Bacterial vaginosis in a subfertile population undergoing fertility treatments: a prospective cohort study.

PURPOSE: This study investigates the role of bacterial vaginosis (BV) on pregnancy rates during various fertility treatments. BV is known to influence several obstetric outcomes, such as preterm delivery and endometritis. Only few studies investigated the effect of BV in subfertile women, and studies found a negative effect on fecundity especially in the in vitro fertilisation population. METHODS: Observational prospective study, 76 couples attending a fertility clinic in the Netherlands between July 2019 and June 2022, undergoing a total of 133 attempts of intra uterine insemination, in vitro fertilization or intra cytoplasmatic sperm injection. Vaginal samples taken at oocyte retrieval or insemination were analysed on qPCR BV and 16S rRNA gene microbiota analysis of V1-V2 region. Logistic regression with a Generalized Estimated Equations analysis was used to account for multiple observations per couples. RESULTS: A total of 26% of the 133 samples tested positive for BV. No significant differences were observed in ongoing pregnancy or live birth rates based on BV status (OR 0.50 (0.16-1.59), aOR 0.32 (0.09-1.23)) or microbiome community state type. There was a tendency of more miscarriages based on positive BV status (OR 4.22 (1.10-16.21), aOR 4.28 (0.65-28.11)) or community state type group III and IV. On baseline qPCR positive participants had significantly higher body mass index and smoked more often. Odds ratios were adjusted for smoking status, body mass index, and socioeconomic status. CONCLUSION: Bacterial vaginosis does not significantly impact ongoing pregnancy rates but could affect miscarriage rates.

Developing an algorithm for the diagnosis of abnormal vaginal discharge in a dutch clinical setting: a pilot study.

Abnormal vaginal discharge may be caused by bacterial vaginosis, vulvovaginal candidiasis, trichomoniasis and/or aerobic vaginitis. For the development of a diagnostic algorithm, tree-based classification analysis was performed on symptoms, signs and bedside test results of 56 patients, and laboratory tests (culture, Nugent score, qPCRs) were compared. Amplicon sequencing of the 16S rRNA gene was used as reference test for bacterial vaginosis and aerobic vaginitis, culture for vulvovaginal candidiasis and qPCR for trichomoniasis. For bacterial vaginosis, the best diagnostic algorithm was to screen at the bedside with a pH and odour test and if positive, to confirm by qPCR (sensitivity 94%; specificity 97%) rather than Nugent score (sensitivity of 59%; specificity 97%; P = 0.031). The analysis for the other infections was less conclusive due to the low number of patients with these infections. For bacterial vaginosis, the developed algorithm is sensitive, specific, and reduces the need for laboratory tests in 50% of the patients.

Perinatal death in a term fetal growth restriction randomized controlled trial: the paradox of prior risk and consent.

BACKGROUND: The disproportionate intrauterine growth intervention trial at term was an intention to treat analysis and compared labor induction with expectant monitoring in pregnancies complicated by fetal growth restriction at term and showed equivalence for neonatal outcomes. OBJECTIVE: To evaluate trial participation bias and to examine the generalizability of the results of an obstetrical randomized trial. STUDY DESIGN: We used data from participants and nonparticipants of a randomized controlled trial-the disproportionate intrauterine growth intervention trial at term (n=1116) -to perform a secondary analysis. This study compared induction of labor and expectant management in women with term growth restriction. Data were collected in the same manner for both groups. Baseline characteristics and neonatal and maternal outcomes were compared. The primary outcome was a composite measure of adverse neonatal outcome. Secondary outcomes were delivery by cesarean delivery and instrumental vaginal delivery; length of stay in the neonatal intensive care, neonatal ward, and the maternal hospital; and maternal morbidity. RESULTS: Nonparticipants were older, had a lower body mass index, had a higher level of education, smoked less, and preferred expectant management. The time between study inclusion and labor onset was shorter in participants than in nonparticipants. Notably, 4 perinatal deaths occurred among nonparticipants and none among participants. Among nonparticipants, there were more children born with a birthweight below the third centile. The nonparticipants who had expectant management were monitored less frequently than the participants in both the intervention and the expectant arm. CONCLUSION: We found less favorable outcomes and more perinatal deaths in nonparticipants. Protocol-driven management, differences between participants and nonparticipants, or the fact that nonparticipants had a preference for expectant management might explain the findings.

