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BMJ Open Sep 2023We conducted a systematic review to evaluate associations between influenza vaccination during pregnancy and adverse birth outcomes and maternal non-obstetric serious...
OBJECTIVE
We conducted a systematic review to evaluate associations between influenza vaccination during pregnancy and adverse birth outcomes and maternal non-obstetric serious adverse events (SAEs), taking into consideration confounding and temporal biases.
METHODS
Electronic databases (Ovid MEDLINE ALL, Embase Classic+Embase and the Cochrane Central Register of Controlled Trials) were searched to June 2021 for observational studies assessing associations between influenza vaccination during pregnancy and maternal non-obstetric SAEs and adverse birth outcomes, including preterm birth, spontaneous abortion, stillbirth, small-for-gestational-age birth and congenital anomalies. Studies of live attenuated vaccines, single-arm cohort studies and abstract-only publications were excluded. Records were screened using a liberal accelerated approach initially, followed by a dual independent approach for full-text screening, data extraction and risk of bias assessment. Pairwise meta-analyses were conducted, where two or more studies met methodological criteria for inclusion. The Grading of Recommendations, Assessment, Development and Evaluation approach was used to assess evidence certainty.
RESULTS
Of 9443 records screened, 63 studies were included. Twenty-nine studies (24 cohort and 5 case-control) evaluated seasonal influenza vaccination (trivalent and/or quadrivalent) versus no vaccination and were the focus of our prioritised syntheses; 34 studies of pandemic vaccines (2009 A/H1N1 and others), combinations of pandemic and seasonal vaccines, and seasonal versus seasonal vaccines were also reviewed. Control for confounding and temporal biases was inconsistent across studies, limiting pooling of data. Meta-analyses for preterm birth, spontaneous abortion and small-for-gestational-age birth demonstrated no significant associations with seasonal influenza vaccination. Immortal time bias was observed in a sensitivity analysis of meta-analysing risk-based preterm birth data. In descriptive summaries for stillbirth, congenital anomalies and maternal non-obstetric SAEs, no significant association with increased risk was found in any studies. All evidence was of very low certainty.
CONCLUSIONS
Evidence of very low certainty suggests that seasonal influenza vaccination during pregnancy is not associated with adverse birth outcomes or maternal non-obstetric SAEs. Appropriate control of confounding and temporal biases in future studies would improve the evidence base.
Topics: Infant, Newborn; Female; Pregnancy; Humans; Abortion, Spontaneous; Stillbirth; Influenza A Virus, H1N1 Subtype; Influenza, Human; Premature Birth
PubMed: 37673449
DOI: 10.1136/bmjopen-2022-066182 -
BMJ Open Dec 2023Recurrent miscarriage is a common condition with a substantial associated morbidity. A hypothesised cause of recurrent miscarriage is chronic endometritis (CE). The...
Preconceptual administration of doxycycline in women with recurrent miscarriage and chronic endometritis: protocol for the Chronic Endometritis and Recurrent Miscarriage (CERM) trial, a multicentre, double-blind, placebo-controlled, adaptive randomised trial with an embedded translational substudy.
INTRODUCTION
Recurrent miscarriage is a common condition with a substantial associated morbidity. A hypothesised cause of recurrent miscarriage is chronic endometritis (CE). The aetiology of CE remains uncertain. An association between CE and recurrent miscarriage has been shown. This study will aim to determine if preconceptual administration of doxycycline, in women with recurrent miscarriages, and CE, reduces first trimester miscarriages, increasing live births.
METHODS AND ANALYSIS
Chronic Endometritis and Recurrent Miscarriage is a multicentre, double-blind adaptive trial with an embedded translational substudy. Women with a history of two or more consecutive first trimester losses with evidence of CE on endometrial biopsy (defined as ≥5 CD138 positive cells per 10 mm) will be randomised to oral doxycycline or placebo for 14 days. A subset will be recruited to a mechanistic substudy in which microbial swabs and preintervention/postintervention endometrial samples will be collected. Up to 3062 women recruited from 29 National Health Service (NHS) hospital sites across the UK are expected to be screened with up to 1500 women randomised in a 1:1 ratio. Women with a negative endometrial biopsy (defined as <5 CD138 positive cells per 10 mm) will also be followed up to test validity of the tool. The primary outcome is live births plus pregnancies ≥24 + 0 weeks gestation at the end of the trial, in the first or subsequent pregnancy. Secondary clinical outcomes will also be assessed. Exploratory outcomes will assess the effect of doxycycline treatment on the endometrial microbiota, the differentiation capacity of the endometrium and the senescent profile of the endometrium with CE.
