I have always said that women with early MS who start and extend families should have no reason to worry about additional problems with their pregnancy and childbirth because. It may be different for women with more advanced MS who are disabled. Maybe I should revise this general advice based on the study below.
In this study, 15 women with MS had 16 children. The cesarean section rate was 14 out of 16 deliveries or a staggering 87.5% of pregnancies. The main reason for C-sections was given as chronic fatigue and neurological deficits. The latter is interesting in that the mean disease duration of this cohort was less than 10 years with an average EDSS of 2.0. I suspect this cohort is biased and recruited women with MS via a high-risk clinic or an obstetric unit.
These results are incongruent with my experience as an MSologist. What about you? If there are any women with MS reading this post who have had children after being diagnosed with MS did you have a natural vaginal delivery, assisted delivery or a C-section?
Objectives: Multiple sclerosis (MS) is a chronic autoimmune and neurodegenerative disease. This study evaluated pregnancy-related issues in patients with MS in one perinatological centre.
Material and methods: A single-centre, retrospective study of the perinatal period in patients with MS admitted at the Dpt. of Gynaecology and Obstetrics, Jessenius Faculty of Medicine, Comenius University and the University Hospital in Martin, Slovak Republic, European Union from January 1, 2015 to December 1, 2020 was performed. Selected parameters from personal, obstetric, and neurological histories were analysed.
Results: A cohort of 15 patients (32.5±5.3 years) with a relapsing-remitting form of MS gave birth to 16 children. The mean length of MS at the time of delivery was 9±3.6 years. The severity of the Expanded Disability Status Scale score was 2.0±1.5. Caesarean section (CS) was indicated in 14 deliveries (87.5%). It was elective CS in 10 patients. The most common indication for elective CS was a combination of significant chronic fatigue syndrome and neurological deficit (paresis).
Conclusions: The basis for the management of pregnancy, childbirth, and the postpartum period in women with MS is a planned pregnancy based on close cooperation among patients, gynaecologists, and neurologists. Vaginal delivery is not primarily contraindicated. Indications for CS should be considered individually. One way to minimise the indications for CS is a more accurate diagnosis and personalised treatment of fatigue in pregnant women with MS. Presumably, both obstetricians and neurologists prefer vaginal delivery as the first choice in patients with fatigue syndrome.
General Disclaimer: Please note that the opinions expressed here are those of Professor Giovannoni and do not necessarily reflect the positions of the Barts and The London School of Medicine and Dentistry nor Barts Health NHS Trust and are not meant to be interpreted as personal clinical advice.
My husband and I were hoping to start a family this year. What do you advise; should I attempt to fall pregnant or wait until after the COVID-19 pandemic?
How long is a piece of string? Mouse Doctor 2 would tell you to divide the string in half and the length of the original piece of string is twice that of one of the halves. With the flattening of the curve and the extension of the tail COVID-19 pandemic is likely to extend beyond 2020 and into 2021. Some epidemiologists are predicting the tail going out to 2022. Therefore, in my opinion, COVID-19 pandemic is not necessarily a reason to put your life on hold.
Image of flattening=the-curve is from the CDC
Clearly, for some people, there are economic reasons why they wouldn’t want to start a family in the current climate. For example, if you or your partner have lost your job, or you are uncertain about your long-term employment prospects, these economic factors will potentially impact on your decision to start a family.
What about SARS-CoV-2, a coronavirus, and pregnancy?
There is no published data that coronavirus infections are associated with foetal abnormalities or a higher miscarriage rate. It looks as if transplacental infection of the foetus with SARS-CoV-2 is unlikely. Saying this there is one case report of a neonate, born by caesarian section from a mother who had severe COVID-19, who tested positive for the virus. The problem with this case is that the neonate could have been infected at the time of birth. The good news is that children, including very young children, don’t seem to get COVID-19. Why children are resistant to COVID-19 is unknown at present, but it must have something to do with the biology of the virus. Therefore, it is unlikely that newborn babies are at significant risk of severe COVID-19 and there is no evidence to suggest worse foetal outcomes.
The other important thing to realise that if you do fall pregnant and get infected with SARS-CoV-2 and develop COVID-19 or not the antibodies you produce against the virus will cross the placenta and should give your newborn child some protection against will-type viral infection in early life (6-12 months). These transplacental antibodies may be sufficient to protect them and bridge the gap until we hopefully have an effective vaccine against SARS-CoV2.
