Volume 49, Issue 2

Objectives Preterm labour is the leading cause of hospitalization during pregnancy. In France, it results in more than 60,000 births before 37 weeks of gestation every year. Recent studies suggest that detection of placental α-microglobulin-1 (PAMG-1) in vaginal secretions among women presenting symptoms of preterm labour with intact membranes has good predictive value for the onset of spontaneous preterm delivery within 7 days. The test is especially interesting, in that the repetition of antenatal corticosteroids for foetal lung maturation is no longer recommended in France and the effect of the initial administration is most beneficial in the 24 h to 7 days afterwards. Methods We included all studies listed in PubMed and clinicaltrials.gov with the terms “PAMG-1” and either “preterm labor” or “preterm labour”, while excluding all studies on the subject of “rupture of the membranes” from 2000 through 2017. Ten studies were thus included. Results In women who had both the PAMG-1 and foetal fibronectin test, the PAMG-1 test was statistically superior to the measurement of cervical length for positive predictive value (p<0.0074), negative predictive value (p=0.0169) and specificity (p<0.001) for the prediction of spontaneous preterm delivery within 7 days. Conclusions The use of PAMG-1 may make it possible to target the women at risk with a shortened cervix on ultrasound (<25 mm) those with an imminent preterm delivery and therefore to adapt management, especially the administration of antenatal corticosteroid therapy.

Objectives To compare the long-term effects of antenatal betamethasone (ANS, ≤16 mg, =24 mg and >24 mg) in twins on infant and childhood growth. Methods A retrospective cohort follow up study among 198 twins after ANS including three time points: U1 first neonatal examination after birth and in the neonatal period; U7 examination from the 21st to the 24th month of life and U9 examination from the 60th to the 64th month of life using data from copies of the children’s examination booklets. Inclusion criteria are twin pregnancies with preterm labor, cervical shortening, preterm premature rupture of membranes, or vaginal bleeding, and exposure to ANS between 23+5 and 33+6 weeks. Outcome measures are dosage-dependent and sex-specific effects of ANS on growth (body weight, body length, head circumference, body mass index and ponderal index) up to 5.3 years. Results Overall, 99 live-born twin pairs were included. Negative effects of ANS on fetal growth persisted beyond birth, altered infant and childhood growth, independent of possible confounding factors. Overall weight percentile significantly decreased between infancy and early childhood by 18.8%. Birth weight percentiles significantly changed in a dose dependent and sex specific manner, most obviously in female-female and mixed pairs. The ponderal index significantly decreased up to 42.9%, BMI index increased by up to 33.8%. Conclusions ANS results in long-term alterations in infant and childhood growth. Changes between infancy and early childhood in ponderal mass index and BMI, independent of dose or twin pair structure, might indicate an ANS associated increased risk for later life disease. Synopsis First-time report on long-term ANS administration growth effects in twin pregnancies, showing persisting alterations beyond birth in infant and childhood growth up to 5.3 years as potential indicator of later life disease risk.

Objectives To report clinical data on maternal outcome, mode of delivery and immediate neonatal outcome in women infected with COVID-19. Methods Retrospective data collection. Results A total of 8.6% of the total population of hospitalised SARS-CoV-2 positive pregnant women were admitted to a critical care unit. The premature birth rate for births before 34+0 weeks of gestation among pregnant women who tested positive for SARS-CoV-2 was 7.1%. One newborn (3.6%) tested positive for SARS-CoV-2 two days after birth and showed symptoms. Conclusions Pregnant women with COVID-19 seem to be at higher risk of invasive ventilation, admission to a critical care unit and preterm birth, and should therefore be considered a high-risk-population.

