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.
Mini-commentary on BJOG-19-1802.R1 & BJOG-19-1803.R1Title: To be decodedZarko Alfirevic,Department of Women’s and Children’s Health, University of LiverpoolSimon GatesCancer Research UK Clinical Trials Unit, University of BirminghamEmail contact: Zarko Alfirevic, Zarko@liverpool.ac.ukRandomised trials remain gold standard for evaluation of effectiveness of medical interventions. However, they are expensive, time consuming and demand huge efforts from participants, researchers and clinical services that facilitate them. Even when trials are successfully completed, peer reviewers often find them wanting. One of the most common criticisms is a ‘lack of power’ to tackle clinically important outcomes. Why is this happening time and again?When an important clinical question creates an equipoise, trialists are faced with difficult choices. If they design a trial to tackle the most important (often rare) outcomes aiming to detect modest, but plausible, risk reductions from a proposed intervention, such studies are rarely feasible and very expensive forcing most funders to simply walk away. Common ‘remedies’ are to change the outcome to something more common and less important (often composite), or to propose an unrealistic risk reduction, sometimes in excess of 50%. Trials of magnesium sulphate for neuroprotection included in the seminal Cochrane review (Doyle LW et al. DOI: 10.1002/14651858.CD004661.pub3) that triggered changes in numerous guidelines world-wide were not an exception (Table 1).Cerebral palsy is a rare, but devastating complication of prematurity and even a very modest reduction would, surely, be worth detecting. The problem is that even in the most ‘at risk’ groups, the incidence of cerebral palsy will not exceed 10%. A conventional sample size calculation estimates that to detect a ‘massive’ 25% risk reduction in cerebral palsy, in excess of 5,000 women would have to be randomised.Interestingly, such a priori sample size calculations are not a feature of most published meta-analyses. Step forward Trial Sequential Analysis (TSA). The TSA is a deceptively simple concept; meta-analysis sample size needs to be increased to allow not only for the heterogeneity of included studies, but also for repeated testing when meta-analyses are being updated and therefore subjected to repeated significance testing. Interested readers can find out more from the Copenhagen Trial Unit’s website - vocal proponents of this methodology (www.ctu.dk/tsa).In their two sister papers, Wolf et al have, quite ingeniously, used TSA to determine the size of their randomised trial and, by doing so, avoided the risk of their randomised trial and updated meta analysis being criticised as ‘underpowered’ (Wolf H et al. BJOG 2020 xxxx (RCT); Wolf H et al. (BJOG 2020 xxxx (SR & MA). Could this concept be a methodological ‘game changer’ in perinatal trials?The concept of TSA has been widely criticised, and a Cochrane Collaboration expert panel recommended against its use (https://methods.cochrane.org/sites/default/files/public/uploads/tsa_expert_panel_guidance_and_recommendation_final.pdf). Key criticisms are, first, that decision-makers require a summary of the currently available evidence and this should not depend on past and future updates. Second, TSA focuses only on statistical significance. Interpretation of meta-analysis should be based on the estimates of the treatment effect and its uncertainty, rather than whether an arbitrary significance threshold is passed. Third, the ways that evidence accumulates in systematic reviews and individual trials are fundamentally different. Review updates are not equivalent to trial interim analyses; updates are not pre-planned and their number cannot be determined in advance. Furthermore, reviews address multiple clinically-relevant effects on several outcomes or subgroup analyses, which need to be integrated into an overall conclusion. The Cochrane expert panel concluded: “Any sequential adjustment procedure is necessarily based on a particular instance of the evolution of evidence that applies to a limited context and cannot satisfy the requirements of all decision makers.”Table 1. Key features of randomised trials of MgSO4given to pregnant women for prevention of cerebral palsy in infants born preterm