What about being pregnant when you get COVID-19?
So far the data is very reassuring in that the case reports from China and elsewhere suggest being pregnant doesn’t increase the risk of getting severe COVID-19 and possibly to the contrary, i.e. less severe disease. However, there are relatively small numbers of pregnant women who do get severe COVID-19, whether this is a smaller proportion than the general aged-matched population is at present unknown.
As severe COVID-19 is a major stressor it may trigger premature labour. In an Italian case series of 42 pregnant women with COVID-19 and who were admitted to hospital only seven required respiratory support and eventually did well. Out of the 42 pregnancies, two premature labours occurred. This suggests COVID-19 in itself is not associated with adverse pregnancy outcomes. Saying this it is clear from the published data that if you are in the third trimester of pregnancy and you present with COVID-19 infection then a large number of women are having their babies born by caesarian section. I assume this is being driven by the medical condition of the mother; I doubt many women hospitalised with COVID-19 will be in a state to go through with normal vaginal delivery.
Overall, I think the data is reassuring in that it is unlikely being pregnant puts you at greater risk of COVID-19 or severe COVID-19. Based on the published data to date it is likely that pregnancy a state of mild immunosuppression may actually protect you from severe COVID-19.
What about the babies of woman who have had COVID-19 and subsequently delivered their babies?
The third-trimester data looks reassuring, but it is too early to make a call on the outcomes of babies born to mother who had COVID-19 during the first and second trimesters of pregnancy. Based on the biology of coronaviruses and pregnancy these babies are likely to be fine but will have to wait for the data to emerge. It will be important that not only the children of mothers with COVID-19 need to be studied but those born to mothers who had asymptomatic SARS-CoV-2 infection. For the latter, we need good population-based antibody studies to be done.
Please note some obstetricians have looked at what happened to pregnancy outcomes from the original SARS and MERS epidemics to make some predictions about SARS-CoV-2. I am not sure we can use this data as these two outbreaks were due to more virulent viruses with a much higher case-fatality rate.
Conclusion: So my advice, in general, would be not to put your lives on hold unless you have to for other reasons. It is unlikely that SARS-CoV-2 causes foetal abnormalities, transplacental transmission of the virus is likely to be rare and there is no suggestion of an increase miscarriage rate due to COVID-19. Pregnancy itself doesn’t put you at increased risk of COVID-19 or severe COVID-19 and may actually protect you from the latter. In the case of getting severe COVID-19 whilst pregnant, there is a small chance of premature labour and a high likelihood that if you are ready to deliver the delivery will be by caesarian section.
Introduction: The pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has exposed vulnerable populations to an unprecedented global health crisis. The knowledge gained from previous human coronavirus outbreaks suggests that pregnant women and their fetuses are particularly susceptible to poor outcomes. The objective of this study was to summarize the clinical manifestations and maternal and perinatal outcomes of COVID-19 during pregnancy.
Material and methods: We searched databases for all case reports and series from February 12 to April 4, 2020. Multiple terms and combinations were used including COVID-19, pregnancy, maternal mortality, maternal morbidity, complications, clinical manifestations, neonatal morbidity, intrauterine fetal death, neonatal mortality and SARS-CoV-2. Eligibility criteria included peer-reviewed publications written in English or Chinese and quantitative real-time polymerase chain reaction (PCR) or dual fluorescence PCR confirmed SARS-CoV-2 infection. Unpublished reports, unspecified date and location of the study or suspicion of duplicate reporting, cases with suspected COVID-19 that were not confirmed by a laboratory test, and unreported maternal or perinatal outcomes were excluded. Data on clinical manifestations, maternal and perinatal outcomes including vertical transmission were extracted and analyzed.
Results: Eighteen articles reporting data from 108 pregnancies between December 8, 2019 and April 1, 2020 were included in the current study. Most reports described women presenting in the third trimester with fever (68%) and coughing (34%). Lymphocytopenia (59%) with elevated C-reactive protein (70%) was observed and 91% were delivered by cesarean section. Three maternal intensive care unit admissions were noted but no maternal deaths. One neonatal death and one intrauterine death were also reported.
Conclusions: Although the majority of mothers were discharged without any major complications, severe maternal morbidity as a result of COVID-19 and perinatal deaths were reported. Vertical transmission of the COVID-19 could not be ruled out. Careful monitoring of pregnancies with COVID-19 and measures to prevent neonatal infection are warranted.
