Increased IL-10-competent regulatory B cells in the decidua of early human pregnancy.

Regulatory B cells (Bregs) may play a pivotal role in maintaining human pregnancy. For the first time, to the best of our knowledge, this study noted that cell percentages of CD24hiCD38hi Bregs and CD24hiCD27+ Bregs, which can potentially produce IL-10, are increased in human decidua compared with the mid-luteal phase endometrium. In each case of decidua, the correlation between Bregs and dendritic cell (DC) or natural killer (NK) cell expression was further explored. A positive correlation between the percentage of CD24hiCD38hi Bregs and CD123-CD11c+ myeloid DCs (mDCs) was noted. Furthermore, a significant positive correlation was also observed between the percentage of CD24hiCD27+ Bregs and CD94+CD56brightCD16- suppressive NK cells. These findings regarding decidual Bregs deepen the understanding of the harmonious immunological microenvironment that sustains early human pregnancy.

Advantages of sensor-augmented insulin pump therapy for pregnant women with type 1 diabetes mellitus.

AIMS/INTRODUCTION: To evaluate the efficacy of sensor-augmented pump (SAP) for improving obstetric and neonatal outcomes among pregnant women with type 1 diabetes mellitus by comparing it with continuous subcutaneous insulin infusion plus self-monitoring of blood glucose (continuous subcutaneous insulin infusion [CSII]/SMBG). MATERIALS AND METHODS: This retrospective cohort study included 40 cases of pregnancy complicated by type 1 diabetes mellitus treated with SAP (SAP group), and 29 cases of pregnancy complicated by type 1 diabetes mellitus treated with CSII/SMBG (CSII/SMBG group). The obstetric and neonatal outcomes were compared between the two groups. RESULTS: The median of the glycoalbumin levels in the first (18.8% vs 20.9%; P < 0.05) and second (15.4% vs 18.0%; P < 0.05) trimesters, the hemoglobin A1c levels in the peripartum period (6.1% vs 6.5%; P < 0.05) and the standard deviation score of birthweights (0.36 vs 1.52; P < 0.05) were significantly lower in the SAP group than in the CSII/SMBG group. The incidence rate of large for gestational age newborns was significantly lower in the SAP group than in the CSII/SMBG group (27.5% vs 65.5%; P < 0.05). No significant differences in the incidence rates of hypertensive disorders of pregnancy, small for gestational age, respiratory distress syndrome, neonatal hypoglycemia, hypervolemia and hyperbilirubinemia were observed between the groups. CONCLUSION: The present study showed that SAP therapy is more effective in preventing large for gestational age newborns in pregnant women with type 1 diabetes mellitus than CSII/SMBG.

Uterine endometrium microbiota and pregnancy outcome in women with recurrent pregnancy loss.

To evaluate whether uterine endometrium microbiota (UEM) is associated with pregnancy outcome in women with recurrent pregnancy loss (RPL). This prospective cohort study enrolled 67 women who had a history of two or more RPL. They underwent endometrial biopsy at midluteal phase for UEM analyses with 16 S ribosomal RNA sequence. Four women with inappropriate specimens were excluded. Therefore, 63 women were followed up for more than 14 months; 44 became pregnant, while 19 did not. Thirty of the 44 pregnancies ended in live births, including 24 full-term and six preterm deliveries. Three pregnancies were ongoing, and the remaining 11 ended in miscarriages, including eight miscarriages with normal chromosome karyotype and three miscarriages with abnormal karyotype. Clinical characteristics and UEM associated with risks for non-pregnancy, miscarriage with normal karyotype, and preterm delivery in subsequent pregnancies were evaluated. Multivariable logistic regression analyses revealed that the number of previous miscarriages (odds ratio 42.2, 95 % CI 1.19-1490, p = 0.040) and relative dominance rate of Ureaplasma species (odds ratio 24.2, 95 % CI 1.55-377, p = 0.023) in UEM were independent risk factors for subsequent miscarriage with normal karyotype; and relative dominance rate of Ureaplasma species in UEM was a risk factor for preterm delivery (odds ratio 109, 95 % CI 1.07-1110, p = 0.047). This study demonstrated for the first time that increases in Ureaplasma species in UEM of women with RPL were risks of miscarriage with normal chromosome karyotype and preterm delivery in subsequent pregnancies. UEM analysis for women with RPL before pregnancy may identify microbiota associated with adverse pregnancy outcomes.

