Obstetric anal sphincter injury by maternal origin and length of residence: a letterIt gives us great pleasure to read the study entitled “Obstetric anal sphincter injury (OASI) by maternal origin and length of residence: a nation-wide cohort study” by Sorbye and Bains et al1. We appreciate the authors for conducting a large scale multicentric cohort study on this newer aspect of OASI. However, we wish to make certain observations to further help in comprehending the results.Firstly, the eligibility criteria for the recruitment of participants needs clarification as to why foreign-born women with Norwegian-born parents were excluded from enrolment. Keeping them as a separate group could have been beneficial in assessing whether environmental factors due to migrating out of Norway had an impact on the incidence of OASI. Futhermore, the greater odds of OASI among women with foreign-born partners has to be digested with a pinch of salt. A subgroup analysis comparing the newborn birth weight (NBW) and head circumference (HC) could be instrumental in solving this dilemma. Prior studies by Vik et al from Norway had demonstrated similar outcomes in neonatal survival as well2. In the absence of significant difference in NBW and HC, social issues need due consideration. It probably opens up the arena for potential future research in this very field.The study does mention that the mean HC of newborns to foreign-born women with OASI did not differ from Norwegian-born counterparts without OASI. But the p value mentioned alongside in the text is 0.000, which would amount to high significance. This area needs clarification.Table 3 has stratified the association between OASI and the length of residence in Norway. We appreciate this robust comparison as this outcome was vital in hypothesizing the impact of environment and lifestyles on the incidence of OASI. But, it is quite strange to note that women who had childbirth before their lawful residence (probably had immigrated recently) had lesser odds of OASI compared to those who had legal residence upto 4 years. Discrete analysis of this subgroup of patients might give us a better comprehension. Another analysis which can be done is to assess whether the place of delivery (government or private setup) was significantly affecting the prevalence of OASI. It can be thought of as an auxiliary outcome. This will ultimately help in addressing the barriers to optimal utilization of resources and will probably stimulate the health care policy to achieve equitable care across the nation.References:Sorbye IK, Bains S, Vangen S, Sundby J, Lindskog B, Owe KM. Obstetric anal sphincter injury by maternal origin and length of residence: a nation-wide cohort study. BJOG. 2021 Oct 28. doi: 10.1111/1471-0528.16985. Epub ahead of print. PMID: 34710268.Vik ES, Aasheim V, Nilsen RM, Small R, Moster D, Schytt E. Paternal country of origin and adverse neonatal outcomes in births to foreign-born women in Norway: A population-based cohort study. PLoS Med. 2020 Nov;17(11):e1003395.
Re: Effects of antenatal corticosteroids on maternal cardiovascular system, an underestimated notion in pregnant womenDear Editor,I am glad to take this opportunity to respond the concerns about our article1, regarding the antenatal corticosteroids (ACSs) on maternal cardiovascular system.The administration of ACSs to expectant mothers in anticipation of preterm birth is one of the most important advances in perinatal medicine; ACSs are now standard care for pregnancies at risk of premature delivery. The widespread uptake of ACSs therapy is due to compelling evidence demonstrating improved neonatal outcomes, stemming most notably from corticosteroid-driven maturation of fetal pulmonary function.2 Our nationwide population-based study also provides evidence to support the hypothesis that ACSs to women at risk of late preterm delivery might reduce the risk of neonatal respiratory complications, the need of glucose within 7 days of birth, the incidence of infant mortality, and medical expenditure.1In our study, we included five untreated women (controls) matched to each woman treated with antenatal corticosteroids. The treated and matched control groups were similar in terms of maternal and gestational age, birth weight, sex, and incidence of nulliparous and gestational diabetes. However, the incidence of preeclampsia or gestational hypertension in the treated group (7.7%) is more than the control groups (6.9%, P = 0.029). Iatrogenic preterm delivery may happen due to maternal cardiovascular diseases and administered antenatal corticosteroid for fetal lung maturation in theses pregnancies.1Because of the limitation of National Health Insurance Research Database, we were not able to investigate blood pressure, heart rate, and laboratory data in the women received ACSs. Considering this limitation, we analyzed the confounding factors to adjust the risk and confirm our results. In the subgroup that had gestational hypertension, the adjusted risks of subgroup were consistent with comprehensive results. Women who received ACSs had significantly fewer days in hospital. No significant difference was found in maternal postpartum disease. Therefore, the