From February 24, 2020, a COVID-19 obstetric task force was structured to deliver management recommendations for obstetric care. From March 1, 2020, six COVID-19 hubs and their spokes were designated. An interim analysis of cases occurring in or transferred to these hubs was performed on March 20, 2020 and recommendations were released on March 24, 2020. The vision of this strict organization was to centralize patients in high-risk maternity centers in order to concentrate human resources and personal protective equipment (PPE), dedicate protected areas of these major hospitals, and centralize clinical multidisciplinary experience with this disease. All maternity hospitals were informed to provide a protected labor and delivery room for nontransferable patients in advanced labor. A pre-triage based on temperature and 14 other items was developed in order to screen suspected patients in all hospitals to be tested with nasopharyngeal swabs. Obstetric outpatient facilities were instructed to maintain scheduled pregnancy screening as per Italian guidelines, and to provide pre-triage screening and surgical masks for personnel and patients for pre-triage-negative patients. Forty-two cases were recorded in the first 20 days of hub and spoke organization. The clinical presentation was interstitial pneumonia in 20 women. Of these, seven required respiratory support and eventually did well. Two premature labors occurred.
Background: 2019 novel coronavirus disease (COVID-19) has become a worldwide pandemic. Under such circumstance pregnant women are also affected significantly.
Objective: This study aims to observe the clinical features and outcomes of pregnant women who have been confirmed with COVID-19.
Methods: The research objects were 55 cases of suspected COVID-19 pregnant women who gave a birth from Jan 20th 2020 to Mar 5th 2020 in our hospital-a big birth center delivering about 30,000 babies in the last 3 years. These cases were subjected to pulmonary CT scan and routine blood test, manifested symptoms of fever, cough, chest tightness or gastrointestinal symptoms. They were admitted to an isolated suite, with clinical features and newborn babies being carefully observed. Among the 55 cases, 13 patients were assigned into the confirmed COVID-19 group for being tested positive severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) via maternal throat swab test, and the other 42 patients were assigned into the control group for being ruled out COVID-19 pneumonia based on new coronavirus pneumonia prevention and control program(the 7th edition).
Results: There were 2 fever patients during the prenatal period and 8 fever patients during the postpartum period in the confirmed COVID-19 group. In contrast, there were 11 prenatal fever patients and 20 postpartum fever patients in the control group (p>0.05). Among 55 cases, only 2 case had cough in the confirmed group. The imaging of pulmonary CT scan showed ground- glass opacity (46.2%, 6/13), patch-like shadows(38.5%, 5/13), fiber shadow(23.1%, 3/13), pleural effusion (38.5%, 5/13)and pleural thickening(7.7%, 1/13), and there was no statistical difference between the confirmed COVID-19 group and the control group (p>0.05). During the prenatal and postpartum period, there was no difference in the count of WBC, Neutrophils and Lymphocyte, the radio of Neutrophils and Lymphocyte and the level of CRP between the confirmed COVID-19 group and the control group(p<0.05). 20 babies (from confirmed mother and from normal mother) were subjected to SARS-CoV-2 examination by throat swab samples in 24 hours after birth and no case was tested positive.
Conclusion: The clinical symptoms and laboratory indicators are not obvious for asymptomatic and mild COVID-19 pregnant women. Pulmonary CT scan plus blood routine examination are more suitable for finding pregnancy women with asymptomatic or mild COVID-19 infection and can be used screening COVID-19, pregnant women, in the outbreak area of COVID-19 infection.
The current outbreak of the novel 2019 coronavirus disease (COVID-19) started in China in December 2019 and has since spread to several other countries. On March 25, 2020, a total of 375,498 cases had been confirmed globally with 2,201 cases in Brazil, showing the urgency of reacting to this international public health emergency. While in most cases, mild symptoms are observed, in some cases the infection leads to serious pulmonary disease. As a result, the possible consequences of the COVID-19 outbreak for pregnant women and its potential effects on the management of assisted reproductive treatments, demand attention. In this review, we summarize the latest research progress related to COVID-19 epidemiology and the reported data of pregnant women, and discuss the current evidence of COVID-19 infections during pregnancy and its potential consequences for assisted reproductive treatments. Reported data suggest that symptoms in pregnant women are similar to those in other people and that there is no evidence for higher maternal or fetal risks. However, considering the initial data and lack of comprehensive knowledge on the pathogenesis of SARS-CoV-2 during pregnancy, human reproduction societies have recommended postponing the embryo transfers and do not initiate new treatment cycles. New evidence must be considered carefully in order to adjust these recommendations accordingly at any time and to guide assisted reproductive treatments.