Objectives To evaluate the relationship between Coronavirus Disease 2019 (COVID-19) in pregnancy and adverse perinatal outcomes. The secondary aim is to analyze the diagnostic value of hematologic parameters in COVID-19 complicated pregnancies. Methods The current study is conducted in a high volume tertiary obstetrics center burdened by COVID-19 pandemics, in Turkey. In this cohort study, perinatal outcomes and complete blood count indices performed at the time of admission of 39 pregnancies (Study group) complicated by COVID-19 were compared with 69 uncomplicated pregnancies (Control group). Results There was no significant difference between the obstetric and neonatal outcomes of pregnancies with COVID-19 compared to data of healthy pregnancies, except the increased C-section rate (p=0.026). Monocyte count, red cell distribution width (RDW), neutrophil/lymphocyte ratio (NLR), and monocyte/lymphocyte ratio (MLR) were significantly increased (p<0.0001, p=0.009, p=0.043, p<0.0001, respectively) whereas the MPV and plateletcrit were significantly decreased (p=0.001, p=0.008) in pregnants with COVID-19. ROC analysis revealed that the optimal cut-off value for MLR was 0.354 which indicated 96.7% specificity and 59.5% sensitivity in diagnosis of pregnant women with COVID-19. A strong positive correlation was found between the MLR and the presence of cough symptom (r=41.4, p=<0.0001). Conclusions The study revealed that, pregnancies complicated by COVID-19 is not related with adverse perinatal outcomes. MLR may serve as a supportive diagnostic parameter together with the Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) in assessment of COVID-19 in pregnant cohort.

Objectives Our aim was to evaluate the effect of standard surgical and N-95 respiratory mask use on maternal oxygen saturation, vital signs and result on non-stress tests in term pregnancies. Methods It is a prospective observational study. The study included healthy, not in labor, singleton pregnant women of 370/7–410/7 weeks who were applied to our hospital for routine obstetric control examination between March 1, 2020, and August 31, 2020. Patients were randomised by coin toss method. Oxygen saturation, systolic, and diastolic arterial blood pressure, pulse, respiratory rate, and temperature of pregnant women using surgical masks and respiratory masks were measured before and after the non-stress test. The tolerance of the masks was also evaluated. Student’s t-test was used for variables showing parametric distribution and the Mann Whitney U-test was used for non-parametric tests. The categorical variables between the groups was analyzed by using the Chi square test or Fisher Exact test. The statistical significance level was taken as p<0.05 in all tests. Results A total of 297 pregnant women using masks were included in the study. The effect of mask type on oxygen saturation before and after the non-stress test was found to be significant (97.1±1.8 corresponds to 95.3±2.6 for the surgical mask, p=0.0001; 97.8±1.7 corresponds to 93.7±2.0 for the respiratory mask, p=0.0001). Mask tolerance of patients using respiratory masks was significantly higher than those using surgical masks (mean 8, 1–10, p=0.0001). Conclusions Surgical mask and respiratory mask usage decreased significantly in oxygen saturation in term pregnancies.

Objectives Pregnancy-associated venous thromboembolism (VTE), including deep venous thrombosis (DVT) and pulmonary embolism (PE), is associated with increased risk of maternal mortality and morbidity. This study aimed to assess potential risk factors for pregnancy-associated VTE. Methods In this case-control study, women with pregnancy-associated VTE were identified via International Classification of Diseases codes and included if they had been objectively diagnosed with VTE during pregnancy or within six weeks postpartum, from 2004 to 2016, at KK Women’s and Children’s Hospital or Singapore General Hospital in Singapore. Controls, i.e. pregnant women without VTE, were selected from a prospective longitudinal study. The odds ratio (OR) for VTE was computed for a range of maternal and obstetric factors. Results and conclusions From 2004 to 2016, 89 cases of pregnancy-associated VTE and 926 controls were identifed and analysed using logistic regression. The most significant risk factors for pregnancy-associated VTE were smoking (OR 5.44, p=0.0002) and preterm delivery (OR 5.06, p=0.023). Malay race, multiparity, non-O blood group and caesarean section, were also identified to be of higher risk. These risk factors should be useful in the development of thromboprophylaxis strategies for pregnancy and the postpartum period, especially in Singapore.