impacts of ACSs may not lead to harmful and long-term effects.Professor Hantoushzadeh mentioned literatures involved short-term steroid use elicited both favorable and unfavorable effects on different cardiovascular risk factors in healthy young male volunteers.3 Pregnancy is a period of continuous change in the maternal cardiovascular system, partly mediated by the autonomic nervous system. Insufficient autonomic adaptation to increasing gestation is associated with pregnancy complications, such as hypertensive disorders of pregnancy and preterm birth (both major causes of perinatal morbidity and mortality). There were scarce studies have investigated the changes in maternal cardiovascular system in response to the administration of routinely used obstetric medications, such as tocolytic agents and magnesium sulphate. Even though the effect of ACSs on fetal heart rate variability has been widely investigated, ACSs use has received less attention in maternal cardiovascular system. And there was no study elaborated maternal cardiovascular effect after ACSs use during late preterm period.4 As Professor Hantoushzadeh stated, it is important to know the side effects of ACSs on the cardiovascular system.5 In the era of personalized medicine, there is both significant scope and imperative need for further research-informed refinement to the use of ACSs.2Disclosure of interestsThe authors declare no conflicts of interest.References1. Liang FW, Tsai HF, Kuo PL, Tsai PY. Antenatal corticosteroid therapy in late preterm delivery: a nationwide population-based retrospective study in Taiwan. BJOG : an international journal of obstetrics and gynaecology. 2021 Aug;128(9):1497-502.2. Kemp MW, Newnham JP, Challis JG, Jobe AH, Stock SJ. The clinical use of corticosteroids in pregnancy. Hum Reprod Update. 2016 Mar-Apr;22(2):240-59.3. Cottin F, Malcurat V, Zorgati H, Prieur F, Labsy Z, Do MC, et al. Effect of oral glucocorticoid intake on autonomic cardiovascular control. Springerplus. 2015;4:622.4. Bester M, Moors S, Joshi R, Nichting TJ, van der Hout-van der Jagt MB, Oei SG, et al. Changes in Maternal Heart Rate Variability in Response to the Administration of Routine Obstetric Medication in Hospitalized Patients: Study Protocol for a Cohort Study (MAMA-Heart Study). Clin Pract. 2021 Jan 21;11(1):13-25.5. Hantoushzadeh S, Saleh M, Maleki A. Effects of antenatal corticosteroids on maternal cardiovascular system, an underestimated notion in pregnant women. BJOG : an international journal of obstetrics and gynaecology. 2021;
An improved understanding of pregnancy in women with Turner’s syndrome may save lives!BJOG-21-1221Around 25% of maternal deaths are related to heart disease and up-to 20% of these are the consequence of aortic dissection (Lameijer et al, Neth Heart J (2020) 28:27–36). Connective tissue disorders (e.g. Marfan’s, Loeys-Dietz, Ehlers Danlos), Bicuspid aortic valve, Turner’s Syndrome (TS) and pre-existing coarctations constitute the bulk of aortopathies encountered in pregnancy. Although a true XO karyotype in pregnancy had been rarely encountered historically due to the reduced fertility in these patients, women with a mosaic TS may have normal fertility and in recent years reproductive technologies with oocyte donation have increasingly been used in the sub-fertile TS population. Although pregnancies in such women remain infrequent, the risk of death during pregnancy amongst all women with TS (inclusive of mosaicism) has been reported as high as 2%, 150-200 times greater than the general population. This increased risk has led to the establishment of guidelines for the use of reproductive technologies in these women (Karnis. Fertility Sterility (2012) 98(4),787-91).The rarity of these cases means that available data, even when drawn from multicenter registries, has been relatively sparse. A study of TS patients gathered from ten cardiovascular centres over 12 years evaluated 68 pregnancies (Grewal J, et al. Heart 2021;107:61–66). Although the majority had no structural cardiac disease and no major cardiovascular complications were observed, the adverse obstetric event rate was around 20% with a similar rate for adverse fetal outcomes. Like the present paper (BJOG-21-1221) which reports a larger population, these cases were followed within centres offering a dedicated obstetric-cardiac clinic.Standardized guidelines for preconceptual and perinatal care of these women have improved outcomes, as evidenced by a French study evaluating cohorts from before and after the establishment of such guidance in France (Cadoret et al, EJOGRB(2018) 229,20–25). Whilst these guidelines encourage the care of TS mothers in dedicated obstetric-cardiac centers, this is not always the case; either due to lack of diagnosis of the condition (esp in mosaic cases with milder phenotypes) or lack of appreciation of the risks. The present paper reports only cases followed in cardiac-obstetric centres; without an overall population pregnancy case number it will remain uncertain what proportion of women with TS were followed in an appropriate centre and whether the reported cohort therefore excludes cases with worse outcomes.Although it might be