Dear Editor,We would like to comment on the systematic review by Li et al.(1)The use of steroid hormones in the first trimester is a serious issue as organogenesis takes place at this time and therefore there is the possibility of harm from not only congenital anomalies, but also long-term, and even inter-generational effects. Anyone investigating the use of steroid hormones in the first trimester should remember the diethylstilbestrol legacy of devastating harm. Oestrogen (C18H24O2) and diethylstilbestrol (C18H20O2) have similar molecular composition, but their effects are poles apart. In this review, the authors have combined progesterone with progestogens; however they are not the same, in the same way that oestrogen and diethylstilbestrol are not the same. Vaginal micronized progesterone, which we used in our large and high-quality trials (the PROMISE (2) and PRISM (3) trials), has identical molecular structure to natural progesterone, but the other drugs included in this review do not (Table 1). We chose to study vaginal micronized progesterone, as it is identical in structure to natural progesterone, and the available evidence and expert opinion suggested that this is least likely to cause harm. It is important to note that there is evidence of potential harm from dydrogesterone, particularly congenital heart disease.(4)The authors make a bold statement in the abstract about the effects of dydrogesterone on live birth rate. However, they don’t fully address the weaknesses in the evidence. Therefore, we wish to highlight the significant deficiencies in the two trials that contributed live birth data that led to the assertion of beneficial effects from dydrogesterone. Both studies were single centre, open-label studies without placebo control. El-Zibdeh et al did not randomise participants, but instead allocated patients to dydrogesterone on Saturdays, Mondays and Wednesdays, and to no treatment on Sundays, Tuesdays and Thursdays. The trial by Pandian RU was not just a single-centre, but also a single-author study, with insufficient details of the methods to assess its quality. Thus, the effectiveness evidence from these trials cannot be considered reliable.Approximately 80% (4038 of 5056) of the data used in this systematic review come from our PRISM trial.(3) The PRISM trial is a prospectively-registered, randomised, placebo-controlled, multi-centre trial conducted to the highest standards in the UK. The trial found a 3% increase in live birth rate, but with borderline statistical significance (RR, 1.03; 95% CI, 1.00 to 1.07; P=0.08). A pre-specified subgroup analysis in women with the dual risk factors of current pregnancy bleeding and one or more previous miscarriages found a 5% increase in live birth rate (RR, 1.09; 95% CI, 1.03-1.15; P=0.003). In those with three or more previous miscarriages, a 15% increase in live birth rate was observed (RR, 1.28; 95% CI, 1.08 to 1.51; P=0.004).(3, 5) No short-term safety concerns were identified. Based on these data, our recommendation is to consider vaginal micronized progesterone for women with early pregnancy bleeding and one or more previous miscarriages. As for the role of dydrogesterone, we need not only high-quality, randomised trial evidence of its effects but also credible evidence of its safety. As dydrogesterone is a synthetic progesterone-like drug, i.e. a progestogen but not progesterone, the burden of proof to demonstrate short- and long-term safety rests on those promoting this drug.