Objectives This study aimed to investigate the role of prolonged second stage of labour and second stage caesarean section on the risk of spontaneous preterm birth (sPTB) in a subsequent pregnancy. Methods This was a retrospective cohort study of nulliparous women with two consecutive singleton deliveries between 2014 and 2017 at a tertiary centre. In the vaginal delivery cohort, subsequent pregnancy outcomes for women with a prolonged second stage (>2 h) were compared with those with a normal second stage (≤2 h). In the caesarean delivery cohort, women with a first stage or a second stage were compared with the vaginal delivery cohort. The primary outcome was subsequent sPTB. Results A total of 821 women met inclusion criteria, of which 74.8% (614/821) delivered vaginally and 25.2% (207/821) delivered by caesarean section. There was no association between a prolonged second stage in the index pregnancy and subsequent sPTB (aOR 0.70, 95% CI 0.13–3.83, p=0.7). The risk of subsequent sPTB was threefold for those with a second stage caesarean section; however this did not reach statistical significance. Conclusions A prolonged second stage of labour in the index pregnancy is not associated with an increased risk of subsequent sPTB. A second stage caesarean section in the index pregnancy may be associated with an increased risk of subsequent sPTB, however there was no statistically significant difference. These findings are important for counseling and suggest that the effects of these factors are not clinically significant to justify additional interventions in the subsequent pregnancy.

Objectives The objectives of this study were to (i) establish the reference range and mean value for normal levels of C1-esterase inhibitor (C1 INH) during pregnancy, and (ii) investigate the association between C1 INH and uterine atony, as measured by blood loss at delivery. Methods We prospectively studied 200 healthy pregnant women who were registered. We studied C1 INH levels in 188 women at 34 and 35 gestational weeks of pregnancy. The reference range for C1 INH during the third trimester of pregnancy was calculated using the value of C1 INH that was determined at registration. Results The mean value of C1 INH was determined to be 70.3% (95% confidence interval, 68.7–71.9). While the C1 INH levels in four women were determined to be 40% lower than the calculated mean value, amniotic fluid embolism (AFE) did not occur in any of the women studied. Conclusions This study successfully demonstrated that a reference value for C1 INH activity can be established using the methods described herein. Further research is needed to determine whether C1 INH is involved in obstetric coagulopathy syndrome such as amniotic fluid embolism.

Objectives This study aims to present the termination of pregnancy (TOP) rates and elucidate the decision-making process following a prenatal diagnosis of Trisomy 21 in Turkey. Methods This retrospective single-center study was conducted with 146 pregnant women between January 2016 and December 2019 in a tertiary hospital. Data on maternal characteristics, sonographic findings, indications for chromosome analysis, and educational, religious, and economic factors that can influence the parental decision process were collected. Results The TOP rate of Down syndrome (DS) in our center was 78.8%. We concluded that maternal age, earlier diagnosis, indication for chromosome analysis, and previous pregnancies had no effect on the TOP decision. On the other hand, not having a minor or a major sonographic sign, employed mothers, middle- and high-income families, and families having a secondary or higher education tended to terminate the pregnancy affected by DS at statistically higher rates. Conclusions There are many studies worldwide investigating the TOP preferences for DS. However, there is limited data about TOP rates and influential factors affecting the decision-making process in Muslim countries. This study contributes by clarifying the factors in the decision-making process and elucidating perspectives about TOP in a Muslim country with a unique status: Turkey.

