Objective
To evaluate whether double‐layer uterine closure after a first caesarean section (CS) is superior compared with single‐layer uterine closure in terms of postmenstrual spotting and niche ...development in the uterine caesarean scar.
Design
Multicentre, double‐blind, randomised controlled superiority trial.
Setting
Thirty‐two hospitals in the Netherlands.
Population
A total of 2292 women aged ≥18 years undergoing a first CS were randomly assigned to each procedure (1:1): 1144 women were assigned to single‐layer uterine closure and 1148 women were assigned to double‐layer uterine closure.
Methods
Single‐layer unlocked closure and double‐layer unlocked closure, with the second layer imbricating the first.
Main outcome measures
Number of days with postmenstrual spotting during one menstrual cycle 9 months after CS. Secondary outcomes: perioperative and menstrual characteristics; transvaginal ultrasound measurements.
Results
A total of 774 (67.7%) women from the single‐layer group and 770 (67.1%) women from the double‐layer group were evaluable for the primary outcome, as a result of drop‐out and amenorrhoea. The mean number of postmenstrual spotting days was 1.33 (bootstrapped 95% CI 1.12–1.54) after single‐layer closure and 1.26 (bootstrapped 95% CI 1.07–1.45) after double‐layer closure (adjusted mean difference −0.07, 95% CI −0.37 to 0.22, P = 0.810). The operative time was 3.9 minutes longer (95% CI 3.0–4.9 minutes, P < 0.001) and niche prevalence was 4.7% higher (95% CI 0.7–8.7%, P = 0.022) after double‐layer closure.
Conclusions
The superiority of double‐layer closure compared with single‐layer closure in terms of postmenstrual spotting after a first CS was not shown. Long‐term obstetric follow‐up of our trial is needed to assess whether uterine caesarean closure guidelines should be adapted.
Tweetable
Double‐layer uterine closure is not superior for postmenstrual spotting after a first caesarean; single‐layer closure performs slightly better on other outcomes.
Tweetable
Double‐layer uterine closure is not superior for postmenstrual spotting after a first caesarean; single‐layer closure performs slightly better on other outcomes.
IntroductionIn women with gestational diabetes mellitus (GDM) requiring pharmacotherapy, insulin was the established first-line treatment. More recently, oral glucose lowering drugs (OGLDs) have ...gained popularity as a patient-friendly, less expensive and safe alternative. Monotherapy with metformin or glibenclamide (glyburide) is incorporated in several international guidelines. In women who do not reach sufficient glucose control with OGLD monotherapy, usually insulin is added, either with or without continuation of OGLDs. No reliable data from clinical trials, however, are available on the effectiveness of a treatment strategy using all three agents, metformin, glibenclamide and insulin, in a stepwise approach, compared with insulin-only therapy for improving pregnancy outcomes. In this trial, we aim to assess the clinical effectiveness, cost-effectiveness and patient experience of a stepwise combined OGLD treatment protocol, compared with conventional insulin-based therapy for GDM.MethodsThe SUGAR-DIP trial is an open-label, multicentre randomised controlled non-inferiority trial. Participants are women with GDM who do not reach target glycaemic control with modification of diet, between 16 and 34 weeks of gestation. Participants will be randomised to either treatment with OGLDs, starting with metformin and supplemented as needed with glibenclamide, or randomised to treatment with insulin. In women who do not reach target glycaemic control with combined metformin and glibenclamide, glibenclamide will be substituted with insulin, while continuing metformin. The primary outcome will be the incidence of large-for-gestational-age infants (birth weight >90th percentile). Secondary outcome measures are maternal diabetes-related endpoints, obstetric complications, neonatal complications and cost-effectiveness analysis. Outcomes will be analysed according to the intention-to-treat principle.Ethics and disseminationThe study protocol was approved by the Ethics Committee of the Utrecht University Medical Centre. Approval by the boards of management for all participating hospitals will be obtained. Trial results will be submitted for publication in peer-reviewed journals.Trial registration numberNTR6134; Pre-results.
•General anxiety was higher in women with early-onset and late-onset preeclampsia.•Women with early-onset preeclampsia had steeper cortisol increases across pregnancy.•Hair cortisol levels are higher ...in early-onset preeclampsia during second trimester.
