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ObjectiveRevised guidelines for caesarean section (CS) advise maternal antibiotic administration prior to skin incision instead of after umbilical cord clamping, unintentionally exposing the infant to antibiotics antenatally. We aimed to investigate if timing of intrapartum antibiotics contributes to the impairment of microbiota colonisation in CS born infants.DesignIn this randomised controlled trial, women delivering via CS received antibiotics prior to skin incision (n=20) or after umbilical cord clamping (n=20). A third control group of vaginally delivering women (n=23) was included. Faecal microbiota was determined from all infants at 1, 7 and 28 days after birth and at 3 years by 16S rRNA gene sequencing and whole-metagenome shotgun sequencing.ResultsCompared with vaginally born infants, profound differences were found in microbial diversity and composition in both CS groups in the first month of life. A decreased abundance in species belonging to the genera Bacteroides and Bifidobacterium was found with a concurrent increase in members belonging to the phylum Proteobacteria. These differences could not be observed at 3 years of age. No statistically significant differences were observed in taxonomic and functional composition of the microbiome between both CS groups at any of the time points.ConclusionWe confirmed that microbiome colonisation is strongly affected by CS delivery. Our findings suggest that maternal antibiotic administration prior to CS does not result in a second hit on the compromised microbiome. Future, larger studies should confirm that antenatal antibiotic exposure in CS born infants does not aggravate colonisation impairment and impact long-term health.

Objective To evaluate the implementation of low-dose aspirin in pregnancy for the prevention of utero-placental complications among gynecologists in the Netherlands between 2016 and 2021. In this timeframe, a national guideline about aspirin in pregnancy was introduced by the Dutch Society of Obstetrics and Gynecology. Materials and methods A national online survey among Dutch gynecologists and residents was performed. An online questionnaire was distributed among the members of the Dutch Society of Obstetrics and Gynecology in April 2016 and April 2021. Main outcome measure was the proportion of gynecologists indicating prescription of aspirin in pregnancy for high and moderate risk indications. Results In 2016, 133 respondents completed the survey, and in 2021 231. For all indications mentioned in the guideline there was an increase in prescribing aspirin in 2021 in comparison to 2016. More specifically, the percentage of gynecologists prescribing aspirin for a history of preeclampsia before 34 weeks, between 34 and 37 weeks and at term increased from respectively 94% to 100%, 39% to 98%, and 15% to 97%. Consultant obstetricians and respondents working in an university hospital did not more often indicate the prescription of aspirin for tertiary care indications in 2021. Future use of a prediction model was suggested in the narrative comments. Conclusion Implementation of aspirin in pregnancy among Dutch gynecologists substantially improved after a five year timeframe in which the national guideline on aspirin during pregnancy was introduced and trials confirming the effect of aspirin were published.

