Circadian characteristics of term and preterm labors.

The labor is a physiological event considered to have its own circadian (diurnal) rhythm, but some of the data remain conflicting, especially for preterm births. In this retrospective study, we analyzed the circadian trends of labor onset times in the Slovenian birth cohort from 1990 to 2018 with over 550,000 cases of singleton births. The number of term and preterm labor onsets was calculated for each hour in a day and circadian trends were evaluated for each of the study groups by modeling with a generalized Poisson distribution linked with the cosinor regression model using logarithmic link function. The induced labors were taken as the control group since the timing of labor depends mostly on the working schedule of personnel and not on the intrinsic rhythmic characteristics. For induced labors, the main peak in the number of labor cases was observed in the late morning hours (around 10 AM) for all gestational ages. The prominence of this peak becomes smaller in spontaneous premature labors with gradually disrupting rhythmicity in very preterm and extremely preterm cases. Labors starting with spontaneous contractions peak between 6 and 7 AM and lose the rhythmicity at 35 weeks of gestation while labors starting with a spontaneous rupture of membranes peak at 1 AM and lose the rhythmicity at 31 weeks of gestation, suggesting differences in underlying mechanisms. According to our knowledge, this is the first study that shows differences of circadian trends between different types of spontaneous labors, i.e., labors initiated with contraction and labors initiated with a spontaneous rupture of membranes. Moreover, the obtained results represent evidence of gradual disruption of rhythmicity from mild to extreme prematurity.

Comparison of Oxytocin vs. Carbetocin Uterotonic Activity after Caesarean Delivery Assessed by Electrohysterography: A Randomised Trial.

Electrohysterography has been used for monitoring uterine contractility in pregnancy and labour. Effective uterine contractility is crucial for preventing postpartum haemorrhage. The objective of our study was to compare postpartum electrohysterograms in women receiving oxytocin vs. carbetocin for postpartum haemorrhage prevention after caesarean delivery. The trial is registered at ClinicalTrials.gov with the identifier NCT04201665. We included 64 healthy women with uncomplicated singleton pregnancies at term scheduled for caesarean section after one previous caesarean section. After surgery, a 15 min electrohysterogram was obtained after which women were randomised to receive either five IU of oxytocin intravenously or 100 µg of carbetocin intramuscularly. A 30 min electrohysterogram was performed two hours after drug application. Changes in power density spectrum peak frequency of electrohysterogram pseudo-bursts were analysed. A significant reduction in power density spectrum peak frequency in the first two hours was observed after carbetocin but not after oxytocin (median = 0.07 (interquartile range (IQR): 0.87 Hz) compared to median = -0.63 (IQR: 0.20) Hz; p = 0.004). Electrohysterography can be used for objective comparison of uterotonic effects. We found significantly higher power density spectrum peak frequency two hours after oxytocin compared to carbetocin.

The effect of antenatal corticosteroids on small-for-gestational age preterm neonates.

OBJECTIVE: Treatment of preterm small-for-gestational age (SGA) neonates with antenatal corticosteroids (ACS) is not entirely straightforward. We sought to examine the effect of a full course of ACS on outcomes of SGA and non-SGA preterm singletons. PATIENTS AND METHODS: We compared maternal characteristics and outcomes of preterm births at <28 and 28 + 0-33 + 0 weeks' gestation that received a complete course of ACS within a week before birth. We further divided our cohort into those with or without a SGA neonate. RESULTS: We included 290 infants: 73 (25.2%) and 217 (74.8%) born at <28 and 28 + 0-33 + 0 weeks' gestation, respectively. Analysis of maternal characteristics showed a strong association of maternal body mass index (p = .01), along with smoking during pregnancy (OR 0.4, 95% CI 0.2, 0.9), with being SGA. Spontaneous onset of delivery more commonly occurred in non-SGA preterm neonates, whereas iatrogenic induction of labor prevailed with SGA neonates (p < .01). There was no significant difference between SGA and non-SGA infants in all the tested neonatal variables except for necrotizing enterocolitis, which prevailed in the SGA group. CONCLUSION: A full course of ACS appears to have the same effect in SGA and non-SGA preterm singletons in our studied cohort on all neonatal outcomes but for necrotizing enterocolitis, where its role in SGA preterm neonates seems to be detrimental rather than beneficial to the fetus.

