Volume 47, Issue 5

Objective To assess the value of incorporating amniotic fluid (AF) analysis in the management of patients with clinical chorioamnionitis. Methods This was a retrospective cohort study of all women carrying a singleton fetus and managed at our center between 2000 and 2009. We included only those women suspected of chorioamnionitis based on one or more of the following: (1) uterine tenderness, (2) maternal fever, (3) maternal and/or fetal tachycardia and (4) purulent discharge. The management was deemed to be justified if (1) pregnancy was terminated <24 weeks and histology confirmed chorioamnionitis; (2) delivery was performed expeditiously after initial assessment and histology confirmed chorioamnionitis; (3) delivery was delayed for 2–7 days and the patient completed a course of antenatal steroids before 34 weeks; and (4) delivery was delayed ≥7 days and histology was not indicative of chorioamnionitis, or delivery occurred after 37 weeks. Univariate and logistic regression analyses were used as appropriate. Results Of the 77 women with suspected chorioamnionitis, AF analysis was performed in 43 (55.8%) cases, and the management was justified in 63 (81.8%) cases based on the aforementioned criteria. Stepwise regression analysis confirmed AF analysis as a predictor of justified management. The rates of composite morbidity, neonatal sepsis, neonatal death and admissions to neonatal intensive care unit were lower in the justified management group. Conclusion Incorporation of AF analysis into clinical assessment does improve the management of suspected chorioamnionitis.

Background The frequency of intra-amniotic infection/inflammation (IAI/I) in patients with midtrimester cervical insufficiency is up to 50%. Our purpose was to determine the perinatal outcomes of cervical cerclage in patients with acute cervical insufficiency with bulging membranes, and to compare the admission-to-delivery interval and pregnancy outcomes according to the results of amniotic fluid (AF) analysis and cerclage placement. Methods This was a retrospective cohort study including singleton pregnancies with cervical insufficiency between 15 and 26.9 weeks in two tertiary health centers. IAI/I was defined when at least one of the following criteria was present in AF: (a) a white blood cell (WBC) count >50 cells/mm 3 ; (b) glucose concentration <14 mg/dL; and/or (c) a Gram stain positive for bacteria. Three different groups were compared: (1) absence of IAI/I with placement of a cerclage; (2) amniocentesis not performed with placement of a cerclage; and (3) IAI/I with or without a cerclage. Results Seventy patients underwent an amniocentesis to rule out IAI/I. The prevalence of IAI/I was 19%. Forty-seven patients underwent a cerclage. Patients with a cerclage had a longer median admission-to-delivery interval (33 vs. 2 days; P < 0.001) and delivered at a higher median gestational age (27.4 vs. 22.6 weeks; P = 0.001) than those without a cerclage. The neonatal survival rate in the cerclage group was 62% vs. 23% in those without a cerclage (P = 0.01). Patients without IAI/I who underwent a cerclage had a longer median admission-to-delivery interval (43 vs. 1 day; P < 0.001), delivered at a higher median gestational age (28 vs. 22.1 weeks; P = 0.001) and had a higher neonatal survival rate (67% vs. 8%; P < 0.001) than those with IAI/I. Conclusion The pregnancy outcomes of patients with midtrimester cervical insufficiency and bulging membranes are poor as they have a high prevalence of IAI/I. Therefore, a pre-operative amniocentesis is key to identify the best candidates for the subsequent placement of a cerclage.

Objectives To evaluate the maternal serum endocan levels in pregnant women complicated by preterm premature rupture of membranes (PPROM) and to compare the results with healthy pregnancies. Methods This cohort study included 31 pregnant women with PPROM and 34 gestational age-matched healthy subjects in the third trimester of pregnancy. The blood for analysis was obtained on the day of diagnosis and serum endocan levels were measured using a commercially available enzyme-linked immunosorbent assay (ELISA) kit. The pregnant women were observed until the delivery and perinatal data were noted. Results No significant differences regarding maternal age, body mass index, gravidity, parity and gestational age at sampling were observed (P > 0.05). Mean serum endocan level was significantly higher in the PPROM group than in healthy controls (1490 ± 632 pg/mL vs. 972 ± 586 pg/mL, respectively; P: 0.001). Serum endocan concentration was positively correlated with C-reactive protein (CRP) (r = 0.754, P < 0.001) and white blood cells count (WBC) (r = 0.712, P:0.001). The receiver operating characteristic (ROC) curve analysis showed that endocan with a cut-off point of 1198 ng/dL indicated women with PPROM with sensitivity of 64.5% and specificity of 35.1% (area under curve 0.731, confidence interval 0.61–0.85). Conclusion Serum endocan level was significantly elevated in the PPROM patients than in healthy controls. The endocan level may be a useful indicator of endothelial dysfunction/inflammation in PPROM cases.