expected that mothers followed within appropriate centres receive optimal care, studies continue to show that this is not always so. In the present cohort only half of the women had a pre-pregnancy cardiac evaluation and 20% had no record of imaging during pregnancy; perhaps reflecting late referral to the tertiary centre. While this remains a high-risk population with risks for both maternal and fetal adverse outcomes with high haemorrhage rates, hypertensive disease rates (~19%) and an SGA rate exceeding 20%, the data from this cohort is reassuring with respect to severe perinatal morbidity. Particularly striking in this cohort was a caesarean rate of 67%.To provide women with TS optimal care, preconceptual evaluation and pregnancy planning with medical optimisation is vital, with subsequent close follow-up in an obstetric-cardiac centre capable of managing whatever complications this cohort might experience, even if rare.Disclosure of InterestRB has no conflicts of interestRB is supported by the CIHR and FRSQ
Genital mycoplasma and preterm birth: a difficult puzzle to solve. Letter re: Genital Mycoplasma infection and spontaneous preterm birth outcome: a prospective cohort studySir.In their recent paper, Cunha and colleagues analyzed data from a diverse group of 1349 Brazilian women who participated in a 2011 study evaluating etiological factors associated with preterm birth. 11Cunha GKP, Bastos LB, de Freitas SF, Cavalli RC, Quintana SM. Genital mycoplasma infection and spontaneous preterm birth outcome: a prospective cohort study. BJOG https://doi-org.uml.idm.oclc.org/10.1111/1471-0528.16949 Women were interviewed and examined at 20-25 weeks’ gestation, and cervicovaginal cultures were taken for mycoplasma, ureaplasma, and bacterial vaginosis. Women were followed until delivery, and clinical associations with preterm birth were evaluated. Positive associations were found for shortened cervix and a history of prior preterm birth. No association was found for infection with mycoplasma, ureaplasma, or bacterial vaginosis. They concluded that “genital mycoplasma infection was not a risk of spontaneous preterm birth, even with other abnormal vaginal microbiota conditions.”There is a flaw in their methodology and conclusion. In the original study, women with a positive culture for ureaplasma or mycoplasma were treated with azithromycin, and those with bacterial vaginosis were treated with oral metronidazole. Treatment would have reduced the presence of these pathogens, limiting their ability to cause preterm birth. Accordingly, this study shows that women with treated mycoplasma, ureaplasma or bacterial vaginosis do not have an increased incidence of preterm birth; however, no comment can be made on whether untreated infection causes preterm birth.Presumably the original investigators who performed the study treated women with genital infection because they believed it might prevent preterm birth; and there lies the rub. An observational study using vaginal culture results unavailable until after birth has shown an association between untreated mycoplasma infection and preterm birth.22Foxman B, Wen A, Srinivasan U, et al. Mycoplasma, bacterial vaginosis, associated bacteria BVAB3, race, and risk of preterm birth in a high-risk cohort. Am J Obstet Gynecol 2014;210:226.e1-7. However, in order to determine whether mycoplasma causes preterm birth and whether treatment prevents it, a randomized trial of treatment or placebo in infected women at elevated risk of preterm birth is needed. This may not be easily feasible. Ethically, investigators may be able to demonstrate research equipoise: that we do not yet know whether treatment reduces preterm birth associated with mycoplasma infection. However, women found to have genital mycoplasma who are at increased risk of preterm birth would need to believe that the benefits and harms of treating or not treating are equal. Given the relative safety of antibiotics and the high morbidity of preterm birth, practically, equipoise may be hard to find.In Northern Canada, with high rates of sexually transmitted infections including mycoplasma, we suspect a causal relationship with preterm birth and late miscarriage. Based on observational studies and anecdotal evidence, our practice is to screen women with a history of prior preterm birth, late miscarriage, or short cervix for ureaplasma, mycoplasma, and bacterial vaginosis in the second trimester and treat those who are positive.2,33Taylor-Robinson D, Lamont R. Mycoplasmas in pregnancy. BJOG 2011;118:164–174.,44Morency AM, Bujold E. The Effect of Second-Trimester Antibiotic Therapy on the Rate of Preterm Birth. J Obstet Gynaecol Can 2007;29(1):35–44 We also test women with threatened preterm labour remote from term and treat those who are positive, sometimes with marked reduction in symptoms. In keeping with Taylor-Robinson’s paper, treatment failures with azithromycin used for Mycoplasma hominis have prompted a switch to Clindamycin, whose activity against both mycoplasma and bacterial vaginosis may explain its better performance than metronidazole in the prevention of preterm birth.3,4 We await better evidence, but are not holding our breath.
