Volume 44, Issue 5 - Highlight: Preterm delivery

Objective: To determine the epidemiology of congenital and acquired cytomegalovirus (CMV) infections in preterm infants and to analyze the efficacy of breast milk freezing in decreasing the vertical transmission rate of CMV. Study design: During 2013 and 2014, preterm newborns who weighed ≤1500 g and were admitted to 22 Spanish neonatal units were included and screened for CMV infection according to the Spanish Neonatology Society recommendations. Each hospital treated the breast milk according to its own protocols. Results: Among the 1236 preterm neonates included, 10 had a congenital infection (0.8%) and 49 had an acquired infection (4.0%) (82% demonstrated positive PCR-CMV in breast milk). The neonates who received only frozen milk presented less frequently with acquired infection (1.2%) than those fed fresh milk (5.5%) (RR=0.22; 95% CI 0.05–0.90; P=0.017). The newborns who received bank milk followed by frozen or fresh breast milk more frequently had an acquired infection (2.1% or 2.2%, respectively) than those fed only frozen breast milk. Conclusions: The incidence of congenital CMV infection in our sample is low, as described in the literature. To reduce acquired CMV infection, freezing breast milk might be an advisable procedure for preterm neonates born from seropositive mothers, either from the beginning of lactation or after a period of bank milk administration.

Aim: Current clinical and laboratory diagnostics for neonatal infection are inadequate. An infant’s systemic inflammatory response may be identified earlier than clinical suspicion by a computerized algorithm (RALIS) incorporating multiple vital signs (VS). We tested the ability of RALIS to detect late onset infection (LOI) earlier than clinically suspected. Methods: We conducted a retrospective review of infants enrolled in a birth cohort study at Prentice Women’s Hospital. VS data (heart rate, respirations, temperature, desaturation, bradycardia) were extracted from electronic records of 73 premature infants (born ≤28 weeks’ gestation; survived first month). RALIS generated a continuous output for the first 28 days of life. A score ≥5 for 6 h triggered an alert. The time of RALIS alert to time of clinical suspicion of infection (time culture sent) was measured for each episode of suspected and/or confirmed LOI. Results: Among the 73 infants followed with RALIS, there were 34 episodes of culture-positive LOI, seven culture-negative but treated episodes, and 13 false-positive culture (untreated) episodes. Twenty-five infants had no culture-positive or treated sepsis events during the observation period. There was a positive linear association between alert and culture (β=0.88, P<0.001). Mean absolute time difference between alert and culture was 59.4 h before culture. Sensitivity and specificity of RALIS for LOI were 0.82 and 0.44. Conclusion: The RALIS algorithm is a sensitive indicator for early detection of infection in preterm infants. Further modifications to improve the specificity of the algorithm are needed prior to application of VS modeling to patient antibiotic treatment decisions.

Objective: To assess the effect of oral propranolol on the progression of early stages of retinopathy of prematurity (ROP) in very low birth weight (VLBW) infants. Methods: We analyzed VLBW infants with ROP (stages 2–3, zones II-III). Newborns received oral propranolol (0.5 mg/kg/dose q8h), and were monitored throughout the treatment period for possible side effects. Propranolol was administered until regression of ROP. A historic control group of patients with equivalent ROP was used. We compared characteristics of both groups and the progression of retinopathy. Results: Forty-seven newborns were included, 20 in the propranolol group and 27 in the control group. There were no significant differences in gestational age, birthweight or gender. The mean duration of treatment with propranolol was 58.2±17.6 days. Most patients started treatment with stage 2 disease (65.0%), and had zone III involvement (55.0%). In the treated group, 90.0% (18/20) of patients did not require intervention with laser or bevacizumab, compared to 51.8% in the control group (P<0.005). No cases of bradycardia, hypotension or hypoglycemia were observed. Conclusions: Oral propranolol in early stages of ROP could prevent disease progression and reduce the need for invasive rescue therapy with laser or bevacizumab. No significant side effects were reported.

