Amniotic fluid Gram stain and interleukin-6 can predict early-onset neonatal sepsis.

AIM: To clarify whether amniotic fluid findings (Gram stain and interleukin [IL]-6 level) can predict early-onset neonatal sepsis (EONS) before delivery. METHODS: We compared the sensitivity and specificity and the values of the area under the receiver-operating characteristic (AUROC) curve of maternal inflammatory responses and amniotic fluid findings using IL-6 and Gram stain to predict EONS. Patients who underwent amniocentesis for suspected intra-amniotic infection (IAI) after 22 weeks and 0 days of gestation and delivered on the same day at our hospital between January 2013 and December 2018 were included. RESULTS: Out of 200 patients, EONS developed in 9 patients. The AUROC curves of maternal white blood cells count, C-reactive protein and body temperature were low (range, 0.6-0.7), whereas that of amniotic fluid IL-6 was high (0.90). Sensitivity and specificity for amniotic fluid findings were, respectively, 100% and 67% for IL-6 (cut-off value: 17.4 ng/mL) and 100% and 88% for the Gram stain; these values were superior to those of maternal inflammatory responses. When examining the accuracy of the amniotic fluid Gram stain separately before and after 34 gestation weeks, similar results were obtained. Amniotic fluid IL-6 before 34 gestation weeks showed specificity similar to that of the Gram stain; however, there were large differences in cut-off values based on gestational age. CONCLUSION: Gram stain results of amniotic fluid can predict EONS with high sensitivity and specificity when IAI is suspected. False-negative amniotic fluid Gram stain results can be prevented by measuring amniotic fluid IL-6 simultaneously.

Gestational age-related changes in shear wave speed of the uterine cervix in normal pregnancy at 12-35 weeks' gestation.

Background This study aimed to analyze age-related changes in shear wave speed (SWS) of the normal uterine cervix. Methods We studied 362 women with a normal singleton pregnancy at 12-35 weeks' gestation. The SWS of the cervix was measured using transvaginal ultrasonography at the internal os region of the anterior cervix (IOA), posterior cervix (IOP) and cervical canal (IOC), and at the external os region of the anterior cervix (EOA), posterior cervix (EOP) and cervical canal (EOC). The following parameters were analyzed: (1) time trend of SWS of the individual sampling points, (2) comparison of SWS in the internal cervical region and SWS in the external cervical region, and (3) comparison of SWS between the internal and external cervical regions. Statistical analyses were performed using mixed-effects models. Results The SWS of IOP decreased in bilinear regression, with a critical change in the rate at 22 weeks, whereas the SWS of the remaining points decreased linearly. The estimated values of SWS of IOP at 84, 154 and 251 days were higher than those of IOA and IOC (P<0.001). The estimated values of SWS of IOP at 84 and 154 days were higher than those of EOP (P<0.001). Significant differences between IOP and EOP were shown until 244 days (P<0.05). The estimated value of SWS of IOC at 84 days was higher than that of EOC (P<0.001). Significant differences between IOC and EOC were shown until 210 days (P<0.05). Conclusion The SWS of the uterine cervix in pregnancy decreases with advancing gestation. The SWS of IOP had the highest value among the sampling points with unique characteristics.

Prediction of histological chorioamnionitis and neonatal and infantile outcomes using procalcitonin in the umbilical cord blood and amniotic fluid at birth.

AIM: We aimed to clarify the usefulness of procalcitonin (PCT) in the evaluation of histological chorioamnionitis (CAM) and in the prediction of neonatal and infantile outcomes as a reference of interleukin-6 (IL-6). METHODS: Subjects were 36 singleton pregnant women delivered at 22-37 weeks' gestation due to threatened premature delivery and/or preterm premature rupture of membranes. Cases were classified into the CAM and non-CAM groups, according to Blanc's criteria. Comparisons were made on umbilical venous and amniotic fluid PCT levels among the groups. The relations between umbilical venous PCT and IL-6 levels and neonatal and infantile outcomes were also analyzed. RESULTS: The umbilical venous PCT level in the CAM group (240.2 pg/mL, 125.4-350.3 pg/mL: median, first quartile-third quartile) was higher than that in the non-CAM group (105.1, 50.2-137.5 pg/mL; P = 0.0006). There were no differences in the amniotic fluid PCT levels between the groups. There was a strong correlation between umbilical venous PCT and IL-6 levels (correlation coefficient: 0.793). Among 10 cases with an umbilical venous PCT level of ≥170.0 pg/mL and six cases with IL-6 ≥ 11.0 pg/mL, six (60.0%) and five cases (83.3%), respectively, had adverse neonatal and infantile outcomes. Among seven cases with adverse neonatal and infantile outcomes, six (85.7%) and five (71.4%) cases showed umbilical venous PCT levels of ≥170.0 pg/mL and IL-6 levels of ≥11.0 pg/mL, respectively. CONCLUSION: Similar to IL-6, the umbilical venous PCT level is a promising parameter for predicting histological CAM and adverse neonatal and infantile outcomes related to in utero inflammatory status.