This Dutch multicenter case-controlled study investigated whether cortisol concentrations and psychosocial stress during pregnancy differed between women with early-onset preeclampsia, late-onset preeclampsia, and uncomplicated pregnancies. Cortisol concentrations were analyzed in three hair segments representing the preconception period, first, and second trimester of pregnancy. Cortisol trajectories differed, with early-onset preeclampsia showing steeper increases in cortisol and higher cortisol concentrations during the second trimester. Reported anxiety in women with preeclampsia was higher compared to women with uncomplicated pregnancies. These results indicate that measures of cortisol and reported anxiety differ between early-onset, late-onset preeclampsia, and uncomplicated pregnancies.
Vascular endothelial growth factor (VEGF) has been implicated in angiogenesis induced by electrical stimulation in skeletal muscle. Less is known about the role of arachidonic acid metabolites in the ...control of growth of blood vessels in vivo. The present study examined the role of 20-hydroxyeicosatetraenoic acid (20-HETE) on the angiogenesis induced by electrical stimulation in skeletal muscle. The tibialis anterior and extensor digitorum longus muscles of rats were stimulated for 7 days. Electrical stimulation significantly increased the 20-HETE formation and angiogenesis in the muscles, which was blocked by chronic treatment with N-hydroxy-N'-(4-butyl-2-methylphenol)formamidine (HET0016) or 1-aminobenzotriazole (ABT). Chronic treatment with either HET0016 or ABT did not block the increases in VEGF protein expression in both muscles. To analyze the role of VEGF on 20-HETE formation, additional rats were treated with VEGF-neutralizing antibody (VEGF Ab). VEGF Ab blocked the increases of 20-HETE formation induced by stimulation. These results place 20-HETE in the downstream signaling pathway for angiogenesis and show that both VEGF and 20-HETE are involved in the angiogenesis induced by electrical stimulation in skeletal muscle.
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.
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%).
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.
We recently described a chymostatin-sensitive elastase-2 as the major angiotensin (ANG) II-forming enzyme in the perfusate of the rat mesenteric arterial bed (MAB) with the same cDNA sequence as rat ...pancreatic elastase-2. The role of this enzyme in generating ANG II was examined in the rat isolated and perfused MAB. The vasoconstrictor effect elicited by ANG I and the renin substrate tetradecapeptide was only partially inhibited by captopril but abolished by the combination of captopril and chymostatin or N-acetyl-Ala-Ala-Pro-Leu-chloromethylketone (Ac-AAPL-CK; inhibitor originally developed for human elastase-2). The effect induced by Pro11,d-Ala12-ANG I, an ANG I-converting enzyme (ACE)-resistant biologically inactive precursor of ANG II, was blocked by chymostatin or Ac-AAPL-CK. It was also demonstrated that cultured rat mesenteric endothelial cells synthesize elastase-2 and that mRNA for this enzyme can be detected in different rat tissues such as the pancreas, MAB, lung, heart, kidney, liver, and spleen. In conclusion, the demonstration of a functional alternative pathway to ACE for ANG II generation in the rat MAB and the fact that cultured MAB endothelial cells are capable of producing and secreting elastase-2 represent strong evidence of a physiological role for this enzyme in the rat vasculature.
The rising rate of cesarean deliveries has led to an increased incidence of long long-term complications, including niche formation in the uterine scar. Niche development is associated with various ...gynecologic complaints and complications in subsequent pregnancies, such as uterine rupture and placenta accreta spectrum disorders. Although uterine closure technique is considered a potential risk factor for niche development, consensus on the optimal technique remains elusive.
We aimed to evaluate the effect of single-layer vs double-layer closure of the uterine incision on live birth rate at a 3-year follow-up with secondary objectives focusing on gynecologic, fertility, and obstetrical outcomes at the same follow-up.
A multicenter, double-blind, randomized controlled trial was performed at 32 hospitals in the Netherlands. Women ≥18 years old undergoing a first cesarean delivery were randomly assigned (1:1) to receive either single-layer or double-layer closure of the uterine incision. The primary outcome of the long-term follow-up was the live birth rate; with secondary outcomes, including pregnancy rate, the need for fertility treatment, mode of delivery, and obstetrical and gynecologic complications. This trial is registered on the International Clinical Trials Registry Platform www.who.int (NTR5480; trial finished).
