Coronavirus

COVID-19: pregnancy, delivery and breastfeeding - May 7th 2020

As part of the wide topic of “infection and maternal sepsis”, the results of the GLOSS [1] study coordinated by WHO in 52 low, medium, and high income countries have been published. Maternal infection and sepsis, which also includes SARS-CoV-2 infection, are a global problem both for their increase, and for the scarce literature and weak recommendations for clinical practice, including the unavailability of a validated definition of maternal sepsis. In Italy, according to the data collected by the ItOSS [2] maternal mortality monitoring system, in the years 2006-2012 sepsis was the fourth for frequency among the causes of direct maternal death and seventh among those of indirect death; in the years 2013-2017 the sepsis appears to be the second cause of direct deaths and the first of indirect deaths, in the same ways as cardiovascular disease. Five of the 9 cases of indirect maternal death from sepsis have been attributed to influenza H1N1. The information described by the GLOSS study, therefore, represents a valuable resource for healthcare professionals who take care of pregnancy and childbirth. GLOSS describes the frequency and management of maternal infections detected in 713 healthcare facilities globally during a week of data collection, carried out between November and December 2017. Thanks to the coordination of ItOSS, Italy participated in the study as one of the 9 high-income countries that contributed to the population-based data collection. The study was carried out in the Lombardy Region where 100 of the 445 cases collected at European level were notified.

Globally, the study enrolled 2,850 pregnant women with suspected or confirmed infection, whose demographic, obstetric and clinical characteristics are described and the measures adopted for their prevention, early identification and treatment are presented. The research produced the first population-based phenomenon assessment, which give a measure of the priority importance of maternal infections as a cause of morbidity and mortality. Infections affected 70.4 women per 1,000 live births, while serious maternal outcomes, directly or indirectly related to an infection, were detected in 10.9 women per 1000 live births. The highest rates pertain low-middle income countries (106.4 per 1,000 live births) and the lower rates pertain high-income countries (38.6 per 1,000 live births).

Infection-related maternal deaths were responsible for over half of intra-hospital deaths. Vital sign recording is available for 63.9% of women and 70.2% have received a prescription for antibiotics on the day of suspected infection.

Direct, obstetric, and indirect infections contribute more to maternal mortality than previously believed. It is, therefore, urgent to improve their identification and the appropriateness of their early treatment through the implementation of effective care and therapeutic evidence-based modalities.

The GLOSS study, an important milestone in the global campaign that WHO is conducting to combat maternal sepsis, was commented on The Lancet [3] to highlight the need for unique definitions that can facilitate the identification of infections and maternal sepsis on a global level, with particular attention to contexts with limited available resources.

With specific regard to SARS-CoV-2 virus infection, several papers are available this week that provide useful information for clinical practice.

The Society of Infectious Disease in Obstetrics and Gynecology (ISIDOG) has published recommendations for clinical practice to support the diagnosis and management of pregnant women during the COVID-19 pandemic [4]. The document was prepared using the available literature and indications from the CDC, RCOG and ANZICS. It is a useful tool for healthcare professionals because it offers a systematic review of the diagnostic, therapeutic and management aspects by summarizing the available evidence and providing recommendations for clinical practice.

The American Journal of Obstetrics and Gynecology MFM has accepted for publication two contributions from Italian and American colleagues [5,6], who propose a guide for territorial and hospital care for pregnancy and childbirth in COVID-positive women. The aim expressed by the authors is to provide a set of indications and suggestions that can be differently adapted according to the clinical judgment, needs and resources available in the individual care settings.

A systematic review published in JAMA [7] includes 18 studies involving a total of 114 pregnant women COVID-19 positive, exclusively in the third trimester of pregnancy. The authors conclude stating that the clinical characteristics of positive pregnant women are similar to those found in women of the general population and that fetal and neonatal outcomes are overall good.

The American Journal of Epidemiology publishes tips for clinical practice [8] for healthcare professionals who assist women with COVID-19 in pregnancy and childbirth.

A retrospective observational study [9] compares the clinical course and outcomes of the COVID-19 infection between 28 pregnant women and 54 women of reproductive age. A regression model highlights the absence of an association between pregnancy and severity of the clinical course of the disease, virus clearance time and length of hospitalization. None of the 23 newborns, 5 born vaginally and 17 through cesarean sections, tested positive for the virus.

A comment on a Chinese work describing 5 uncomplicated childbirth cases in positive COVID-19 women, highlights the data concerning an increased risk of preterm birth and consequent comorbidity in case of SARS-CoV-2 virus infection [10].

A study carried out at the Policlinico Gemelli in Rome [11] describes a series of 4 pregnant women with COVID-19 infection in which lung ultrasound was used as a useful aid in both diagnosis and monitoring of the clinical situation.

A letter from colleagues at Mangiagalli in Milan published in Thrombosis Research [12] describes a case of a young obese woman positive for the SARS-CoV-2 who, after 4 days of heparin prophylaxis, developed a pulmonary embolism at 19 weeks of pregnancy complicated by respiratory impairment and Staphylococcus Aureus bacteremia.