Difficulty in the Diagnosis of Biliary Atresia Splenic Malformation Syndrome In Utero.

The fetus of a 30-year-old pregnant Japanese woman was diagnosed with absence of inferior vena cava (IVC) and azygos continuation of interrupted IVC without cardiac anomalies at 34 weeks of gestation, and a healthy male neonate weighing 2,910 g was delivered at 37 weeks of gestation. On day 42 after birth, direct bilirubin predominant hyperbilirubinemia and high serum gamma-GTP levels were detected. Computed tomography revealed the presence of a lobulated and accessory spleen, and laparotomy demonstrated type III biliary atresia (BA), confirming the final diagnosis of BA splenic malformation (BASM) syndrome. In retrospect, non-visualization of the gallbladder was missed in utero. The combination of the absence of IVC and BA without cardiac anomalies is far less likely to occur in left isomerism. Although BA remains difficult to detect in utero, special attention should be paid to cases of BA associated with findings of left isomerism, including the absence of IVC, to enable early diagnosis and treatment of BASM.

Estimated time to emergence of secondary intra-amniotic infection or inflammation since the onset of the preterm premature rupture of membranes.

OBJECTIVE: Prematurity is the most important prognostic factor for infants born following preterm premature rupture of membranes (PPROM). Therefore, when PPROM occurs between 22 and 33 weeks of gestation, prolonging pregnancy is recommended. Determination of management strategies requires screening for the presence of intra-amniotic infection or inflammation at the time of PPROM diagnosis. If intra-amniotic infection/inflammation is not detected, it is important to monitor the patient to diagnose any new infection/inflammation. We examined the period from PPROM to secondary intra-amniotic infection/inflammation and associated factors. MATERIALS AND METHODS: This retrospective study was conducted at a single facility. We examined 26 patients who experienced PPROM between 26 and 33 weeks of gestation and were negative for intra-amniotic infection/inflammation at the time of diagnosis and underwent serial amniocentesis. Antibiotic therapy comprising ampicillin, amoxicillin, and clarithromycin for 7 days was started after the first amniocentesis. The period from PPROM to secondary intra-amniotic infection/inflammation was analyzed using a Kaplan-Meier survival curve. The onset of intra-amniotic infection/inflammation was considered as the time at which amniotic fluid bacterial culture results became positive, the time when amniotic fluid Interleukin (IL)-6 increased beyond 2.6 ng/mL, or the day of delivery if histological chorioamnionitis was observed in the delivered placenta. Patients were treated as censored if no intra-amniotic infection/inflammation could be confirmed in the amniotic fluid and delivered placenta. RESULTS: The median time from PPROM to secondary intra-amniotic infection/inflammation was 18 days. Six patients developed intra-amniotic infection/inflammation, while 13 patients without intra-amniotic infections/inflammation delivered fewer than 7 days after PPROM. No confounding factors at the time of PPROM diagnosis were associated with the time from PPROM until secondary intra-amniotic infection/inflammation. CONCLUSIONS: The time between PPROM and onset of secondary intra-amniotic infection/inflammation appears prolonged. Treatments other than antimicrobial agents may need to be added to prolong pregnancy.

Diagnosis of Fetal Abnormalities during the First Trimester.

The quality of prenatal diagnosis of fetal abnormalities has advanced with improved resolution of ultrasound imaging and cytogenetic/molecular analysis. In this article, we briefly review the history of diagnosing fetal abnormalities and the current status of prenatal diagnosis during the first trimester (up to the first 14 weeks' gestation), focusing especially on fetal malformations and chromosomal abnormalities. As for detectable morphological abnormalities, roughly half of all major structural anomalies including those in the central nervous system, cardiovascular system and gastrointestinal system can be detected, if not definitely diagnosed. For screening of chromosomal abnormalities, especially for trisomy 21, ultrasound soft markers such as increased nuchal translucency, maternal serum markers and their combinations have been implemented. More recently, non-invasive prenatal testing, by analyzing cell-free DNA in maternal serum, is now available to detect chromosomal abnormalities with higher predictability. Although invasive chorionic villus sampling offers definite diagnosis for chromosomal abnormalities during the first trimester, non-invasive diagnostic techniques are patient-friendly and promising in the future perspectives on prenatal diagnosis for chromosomal abnormalities.

