Oral microbiome and preterm birth.

Background: The etiology of preterm birth (PTB) is heterogeneous and not yet well known. Maternal periodontal disease has been investigated for decades and is a known risk factor for adverse pregnancy outcomes. However, no particular bacterial species or higher taxonomic order has been found as causative of PTB, leading to studies of the whole oral microbiome. In order to determine if and how the composition of the oral microbiome is associated with PTB, we performed a large case-control study including women with term (TB) and PTB. Methods: We compared oral microbiomes in PTB to TB, to examine differences in the microbial richness, diversity, and differential abundance of specific taxa. We obtained oral swab samples from 152 Caucasian pregnant women who were classified as either PTB (≤36 6/7 weeks, n = 61) or TB (≥38 0/7 weeks, n = 91) in exclusion of any other major medical or obstetric conditions. The oral microbiomes of these women were characterized by 16S ribosomal RNA (rRNA) gene sequencing of the V3-V4 region on the MiSeq platform. Results: The dominant microorganisms at the phylum level in all pregnant women regardless of birth week outcomes as belonging to Firmicutes, Proteobacteria, Bacteroidetes, Fusobacteria, and Actinobacteria. The phyla Firmicutes and Bacteroidetes were relatively more abundant in women with a PTB than in women with a TB, while Proteobacteria was less prevalent in women with a PTB. At the genus level, Veillonella, Prevotella, and Capnocytophaga were enriched in the PTB, and while many of the members of these genera could not be resolved to the species level, Veillonella massillensis was shown to be increased in the PTB group. Conclusion: We identified the genera Veillonella, Prevotella, and Capnocytophaga in the maternal oral microbiome as being associated with PTB independently of clinically apparent infection, uterine anomalies, and other pregnancy complications, including placenta previa, and placental abruption. The clarification of the role of those taxa in the etiology of PTB merits further research.

Perinatal outcomes in women with severe acute respiratory syndrome coronavirus 2 infection: comparison with contemporary and matched pre-COVID-19 controls.

OBJECTIVES: To compare perinatal outcomes in women with vs. without severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: Perinatal outcomes in SARS-CoV-2 positive pregnant women who delivered at our institution between October 27th 2020 and January 31st 2021 were compared to SARS-CoV-2 negative pregnancies (contemporary controls) and historical 2019 controls matched by maternal age, pre-pregnancy body mass index and parity. Testing was performed based on symptoms or close contact at any time during pregnancy and as part of universal screening at hospital admission. Multivariable log-linear regression models were used adjusting for potential confounders (p < 0.05 statistically significant). RESULTS: One thousand three hundred seventeen women delivered at our institution during the study period. 1,124 (85%) tested negative and 193 (15%) positive for SARS-CoV-2. 189 (98%) were infected during third trimester. 19 (10%) were asymptomatic, 171 (89%) had mild to moderate coronavirus disease 2019 (COVID-19), and 3 (2%) were critically ill with one case of maternal death. There were no significant differences in preterm birth, small-for-gestational-age birth weight, congenital anomalies, operative delivery, intrapartum hypoxia, and perinatal mortality in SARS-CoV-2 positive pregnancies compared to contemporary reference group or historical controls from pre-COVID-19 period. Labor was more commonly induced in SARS-CoV-2 positive women compared to reference SARS-CoV-2 negative group (68 [35%] vs. 278 [25%], adjusted odds ratio 1.62; 95% confidence interval 1.14-2.28). CONCLUSIONS: SARS-CoV-2 infection in pregnancy was not strongly associated with adverse perinatal outcomes. While the majority of SARS-CoV-2 positive women had no or mild/moderate symptoms, 2% were critically ill, with one case of maternal death.

Treatment of preeclampsia at extremely preterm gestation with therapeutic plasma exchange.