Rates of obstetric anal sphincter injuries among immigrant womenMarie-Louise MarschalekKlinik Floridsdorf, Vienna, AustriaLinked article: This is a mini commentary on Sorbye et al.The Norwegian-wide cohort study by Sorbye et al addresses the question of whether the maternal region of origin and birthplace have an influence on the risk of obstetric anal sphincter injury (BJOG 2021).Obstetric anal sphincter injuries (OASI), as a complication of vaginal delivery, are associated with potential long-term complications such as anal and fecal incontinence, perineal pain, sexual dysfunction and increased rates of caesarean section in subsequent deliveries. Established risk factors for OASI are high birthweight, operative vaginal delivery and prolonged second stage of labor.When it comes to ethnicity as a risk factor, retrospective studies suggest Asian women are at increased risk for OASI (Brown J et al. Aust N Z J Obstet Gynaecol. 2018;58(1):79-85.). However, it has remained unclear whether the biological or the migration factor is the cause.Maternal origin, immigrant status and duration of residence have been the subject of many studies, in order to identify risks of various adverse obstetric outcomes, with known increased risk of both giving birth to small for gestational age fetuses, and preterm delivery (Urquia et al. BJOG 2010 Apr;117(5):591-601.)The present study analyzed a 9-year comprehensive data set from birth registries, and concluded that, compared to Norwegian women, women from South Asia were most likely to experience OASI, with an aOR of 2.24, followed by women from Southeast/East Asian/Pacific and Sub-Saharan Africa. Furthermore, the authors found newly arrived migrant women to be at highest risk for OASI.Migrant women are exposed to a new physical and social environment, with limited language competence a significant factor in preventing social integration, resulting in limited health literacy and sub-optimal care after migration.Language skills are particularly significant in OASI cases, being important for collaboration between the woman and birth attendant during delivery. Interestingly, a difference was found regarding whether the partner was Norwegian-born or foreign-born, indicating that good communication at giving birth was important. The inference is that an understanding of the birth process and an explanation of the difficulties that might arise is an advantage. Undoubtedly educating women during pregnancy itself about OASI risks is of value.Sorbye et al do not address the topic of perineal laceration protection techniques, experience of birth attendants or birth position. As studies have identified certain positions, such as the lithotomy position, to be a risk factor for OASI, whilst others, such as the lateral position, are considered to be protective, this information would have been interesting.In other nationwide studies the incidence of OASI is shown to have increased, explained by improved awareness, diagnostic recognition and documentation (Andrews V et al. BJOG. 2006;113:195‐200.). However, in this and another recent study, the incidence has decreased in Norway and Sweden, possibly due to implemented perineal protection programs for midwives/physicians (Gyhagen et al. Acta Obstet Gynecol Scand. 2021 Aug 25).Sorbye and colleagues highlight the influence of environmental factors on OASI, which in theory could be preventable, and confirm that there are migration specific factors. Hence, the vulnerable group of migrant women need special attention and care in order to reduce morbidity.