For the first time, Chinese authors define safe vaginal delivery for COVID-19 positive mothers at the conclusion of the presentation of the study results that presents a retrospective analysis of the medical records of 10 women diagnosed with COVID-19 and 53 unaffected women who gave birth vaginally in a Chinese hospital [13]. There were no significant differences between the two groups of mothers in terms of gestational age at birth and incidence of EPP and rate of episiotomies. Even the infants of the two groups compared did not show any differences in weight and asphyxia rates detected at birth. All infants of positive mothers tested negative for SARS-CoV-2 virus.

Two new available papers are dedicated to anesthesiologists involved in the management of COVID-19 positive patients during pregnancy. The first contribution [14] describes the reorganization of obstetric anesthesia training during the COVID-19 pandemic at the Women’s and Children’s Hospital in Singapore, which is responsible for the training of anesthesiologists dedicated to obstetric care.

The second [15] describes the initial ventilatory support interventions to be offered to pregnant women with COVID-19 infection in case of severe respiratory impairment.

Some publications trying to answer the question on the possible vertical transmission of the SARS-CoV-2 continue to be published. A narrative review [16] of the literature concludes that vertical transmission of the virus has not been demonstrated in any newborn of an infected mother during the third trimester of pregnancy.

Another publication [17] reviews the literature related to the vertical transmission of Coronaviruses and other RNA respiratory viruses and concludes that, in light of the evidence currently available, also for the SARS-CoV-2, in analogy to what has been observed for all the other viruses of the Coronaviruses family and RNA respiratory viruses, fetal maternal transmission is absent or limited to a few suspected cases.

A second trimester miscarriage case in a positive COVID-19 woman is presented in a letter on JAMA [18]. The researchers set up maternal (nasopharynx, vagina and peripheral blood) and fetal/adnexal samples (cord blood, amniotic fluid, multiple fetal and placental samples) for the detection of the virus. Nasopharyngeal and placental swabs are the only SARS-CoV-2 positive results. Placental histology has highlighted inflammatory infiltrates but it is not possible to say with certainty that the virus has passed the placenta, and the authors wonder about the possible relationship between infection and miscarriage.

A case report by colleagues from the University of Turin [19] describes the positivity at birth of the nasopharyngeal and anorectal swab collected from a newborn of the positive COVID-19 mother. The authors suggest to perform anorectal swab to COVID-19 positive women before the start of labor to reduce the risk of potential vertical transmission of the infection during vaginal delivery.

A Canadian work proposes a classification system that provides 5 mutually exclusive classes to define the probability of infection which is divided into: certain, probable, possible, improbable, and absent. For each class the diagnostic tests and the interpretative criteria of their answers are defined. About the case definition, the authors propose to replace the generic terminology “vertical or horizontal transmission of the infection” with those of: “congenital infection in intrauterine death/stillbirth”, “congenital infection in live born”, “neonatal infection acquired intrapartum”, “neonatal infection acquired postnatally”. The fact that a significant number of maternal and neonatal infections is asymptomatic makes it difficult to evaluate the real impact of the condition on newborns and at the same time compromises the possibility of adequate protection of the health professionals who take care of them. The summary of this work is identical to that already presented in the EpiCentro update of April 16, presenting the publication of Shah, S., Diambomba, Y., Acharya, G., Shaun, K. & Bitnun, A. Classification system and case definition for SARS-CoV-2 infection in pregnant women, fetuses, and neonates (2020) [20] of which this work reports the same contents.

With regard to the care of the newborn of mother affected by SARS-CoV-2, a paper [21] reviews the available evidence about perinatal transmission and respiratory outcomes in infants of COVID-19 positive mothers, as well as of children with documented infection. Compared to about 2 million cases of COVID infection globally, the number of infants who developed the disease appears to be very limited. The infection appears to be transmitted in the postnatal period and associated with favorable respiratory outcomes. The document describes the care modalities and recommends professionals to update continuously, in consideration of the rapid evolution of knowledge.

A narrative review by the study group of neonatal infectious diseases of the Italian Society of Neonatology [22] showed a favorable clinical course compared to that observed in the adult population. The review examined 69 infants of COVID-19 positive mothers with negative swab at birth and 5 infants less than 6 months of age with confirmed COVID-19 diagnosis who presented no major complications.

An article [23] describes the possible e-learning resources and their characteristics in terms of effectiveness, costs and accessibility to support young doctors in training, who, during the Coronavirus pandemic, are forced to suspend their surgical training.

A letter from colleagues from Karolinska Hospital in Stockholm [24] summarizes in a clear and concise way the positions of the main international scientific reference companies on the global recommendation to suspend and/or reduce the offer of treatments for fertility during the COVID-19 pandemic.

