Janus kinase (JAK) inhibitors are effective anti-inflammatory agents for treatment of ulcerative colitis (UC).1 According to drug regulatory agencies and international guidelines, JAK inhibitors should be avoided during pregnancy and lactation.2-4 The existing evidence on safety of JAK inhibitors during pregnancy is scarce and almost exclusively limited to tofacitinib.4-7.
- MeSH
- Adult MeSH
- Fetal Blood * chemistry MeSH
- Janus Kinase Inhibitors therapeutic use MeSH
- Pregnancy Complications drug therapy MeSH
- Humans MeSH
- Milk, Human * chemistry MeSH
- Infant, Newborn MeSH
- Piperidines * therapeutic use MeSH
- Pyrimidines * therapeutic use MeSH
- Pregnancy MeSH
- Colitis, Ulcerative drug therapy blood MeSH
- Pregnancy Outcome * MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Infant, Newborn MeSH
- Pregnancy MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Keywords
- novorozenecké záchvaty,
- MeSH
- Hyponatremia blood MeSH
- Case Reports as Topic MeSH
- Humans MeSH
- Infant, Newborn MeSH
- Poisoning diagnosis etiology classification MeSH
- Amniotic Fluid * MeSH
- Seizures * diagnosis etiology drug therapy classification MeSH
- Check Tag
- Humans MeSH
- Infant, Newborn MeSH
- Publication type
- Review MeSH
The fetus develops normally in a hypoxic environment but exaggerated hypoxia late in pregnancy is a worrisome sign often observed in hypertensive disorders of pregnancy, placental insufficiency, or fetal growth restriction (FGR). Serial fetal biometry and the cerebroplacental ratio (CPR, calculated as the middle cerebral artery [MCA] / the umbilical artery [UmbA] pulsatility indices [PI]), are commonly used to indicate fetal "brain sparing" resulting from exaggerated fetal hypoxia. But unclear is the extent to which a low CPR indicates pathology or is a physiological response for maintaining cerebral blood flow. We studied 31 appropriate for gestational age (AGA) pregnancies at low (LA, 1670 m) or high (HA, 2879 m) altitude, given the chronic hypoxia imposed by HA residence, and 54 LA women with a clinical diagnosis of FGR. At week 34, the MCA PI was lower in the LA-FGR than the LA-AGA group but lower still in the HA-AGA compared to either LA groups due to a trend toward higher end-diastolic velocity (EDV). We concluded that the lower MCA PI was likely due to greater cerebral vasodilation in the HA AGA group and an indication of physiological versus pathological fetal hypoxia. Future reporting of serial MCA and UmbA values and their determinants along with the CPR could improve our ability to distinguish between physiological and pathological fetal brain sparing. Keywords: Birth weight, Cerebroplacental ratio, Fetal physiology, HDP, High altitude.
- MeSH
- Middle Cerebral Artery * diagnostic imaging physiopathology MeSH
- Umbilical Arteries diagnostic imaging physiopathology MeSH
- Adult MeSH
- Fetal Hypoxia * physiopathology MeSH
- Hypoxia physiopathology MeSH
- Humans MeSH
- Brain physiopathology blood supply diagnostic imaging MeSH
- Cerebrovascular Circulation physiology MeSH
- Altitude MeSH
- Fetal Growth Retardation * physiopathology MeSH
- Pregnancy MeSH
- Ultrasonography, Prenatal methods MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Pregnancy MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
In the first days of life, the newborns' intestinal microbiota develops simultaneously with the intestinal gut barrier and follows intestinal immunity. The mode of delivery shows significant impact on microbial development and, thus, the initiation of the tryptophan catabolism pathway. Further antibiotics (ATB) treatment of mothers before or during delivery affects the microbial and tryptophan metabolite composition of stool of the caesarean- and vaginal-delivered newborns. The determination of microbiome and levels of tryptophan microbial metabolites in meconium and stool can characterize intestinal colonization of a newborn. From 134 samples from the Central European Longitudinal Studies of Parents and Children: The Next Generation (CELSPAC: TNG) cohort study, 16S rRNA gene sequencing was performed, and microbial tryptophan metabolites were quantified using ultra-high-performance liquid chromatography with triple-quadrupole mass spectrometry. Microbial diversity and concentrations of tryptophan metabolites were significantly higher in stool compared to meconium. Treatment of mothers with ATB before or during delivery affects metabolite composition and microbial diversity in stool of vaginal- and caesarean-delivered newborns. Correlation of microbial and metabolite composition shows significant positive correlations of indol-3-lactic acid, N-acetyl-tryptophan and indol-3-acetic acid with Bifidobacterium, Bacteroides and Peptoclostridium. The positive effect of vaginal delivery on newborns' microbiome development is degraded when mother is treated with ATB before or during delivery. KEY POINTS: • Antibiotic treatment diminishes the positive effects of vaginal delivery. • Antibiotic treatment affects metabolite and microbial composition in newborns. • Bifidobacterium and Peptoclostridium could be the producer of indole-lactic acid.