Preterm neonatal survival: what is the role of prognostic models?Elizabeth M McClure, PhD1Robert L Goldenberg, MD21Social, Statistical and Environmental Sciences, RTI International, Durham, NC2Columbia University, New York, NYEven before the 1960’s and the introduction of the specialty of neonatology, and continuing to the present, numerous efforts have been made to understand the relationship between newborn birthweight and the risk of mortality. (1) With the development of neonatal intensive care units (NICUs), attention to survival rates and neurologic outcomes among those at the lowest birthweights and gestational ages (GA) has grown. (2) Defining the lower limits of GA or birthweight associated with the neonatal outcomes is important for clinicians, families, and others to inform appropriate decision-making and clinical care.To predict newborn survival, numerous models have been developed to estimate risk at specific birthweights and/or GAs. To date, more than 35 have been published, almost exclusively from high-income countries with advanced NICU care. In a study published recently, van Beek et al sought to validate one of these predictive models from the United Kingdom (UK), deemed to be among the highest quality, with the objective of assessing its value for clinical use. (3)Van Beek et al used an independent Dutch population to validate survival among very preterm infants using the UK model’s parameters. Because they found relatively good performance, the authors’ concluded that the model could inform daily clinical practice. However, the generalizability of their results, especially to other populations differing by ethnicity or socioeconomic status, is questionable. The parameters for the model quality focused on birthweight, GA, and gender, but many other metrics (including the racial diversity, quality of care, etc.) were limited. In particular, the interventions available and utilized for obstetric and neonatal care were not specified, which would be important for their goal of clinical use of the model. Importantly, the quality of obstetric care is not considered. (4) Both the availability and quality of specific obstetric and neonatal interventions in any given setting may be among the most important factors impacting survival.Especially important for clinical considerations, long-term outcomes, including severe disabilities, were not addressed. Concerns about neurodevelopmental outcomes in infants at the lower limits of birthweight and GA are as or more important to parents and caregivers than survival. (5) It is thus unclear how this – or virtually any other model - can be useful for “daily clinical practice”.A better strategy to inform clinical care is for individual health-care facilities to maintain neonatal survival and neurological outcome statistics. These types of data within a specific context may be more helpful to physicians, including obstetricians and neonatologists, who often, together with parents and caregivers, make decisions related to interventions prior to delivery or during NICU care. Newborn outcomes, especially at the extreme lower limits of birthweight and GA, remains an area of intense interest. While models may provide some supportive information, it is difficult to imagine that these will ever replace clinical decisions informed by actual outcome data from the specific facility.Conflicts of interest: The authors declare no conflicts of interest.References:1. Goldenberg RL, Nelson KG, Dyer RL, Wayne JB. The variability of viability: the effect of physicians’ perceptions of viability on the survival of very low birth weight infants. Am J Obstet Gynecol 1982; 143:678-84.2. Bottoms SF, Paul RH, Mercer BM, MacPherson CA, Caritis SN, Moawad AW. Obstetric determinants of neonatal survival: antenatal predictors of neonatal survival and morbidity in extremely low birth weight infants. Am J Obstet Gynecol. 1999 80(3 Pt 1):665-9.3. Van Beek P.E, Groenendaal F, Onland W, Koole S, Dijk PH, Dijkmanet KP et al. Prognostic model for predicting survival in very preterm infants: an external validation study. BJOG (in press)4. Goepfert AR, Goldenberg RL, Hauth JC, Bottoms SF, Iams JD, Mercer BM Obstetrical determinants of neonatal neurological morbidity in < or = 1000-gram infants. Am J Perinatol. 1999;16(1):33-42.5. Iams JD, Mercer BM. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. What we have learned about antenatal prediction of neonatal morbidity and mortality. Semin Perinatol 2003:247-52.
Mini commentary on BJOG-21-0823: Pregnancy outcomes in women with Budd-Chiari syndrome or portal vein thrombosis - A multicentre retrospective cohort study.Budd-Chiari syndrome (BCS) and portal vein thrombosis (PVT) are rare thrombotic disorders which can affect females of reproductive age. Physiological changes in pregnancy may result in or exacerbate pre-existing known portal hypertension related issues associated with these conditions. These conditions may also present de-novo in pregnancy with acute onset ascites or variceal haemorrhage. Both in pregnancy and in the non-pregnant state, in those with established disease, in general, the overall balance of risk, favours continued anticoagulation.The study by Wiegers et al. has shown favourable maternal and foetal outcomes once greater than 20 weeks gestation is reached in patients with BCS and/or PVT. However, the risk of preterm birth and early pregnancy loss remains. These results are in keeping with the recent study by Andrade et al. (Journal of Hepatology 2018; 69: 1242-1249) looking at pregnancy outcomes from 24 pregnancies in 16 women with idiopathic non-cirrhotic portal hypertension (INCPH). Rautou et al. (Journal of Hepatology 2009; 51: 47-54) reviewed 24 pregnancies in 16 women with BCS and also reported similar findings. Taken as a whole, these results support the concept that patients with vascular liver disease can achieve favourable pregnancy outcomes but warrant careful consideration in pregnancy.Preconception counselling is a crucial opportunity to optimise patients with vascular liver disease who are considering pregnancy. This can be achieved in a multidisciplinary forum with input from obstetricians, haematologists and hepatologists. It is useful