Another contribution that addresses the same issue [25] describes the consequences of the interruption of services in support of sexual and reproductive health, such as family planning services, those for voluntary abortion or medically assisted procreation (MAP), due to the Coronavirus emergency. A comment supports the opportunity and urgency to restore MAP services by allowing infertile couples to access fertilization and freezing of embryos, only delaying the implantation phase.

SIGO and AOGOI have published a press release in support of a greater spread of medical abortion. The initiative would allow to protect the health and rights of women, who risk being denied due to the ongoing emergency, and to reduce the workload of anesthesiologists and the use of operating rooms. To achieve a full application of the pharmacological procedure, the scientific society also request to review some aspects of the current procedures, in the first place the shift of the treatment limit from 7 to 9 weeks, as happens in other countries and as indicated by the WHO [26], and the renunciation of hospitalization under ordinary regime. During the pandemic period, COVID-19 suggests the introduction of the outpatient regime and a remote procedure, monitored by telemedicine services, as has already happened in other European countries [27].

The Italian Society of Fertility, Sterility and Reproductive Health has published a position statement [28] describing the priorities for assisted reproduction interventions during and after the Coronavirus pandemic. The authors underline how the suspension of services has a dramatic impact, in particular on some categories of patients such as women with oncological pathology awaiting oocyte sampling or infertile patients with high maternal age or with reduced oocyte reserve, for whom uncertainty waiting is particularly critical.

SIGO and its Special Interest Group (GISS) in Reproductive Health have developed new recommendations for the prompt resumption of MAP treatments when the Government decrees the start of “phase 2” of the pandemic [29,30].

An article addresses the issue of equity in the offer of obstetrics-gynecological services in the time of Coronavirus [31]. The authors describe how the reorganization of services, aimed at minimizing the risk of transmission of the virus, entails a greater risk of exclusion of the socially more vulnerable population.

On the same topic, a summary of the contents of a webinar [32] was published. This publication aimed to discuss how the COVID-19 pandemic compromised the sexual and reproductive rights of the most fragile people. The thematic areas examined involve access to sexual and reproductive health services, contraception, safe abortion, violence against women and the needs of the most vulnerable populations such as refugees and disabled people.

A release published by BMJ [33] reconstructs what happened in Texas and other American States, where the Coronavirus emergency allowed governors against voluntary abortion to include it among non-essential medical procedures and stop offering the service, forcing women to give up surgery or move to other States to get it during the new Coronavirus epidemic.

This week, some contributions have been published regarding the aspects of research in the context of the emergency from the new Coronavirus and the possible repercussions in terms of public health. Three US authors [34] report the exclusion of pregnant and lactating women from ongoing clinical trials during the COVID-19 pandemic, as has also happened in previous epidemics. The authors argue that this choice of “protection that passes through the exclusion” of a population defined as “fragile” is another missed opportunity to obtain information on the safety and efficacy of the drugs to be used during pregnancy. Appealing to the concepts of justice, equity, autonomy and informed consent, the authors invite the scientific community to include pregnant women in clinical trials to study the COVID-19 infection.

With a letter to The Lancet [35], an appeal is launched to participate in an international maternity registry that collects reports of SARS-CoV-2 clinical cases. The promoters underline the importance of collecting and sharing robust data quickly in order to have knowledge useful for the action.

The Guttamcher Institute [36] has published a very interesting and documented comment on the dramatic impact that emergencies such as the one underway, can have on sexual and reproductive health services in the world, with particular regard to low income countries. The researchers estimated the impact in terms of health consequences for women of reproductive age through the simulation of different scenarios. Assuming the closure of 10% of sexual and reproductive health services in low- and middle-income countries, the effects on communities and the expected numbers of illegal abortions, maternal and neonatal morbidity and mortality are impressive and worthy of attention by decision-makers politicians and the international community.

Despite some suggestions on individual cases [18], a large number of evidences continue to demonstrate the absence of vertical transmission [4,7,9,11,13,16,21,22,37].

The guidelines of the International Society for Infectious Diseases in Obstetrics and Gynaecology (ISIDOG) indicate that postnatal transmission from parents or other caregivers to the newborn is possible. They therefore recommend strict hygiene measures, including the use of a mask, hand hygiene and physical distancing [4].

The Royal College of Obstetricians and Gynaecologists (RCOG), with the Royal College of Midwives, the Royal College of Paediatrics and Child Health (RCPH), the Royal College of Anaesthetists, and the Obstetric Anaesthetists' Association have published a summary of their Interim Guidance of April 17, 2020 [38]. Among the key recommendations related to childbirth and postpartum, it is recommended that COVID-19 positive women should be accompanied by a person of their choice, asymptomatic, for labor and delivery. For positive women, water birth should be avoided. With regard to breastfeeding, the expected benefits currently outweigh the risks of infection from mother to baby; there is no need to separate positive mothers and healthy babies [39].

The Italian translation of the April 28 [40] document “Frequently Asked Questions (FAQ): Breastfeeding and COVID-19. For healthcare professionals” [41] is available on the Italian Committee for UNICEF website. In this document, the WHO summarizes its positions related to breastfeeding and newborn care.

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