There are few cases of pregnant women with novel coronavirus 2019 (COVID-19) in the literature, most of them with a mild illness course. There is limited evidence about in utero infection and early positive neonatal testing. A 41-year-old G3P2 with a history of previous cesarean deliveries and diabetes mellitus presented with a 4-day history of malaise, low-grade fever, and progressive shortness of breath. A nasopharyngeal swab was positive for COVID-19, COVID-19 serology was negative. The patient developed respiratory failure requiring mechanical ventilation on day 5 of disease onset. The patient underwent a cesarean delivery, and neonatal isolation was implemented immediately after birth, without delayed cord clamping or skin-to-skin contact. The neonatal nasopharyngeal swab, 16 hours after delivery, was positive for severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) real-time polymerase chain reaction (RT-PCR), and immunoglobulin (Ig)-M and IgG for SARS-CoV-2 were negative. Maternal IgM and IgG were positive on postpartum day 4 (day 9 after symptom onset). We report a severe presentation of COVID-19 during pregnancy. To our knowledge, this is the earliest reported positive PCR in the neonate, raising the concern for vertical transmission. We suggest pregnant women should be considered as a high-risk group and minimize exposures for these reasons.
…… In 2 reports describing 18 pregnancies with coronavirus disease 2019, all were infected in the third trimester, and clinical findings were similar to those in nonpregnant adults. Fetal distress and preterm delivery were seen in some cases. All but 2 pregnancies were cesarean deliveries and no evidence of in utero transmission was seen. Data on severe acute respiratory syndrome and Middle East respiratory syndrome in pregnancy are sparse. For severe acute respiratory syndrome, the largest series of 12 pregnancies had a case-fatality rate of 25%. Complications included acute respiratory distress syndrome in 4, disseminated intravascular coagulopathy in 3, renal failure in 3, secondary bacterial pneumonia in 2, and sepsis in 2 patients. Mechanical ventilation was 3 times more likely among pregnant compared with nonpregnant women. Among 7 first-trimester infections, 4 ended in spontaneous abortion. Four of 5 women with severe acute respiratory syndrome after 24 weeks’ gestation delivered preterm. For Middle East respiratory syndrome, there were 13 case reports in pregnant women, of which 2 were asymptomatic, identified as part of a contact investigation; 3 patients (23%) died. Two pregnancies ended in fetal demise and 2 were born preterm. No evidence of in utero transmission was seen in severe acute respiratory syndrome or Middle East respiratory syndrome. Currently, no coronavirus-specific treatments have been approved by the US Food and Drug Administration. Because coronavirus disease 2019 might increase the risk of pregnancy complications, management should optimally be in a health care facility with close maternal and fetal monitoring. Principles of management of coronavirus disease 2019 in pregnancy include early isolation, aggressive infection control procedures, oxygen therapy, avoidance of fluid overload, consideration of empiric antibiotics (secondary to bacterial infection risk), laboratory testing for the virus and coinfection, fetal and uterine contraction monitoring, early mechanical ventilation for progressive respiratory failure, individualized delivery planning, and a team-based approach with multispecialty consultations. Information on coronavirus disease 2019 is increasing rapidly. Clinicians should continue to follow the Centers for Disease Control and Prevention website to stay up to date with the latest information (https://www.cdc.gov/coronavirus/2019-nCoV/hcp/index.html).
One of the problems of immune reconstitution therapies (IRTs), such as HSCT, alemtuzumab and cladribine, is nagging worry that at some time in the future your MS will reactivate. Some people with MS (pwMS) try and avoid potential triggers of disease activity, for example, vaccinations and pregnancy, particularly the post-partum state. Unfortunately, there is some evidence the latter may trigger disease activity, but at quite a low rate.