to identify those women with significant portal hypertension and varices before pregnancy so that appropriate surveillance and eradication with endoscopic band ligation and/or prophylaxis with beta blockers is undertaken. If pregnancy is achieved before surveillance, then a second trimester endoscopy for those with significant portal hypertension should be performed. In patients with portal and mesenteric vein thrombosis, magnetic resonance imaging of the pelvis may be needed to assess for the presence of abdominal wall/pelvic varices. This stratifies the risk of a variceal bleed and allows planning of the mode of delivery (caesarean, vaginal or assisted vaginal delivery). Wiegers et al. reported 2 variceal bleeds in pregnancy but did not find a significant association with adverse maternal outcomes, though this may be related to the low number of patients. Andrade et al. also reported 2 variceal bleeds including 1 patient with PVT without adequate endoscopic prophylaxis who required a portosystemic shunt. This outlines the need for appropriate screening and portal hypertension management according to findings.The majority of patients with BCS and PVT have an underlying pro-thrombotic tendency and the intra-partum and the post-partum periods are associated with thrombotic events. Vitamin K antagonists are historically the commonest anticoagulation used in BCS and PVT which should be switched to low molecular heparin ideally before conception. The use of anticoagulation is more common in patients with BCS and PVT than in INCPH (38/45 women in BCS and/or PVT compared to 4/16 in INCPH). 4 out of 6 women with BCS and/or PVT who experienced post-partum haemorrhage (PPH) were on anticoagulation. 2 patients with INCPH had PPH whilst on anticoagulation which may be confounded by the thrombocytopenia and type-2 error. In the study by Rautou et al., 17/24 pregnancies received anticoagulation and the 4 women who experienced post-partum bleeding (vaginal or intrauterine/parietal haematoma) were on anticoagulation which includes one woman with an ectopic pregnancy. No maternal deaths were reported in the three studies and the continued use of anticoagulation when indicated is safe and appropriate.The mode of delivery did not affect the risk of PPH in the three studies. The mode of delivery should be decided based on the individual risk profile taking into account the severity of portal hypertension, distribution of venous thrombosis, presence of coagulopathy and thrombocytopenia, obstetric indications and the presence of oesophageal or abdominal wall/pelvic varices.The live birth rates may be lower in patients with BCS compared to PVT (75% versus 82% after excluding first trimester pregnancy loss) but due to the low number of patients it remains difficult to interpret the results in this study. In the study by Andrade et al., all 18 pregnancies reaching 20 weeks gestation were delivered with 2 infant deaths (both preterm births). Rautou et al. reported 16/17 live births in pregnancies reaching 20 weeks gestation.To conclude, patients with BCS and PVT after 20 weeks gestation and appropriate planning can have a reasonable expectation for delivery and successful outcomes. Preconception counselling and antenatal care with multidisciplinary input is key to achieving this goal.
Unlike many viral infections such as influenza, and the two previous incarnations of the coronavirus, SARS and MERS, Covid-19 originally appeared to be of similar severity, after adjusting for age, BMI and other co-morbidities, in the pregnant as in the non-pregnant population. Worryingly the paper from the Italian Obstetric Surveillance System COVID-19 Working Group (p …), suggests that, in pregnancy, the virus may be getting more virulent with the advent of newer variants. Specifically the need for ventilation or ICU admission was significantly increased during the second wave (alpha variant predominant) compared to the first (wild-type predominant), albeit with no maternal deaths during the first wave and only one during the second. If real, this is both unexpected and concerning. Unexpected, because viruses tend to mutate in the direction of reduced severity; it is not in the interests of the virus that the host dies. Concerning, because it suggest that the newer variants are behaving more like other viral diseases; causing more severe disease in pregnancy.The evidence from Italy is supported by at least three other sources. In August a preprint from the UK Obstetric Surveillance Service (Vousden et al. MedRxiv 2021.07.22.21261000; doi: https://doi.org/10.1101/2021.07.22.21261000 accessed 30 September) reported disease severity in pregnancy when wild type predominated, when alpha predominated and when delta predominated. In each succeeding phase disease severity in increased. On 24 September the UK Intensive Care National Audit & Research Centre reported (ICNARC 17 September 2021 https://www.icnarc.org/Our-Audit/Audits/Cmp/Reports accessed 30 September) that the absolute numbers of pregnant women admitted to critical care with Covid were significantly higher in the second (alpha) wave than the first (wild type), and looked set to be significantly higher again in the third (delta) wave. Finally a large series from Nair Hospital, the largest hospital caring for Covid in Mumbai (Mahajan et al. Obstet Gynecol: July 7, 2021 doi: 10.1097/AOG.0000000000004529), reported significantly higher maternal mortality during the second (alpha predominant) wave than the first (wild type).The lesson for women is simple, get vaccinated. Vaccines are safe and if the disease is really getting more severe, the balance of risks and benefits will be moving overwhelmingly in favour of vaccination. The lesson for obstetricians is more complicated. Encourage women to get vaccinated and take the disease seriously. Keep women with Covid out of hospital if possible, but monitor them with saturation monitors reliably, so those who deteriorate can be picked up quickly. When they need admission follow evidence-based treatment guidelines, and keep using personal protective equipment. We’re not yet done with Covid.Jim Thornton MD FRCOGEmeritus Professor of Obstetrics & Gynaecology, University of Nottingham.