Postnatal Catch-Up Growth After Suspected Fetal Growth Restriction at Term.

Objective: The aim of this study was to study growth patterns of children born after suspected fetal growth restriction (FGR) at term and to compare the effect of induction of labor (IoL) and expectant management (EM), also in relation to neurodevelopmental and behavioral outcome at age 2. Methods: We performed a 2 years' follow-up of growth of children included in the Disproportionate Intrauterine Growth Restriction Trial at Term (DIGITAT) study, a Randomized Controlled Trial (RCT) comparing IoL with EM in pregnancies with suspected FGR at term. We collected data on child growth until the age of 2 years. Standard deviation scores (SDSs) for height and weight were calculated at different ages. We assessed the effects of IoL compared with EM and the effects of a birth weight below or above the 3rd or 10th centile on catch-up growth. Target height SDSs were calculated using the height of both parents. Results: We found a significant increase in SDS in the first 2 years. Children born after EM showed more catch-up growth in the first month [height: mean difference -0.7 (95% CI: 0.2; 1.3)] and weight [mean difference -0.5 (95% CI: 0.3; 0.7)]. Children born with a birth weight below the 3rd and 10th centiles showed more catch-up growth after 1 year [mean difference -0.8 SDS (95% CI: -1.1; -0.5)] and after 2 years [mean difference -0.7 SDS (95% CI: -1.2; -0.2)] as compared to children with a birth weight above the 3rd and 10th centiles. SDS at birth had the strongest effect on adverse neurodevelopmental outcome at 2 years of age. Conclusion: After FGR at term, postnatal catch-up growth is generally present and associated with the degree of FGR. Obstetric management in FGR influences postnatal growth. Longer-term follow-up is therefore needed and should be directed at growth and physical health. Clinical Trial Registration: www.ClinicalTrials.gov, identifier SRCTN10363217.

Short report: Post-operative wound infections after the gentle caesarean section.

OBJECTIVES: Worldwide, the caesarean section (CS) is the most performed type of surgery and numbers are still rising. The gentle CS has become a more common procedure as it allows the parents to experience birth. Early and continuous skin-to-skin contact between the mother and her newborn is pursued. Parents are not separated from their newborns and stay with their child in the operation theatre and recovery room. However, data are limited on the incidence of surgical site infections (SSI) after gentle CS. The aim of our study was to examine the risk of postoperative wound infections after gentle CS. Secondary outcomes included other maternal complications and neonatal outcomes. STUDY DESIGN: In this multicenter prospective cohort study, all women who underwent an elective gentle CS between January 2015 and January 2017 were eligible. Demographics, per procedural data, maternal complications and neonatal outcomes were collected. The follow-up lasted until six weeks post partum. RESULTS: Of the 243 performed CSs, two (0.8%) SSIs occurred; one superficial and one deep wound infection. One patient (0.4%) was readmitted for treatment of endometritis. In total, 20 (8.2%) maternal complications were identified. Median time to skin-to-skin contact was 3 minutes (IQR 2-4.25) with a median neonatal oxygen saturation 10 minutes after birth of 95% (IQR 92-98). Mean gestational age was 274 ±â€¯4.1 days (39 + 1 weeks) and mean neonatal pH was 7.28 (±SD 0.07). All children had Apgar scores >7 at 5 minutes after birth. Neonatal admission occurred in 19 cases (7.8%) and neonatal readmission in 10 cases (4.1%). CONCLUSION: The gentle CS seems to be a safe procedure for both mother and child and is not associated with an increased risk of surgical site infections or direct suboptimal neonatal outcomes. Therefore, more intensive mother-child interaction during CS is allowed.

Comparison of Amsel criteria, Nugent score, culture and two CE-IVD marked quantitative real-time PCRs with microbiota analysis for the diagnosis of bacterial vaginosis.