- MeSH
- Anti-Bacterial Agents * MeSH
- Bifidobacterium metabolism growth & development MeSH
- Feces * microbiology chemistry MeSH
- Indoles metabolism MeSH
- Indoleacetic Acids metabolism MeSH
- Humans MeSH
- Longitudinal Studies MeSH
- Meconium * microbiology chemistry MeSH
- Infant, Newborn MeSH
- RNA, Ribosomal, 16S * genetics MeSH
- Gastrointestinal Microbiome * drug effects MeSH
- Tryptophan * metabolism MeSH
- Chromatography, High Pressure Liquid MeSH
- Check Tag
- Humans MeSH
- Infant, Newborn MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
OBJECTIVE: The aim of this study was to evaluate changes in the relative counts of different leukocyte subsets in peripheral and umbilical cord blood in pregnancies complicated by preterm prelabor rupture of membranes (PPROM) with respect to the presence of intraamniotic inflammation (IAI) and fetal inflammatory response syndrome (FIRS). METHODS: Fifty-two women with singleton pregnancies complicated by PPROM were included in this study. From samples of peripheral and umbilical cord blood, relative counts of these leukocyte subpopulations were determined using multicolor flow cytometry: granulocytes, monocytes, lymphocytes, T cells and their subpopulations, B cells and their subpopulations, and NK cells and their subpopulations. IAI was defined as increased concentrations of interleukin 6 in the amniotic fluid. Amniotic fluid samples were obtained by transabdominal amniocentesis. RESULTS: Women with IAI had higher relative counts of monocytes (p = 0.04) in peripheral blood. There was an increased relative number of granulocytes (p = 0.003) and a decreased number of lymphocytes (p = 0.0048), helper CD4+ T cells (p = 0.019), NK cells (p = 0.0001) within leukocytes, NK cells within lymphocytes (p = 0.003) and CD16+ NK cells within NK cells (p = 0.005) in umbilical cord blood samples of women with FIRS. However, after adjusting the results for gestational age at sampling, all differences disappeared. CONCLUSIONS: The presence of IAI or FIRS is not accompanied by significant changes in the relative counts of immune cells in peripheral blood or umbilical cord blood in pregnancies complicated by PPROM.
- MeSH
- Chorioamnionitis immunology blood MeSH
- Adult MeSH
- Fetal Blood * immunology cytology MeSH
- Interleukin-6 blood metabolism MeSH
- Leukocytes immunology MeSH
- Humans MeSH
- Amniotic Fluid immunology metabolism MeSH
- Leukocyte Count MeSH
- Fetal Membranes, Premature Rupture * immunology blood MeSH
- Flow Cytometry MeSH
- Systemic Inflammatory Response Syndrome immunology blood MeSH
- Pregnancy MeSH
- Inflammation immunology MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Pregnancy MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
The main aim of this study was to determine expanded sequence types (eSTs) of Ureaplasma species (U. spp.). DNA isolated from the amniotic fluid of pregnancies complicated by preterm prelabor rupture of membranes (PPROM) using an expanded multilocus sequence typing scheme. Additionally, the study sought to examine whether phylogenetic subgroups of U. spp. DNA differ with respect to maternal demographic and clinical parameters and selected aspects of short-term neonatal morbidity. This retrospective cohort study was focused on singleton pregnancies complicated by PPROM occurring between the gestational ages of 24+0 and 36+6 weeks, where amniocentesis was conducted to assess the intra-amniotic environment and the presence of U. spp. DNA in the amniotic fluid samples was confirmed. The stored aliquots of U. spp. DNA were used to assess differences in nucleotide sequences in six U. spp. genes (ftsH, rpL22, valS, thrS,ureG, and mba-np1) using the eMLST scheme. The expanded multilocus sequence typing scheme was performed in 73 samples of U. spp. DNA isolated from pregnancies complicated by PPROM. In total, 33 different U. spp. DNA eSTs were revealed, 21 (#20, 233-244, 248-251, 253, 255, 259, and 262) of which were novel. The most frequently identified eST was #41, identified in 18% (13/73) of the aliquots. Based on their genetic relationships, the U. spp. DNA was divided into two clusters and four subgroups [cluster I (U. parvum): A, 43% (n = 31); B, 15% (n = 11); and C, 26% (n = 19); cluster II (U. urealyticum): 1; 16% (n = 12)]. Cluster II had a higher rate of polymicrobial findings than cluster I (58% vs 16%; p = 0.005), while subgroup A had the highest rate of concomitant Mycoplasma hominis in the amniotic fluid samples (66%; p = 0.04). In conclusion, Ureaplasma spp. DNA obtained from PPROM consisted of 33 different eSTs of U. spp. DNA. No differences in maternal and neonatal characteristics were found among the phylogenetical subgroups of U. spp. DNA, except for a higher rate of polymicrobial amniotic fluid findings in those with U. urealyticumand the concomitant presence of M. hominis in the amniotic fluid in those with the presence of U. parvum.