Objective: To examine the proportion of iatrogenic births among all preterm births over a 26-year period. Patients and methods: A registry-based survey of preterm deliveries between 1987 and 2012 analyzed by the onset of labor: spontaneous with intact membranes, preterm premature rupture of membranes (PPROM) or iatrogenic. Stratification into categories by gestation (22 weeks to 27 weeks and 6 days, 28 weeks to 31 weeks and 6 days, 32 weeks to 33 weeks and 6 days, 34 weeks to 36 weeks and 6 days) was performed. Preterm birth rates were analyzed using the Mantel-Haenszel linear-by-linear association χ 2 -test (P<0.05 significant). Logistic regression was used to account for potential confounders. Results: Overall preterm birth rate was 5.9% (31328 deliveries) including 2358 (0.4%) before 28 completed weeks, 3388 (0.6%) between 28 weeks and 31 weeks 6 days, 3970 (0.8%) between 32 weeks and 33 weeks and 6 days, and 21611 (4.1%) between 34 weeks and 36 weeks and 6 days There was an increase in overall preterm birth rate (P<0.001). The rate of iatrogenic preterm births and PPROM increased over time (P<0.001 and P<0.014, respectively). Rates of spontaneous preterm birth decreased (P<0.001). After accounting for potential confounders, year of birth remained an independent risk factor for iatrogenic preterm delivery in all four gestational age categories (P<0.001). Conclusion: The incidence of iatrogenic preterm birth is increasing with a concomitant decrease in the incidence of spontaneous preterm birth. Attempts to analyze, interpret and decrease preterm birth rates should consider spontaneous and iatrogenic preterm births separately.

Objective: To assess the risk for preterm deliveries <37 week of gestation and associated prevalence of vaginal infection in a rural setting after the tsunami in Banda Aceh, Indonesia. Methods: Wet mount microscopy, vaginal pH and vaginal swabs for microbiological culture were collected in pregnant women during the 2 nd trimester from February to June of 2005 in four temporary outpatient clinics and the patients were followed up until delivery. Results: One hundred and fifty-nine pregnant patients were screened. Sixty-two could be followed up until delivery. Thirty-nine (62.9%) delivered at term and 23 (37.1%) delivered prematurely. Significant risk factors for preterm delivery were a history of preterm delivery and group B streptococcus infection. Increased vaginal pH alone had no significant influence on preterm delivery, although there was a trend. Conclusion: The rate of preterm delivery was high in this cohort. We suggest risk stratification for preterm delivery in rural conditions by performing a vaginal pH and wet mount microscopy. If either is suspect we suggest collecting a vaginal swab for microbiological culture for targeted treatment. Patients with a history of preterm delivery are at increased risk and should be monitored closely.

Objective: To investigate if early pregnancy serum neopterin concentrations (EPSN) could predict spontaneous preterm birth (SPB). Methods: EPSN was measured in 92 sera collected from 46 pregnant women with birth at term and 40 sera from 20 pregnant women with preterm birth. Two sera were collected for each case: in the first and early second trimester. Results: EPSN concentrations correlate with gestational age (ρ=0.275, P=0.001), a correlation which was present in both groups: term and preterm birth. EPSN were higher in pregnancies with SPB compared with normal pregnancies (6.27±1.03 vs. 6.04±0.15, P=0.039). Patients with SPB showed a considerable increase of EPSN in the second trimester compared with patients with birth at term (7.30±1.53 vs. 6.16±0.23, P=0.043). A sharper increase was found in the group with SPB before 32 weeks of pregnancy (wp) (9.83±4.36 vs. 6.16±0.23, P=0.016). Pregnant women with an early second trimester serum neopterin value of above 8 nmol/L are associated with a risk of SPB before 32 wp (odds ratio=14.4, P=0.01) and of SPB before 34 wp (odds ratio=3.6, P=0.05), respectively. Conclusions: EPSN increases with the gestational age and predicts SPB in asymptomatic pregnant women.