ETHICS AND DISSEMINATION
Ethical approval has been obtained from the NHS Research Ethics Committee Northwest-Haydock (19/NW/0462). Written informed consent will be gained from all participants. The results will be published in an open-access peer-reviewed journal and reported in the National Institute for Health and Care Research journals library.
TRIAL REGISTRATION NUMBER
ISRCTN23947730.
Topics: Pregnancy; Female; Humans; Doxycycline; Endometritis; State Medicine; Abortion, Habitual; Chronic Disease; Double-Blind Method; Randomized Controlled Trials as Topic; Multicenter Studies as Topic
PubMed: 38040426
DOI: 10.1136/bmjopen-2023-081470 -
Best Practice & Research. Clinical... Aug 2023This review on early pregnancy complications and obesity will focus on the known pregnancy complications such as miscarriage (whether spontaneous or after fertility... (Review)
Review
This review on early pregnancy complications and obesity will focus on the known pregnancy complications such as miscarriage (whether spontaneous or after fertility treatment), polycystic ovaries and risk of miscarriage, recurrent pregnancy loss, ectopic pregnancy, hyperemesis gravidarum and birth defects. Evidence will be assessed and mechanistic pathways for the outcomes will be described. We know that obesity is now a pandemic and has an impact on early pregnancy complications. The evidence has been summarised to provide the reader with a comprehensive overview and advice for pregnant women with obesity in early pregnancy.
Topics: Pregnancy; Female; Humans; Abortion, Spontaneous; Infertility, Female; Ovulation Induction; Abortion, Habitual; Pregnancy Rate; Polycystic Ovary Syndrome; Obesity; Pregnancy Complications
PubMed: 37451193
DOI: 10.1016/j.bpobgyn.2023.102372 -
Obstetrics and Gynecology Sep 2023To evaluate the association between seasonal influenza vaccination and miscarriage using data from an ongoing, prospective cohort study.
OBJECTIVE
To evaluate the association between seasonal influenza vaccination and miscarriage using data from an ongoing, prospective cohort study.
METHODS
We analyzed 2013-2022 data from PRESTO (Pregnancy Study Online), a prospective prepregnancy cohort study of female pregnancy planners and their male partners in the United States and Canada. Female participants completed a baseline questionnaire and then follow-up questionnaires every 8 weeks until pregnancy, during early and late pregnancy, and during the postpartum period. Vaccine information was self-reported on all questionnaires. Miscarriage was identified from self-reported information during follow-up. Male partners were invited to complete a baseline questionnaire only. We used Cox proportional hazard models to estimate the hazard ratio (HR) and 95% CI for the association between vaccination less than 3 months before pregnancy detection through the 19th week of pregnancy and miscarriage, with gestational weeks as the time scale. We modeled vaccination as a time-varying exposure and used propensity-score fine stratification to control for confounding from seasonal and female partner factors.
RESULTS
Of 6,946 pregnancies, 23.3% of female partners reported exposure to influenza vaccine before or during pregnancy: 3.2% during pregnancy (gestational age 4-19 weeks) and 20.1% during the 3 months before pregnancy detection. The miscarriage rate was 16.2% in unvaccinated and 17.0% among vaccinated participants. Compared with no vaccine exposure, influenza vaccination was not associated with increased rate of miscarriage when administered before (HR 0.99, 95% CI 0.81-1.20) or during (HR 0.83, 95% CI 0.47-1.47) pregnancy. Of the 1,135 couples with male partner vaccination data available, 10.8% reported vaccination less than 3 months before pregnancy. The HR for the association between male partner vaccination and miscarriage was 1.17 (95% CI 0.73-1.90).
CONCLUSION
Influenza vaccination before or during pregnancy was not associated with miscarriage.