Dear EditorBirth Trauma organisations advocate on behalf of women and babies who have experienced adverse outcomes and naturally they will take a risk-averse perspective on birth-related care. The latest version of the Assisted Vaginal Birth (AVB) RCOG Guideline (previously called Operative Vaginal Delivery) has focussed specifically on revisions designed to minimise the risk of traumatic injuries for the mother and baby.1 The landmark Montgomery ruling that raised the bar on the standard required for informed consent has been embraced and endorsed within the guideline. 2 It is disappointing to read that Hull et al have concluded that “Montgomery is missing from RCOG’s Assisted Vaginal Birth guideline”.3Hull et al have acknowledged the important counselling advice that has been recommended – antenatal discussion about AVB when planning birth in the third trimester (especially for first-time mothers), review of birth preferences when conducting routine labour ward rounds, and in depth counselling, where circumstances allow, if complications arise during the course of labour particularly during the second stage. However, the guideline apparently falls short of the Montgomery ruling in that we have not recommended “planned caesarean” as an option to prevent assisted vaginal birth.The AVB guideline went through an extensive scoping process. The agreed scope was to address all key questions that arise in relation to labouring women who may require obstetric assistance in the second stage of labour - the assumption being that these women have the intention to labour and deliver vaginally. A guideline addressing maternal request “planned” caesarean section is an entirely different guideline. It is also incorrect to state that the RCOG have provided no direct guidance on this (see Choosing to have a Caesarean section , RCOG Patient Information (2015) based on NICE Clinical Guideline Caesarean Section (2011)).4 The issue of pelvic floor morbidity was included in the literature search and has been discussed in detail.The Montgomery ruling related to a woman with diabetes in pregnancy and a large for gestational age fetus who experienced shoulder dystocia resulting in her baby developing cerebral palsy. The importance of outlining, in advance, the birth options for this woman is clear, given the specific known risks associated with labour in her circumstances. Hull et al suggest on the same basis that all women should be advised that a planned caesarean section is an option to prevent assisted vaginal birth. If taken one step further the Montgomery ruling could be cited to support the argument that all women should be advised that the best way to avoid pregnancy-related complications is to avoid getting pregnant. Common sense would infer that this was not the intention of the Montgomery ruling.Where this RCOG guideline is likely to be consistent with Birth Trauma organisations is in the recommendations on careful assessment, supervision and decision-making; clear communication and transparent consent procedures; and an overall approach that places safety as the first priority when deciding when and when not to attempt a vacuum or forceps assisted delivery, and when to discontinue any such attempt. It is hoped that all relevant health professionals will review and implement the evidence-based, peer-reviewed recommendations within this guideline. They are designed to support women in achieving safe and joyful births, even when obstetric assistance is required.Deirdre J Murphy,1 Rachna Bahl,2Bryony Strachan21) Coombe Women & Infants University HospitalCork St, Dublin 8, Republic of Ireland2) St Michael’s Hospital, Bristol
Objective: To assess psychosexual distress among women receiving different human papillomavirus (HPV) and cytology results in the context of the English HPV primary screening pilot, shortly after women received their results and 6 and 12-months later. Design: Longitudinal, between-groups study. Setting: Five sites in England where primary HPV testing was piloted. Population: Women aged 24-65 years (n=1133) who had taken part in the NHS Cervical Screening Programme. Methods: Women were sent a postal questionnaire soon after receiving their screening results and 6 and 12-months later. Data were analysed using linear regression models to compare psychosexual outcomes between groups receiving six possible screening results. Main Outcome Measures: Psychosexual distress, assessed using six items from the Psychosocial Effects of Abnormal Pap Smears Questionnaire (PEAPS-Q). Results: At all three time-points, there was an association between screening result and overall psychosexual distress (all p<0.001). At baseline, psychosexual distress was significantly higher among women with HPV and normal cytology (B=1.15, 95% CI:0.961-1.337), HPV and abnormal cytology (B=1.02, 95% CI:0.783-1.266) and persistent HPV (B=0.90, 95% CI:0.703-1.102) compared with the control group (all p<0.001). At 6 and 12-month follow-up the pattern of results was similar, but coefficients were smaller. Conclusions: Our findings suggest that while simply participating in HPV testing does not appear to cause psychosexual distress, receiving an HPV-positive result does, particularly in the short-term. Developing interventions to minimise the psychosexual burden of testing HPV-positive will be essential to avoiding unnecessary harm to the millions of women taking part in cervical screening.
The decision to implement screening for infections during pregnancy depends upon epidemiological, economic, therapeutic and test performance criteria. It therefore varies with public health priorities from country to country. When screening is implemented, first trimester has become the best time slot to build individual care pathways also in this field. This is most relevant for evaluating the risk of embryonic consequences, plan diagnostic testing, initiate primary or secondary prevention and increase the accuracy of ultrasound follow-up. This is a critical appraisal of epidemiological data and current international screening recommendations for infections in pregnancy.