AIMS: Different forms of apheresis have been proposed as potential therapeutic approaches to remove soluble Fms-like tyrosine kinase-1 (sFlt-1) and allow safe pregnancy prolongation in cases of extremely preterm preeclampsia. This is a follow-up study presenting our experiences with therapeutic plasma exchange (TPE) in 5 women with preeclampsia at < 28 weeks of gestational age. MATERIALS AND METHODS: All women received standard treatment for preeclampsia and 2 - 3 TPE treatments per week. Blood samples for sFlt-1 and placental growth factor (PlGF) measurements were collected before and after each TPE. RESULTS: Seventeen TPE procedures were performed, 2 - 5 per patient. TPE significantly reduced sFlt-1 (by 35 ± 6%), sFlt-1/PlGF ratio (by 24 ± 13%), and to a lesser degree also PlGF (by 12 ± 16%), with a rebound observed on day 1 post procedure. TPE procedures were well tolerated by pregnant women and fetuses. Stabilization of sFlt-1 allowed pregnancy prolongation for a median of 8 (range 2 - 14) days from first TPE and for a median of 10 (range 4 - 17) days from hospital admission. There were no signs of increased risks of adverse neonatal outcome associated with TPE. One neonate died due to extreme prematurity 3 days after delivery, 2 had bronchopulmonary dysplasia, and 1 had retinopathy of prematurity. CONCLUSION: This study provides new evidence of effective reduction in sFlt-1 and sFlt-1/PlGF ratio with TPE treatment, which seems to allow a clinically meaningful prolongation of pregnancy. Controlled studies are necessary to convincingly show the potential benefit of apheresis treatment in preeclampsia at extremely preterm gestation.

The impact of the COVID-19 pandemic on organised cervical cancer screening: The first results of the Slovenian cervical screening programme and registry.

BACKGROUND: The COVID-19 pandemic threatens the impact of cervical cancer screening and global cervical cancer elimination goals. As cervical cancer screening programmes were adjusting to the new situation, we evaluated the intensity, quality, and outcomes of cervical cancer screening in Slovenia in the first seven months of the pandemic. METHODS: Historical observational study on data from a population-based cervical cancer screening registry. Number of cervical cytopathology (screening and follow-up), histopathology (diagnostic procedures, invasive procedures and number of newly diagnosed CIN2+ cases) and HPV test results from the entire Slovenian women population between January 1st and September 30th 2020 were compared to a three-year average of the years 2017-19. FINDINGS: A two-month screening lock-down between March 12th and May 8th 2020 resulted in an epidemic deficit of screening (-92%), follow-up (-70%), and HPV triage tests (-68%), as well as invasive diagnostic (-47%) and treatment (-15%) of cervical lesions. Time to diagnosis and treatment did not increase; times to laboratory results fluctuated but stayed within standards. Slovenia has entered the second epidemic intending to add as little as possible to the pandemic deficit of screening smears (-23%) and yearly CIN2+ cases (-10%). Women aged 30-39 were most affected, with the highest pandemic deficit of screening smears (-26%) and yearly CIN2+ cases (-19%). INTERPRETATION: The pandemic has deeply affected all levels of our lives. New vulnerable groups and inequalities have emerged that require recognition and action. To prevent long-term increases in the cervical cancer burden due to the COVID-19 pandemic, it is crucial that organised screening is maintained and monitored in settings where it can be safely and comprehensively provided. FUNDING: None.

Therapeutic plasma exchange and dextran-sulfate plasma adsorption as extracorporeal treatments of extremely preterm preeclampsia with fetal growth restriction.

AIM: To evaluate effectiveness and safety of therapeutic plasma exchange (TPE) and dextran-sulfate plasma adsorption (DSA) for extracorporeal removal of soluble Fms-like tyrosine kinase-1 (sFlt-1) as part of expectant management of preeclampsia at extremely preterm gestational age. METHODS: Retrospective case series of six patients with preeclampsia at <28 weeks of gestation, treated with DSA or TPE. Laboratory results, clinical characteristics and neonatal outcomes were collected from charts and National Perinatal Information System. RESULTS: Fetal growth restriction (FGR) was diagnosed in all cases. Pregnancy was prolonged for a median of 14 (range 5-74) days from admission and 10 (3-73) days from first apheresis. A mixed effects model showed a decrease in sFlt-1 and sFlt-1/PlGF ratio during DSA/TPE (significant effect of time [before/after]), which was comparable between DSA and TPE (no effect of procedure type). Median absolute reduction in sFlt-1 was 42% (inter-quartile range [IQR] 13%-57%) during DSA and 34% (16%-40%) during TPE; for sFlt-1/PlGF ratio it was 29% (22%-36%) and 38% (29%-42%), respectively. All procedures were well tolerated by fetuses. Anaphylactoid reaction, often with angioedema, occurred in 4/6 patients undergoing DSA and was attributed to bradykinin activation. One patient developed wound hematoma after cesarean section, possibly attributed to depletion coagulopathy. CONCLUSIONS: As potential novel treatment of early preeclampsia, a non-selective and widely available TPE was comparable to DSA regarding sFlt-1 reduction but was associated with fewer side-effects. Both seem to allow maternal stabilization and pregnancy prolongation even when early preeclampsia is complicated by FGR.