Topics: Pregnancy; Humans; Male; Female; Infant, Newborn; Infant; Abortion, Spontaneous; Influenza, Human; Prospective Studies; Cohort Studies; Seasons; Influenza Vaccines
PubMed: 37535959
DOI: 10.1097/AOG.0000000000005279 -
Obstetrical & Gynecological Survey Sep 2023Cervical cerclage (CC) represents one of the few effective measures currently available for the prevention of preterm delivery caused by cervical insufficiency, thus... (Review)
Review
IMPORTANCE
Cervical cerclage (CC) represents one of the few effective measures currently available for the prevention of preterm delivery caused by cervical insufficiency, thus contributing in the reduction of neonatal morbidity and mortality rates.
OBJECTIVE
The aim of this study was to review and compare the most recently published major guidelines on the indications, contraindications, techniques, and timing of placing and removal of CC.
EVIDENCE ACQUISITION
A descriptive review of guidelines from the American College of Obstetricians and Gynecologists (ACOG), the Royal College of Obstetricians and Gynaecologists (RCOG), the Society of Obstetricians and Gynaecologists of Canada (SOGC), and the International Federation of Gynecology and Obstetrics (FIGO) on CC was carried out.
RESULTS
There is a consensus among the reviewed guidelines regarding the recommended techniques, the indications for rescue CC, the contraindications, as well as the optimal timing of CC placement and removal. All medical societies also agree that ultrasound-indicated CC is justified in women with history of prior spontaneous PTD or mid-trimester miscarriage and a short cervical length detected on ultrasound. In addition, after CC, serial sonographic measurement of the cervical length, bed rest, and routine use of antibiotics, tocolysis, and progesterone are unanimously discouraged. In case of established preterm labor, CC should be removed, according to ACOG, RCOG, and SOGC. Furthermore, RCOG and SOGC agree on the prerequisites that should be met before attempting CC. These 2 guidelines along with FIGO recommend history-indicated CC for women with 3 or more previous preterm deliveries and/or second trimester pregnancy miscarriages, whereas the ACOG suggests the use of CC in singleton pregnancies with 1 or more previous second trimester miscarriages related to painless cervical dilation or prior CC due to painless cervical dilation in the second trimester. The role of amniocentesis in ruling out intra-amniotic infection before rescue CC remains a matter of debate.
CONCLUSIONS
Cervical cerclage is an obstetric intervention used to prevent miscarriage and preterm delivery in women considered as high-risk for these common pregnancy complications. The development of universal international practice protocols for the placement of CC seems of paramount importance and will hopefully improve the outcomes of such pregnancies.
Topics: Pregnancy; Infant, Newborn; Female; Humans; Premature Birth; Cerclage, Cervical; Abortion, Spontaneous; Obstetric Labor, Premature; Cervix Uteri
PubMed: 37976303
DOI: 10.1097/OGX.0000000000001182 -
BMC Women's Health Aug 2023Hysteroscopic surgery and assisted reproduction technology are feasible ways to improve the reproductive outcome. Our aim was to study hysteroscopic septoplasty and...
INTRODUCTION
Hysteroscopic surgery and assisted reproduction technology are feasible ways to improve the reproductive outcome. Our aim was to study hysteroscopic septoplasty and myomectomy's effect on infertility and reproductive performance.
METHODS
Retrospective cohort of patients who had unexplained infertility and/or recurrent miscarriages and had myomectomy or septoplasty in the period September 2016-october 2021 with a total of 18 months' follow up. The main outcome measures were spontaneous pregnancy, term pregnancy and miscarriage. For analysis, we used Statistical Package for Social Sciences (SPSS) version 20.
