Mother-to-child transmission of SARS-CoV-2 infection in high-income countries: a systematic review and meta-analysis of prospective observational studies.

Mother-to-child transmission of SARS-CoV-2 has been reported since the onset of the COVID-19 pandemic. We conducted a study to summarize evidence on the risk of mother-to-child transmission in the first 30 days after birth in high-income countries and to evaluate the association between preventive measures and the risk of infection for the neonate. A systematic review and meta-analysis were undertaken following PRISMA guidelines. The National Library of Medicine, Web of Science, and Excerpta Medica databases were screened on February 26, 2022. All prospective observational studies addressing the frequency of infection in infants born to mothers SARS-CoV-2 positive were included. Twenty-six studies were included, reporting data of 2653 mothers with SARS-CoV-2 and 2677 neonates. The proportion meta-analysis pointed out an overall estimate of SARS-CoV-2 infection among infants of 2.3% (95% CI: 1.4-3.2%). Data from studies with (1.4%, 95% CI: 0.8-2) and without (1.3%, 95% CI: 0.0-2.7%) rooming-in provided similar risk of infection. Adopting at least two prevention measures during rooming-in resulted in a rate of mother-to-child infection of 1.0% (95%CI: 0.3-1.7%). The results of this study show a low rate of perinatal infection, support the rooming-in and confirm the effectiveness of preventive measures in reducing the risk of mother-to-child viral transmission.

Modulating Role of Breastfeeding Toward Long COVID Occurrence in Children: A Preliminary Study.

The SARS-CoV-2 (Severe acute respiratory syndrome Coronavirus-2) pandemic has forced the global health system to face new challenges both in the acute management of COVID-19 (Coronavirus Disease 2019) patients and in its consequences. In particular, the long-term effects of this new virus, especially in children, are still poorly understood. Scientific research is currently trying to understand the mechanisms underlying the so called "long COVID syndrome". Since the beginning of the pandemic, breastmilk has been studied for its antiviral and immunomodulatory properties. Based on these assumptions, we conducted a preliminary study in order to investigate the prevalence of long COVID in a cohort of Italian children with previously detected SARS-CoV-2 infection and evaluate if breastfeeding might play a role in modulating long COVID occurrence.

Humoral response to anti-SARS-CoV-2 vaccine in breastfeeding mothers and mother-to-infant antibody transfer through breast milk.

The magnitude of mother-to-infant transfer of anti-SARS-CoV-2 antibodies through breast milk (BM) after maternal vaccination during breastfeeding, in the absence of transplacental transfer of IgG, remains unclear. Here, we quantified anti-S and anti-RBD IgG, IgA, IgA1, and IgA2 in maternal serum, maternal saliva, BM, infant buccal swabs, and infant feces up to 90 days after the second maternal vaccine dose. BNT162b2 vaccine induced long-lasting IgG in maternal serum, but weaker mucosal antibody production, with anti-SARS-CoV-2 IgG and IgA amounts in BM between 10- and 150-fold lower compared to serum. BM IgA were exclusively of the IgA1 isotype, with no production of the mucosal-specific and protease-resistant IgA2. Accordingly, only traces of antibodies were retrieved from the feces of breastfed infants, and no IgG nor IgA were retrieved from infants' buccal swabs. Newly engineered anti-SARS-CoV-2 vaccines may be needed to stimulate the antibody production at mucosal sites such as breast milk.

Coronavirus Disease 2019 Vaccination During Pregnancy and Breastfeeding: A Review of Evidence and Current Recommendations in Europe, North America, and Australasia.