Cervical cerclage after prior uterine and cervical surgery.

OBJECTIVE: To evaluate cerclage placement after uterine and cervical surgery. PATIENTS AND METHODS: We compared patients with a prior uterine surgery (with or without cervical surgery) with women having a cerclage for the "classical" indications. Under the classical indications fall history of one or more second-trimester pregnancy losses related to painless cervical dilation, prior cerclage due to painless cervical dilation in the second trimester, painless cervical dilation in the second trimester, ultrasonographic finding with a history of prior preterm birth, prior spontaneous preterm birth at less than 34 weeks of gestation and short cervical length (less than 25 mm) before 24 weeks of gestation. RESULTS: Forty-seven (44.8%) patients had uterine surgery whereas 58 (55.2%) had the "classical" indications for cerclage. The risk of birth at <37 weeks and birth weight <2500 g was similar, but lower for cerclage after previous uterine/cervical surgery for births >37 weeks (OR 0.3, 95% CI 0.1, 0.8) and hence, for birth weights >2500 g (OR 0.4, 95% CI 0.2-0.9). Both groups had similar incidence of preterm rupture of membranes, chorioamnionitis, need for induction of labor, cesarean births as well as low Apgar scores and admission rates to the NICU. CONCLUSIONS: The major goals of reducing births at <37 weeks and low birth weight of <2500 g are achievable with a cerclage in patients with a prior uterine/cervical surgery as it is in patients with a "classical" indication for cerclage placement.

Usefulness of COVID-19 screen-and-test approach in pregnant women: an experience from a country with low COVID-19 burden.

OBJECTIVES: Information on the usefulness of screen-and-test strategies of pregnant women for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is lacking. METHODS: We retrospectively reviewed the Ljubljana Maternity Hospital database and searched for pregnant women, who were admitted to the hospital between March 15 and May 16, 2020, for a planned procedure or hospitalization. Their medical records were examined and SARS-CoV-2 test results were retrieved. RESULTS: During the two-month period analyzed, there were a total of 265 scheduled admissions of pregnant women to our hospital. Two hundred two (76.2%) were tested for SARS-CoV-2 1 day prior to admission. All tested negative for SARS-CoV-2 RNA, regardless of having coronavirus disease 2019 (COVID-19)-compatible signs or symptoms (n=28) or not (n=174). CONCLUSIONS: In a population with a low SARS-CoV-2 burden, usefulness of universal testing of pregnant women before admission to the hospital is limited. We recommend that obstetric units in regions with low SARS-CoV-2 burden enforce rational use of personal protective equipment and diligent screening protocols using targeted questionnaires, whereas SARS-CoV-2 laboratory testing should be performed only in screen-positives: those with high clinical suspicion of COVID-19 and/or suspected epidemiological history.

Assessing Velocity and Directionality of Uterine Electrical Activity for Preterm Birth Prediction Using EHG Surface Records.

The aim of the present study was to assess the capability of conduction velocity amplitudes and directions of propagation of electrohysterogram (EHG) waves to better distinguish between preterm and term EHG surface records. Using short-time cross-correlation between pairs of bipolar EHG signals (upper and lower, left and right), the conduction velocities and their directions were estimated using preterm and term EHG records of the publicly available Term-Preterm EHG DataSet with Tocogram (TPEHGT DS) and for different frequency bands below and above 1.0 Hz, where contractions and the influence of the maternal heart rate on the uterus, respectively, are expected. No significant or preferred continuous direction of propagation was found in any of the non-contraction (dummy) or contraction intervals; however, on average, a significantly lower percentage of velocity vectors was found in the vertical direction, and significantly higher in the horizontal direction, for preterm dummy intervals above 1.0 Hz. The newly defined features-the percentages of velocities in the vertical and horizontal directions, in combination with the sample entropy of the EHG signal recorded in the vertical direction, obtained from dummy intervals above 1.0 Hz-showed the highest classification accuracy of 86.8% (AUC=90.3%) in distinguishing between preterm and term EHG records of the TPEHGT DS.

Gestational diabetes mellitus in underweight women.

