17%) vs. non-Caucasians (42%, P < 0.0001). There were 34 (7.5%) cases of intrauterine growth restriction (7% Caucasians, 16% Asians, 12% Aborigines and 0% Pacific Islanders). Intrauterine growth restriction was more common in H. pylori-seropositive women than in H. pylori-seronegative women [13.5% vs. 6%; odds ratio (OR) = 2.41; 95% confidence interval (CI), 1.14-5.08; P = 0.018]. A multiple logistic regression model revealed that smoking (OR = 3.55; 95% CI, 1.62-7.79; P = 0.002), maternal height (OR = 0.48; 95% CI, 0.28-0.80; P = 0.005) and H. pylori seropositivity (OR = 2.59; 95% CI, 1.12-5.95; P = 0.025) were all independent risk factors for intrauterine growth restriction. CONCLUSIONS: H. pylori infection in pregnant women may affect foetal intrauterine growth.

[Thoughts on a case of unrecognized congenital rubella]. / Réflexions à propos d'une primo-infection rubéolique méconnue.

We recently observed a case of congenital rubella which had gone unrecognized despite regular obstetrical care. This case emphasizes the importance of careful screening for rubella at diagnosis of pregnancy. Minute analysis of the initial maternal antibody levels is essential to rule out possible contamination during pregnancy. The problem of interpreting serodiagnostic data is discussed.