Volume 47, Issue 2

Background Worldwide, 14.9 million infants (11%) are born preterm each year. Up to 40% of preterm births (PTBs) are associated with genital tract infections. The vaginal pH can reflect changes in the vaginal milieu and, if elevated, indicates an abnormal flora or infection. Objective The aim of the study was to investigate whether an increased antenatal vaginal pH >4.5 in pre-labour pregnant women is associated with an increased PTB rate <37 completed weeks gestation. Search strategy Key databases included SCOPUS, EMBASE, MEDLINE, PsycInfo and the Cochrane Central Register of Controlled Trials, complemented by hand search, up to January 2017. Selection criteria Primary research reporting vaginal pH assessment in pre-labour pregnant women and PTB rate. Data collection and analysis Data extraction and appraisal were carried out in a pre-defined standardised manner, applying the Newcastle-Ottawa scale (NOS) and Cochrane risk of bias tool. Analysis included calculation of risk difference (RD) and narrative synthesis. It was decided to abstain from pooling of the studies due to missing information in important moderators. Main results Of 986 identified records, 30 were included in the systematic review. The risk of bias was considered mostly high (40%) or moderate (37%). Fifteen studies permitted a calculation of RD. Of these, 14 (93%) indicated a positive association between increased antenatal vaginal pH and PTB (RD range: 0.02–0.75). Conclusion An increased antenatal vaginal pH >4.5 may be associated with a higher risk for PTB. It is recommended to conduct a randomised controlled trial (RCT) to investigate the effectiveness of antenatal pH screening to prevent PTB. Tweetable abstract Pregnant women with an increased vaginal pH >4.5 may be at higher risk to experience preterm birth.

Uterine tachysystole (TS) is a potentially significant intrapartum complication seen most commonly in induced or augmented labors but may also occur in women with spontaneous labor. When it occurs, maternal and perinatal complications can arise if not identified and managed promptly by obstetric care providers. Over recent years, new definitions of the condition have facilitated further research into the field, which has been synthesized to inform clinical management guidelines and protocols. We propose a set of recommendations pertaining to TS in line with contemporary evidence and obstetric practice.

Objectives To evaluate the first trimester maternal biomarkers for early pregnancy prediction of gestational diabetes mellitus (GDM). Methods The study was a case-control study of healthy women with singleton pregnancies at the first trimester carried out at the Obstetrics and Gynecology Unit, Clinica Davila, Santiago, Chile. After obtaining informed consent, peripheral blood samples of pregnant women under 14 weeks of gestation were collected. At 24–28 weeks of pregnancy, women were classified as GDM (n=16) or controls (n=80) based on the results of a 75-g oral glucose tolerance test (OGTT). In all women, we measured concentrations of fasting blood glucose, insulin, glycated hemoglobin, uric acid, cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL), very low density lipoprotein (VLDL), triglycerides, aspartate aminotransferase (AST), alanine aminotransferase (ALT), γ-glutamyl transpeptidase (GGT), alkaline phosphatase (AP), sex hormone-binding globulin (SHBG), adiponectin, tissue plasminogen activator (t-PA), leptin and placental growth factor (PGF). Results The GDM group displayed an increased median concentration of cholesterol (P=0.04), triglycerides (P=0.003), insulin (P=0.003), t-PA (P=0.0088) and homeostatic model assessment (HOMA) (P=0.003) and an increased mean concentration of LDL (P=0.009) when compared to the control group. The receiver operating characteristic (ROC) curve for significant variables achieved an area under the curve (AUC) of 0.870, a sensitivity of 81.4% and a specificity of 80.0%. The OGTT was positive for GDM according to the IADPSG (International Diabetes in Pregnancy Study Group) criteria. Conclusion Women who subsequently developed GDM showed higher levels of blood-borne biomarkers during the first trimester, compared to women who did not develop GDM. These data warrant validation in a larger cohort.