Bacterial vaginosis (BV) is a common gynaecological condition. Diagnosis of BV is typically based on Amsel criteria, Nugent score and/or bacterial culture. In this study, these conventional methods and two CE-IVD marked quantitative real-time (q)PCR assays were compared with microbiota analysis for the diagnosis of BV. Eighty women were evaluated for BV during two sequential hospital visits by Amsel criteria, Nugent score, culture, the AmpliSens® Florocenosis/Bacterial vaginosis-FRT PCR kit (InterLabService, Moscow, Russia), and the BD MAX™ Vaginal Panel (BD Diagnostics, MD, USA). Microbiota analysis based on amplicon sequencing of the 16S ribosomal RNA gene was used as reference test. The microbiota profile of 36/115 (31%) included cases was associated with BV. Based on microbiota analysis, the sensitivity of detecting BV was 38.9% for culture, 61.15% for Amsel criteria, 63.9% for Nugent score and the BD MAX assay, and 80.6% for the AmpliSens assay, while the specificity of all methods was ≥ 92.4%. Microbiota profiles of the cases with discrepant results between microbiota analysis and the diagnostic methods were variable. All five diagnostic methods missed BV positive cases with a relatively high abundance of the genus Alloscardovia, Bifidobacterium, or Dialister, which were categorised as unspecified dysbiosis by the AmpliSens assay. Compared to Amsel criteria, Nugent score, culture, and the BD MAX assay, the AmpliSens assay was most in agreement with microbiota analysis, indicating that currently, the AmpliSens assay may be the best diagnostic method available to diagnose BV in a routine clinical setting.

Neonatal Safety of Elective Family-Centered Caesarean Sections: A Cohort Study.

BACKGROUND: Although little data are available concerning safety for newborns, family-centered caesarean sections (FCS) are increasingly implemented. With FCS mothers can see the delivery of their baby, followed by direct skin-to-skin contact. We evaluated the safety for newborns born with FCS in the Leiden University Medical Center (LUMC), where FCS was implemented in June 2014 for singleton pregnancies with a gestational age (GA) ≥38 weeks and without increased risks for respiratory morbidity. METHODS: The incidence of respiratory pathology, unplanned admission, and hypothermia in infants born after FCS in LUMC were retrospectively reviewed and compared with a historical cohort of standard elective cesarean sections (CS). RESULTS: From June 2014 to November 2015, 92 FCS were performed and compared to 71 standard CS in 2013. Incidence of respiratory morbidity, hypothermia, temperatures at arrival at the department, GA, and birth weight were comparable (ns). Unplanned admission occurred more often after FCS when compared to standard CS (21 vs 7%; p = 0.03), probably due to peripheral oxygen saturation (SpO2) monitoring. There was no increase in respiratory pathology (8 vs 6%, ns). One-third of the babies were separated from their mother during or after FCS. CONCLUSION: Unplanned neonatal admissions after elective CS increased after implementing FCS, without an increase in respiratory morbidity or hypothermia. SpO2 monitoring might have a contribution. Separation from the mother occurred often.

Determinants of health-related quality of life in the postpartum period after obstetric complications.

OBJECTIVE: To determine the influence of socio-demographic, clinical parameters and obstetric complications on postpartum health-related quality of life (HRQoL). STUDY DESIGN: We used data of three randomized controlled trials to investigate HRQoL determinants in women after an obstetric complication. The DIGITAT and HYPITAT trials compared induction of labor and expectant management in women with intra-uterine growth restriction (IUGR) and hypertensive disorders. The WOMB trial randomized anemic women after postpartum hemorrhage to red blood cell transfusion or expectant management. The HRQoL-measure Short-Form36 was completed at six weeks postpartum. Multivariable analyses were used to identify which parameters affected the Short-Form36 physical component score (PCS) and mental component score (MCS). RESULTS: HRQoL analyses included 1391 women (60%) of the 2310 trial participants. HYPITAT and DIGITAT participants had significantly lower MCS than WOMB participants. In multivariable analysis, PCS after elective and emergency cesarean section was 5-6 points lower than after vaginal delivery. Gestational hypertension, neonatal admission and delivery in an academic hospital had a small negative effect on PCS. No effect was found for randomization status, maternal age, BMI, country of birth, education, parity, induction of labor, analgesics, birth weight, perineal laceration, delivery of placenta, postpartum hemorrhage, congenital anomaly, urinary tract infection, thromboembolic event or endometritis. MCS was influenced only mildly by these parameters. CONCLUSIONS: IUGR and hypertensive disorders lead to lower HRQoL scores postpartum than PPH. In a heterogeneous obstetric population, only mode of delivery by cesarean section has a profound, negative impact, on physical HRQoL (PCS). No profound impacts on MCS were detected.