Sir,We read with great interest the recent study by Misra et al.evaluating different surgical interventions for the treatment of pain associated with endometriosis.1 We understand the importance of this research to inform our clinical practice and extend our gratitude to the researchers, the women who participated in the study, and the research funder.BJOG: An International Journal of Obstetrics and Gynaecology has been at the forefront of reducing research waste by implementing several important interventions including the requirement to prospectively register randomised trials, implementing the Consolidated Standards of Reporting Trials (CONSORT) statement, and mandating the reporting of core outcome sets.2Reflecting upon this recent study presents an opportunity to consider the impact of implementing such initiatives on selective outcome reporting. The authors prospectively registered their trial (ISRCTN50928834) and reported their pre-specified primary outcome as pelvic pain. This differs from the primary outcome reported in the final publication. A secondary outcome, dyspareunia, reported in the final publication, was not prospectively registered. The CONSORT statement commits researchers to report all prespecified primary and secondary outcomes. When new outcomes are added this should be made clear in the final publication and a comprehensive explanation provided. It would be useful for the authors to clarify the discrepancies between the prospective registry record and the published trial report.Core outcomes aim to address the challenges of poorly selected, collected, and reporting outcomes, including tackling outcome reporting bias.3 We are grateful to the authors for acknowledging the development of a core outcome set for endometriosis research within their study report. The core outcome set for endometriosis has recently been published and was developed using formal consensus methods involving 116 healthcare professionals, 32 researchers, and 206 women with endometriosis from 29 countries.4 The core outcomes include overall pain, improvement in most troublesome symptom, quality of life, adverse events, and patient satisfaction with treatment. It would be useful for the authors to clarify if the core outcomes had been collected as part of the trial and report available data.Over eighty speciality journals, including the Cochrane Gynaecology and Fertility Group, have committed to supporting the development, dissemination, and implementation of the core outcome set for endometriosis. The collaboration who have developed the core outcome set for endometriosis are now assisting with implementation and are systematically examining published endometriosis trials. Where inconsistencies between the trial registry record and the outcomes reported in the published trial report are identified or when the core outcome set has not been fully reported we are writing to the authors seeking clarification. Our progress can be followed at https://twitter.com/EndoOutcomes where we will be posting the prospective registry record, final publication, and response to this letter.
Pregnancy provides optimal opportunities for health promotion and disease prevention. Smoking before and during pregnancy is one of the largest modifiable risk factors for a range of adverse pregnancy outcomes. Concerns over the risks of smoking motivate many pregnant smokers to quit. However, most of their partners continue to smoke throughout pregnancy. More than one-third (35%) of men in the world smoke, and just over 6% of women do (Ritchie et al. Published online at OurWorldInData.org 2020). The impact of paternal smoking, second-hand or third-hand smoking on the perinatal health is largely overlooked. Given the vast majority of studies focusing on the pregnant smokers, less is known about paternal smoking on their future children.In this paper (Zhou et al. BJOG 2020), using a large national prepregnancy registry database, Zhou et al. found that paternal smoking may be associated with birth defects such as congenital heart diseases, limb abnormalities and neural tube defects in the offspring. The result was consistent with previous retrospective studies, but a medium to large effect size was seen. All of the odd ratios exceeded 2.5, with one even over 20 (congenital heart diseases OR=2.51, 95%CI 1.04-6.05; limb abnormalities OR=20.64 95%CI 6.46-68.02; digestive tract anomalies OR=3.67 95%CI 1.44-9.37; neural tube defect OR=4.87,95%CI 1.66-14.28). Such difference might be partially explained by potential confounding factors. For example, the extent of tobacco exposure, in the National Birth Defects Prevention Study (Malik et al. Pediatrics 2008; 121: e810), compared with light smoking exposure (<14 cigarettes per day), heavy smoking women (≥25 cigarettes per day) were more likely to have infants with septal defects (OR 2.06; 95%CI: 1.20-3.54), suggesting a dose-dependent relationship between tobacco exposure and birth defects.In addition, a reduced risk of birth defects after changing smoking behaviors was found in Zhou’s paper. It is no surprise that paternal smoking cessation could improve the adverse outcomes. Limited evidences address whether there is a critical window period by which smoking must be stopped to prevent subsequent adverse perinatal outcomes. Results from a retrospective case-control study indicated that the risk of fetal congenital heart diseases increased as women smoked during the first trimester (Sullivan et al. J Pediatr; 2015; 166:978). In a prospective cohort study (McCowan et al. BMJ 2009; 338: b1081), the authors concluded that stopping smoking early in pregnancy, and certainly by 15-16 weeks’ gestation, may minimize the adverse effects of smoking on late pregnancy complications and should be an important goal for pregnant smokers. Yet, such critical time for paternal smoking cessation remains unknown.Tobacco smoke is also a human germ cell mutagen. It is estimated that with even a modest 25% increase in sperm mutation frequency caused by smoke-exposure, for each generation across the global population there will be millions of smoking-induced de novo mutations transmitted from father to offspring (Beal et al. Mutation Research;2017; 773:26).Therefore, it is strongly recommended that women and men should immediately stop smoking in advance of reproduction.No disclosures: A completed disclosure of interest form is available to view online as supporting information.