Maternal and perinatal outcomes in high compared to low risk pregnancies complicated by severe acute respiratory syndrome coronavirus 2 infection (phase 2): the World Association of Perinatal Medicine working group on coronavirus disease 2019.

BACKGROUND: It has still to be ascertained whether severe acute respiratory syndrome coronavirus 2 infection in pregnancy is associated with worse maternal and fetal outcomes compared to low risk gestations. OBJECTIVE: This study aimed to evaluate maternal and perinatal outcomes in high- and low-risk pregnancies complicated by severe acute respiratory syndrome coronavirus 2 infection. STUDY DESIGN: This was a multinational retrospective cohort study involving women with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection from 76 centers from 25 countries in Europe, the United States, South America, Asia, and Australia from April 4, 2020, to October 28, 2020. The primary outcome was a composite measure of maternal mortality and morbidity, including admission to the intensive care unit, use of mechanical ventilation, or death. The secondary outcome was a composite measure of adverse perinatal outcome, including miscarriage, fetal loss, neonatal and perinatal death, and admission to the neonatal intensive care unit. All outcomes were assessed in high- and low-risk pregnancies. Pregnancies were considered high risk in case of either preexisting chronic medical conditions in pregnancy or obstetrical disorders occurring in pregnancy. The Fisher exact test and logistic regression analysis were used to analyze the data. RESULTS: A total of 887 singleton pregnancies who tested positive for severe acute respiratory syndrome coronavirus 2 infection using reverse transcription-polymerase chain reaction of nasal and pharyngeal swab specimens were included in the study. The risk of composite adverse maternal outcomes was higher in high-risk pregnancies than in low-risk pregnancies (odds ratio, 1.52; 95% confidence interval, 1.03-2.24; P=.035). In addition, women carrying high-risk pregnancies were at higher risk of hospital admission (odds ratio, 1.48; 95% confidence interval, 1.07-2.04; P=.002), presence of severe respiratory symptoms (odds ratio, 2.13; 95% confidence interval, 0.41-3.21; P=.001), admission to the intensive care unit (odds ratio, 2.63; 95% confidence interval, 1.42-4.88), and invasive mechanical ventilation (odds ratio, 2.65; 95% confidence interval, 1.19-5.94; P=.002). When exploring perinatal outcomes, high-risk pregnancies were at high risk of adverse perinatal outcomes (odds ratio, 1.78; 95% confidence interval, 0.15-2.72; P=.009). However, such association was mainly because of the higher incidence of miscarriage in high-risk pregnancies compared with that in low-risk pregnancies (5.3% vs 1.6%, P=.008); furthermore, there was no difference in other explored outcomes between the 2 study groups. At logistic regression analysis, maternal age (odds ratio, 1.12; 95% confidence interval, 1.02-1.22; P=.023) and high-risk pregnancy (odds ratio, 4.21; 95% confidence interval, 3.90-5.11; P<.001) were independently associated with adverse maternal outcomes. CONCLUSION: High-risk pregnancies complicated by severe acute respiratory syndrome coronavirus 2 infection were at higher risk of adverse maternal outcomes than low-risk pregnancies complicated by severe acute respiratory syndrome coronavirus 2 infection.

Preterm delivery risk in infertile women who conceived after reproductive surgery: natural conception versus IVF/ICSI.