The following is the data on 122 pregnancies post-alemtuzumab presented earlier this year at ECTRIMS. The annualised relapse rate (ARR) fell to 0.02 during pregnancy, i.e. 2 relapses in 100 years, with 98% of patients being relapse-free. In comparison, in the first year after pregnancy, the ARR was 0.22, i.e. 22 relapses in 100 years of follow-up, with 82% of patients being free of relapse. The ARR was then similar to pre-pregnancy levels in the second and third years after pregnancy (0.12 each year; with 89% and 92% of patients relapse-free in each year, respectively).
One of the reasons for women with MS choosing an IRT is to start or extend their families. Based on this data I would recommend that they do just that and in the unlikely event of post-partum disease activity (1 in 5 chance) it can be dealt with by an additional course of treatment or possibly starting another DMT. What do you think?
We have many patients in our centre who have had children after alemtuzumab in our centre. I refer to them as the alemtuzumab babies because they represent the success of treating MS early and effectively. It was only 20 years ago that the previous generation of neurologists were advising their patients with MS not to have children. How times have changed?
Introduction: In childbearing women with MS, relapses may increase in frequency and severity during the postpartum period. In phase 2 and 3 clinical trials of alemtuzumab (CAMMS223 [NCT00050778]; CARE-MS I [NCT00530348]; CARE-MS II [NCT00548405]) and their extensions (CAMMS03409 [NCT00930553]; TOPAZ [NCT02255656]), alemtuzumab significantly reduced relapse rates in RRMS patients versus SC IFNB-1a and maintained efficacy over 8 years. Product labelling recommends use of contraception in women of childbearing potential for 4 months after treatment.
Aims: To examine over 8 years relapse rates before, during, and after the first pregnancy in alemtuzumab-treated patients in the CARE-MS and extension trials.
Methods: Contraceptive use was required during core studies, and for 6 months after alemtuzumab administration in the extension studies. The analysis included patients who received alemtuzumab (baseline: 5 days; 12 months later: 3 days) in phase 2 or phase 3 trials or their extension studies and became pregnant after receiving at least one dose of alemtuzumab. Patients could receive other DMT or additional as-needed alemtuzumab (12 mg/day on 3 days; ≥12 months apart) in the extensions. After pregnancy, other DMT was allowed in CAMMS03409; other DMT or further alemtuzumab was allowed in TOPAZ. The analysis only considered a patient’s first pregnancy, regardless of the outcome. Pregnancy had to occur by Month 85 to allow for at least 1-year follow-up post-pregnancy onset.
Results: Over 8 years, 122 pregnancies met inclusion criteria; 72% of pregnancies began >12 months after the last alemtuzumab dose, 18% began >4 to 12 months after the last dose, and 10% began ≤4 months after the last dose. Annualised relapse rate (ARR) in the year prior to study entry was 1.8. Two years and 1 year before pregnancy, ARR was 0.10 and 0.12 respectively, with 91% and 89% of patients free of relapse. ARR fell to 0.02 during pregnancy (98% of patients relapse-free). In the first year after pregnancy, ARR was 0.22, and 82% of patients were free of relapse. ARR was similar to pre-pregnancy levels in the second and third years after pregnancy (0.12 each year; 89% and 92% of patients relapse-free in each year). Safety will be discussed in the presentation.
Conclusion: In the year after the first pregnancy in alemtuzumab-treated patients, an increase in relapse rates was minimal and less than that expected from the literature. Relapse rates returned to pre-pregnancy levels by the second year postpartum.
Prof G what can be done to manage my hyperthyroidism if I want to fall pregnant?
Carbimazole is associated with an increased risk of congenital malformations, especially when administered in the first trimester of pregnancy and at high doses. Women of childbearing potential should use effective contraception during treatment with carbimazole.
As you know about 40% of women treated with alemtuzumab go onto to develop hyperthyroidism. The number one drug for controlling thyrotoxicosis is carbimazole. The fact that it is teratogenic is a problem as a lot of women with MS choose to be treated with alemtuzumab so that they can fall pregnant safely off a DMT.
Endocrinologists will have to rely on using propylthiouracil another oral medication that is used to manage hyperthyroidism. Although propylthiouracil may be given in pregnancy it crosses the placenta and in high doses may cause foetal goitre and hypothyroidism, therefore the lowest possible dose should be given and thyroid function monitored every 4-6 weeks to maintain optimum control. Propylthiouracil also transfers to breast milk but this does not necessarily preclude breastfeeding. Neonatal development and infant thyroid function should be closely monitored.
The management of MS gets more complex. I am becoming an endocrinologist in my spare time 😉