In the late 2020s, less than 1 year into the coronavirus disease 2019 (COVID-19) pandemic, several anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines were introduced on a worldwide scale, with a significant positive impact on the consequences of the disease for several high-risk population groups. In the case of most bacterial or viral respiratory infections, pregnant women are at increased risk of complications, however, neither pregnant nor breastfeeding women were included in the first round of randomized clinical trials evaluating the safety and effectiveness of COVID-19 vaccines, because of safety and ethical concerns. Nevertheless, most anti-SARS-CoV-2 vaccines have not been expressly contraindicated during pregnancy or breastfeeding, and observational data on immune response, adverse effects, and clinical efficacy in pregnant and breastfeeding women have been progressively gathered during 2021. The vast majority of these data is reassuring for what concerns side effects for women and infants and points out the efficacy of vaccines in protecting women against COVID-19-related complications. Despite this, the hesitancy of pregnant and breastfeeding women at being vaccinated is still real. In this mini-review, we resume the available data on the clinical consequences of COVID-19 in pregnant women, as well as adverse effects, systemic and mucosal immune response, and clinical effectiveness of COVID-19 vaccines in pregnant and breastfeeding women. Moreover, we offer an updated overview of European, North American, and Australasian recommendations concerning COVID-19 vaccination in pregnant and breastfeeding women, in order to safely ensure the highest protection of women and their infants.

SARS-CoV-2 infection and neonates: Evidence-based data after 18 months of the pandemic.

After 18 months of the COVID-19 pandemic, data concerning SARS-CoV-2 infection in pregnant women and their neonates are progressively taking the place of complete uncertainty. Here, we summarize updated evidence regarding several critical aspects of perinatal SARS-CoV-2 infection, including 1) vertical transmission of the virus in utero, which is possible but seems rare according to current epidemiological data; 2) how COVID-19 during pregnancy can shape maternal and neonatal outcomes, either directly or indirectly; 3) how recommendations regarding the management of infected dyads have been progressively modified in light of new scientific evidence; and 4) how maternal infection or vaccination can induce the passive protection of fetuses and neonates against the infection, through the transfer of specific antibodies before and after birth.

Human Milk, More Than Simple Nourishment.

Human breast milk not only has nutritional properties but also holds a functional role. It contains various bioactive factors (lactoferrin, lysozyme, leukocytes, immunoglobulins, cytokines, hormones, human milk oligosaccharides, microbiome, microRNAs and stem cells) shown to contribute to several short- and long-term health outcomes. Some of these factors appear to be involved in the infant's neuro-cognitive development, anti-oncogenic processes, cellular communication and differentiation. Furthermore, breast milk is increasingly recognized to have dynamic characteristics and to play a fundamental role in the cross-talking mother-neonate. This narrative review aims to provide a summary and an update on these bioactive substances, exploring their functions mainly on immunomodulation, microbiome and virome development. Although the knowledge about breast milk potentiality has significantly improved, leading to discovering unexpected functions, the exact mechanisms with which breast milk exercises its bioactivity have not been completely clarified. This can represent a fertile ground for exploring and understanding the complexity behind these functional elements to develop new therapeutic strategies.

Breastfeeding supportive practices in European hospitals during the COVID-19 pandemic.