RESULTS
One hundred and sixty-five patients were included. The mean age of patients was 39 years. 40 patients had septum resection and 125 patients had hysteroscopic myomectomy. A spontaneous pregnancy rate after surgery was achieved in 46 patients (27.9%). Out of the 64 patients who had failed IVF preoperatively, 32 patients (50%) had a successful IVF post-hysteroscopic surgery and there were more successful cases in the patients who had fibroid resection but this difference did not reach a statistical significance (P value 0.055). In the 79 pregnancies after surgery, preterm birth and miscarriage were seen in 10 patients (12.7%), similarly, respectively after septal or fibroid resection. Miscarriages were less post-operatively. Hysteroscopic myomectomy, compared with hysteroscopic metroplasty, was significantly associated with higher spontaneous pregnancy rate (63.0% Vs 37.0%, P value 0.018), more term pregnancies (87.5% vs. 12.5%, P value 0.001) and less miscarriage rate (40%vs 60%, P value 0.003). Pregnancy post-operatively in patients with primary infertility was more statistically significantly associated with hysteroscopic myomectomy than with hysteroscopic septoplasty (95.8% vs. 4.2%, p value 0.030). In patients who got pregnant postoperatively there was no statistically significant difference in the mode of delivery.
CONCLUSION
In carefully selected patients with unexplained infertility and recurrent miscarriage, hysteroscopic myomectomy, compared with hysteroscopic metroplasty, was significantly associated with higher spontaneous pregnancy, more term pregnancies and less miscarriage rates. More than metroplasty, hysteroscopic myomectomy led to higher spontaneous pregnancies in patients with primary infertility.
TRIAL REGISTRATION
NCT05560295.
Topics: Adult; Female; Humans; Infant, Newborn; Pregnancy; Abortion, Habitual; Fertility; Hysteroscopy; Infertility; Leiomyoma; Premature Birth; Reproduction; Retrospective Studies; Uterine Myomectomy
PubMed: 37644542
DOI: 10.1186/s12905-023-02562-2 -
The Journal of Maternal-fetal &... Dec 2023N6-methyladenosine (m6A) is one of the predominant RNA epigenetic modifications that modify RNAs reversibly and dynamically by "writers" (methyltransferase), "erasers"... (Review)
Review
BACKGROUND
N6-methyladenosine (m6A) is one of the predominant RNA epigenetic modifications that modify RNAs reversibly and dynamically by "writers" (methyltransferase), "erasers" (demethylase), and "readers."
OBJECTIVE
This review aimed to provide a comprehensive understanding of the complexity of m6A regulation in the great obstetrical syndromes to understand its pathogenesis and potential therapeutic targets.
METHODS
The terms "placenta or trophoblast" and "m6A or N6-methyladenosine" were searched in PubMed databases (June 2023).
RESULTS
In this review, we discuss the regulatory role of m6A in the great obstetrical syndromes such as preeclampsia (PE), spontaneous abortion (SA), hyperglycemia in pregnancy (HIP) and fetal growth to emphasize the clinical relevance of m6A dysregulation in pregnancy. We also describe mechanisms that potentially involve the participation of m6A methylation, such as proliferation, invasion, migration, apoptosis, autophagy, endoplasmic reticulum stress, macrophage polarization, and inflammation.
CONCLUSION
We summarize the recent research progress on the role of m6A modification in the great obstetrical syndromes and placental function and provide a brief perspective on its prospective applications.
Topics: Pregnancy; Humans; Female; Placenta; Syndrome; Abortion, Spontaneous; Adenosine; Apoptosis
PubMed: 37474299
DOI: 10.1080/14767058.2023.2234541 -
Human Reproduction (Oxford, England) Nov 2023Does the exposure to job loss during pregnancy increase the risk of miscarriage or stillbirth?
STUDY QUESTION
Does the exposure to job loss during pregnancy increase the risk of miscarriage or stillbirth?
SUMMARY ANSWER
The experience of own or partner's job loss during the pregnancy is associated with an increased risk of miscarriageand stillbirth.
WHAT IS KNOWN ALREADY
Prior research on the psycho-social aspect of pregnancy loss has investigated the contextual and the individual-level stressors. At the contextual level, natural disasters, air pollution, and economic downturns are associated with higher risk of pregnancy loss. At the individual level, intense working schedules and financial strain are linked with increased risk of pregnancy loss both at early and later stages of the gestation.
STUDY DESIGN, SIZE, DURATION
This work draws on high-quality individual data of 'Understanding Society', a longitudinal survey that has interviewed a representative sample of households living in the UK annually since 2009. Approximately 40 000 households were recruited. The analyses use all the available survey waves (1-12, 2009-2022).