Which intrauterine growth restricted fetuses at term benefit from early labour induction? A secondary analysis of the DIGITAT randomised trial.

OBJECTIVE: The Disproportionate Intrauterine Growth Intervention Trial at Term (DIGITAT trial) showed that in women with suspected intrauterine growth restriction (IUGR) at term, there were no substantial outcome differences between induction of labour and expectant monitoring. The objective of the present analysis is to evaluate whether maternal or fetal markers could identify IUGR fetuses who would benefit from early labour induction. STUDY DESIGN: The DIGITAT trial was a multicenter, parallel and open-label randomised controlled trial in women who had a singleton pregnancy beyond 36+0 weeks' gestation with suspected IUGR (n=650). Women had been randomly allocated to either labour induction or expectant monitoring. The primary outcome was a composite measure of adverse neonatal outcome, defined as neonatal death before hospital discharge, Apgar score <7, umbilical artery pH <7.05, or admission to neonatal intensive care. Using logistic regression modelling, we investigated associations between outcome and 17 markers, maternal characteristics and fetal sonographic and Doppler velocimetry measurements, all collected at study entry. RESULTS: 17 (5.3%) infants in the induction group had an adverse neonatal outcome compared to 20 (6.1%) in the expectant monitoring group. The only potentially informative marker for inducing labour was maternal pre-pregnancy body mass index (BMI). Otherwise, we observed at best weak associations between a benefit from labour induction and maternal age, ethnicity, smoking, parity, pregnancy-induced hypertension or preeclampsia, Bishop score and gestational age, or fetal sonographic markers (gender, estimated fetal weight, body measurements, oligohydramnios, or umbilical artery pulsatility index and end diastolic flow). CONCLUSION: In late preterm and term pregnancies complicated by suspected intrauterine growth restriction, most of the known prognostic markers seem unlikely to be helpful in identifying women who could benefit from labour induction, except for maternal pre-pregnancy BMI.

Economic analysis comparing induction of labour and expectant management for intrauterine growth restriction at term (DIGITAT trial).

OBJECTIVE: Pregnancies complicated by intrauterine growth restriction (IUGR) are at increased risk for neonatal morbidity and mortality. The Dutch nationwide disproportionate intrauterine growth intervention trial at term (DIGITAT trial) showed that induction of labour and expectant monitoring were comparable with respect to composite adverse neonatal outcome and operative delivery. In this study we compare the costs of both strategies. STUDY DESIGN: A cost analysis was performed alongside the DIGITAT trial, which was a randomized controlled trial in which 650 women with a singleton pregnancy with suspected IUGR beyond 36 weeks of pregnancy were allocated to induction or expectant management. Resource utilization was documented by specific items in the case report forms. Unit costs for clinical resources were calculated from the financial reports of participating hospitals. For primary care costs Dutch standardized prices were used. All costs are presented in Euros converted to the year 2009. RESULTS: Antepartum expectant monitoring generated more costs, mainly due to longer antepartum maternal stays in hospital. During delivery and the postpartum stage, induction generated more direct medical costs, due to longer stay in the labour room and longer duration of neonatal high care/medium care admissions. From a health care perspective, both strategies generated comparable costs: on average €7106 per patient for the induction group (N=321) and €6995 for the expectant management group (N=329) with a cost difference of €111 (95%CI: €-1296 to 1641). CONCLUSION: Induction of labour and expectant monitoring in IUGR at term have comparable outcomes immediately after birth in terms of obstetrical outcomes, maternal quality of life and costs. Costs are lower, however, in the expectant monitoring group before 38 weeks of gestation and costs are lower in the induction of labour group after 38 weeks of gestation. So if induction of labour is considered to pre-empt possible stillbirth in suspected IUGR, it is reasonable to delay until 38 weeks, with watchful monitoring.