INTRODUCTION: During the first year of the COVID-19 pandemic, international recommendations and guidelines regarding breastfeeding-supportive hospital practices changed frequently. For example, some recommended separation of mothers and infants; others, feeding pumped milk instead of milk fed directly from the breast. Many recommendations were inconsistent or in direct conflict with each other. Guidance from UENPS (the Union of European Neonatal and Perinatal Societies) published in April 2020 recommended rooming in and direct breastfeeding where feasible, under strict measures of infection control, for women who were COVID-19 positive or under investigation for COVID-19. KEY FINDINGS: Our study assessed data from respondents from 124 hospitals in 22 nations, with over 1000 births per year, who completed a survey on practices during the COVID-19 epidemic, as they related to the World Health Organization (WHO) Ten Steps to Successful Breastfeeding, considered to be the gold standard for breastfeeding support. The survey was conducted in the fall of 2020/winter of 2021. Overall 88% of responding hospitals had managed COVID positive mothers, and 7% had treated over 50 birthing women with confirmed COVID-19. The biggest change to hospital policy related to visitation policies, with 38% of hospitals disallowing all visitors for birthing women, and 19% shortening the postpartum stay. Eight hospitals (6%) recommended formula feeding instead of breastfeeding for women who tested positive for COVID-19 or were under investigation, whereas 73% continued to recommend direct, exclusive breastfeeding, but with some form of protection such as a mask or hand sanitizer for the mother or cleaning the breast before the feed. While 6% of hospitals discontinued rooming in, 31% strengthened their rooming in policy (keeping mothers and their babies together in the same room) to protect infants against possible exposure to the virus elsewhere in the hospital . Overall, 72% of hospitals used their country's national guidelines when making policy, 31% used WHO guidelines and 22% UENPS/SIN guidelines. Many European hospitals relied on more than one accredited source. DISCUSSION: Our most concerning finding was that 6% of hospitals recommended formula feeding for COVID positive mothers, a measure that was later shown to be potentially harmful, as protection against the virus is transmitted through human milk. It is encouraging to note that a third of hospitals strengthened rooming in measures. Especially given the emergence of the highly transmissible Delta variant, the situation around postnatal care in maternity hospitals requires ongoing monitoring and may require proactive investment to regain pre-COVID era practices.

COVID-19 pandemic in the neonatal intensive care unit: any effect on late-onset sepsis and necrotizing enterocolitis?

The study was aimed at describing potential indirect effects of pandemic-related measures on very-low-birthweight infants in four Italian NICUs. No overall change in late-onset sepsis (LOS) and necrotizing enterocolitis was documented. However, in the NICU where baseline LOS rate was high, a significant reduction in LOS incidence was recorded. Conclusion: COVID-19-related implementation of NICU hygiene policies is likely to reduce the occurrence of LOS in high-risk settings. What is Known: • COVID-19 pandemic has disrupted routine care in Neonatal Intensive Care Units (NICUs), mostly by tightening infection control measures and restricting parental presence in the NICU. • Beyond the described psychological impact of COVID-19 related measures on healthcare workers and NICU families, their consequences in terms of preterm infants' clinical outcomes have not been described in detail yet. What is New: • Strengthened infection-control measures do not seem to have an overall influence on the incidence of necrotising enterocolitis and late-onset sepsis in very-low-birth-weight infants. • However, the implementation of these measures appears to reduce the occurrence of late-onset sepsis in settings where the baseline incidence of the disease is high.

Exploring the Impact of Restricted Partners' Visiting Policies on Non-Infected Mothers' Mental Health and Breastfeeding Rates during the COVID-19 Pandemic.

Changes in perinatal care occurring during the coronavirus disease 2019 (COVID-19) pandemic may negatively affect mothers' mental health and breastfeeding. This study, performed between April and May 2020, aimed to investigate the effect of restricted partners' visiting policies on non-infected mother's anxiety symptoms, the perceived postpartum support, and the breastfeeding outcomes at discharge. A cross-sectional study was conducted in a neonatal tertiary referral center in northern Italy during Italy's lockdown. We enrolled mothers with a negative nasopharyngeal swab for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), adequate oral and written comprehension of the Italian language, and absence of underlying maternal or neonatal clinical conditions. Maternal anxiety levels were assessed through the State-Trait Anxiety Inventory-Form Y (STAI-Y). Maternal perception of staff's support was evaluated by the Nurse Parent Support Tool (NPST). A STATE-A (concurrent emotional state after a specific situation) score ≥ 40 was considered indicative of clinically significant symptoms of anxiety. A total of 109 mothers completed the study. Mean STATE-A score was ≥40 in 42% of mothers, and median NPST score was 4.23. Mothers separated from their partner had a mean STATE-A score ≥ 40 in a higher percentage of cases than those who were not (51% vs. 30%, p = 0.03) and a lower perception of caregiver support. A NPST score ≤4.23, partner 's absence during the hospital stay and primiparity were independently associated with a STATE-A score ≥ 40. Breastfeeding rates at discharge were not influenced by maternal anxiety levels and partner's restricted policies. Instead, they were influenced by mode of delivery, a well-known risk factor, and pre-pandemic intention to breastfeed. Our study demonstrates the positive impact of a partner's presence on maternal mental health and perception of caregiver support.