Background Preterm birth is the leading cause of neonatal morbidity and mortality. The recurrence rate of spontaneous preterm birth is high, and additional preventive measures are required. Our objective was to assess the effectiveness of low-dose aspirin compared to placebo in the prevention of preterm birth in women with a previous spontaneous preterm birth. Methods and findings We performed a parallel multicentre, randomised, double-blinded, placebo-controlled trial (the APRIL study). The study was performed in 8 tertiary and 26 secondary care hospitals in the Netherlands. We included women with a singleton pregnancy and a history of spontaneous preterm birth of a singleton between 22 and 37 weeks. Participants were randomly assigned to aspirin 80 mg daily or placebo initiated between 8 and 16 weeks of gestation and continued until 36 weeks or delivery. Randomisation was computer generated, with allocation concealment by using sequentially numbered medication containers. Participants, their healthcare providers, and researchers were blinded for treatment allocation. The primary outcome was preterm birth grade 1, intraventricular hemorrhage > grade 2, necrotising enterocolitis > stage 1, retinopathy of prematurity, culture proven sepsis, or perinatal death). Analyses were performed by intention to treat. From May 31, 2016 to June 13, 2019, 406 women were randomised to aspirin (n = 204) or placebo (n = 202). A total of 387 women (81.1% of white ethnic origin, mean age 32.5 ± SD 3.8) were included in the final analysis: 194 women were allocated to aspirin and 193 to placebo. Preterm birth, Anadeijda Landman and colleagues assess the effectiveness of low-dose aspirin in the prevention of preterm birth in women with a previous spontaneous preterm birth., Author summary Why was this study done? Complications of preterm birth are the leading cause of neonatal morbidity and mortality worldwide. As spontaneous preterm birth has a multifactorial etiology, different preventive measures, in addition to, e.g., progesterone, may be needed depending on the underlying cause in individual cases. Due to the partially similar pathophysiology of uteroplacental ischemia between spontaneous preterm birth and preeclampsia, it has been suggested that low-dose aspirin may also prevent spontaneous preterm birth. What did the researchers do and find? We performed a multicentre, randomised, double-blinded, placebo-controlled trial including 387 women with a singleton pregnancy and a previous spontaneous preterm birth of a singleton. Women were allocated to aspirin 80 mg or placebo starting between 8 and 16 weeks of gestation and continued until 36 weeks of gestation. The preterm birth rate was slightly lower in the aspirin group (21.2%) as compared to the placebo group (25.4%), especially among women with good adherence to medication (19.2% in the aspirin group versus 24.8% in the placebo group). These differences were not statistically significant. What do these findings mean? The study sample was too small to draw firm conclusions on the effectivity of low-dose aspirin for the prevention of spontaneous preterm birth, and, therefore, we do not recommend implementation of low-dose aspirin for this indication at this time. Further research is necessary to evaluate the possible beneficial effect of low-dose aspirin on the prevention of spontaneous preterm birth.

OBJECTIVE: Determine the risk of hypertensive disorders of pregnancy (HD) in women with a history of spontaneous preterm birth (SPTB).STUDY DESIGN: Longitudinal linked national cohort study within the Dutch Perinatal Registry (1999-2009) on linked data among 349,291 women with a first and second singleton pregnancy in the Netherlands.MAIN OUTCOME MEASURES: The incidence of HD, small for gestational age (SGA) and placental abruption in the second pregnancy.RESULTS: Out of 349,291 women with a singleton first pregnancy, 19,991 (5.7%) had a SPTB. The incidence of HD in the second pregnancy was 8.1% in women with a previous SPTB, as compared to 5.6% in women with a previous term birth (aOR 1.49 (CI 1.41-1.57)). Also after excluding HD, SGA and/or placental abruption in the first pregnancy, women with a history of SPTB had a higher risk of HD in their second pregnancy compared to women with a previous term birth (4.6% versus 2.7%, aOR 1.77 (CI 1.64-191)). Similarly, the incidence of SGA and placental abruption was higher in the second pregnancy in women with a history of SPTB compared to term birth in the first pregnancy.CONCLUSIONS: Women with a history of SPTB are at elevated risk of HD in the subsequent pregnancy. These results support shared pathophysiology between SPTB and HD.

Introduction: Spontaneous preterm birth (SPTB) has several causes and its pathophysiology remains unclear. In a significant proportion of SPTB, placental histology shows signs of maternal vascular malperfusion (MVM); commonly associated with hypertensive disorders of pregnancy (HD), fetal growth restriction (FGR) and placental abruption, together referred to as clinical ischemic placental diseases (IPD). We hypothesized that women with SPTB and placental MVM are at elevated risk for IPD in a subsequent pregnancy. Methods: We included women with SPTB in our cohort and followed the subsequent ongoing pregnancy (n = 110). Histological placental characteristics in the index were reported according to new international guidelines, and related to the clinical outcome of the subsequent pregnancy. Results: In the SPTB placentas, we observed MVM in 61.8% (n = 68). In the subsequent pregnancies in 19.1% (n = 21) at least one clinical sign of IPD was present (HD (12.7%), FGR (5.5%) or placental abruption (0.9%)). There was no significant difference in the prevalence of clinical IPD or recurrence of SPTB in the subsequent pregnancy between women with and without placental MVM in the index pregnancy, although our study was not powered to detect small differences. Discussion: Women with a history of SPTB have an elevated risk of IPD in the subsequent pregnancy. MVM is present in a large proportion of SPTB placentas. The presence of placental MVM in the index pregnancy does not predict clinical IPD or recurrent SPTB in a subsequent pregnancy.