Objective. To externally validate five approaches to predict ectopic pregnancy (EP) in pregnancies of unknown location (PUL): the M6P and M6NP risk models, the two-step triage strategy (2ST, which incorporates M6P), the M4 risk model, and beta human chorionic gonadotropin ratio cut-offs (BhCG-RC). Design. Secondary analysis of a prospective cohort study.Setting. Eight UK early pregnancy assessment units.Population. Women presenting with a PUL and BhCG >25 IU/L.Methods. Women were managed using the 2ST protocol: PUL were classified as low risk of EP if presenting progesterone ≤2 nmol/L; the remaining cases returned two days later for triage based on M6P. EP risk ≥5% was used to classify PUL as high risk. Missing values were imputed, and predictions for the five approaches were calculated post hoc. We meta-analysed centre-specific results. Main outcome measures. Discrimination, calibration and clinical utility (decision curve analysis) for predicting EP.Results. Of 2899 eligible women, the primary analysis excluded 297 (10%) women who were lost to follow-up. The area under the ROC curve for EP was 0.89 (95% confidence interval 0.86-0.91) for M6P, 0.88 (0.86-0.90) for 2ST, 0.86 (0.83-0.88) for M6NP, and 0.82 (0.78-0.85) for M4. Sensitivities for EP were 96% (M6P), 94% (2ST), 92% (N6NP), 80% (M4), and 58% (BhCG-RC); false positive rates were 35%, 33%, 39%, 24%, and 13%. M6P and 2ST had the best clinical utility and good overall calibration, with modest variability between centres.Conclusions. 2ST and M6P performed best to predict and triage PUL.Funding. Research Foundation – Flanders (FWO; G0B4716N), Internal Funds KU Leuven (C24/15/037), NIHR Collaboration for Leadership in Applied Health Research & Care, NorthWest London (RDIP033), NIHR Biomedical Research Centre based at Imperial College Healthcare NHS Trust. Keywords Pregnancy of unknown location, ectopic pregnancy, beta human chorionic gonadotrophin (BhCG) ratio, progesterone, prediction model, prediction model validation
Specific therapies in pregnant women are discussedThe health crisis caused by the novel SARS-cov-2 (2019-nCoV) related pandemic requires urgent and necessary therapeutic response. Pregnant women are just as exposed as the general population and should not be excluded, because of their status, from discussions on effective and well tolerated candidate treatments. While in countries that have opted for national containment, daily non-emergency medical and surgical activities are suspended, obstetric services continue to operate relentlessly and are experiencing a surge in so-called ”at-risk” pregnancies. Some countries have now recommended routine screening of all pregnant women 1 but the low availability and performance of the current tests limits their use. Management of an infected pregnant women is essentially conditioned by maternal symptomatology. Women with little or no symptoms do not require routine treatment or in-patient care and simply need to be monitored for up to 15 days for evidence of respiratory deterioration. In the absence of validated specific treatment, the primary approach to therapy is mainly symptomatic and delivery is considered in the event of critical respiratory distress in order to maximize oxygenation and lung capacity2–4 . However, it has been reported that women with respiratory signs may be given antiviral treatment to improve their clinical condition 2,4To date, there is no proven effective strategy, although many teams are working tirelessly to identify an effective treatment. Four molecules are leading in this race:1) Remdesivir is a novel nucleotide analogue prodrug which incorporates into nascent viral RNA chains and results in pre-mature termination. Its effectiveness has been already demonstrated against others coronaviruses such as SARS-Cov and MERS-Cov5, and it has proven to be highly effective on in vitro 2019-nCoV infection6. Compassionate use in human were also reported 7 and phase 3 studies are currently underway.2) (Hydroxy)chloroquine has been known for years because of its effectiveness in the treatment of inflammatory diseases and against malaria. Recent studies have shown antiviral effects of chloroquine and in vitro studies concluded that it was highly effective in the control of 2019-nCoV 6,8. Elevation of endosomal pH and interference with terminal glycosylation of the cellular receptor, angiotensin-converting enzyme 2 conduct to block virus infection. (Hydroxy)chloroquine has been used in 2019-nCoV infected humans with highly controversial restuls9,10 and well-designed randomized studies should be available soon.3) Lopinavir, a viral protease inhibitor, with its pharmacological booster Ritonavir (LPV/R) are commonly used in HIV positive patients. It has already been used for SARS-Cov. Some countries such as China and India approved its use in symptomatic infected patients although a first randomized, controlled, open-label trial showed no benefit of LPV/R over standard care in patients with severe 2019-nCoV disease11.4) Ribavirin, is a guanosine analog that interferes with the replication of RNA and DNA viruses. It has been used for years in the treatment of chronic hepatitis C. Based on its direct anti‐viral activity against 2019‐nCoV in vitro and some evidence for its potential efficacity during the prior SARS-Cov and MERS-Cov outbreaks, it has been suggested as a potential candidate for the treatment of 2019-nCoV diease12. 