Objective: To compare the frequency of histologic chorioamnionitis and funisitis among women experiencing preterm labor, preterm premature rupture of membranes (PROM) and cervical insufficiency. Methods: This retrospective cohort study included singleton pregnant women who delivered at ≤36 weeks of gestation. The patients with preterm birth were subdivided into preterm labor (n=117), preterm PROM (n=153), and cervical insufficiency (n=20). All placentas were examined for pathology, according to the criteria of Salafia with minor modification. Frequencies of histologic chorioamnionitis and funisitis were evaluated according to the causes of preterm birth. Results: 1) Histologic chorioamnionitis was diagnosed in 48.7% (57/117) of cases with preterm labor, 47.4% (73/153) with preterm PROM, and 75.0% (15/20) with cervical insufficiency. Funisitis was detected in 11.1% (13/117) of cases with preterm labor, 15.7% (24/153) with preterm PROM, and 40.0% (8/20) with cervical insufficiency. 2) Frequency of histologic chorioamnionitis was higher in cases with cervical insufficiency compared to preterm PROM. Frequency of funisitis was higher in cases with cervical insufficiency compared to both preterm labor and preterm PROM (P<0.05). The difference in frequency of funisitis remained significant after adjustment for gestational age at delivery and cervical dilatation at diagnosis. 3) Frequency of grade 2 funisitis was higher in cases with cervical insufficiency (35.0%, 7/20) compared to both preterm labor (6.8%, 8/117) and preterm PROM (9.8%, 15/153) (P=0.001). And the difference remained significant after adjustment for gestational age at delivery and cervical dilatation at diagnosis. Conclusion : The highest frequency of funisitis was observed in cervical insufficiency among cases with spontaneous preterm birth.

Lysophosphatidylcholine acyltransferase 1 (LPCAT1) is required in the biosynthesis of pulmonary surfactant. This short communication describes our assessment of LPCAT1 mRNA levels in human amniotic fluid. We found a direct correlation between LPCAT1 mRNA copies and the amniotic fluid lamellar body count (LBC). This finding corroborates an association between LPCAT1 and surfactant phospholipid biosynthesis in humans. It may provide a model for future research in perinatal medicine.

Magnetic resonance imaging (MRI) has been increasingly adopted in obstetrics practice in the past three decades. MRI aids prenatal ultrasound and improves diagnostic accuracy for selected maternal and fetal conditions. However, it should be considered only when high-quality ultrasound cannot provide certain information that affects the counseling, prenatal intervention, pregnancy course, and delivery plan. Major indications of fetal MRI include, but are not restricted to, morbidly adherent placenta, selected cases of fetal brain anomalies, thoracic lesions (especially in severe congenital diaphragmatic hernia), and soft tissue tumors at head and neck regions of the fetus. For fetal anatomy assessment, a 1.5-Tesla machine with a fast T2-weighted single-shot technique is recommended for image requisition of common fetal abnormalities. Individual judgment needs to be applied when considering usage of a 3-Tesla machine. Gadolinium MRI contrast is not recommended during pregnancy. MRI should be avoided in the first half of pregnancy due to small fetal structures and motion artifacts. Assessment of fetal cerebral cortex can be achieved with MRI in the third trimester. MRI is a viable research tool for noninvasive interrogation of the fetus and the placenta.

Objective: To examine potential correlations between maternal serum placental protein-13 (PP-13) and first trimester maternal and placental factors, and to evaluate the association of this marker with adverse pregnancy outcome. Methods: Serum samples from prospectively enrolled patients between 11 and 13 weeks and 6 days were analyzed for PP-13 using an ELISA assay. The relationships between maternal serum PP-13 levels and gestational age, maternal age, ethnicity, parity, smoking status, body mass index (BMI), mean arterial blood pressure, uterine and umbilical artery Doppler parameters were examined. The association between first-trimester PP-13 levels and subsequent pre-eclampsia and delivery of a small for gestational age (SGA) neonate was also investigated, after excluding patients who received aspirin. Results: In 908 patients, PP-13 levels ranged from 8.0 to 537.5 pg/mL. A significant negative correlation was identified between PP13 and BMI (Spearman rho –0.20, P<0.0001). Smoking significantly decreased PP-13 (P<0.01). No relationship was identified with the other parameters. In a subgroup of 668 low-risk patients who did not receive aspirin, PP-13 levels were not associated with development of pre-eclampsia, SGA or the combination of them. Conclusion: First-trimester PP-13 levels are significantly correlated with BMI and smoking. These correlations appear independent of uterine and umbilical artery resistance. In low risk patients, PP-13 levels fail to predict the risk for pre-eclampsia or SGA.