Objective: To compare outcomes of pregnancies complicated by gestational diabetes mellitus (GDM) in underweight women with those of normal pregravid BMI.Methods: We used a population-based dataset to identify singleton pregnancies complicated by GDM in underweight and normal weight women.Results: Among women with GDM, we identified 301 and 6494 women with pregravid underweight and normal BMI. Underweight women were younger, more often nulliparous, and had lower birth weight (p < .05) and lower incidence of birth weight > 4000 g (OR 0.3, 95% CI 0.1, 0.6) as compared to normal weight GDM women.Conclusions: It appears that pregravid maternal weight rather than GDM might be responsible for larger babies. A dose-response relationship should be established, however.

The effect of interaction between parity, gestational diabetes, and pregravid obesity on the incidence of preeclampsia.

Objective: To examine the effect of parity, prepregnancy obesity and gestational diabetes on the incidence of preeclampsia in singleton pregnancies using a population-based dataset.Methods: We used the national perinatal information system (NPIS) to identify singleton pregnancies complicated by preeclampsia and analyzed dichotomous-independent variables: being obese or normal weight before pregnancy, being primiparous or multiparous, and being without gestational diabetes mellitus (GDM), with GDMA1, or GDMA2.Results: We found a significantly higher incidence of pregravid obesity among primiparas with preeclampsia (OR 1.6, 95% CI 1.55, 1.66). The data indicate that multiparas had always a significantly lower incidence of preeclampsia, regardless if the women had GDMA1, GDMA2 or had no GDM, and regardless of being of normal weight or obese before pregnancy. The data indicate that the incidence of preeclampsia was not influenced by GDM status, irrespective of parity pregravid BMI category.Conclusions: Our data indicate that GDM is not significantly associated with the development of preeclampsia.

Effect of pre-gravid body mass index on outcomes of pregnancies following in vitro fertilization.

PURPOSE: To examine the effect of pre-gravid body mass index (BMI) on perinatal outcomes in in vitro fertilization (IVF) singleton pregnancies. METHODS: Retrospective population-based cohort study. All singleton pregnancies delivered at ≥ 22 weeks' in Slovenia between 2002 and 2015 were included. Logistic regression analysis was used to examine the relationship between BMI category and outcomes, controlling for potential confounding variables. Interaction term was included to evaluate whether effects of obesity on perinatal outcomes differ in IVF vs. non-IVF pregnancies. We counted the frequencies of hypertensive disorders of pregnancy, gestational diabetes, cesarean delivery, preterm births, and small as well as large for gestational age neonates, neonatal respiratory distress syndrome, neonatal intraventricular hemorrhage, and perinatal deaths. RESULTS: Pre-gravid overweight and obesity were associated with higher rates of hypertensive disorders, gestational diabetes, and cesarean deliveries in both IVF and non-IVF pregnancies. Pre-gravid underweight was associated with small for gestational age neonates in IVF and non-IVF pregnancies. There was a significantly lower effect of pre-gravid obesity on the incidence of hypertensive disorders (odds ratio (OR) 0.7; 95% confidence interval (CI) 0.5-0.9) and cesarean delivery (OR 0.8; 95% CI 0.7-0.99) in IVF vs. non-IVF pregnancies. The effect of pre-gravid obesity on neonatal mortality was significantly greater in IVF compared to non-IVF pregnancies (OR 4.6; 95% CI 1.4-15.8). CONCLUSIONS: Pre-gravid BMI has an important effect on perinatal outcomes in pregnancies following IVF.

Effects of vaginal progesterone for maintenance tocolysis on uterine electrical activity.

