Female ; Humans ; Infant, Low Birth Weight ; Infant, Newborn ; Infant, Premature ; Periodontitis ; complications ; physiopathology ; Pregnancy ; Pregnancy Complications, Infectious ; physiopathology ; Pregnancy Outcome

OBJECTIVETo investigate the impact of intrauterine infection induced by LPS injection on long-term brain development of premature rats.

METHODSEighteen day-gestation pregnant rats were randomly assigned to a control group receiving an intraperitoneal injection of normal saline, and two infection groups that were intraperitoneally injected with 0.3 mg/kg or 0.6 mg/kg LPS. Twenty-four hours after injection, 7 pregnant rats of each group were sacrificed. The pathological changes of the placenta after hematoxylin and eosin staining were observed under a light microscope. The neural cell apoptosis of fetal brains was examined by the TUNEL assay. The remained pregnant rats were induced to labour before 21 gestation days. The long-term brain development of premature rats was tested with the Y type electric maze on postnatal day 42.

RESULTSObvious pathological changes were observed in the placenta in the infection groups. The apoptotic neural cells in the fetal brain increased in the infection groups compared with that in the control group (32.41+/-5.36 in the 0.3 mg/kg infection group and 66.41+/-7.61 in the 0.6 mg/kg infection group vs 8.00+/-0.36 in the control group; P<0.01). The number of trials to criterion in the Y type maze test in the infection groups was much more than that in the control group [117.8+/-8.7 (0.3 mg/kg infection group) and 194.4+/-13.7 (0.6 mg/kg infection group) vs 56.8+/-3.7 (control group); P<0.01]. The number of correct reactions in memory retaining in the infection groups was lower than that in the control group (0.62+/-0.09 in the 0.3 mg/kg infection group and 0.37+/-0.09 in the 0.6 mg/kg infection group vs 0.92+/-0.06 in the control group; P<0.05).

CONCLUSIONSIntrauterine infection can cause fetal rats' neural cell apoptosis and affect adversely long-term brain development of neonatal rats.

Animals ; Apoptosis ; Bacterial Infections ; physiopathology ; Blood-Brain Barrier ; Brain ; growth & development ; pathology ; Female ; Maze Learning ; Neurons ; pathology ; Pregnancy ; Pregnancy Complications, Infectious ; physiopathology ; Rats ; Rats, Wistar ; Uterus ; microbiology

To explore the effects of intrauterine infection on early growth and neurobehavioral development in neonatal rats. (E. coli) was inoculated into uterine cervix of pregnant rats with gestation of 15 d to establish the intrauterine infection model, and the effect on the delivery of pregnant rats was observed. The neonatal rat brain tissue was stained with Hematoxylin-Eosin and the cerebral white matter damage was assessed. Immunohistochemical staining and Western blot analysis were performed to evaluate the expression of glial fibrillary acidic protein (GFAP), 2', 3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) and neurofilament (NF) in pup brains. Birth weight and early growth development indices were monitored,and neurobehavioral tests were performed to access the change of neurobehavioral development in neonatal rats. The white blood cell count increased significantly in the uterus and placenta of the pregnant rats after intrauterine E. coli infection and no significant impact was observed on the delivery of pregnant rats. Weak staining and focal rarefaction of cerebral white matter from rats at P7 in intrauterine infection group were observed. The expression of GFAP markedly increased (<0.05) in infection group, while the level of CNPase and NF in pup brains at P7 significantly decreased (<0.05 or <0.01). Compared with control group, the neonatal rats in infection group had lower birth weight and slower weight gain during the suckling period (<0.05 or <0.01), and the completion times of ear opening, eye opening, surface righting, negative geotaxis, acoustic startle and swimming test in infection group were significantly delayed (<0.05 or <0.01). Intrauterine infection in pregnant rats can induce cerebral white matter damage and retardation of early growth and neurobehavioral development in neonatal rats.
Animals ; Animals, Newborn ; Behavior, Animal ; Body Weight ; Disease Models, Animal ; Escherichia coli ; Escherichia coli Infections ; complications ; physiopathology ; Female ; Glial Fibrillary Acidic Protein ; genetics ; Growth Disorders ; etiology ; Leukoencephalopathies ; etiology ; Pregnancy ; Pregnancy Complications, Infectious ; physiopathology ; Rats ; Rats, Sprague-Dawley