2019-nCoV infected patients treated with Ribavirin have been reported by Chinese studies4,13but its exact benefit remains to be demonstrated in well designed randomized studies as well.To date, all four drugs are being independently tested in Phase 3 studies, mostly national, to investigate their efficacy and safety in the management of 2019-nCoV disease. Several European countries have also set up, as a result of joint efforts since mid-March, a randomized, multicentre, open-label trial to evaluate and compare the efficacy and toxicity of the first three treatments mentioned above.14With regard to the possibility of treating pregnant patients with these molecules, few data are available for Remdesivir. Only one study reports its use in six pregnant women in a randomized trial during Ebola epidemics. The authors reported no adverse effect15.Many more pharmacological studies on maternal-fetal tolerance of Hydroxy(chloroquine), Lopinavir and Ribavirin are available. The historical use of (hydroxy)chloroquine in antimalarial treatment, but also in connective tissue diseases, has resulted in a well-documented safety and tolerance profile in pregnant women16. Animal studies, undertaken during the Zika virus epidemic, have also suggested that chloroquine may also reduce the risk of viral transplacental transmission to the fetus17. The optimal dosage to be used in pregnant women will have to be specified, but it appears that there is no pharmacokinetic difference between chloroquine and its major metabolite between pregnant and non-pregnant women18. With respect to the use of protease inhibitors during pregnancy, such as Lopinavir, some teams have reported an increased risk of preterm delivery. However, a specific analysis of more than 4,000 pregnant women found a similar incidence and rate of adverse pregnancy outcomes than in controls at all three trimesters of pregnancy, including preterm birth, low birth weight and birth defects19. Significant teratogenic effects have been demonstrated in all animal species exposed to Ribavirin, it is therefore currently contraindicated in pregnant women and in their male sexual partners, although the ribavirin pregnancy registry did not bring evidence of teratogenicity in humans20.The use of antiviral therapy in infected pregnant patients should follow the same indication as in the general population, but some obstetric specificities should be emphasized.1) The main goal should be to slow down and at best stop the clinical progression of the disease, i.e to remain asymptomatic and to avoid progression to acute respiratory distress syndrome in symptomatic cases. In the latter, the obstetrician is often called on to perform an emergency delivery and thus to induce extreme prematurity. Expert consensus provided obstetric guidance, but the management of cases at between 25 and 32 weeks’ remains challenging in the absence of effective antiviral treatment1.2) The second objective would be to rapidly decrease viral load and duration of contagiousness in infected pregnant women. The majority of them are doing well, but the infection can disrupt their obstetrical calendar. Some procedures need to be performed at a specific age, such as first trimester serum markers, ultrasound examinations, chorionic villi sampling (CVS). The same applies to access to termination of pregnancy. All such procedures may indeed be delayed, either to limit contagion, to limit the burden on the health care team (due to reinforced barrier measures…) or in the particular case of CVS/amniocentesis, to limit the theoretical risk of fetal transmission.3) Finally, the third advantage could be to introduce preventive treatment in case of maternal contact with an infected person, similar to what is done for seasonal influenza and oseltamivir21.The use of immunotherapy such as Tocilizumab, plasma of recovered coronavirus patient, Interferons, were not discussed here as they are currently understudy only for critically ill COVID-19 patients. No place for these treatments in a patient who is still pregnant should be considered for the time being, since if the pregnant woman presents a very severe form, the birth will be considered as a priority.The results of the Phase 3 therapeutic studies should be available soon. However, it is unfortunate that infected pregnant women are not included in any appropriate research protocols. Consequently, in this period of pandemic, mutual exchanges of experience between all countries’ maternity hospitals must be carried out in order to ensure the best possible management of infected pregnant women.