The interesting article published on this issue by Helen Perry et al (BJOG 2020 xxxx) is an important contribution to the idea demonstrated several years ago with echocardiographic evaluation of maternal central parameters, that the blood pressure value alone is not useful to understand the degree of compromise of the maternal condition in the evaluation of gestational hypertension and Preeclampsia (Valensise H et al. BJOG. 2006 Sep;113(9):1044-52. Epub 2006 Jul 7). The authors present an elegant study in which the evaluation of the maternal cardiovascular parameters obtained through non-invasive methods (Continuous Waveform Doppler USCOM) show major differences in cardiac output, systemic vascular resistances and heart rate in those patients with the diagnosis of Preeclampsia with a reduced fetal growth.These findings open two lines of research that needs to be implemented on the future: the first is linked to the possibility to identify ‘personal targeted therapy’ according to the parameters found to ameliorate the placental perfusion and fetal growth increasing the heart rate when below the normal values, reducing the systemic vascular resistances and increasing the plasma volume so as to try to bring back to normal the cardiocirculatory conditions (Valensise H et al. Ultrasound Obstet Gynecol. 2008 Jan;31(1):55-64).The second most important research line has to concentrate to the maternal circulatory condition before pregnancy (Vasapollo B et al. Am J Obstet Gynecol. 2020 Mar 3. pii: S0002-9378(20)30234-9. doi: 10.1016/j.ajog.2020.02.043) that in high risk pregnancies might induce not only an automatic passive calculation of the risk factors, but an active therapy based on the modifications of the maternal cardiac parameters to bring them back to normal as much as possible to PREVENT the appearance of the abnormal adaptation to pregnancy.In the future maternal health control in pregnancy will not be possible without the knowledge of maternal cardiac hemodynamics before pregnancy, in the first and second trimester, and at the appearance of hypertension or signs of fetal growth restriction. For this reason the implementation of clinical research with the use of non-invasive devices accessible to any doctor need to be recommended.No disclosures: A completed disclosure of interest form is available to view online as supporting information.
Dear Editor, We would like to thank Dr. Lamont and colleagues for their interesting commentary.1 The authors point out very pressing topics that deserve more attention than we could provide in the original manuscript.They expressed concerns in their letter towards the heterogeneity of the data that were used in our meta-analysis. If incidences differ between regions and populations, absolute numbers on colonisation and neonatal infections might not be comparable. However, new policies were implemented in various settings, where differences in outcomes were measured under the same local circumstances. So as rightly mentioned by Lamont et al, data from the US cannot and should not be used as a blueprint for other parts of the world.1 Yet the general trend in developed countries that we observed, might shed some new light on the respective effectiveness of the strategies currently available.