PARTICIPANTS/MATERIALS, SETTING, METHODS
The final sample consisted of 8142 pregnancy episodes that contain complete informationon pregnancy outcome and date of conception. Ongoing pregnancies at the time of the interview were excluded from the final sample. The outcome variable indicated whether a pregnancy resulted in a live birth or a pregnancy loss whereas the exposure variable identified the women's or their partner's job loss because of redundancy or a dismissal. Logistic regression models were employed to estimate the relation between job loss during pregnancy and pregnancy loss. The models were adjusted for an array of socio-demographic and economic characteristics following a stepwise approach. Several sensitivity analyses complemented the main findings.
MAIN RESULTS AND THE ROLE OF CHANCE
Baseline models controlling for women's demographic background and prior experience of miscarriage estimated an increased risk of pregnancy loss when women were exposed to their own or their partner's job loss during their pregnancy (odds ratio (OR) = 1.99, 95% CI: 1.32, 2.99). When the models were adjusted for all socio-economic and partnership-related covariates the association remained robust (OR = 1.81, 95% CI: 1.20, 2.73).
LIMITATIONS, REASONS FOR CAUTION
First, the pregnancy outcome and the date of conception were self-reported and may besubjected to recall and social desirability bias. Second, although we adjusted for an array socio-demographic characteristics and self-reported health, other contextual factors might be correlated with both job loss and pregnancy loss. Third, owing to the limited sample size, we could not assess if the main finding holds across different socio-economic strata.
WIDER IMPLICATIONS OF THE FINDINGS
By showing that exposure to a job loss during pregnancy increases the risk of miscarriage and stillbirth, we underline the relevance of pregnancy loss as a preventable public health matter. This result also calls for policy designthat enhances labour market protection and social security buffers for pregnant women and their partners.
STUDY FUNDING/COMPETING INTERESTS
The authors received the following financial support for the research, authorship, and/or publication of this article: H2020 Excellent Science, H2020 European Research Council, Grant/Award Number: 694262 (project DisCont-Discontinuities in Household and Family Formation) and the Economic and Social Research Centre on Micro-Social Change (MiSoC). There are no conflicts of interest to declare.
Topics: Pregnancy; Female; Humans; Abortion, Spontaneous; Stillbirth; Pregnancy Outcome; Abortion, Induced; Live Birth
PubMed: 37758648
DOI: 10.1093/humrep/dead183 -
Human Reproduction (Oxford, England) Apr 2024The human endometrium is a dynamic entity that plays a pivotal role in mediating the complex interplay between the mother and developing embryo. Endometrial disruption... (Review)
Review
The human endometrium is a dynamic entity that plays a pivotal role in mediating the complex interplay between the mother and developing embryo. Endometrial disruption can lead to pregnancy loss, impacting both maternal physical and psychological health. Recent research suggests that the endometrial microbiota may play a role in this, although the exact mechanisms are still being explored, aided by recent technological advancements and our growing understanding of host immune responses. Suboptimal or dysbiotic vaginal microbiota, characterized by increased microbial diversity and reduced Lactobacillus dominance, has been associated with various adverse reproductive events, including miscarriage. However, the mechanisms linking the lower reproductive tract microbiota with pregnancy loss remain unclear. Recent observational studies implicate a potential microbial continuum between the vaginal and endometrial niche in patients with pregnancy loss; however, transcervical sampling of the low biomass endometrium is highly prone to cross-contamination, which is often not controlled for. In this review, we explore emerging evidence supporting the theory that a dysbiotic endometrial microbiota may modulate key inflammatory pathways required for successful embryo implantation and pregnancy development. We also highlight that a greater understanding of the endometrial microbiota, its relationship with the local endometrial microenvironment, and potential interventions remain a focus for future research.
Topics: Pregnancy; Female; Humans; Abortion, Spontaneous; Endometrium; Embryo Implantation; Microbiota; Vagina
PubMed: 38195891
DOI: 10.1093/humrep/dead274 -
Journal of Medical Ethics May 2024
Topics: Female; Humans; Pregnancy; Abortion, Spontaneous
PubMed: 38383150
DOI: 10.1136/jme-2024-109934