AIM: The effectiveness of vaginal progesterone for maintenance tocolysis after arrested preterm labor remains controversial. Myometrial contractility can be assessed objectively and non-invasively after progesterone treatment by monitoring uterine electromyography (EMG). We examined the effects of vaginal progesterone on uterine EMG after successful acute tocolysis. METHODS: This was a randomized, double-blind, single-center study performed between 2012 and 2015. Thirty women who experienced preterm labor between 24 0/7 and 33 6/7 weeks were randomly allocated to groups administered either 400 mg vaginal progesterone or a placebo 48 h after acute tocolysis. EMG measurements were taken prior to and 1 h and 2 h following treatment. Mann-Whitney U tests were used to compare EMG power density spectrum peak frequency and peak amplitude, propagation velocity of EMG signals, and duration and number of EMG bursts in 30 min recordings between the groups (P < 0.05). RESULTS: EMG propagation velocity was higher in patients receiving the placebo compared to those treated with progesterone at 1 h (27.83 ± 10.66 vs 15.60 ± 2.94 cm/s) and 2 h (26.97 ± 13.39 vs 15.12 ± 2.58 cm/s) following treatment (P = 0.001). PDS peak frequencies were higher in the placebo compared to the progesterone group at 2 h following treatment (0.54 ± 0.11 vs 0.44 ± 0.06 Hz; P = 0.003). CONCLUSIONS: Treatment of 400 mg of vaginal micronized progesterone as maintenance tocolysis significantly reduces the propagation velocity of electrical signals within the myometrium and is associated with a shift toward lower uterine electrical signal frequencies.

The effect of gestational diabetes, pre-gravid maternal obesity, and their combination ('diabesity') on outcomes of singleton gestations.

OBJECTIVE: To assess the effect of the combination of gestational diabetes mellitus (GDM) and pre-gravid obesity ('diabesity') in singleton gestations. METHODS: We compared perinatal outcomes of singleton gestations in mothers with GDM and pre-gravid obesity, with GDM but with normal pre-gravid BMI, and obese mothers without GDM. RESULTS: We compared diabesity mothers (n = 1525, 24.4% of mothers with GDM, 9.9% of all obese women) to mothers with GDM but with normal BMI (n = 4704, 75.6% of mothers with GDM) and to obese mothers without GDM (n = 13,937, 90.1% of all obese mothers). Obesity, with and without GDM, increased the odds of having chronic hypertension whereas preeclampsia appears to be influenced by obesity only, as were the risk of births at <33 weeks' gestation, of birth weight >4000 g, low 5-min Apgar scores and NICU admissions. CONCLUSION: Obesity (without diabetes) is more frequently associated with adverse perinatal outcomes than diabesity or GDM in non-obese mothers. A campaign to decrease pre-gravid obesity should have at least the same priority as any campaign to control GDM.

A dose-response relation exists between different classes of pre-gravid obesity and selected perinatal outcomes.

OBJECTIVE: To examine if a "dose-response" relation exists between different classes of pre-gravid obesity and selected perinatal outcomes. METHODS: We evaluated 16,566 obese mothers, including 12,064 (72.8%), 3410 (20.6%), and 1092 (6.6%) with obesity class I, II, and III, respectively. We compared maternal age, primiparity, gestational age at birth, birth weight, GDM, hypertensive disorders, and the incidence of cesarean sections. RESULTS: There was a significantly increased incidence (from class I to class III) for GDM (8.5-14.4%), chronic hypertension (2.8-9.0%), gestational hypertension (6.7-14.2%), and for preeclampsia (5.3-9.3%). No such relationship existed for birth weight and gestational duration. CONCLUSION: Classes of obesity during pregnancy exhibit a "dose-response" relationship with maternal morbidity, but no such relationship was found with pregnancy duration and birth weight.

Growth curves for twins in Slovenia.

Abnormalities of fetal growth are more common in twins. We introduce the growth curves for monitoring fetal growth in twin pregnancies in Slovenia. Slovenian National Perinatal Information System for the period between 2002 and 2010 was used to calculate birth weight percentiles for all live born twins for each week from 22nd to 40th week. The calculated percentiles of birth weight for all live-born twins in Slovenia served as the basis for drawing 'growth' curves. The calculated growth curves for twins will help accurately diagnose small or large twin fetuses for their gestational age in the native central European population.

Perinatal Advantages and Disadvantages of Being Underweight before Pregnancy: A Population-Based Study.