STUDY QUESTION: Is preterm delivery an infertility treatment-related adverse outcome in infertile women who conceived after reproductive surgery? SUMMARY ANSWER: Compared with matched fertile women, preterm delivery appears to be a modest infertility treatment-related adverse outcome in infertile women who have reproductive surgery then conceived naturally or after IVF/ICSI. WHAT IS KNOWN ALREADY: Most observational studies have shown that women who receive any infertility treatment are more likely to deliver preterm than do fertile women. However, studies on the outcome of pregnancies in infertile women who conceive naturally after reproductive surgery are scarce. STUDY DESIGN, SIZE, DURATION: This was a single-centre historical two-part study: cohort and matched cohort study. Anonymized data of 761 infertile women who conceived after reproductive surgery and 758 fertile women were obtained by linking three computerized databases from 1 July 2012 to 31 December 2015. PARTICIPANTS/MATERIALS, SETTING, METHODS: In the cohort study, we evaluated the association between the mode of conception and preterm delivery <37 and <32 gestational weeks in 703 infertile women, with a singleton pregnancy who conceived after reproductive surgery, using logistic regression adjusted for relevant co-variates to calculate the adjusted odds ratio with a 95% CI. In the matched cohort study, we evaluated preterm delivery as infertility treatment-related adverse outcome using the propensity score (PS) method. The matched cohort comprised 758 infertile women and 758 fertile women with a twin or singleton pregnancy. Infertile women conceived after reproductive surgery either naturally or through IVF/ICSI. Infertile and fertile women were matched using PS matching. Infertile and fertile women were matched for pre-defined risk factors for preterm delivery. Three infertile women out of an original 761 were not included in the analysis because they lacked all required matching variables. We performed a 1:1 matching with an optimal matching algorithm with a caliper width of the linear predictor of 0.1 standard deviations. The effect of reproductive surgery on preterm delivery was evaluated in the PS-matched sample using Pearson's χ2 test and presented as the odds ratio (OR) with 95% CI. All women delivered at the Department of Perinatology, University Medical Centre Ljubljana, Slovenia. MAIN RESULTS AND THE ROLE OF CHANCE: Among 761 infertile women who conceived after reproductive surgery, 428 (56.2%) women conceived naturally and 333 (43.8%) conceived after IVF/ICSI. The incidence of twin pregnancies was significantly lower after natural conception (2.6% vs 14.1%). Among the 703 infertile women with a singleton pregnancy, 417 (59.3%) conceived naturally and 286 (40.7%) conceived after IVF/ICSI. Adjusted for maternal age and parity in infertile women with singleton pregnancies, IVF/ICSI showed a moderate association with preterm delivery <32 weeks. Compared with natural conception after reproductive surgery, the odds for preterm delivery after IVF/ICSI was 1.07 (95% CI 0.63-1.81) <37 weeks and 2.25 (95% CI 0.80-6.34) <32 weeks. Preterm delivery appears to be a modest infertility treatment-related adverse outcome. Compared with fertile women in the PS-matched sample, infertile women who conceived after reproductive surgery either naturally or after IVF/ICSI the odds of preterm delivery <37 weeks were 1.31 (95% CI 0.97-1.78) and odds of preterm delivery <32 weeks were 1.57 (95% CI 0.78-3.18). However, none of the estimations were statistically significant. LIMITATIONS, REASONS FOR CAUTION: The main limitations of the study were the retrospective design, the heterogeneity of the types of reproductive surgery performed and underlying reproductive pathologies. The low number of preterm deliveries in the present study might influence the precision of estimations. WIDER IMPLICATIONS OF THE FINDINGS: The present study aims to alter the prevailing opinion that reproductive surgery should only be considered preceding IVF to increase implantation and pregnancy rates after IVF. It implies that in selected infertile women who have had reproductive surgery, a high rate of natural conception, a low rate of multiple pregnancies, and a modest infertility treatment-related effect on preterm delivery should be the reasons to encourage natural conception after reproductive surgery. Furthermore, by allowing for natural conception, we can avoid a high-cost invasive medical procedure. STUDY FUNDING/COMPETING INTEREST(S): The study received no funding. We have no competing interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Effect of hysteroscopic septum resection on preterm delivery rate in singleton pregnancies.