Visual diagnosis in utero: Prenatal diagnosis of Treacher-Collins syndrome using a 3D/4D ultrasonography.

OBJECTIVE: We present a case with prenatal diagnosis of Treacher-Collins syndrome in which micrognathia and other facial and ear abnormalities were described using a three- and four-dimensional (3D/4D) ultrasonography in utero. CASE REPORT: A 39-year-old Japanese pregnant woman was referred because of polyhydramnios at 29 weeks' gestation. Conventional ultrasonography showed a hypoplastic mandible on the sagittal section of fetal head. Continuous observation using a 3D ultrasonography additionally demonstrated bilateral downslanting palpebral fissures with symmetry and macrostomia as well as micrognathia. Both ears were microtia and no polydactyly or missing fingers were found. CONCLUSION: The advantage of the rendering mode of 3D images covering entire face including ears and limbs was enhanced by a continuous observation, so called 4D ultrasonography, under a condition of polyhydramnios, providing visual diagnosis in utero.

Predictors of Abnormal Glucose Tolerance in the Early Postpartum Period in Patients with Gestational Diabetes.

This study was designed to investigate the clinical predictors of abnormal glucose tolerance 5-7 weeks after delivery. Subjects were 155 women diagnosed with gestational diabetes mellitus (GDM) between October 2005 and September 2013 whose pregnancy and delivery were managed at our center. Subjects were divided into a normal glucose tolerance group (NGT; n = 113), or abnormal glucose tolerance group (AGT; n = 42) with borderline or overt diabetes mellitus, based on 75-g oral glucose tolerance test (75 gOGTT) results 5-7 weeks after delivery. We extracted profiles by which abnormal glucose tolerance levels 5-7 weeks after delivery were predicted using a classification and regression tree (CART) from parameters measured at the time of GDM diagnosis. Logistic regression analysis was used to determine prediction accuracy. Subjects with fasting plasma glucose (FPG) ≥92 mg/dL and immuno-reactive insulin level <100 µU/mL 60 min after load (IRI60min) at time of diagnosis showed a significantly higher risk of developing abnormal glucose tolerance 5-7 weeks after delivery than subjects with FPG <92 mg/dL (p < 0.0001). Subjects with FPG ≥92 mg/dL and IRI60min ≥ 100 µU/mL had the same risk as those with FPG of <92 mg/dL. Patients with gestational diabetes who met the criteria specified above at diagnosis were at a higher risk of developing diabetes mellitus in the future. By explaining this issue to patients, we expect to improve the rate of postpartum follow-up. This should facilitate early detection of diabetes, and help prevent associated complications.

Prognosis of Pregnant Women with One Abnormal Value on 75g OGTT.

The aim of this study was to identify risk factors to allow us to detect patients at high risk of requiring insulin therapy, among Japanese pregnant women with one abnormal value (OAV) on a 75-g oral glucose tolerance test (75-g OGTT). A total of 118 pregnant women with OAV on a previous 75-g OGTT between 1997 and 2010 were studied. We identified the factors which can predict patients at high risk of requiring insulin therapy among Japanese pregnant women with OAV, by comparing severe abnormal glucose tolerance (insulin treatment; n=17) with mild glucose tolerance patients (diet only; n=101). The following factors were examined; plasma level of glucose (PG) and immunoreactive insulin (IRI) at fasting, 0.5, 1 and 2 hours after loading glucose, insulinogenic index, homeostasis model assessment insulin resistance (HOMA-IR), insulin sensitivity index-composite (ISI composite), and HbA1c at the time of the 75-g OGTT. Univariate analysis showed a positive correlation between insulin therapy and 2-h PG value, 0.5-h and 1-h IRI values, AUC-IRI and insulinogenic index (p<0.05). Multivariate analysis showed that the PG 2-h value and insulinogenic index were independent predictive factors of insulin therapy. A 2-h PG ≥153 mg / dl and an insulinogenic index of <0.42 had a sensitivity of 81.8%, a specificity of 83.8%, a positive predictive value of 60.0% and a negative predictive value of 93.9% for the prediction of patients who required insulin therapy among pregnant women with OAV. These results suggest that a level of 2-h PG ≥153 mg/dl and an insulinogenic index of <0.42 on 75-g OGTT are predictive factors for insulin therapy in Japanese pregnant women with OAV.