- MeSH
- DNA, Bacterial analysis genetics MeSH
- Adult MeSH
- Phylogeny MeSH
- Gestational Age MeSH
- Pregnancy Complications, Infectious microbiology MeSH
- Humans MeSH
- Multilocus Sequence Typing * MeSH
- Amniotic Fluid * microbiology MeSH
- Fetal Membranes, Premature Rupture * microbiology MeSH
- Retrospective Studies MeSH
- Pregnancy MeSH
- Ureaplasma * genetics isolation & purification MeSH
- Ureaplasma Infections * microbiology MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Pregnancy MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: This study aimed to assess variations in the absolute counts of various leukocyte subsets in the peripheral blood of women with pregnancies affected by preterm prelabour rupture of membranes (PPROM), in relation to the presence of intra-amniotic inflammation (IAI). METHODS: The study included fifty-two women with singleton pregnancies experiencing PPROM. Absolute counts of different leukocyte subpopulations, such as granulocytes, monocytes, lymphocytes, T cells and their subsets, B cells and their subsets, and NK cells and their subsets, were measured in maternal peripheral blood samples using multicolour flow cytometry. IAI was identified by elevated concentrations of interleukin 6 (IL-6) in the amniotic fluid, which was collected through transabdominal amniocentesis. RESULTS: Women with IAI exhibited higher absolute counts of leukocytes (p = 0.003), granulocytes (p = 0.008), and monocytes (p = 0.009). However, the presence of IAI did not significantly affect the absolute counts of lymphocytes or their subpopulations. CONCLUSIONS: The study found that IAI is associated with changes in the absolute counts of leukocytes from the innate immunity compartment in the peripheral blood of women with pregnancies complicated by PPROM. Conversely, it does not significantly alter the counts of cells from the adaptive immune system. The changes observed may reflect the natural, temporal, and localised characteristics of IAI.
- MeSH
- Amniocentesis MeSH
- Chorioamnionitis * blood MeSH
- Adult MeSH
- Interleukin-6 blood analysis MeSH
- Leukocytes MeSH
- Humans MeSH
- Amniotic Fluid cytology MeSH
- Leukocyte Count MeSH
- Fetal Membranes, Premature Rupture * blood MeSH
- Immunity, Innate MeSH
- Flow Cytometry MeSH
- Pregnancy MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Pregnancy MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Intrapartum antibiotic prophylaxis (IAP) is commonly used during C-section delivery and in Group B Streptococcus-positive women before vaginal delivery. Here, we primarily aimed to investigate the effect of IAP on the neonatal oral and fecal bacteriomes in the first week of life. In this preliminary study, maternal and neonatal oral swabs and neonatal fecal (meconium and transitional stool) swabs were selected from a pool of samples from healthy mother-neonate pairs participating in the pilot phase of CELSPAC: TNG during their hospital stay. The DNA was extracted and bacteriome profiles were determined by 16S rRNA amplicon sequencing (Illumina). In the final dataset, 33 mother-neonate pairs were exposed to antibiotics during C-section or vaginal delivery (cases; +IAP) and the vaginal delivery without IAP (controls, -IAP) took place in 33 mother-neonate pairs. Differences in alpha diversity (Shannon index, p=0.01) and bacterial composition (PERMANOVA, p<0.05) between the +IAP and -IAP groups were detected only in neonatal oral samples collected ≤48 h after birth. No significant differences between meconium bacteriomes of the +IAP and -IAP groups were observed (p>0.05). However, the IAP was associated with decreased alpha diversity (number of amplicon sequence variants, p<0.001), decreased relative abundances of the genera Bacteroides and Bifidobacterium, and increased relative abundances of genera Enterococcus and Rothia (q<0.01 for all of them) in transitional stool samples. The findings of this study suggest that exposure to IAP may significantly influence the early development of the neonatal oral and gut microbiomes. IAP affected the neonatal oral bacteriome in the first two days after birth as well as the neonatal fecal bacteriome in transitional stool samples. In addition, it highlights the necessity for further investigation into the potential long-term health impacts on children.