INTRODUCTION: Uterine septum is the most common uterine anomaly and is often found during the work-up in primary infertile women. In this study, we aimed to evaluate the potential effect of hysteroscopic septum resection (HSR) on preterm delivery (PTD) in primary infertile women who had singleton pregnancies. MATERIAL AND METHODS: We analyzed 420 singleton pregnancies after primary infertility treatment and compared the PTD rates in women who underwent previous HSR (cases) and women who did not undergo previous operative hysteroscopy or cervical dilation (controls), regardless of the modality of conception (spontaneous or by in vitro fertilization). RESULTS: We did not find significant differences between cases and controls for the incidence of overall PTD rate (p = .237), PTD before 32 gestational weeks (p = .848), and between 32 and 37 gestational weeks (p = .324), premature rupture of membranes (p = .419), and neonatal birth weight (p = .129). Overall, the risk of spontaneous PTD <37 gestational weeks after HSR was not found to be significantly higher compared to controls (RR 1.29, 0.61-2.73 95% CI; p = .561). CONCLUSION: According to our results, previous HSR could be not considered a risk factor for PTD in singleton pregnancies, regardless of the modality of conception (spontaneous or by in vitro fertilization).

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.

Effect of current guidelines on prevention of pre-eclampsia with low-dose aspirin in primary settings: A population-based case-control study.

OBJECTIVE: To evaluate the effect of low-dose aspirin, which was administered at or before the 16th week of pregnancy due to maternal characteristics and history of a pre-existing medical condition, on prevention of pre-eclampsia, and on the birth of a small-for-gestational-age (SGA) neonate without pre-eclampsia in nulliparas in primary settings. METHODS: We performed a case-control study using population-based data on 47 271 nulliparas with a singleton pregnancy who delivered in Slovenia from 2013 to 2017. The treated group received low-dose aspirin. For the untreated group, propensity score matching was used to perform a 1:1 matching. In the matched sample, we calculated the odds ratios (OR) with a 95% confidence interval (95% CI) with a two-way test for pre-eclampsia, as well as SGA neonates. RESULTS: In the treated group (n=584), the odds for an SGA neonate were significantly increased by 42.7% (OR 1.427, 95% CI 1.001-2.034). However, we found no significant effect on the odds for pre-eclampsia (OR 1.308, 95% CI 0.847-2.022). CONCLUSIONS: In anticipation of more substantial population-based data studies, in the Slovenian population, preventive treatment with low-dose aspirin due to maternal characteristics and history of a pre-existing medical condition is not beneficial for the prevention of pre-eclampsia and can harm fetal growth.

Changes in perinatal outcomes after implementation of IADPSG criteria for screening and diagnosis of gestational diabetes mellitus: A national survey.

OBJECTIVE: To compare perinatal outcomes before and after implementation of the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria for testing of gestational diabetes mellitus (GDM). METHODS: A national, perinatal, registry-based cohort study of prospectively collected data was conducted. Patients with diabetes type 1 or 2 were excluded. Outcomes of 135 786 pregnancies before (January 1, 2004 to May 31, 2010) and 140 524 after (June 1, 2011 to December 31, 2017) the introduction of IADPSG criteria were compared using Student t test and χ2 test (P<0.05 was significant). Multivariable logistic regression was used to compare outcomes controlling for potential confounders. RESULTS: Prevalence of GDM increased from 2.6% to 9.7% (adjusted odds ratio 3.92; 95% confidence interval 3.78-4.08). Incidence of large-for-gestational age (LGA), macrosomia (birth weight >4500 g), Erb's palsy, and hypertensive disorders in pregnancy decreased despite increasing maternal age and pre-pregnancy obesity. Rates of cesarean delivery increased in both GDM and non-GDM groups, with a less pronounced increase in GDM mothers. Incidence of small-for-gestational age (SGA) increased in GDM but not in non-GDM group. CONCLUSION: Implementation of IADPSG criteria in a country with a relatively low prevalence of GDM did not result in higher rates of cesarean delivery and was associated with reductions in LGA and hypertensive disorders in pregnancy.

Abuse of pregnant women in the healthcare system.

Objective: The purpose of this study was to determine the incidence of abuse in healthcare system during pregnancy and its impact on pregnancy outcomes.Materials and methods: A validated screening Norvold Abuse Questionnaire for the identification of female victims of four kinds of abuse: emotional, physical, sexual, and the abuse in the healthcare system was anonymously offered to all women in the first 2 days postpartum.Results: The study group consisted of 1018 women, 6.2% of which reported experiencing abuse in healthcare system during pregnancy. Affected women had a higher incidence of preterm delivery (OR 2.4; 95% CI 1.2-4.8) and cesarean section rate (OR 2.0; 95% CI 1.1-3.6). Sexual abuse and abuse in healthcare system during childhood were associated with abuse in healthcare system during pregnancy (OR 4.4; CI 95% 1.2-16.2 and OR 6.9; CI 95% 1.3-35.4, respectively).Conclusions: Our study indicates that as many as 6.2% of pregnant women experience abusive encounters with perinatal care providers. These pregnancies eventually end more often preterm and by cesarean section. This possibly causal relationship should be further explored.