Introduction Preterm birth (PTB) is one of the greatest challenges in obstetric and children’s healthcare. PTB remains the most important cause of perinatal morbidity and mortality worldwide. We studied the number of publications concerning PTB over the last two decades using advanced bibliometric visualization methodology. We put the number of publications in perspective of growing awareness of PTB as a major health problem. Methods We analyzed publications over time and performed bibliometric analysis of publications on PTB in the Web of Science from 1997 to 2016. The subjects of publications were visualized using a term map showing the relevant terms occurring in titles and abstracts. Results We identified 47,811 publications. The annual number of publications on PTB increased significantly by 443% in 2016 (n = 5027) compared to 1997 (n = 1135). Obstetrics & Gynecology is the leading research field (with 10.4% on the subject PTB in 2016) followed closely by Pediatrics (7.6% on the subject PTB in 2016), within the field Public, Environmental & Occupational Health minimal increase was observed (only 1% was published on the subject PTB in 2016). The publications on PTB have increased at higher rates than the overall increase of publications. In recent years we found more publications on PTB describing epidemiology and clinical characteristics/outcomes whereas in earlier years publications focused more on translational, basic research. Conclusion A significant increase in research concerning PTB was observed over the last two decades. This increase of publications is in line with the growing global awareness of the need to reduce PTB by clinical research. Electronic supplementary material The online version of this article (10.1007/s10995-019-02772-x) contains supplementary material, which is available to authorized users.

Background A disturbance in the early colonisation of the gut by microorganisms is associated with an aberrant innate immune system and a variety of clinical conditions later in life. Several factors are considered to influence this initial colonisation, including maternally administered antibiotics during pregnancy and delivery. Recent revisions to international obstetric guidelines have resulted in the exposure of all infants born by caesarean section (CS) to broad-spectrum antibiotics perinatally. To date, the consequences of these new guidelines on neonatal gut colonisation and the associated short- and long-term health implications have not yet been addressed. The aim of this study is to investigate the influence of the timing of antibiotic administration during CS to the mother on the course of neonatal intestinal colonisation up to 2 years of age. Methods/design This single-centre randomised controlled trial will recruit 40 women scheduled for an elective CS. The subjects will be randomised to receive 1500 mg of cefuroxime intravenously either prior to the skin incision (n = 20) or after clamping of the umbilical cord (n = 20). Levels of cefuroxime in cord blood will be determined for exposed neonates. Faecal samples from the children will be collected on days 1, 7 and 28 days and at 2 years old and analysed by 16S sequencing. Shannon-diversity indices, absolute and relative abundances, and unsupervised and supervised classification methods will be used to evaluate the effect of the timing of intrapartum cefuroxime administration on the composition of the microbiota. The outcomes for both study groups will be compared to the intestinal microbiota of vaginally born infants (n = 20). To detect possible effects on health state, a questionnaire on health-related issues will be taken at the age of 2 years. Discussion In the proposed study, changes in the intestinal microbiota of 40 children born by CS will be followed until the age of 2 years. Research on this topic is necessary since significant effects relating to the timing of antibiotic administration on microbial colonisation may conflict with the current guidelines, as this may have health consequences later in life. Trial registration Netherlands Clinical Trial Registry, NTR6000. Retrospectively registered on 25 July 2016. Electronic supplementary material The online version of this article (10.1186/s13063-019-3552-8) contains supplementary material, which is available to authorized users.