AIMS: To evaluate the advantages and disadvantages of being underweight before pregnancy. METHODS: Cohort study of a large population-based dataset of singleton births was used to compare maternal and neonatal outcomes of pre-gravid underweight body mass index (BMI <18.5 kg/m2) women with pre-gravid normal weight controls (BMI 18.5-24.9 kg/m2). RESULTS: A total of 10,995 pre-gravid underweight and 146,155 pre-gravid normal weight mothers were compared. The mean maternal age and gestational age were not different but lean mothers were significantly and more frequently primiparous, had a higher incidence of births at <36 and <32 weeks' gestation, and had a significantly higher incidence of low and very low birth weight infants. Lean mothers had a significantly lower incidence of birth weights >4,000 g, less cesarean births and a lower incidence of gestational diabetes and hypertensive disorders. CONCLUSIONS: A tradeoff exists between the advantages of being lean before pregnancy in terms of less maternal morbidity in return for gaining a more advanced gestational age and higher birth weight.

Does an ideal prototype of a twin mother exist?

Objective To evaluate the association of a set (or the lack thereof) of pre-gravid maternal features with a better outcome in terms of gestational age and birth weight of twins. Methods Analysis of a Slovenian population-based cohort of all dichorionic twin pairs born at ≥22 weeks during an 11-year period from 2002 to 2013. The independent variables included tall stature (≥170 cm), multiparity, and normal pregravid body mass index (BMI). The outcome variables included gestational age and total twin birth weight. Results We studied 3232 dichorionic twins. Being "tall", multiparous, and with a normal pregravid BMI was significantly associated with a higher total twin birth weight, more advanced gestational age, fewer sets with a total twin birth weight <3000 g, fewer births at ≤32 weeks, more pairs with a total twin birth weight >5000 g and more pairs born at ≥37 weeks. In contrast, women with the converse features had a significantly worse outcome. Being just multiparous was different only in the incidence of total twin birth weight >5000 g. Conclusion Maternal stature >170 cm, being multiparous, and having a normal pregravid BMI is association with improved outcomes in terms of gestational age and birth weight of twins.

Outcome of monochorionic-biamniotic twins conceived by assisted reproduction: a population-based study.

Objecive: To evaluate the perinatal outcome of monochorionic-diamniotic twins conceived by assisted reproduction technology (ART). METHODS: We compared data from a national population-based perinatal registry on perinatal outcomes of monochorionic-diamniotic twins conceived by ART with their dichorionic counterparts and with spontaneous monochorionic-diamniotic twins. We compared maternal characteristics, pregnancy complications and perinatal outcomes. RESULTS: Monochorionic-diamniotic twin pregnancies (n=45) comprised 5.5% of all ART twins, and 9.3% of all monochorionic twins in this dataset. ART does not appear to increase the already high risk of monochorionicity compared to spontaneous conception, with the latter having an increased incidence for birth weight <1500 g [odds ratio (OD) 2.6, 95% confidence interval (CI) 1.2-5.4]. CONCLUSION: Our results disagree with hospital-based data and suggest that monochorionic-diamniotic twins following ART are not at increased risk of adverse perinatal outcomes compared to spontaneous monochorionic-diamniotic twins as well as to dichorionc twins conceived by ART.

Uterine electromyography during active phase compared with latent phase of labor at term.

INTRODUCTION: In a prospective study in a tertiary university hospital we wanted to determine whether uterine electromyography (EMG) can differentiate between the active and latent phase of labor. MATERIAL AND METHODS: Thirty women presenting at ≥37(0/7) weeks of gestation with regular uterine contractions, intact membranes, and a Bishop score <6. EMG was recorded from the abdominal surface for 30 min. Latent phase was defined as no cervical change within at least 4 h. Student's t-test was used for statistical analysis (p ≤ 0.05 significant). Diagnostic accuracy of EMG was determined by receiver operator characteristics (ROC) analysis. The integral of the amplitudes of the power density spectrum (PDS) corresponding to the PDS energy within the "bursts" of uterine EMG activity was compared between the active and latent labor groups. RESULTS: Seventeen (57%) women were found to be in the active phase of labor and 13 (43%) were in the latent phase. The EMG PDS integral was significantly higher (p = 0.02) in the active (mean 3.40 ± 0.82 µV) compared with the latent (mean 1.17 ± 0.33 µV) phase of labor. The PDS integral had an area under the ROC curve (AUC) of 0.80 to distinguish between active and latent phases of labor, compared with number of contractions on tocodynamometry (AUC = 0.79), and Bishop score (AUC = 0.78). The combination (sum) of PDS integral, tocodynamometry, and Bishop score predicted active phase of labor with an AUC of 0.90. CONCLUSIONS: Adding uterine EMG measurements to the methods currently used in the clinics could improve the accuracy of diagnosing active labor.