Establishing a Differential Marker Profile for Pregnancy Complications Near Delivery.

OBJECTIVE: The aim of this work was to define a differential marker profile for pregnancy complications near delivery. METHODS: We enrolled pregnant women who were referred to the outpatient pregnancy clinic of the University Medical Center, Ljubljana, Slovenia, due to symptoms of pregnancy complications and women with a history of pregnancy complications attending the high-risk hospital clinic for close surveillance. They were evaluated for prior risk and were tested for biophysical and biochemical markers at the time of enrolment. Biochemical markers included the pro- and anti-angiogenic markers, along with additional previously reported markers of potential value, all tested by various formats of immuno-diagnostics. Biophysical markers included blood pressure, sonographic markers, and EndoPAT. Statistical differences were determined with Kruskal-Wallis and Mann-Whitney tests for continuous parameters, and Pearson χ2 for categorical values. p < 0.05 was considered significant. RESULTS: The cohort included 125 pregnant patients, 31 developed preeclampsia (PE) alone (13 were <34 weeks' gestation), 16 had intrauterine growth restriction (IUGR) alone (12 were <34 weeks), 42 had both IUGR and PE (22 were <34 weeks), and 15 had an iatrogenic preterm delivery (PTD; 6 were <34 weeks). Twenty-one were unaffected and delivered a healthy baby at term. Mean arterial blood pressure and proteinuria were significantly higher in PE and PE+IUGR but not in pure IUGR or PTD. In PE, IUGR, and PE+IUGR, the levels of soluble fms-like tyrosine kinase 1 (sFlt-1) and soluble endoglin (sEng) were significantly higher, while placental growth factor (PlGF) was very low compared to unaffected controls and PTD. PE, IUGR, and PE+IUGR also had a high anti-angiogenic ratio (sFlt-1/PlGF) and a low proangiogenic ratio of PlGF/(sFlt-1+Eng). Levels of inhibin A were significantly higher in pure PE across subgroups but had many extreme values, which made it a poor differentiator. Higher uterine artery Doppler pulsatility indexes were detected in PE, IUGR, and PE+IUGR, with similar resistance indexes and peaks of systolic velocity. A significantly different marker level between PE and IUGR was found using arterial stiffness that was 10 times higher in PE; concurrently with an increase of the reactive hyperemia index, both were accompanied by a slight increase in placental protein 13. Higher tumor necrosis factor alpha (TNFα) differentially identified iatrogenic very early PTD (<34 weeks). CONCLUSION: Arterial stiffness can serve as a major marker to differentiate PE (with/without IUGR) from pure IUGR near delivery. TNFα can differentiate iatrogenic early PTD from other complications of pregnancy and term IUGR.

Contextual-relationship and stress-related factors of postpartum depression symptoms in nulliparas: a prospective study from Ljubljana, Slovenia.