Between 2016 and 2018, the 2Close study randomly assigned 2292 women, with 830 of 1144 and 818 of 1148 responding to the 3-year questionnaire in the single-layer and double-layer closure. No differences were observed in live birth rates; also there were no differences in pregnancy rate, need for fertility treatments, mode of delivery, or uterine ruptures in subsequent pregnancies. High rates of gynecologic symptoms, including spotting (30%–32%), dysmenorrhea (47%–49%), and sexual dysfunction (Female Sexual Function Index score, 23) are reported in both groups.
The study did not demonstrate the superiority of double-layer closure over single-layer closure in terms of reproductive outcomes after a first cesarean delivery. This challenges the current recommendation favoring double-layer closure, and we propose that surgeons can choose their preferred technique. Furthermore, the high risk of gynecologic symptoms after a cesarean delivery should be discussed with patients.
•This is the first prediction model for development of a niche, including important surgical factors, in a population with a first elective or emergency CS.•More attention should be paid to surgical ...factors (double-layer closure, less surgical experience, other suture material than Vicryl) given their effect on niche development.•Different factors contribute to development of a niche compared to development of a large niche.•This prediction model is, unfortunately, not usable in clinical practice due to lack of discriminative ability and accuracy.•Proper suturing and correct approximation rather than single- versus double-layer uterine closure could play an important role and needs attention during training of residents.•Clinicians should be aware that suture material influences niche development.
To develop and internally validate a prognostic prediction model for development of a niche in the uterine scar after a first caesarean section (CS).
Secondary analyses on data of a randomized controlled trial, performed in 32 hospitals in the Netherlands among women undergoing a first caesarean section. We used multivariable backward logistic regression. Missing data were handled using multiple imputation. Model performance was assessed by calibration and discrimination. Internal validation using bootstrapping techniques took place. The outcome was ‘development of a niche in the uterus’, defined as an indentation of ≥ 2 mm in the myometrium.
We developed two models to predict niche development: in the total population and after elective CS. Patient related risk factors were: gestational age, twin pregnancy and smoking, and surgery related risk factors were double-layer closure and less surgical experience. Multiparity and Vicryl suture material were protective factors. The prediction model in women undergoing elective CS revealed similar results. After internal validation, Nagelkerke R2 ranged from 0.01 to 0.05 and was considered low; median area under the curve (AUC) ranged from 0.56 to 0.62, indicating failed to poor discriminative ability.
The model cannot be used to accurately predict the development of a niche after a first CS. However, several factors seem to influence scar healing which indicates possibilities for future prevention such as surgical experience and suture material. The search for additional risk factors that play a role in development of a niche should be continued to improve the discriminative ability.
While some studies argue that maternal stress during pregnancy is a risk-factor for preeclampsia (PE), other studies do not support this hypothesis. These studies did not incorporated physiological ...stress measures and recall bias may explain their results.
To investigate whether maternal stress during pregnancy, as measured by questionnaires and cortisol concentrations in hair, differ between a group of women with early onset PE, late onset PE and uncomplicated pregnancies.
This multicentre case-controlled study included women with early-onset PE (<34 wks gestation; n = 15), late-onset PE (>34 wks gestation; n = 18), and uncomplicated pregnancies (n = 26). At admission in the hospital (early-onset PE and late-onset PE), or at term pregnancy (controls), mothers filled out stress and anxiety questionnaires. Participants also donated a strand of hair at admission, not influenced by corticosteroid administration. The average hair growth rate is 1 cm a month, with the hair closest to the scalp representing the most recent part of pregnancy. Cortisol concentration in hair were analyzed in three periods: 3 months before conception (preconception), 0–3 months of pregnancy (1st trimester) and 3–6 months pregnancy (2nd trimester).
ANOVA’s showed that reported anxiety levels were higher in women with preeclampsia compared to the controls (p < .01). Furthermore, a repeated measurements ANOVA showed that cortisol trajectories from preconception to the 2nd trimester differed between early onset preeclampsia, late onset preeclampsia and uncomplicated pregnancies (p = .04). Post-hoc analyses indicated that mothers with early-onset PE showed steeper increases in cortisol, with significantly higher cortisol concentrations during the second trimester.
These results indicate that measures of psychosocial anxiety and physiological stress differ between early-onset PE, comparing to late-onset PE and uncomplicated pregnancies. Late-onset PE might be associated with a higher level of preconceptional cortisol concentration, although these results were underpowered, cortisol concentrations may be utilized to assess the differentiation between early-onset and late-onset PE.
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