Objectives To determine the relationship between the intensity of the intra-amniotic inflammatory response and the gestational age at the time of diagnosis in cases with preterm premature rupture of membranes (PROM) and intra-amniotic infection caused by Ureaplasma spp. Methods A retrospective cohort study was conducted which included 71 women with preterm PROM and a positive amniotic fluid culture with Ureaplasma spp. Women with mixed intra-amniotic infections were excluded. The study population was classified into three groups according to gestational age: group 1, <26 weeks (extreme preterm PROM, n = 17); group 2, 26.0–33.9 weeks (moderate preterm PROM, n = 39); group 3, 34.0–36.9 weeks (late preterm PROM, n = 15). The intensity of the intra-amniotic and maternal inflammatory response was compared among the three groups. The intensity of the intra-amniotic inflammatory response was assessed by the concentration of amniotic fluid matrix metalloproteinase-8 (MMP-8) and white blood cell (WBC) count. The maternal inflammatory response was assessed by the concentration of C-reactive protein (CRP) and WBC count in maternal blood at the time of amniocentesis. Results (1) The median values of amniotic fluid MMP-8 concentration and WBC count were the highest in the extreme preterm PROM group and the lowest in the late preterm PROM group (P < 0.001 and P = 0.01, respectively); (2) the intensity of the maternal inflammatory response measured by maternal blood WBC count and CRP concentration was not significantly associated with gestational age at the time of diagnosis. Conclusion The earlier the gestational age at the time of PROM, the higher the intensity of the intra-amniotic inflammatory response in women with preterm PROM and intra-amniotic infection caused by Ureaplasma spp.

Objective To assess the maternal group B streptococcal (GBS) colonization rate and neonatal early-onset GBS (EOGBS) disease in term deliveries, a decade apart. Methods This was a retrospective computerized study between 2005 and 2016. A universal GBS culture-based approach gradually replaced the GBS risk-oriented screening. A vaginal-rectal culture taken at 35–37 weeks was recorded at admission for delivery. Results We identified 149,910 term deliveries during the study period. GBS status was recorded in 53,879 (35.9%) cases. The GBS screening rate constantly increased from 20% in 2005 to 47.5% in 2016. GBS colonization rates significantly decreased, from 50.3% in 2005 to 31.7% in 2016, P<0.001. Overall, EOGBS disease was diagnosed in 37 term neonates (0.25 per 1000 live births.). The rate of EOGBS in neonates decreased dramatically from 0.361 per 1000 deliveries between 2005 and 2009 to 0.19 per 1000 deliveries between 2010 and 2016 (P<0.05). During the latter period, over 35% of the deliveries were screened for GBS. Remarkably, 64.9% of the EOGBS originated in the non-screened population. Conclusion The universal screening policy was associated with a significant decrease in neonatal EOGBS and therefore should be adopted. Further national surveillance studies should be performed in order to validate this approach.

Objective To demonstrate clinical importance of the 75-g glucose tolerance test (GTT) in the prediction of large for gestational age (LGA) fetuses in non-diabetic pregnancies. Methods We retrospectively evaluated 75-g GTT screening results of 356 pregnancies without prompt diagnosis of gestational diabetes mellitus (GDM) between January 2013 and December 2017. Newborns with a birthweight greater than the 90 th percentile were evaluated as LGA. Pregnancies with LGA and non-LGA fetuses were compared by demographic and historical factors – maternal age, gravidity, parity, birthweight, birthweek, GTT results and birthweight percentiles – via Student’s t -test. Multiple linear regression using the backward elimination method was performed to define the correlation between parameters and LGA (P-value of <0.20 was identified as the threshold). Receiver operator characteristics (ROC) curve analysis was performed for further analysis. Results The cohort was consisted of 45 (12.6%) and 311 (87.4%) pregnancies with LGA and non-LGA fetuses, respectively. Maternal age and 2 nd -h GTT results were found to be significantly higher in patients with LGA newborns (P<0.001 and P=0.016, respectively). Fasting glucose levels and GTT 1 st -h results were also higher (P=0.112, P=0.065). The coefficient of multiple determination (R 2 ) was 0.055 by multiple linear regression analysis. Accordingly, GTT 2 nd -h result and maternal age were statistically significant and contributed to the explanation of LGA, although the R 2 value was not that much higher (P=0.016; P=0.001). Maternal age and GTT 2 nd -h results were found to be associated with LGA fetuses with area under the curve (AUC) values of 0.662 and 0.608 according to ROC curve analysis. Conclusion Maternal age and 75-g GTT 2 nd -h results were significantly higher in gestations with LGA newborns without GDM.