BACKGROUND: For a significant proportion of women, postpartum depression (PPD) is the first mood episode in their lives, yet its aetiology still remains unclear. Insecure attachment in close adult relationships is considered to be a risk factor for depressive symptoms. This study aimed to gain further insight into the risk factors for postpartum depression symptoms (PPDS) of nulliparas in Slovenia and to examine vulnerability to developing depressive symptoms, with an emphasis on contextual and stress-related characteristics. METHODS: The sample consisted of 156 nulliparas in the third trimester of pregnancy enrolled in a childbirth preparation program. The following instruments were applied: Experiences in Close Relationships-Revised, the Edinburgh Postpartum Depression Scale (EPDS), the Zung Anxiety Scale and a question battery designed by the research team including questions about emotional support and work-related stress. Logistic regression was used to test the association between demographic, social, environmental, personality and attachment variables and PPD of nulliparas (EPDS ≥10), controlling for baseline (prepartum) depression score. A multivariable linear regression model was built with the postpartum EPDS continuous score as a dependent variable. RESULTS: 28/156 (17,9%) were evaluated as being at risk for depression (EPDS≥10) in the last trimester and 25/156 (16%) at six weeks postpartum. The results of the logistic regression model controlled for prepartum depression score showed that increased risk for developing PPDS was associated with anxiety level postpartum, intimate-partner-attachment anxiety postpartum, and elevated stress due to loss of employment or an unsuccessful search for employment in the previous year. The results of the multivariable regression model, however, showed the association with education and postpartum anxiety with PPDS continuous score; EPDS after giving birth was higher for more educated and more anxious primiparas. CONCLUSIONS: Our findings demonstrate the importance of anxiety symptoms and higher education level in assessments of nulliparas' mental health. The results of our study show and confirm the results of previous research that anxiety symptoms in the immediate postpartum period are likely to be associated with depressive symptoms in nulliparas. The results also suggest that higher level of education of first-time mothers might not be a protective factor, especially for nulliparas with the university level of education. Further studies on larger samples should be considered.

Planned home birth in Slovenia-Are we ready?

Nowadays, women want a more intimate and familiar atmosphere during labour, which results in increased planned home birth rates. Every woman has the autonomy to decide where she will give birth; however, it is important that she is informed of risks and advantages beforehand. Home births can be distinguished between planned and unplanned home births. Planned home births can be conducted by professional birth attendants (licensed midwives) or birth assistants (doulas, etc). The rates of Slovenian women who decided to deliver at home are increasing year by year. Researches on home births still present discordant data about home birth safety. Their findings have shown that the main advantage of home birth is a spontaneous birth without medical interventions, especially in multiparous low-risk women. The main disadvantage, however, is a higher risk for neonatal death, in particular on occurrence of complications requiring a transfer to hospital and surgical intervention. Global guidelines emphasize careful selection of candidates suitable for home birth, well-informed pregnant women, education of birth attendants, and strict formation of transfer indications.

Total gestational weight gain and the risk of preeclampsia by pre-pregnancy body mass index categories: a population-based cohort study from 2013 to 2017.

Background Identifying the risk factors for preeclampsia (PE) is essential for the implementation of preventive actions. In the present study, we aimed at exploring the association between total gestational weight gain (GWG) and PE. Methods We performed a population-based cohort survey of 98,820 women with singleton pregnancies who delivered in Slovenia from 2013 to 2017. Aggregated data were obtained from the National Perinatal Information System (NPIS). The main outcome measure was the incidence of PE. The main exposure variable was total GWG standardized for the gestational duration by calculating the z-scores. The associations between total GWG and PE stratified by pre-pregnancy body mass index (BMI) categories adjusted for a variety of covariates were determined using multivariable logistic regression. We calculated the crude odds ratio (OR) and adjusted odds ratio (aOR) with a 95% confidence interval using a two-way test. Results Excessive GWG was associated with increased odds of PE in all pre-pregnancy BMI categories. The increase in the odds of PE by 445% was the highest in underweight women and by 122% was the lowest in obese women. Low GWG was associated with decreased odds of PE in all pre-pregnancy BMI categories except in normal-weight women with a GWG below -2 standard deviation (SD) and underweight women. The decrease in the odds of PE by 67% was the highest in obese women and by 41% was the lowest in normal-weight women. Conclusion Excessive GWG is a significant risk factor for PE, especially in underweight women, while low GWG is an important protective factor against PE, especially in obese women.

Customised birthweight standard for a Slovenian population.

Objective To produce a customised birthweight standard for Slovenia. Methods This retrospective study used a cohort from the National Perinatal Information System of Slovenia (NPIS). Prospectively collected information from pregnancies delivered in all of Slovenia's 14 maternal hospitals between 1st January 2003 and 31st December 2012 was included. Coefficients were derived using a backward stepwise multiple regression technique. Results A total of 126,627 consecutive deliveries with complete data were included in the multivariable analysis. Maternal height, weight in early pregnancy and parity as well as the baby's sex were identified as physiological variables, with coefficients comparable to findings in other countries. The expected 280-day birthweight, free from pathological influences, of a standard size mother (height 163 cm, weight 64 kg) in her first pregnancy was 3451.3 g. Pathological influences on birthweight within this population included low and high maternal age, low and high body mass index (BMI), smoking, pre-existing and gestational diabetes and pre-existing and gestational hypertension. Conclusion The analysis confirmed the main physiological variables that affect birthweight in studies from other countries, and was able to quantify additional pathological factors of maternal age and gestational diabetes. Development of a country-specific customised birthweight standard will aid clinicians in Slovenia with the distinction between normal and abnormal small-for-gestational age (SGA) fetuses, thus avoiding unnecessary interventions and improving identification of at risk pregnancies, and long-term outcomes for infants.