I moved out of our shared bedroom of nearly 10 years on 3/22/2020. It was not a difficult decision as we have two young children and wondered what would happen if both of us became ill at the same time. As a Maternal-Fetal medicine physician in New York City, I was acutely aware of the coming COVID-19 crisis, and its potential ramifications on the health of my family, friends, patients and community. I am trained to function well in emergencies, and in this case, it was a quick and seemingly logical next-step to sleep separately.This decision also comes along with an already in place full-scale decontamination effort that begins as soon as I enter our home. This involves minimizing what jewelry, clothing, food and bags go back and forth between the hospital and my home, 3-shoe changes, stripping off my clothing and placing everything into the wash, and then running to the shower. None of these choices were rooted in years of medical science, given the novelty of the virus, and paucity of data on the SARS-CoV-2 (COVID-19). I used early data regarding transmission as well as anecdotal reports from friends in Asia who seemed to suggest that it was highly contagious and highly transmissible. Thus, when I recently learned that there is a science and a history surrounding how pathogens have shaped human psychological adaptations. As we are forced to confront the longstanding evolutionary pressure of pathogen avoidance regarding what to eat, and touch and who to be intimate with, it no longer feels theoretical.1Looking back at what I’ve gained and what I’m missing over this last month, I am acutely aware of how much less we are touching as a family and in my medical practice, and I miss it. As I say goodnight to my family and retreat to our windowless den, I am both thankful for a place to sleep that is near enough to be able to peek at their beautiful sleeping faces, while sad that I feel less at ease hugging or kissing them. While every health care worker on the front-line of this crisis has drawn different boundaries (some more or less extreme), my decision to sleep in a separate room, create a decontamination routine, and be less physically affectionate with my children was the only way I could feel in control in an uncontrollable situation.Medical professionals know that touch, rooted in the amygdala of the brain, cannot be separated from the expression of empathy and solidarity that it provides.2 In medicine, touch has long been hypothesized to have an impact on health and development over our lifespan. Dr. Cascio and her team at the Vanderbilt Kennedy Center for Human Development describe social touch as “a powerful force in human development, shaping social reward, attachment, cognitive, communication, and emotional regulation from infancy and throughout life.3” Many of the babies of the mothers I care for will begin their lives in the Neonatal Intensive Care Unit where the science surrounding touch as part of healthcare is widely accepted and engrained in the culture. Skin-to-skin and kangaroo care, the act of carrying your child in a pouch-like device, have been shown to improve breastfeeding, bonding, and neurocognitive development4,5 In fact, the World Health Organization currently has an ongoing international trial looking at the benefits of survival on low-birthweight infants of kangaroo care initiated immediately after birth on survival of low birth weight infants.6 Later in life, touch, relationship quality and intimacy continue to drive good health and have been associated with improved cognitive function in the Rotterdam Study7,8and improved cardiovascular outcomes in the National Social Life Health and Aging Project.8 Their findings suggest physical touch may have positive health implications for older adults.Prior to the pandemic, physicians were already sounding alarms about the loss of medical touch in modern medicine. In a 2011 TED talk with over 1.7 million views, renowned author and physician Abraham Verghese discussed the power of physician touch and the physical exam as he tried to revive the culture of bedside medicine.9 With this pandemic all of that has changed. We are all exceedingly careful to prevent transmission and yet try to provide care and solace in new ways. At the bedside, a gloved hand continues to provide care and comfort. I am happily finding ways to connect with patients through smiling eyes behind a mask, and jokes or phrases that now replace touch. I find myself more commonly expressing words of empathy in telemedicine visits to fill in for the gaps that touch might have provided before. I ask many, many questions to understand symptoms if I cannot see the patient in person. Due to the surrounding events, I am undertaking the fulfilling process of learning a new skill in medicine, to express my emotions on a screen and affect patients’ lives in ways similar to that of an in-person visit.As we raise our family in this time of pandemic, I am thankful that my husband is doing “double-duty” in the realm of hugging and kissing, and has always been a physically affectionate father to our children. I try to tell them how much I love them with greater frequency and despite the concerted effort there are days it’s almost impossible to share our apartment without being physically close. The psychological impact this crisis will have on them is yet to be determined. I hope time will find them healthy, more resilient and grateful at the end of this journey.But tonight, as they sleep soundly in their beds for another night, I am still saddened that I’m not doing the usual kissing and hugging as I tuck them into bed, and it feels like a true loss, among the many others. I am not sleeping as soundly these days for a multitude of reasons including the guest bed, the strangeness of being alone after so many years, and the exponential rise in screen time for work and media consumption. I am truly hopeful we will return to a time when we can more freely touch and care for the people we love and the patients we value so much. In the simplest of internet searches, touch has so many definitions. Touch can mean to be in close contact, but it can also mean to affect.10 COVID-19 has affected us in innumerable ways, and as healthcare workers navigate a post-COVID landscape, I’m hopeful we can continue to innovate and find safe ways to incorporate medical touch into a practice that will be forever changed.Acknowledgements : I would like to acknowledge our patients for their immense flexibility in this changing landscape, the support of my division and department, and my family. I’d like to thank Dr. Gwendolyn Quinn and my husband David Lee, for their significant editorial assistance.