Aims: This study aimed to determine effective predictive factors for primary postpartum hemorrhage (PPH) among clinical blood parameters associated with coagulation and fibrinolysis and demographic characteristics. Methods: We retrospectively studied 1032 women who underwent determinations of clinical blood parameters at gestational week (GW) 29–32 and GW 35–37 and gave birth to singleton infants at our hospital between January 2011 and December 2013. PPH was defined as estimated blood loss ≥700 mL. Multivariate logistic regression analyses were used to determine independent risk factors and odds ratios (OR) for PPH. Results: PPH occurred in 104 of 1032 women (10%). Three blood variables, fibrinogen level <4.0 g/L (OR [95% CI], 1.96 [1.18–3.27]), antithrombin activity <85% of normal activity level (1.84 [1.05–3.21]), and D-dimer level >2.7 μg/mL (2.03 [1.29–3.19]) at GW 35–37, and three demographic characteristics, maternal age ≥35 years (1.75 [1.15–2.68]), BMI >28.2 kg/m 2 on admission for childbirth (1.95 [1.20–3.16]), and previous cesarean delivery (2.77 [1.31–5.83]), were identified as independent risk factors for PPH. Conclusion: Among blood parameters, higher D-dimer levels and lower levels of antithrombin activity and fibrinogen in late gestation were independent risk factors for PPH.

Aim: To evaluate intraoperative and early postoperative outcomes of a novel placenta delivery technique; extra-abdominal removal vs. intra-abdominal removal of the placenta during cesarean section (CS). Methods: A total of 210 women delivering by CS at term in a tertiary university hospital between March 2014 and January 2015 were randomized to extra-abdominal removal vs. intra-abdominal removal of the placenta. The women were randomly allocated to the extra- (group 1) or intra-abdominal removal group (group 2) according to random sampling method, where women with even and odd numbers were allocated to intra- and extra-abdominal groups, respectively. The amount of intra-abdominal hemorrhagic fluid accumulation, the duration of operation and estimated blood loss during operation were the primary outcomes. The secondary outcomes included the mean difference between pre- and post-operative hemoglobin and hematocrit levels, the mean postoperative pain score, any additional need of analgesia, postoperative bowel function, postoperative endometritis and wound infections. Results: The amount of aspirated hemorrhagic fluid was significantly higher in the intra-abdominal group compared to the extra-abdominal group (34.6±22.2 mL vs. 9.4±4.8 mL, P<0.001). Mean duration of the operation, intraoperative blood loss, postoperative requirement of additional analgesia, postoperative pain scores, postoperative endometritis or wound infection, and length of hospital stay were not significantly different between the intra- and extra-abdominal placental removal groups. Conclusion: By extra-abdominal removal of the placenta, the accumulation of bloody fluid in the abdominal cavity is significantly less compared to the intra-abdominal removal method, which, in turn, provides avoidance of excessive mounted-gauze use, intra-abdominal manipulations, or iatrogenic trauma.

Aims: Intrapartum translabial ultrasound [ITU] can be an objective, reproducible and more reliable method than digital vaginal examination when evaluating fetal head position and station in prolonged second stage of labor. However, two-dimensional (2D) ultrasound is not sufficient to demonstrate the ischial spines and other important “landmarks” of the female pelvis. Therefore, the purpose of this study was to evaluate the distance of the interspinous plane as a parallel line to the infrapubic line in 2D ITU with the help of 3D computed tomography and digital reconstruction. Results: Mean distance between the infrapubic plane and the tip of the ischiadic spine was 32.35 (±4.46) mm. The mean height was 166 (±7) cm; the mean weight was 67.5 (±18.4) kg. Body height and the measured distance were significantly correlated (P=0.025; correlation coefficient of 0.5), whereas body weight was not (P=0.37; correlation coefficient of –0.214). Conclusions: With the present results, clinicians were enabled to transfer the reproducible measurements of the “head station” by ITU to the widespread but observer-depending vaginal examination. Furthermore, ITU can be verified as an objective method in comparison to subjective palpation with the ability to optimize the evaluation of the head station according to bony structures as landmarks in a standardized application.