Objective To investigate the placental gene expression of substances in the inflammatory cascade and growth factors at nine different well-defined sampling sites in full-term placentas from 12 normal weight healthy non-smoking women with an uncomplicated singleton pregnancy. Methods All placentas (six girls and six boys) were delivered vaginally. Quantitative real-time polymerase chain reaction was used to analyze toll receptor-2 and -4, interleukin-6 and -8, tumor necrosis factor-α, leptin, ghrelin, insulin-like growth factor-1 and -2, hepatocyte growth factor, hepatocyte growth factor receptor and insulin receptor (IR). Results The leptin gene and the IR gene showed higher expression in lateral regions near the chorionic plate compared to central regions near the basal plate (P = 0.028 and P = 0.041, respectively). Conclusion Our results suggest that the sampling site may influence the gene expression for leptin and IR in placental tissue obtained from full-term normal pregnancies. We speculate that this may be due to differences in placental structure and perfusion and may be important when future studies are designed.

Objective To evaluate the impact of cell-free fetal DNA (cfDNA) test on the number of invasive tests carried out in a public hospital that does not include this test in its services. Methods This was a retrospective cohort study in singleton pregnancies with a high risk (>1:270) on the first-trimester screening for aneuploidies. The options of performing an invasive test or a cfDNA test were explained to all women, the latter being especially recommended to those with a 1:50–1:270 risk (Group 1). If the risk was >1:50 (Group 2), or nuchal translucency (NT) was >99 th percentile or there were major malformations (Group 3), invasive test was recommended. Results A total of 755 of 14,398 (5.2%) cases had a high-risk first-trimester screening, of whom 46 cases were excluded due to incomplete follow-up. In the remaining 709 cases, the percentage of aneuploidies was 9.9% (70 cases) and 110 opted for a cfDNA test (15.5%). There were two true-positive results of cfDNA (one in Group 2 and another in Group 3). In Group 1, 67.4% [95% confidence interval (CI) 60.0%–72.1%, P < 0.01] fewer invasive procedures were performed in those who opted for a cfDNA test, without having false negatives. Conclusion Pregnant women with a 1:50–1:270 risk who opt for cfDNA save two out of three invasive tests, without affecting the aneuploidy detection rate.

Objectives To evaluate whether gestational diabetes mellitus (GDM) diagnosed by different criteria impacts perinatal outcome. Methods This was a retrospective study of deliveries with a diagnosis of GDM (2014–2016). Perinatal outcomes were compared between patients with: (1) GDM diagnosed according to a single abnormal value on the 100-g oral glucose tolerance test (OGTT); (2) two or more abnormal OGTT values; and (3) a 50-g glucose challenge test (GCT) value ≥200 mg/dL. Results A total of 1163 women met the inclusion criteria, of whom 441 (37.9%) were diagnosed according to a single abnormal OGTT value, 627 (53.9%) had two or more abnormal OGTT values and 95 (8.17%) had a GCT value ≥200 mg/dL. Diet-only treatment was significantly higher in the single abnormal value group (70.3% vs. 65.1% vs. 50.5%) and rates of medical treatment were significantly higher in the GCT ≥ 200 mg/dL group (P < 0.05). Women in the GCT ≥ 200 mg/dL group had higher rates of neonatal intensive care unit (NICU) admission (10.5% vs. 2.7% vs. 2.8%, P < 0.001) and neonatal hypoglycemia (5.3% vs. 0.5% vs. 0.8%, P < 0.001). On multivariate logistic regression, GCT ≥ 200 mg/dL was no longer associated with higher rates of NICU admission and neonatal hypoglycemia (P > 0.05). Conclusion No difference was noted in the perinatal outcome amongst the different methods used for diagnosing GDM.