Objective: To study the impact of absolute uterine factor infertility (AUFI) and uterus transplantation (UTx) on women, and UTx recipients’ perceptions of Utx and reproductive autonomy Design: Convergent mixed-methods study. Setting: UTx program in a large academic medical centre in the United States. Population/Sample: 20 Utx recipients Methods: A medical chart review was conducted to collect patient demographic information, and clinical outcomes. Semi-structured interviews collected information regarding participants’ experience. Main Outcome Measure(s): The outcomes of interest were participants’ experience of infertility, experience with UTx, and general perceptions of UTx. Results: 7 participants were pregnant (one with a second child), 6 had experienced early graft failure and removal, 5 had delivered a healthy baby, and 4 had a viable graft and were awaiting embryo transfer. The primary themes identified were: the negative impact of AUFI diagnosis on psychological wellbeing, relationships, and female identity; the positive impact of UTx on healing the emotional scars of AUFI, female identity, and value of research trial participation; and the perception of UTx as an expansion of reproductive autonomy. All participants reported Utx was worthwhile, regardless of individual outcome. On bivariate analysis, disease aetiology, having a child after uterus transplantation, experiencing graft failure and current pregnancy were not significantly associated with the impact of AUFI or of UTx on participants’ identities. Conclusion: AUFI has a negative impact on women from a young age, affects multiple relationships, and challenges female identity. UTx helps reverse this impact, transforming women’s life narrative of infertility and enhancing female identity.
Obstetric care for women that use antidepressants in pregnancyLine Kolding, MD, PhDVera Ehrenstein, MPH, DSc, ProfessorLars Pedersen, MSc, PhD, ProfessorPuk Sandager, MD, PhD, Associate ProfessorOlav B. Petersen, MD, PhD, ProfessorNiels Uldbjerg, MD, DMSc, ProfessorLars H. Pedersen, MD, PhD, ProfessorCorresponding:Lars Henning PedersenAarhus University Hospital / Aarhus UniversityPalle Juul-Jensens Blvd. 99, 8200 Aarhus N, DenmarkEmail: firstname.lastname@example.orgPhone: +45 50526512We are grateful to Drs. Braillon and Bewley for their interest in our recent paper in the BJOG 1 and would like to elaborate on some of the important points they raise.We agree with Braillon and Bewley on the urgent need for improved pharmacovigilance of medication in pregnancy in general, and for antidepressants in particular. There are excellent international collaborations (e.g., the EuroCat) and local initiatives (e.g., the Swedish JanusInfo), but clinically we’re often forced to rely on very limited information indeed. Systematic international recording as suggested by Braillon and Bewley would represent an important step forward.On a smaller scale, we are establishing an automated surveillance system based on curated data that include information on both pre- and postnatally diagnosed malformations. We have, however, faced substantial legal and bureaucratic challenges, and have been forced to use data from the Central Denmark Region only, instead of national data. The surveillance system is consequently based on information on approx. 75,000 pregnancies, and even though it has the potential to aide clinical management, it is a drop in the ocean of the huge potential of for instance a comparable European collaboration.In our study, we used ≥2 redeemed prescriptions to define exposure with a prevalence 1.1%.1 The prevalence of pregnant women that redeemed ≥1 prescription was 3.2% (p. 3/ Table S1), and even though this is likely an overestimation due to non-adherence, the estimates are in line with previously reported prevalences in Scandinavia.2Braillon and Bewley emphasise the need to also consider non-pharmacological treatment of some pregnant women with depression and, further, to provide evidence-based and individualised treatment of women in the reproductive ages. Optimal individualised care will definitely result in non-pharmacological treatment of some pregnant women but, reversely, will cause yet other women to continue or initiate pharmacological treatment. This is in line with what is almost a truism in this field, that the potential harmful foetal effects must be balanced against the potential benefits of a pharmacological treatment, but it is no easy task. Pregnant women might overestimate the foetal risks associated with use of medication3 and discontinue important treatment, on the other hand some may use medication when there may