Objectives To compare the safety and efficacy between high dose and low dose oxytocin administration for labor augmentation. Methods We searched for the available studies during March 2020 in PubMed, Cochrane Library, Scopus, and ISI Web of science. All randomized clinical trials (RCTs) that assessed safety and efficacy of high dose vs. low dose oxytocin for labor augmentation were considered. The extracted data were entered into RevMan software. Dichotomous and continuous data were pooled as odds ratio (OR) and mean difference (MD) respectively, with the corresponding 95% confidence intervals (CI). Our main outcomes were cesarean delivery rate, spontaneous vaginal delivery rate, uterine hyperstimulation and tachysystole, and labor duration from oxytocin infusion. Results Eight RCTs with 3,154 patients were included. High dose oxytocin did not reduce cesarean delivery rate compared to low dose oxytocin (OR=0.76, 95% CI [0.52, 1.10], p=0.15). After solving the reported heterogeneity, high dose oxytocin did not increase the rate of spontaneous vaginal deliveries vs. low dose oxytocin (OR=1.06, 95% CI [0.84, 1.32], p=0.64). Low dose oxytocin was linked to a significant decline in uterine hyperstimulation and tachysystole (p>0.001). A reduction in labor duration was found in high dose oxytocin group over low oxytocin regimen (MD=−1.02 h, 95% CI [−1.77, −0.27], p=0.008). Conclusions We found no advantages for high dose oxytocin over low dose oxytocin in labor augmentation except in reducing labor duration. Low dose oxytocin is safer as it decreases the incidence of uterine hyperstimulation and tachysystole. More trials are needed to confirm our findings.

Objectives To evaluate the association between extremely elevated alkaline phosphatase (ALKP) levels (above 1000 U/L) and adverse perinatal outcome. Methods A retrospective case series of all parturients with extremely elevated ALKP levels taken throughout pregnancy at a single university-affiliated medical center (2010–2018). Demographics and medical data were retrieved. Following literature review, previously reported similar cases were added to the cohort. We report perinatal outcome of our cohort as well as literature review. Results During study period 11 parturients with high ALKP were identified. Ten more cases were retrieved from PubMed search. Overall, median ALKP levels were 1880 (range 1052–4488 U/L). Reasons for evaluation were mostly nonspecific symptoms (pruritus, headache, abdominal pain) or routine obstetrical evaluation. In 10/12 (83%) cases, elevated ALKP levels were of placental origin; the rest had osteal origin. Median gestational age at delivery was 38 (range 35–41); four (19%) women had preterm delivery. Six patients (29%) had gestational diabetes mellitus and six (29%) had hypertensive disorders. Histopathology of the placenta was available in eight cases: three normal histology (38%) and five with different non-specific pathologies. Conclusions We report the largest case series of extremely elevated levels of ALKP in pregnancy thus far. Our data suggest association with adverse perinatal outcome.

Objectives The aim of this study was to introduce cervical strain elastography to objectively assess the cervical tissue transformation process during induction of labour (IOL) and to evaluate the potential of cervical elastography as a predictor of successful IOL. Methods A total of 41 patients with full-term pregnancies elected for an IOL were included. Vaginal ultrasound with measurement of cervical length and elastography and assessment of the Bishop Score were performed before and 3 h after IOL. The measured parameters were correlated to the outcome of IOL and the time until delivery. Results We observed an association between the strain pattern and the value of the strain ratio 3 h after IOL and a successful IOL (p=0.0343 and p=0.0342, respectively) which can be well demonstrated by the results after 48 h. In our study population the cervical length and the Bishop Score did not prove to be relevant parameters for the prediction of a successful IOL. Conclusions We demonstrated for the first time that the cervical elastography pattern after the first prostaglandine application can help predict the outcome of IOL.

Objectives EXIT (ex-utero intrapartum treatment) procedure is a fetal survival-increasing modification of cesarean section. Previously we found an increase incidence of fetal vascular malperfusion (FVM) in placentas from EXIT procedures which indicates the underlying stasis of fetal blood flow in such cases. This retrospective analysis analyzes the impact of the recently introduced CD34 immunostain for the FVM diagnosis in placentas from EXIT procedures. Methods A total of 105 placentas from EXIT procedures (48 to airway, 43 to ECMO and 14 to resection) were studied. In 73 older cases, the placental histological diagnosis of segmental FVM was made on H&E stained placental sections only (segmental villous avascularity) (Group 1), while in 32 most recent cases, the CD34 component of a double E-cadherin/CD34 immunostain slides was also routinely used to detect the early FVM (endothelial fragmentation, villous hypovascularity) (Group 2). Twenty-three clinical and 47 independent placental phenotypes were compared by χ 2 or ANOVA, where appropriate. Results There was no statistical significance between the groups in rates of segmental villous avascularity (29 vs. 34%), but performing CD34 immunostain resulted in adding and/or upgrading 12 more cases of segmental FVM in Group 2, thus increasing the sensitivity of placental examination for FVM by 37%. There were no other statistically significantly differences in clinical (except for congenital diaphragmatic hernias statistically significantly more common in Group 2, 34 vs. 56%, p=0.03) and placental phenotypes, proving the otherwise comparability of the groups. Conclusions The use of CD34 immunostain increases the sensitivity of placental examination for FVM by 1/3, which may improve the neonatal management by revealing the increased likelihood of the potentially life-threatening neonatal complications.