Background Peripartal hysterectomy (PH) is a challenging surgical procedure with elevated maternal morbidity. Methods From 2004 to 2016, 41 emergency PHs were performed at the tertiary care center of the Department of Gynecology and Obstetrics at University Hospital Ulm. In our retrospective analysis, the incidence of PH in our hospital was 12.8 per 10,000 deliveries with a maternal mortality of 2.4%. PH followed in 80.5% after cesarean section (c-section). Underlying causes/indications for PH were abnormal placentation (53.7%; n=22), uterine atony (26.8%; n=11), uterine lacerations (14.6%; n=6) and in rare cases uterine infection (4.9%; n=2). The median number of transfused products was 11 packed red blood cells (range 0–55 products), 10 fresh frozen plasma units (range 1–43) and two platelet concentrates (0–16). Results Loss of blood as estimated by surgeons was significantly correlated with actual transfused blood volume (P<0.001). Clinically relevant intra- and/or postoperative complications occurred in 53.7% of patients (n=22). Abnormal placentation was the leading cause for PH with an increased incidence during the last 10 years presumptively representing the elevated rate of c-sections. Conclusion PH goes along with increased rates of blood product transfusions independently of indication for surgery and has a high morbidity with a major complication rate of more than 50%. Prepartal assessment of risk factors like abnormal invasive placenta are crucial for reducing maternal morbidity.

Objectives To compare the oral application form of misoprostol with the misoprostol vaginal insert (MVI) in a Swiss cohort with special regards to the efficacy and safety. Methods We performed a retrospective case series including a historical group induced with oral misoprostol (MO, n=101) and an MVI group (n=101). The primary outcome was time to delivery. Secondary outcomes were mode of delivery, occurrence of tachysystole, use of analgesia and neonatal adverse outcome. Results A total of 202 women were included in the analysis (101 in the MVI as well as in the MO group). Time from start of induction to delivery was significantly shorter in the MVI group compared to the MO group (15.91 h vs. 37.68 h, P<0.001). Within the first 24 h, 78.2% of the women in the MVI group had given birth compared to 28.7% in the MO group (P<0.001). Tachysystole occurred more often in the MVI group (22.8% vs. 5.0%, P<0.001). Women in the MVI group more often needed opioid analgesia during the induction before onset of active labor (31.7% vs. 2.0%, P<0.001). There was no significant difference between neonatal outcomes in the two groups. Conclusion Time to delivery was significantly shorter in the MVI group with a higher rate of vaginal deliveries within the first 24 h. However, patients needed more opioids for pain relief during induction with MVI. There was no difference in neonatal outcomes.

Background As breastfeeding awareness and social acceptance are increased, maternal nutritional deficiency requires more investigation. Methods A prospective cohort study was conducted to determine if vitamin A deficiency is more common in pregnant, lactating post-bariatric surgery women in an inner city population. Antepartum, women after bariatric surgery and controls with no history of malabsorption were recruited. Third trimester, postpartum maternal blood and cord blood were collected as well as three breast milk samples: colostrum, transitional and mature milk. A nutritional survey of diet was completed. Each serum sample was analyzed for total retinol and β-carotene; breast milk samples were analyzed for retinol and retinyl esters, total retinol and β-carotene. Results Fifty-three women after bariatric surgery and 66 controls were recruited. Postpartum serum retinol was significantly higher in women after bariatric surgery in the univariate analysis (P<0.0001) and confirmed in the multiple linear mixed model (P=0.0001). Breast milk colostrum retinol and transitional milk total retinol were significantly greater in the bariatric surgery group in the univariate analysis (P=0.03 and P=0.02, respectively), but not after adjusting for confounders. Serum β-carotene in the third trimester and postpartum were lower (P<0.0001 and P=0.003, respectively) in the bariatric surgery group but not after adjusting for confounders. Vitamin A deficiency was high in both groups in serum and breast milk samples. Conclusion Nutritional deficiencies in breastfeeding women after bariatric surgeries may in fact be less common than in control women in an inner city.

Objectives To measure the tocolytic effect of the combination of the oxytocin receptor antagonist atosiban with the β-mimetic agent fenoterol on human myometrium of pregnant women. Methods An in vitro study of contractility in human myometrium at the Laboratory of the Department of Obstetrics, University Hospital of Zürich, Switzerland, was performed. Thirty-six human myometrial biopsies were obtained during elective caesarean sections of singleton pregnancies at term. Tissue samples were exposed to atosiban, fenoterol and the combination of atosiban with fenoterol. Contractility was measured as area under the curve during 30 min of spontaneous contractions. The effect of treatment was expressed as the percentage of change from basal activity during 30 min of exposure. Differences were calculated using a paired Wilcoxon signed-rank test. An additive effect of dual tocolysis was assumed when no significant difference was detected between the observed and expected inhibition of dual tocolysis. When inhibition was greater or lower than expected, the dual combination was characterised as “synergistic” or “antagonistic”, respectively. Results Atosiban and fenoterol alone suppressed contractions by a median of 43.2% and 29.8%, respectively. The combination of atosiban plus fenoterol was measured at a level of 67.3% inhibition. There was no significant difference in the expected (63.2%) and observed inhibition effect of dual tocolysis (P=0.945). Conclusion This study demonstrated an additive effect of dual tocolysis of atosiban and fenoterol on human myometrium in vitro , but no synergistic or antagonistic effect.