Objectives: To investigate the mental status of pregnant women and to describe their obstetrical choices during the outbreak of COVID-19. Design: A cross-sectional study. Setting: Wuhan and Chongqing, two different epidemic areas. Population: A total of 1947 valid questionnaires were received. Methods: We collected information on demographic, pregnancy, and epidemic, along with their attitudes towards the epidemic, anxiety status and obstetrical choices. We described and compared the city-based distribution of all above factors, aiming to explain how anxiety and obstetrical choices existed and differed. Main Outcome Measures: To explore why differences existed, we estimated the impact of the epidemic on women’s anxiety by multivariable analysis. Results: Distribution differences could be seen between cities in employment status, household income, gestational age, fetal number, and exposure history. Women’s attitudes towards COVID-19 in Wuhan were more extreme than that in Chongqing. The anxiety rate was more than double in Wuhan (24.47%) compared to that in Chongqing (10.44%). Generally speaking, obstetrical choices were similar among the 1947 participants, but more obvious in Wuhan. Conclusions: Our study found that the outbreak aggravated prenatal anxiety, and the influence factors could be targets of mental care. Synchronously, vital obstetrical choices changed, followed by pertinent professional advice to prevent irreversible adverse pregnancy outcomes. Online platforms may play crucial roles to address patients’ needs in future PHEs. Funding: National Natural Science Foundation of China (No. 81771614 and No. 81771613), and the National Key Research and Development Program of China (No. 2016YFC1000407). Keywords: COVID-19; Pregnancy; Prenatal Anxiety; Obstetrical Choices.
Dear Editor,We read the letter from colleagues Dr. Seedat and Dr. Marshall, commenting on our article, with great interest (1, 2). Their clarifications on the UK National Screening Committee (UK NSC) position are very clear. The UK NSC decided against a general screening since they cannot assess the benefits and harms in the patient populations of women (3) but they could indeed in newborns. The on-going clinical trial (GBS3 Trial; ISRCTN49639731) in the UK will compare the current risk-based strategy to two different screening tests. A lab based culture test at 3 to 5 weeks before anticipated delivery date will use an established microbiological technique [Enriched Culture Medium Testing] to reduce false-negative results and a molecular point of care test at the onset of labour. The latter test reduces the time period between screening and the start of labour. The predictive value of antenatal GBS cultures decreases if the interval between culture and delivery is longer than 5 weeks. The results of the trial will help to determine the appropriate screening technique and the rational use of antibiotics for the prevention of early onset GBS sepsis in newborn babies.Perinatal empirical therapy of newborns at risk for or with suspected EOS represents the main contributor to the use of antibiotics in early life (4). There is growing concern about the effects that unnecessary exposure to antibiotics in the perinatal period may have on the future health of these children (5, 6). Antibiotic-related alterations in the microbiome may have downstream effects on the developing immune system and may increase the risk of allergic, autoimmune, and metabolic diseases (5, 6).Seedat and Marshall state that according to another study, the use of IAP would indeed increase if screening were implemented, and that the portion of women receiving IAP would be ‘low risk women’ who… ‘would not have a neonate with EOGBS in the absence of IAP’ (1). In this statement is embedded the assumption that the currently established risk factors are indeed a good prediction of EOGBS transmission. However, 50% of neonates with early onset sepsis with GBS did not have risk factors. To the contrary, we confirm in our meta-analysis and systematic review that universal screening lowered the incidence of early onset GBS sepsis in newborn whereas risk-based approaches did not (2). This might indicate that although screening is imperfect, risk factors might be worse in predicting EOGBS outcomes.Besides, we found no evidence that the rate of intrapartum antibiotic treatment was different in risk-based screening than in universal screening. Administration of antibiotics in risk-based policies was in our study neither lower nor associated with a reduction in the burden of disease in early onset GBS sepsis (2). We are looking forward to the results of the GBS3 trial since there is a need for unbiased evidence on the appropriate policy. A trial comparing screening with risk-factor based intrapartum antibiotic prophylaxis is hard to conduct in areas that currently have a screening policy. Recruitment of participants is very challenging and a premature stop for futility is very likely. A lot of women might not want a risk-based protocol if screening is already the standard of care or easily available. Therefore, the UK data will be very helpful in guiding the future way.References1. Seedat F, Marshall J. Re: Universal screening versus risk-based protocols for antibiotic prophylaxis during childbirth to prevent early-onset Group B streptococcal disease: A systematic review and meta-analysis. (First comment letter. Reference to be added). BJOG. 2020.2. Hasperhoven GF, Al-Nasiry S, Bekker V, Villamor E, Kramer B. Universal screening versus risk-based protocols for antibiotic prophylaxis during childbirth to prevent early-onset Group B streptococcal disease: a systematic review and meta-analysis. BJOG. 2020. https://doi.org/10.1111/1471-0528.160853. Seedat F, Geppert J, Stinton C, Patterson J, Freeman K, Johnson SA, et al. Universal antenatal screening for group B streptococcus may cause more harm than good. BMJ. 2019;364:l463.4. Achten NB, Klingenberg C, Benitz WE, Stocker M, Schlapbach LJ, Giannoni E, et al. Association of Use of the Neonatal Early-Onset Sepsis Calculator With Reduction in Antibiotic Therapy and Safety: A Systematic Review and Meta-analysis. JAMA Pediatr. 2019.5. Cotten CM. Adverse consequences of neonatal antibiotic exposure. Curr Opin Pediatr. 2016;28(2):141-9.6. Esaiassen E, Fjalstad JW, Juvet LK, van den Anker JN, Klingenberg C. Antibiotic exposure in neonates and early adverse outcomes: a systematic review and meta-analysis. J Antimicrob Chemother. 2017;72(7):1858-70.