Contains fulltext : 177805.pdf (Publisher’s version ) (Open Access) BACKGROUND: Preterm birth (birth before 37 weeks of gestation) is a major problem in obstetrics and affects an estimated 15 million pregnancies worldwide annually. A history of previous preterm birth is the strongest risk factor for preterm birth, and recurrent spontaneous preterm birth affects more than 2.5 million pregnancies each year. A recent meta-analysis showed possible benefits of the use of low dose aspirin in the prevention of recurrent spontaneous preterm birth. We will assess the (cost-)effectiveness of low dose aspirin in comparison with placebo in the prevention of recurrent spontaneous preterm birth in a randomized clinical trial. METHODS/DESIGN: Women with a singleton pregnancy and a history of spontaneous preterm birth in a singleton pregnancy (22-37 weeks of gestation) will be asked to participate in a multicenter, randomized, double blinded, placebo controlled trial. Women will be randomized to low dose aspirin (80 mg once daily) or placebo, initiated from 8 to 16 weeks up to maximal 36 weeks of gestation. The primary outcome measure will be preterm birth, defined as birth at a gestational age (GA) < 37 weeks. Secondary outcomes will be a composite of adverse neonatal outcome and maternal outcomes, including subgroups of prematurity, as well as intrauterine growth restriction (IUGR) and costs from a healthcare perspective. Preterm birth will be analyzed as a group, as well as separately for spontaneous or indicated onset. Analysis will be performed by intention to treat. In total, 406 pregnant women have to be randomized to show a reduction of 35% in preterm birth from 36 to 23%. If aspirin is effective in preventing preterm birth, we expect that there will be cost savings, because of the low costs of aspirin. To evaluate this, a cost-effectiveness analysis will be performed comparing preventive treatment with aspirin with placebo. DISCUSSION: This trial will provide evidence as to whether or not low dose aspirin is (cost-) effective in reducing recurrence of spontaneous preterm birth. TRIAL REGISTRATION: Clinical trial registration number of the Dutch Trial Register: NTR 5675 . EudraCT-registration number: 2015-003220-31.

Commentary on: Wong LF, Wilkes J, Korgenski K, et al. Risk factors associated with preterm birth after a prior term delivery. BJOG 2016;123:1772–8.[OpenUrl][1] The aetiology of spontaneous preterm birth remains, despite many publications on the subject, largely indefinite.1 Studies focus on identification of risk factors for preterm birth in order to develop tailor-made care. Risk factor identification might however also provide clues in unravelling the pathophysiological processes leading … [1]: {openurl}?query=rft.jtitle%253DBJOG%26rft.volume%253D123%26rft.spage%253D1772%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx

Directive 2006/17/EC requires that all available medical information, including autopsy reports, is evaluated before releasing tissues for transplantation. The aim of this study was to investigate whether evaluation of results of autopsy and other histological examinations contributes to the safety of tissue transplantation. From the files of all deceased Dutch donors, from whom tissues were retrieved in a 6-month period, results of autopsy and other histological examinations (remnant heart after valve donation and biopsies obtained during retrieval) were evaluated for contraindications for transplantation. Of 758 donors at least one tissue was considered suitable for transplantation at initial assessment. 637 Donors donated corneas, 256 skin, 177 heart valves and 61 musculoskeletal tissues. On 220 donors (29.0%) autopsy was done. Of seven donors no autopsy results were requested, since a contraindication was detected earlier in the medical screening. In 19 donors with autopsy (8.9%) general or tissue-specific contraindications were detected. There were no differences in distribution of detected contraindications among donors who donated different tissues. For 136 donors (17.9%) results of histological examinations other than autopsy were available; results of examination of remnant hearts for all, brain autopsy for two (0.3%) and retrieval biopsy for four donors (0.5%). Contraindications were detected in nine of these donors with histology results other than autopsy (6.6%). For 402 donors (53%) no histological examinations were done. Evaluation of results of autopsy and other histological examinations improves the safety of tissue transplantation for all types of tissues. In donors without autopsy alternative histological examinations can contribute to enhance the safety of tissue transplantation.

Needlestick and other sharps injuries are a key Canadian public health issue, affecting 70,000 people per year and costing some dollar 140 million. A safety program at Toronto East General Hospital--focusing on blood collection and patient injection--achieved an 80% reduction in injuries within one year (from 41 in 2003 to eight in 2004), with blood collection injuries eliminated entirely.