INTRODUCTION: Pregnant women are reported to be at increased risk of severe coronavirus disease 2019 (COVID-19) due to underlying immunosuppression during pregnancy. However, the clinical course of COVID-19 in pregnancy and risk of vertical and horizontal transmission remain relatively unknown. We aim to describe and evaluate outcomes in pregnant women with COVID-19 in Singapore. METHODS: Prospective observational study of 16 pregnant patients admitted for COVID-19 to 4 tertiary hospitals in Singapore. Outcomes included severe disease, pregnancy loss, and vertical and horizontal transmission. RESULTS: Of the 16 patients, 37.5%, 43.8% and 18.7% were infected in the first, second and third trimesters, respectively. Two gravidas aged ≥35 years (12.5%) developed severe pneumonia; one patient (body mass index 32.9kg/m2) required transfer to intensive care. The median duration of acute infection was 19 days; one patient remained reverse transcription polymerase chain reaction (RT-PCR) positive >11 weeks from diagnosis. There were no maternal mortalities. Five pregnancies produced term live-births while 2 spontaneous miscarriages occurred at 11 and 23 weeks. RT-PCR of breast milk and maternal and neonatal samples taken at birth were negative; placenta and cord histology showed non-specific inflammation; and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific immunoglobulins were elevated in paired maternal and umbilical cord blood (n=5). CONCLUSION The majority of COVID-19 infected pregnant women had mild disease and only 2 women with risk factors (obesity, older age) had severe infection; this represents a slightly higher incidence than observed in age-matched non-pregnant women. Among the women who delivered, there was no definitive evidence of mother-to-child transmission via breast milk or placenta.
Abortion, Spontaneous/epidemiology* ; Adult ; COVID-19/transmission* ; COVID-19 Nucleic Acid Testing ; COVID-19 Serological Testing ; Cohort Studies ; Disease Transmission, Infectious/statistics & numerical data* ; Female ; Fetal Blood/immunology* ; Humans ; Infectious Disease Transmission, Vertical/statistics & numerical data* ; Live Birth/epidemiology* ; Maternal Age ; Milk, Human/virology* ; Obesity, Maternal/epidemiology* ; Placenta/pathology* ; Pregnancy ; Pregnancy Complications, Infectious/physiopathology* ; Pregnancy Outcome/epidemiology* ; Pregnancy Trimester, First ; Pregnancy Trimester, Second ; Prospective Studies ; RNA, Viral/analysis* ; Risk Factors ; SARS-CoV-2 ; Severity of Illness Index ; Singapore/epidemiology* ; Umbilical Cord/pathology* ; Young Adult

OBJECTIVETo investigate the expression of glial fibrillary acidic protein (GFAP), GFAP mRNA and interleukin-1beta mRNA (IL-1beta mRNA), tumor necrosis factor-alpha mRNA (TNF-alpha mRNA) in neonatal rat brain after intrauterine infection.

METHODSEscherichia coli (E. coli) was inoculated into both uterine horns of pregnant rats when gestation was 70% complete (15 days). The control group was treated with normal saline. The pups were killed on the postnatal day 1 (P1), P3 and P7, respectively. The cerebral white matter damage of the neonatal rats was determined by HE staining. Immunohistochemistry was used for evaluation of GFAP expression in neonatal rat brains and RT-PCR to analyze GFAP mRNA, IL-1beta mRNA and TNF-alpha mRNA expression at P1, P3 and P7.

RESULTSThe major histopathological changes in neonatal cerebral white matter at P7 after intrauterine infections were: weak staining of cerebral white matter and focal rarefaction. GFAP-positive cells were observed in both the control and the E. coli-treated groups. The numbers of GFAP-positive cells of the E. coli-treated group pups were markedly increased in periventricular white matter and hippocampus at P7 compared with those of the control group (periventricular white matter: 9.73 +/- 3.55 vs 5.67 +/- 1.90, P < 0.05 and hippocampus: 7.81 +/- 3.61 vs 2.16 +/- 1.11, P < 0.05, respectively). No significantly different levels of GFAP expression in corpus callosum were found between two groups (P > 0.05). The expression of GFAP mRNA in brain of the E. coli-treated neonatal rat was higher than the control at P1, P3 (P1: 0.25 +/- 0.07 vs 0.15 +/- 0.08, P < 0.05 and P3: 0.50 +/- 0.09 vs 0.39 +/- 0.08, P < 0.05, respectively), but the expression of GFAP mRNA in brain of the neonatal rat at P7 had no significant difference between two groups (P > 0.05). The expression of IL-1beta mRNA and TNF-alpha mRNA in brain of the E. coli-treated neonatal rat were higher than of the control at P1 (IL-1beta mRNA: 0.83 +/- 0.19 vs 0.50 +/- 0.30, P < 0.05 and TNF-alpha mRNA: 0.74 +/- 0.30 vs 0.30 +/- 0.20, P < 0.05, respectively), but the expression of IL-1beta mRNA and TNF-alpha mRNA in brain of the neonatal rat at P3 and P7 had no significant difference between two groups (P > 0.05).

CONCLUSIONSThe intrauterine infection could cause neonatal white matter damage and IL-1beta, TNF-alpha may be a mechanism mediating between the two events.

Animals ; Animals, Newborn ; Brain ; metabolism ; pathology ; Disease Models, Animal ; Escherichia coli Infections ; microbiology ; physiopathology ; Female ; Glial Fibrillary Acidic Protein ; analysis ; genetics ; Immunohistochemistry ; Interleukin-1 ; genetics ; Pregnancy ; Pregnancy Complications, Infectious ; microbiology ; physiopathology ; RNA, Messenger ; metabolism ; Rats ; Reverse Transcriptase Polymerase Chain Reaction ; Tumor Necrosis Factor-alpha ; genetics ; Uterus ; microbiology