- MeSH
- Anti-Bacterial Agents * administration & dosage MeSH
- Antibiotic Prophylaxis * methods MeSH
- Bacteria genetics classification isolation & purification drug effects MeSH
- Cesarean Section MeSH
- Adult MeSH
- Feces * microbiology MeSH
- Humans MeSH
- Meconium microbiology MeSH
- Infant, Newborn MeSH
- RNA, Ribosomal, 16S genetics MeSH
- Gastrointestinal Microbiome drug effects MeSH
- Pregnancy MeSH
- Mouth * microbiology MeSH
- Delivery, Obstetric MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Male MeSH
- Infant, Newborn MeSH
- Pregnancy MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: Idiopathic bleeding in the second trimester of pregnancy complicates <1% of all pregnancies. This pregnancy complication can be caused by alterations in local hemostasis in the decidua due to infection/inflammation in the choriodecidual niche. This condition is associated with intraamniotic inflammatory complications. Antibiotic therapy effectively reduces the intensity of intraamniotic inflammation in certain pregnancy pathologies. However, whether antibiotic administration can reduce the intensity of the intraamniotic inflammatory response or eradicate microorganisms in patients with idiopathic bleeding during the second trimester of pregnancy remains unclear. OBJECTIVE: This study primarily aimed to determine whether antimicrobial agents can reduce the magnitude of intraamniotic inflammation in patients with idiopathic bleeding in the second trimester of pregnancy by assessing the concentration of interleukin-6 in the amniotic fluid before and after 7 days of antibiotic treatment. The secondary aim was to determine whether treatment with a combination of antibiotics altered the microbial load of Ureaplasma species DNA in amniotic fluid. STUDY DESIGN: This retrospective cohort study included singleton-gestation patients with idiopathic bleeding between 15+0 and 27+6 weeks who underwent transabdominal amniocentesis at the time of admission. Follow-up amniocentesis was performed in a subset of patients unless abortion or delivery occurred earlier. Concentrations of interleukin-6 were measured in the amniotic fluid samples, and the presence of microbial invasion of the amniotic cavity was assessed using culture and molecular microbiological methods. Intraamniotic inflammation was defined as an interleukin-6 concentration ≥3000 pg/mL in the amniotic fluid samples. RESULTS: A total of 36 patients with idiopathic bleeding in the second trimester of pregnancy were included. All the patients underwent initial amniocentesis. Patients with intraamniotic inflammation (n=25) were treated using a combination of antibiotics consisting of intravenous ceftriaxone, intravenous metronidazole, and peroral clarithromycin. The patients without intraamniotic inflammation (n=11) were treated expectantly. In total, 25 patients delivered 7 days after admission. All patients with intraamniotic inflammation at the initial amniocentesis who delivered after 7 days underwent follow-up amniocentesis. Treatment with antibiotics decreased the interleukin-6 concentration in the amniotic fluid at follow-up amniocentesis compared with that at the initial amniocentesis in patients with intraamniotic inflammation (median [interquartile range]: 3457 pg/mL [2493-13,203] vs 19,812 pg/mL [11,973-34,518]; P=.0001). Amniotic fluid samples with Ureaplasma species DNA had a lower microbial load at the time of follow-up amniocentesis compared with the initial amniocentesis (median [interquartile range]: 1.5×105 copies DNA/mL [1.3×105-1.7×105] vs 8.0×107 copies DNA/mL [6.7×106-1.6×108]; P=.02). CONCLUSION: Antibiotic therapy was associated with reduced intraamniotic inflammation in patients with idiopathic bleeding in the second trimester complicated by intraamniotic inflammation. Moreover, antibiotic treatment has been associated with a reduction in the microbial load of Ureaplasma species DNA in the amniotic fluid.
- MeSH
- Amniocentesis adverse effects MeSH
- Anti-Bacterial Agents therapeutic use MeSH
- Chorioamnionitis * microbiology MeSH
- Uterine Hemorrhage MeSH
- DNA MeSH
- Pregnancy Trimester, Second MeSH
- Interleukin-6 MeSH
- Humans MeSH
- Amniotic Fluid microbiology MeSH
- Fetal Membranes, Premature Rupture * drug therapy MeSH
- Retrospective Studies MeSH
- Pregnancy MeSH
- Ureaplasma MeSH
- Inflammation complications MeSH
- Check Tag
- Humans MeSH
- Pregnancy MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