Background Hemorrhage is a critical contributor to maternal morbidity but estimation of blood loss at delivery is frequently inaccurate. Due to this inaccuracy we sought to examine blood transfusion as a surrogate marker for morbidity in a large non-population based consecutive cohort. Methods A retrospective analysis of prospectively gathered data was carried out at two university institutions serving a heterogeneous urban obstetric population from January to December 2016. Data were analyzed to determine whether individual characteristics were associated with perinatal transfusion. Hematological indices and requirement for other blood products were also characterized. Results A total of 16,581 deliveries were recorded during the study and 1.7% (289/16,581) of the cohort required red cell transfusion. Those who received transfusion were more likely to be nulliparous, and to deliver <37 weeks’ or >42 weeks’ gestation. They were also more likely to have a macrosomic infant (birthweight >4 kg) and to have had a multiple pregnancy. Characteristics not associated with risk of transfusion included obesity [18% (52/289) vs. 15% (2445/16,292); P=0.18], and maternal age ≥35 years [28% (82/289) vs. 33% (5537/16,292); P=0.05]. Additional blood products were necessary in a small number of patients who received red cells. Conclusion The rate of transfusion in a contemporary Irish cohort has risen compared with previous data. Several variables associated with transfusion are consistent with older studies but importantly; maternal obesity and advanced maternal age are not associated with transfusion. These data may encourage the investment of resources in a population previously considered low-risk and, following future studies, to improve strategies aimed at limiting blood transfusion.

Background The objective of the study was to compare the effect of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) dietary supplementation on their concentration in total lipids (TL) and lipid fractions of maternal and umbilical vein (UV) blood. The specific objective was to analyze the impact of EPA and DHA supplementation on pregnancy outcome and neonatal birth weight. Methods Women were randomly single-blinded (randomized controlled trial; ISRCTN36705743) allocated to the group receiving EPA and DHA supplementation (supplemented group) or the group receiving placebo-corn oil (control group) in the time period from January 1 st , 2016 until March 1 st , 2017. Women in the supplemented group (n=45) took 360 mg EPA and 240 mg DHA daily while controls (n=42) were given a placebo. Maternal and UV bloods were obtained at delivery. After lipid extraction, phospholipids (PL), cholesterol esters (CE), triacylglycerols (TG) and non-esterified fatty acids were separated by thin layer chromatography and analyzed by gas chromatography. Results Higher DHA concentrations in TL (37.24±21.87 mg/L), PL (13.14±8.07 mg/L) and triacylglycerols (2.24±2.21 mg/L) were recorded in mothers from the supplemented group when compared to the study group (TL 21.89±14.53 mg/L; P<0.001; PL 9.33±5.70 mg/L; P=0.013; TG 0.56±0.43 mg/L; P<0.001). Higher DHA concentrations in UV samples were found in TL (11.51±7.34 mg/L), PL (5.29±3.31 mg/L) and triacylglycerols (0.62±0.46 mg/L) from the supplemented groups compared with controls (TL 7.37±3.60 mg/L; P=0.002; PL 3.52±2.19 mg/L; P=0.005; TG 0.40±0.46 mg/L; P=0.035). The ratio of AA:DHA was lower in maternal (2.43) and UV serum (4.0) of the supplemented group than in the control group (maternal 3.85 P<0.001; UV 4.91 P<0.001). Conclusion The study demonstrated the higher ratio of AA/DHA in the control group indicating that pregnant women on the traditional Herzegovina diet need supplementation with DHA and EPA.