Ultrasound-detected structural anomalies have an impact on fetal mortality and morbidity. Prenatal Exome Sequencing is incorporated into clinical care pathways for paediatric populations but maybe used to delineate the prognosis of fetal structural anomalies. This paper reviews the literature defining the clinical utility of prenatal ES and discusses the potential promise and challenges for implementation of this technology into clinical practice. Prospective case selection with accurate and informative pre-test counselling by multidisciplinary, clinical genetic-led teams is imperative. Robust, regulated laboratory sequencing, informative bioinformatic pathways with variant identification and conservative matching with the phenotype (within clinical review panels) is also important.
Two papers in this issue, on births to Covid-19 infected mothers, are important additions to this rapidly evolving literature. They are both broadly reassuring.The paper from Lombardy, the epicentre of the pandemic in Italy, is the first detailed report of pregnancies from this large region (Ferrazzi et al. BJOG 2020 xxxx). Among 42 affected women, 19 developed pneumonia, of whom seven required oxygen and four critical care. Eighteen babies were delivered by Caesarean, although in eight the indication was unrelated to Covid-19. Three babies tested positive for SARS-COV-2. Two to women who had developed Covid-19 postnatally and had breast-fed without a mask; the presumed source was the mother. One baby who delivered vaginally and did not breast-feed, developed respiratory symptoms requiring one day’s ventilation and tested positive. No mothers or babies died.The paper from China reports SARS-COV-2 viral tests in a range of body fluids from mothers and babies with COVID-19, cared for at Renmin Hospital of Wuhan University (RHWU) (Yanting Wu et al. BJOG 2020 xxxx). This hospital appears on the Global Research Identifier Database (GRID) here https://grid.ac/institutes/grid.412632.0. Readers should know that the GRID database reports that RHWU has the following English aliases “People’s Hospital of Wuhan University”, “Hubei Provincial People’s Hospital”, “First Affiliated Hospital of Wuhan University”, “Wuhan University Renmin Hospital” and “Hubei General Hospital”. This raises the possibility that some or all of the cases may have been reported previously.With this proviso, the detailed information that 1/9 stool samples, 0/13 vaginal samples, and 1/3 breast milk samples were positive is important. Of the five babies who have delivered, none tested positive for Covid-19, although two, both preterm, had pneumonia diagnosed on chest x ray. Apart from one biochemical pregnancy in the first trimester in which a serum human chorionic gonadotrophin of 25.9 IU/L reverted to negative, no mothers or babies died.Taken together with other accumulating data, it is already clear that Covid-19 is less severe in pregnancy than the two previous coronavirus infections, Severe Acute Respiratory Syndrome-related coronavirus (SARS) and Middle East Respiratory Syndrome-related coronavirus (MERS). Nevertheless, four of the mothers from Lombardy required critical care, and there have been other reports of both mother and baby deaths in association with Covid-19. It remains an important disease in pregnancy, which should be taken seriously.No disclosures. A completed disclosure of interest form is available to view online as supporting information.