The relationship between cesarean section rate in term singleton pregnancies, maternal weight, and weight gain during pregnancy.

OBJECTIVE: Pregravid maternal weight and appropriate weight gain during pregnancy might be associated with increased cesarean section rate. STUDY DESIGN: We used data from the Slovenian National Perinatal Information System to select singleton pregnancies born at ≥38 weeks, during the period between 2003 and 2012. We calculated the frequencies of urgent and elective cesarean sections (UCS and ECS, respectively) in mothers who gained less than, more than, and as recommended by the Institute of Medicine (IOM) according to their pregravid body mass index (BMI). RESULTS: The analysis included 170,121 women who delivered singletons ≥38 weeks. A total of 24,327 (14.3%) women underwent cesarean section: 14,692 (8.6%) UCS and 9635 (5.7%) ECS. The frequency of cesareans, both UCS and ECS, increases as BMI increases irrespective of weight gain pattern. The frequency of urgent cesareans in all women increases and that of elective cesareans among obese women decreases as the level of weight gain increases from undergainers to overgainers. CONCLUSION: The combination of pregravid BMI and weight gain pattern is an important determinant of cesarean section rates at term.

Do tall women beget larger babies?

OBJECTIVE: To evaluate the possible relationship between maternal height and fetal size. PATIENTS AND METHODS: We used a population-based cohort of apparently healthy mothers of singletons to evaluate quartiles of the maternal height distribution for parity, being overweight or obese, and for gestational age and birth weight parameters. We also generated birth weight by gestational age curves for each quartile. RESULTS: We analyzed data of 198,745 mothers. Mother from the four quartiles had similar parity, pre-gravid BMI, and gestational age at birth. Short mothers had a significantly higher rate of VLBW and LBW and 2501-4000 g infants, for an OR = 1.38 (95% CI: 1.17-1.62), OR = 2.2 (95% CI: 2.05-2.37) and OR = 1.82 (95% CI: 1.73-1.87) between the shortest and tallest mothers, respectively. By contrast, the opposite trend was noticed for birth weights >4000 g, for an OR = 2.77 (95% CI: 2.65-2.89) between the tallest and shortest mothers. A very similar "growth curve" was apparent until 33 weeks, when a slower growth velocity was observed for shorter compared with taller women. CONCLUSIONS: Maternal stature does not appear to be associated with gestational age but significantly influences birth weight. Height-related differences between mothers appears to begin after 33 weeks' gestation.

Maternal obesity in singleton versus twin gestations: a population-based matched case-control study.

OBJECTIVE: To examine the impact of pre-pregnancy obesity on adverse outcomes in twin compared to singleton pregnancies. METHODS: Dichorionic twin gestations with maternal body mass index >30 were matched to three singleton controls. Both obese groups were matched (1:3) with non-obese controls. Rates of preeclampsia, gestational diabetes, cesarean section, and preterm birth were compared. RESULTS: One hundred eighty-nine dichorionic twin pregnancies in obese mothers were matched to 567 twin pregnancies in non-obese mothers, and to 567 singleton pregnancies in obese mothers. The latter were matched to 1701 non-obese mothers with singletons. Preeclampsia was more common in obese mothers with both twins and singletons (odds ratio (OR) 3.95, 95% confidence interval (CI) 2.18-7.16 and OR 6.53, 95% CI 3.75-11.4, respectively) as was gestational diabetes (OR 4.35, 95% CI 2.18-8.69; OR 5.53 95% CI 3.60-8.50). Obese mothers with singletons were more likely to deliver abdominally, but the cesarean rates were obesity independent in twins. Obese mothers were more likely to deliver at < 34 weeks in both twin and singleton groups (OR 1.65, 95% CI 1.10-2.48, and OR 2.41, 95% CI 1.21-4.77, respectively). CONCLUSION: Obesity-attributable adverse outcomes are lower in twins compared to singletons. Obesity increases the risk of preterm birth regardless of plurality.