Effects on (neuro)developmental and behavioral outcome at 2 years of age of induced labor compared with expectant management in intrauterine growth-restricted infants: long-term outcomes of the DIGITAT trial.

OBJECTIVE: We sought to study long-term (neuro)developmental and behavioral outcome of pregnancies complicated by intrauterine growth restriction at term in relation to induction of labor or an expectant management. STUDY DESIGN: Parents of 2-year-old children included in the Disproportionate Intrauterine Growth Intervention Trial at Term (DIGITAT) answered the Ages and Stages Questionnaire (ASQ) and Child Behavior Checklist (CBCL). RESULTS: We approached 582 (89.5%) of 650 parents. The response rate was 50%. Of these children, 27% had an abnormal score on the ASQ and 13% on the CBCL. Results of the ASQ and the CBCL for the 2 policies were comparable. Low birthweight, positive Morbidity Assessment Index score, and admission to intermediate care increased the risk of an abnormal outcome of the ASQ. This effect was not seen for the CBCL. CONCLUSION: In women with intrauterine growth restriction at term, neither a policy of induction of labor nor expectant management affect developmental and behavioral outcome when compared to expectant management.

Neonatal morbidity after induction vs expectant monitoring in intrauterine growth restriction at term: a subanalysis of the DIGITAT RCT.

OBJECTIVE: The Disproportionate Intrauterine Growth Intervention Trial at Term (DIGITAT) compared induction of labor and expectant management in suspected intrauterine growth restriction (IUGR) at term. In this subanalysis, we report neonatal morbidity between the policies based on the Morbidity Assessment Index for Newborns (MAIN). STUDY DESIGN: We used data from the DIGITAT. For each neonate, we calculated the MAIN score, a validated outcome scale. RESULTS: There were no differences in mean MAIN scores or in MAIN morbidity categories. We found that neonatal admissions are lower after 38 weeks' gestational age compared with 36 and 37 weeks in both groups. CONCLUSION: The incidence of neonatal morbidity in IUGR at term is comparable and relatively mild either after induction or after an expectant policy. However, neonatal admissions are lower after 38 weeks of pregnancy, so if induction to preempt possible stillbirth is considered, it is reasonable to delay until 38 weeks, provided watchful monitoring.

Maternal health-related quality of life after induction of labor or expectant monitoring in pregnancy complicated by intrauterine growth retardation beyond 36 weeks.

OBJECTIVE: Pregnancies complicated by intrauterine growth retardation (IUGR) beyond 36 weeks of gestation are at increased risk of neonatal morbidity and mortality. Optimal treatment in IUGR at term is highly debated. Results from the multicenter DIGITAT (Disproportionate Intrauterine Growth Intervention Trial At Term) trial show that induction of labor and expectant monitoring result in equal neonatal and maternal outcomes for comparable cesarean section rates. We report the maternal health-related quality of life (HR-QoL) that was measured alongside the trial at several points in time. METHODS: Both randomized and non-randomized women were asked to participate in the HR-QoL study. Women were asked to fill out written validated questionnaires, covering background characteristics, condition-specific issues and the Short Form (SF-36), European Quality of Life (EuroQoL 6D3L), Hospital Anxiety and Depression scale (HADS), and Symptom Check List (SCL-90) at baseline, 6 weeks postpartum and 6 months postpartum. We compared the difference scores of all summary measures between the two management strategies by ANOVA. A repeated measures multivariate mixed model was defined to assess the effect of the management strategies on the physical (PCS) and mental (MCS) components of the SF-36. Analysis was by intention to treat. RESULTS: We analyzed data of 361 randomized and 198 non-randomized patients. There were no clinically relevant differences between the treatments at 6 weeks or 6 months postpartum on any summary measures; e.g., on the SF-36 (PCS: P = .09; MCS: P = .48). The PCS and the MCS were below norm values at inclusion. The PCS improved over time but stayed below norm values at 6 months, while the MCS did not improve. CONCLUSION: In pregnancies complicated by IUGR beyond 36 weeks, induction of labor does not affect the long-term maternal quality of life.