Objective To assess fetal behavioral changes in response to vibroacoustic stimulation (VAS) in normal singleton pregnancies using four-dimensional (4D) ultrasound. Methods Ten types of fetal movements and facial expressions in 68 healthy pregnant women between 24 and 40 weeks were studied using 4D ultrasound for 3 min before and after 3-s VAS. The frequencies of mouthing, yawning, tongue expulsion, back arch, jerky arm movement, startle movement, smiling, scowling, hand-to-face movement, and blinking were evaluated. The fetuses were subdivided into four gestational age groups (24–27, 28–31, 32–35, and ≥36 weeks). Comparison of the frequencies of the fetal behaviors before and after the stimulation in each gestational age group was conducted to detect the response to stimulation with advancing gestation. Results There were no significant differences in the frequency of each fetal behavior before and after VAS at 24–27, 28–31, and 32–35 weeks of gestation. However, the frequencies of blinking and startle movements were significantly higher after VAS in the 36–40 gestational age group (P < 0.05). Conclusion The age of 36 weeks of gestation might represent an advanced stage of brain and central nervous system development and maturation as the response to stimuli is prominent at this age compared with earlier gestation.

Background Our objective was to determine the predictive value of the prenatal diagnosis of isolated clubfoot in twin gestations compared to singleton gestations. Methods A prospectively entered ultrasound database was reviewed for all pregnancies scanned at our institution from 2002 to 2014. Cases of suspected clubfoot were identified. Neonates with associated anomalies or aneuploidy, and patients who delivered at other institutions were excluded. Neonatal charts were reviewed for the confirmation of clubfoot. The chi-squared (χ 2 ) test, Fisher’s exact test and the Mann-Whitney U test were used in the analysis, with p < 0.05 considered significant. Results Of those women who had prenatal ultrasound and subsequently delivered at our hospital, 84 pregnancies had isolated clubfoot suspected in the antenatal period. Of these pregnancies, 20 were twin gestations and 64 were singleton gestations. Overall, 51/84 (60.7%) pregnancies had clubfoot confirmed during the neonatal period. Of the twin pregnancies, only 35% (7/20) had a confirmed diagnosis of clubfoot at birth compared to 68.8% (44/64) of the singleton pregnancies (P = 0.008). Gestational age at diagnosis, breech presentation, neonatal gender, unilateral vs. bilateral clubfoot and suspicion of clubfoot in the presenting twin (Twin A) vs. the non-presenting twin (Twin B) did not correlate with an accurate diagnosis of clubfoot in twins. Conclusion False-positive prenatal diagnosis of isolated clubfoot is more common in twin gestations compared to singletons. This may be due to transient malpositioning or a result of diminished space. Obstetric providers should consider the possibility of a false-positive diagnosis and use caution when counseling patients about a prenatal suspicion for clubfoot, especially in twin gestations.

Background Transcutaneous bilirubinometers are a non-invasive tool to estimate serum bilirubin. However, once on phototherapy (PHT) and after PHT, its usefulness is precluded. The objective of this study was to prove the hypothesis that transcutaneous bilirubin (TcB) assessment in a covered skin area during PHT could be used to guide the duration of PHT in term and moderate-late preterm infants with non-isoimmune hyperbilirubinemia. Methods A small area of parasternal skin was covered before starting on PHT. Total serum and TcB (both in exposed and non-exposed areas) were determined before starting treatment, every 12 h once on PHT and 12 h after its discontinuation. Pearson’s correlation coefficient and paired mean differences between TcB and total serum bilirubin (TSB) were calculated. Bland-Altman plots were obtained. The percentage of correct treatment decisions made based on non-exposed TcB values was calculated. Results During PHT, there was a relatively good correlation between TSB and non-exposed TcB (0.74) estimates, in contrast to exposed TcB estimates (0.52). However, even when comparing non-exposed TcB with TSB, there was a wide range of agreement limits (−3.8 to 4.6 mg/dL). Decisions based on non-exposed TcB values would have been incorrect in 26.6% of the cases. Conclusion Although there is a relatively strong correlation between total serum and TcB in non-PHT-exposed regions, the difference is not narrow enough to be utilized in guiding clinical decisions on the duration of PHT.