Clinical factors associated with a placenta accreta spectrum.

INTRODUCTION: Placenta accreta spectrum (PAS) is a life-threating obstetric complication, and prenatal prediction of PAS can decrease maternal morbidity and mortality. The aim of this prospective cohort study was to determine the clinical factors associated with PAS. METHODS: Pregnant women who delivered at a university hospital were enrolled. Clinical data were collected from medical records, and logistic regression analyses were performed to determine which clinical factors were associated with PAS. RESULTS: Eighty-seven (2.1%) of the 4146 pregnant women experienced PAS. Multivariable analyses revealed that a prior history of cesarean section (CS) (OR 3.3; 95% CI 1.9-5.7; p < 0.01), dilation and curettage (D&C) (OR 2.8; 95% CI 1.7-4.6; p < 0.01), hysteroscopic surgery (OR 5.7; 95% CI 2.3-14.4; p < 0.01), uterine artery embolization (UAE) (OR 44.1; 95% CI 13.8-141.0; p < 0.01), current pregnancy via assisted reproductive technology (ART) (OR 4.1; 95% CI 2.4-7.1; p < 0.01), and the presence of placenta previa in the current pregnancy (OR 13.1; 95% CI 7.9-21.8; p < 0.01) were independently associated with the occurrence of PAS. CONCLUSION: Pregnant women who have a prior history of CS, D&C, hysteroscopic surgery, UAE, current pregnancy via ART, and the presence of placenta previa in the current pregnancy are high risk for PAS.

Sudden fetal death with placental mesenchymal dysplasia complicated by placenta previa.

Placental mesenchymal dysplasia (PMD) is a rare placental abnormality that is closely related to severe pregnancy complications. A 27-year-old woman with fetal growth restriction and placenta previa was referred to a university hospital at 22 gestational weeks (GW). She was suspected of having a twin pregnancy with a complete or partial hydatidiform mole and coexisting normal live fetus, because two separate placentas, an enlarged one with multiple cystic lesions and a normal one, were shown on ultrasound examinations. At 27 GW, she experienced a sudden intrauterine fetal death (IUFD) after bleeding due to placenta previa, despite confirmation of fetal well-being at 2 h before bleeding. After delivery, histopathological examination confirmed the diagnosis of PMD. This is the first documented case of a woman with PMD and placenta previa who had a sudden IUFD after bleeding. Patients with both PMD and placenta previa should be considered at extremely high risk for IUFD.

Immunoglobulin fetal therapy and neonatal therapy with antiviral drugs improve neurological outcome of infants with symptomatic congenital cytomegalovirus infection.

Infants with symptomatic congenital cytomegalovirus infection (cCMV) suffer from long-term sequelae. This study aimed at evaluating the efficacy of combining immunoglobulin (Ig) fetal therapy (FT) and neonatal therapy (NT) with antiviral drugs to improve neurological outcomes of affected infants. Women whose fetuses had symptomatic cCMV received Ig injection into the fetal peritoneal cavity and/or maternal blood as FT, while affected newborns received oral valganciclovir or intravenous ganciclovir as NT. We compared the neurological outcomes at ≥18 months old between infants receiving FT with or without NT (FT group) and those receiving NT only (NT group). From 2009-2019, 15 women whose fetuses had symptomatic cCMV received FT, while 19 newborns received NT only. In FT group, two newborns died, and two were <18 months old. Neurological outcomes of the remaining 11 infants in FT group were as follows: normal 45.5 %, mild impairments 36.4 %, and severe impairments 18.2 %. In NT group, one newborn died, one's parents refused the follow-up, one was <18 months old, and two had only chorioretinitis as symptoms. Neurological outcomes of the remaining 14 infants in NT group were as follows: normal 21.4 %, mild impairments 14.3 %, and severe impairments 64.3 %. The proportion of infants with severe impairments in FT group was significantly lower than that in NT group (18.2 % vs 64.3 %, p < 0.05). This is the first trial demonstrating that the combination of Ig FT and NT with antiviral drugs may be more effective in improving neurological outcomes of newborns with symptomatic cCMV as compared to NT only.