Dear Editor,Thank you for the opportunity to respond to Dr Sahu’s letter1. We would like to thank Dr Sahu and his team for their valuable points and ourselves recognise and acknowledge the gaps in our early commentary2 which reflected on the early practice at our hospital, with an aim to help fellow obstetricians with the management of COVID-19 at the start of the outbreak. Since then, more literature has been published providing us with greater knowledge regarding this new infection. Guidance from the Royal College of Obstetricians and Gynaecologists (RCOG)3 and International Society of Ultrasound in Obstetrics and Gynaecology (ISUOG)4 amongst others help us streamline management of COVID-19 in pregnant patients.Both guidelines concur that radiographic investigations should be performed in pregnant patients – protecting the fetus by using a radiation shield over the gravid uterus. Chest CT has high sensitivity up to 97% for diagnosis of COVID-19 and may be considered as primary tool for COVID-19 detection.Both guidelines recommend the use of antenatal corticosteroids (ANC) for the usual indications but cautions use in critically ill women with COVID-19 infection as it may worsen their clinical condition. Importantly, urgent deliveries should not be delayed for the administration of ANC.Li et al5 compared clinical characteristics, maternal and neonatal outcomes of pregnant women with and without COVID-19. They found that COVID-19 infection generally causes mild respiratory symptoms in pregnant women, with no deaths or severe respiratory complications requiring critical care. They observed a higher rate of preterm deliveries in confirmed cases (33.3%) compared to control groups (¬5%). This study included two patients who had vaginal deliveries prior to COVID-19 diagnosis. Their newborns did not show any respiratory symptoms.New reports of SARS-COV-2 IgM in infants6 at birth suggest possibility of vertical transmission although COVID-19 infection in newborns is more commonly likely due to neonatal transmission.During breastfeeding, the main risk for infants lies in their close contact with mothers and transmission of infective respiratory droplets. Infected mothers wishing to breastfeed should do so with precautions such as wearing surgical masks, practising good hand hygiene and thorough cleaning of equipment after use. While the decision for separation of mother and baby has serious consequences on bonding and mental health, we continue to advise separation of baby from mothers infected with COVID-19 due to risk of neonatal transmission.Current data suggests that the adverse effects of COVID-19 in pregnancy are less severe than those of SARS-CoV and MERS-CoV. All presently reported patients were diagnosed in the third trimester and the potential effects of COVID-19 infections in the first and second trimesters remain to be investigated.As Dr Sahu mentioned, comparative studies are scarce. Establishment of international registries will improve our understanding of COVID-19 in pregnancy. Meanwhile, we shall continue to support one another and work together in the fight against this pandemic.We would like to thank the all departments from the Division of Obstetrics and Gynaecology, Infectious Diseases Department and all staff in KK Womens’ and Children’s Hospital for leading the COVID-19 fight locally.Monica Shi Qi Chua1, Jill Cheng Sim Lee2, Suzanna Sulaiman1, Hak Koon Tan31Department of Obstetrics and Gynaecology,2Department of Urogynaecology,3Division of Obstetrics and GynaecologyKK Women’s and Children’s Hospital, Singapore