be a better alternative for them. Regardless, we need to provide optimal obstetric care for the pregnant women that choose treatment with antidepressants. If our results are correct, prenatal follow-up of pregnant women treated with venlafaxine may include targeted foetal heart scans, even though the underlying causal explanation for the observed association with cardiac malformations is undetermined.1. Kolding L, Ehrenstein V, Pedersen L, Sandager P, Petersen OB, Uldbjerg N, et al. Antidepressant use in pregnancy and severe cardiac malformations: Danish register-based study. BJOG. 2021 May 25.2. Zoega H, Kieler H, Norgaard M, Furu K, Valdimarsdottir U, Brandt L, et al. Use of SSRI and SNRI Antidepressants during Pregnancy: A Population-Based Study from Denmark, Iceland, Norway and Sweden. PLoS One. 2015;10(12):e0144474.3. Wolgast E, Lindh-Åstrand L, Lilliecreutz C. Women’s perceptions of medication use during pregnancy and breastfeeding—A Swedish cross-sectional questionnaire study. Acta Obstetricia et Gynecologica Scandinavica. 2019;98(7):856-64.
BJOG-21-0667.R1: Our Guidelines Are Not Good EnoughAlexandra Wojtaszewskaa, Martin HirschbaWatford General Hospital, Watford, United KingdombOxford Endometriosis CaRe Centre, Nuffield Department of Women’s & Reproductive Health, University of Oxford, Oxford, United Kingdom.Declarations of interest: noneFinancial support received: noneBJOG-21-0667.R1: Our Guidelines Are Not Good EnoughAmoah et al. highlight the lack of high-quality fibroid guidelines in their appraisal of uterine fibroid management guidelines. This paper sheds light on the association between low quality research informing low quality clinical guidance. The authors included nine national and international guidelines on fibroid management in their analysis and screened 189 recommendations and statements made across these documents. Guideline quality was assessed using the AGREE-II instrument and no high-quality guidelines were identified. No guidelines reported involvement of patients with fibroids in their development and across all guidelines consensus was reached on only three (1.6%) of 189 statements. The authors explored the quality of evidence base behind the recommendations concluding that 25.3% were developed from good-quality evidence while 27.7% were based on lowest quality evidence (expert opinion or clinical consensus).These findings of poor quality and high discrepancy between guideline recommendations for fibroids are not unique to the condition. Other systematic reviews found similar results when analysing guidelines for management of endometriosis (Hirsch et al. BJOG 2018;125:556-564) and uncomplicated birth (Zhao et al. BJOG 2020;127:789-797).When writing or updating guidelines, locally or nationally, authors must consider how to ensure highest possible quality. There are several validated tools for quality assessment available (including AGREE II, ADAPTE, AMTAR and INAHTA and iCAHE Guideline Quality Checklists).The landscape for guideline development is changing. The rapid development of novel technologies requires a prompt response and evaluation of not only efficacy but the wider environmental impact and health economic assessment. The current system of laborious static single point assessments of evidence-based medicine producing clinical guidelines every few years is no longer appropriate. The National Institute for Health and Care Excellence (NICE) acknowledge the need for proactive, fluid, and flexible processes to enable the digitalisation of health systems to inform practice through real-world evidence (NICE 2021, The NICE Strategy 2021 to 2026 ). Guidelines will respond in a dynamic manner to population changes using contemporaneous evaluation of clinical data available from digitalised care systems. We look forward to integrated care systems delivering population-based healthcare on a regional basis. Guidelines will extend across health, social care, and public health focusing on health prevention, reducing health inequality, and delivering those interventions that offer the greatest benefit.As highlighted by this study, the development of guidelines without standardised methods is commonplace. This may lead to exclusion of beneficial treatments, a paucity of comparable recommendations, recommendations based on poor quality data, and poor patient outcomes. Looking to the future we do not see the need to fix a fractured guideline development system but rather build a new one. We must adapt and adopt the integration of digitalised real-world health system data to facilitate rapid and robust clinical decisions on a regional or national basis.