Objectives Our primary aim was to evaluate the ability of various cerebroplacental ratio (CPR) reference values suggested by the Fetal Medicine Foundation to predict adverse neonatal outcomes in term fetuses exhibiting late-onset fetal growth restriction (LOFGR). Our secondary aim was to evaluate the effectiveness of other obstetric Doppler parameters used to assess fetal well-being in terms of predicting adverse neonatal outcomes. Methods This was a retrospective cohort study of 317 pregnant women diagnosed with LOFGR at 37–40 weeks of gestation between January 1, 2016, and September 1, 2019. Receiver operating characteristic (ROC) curves were drawn to determine the predictive performance of CPR <1, CPR <5th or <10th percentile, and umbilical artery pulsatility (PI) >95th percentile in terms of predicting adverse neonatal outcomes. Results Pregnant women exhibiting LOFGR who gave birth in our clinic during the study period at a mean of 38 gestational weeks (minimum 37+0; maximum 40+6 weeks); the median CPR was 1.51 [interquartile range (IQR) 1.12–1.95] and median birthweight 2,350 g (IQR 2,125–2,575 g). The CPR <5th percentile best predicted adverse neonatal outcomes [area under the curve (AUC) 0.762, 95% confidence interval (CI) 0.672–0.853, p<0.0001] and CPR <1 was the worst predictor (AUC 0.630, 95% CI 0.515–0.745, p=0.021). Of other Doppler parameters, neither the umbilical artery systole/diastole ratio nor the mid-cerebral artery to peak systolic velocity ratio (MCA–PSV) predicted adverse neonatal outcomes (AUC 0.598, 95% CI 0.480–0.598, p=0.104; AUC 0.521, 95% CI 0.396–0.521, p=0.744 respectively). Conclusions The CPR values below the 5th percentile better predicted adverse neonatal outcomes in pregnancies complicated by LOFGR than the UA PI and CPR <1 by using Fetal Medicine Foundation reference ranges.

Objectives Late-onset fetal growth restriction (FGR) has heterogeneous prenatal and postnatal diagnostic criteria. We compared the prenatal and postnatal diagnosis of late-onset FGR and their ability to predict adverse perinatal outcomes. Methods Retrospective cohort study of 5442 consecutive singleton pregnancies that delivered beyond 34 + 0 weeks. Prenatal diagnosis of FGR was based on customized fetal growth standards and fetal Doppler while postnatal diagnosis was based on a birthweight <3rd percentile according to newborn charts (Olsen’s charts and Intergrowth 21st century programme). Perinatal outcomes were analyzed depending on whether the diagnosis was prenatal, postnatal or both. Results A total of 94 out of 5442 (1.7%) were diagnosed as late-onset FGR prenatally. Olsen’s chart and Intergrowth 21st chart detected that 125/5442 (2.3%) and 106/5442 (2.0%) of infants had a birthweight <3rd percentile, respectively. These charts identified 35/94 (37.2%) and 40/94 (42.6%) of the newborns with a prenatal diagnosis of late-onset FGR. Prenatally diagnosed late-onset FGR infants were at a higher risk for hypoglycemia, jaundice and polycythemia. Both prenatally and postnatally diagnosed as late-onset FGR had a higher risk for respiratory distress syndrome when compared to non-FGR. The higher risks for intensive care admission and composite adverse outcomes were observed in those with a prenatal diagnosis of late-onset FGR that was confirmed after birth. Conclusions Current definitions of pre- and postnatal late-onset FGR do not match in more than half of cases. Infants with a prenatal or postnatal diagnosis of this condition have an increased risk of neonatal morbidity even if these diagnoses are not coincident.