Objective: There is an increasing body of literature supporting universal umbilical cord blood gas analysis (UCBGA) into all maternity units. A significant impediment to UCBGA’s introduction is the perceived expense of the introduction and associated ongoing costs. Consequently, this study set out to conduct the first cost-effectiveness analysis of introducing universal UCBGA. Methods : Analysis was based on 42,100 consecutive deliveries ≥23 weeks of gestation at a single tertiary obstetric unit. Within 4 years of UCBGA’s introduction there was a 45% reduction in term special care nursery (SCN) admissions >2499 g. Incurred costs included initial and ongoing costs associated with universal UCBGA. Averted costs were based on local diagnosis-related grouping costs for reduction in term SCN admissions. Incremental cost-effectiveness ratio (ICER) and sensitivity analysis results were reported. Results : Under the base-case scenario, the adoption of universal UCBGA was less costly and more effective than selective UCBGA over 4 years and resulted in saving of AU$641,532 while adverting 376 SCN admissions. Sensitivity analysis showed that UCBGA was cost-effective in 51.8%, 83.3%, 99.6% and 100% of simulations in years 1, 2, 3 and 4. These conclusions were not sensitive to wide, clinically possible variations in parameter values for neonatal intensive care unit and SCN admissions, magnitude of averted SCN admissions, cumulative delivery numbers, and SCN admission costs. Conclusions: Universal UCBGA is associated with significant initial and ongoing costs; however, potential averted costs (due to reduced SCN admissions) exceed incurred costs in most scenarios.

Aim: To evaluate the sex difference in fetal behavior between male and female fetuses. Methods: Fetal behavior was assesed by Kurjak’s antenatal neurodevelopmental test (KANET) using four-dimensional (4D) ultrasound between 28 and 39 weeks of gestation. Fifty-nine male and 53 female fetuses in middle- and high-class nulliparaous Japanese women were studied. The total value of the KANET score and values of each parameter (eight parameters) were compared. Results: The total KANET score was normal in both groups, and there was no significant difference in the total KANET score. When individual KANET parameters were compared, no significant differences were noted in all eight parameters. Conclusion: Our results show that there is no difference in fetal behavior between male and female fetuses in the third trimester of pregnancy. These results suggest that 4D ultrasound study examining fetal behavior does not need to consider the factor of fetal sex.

Objective: To determine antepartum and intrapartum factors that are associated with admission to neonatal intensive care unit (NICU) among infants delivered between 36.0 and 42.0 weeks at our institution. Methods: The retrospective cohort study included 73 consecutive NICU admissions and 375 consecutive non-NICU admissions. Data on demographic, antepartum, intrapartum and neonatal factors were collected. The primary endpoint defined was admission to NICU. Univariate analyses using the Student’s t -test, Mann-Whitney U -test, χ 2 Fisher’s exact test was performed along with multivariate analysis of significant non-redundant variables. Results: Those with a significantly higher risk of NICU admission underwent induction of labor with prostaglandin analogs (12.5% vs. 24.7%, P=0.007). Length of first stage ≥720 min (33.5% vs. 51.9%, P=0.011), length of second stage of labor ≥240 min (10.6% vs. 31.6%, P<0.001) and prolonged rupture of membranes ≥120 min (54.0% vs. 80.0%, P=0.001) were all associated with an increased chance of NICU admission. Intrapartum factors predictive of NICU admission included administration of meperidine (11.7% vs. 27.4%, P<0.001), presence of preeclampsia (5.5% vs. 0.8%, P=0.015), use of intrapartum IV antihypertensives (1.1% vs. 13.7%, P<0.001), maternal fever (5.3% vs. 31.5%, P<0.001), fetal tachycardia (1.9% vs. 12.3%, P<0.001), and presence of meconium (30% vs. 8%, P<0.001). Conclusion: Identification of modifiable risk factors may reduce neonatal morbidity and mortality. Results from this study can be used to develop and validate a risk model based on combined antepartum and intrapartum risk factors.

Cervical cerclage is a experience demanding procedure and which is difficult for most of the residents and maternal fetal medicine fellows to have the first experience on real patients. In this study we presented an in-expensive and easy to build model for cervical cerclage training.