Aim: To assess the effect of psychotropic drugs on fetal behavior using four-dimensional (4D) ultrasound in the third trimester of pregnancy. Methods: Fetal behavior was assessed using Kurjak’s antenatal neurodevelopmental test (KANET) using 4D ultrasound between 28 and 36 weeks of gestation. Thirty healthy (control group) and 10 psychotropic-drug-administered pregnant (case group) women were studied. The total value of the KANET score and values of each parameter (eight parameters) were compared between the two groups. Results: The total KANET score was normal (except for one fetus in the case group: total score of 9) 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 any of the eight parameters. Conclusion: Our results showed that there is no difference in fetal behavior between fetuses of normal pregnant women and those of psychotropic-drug-administered pregnant women in the third trimester of pregnancy. These results suggest that psychotropic drugs may not affect fetal behavioral development in utero . However, the data and their interpretation in the present study should be taken with some degree of caution because of the small number of subjects studied. Further studies involving a larger sample size are needed to assess the effect of psychotropic drugs on fetal neurobehavior during pregnancy.

Background As conflicting results have been reported about the association of reversed flow on the aortic isthmus (AoI) and adverse perinatal results in fetal growth restriction (FGR), we aim to compare perinatal outcomes (including tolerance to labor induction) of late-onset FGR between those with anterograde and reversed AoI flow. Methods This was an observational retrospective cohort study on 148 singleton gestations diagnosed with late-onset FGR (diagnosis ≥32+0 weeks), with an estimated fetal weight (EFW) <10 th centile and mild fetal Doppler alteration: umbilical artery (UA) pulsatility index (PI) >95 th centile, middle cerebral artery (MCA)-PI <5 th centile or cerebral-placental ratio <5 th centile. Anterograde AoI flow was present in n=79 and reversed AoI flow in n=69. Delivery was recommended from 37 weeks in both groups. Perinatal results were compared between the groups. Results The global percentage of vaginal delivery of fetuses with anterograde and reversed blood flow was 55.7% vs. 66.7% (P=0.18) and the percentage of cesarean section (C-section) for non-reassuring fetal status was 12.7% vs. 15.9% (P=0.29), respectively. When evaluating those that underwent labor induction, the vaginal delivery rate was 67.9% vs. 77.2% (P=0.17), respectively. There were no significant differences regarding any other perinatal variables and there were no cases of severe morbidity or mortality. Conclusion We observed that the presence of reversed AoI flow does not worsen perinatal outcomes on fetuses with late-onset growth restriction with mild Doppler alterations. Attempt of labor induction is feasible in these fetuses regardless of the direction of AoI flow.

Background The Doppler effect has allowed the characterization of several vessels in maternal-fetal circulation that have been used for practical purposes. Our review of the literature showed a paucity of information about fetal pulmonary artery pressure (FMPAP) and its behavior in regard to gestational age (GA). The objectives of the study were to evaluate a formula to calculate the main FMPAP and its correlation with GA. Methods A total of 337 fetuses without obvious pathology were studied prospectively using Doppler evaluation of the FMPAP. Using the fetal main pulmonary artery Doppler acceleration time (FMPAT), we obtained the FMPAP using the following formula: FMPAP=90 – (0.62×FMPAT). Regression analyses, Pearson’s bivariate correlation and paired sample t -test were used when appropriate. Results FMPAT increases while FMPAP decreases with GA. Pearson’s correlation coefficient for FMPAP and GA was −0.544 (P-value<0.001) and for FMPAT and GA was 0.556 (P-value<0.001). FMPAP and FMPAT were highly correlated (R=−0.972; P<0.001). Conclusion Pulmonary artery pressure in the fetus decreases with GA.

Objectives To investigate mechanisms of in utero death in normally formed fetuses by measuring amniotic fluid (AF) biomarkers for hypoxia (erythropoietin [EPO]), myocardial damage (cardiac troponin I [cTnI]) and brain injury (glial fibrillary acidic protein [GFAP]), correlated with risk factors for fetal death and placental histopathology. Methods This retrospective, observational cohort study included intrauterine deaths with transabdominal amniocentesis prior to induction of labor. Women with a normal pregnancy and an indicated amniocentesis at term were randomly selected as controls. AF was assayed for EPO, cTnI and GFAP using commercial immunoassays. Placental histopathology was reviewed, and CD15-immunohistochemistry was used. Analyte concentrations >90 th centile for controls were considered “raised”. Raised AF EPO, AF cTnI and AF GFAP concentrations were considered evidence of hypoxia, myocardial and brain injury, respectively. Results There were 60 cases and 60 controls. Hypoxia was present in 88% (53/60), myocardial damage in 70% (42/60) and brain injury in 45% (27/60) of fetal deaths. Hypoxic fetuses had evidence of myocardial injury, brain injury or both in 77% (41/53), 49% (26/53) and 13% (7/53) of cases, respectively. Histopathological evidence for placental dysfunction was found in 74% (43/58) of these cases. Conclusion Hypoxia, secondary to placental dysfunction, was found to be the mechanism of death in the majority of fetal deaths among structurally normal fetuses. Ninety-one percent of hypoxic fetal deaths sustained brain, myocardial or both brain and myocardial injuries in utero . Hypoxic myocardial injury was an attributable mechanism of death in 70% of the cases. Non-hypoxic cases may be caused by cardiac arrhythmia secondary to a cardiac conduction defect.