Clinical and ultrasound features associated with congenital cytomegalovirus infection as potential predictors for targeted newborn screening in high-risk pregnancies.

This prospective cohort study aimed to determine clinical factors associated with congenital cytomegalovirus (CMV) infection in pregnancy. Newborns born at a perinatal medical center received PCR analyses for CMV-DNA in their urine with informed consent. Clinical data, including age, maternal fever or flu-like symptoms, complications, ultrasound fetal abnormality, gestational weeks at delivery, and birth weight, were collected. Logistic regression analyses determined clinical findings associated with congenital CMV infection (cCMV). cCMV was diagnosed in 32 of 4380 pregnancies. Univariate and multivariable analyses revealed that age < 25 years old (OR 2.7, 95% CI 1.1-6.6; p < 0.05), the presence of maternal fever or flu-like symptoms (5.4, 2.6-11.2; p < 0.01), ultrasound fetal abnormalities (12.7, 5.8-27.7; p < 0.01), and preterm delivery at less than 34 gestational weeks (2.6, 1.1-6.0; p < 0.05) were independent clinical findings associated with cCMV. A combination of maternal fever/flu-like symptoms, ultrasound fetal abnormalities, or preterm delivery at less than 34 gestational weeks as optimal predictive factors showed 90.6% sensitivity, 66.4% specificity, and a maximum Youden index of 0.57. CMV-DNA tests in the urine of newborns born to mothers with these clinical manifestations may be an effective method in detecting cCMV as a targeted screening with a high sensitivity.

Vaginal microbiota associated with preterm delivery.

OBJECTIVES: The aim of this study was to evaluate whether vaginal microbiota is associated with threatened premature labor and preterm delivery. METHODS: This prospective study enrolled 64 pregnant women who underwent vaginal microbiome analyses using 16S ribosomal RNA sequence method with informed consent. The 64 pregnant women consisted of 47 women with threatened premature labor and 17 women with other diseases (non-threatened premature labor) in a case-control study. In a cohort study of threatened premature labor group, 23 pregnancies ended in preterm delivery, and the remaining 24 ended in full-term deliveries. The differences in vaginal microbiota between threatened and non-threatened premature labor groups, and between preterm and full-term delivery groups were evaluated. RESULTS: There were no differences in vaginal microbiota between threatened and non-threatened premature labor groups. There were significant differences between preterm and full-term delivery groups in Nugent score [median 3 (range 0-7) vs. 0 (0-4), p < 0.05], percentage of Lactobacillus species [88% (0-100) vs. 99.8% (55.4-100), p < 0.01], the number of bacterial species [3 (1-13) vs. 2 (1-5), p < 0.05], and positivity of Ureaplasma species (61% vs. 17%, p < 0.01). Univariate and multivariable analyses revealed that positivity of Ureaplasma species was a predictive factor of preterm delivery in women with threatened premature labor (OR, 6.5; 95% CI, 1.3-33.0; p < 0.05). CONCLUSION: Increased positivity of Ureaplasma species in vaginal microbiota was a risk factor for preterm delivery among women with threatened premature labor. Vaginal microbiome analysis may identify high risk pregnancies for preterm delivery.