Well being of obstetric patients on minimal blood transfusions (WOMB trial).

BACKGROUND: Primary postpartum haemorrhage is an obstetrical emergency often causing acute anaemia that may require immediate red blood cell (RBC) transfusion. This anaemia results in symptoms such as fatigue, which may have major impact on the health-related quality of life. RBC transfusion is generally thought to alleviate these undesirable effects although it may cause transfusion reactions. Moreover, the postpartum haemoglobin level seems to influence fatigue only for a short period of time. At present, there are no strict transfusion criteria for this specific indication, resulting in a wide variation in postpartum policy of RBC transfusion in the Netherlands. METHODS/DESIGN: The WOMB trial is a multicentre randomised non-inferiority trial. Women with acute anaemia due to postpartum haemorrhage, 12-24 hours after delivery and not initially treated with RBC transfusion, are eligible for randomisation. Patients with severe physical complaints are excluded. Patients are randomised for either RBC transfusion or expectant management. Health related quality of life (HRQoL) will be assessed at inclusion, at three days and one, three and six weeks postpartum with three validated measures (Multi-dimensional Fatigue Inventory, ShortForm-36, EuroQol-5D). Primary outcome of the study is physical fatigue three days postpartum. Secondary outcome measures are general and mental fatigue scores and generic health related quality of life scores, the number of RBC transfusions, length of hospital stay, complications and health-care costs. The primary analysis will be by intention-to-treat. The various longitudinal scores will be evaluated using Repeated Measurements ANOVA. A costs benefit analysis will also be performed. The power calculation is based on the exclusion of a difference in means of 1.3 points or greater in favour of RBC transfusion arm regarding physical fatigue subscale. With missing data not exceeding 20%, 250 patients per arm have to be randomised (one-sided alpha = 0.025, power = 80%). DISCUSSION: This study will provide evidence for a guideline regarding RBC transfusion in the postpartum patient suffering from acute anaemia. Equivalence in fatigue score, remaining HRQoL scores and physical complications between both groups is assumed, in which case an expectant management would be preferred to minimise transfusion reactions and costs.

Disproportionate Intrauterine Growth Intervention Trial At Term: DIGITAT.

BACKGROUND: Around 80% of intrauterine growth restricted (IUGR) infants are born at term. They have an increase in perinatal mortality and morbidity including behavioral problems, minor developmental delay and spastic cerebral palsy. Management is controversial, in particular the decision whether to induce labour or await spontaneous delivery with strict fetal and maternal surveillance. We propose a randomised trial to compare effectiveness, costs and maternal quality of life for induction of labour versus expectant management in women with a suspected IUGR fetus at term. METHODS/DESIGN: The proposed trial is a multi-centre randomised study in pregnant women who are suspected on clinical grounds of having an IUGR child at a gestational age between 36+0 and 41+0 weeks. After informed consent women will be randomly allocated to either induction of labour or expectant management with maternal and fetal monitoring. Randomisation will be web-based. The primary outcome measure will be a composite neonatal morbidity and mortality. Secondary outcomes will be severe maternal morbidity, maternal quality of life and costs. Moreover, we aim to assess neurodevelopmental and neurobehavioral outcome at two years as assessed by a postal enquiry (Child Behavioral Check List-CBCL and Ages and Stages Questionnaire-ASQ). Analysis will be by intention to treat. Quality of life analysis and a preference study will also be performed in the same study population. Health technology assessment with an economic analysis is part of this so called Digitat trial (Disproportionate Intrauterine Growth Intervention Trial At Term). The study aims to include 325 patients per arm. DISCUSSION: This trial will provide evidence for which strategy is superior in terms of neonatal and maternal morbidity and mortality, costs and maternal quality of life aspects. This will be the first randomised trial for IUGR at term. TRIAL REGISTRATION: Dutch Trial Register and ISRCTN-Register: ISRCTN10363217.

Schistosomiasis of the uterus in a patient with dysmenorrhoea and menorrhagia.

Abdominal hysterectomy was performed in a patient because of complaints of dysmenorrhoea and menorrhagia and the uterus was sent for histopathological analysis. Besides adenomyosis an extensive granulomatous infection with Schistosoma mansoni eggs was found.