Objectives To assess the diagnostic value of an early anomaly scan in fetuses with increased nuchal translucency (NT) in the prediction of aneuploidy. Methods In this study we analyzed the data of pregnant women obtained at their first trimester screening in our unit. The detailed examination routinely includes measurement of NT and a scan for anatomical defects. For fetuses with an NT≥3.5 mm, the diagnostic power of early major sonographic findings (MSF) regarding abnormal karyotype was calculated. Results A total of 7352 first trimester examinations were screened. Two hundred and twenty-two fetuses with an NT≥3.5 mm were analyzed. The median gestational age was 12.5 weeks (range 11.0–14.6) and the median NT was 5.1 mm (range 3.5–15.3). MSF were detected in 51.8% of fetuses with increased NT. Among 115 fetuses with MSF, 91 were aneuploid, yielding a positive predictive value for aneuploidy of 79.1%. In the absence of MSF, the negative predictive value was 70.1%. The presence of MSF was significantly predictive for aneuploidy both in bivariate and multivariate regression analysis. Conclusion Our study underlines the importance of a detailed anatomical ultrasound in fetuses with increased NT, as MSF occurred frequently. However, the diagnostic value of MSF regarding aneuploidies appears to be moderate.

Background Small for gestational age (SGA) infants are less likely to develop respiratory distress syndrome (RDS), but more likely to develop bronchopulmonary dysplasia (BPD) and have a higher mortality. Our aim was to focus on outcomes of those with a birth weight less than or equal to 750 g. Methods The mortality, BPD severity, necrotising enterocolitis (NEC), home oxygen requirement and length of hospital stay were determined according to SGA status of all eligible infants in a 5-year period admitted within the first 24 h after birth. Results The outcomes of 84 infants were assessed, and 35 (42%) were SGA. The SGA infants were more mature (P<0.001), had a lower birth weight centile (P<0.001) and a greater proportion exposed to antenatal corticosteroids (P=0.022). Adjusted for gestational age (GA), there was no significant difference in mortality between the two groups (P=0.242), but a greater proportion of the SGA infants developed severe BPD (P=0.025). The SGA infants had a lower weight z-score at discharge (−3.64 vs. −1.66) (P=0.001), but a decrease in z-score from birth to discharge was observed in both groups (median −1.53 vs. −1.07, P=0.256). Conclusion Despite being more mature, the SGA infants had a similar mortality rate and a greater proportion developed severe BPD.

Background Prematurity and its respective comorbidities may result in longer periods of mechanical ventilation in intensive care units (ICU). A method for the assessment of organic maturity would be useful for this population. Heart rate variability (HRV), as an indicator of homeostasis, is a well-established tool for this approach. The objective of the study was to assess HRV in intubated preterm infants in ICU immediately prior to extubation and correlate HRV with clinical evaluation outcomes. Methods A total of 46 preterm infants, 13 (28.2%) males, were prospectively studied and divided into a group with failed extubation (FEG: n=11) and a group with successful extubation (SEG: n=35). HRV was evaluated in time, frequency and nonlinear domains with a Polar RS800 device. HRV measurements were assessed with Kubios HRV Premium Software and statistically analyzed with the StatsDirect Statistical Software, version 1.9.2015 (2002). P<0.05 values were considered as statistically significant. Results There were no significant differences between heart rate variables of failed and successful extubation when analyzing the total group. However, the analysis of the sub-group of preterm infants weighing less than 1000 g showed a clear differentiation between the groups, when the nonlinear variables (approximate entropy, sample entropy and multiscale entropy 1, 2 and 3) were used, demonstrating that the group with successful extubation shows greater complexity and, therefore, relatively greater autonomic stability. Conclusion HRV was effective in predicting failed extubation in preterm infants when evaluated in a nonlinear domain and in preterm infants weighing less than 1000 g.