Correlation between uterine artery Doppler and the sFlt-1/PlGF ratio in different phenotypes of placental dysfunction.

OBJECTIVE: To explore correlations between the sFlt-1/PlGF ratio and uterine arteries (UtA) Doppler indexes in placental dysfunction-related disorders (PDD). METHODS: We prospectively included women with a singleton pregnancy with preeclampsia (PE) only (n = 22), preeclampsia with fetal growth restriction (FGR) (n = 32), FGR only (n = 12), or normal pregnancy (n = 29). RESULTS: In PDDs, significantly positive correlations between the sFlt-1/PlGF ratio and the mean UtA pulsatility (mPI-UtA), as well as the resistance index (mRI-UtA) were found (p = 0.015, p = 0.019, respectively), but not in normal pregnancies. PDD with signs of impaired placentation, evidenced by the increased sFlt-1/PlGF ratio and mPI-UtA, was found in 50.0%, and, by the increased sFlt-1/PlGF ratio and mRI-UtA, in 65.2%. PDD without signs of impaired placentation, evidenced by the increased sFlt-1/PlGF ratio but normal mPI-UtA, was found in 24.2%, and, by the increased sFlt-1/PlGF ratio but normal mRI-UtA, in 7.6%. A substantial proportion of women with signs of impaired placentation were diagnosed with FGR with or without PE. CONCLUSION: In PDD, the sFlt-1/PlGF ratio and UtA Doppler indexes increase proportionally. Correlations between the sFlt-1/PlGF ratio and UtA Doppler indexes might help to distinguish between PDDs with and without impaired placentation. However, further studies are needed to explore the correlations in different phenotypes of PDD.

Peripheral arterial tonometry and angiogenic biomarkers in preeclampsia.

OBJECTIVE: To evaluate changes in vascular function and serum biomarkers in women with and without preeclampsia (PE) to create a model for the easier and more precise diagnosis of PE in the future. METHODS: Endothelial function and arterial stiffness were evaluated using peripheral arterial tonometry and concentrations of placental growth factor (PlGF), soluble fms like tyrosine kinase 1 (sFlt-1) and soluble endoglin (sEng) were determined by immunoassay. RESULTS: Arterial stiffness deteriorates and endothelial function is better in women with PE compared with a healthy pregnancy. Women who developed PE had a decreased PlGF and PlGF/(sFlt-1+ sEng) ratio and an increased sEng, and sFlt-1/PlGF ratio. CONCLUSION: Peripheral arterial analysis did provide additional information beyond serum biomarkers in the diagnosis of PE.

Infant mortality and causes of death by birth weight for gestational age in non-malformed singleton infants: a 2002-2012 population-based study.

OBJECTIVE: To explore the associations between birth weight for gestational age (GA) and infant mortality as well as causes of infant death. STUDY DESIGN: A population-based observational study conducted between 2002 and 2012 included 203,620 non-malformed singleton live births from Slovenia. Poisson regression analyses were performed to estimate the crude relative risk (RR) and adjusted RR (aRR) for infant mortality by birth weight percentiles stratified by the GA subgroups term, moderate-to-late preterm, very preterm and extremely preterm. RESULTS: Compared with appropriate for GA (AGA) term infants (referent-AGA), infant mortality was significantly higher in small for GA (SGA) term infants [aRR=2.79 (1.41-5.50)], with significant cause-specific infant mortality risk for neuromuscular disorders [RR=10.48 (2.62-41.91)]. The differences in infant mortality and cause-specific infant mortality in preterm subgroups between referent-AGA and SGA were insignificant. CONCLUSIONS: In the Slovenian population, birth weight for GA is significantly associated with infant mortality only in infants born at term.