Objectives Human milk supports the development of a beneficial newborn intestinal microflora. We have shown previously that human milk had reduced bacteria but unchanged nutrient composition when stored at −20 °C for up to nine months. We suspected declining bacterial colony counts were manifestations of bacterial dormancy and not failure of survival. We investigated differences in selected bacterial colony counts (lactobacillus, bifidobacteria, staphylococcus, streptococcus and enterococcus) in human milk stored for 2 and 12 weeks at −20 °C in either manual or automatic defrost freezers and whether reduced bacterial counts at 12 weeks were the result of dormancy or failure of survival. Methods Freshly expressed milk was obtained from mothers in the NICU, divided into aliquots and stored for 2 and 12 weeks at −20 °C in either automatic or manual defrost freezers. Subsequently, duplicate aliquots, one thawed and the other thawed and maintained at room temperature for 4 h, were plated to assess bacterial colony counts. Results Significant declines in bacterial colony counts were seen from 2 to 12 weeks freezer storage for all bacteria. There were no differences in colony counts between freezer types. Once thawed, no further bacterial growth occurred. Conclusions Short-term freezer storage for 12 weeks resulted bacterial killing. Type of freezer used for storage did not have an impact on bacterial survival. It is unknown whether the paucity of important probiotic bacteria in stored human milk has adverse effects on infants.

Background Umbilical cord (UC) abnormalities are related to neurological outcome and death; specific molecular factors that might be involved are, as yet, unknown; however, protein-coding genes insulin-like growth factor 2 ( IGF2 ) and cyclin-dependent kinase inhibitor 1C ( CDKN1C ) have been identified as potential candidates. Methods An analytical observational study was carried out. Newborn UCs were collected, along with their clinical and morphological features. Immunohistochemical analysis was made on paraffin-embedded sections and quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed in fresh UC tissue for the assessment of gene expression. Results A total of 100 newborns were included. A significant association was found between long UC and prematurity [odds ratio (OR) 9] and long UC and respiratory distress (OR 4.04). Gestational diabetes (OR 8.55) and hypertensive disorders of pregnancy (HDP) (OR 4.71) were found to be related to short UCs. The frequency for abnormal UC length was higher than expected. UC length was positively correlated with maternal, newborn and placental weight. No statistical association was found between IGF2 and CDKN1C (p57) expression and UC length; however, there was a tendency for higher CDKN1C expression in short UCs, while, on the contrary, higher IGF2 expression for long UCs. Conclusion UC length was observed to be associated with maternal and newborn complications. Protein expression, messenger RNA (mRNA) activity and the activity of said genes seem to be related to UC length.

Objectives The coronavirus disease 2019 (COVID-19) had become a worldwide pandemic, however, information is limited on the asymptomatic proportion and thromboembolism risk of pregnant women with infection. Methods All 32 pregnant women with COVID-19 who were admitted to the hospital in Wuhan during the outbreak from January 20 to March 18, 2020, were retrospectively reviewed for the clinical records, laboratory tests, chest CT scans, and neonatal outcomes. Results There were 17 of the 32 patients (53%) with no subjective symptoms before admission, and 13 (41%) remained asymptomatic throughout hospitalization. There were 28 patients (88%) showing typical radiographic evidence of pneumonia on chest CT. The patients with COVID-19 were found in an increased risk of thromboembolism with much higher D-dimer levels than uninfected pregnant women. One neonate with asphyxia and positive immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies was reported. Conclusions The considerable asymptomatic proportion of pregnant women with COVID-19 indicates symptom-based screening would miss a number of cases. Chest CT could provide a useful screening resource during the COVID-19epidemic outbreak. Anticoagulation therapy for the postpartum patients may be helpful for good prognosis. The findings provide important information for the hospital isolation, control strategies and clinical therapy.