Italian neonatologists and SARS-CoV-2: lessons learned to face coming new waves.

The aim of this review was threefold: (a) to retrieve all SARS-CoV-2 evidences published by Italian neonatologists working in maternity centers and NICUs during the pandemic; (b) to summarize current evidence for the management of term and preterm infants with a SARS-CoV-2-related illness; and (c) to provide an update for dealing with the second wave of COVID-19 and discuss open questions. A review was conducted using MEDLINE/PubMed and the national COVID-19 registry of the Italian Society of Neonatology including citations from December 1, 2019 to October 28, 2020. Sixty-three articles were included. Collected data were divided into the following topics: (a) antenatal management, (b) management in delivery room, (c) postnatal management, (d) mother-baby dyad and breastfeeding management, (e) neonatal emergency transport system reorganization, (f) parents' management and perspective during SARS-CoV-2 pandemic, and (g) future perspective. Evidences have evolved over the pandemic period and the current review can be useful in the management of the mother-neonate dyad during SARS-CoV-2 future waves. Italian neonatologists have played an active role in producing official guidelines and reporting data that have contributed to improve the care of neonates. A joint European action plan is mandatory to face COVID-19 in neonates with more awareness. IMPACT: A joint European action plan is mandatory to face COVID-19 in neonates with more awareness. This review summarizes the available evidences from neonatal COVID-19 management in Italy analyzing all the published paper in this specific field of interest. The current review can be useful in the management of the mother-neonate dyad during the SARS-CoV-2 future waves.

Breastfeeding and COVID-19 vaccination: position statement of the Italian scientific societies.

The availability of a COVID-19 vaccine has raised the issue of its compatibility with breastfeeding. Consequently, the Italian Society of Neonatology (SIN), the Italian Society of Pediatrics (SIP), the Italian Society of Perinatal Medicine (SIMP), the Italian Society of Obstetrics and Gynecology (SIGO), the Italian Association of Hospital Obstetricians-Gynecologists (AOGOI) and the Italian Society of Infectious and Tropical Diseases (SIMIT) have made an ad hoc consensus statement. Currently, knowledge regarding the administration of COVID-19 vaccine to the breastfeeding mother is limited. Nevertheless, as health benefits of breastfeeding are well demonstrated and since biological plausibility suggests that the health risk for the nursed infant is unlikely, Italian scientific societies conclude that COVID-19 vaccination is compatible with breastfeeding.

The Antiviral Properties of Human Milk: A Multitude of Defence Tools from Mother Nature.

The anti-infective properties of breast milk have been known for decades. In recent years, an increasing number of papers have described the variety of bioactive compounds that are present in breast milk with varying degrees of antiviral activity. However, to date, the totality of the properties of these compounds is not fully understood and, above all, their synergistic interaction is not yet known. The purpose of this review is to describe the current knowledge about the antiviral compounds in breast milk, both with specific and non-specific action against pathogens. Due to the current pandemic situation from SARS-CoV-2 (Severe acute respiratory syndrome Coronavirus-2), research has focused on a multitude of potential antiviral substances, taking breast milk as a biological model of reference. Future research is needed to expand the knowledge of these compounds, which will hopefully assist in the development of therapies applicable even at later ages.

Assessment of Platelet Thrombus Formation under Flow Conditions in Adult Patients with COVID-19: An Observational Study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with systemic inflammation, which may dysregulate platelet function. Total Thrombus-Formation Analysis System (T-TAS) is a flow-chamber device that analyses platelet-mediated thrombus formation in capillary channels through the following parameters: (1) the area under the flow-pressure curve (AUC), (2) occlusion start time (OST), time needed to reach OST, and (3) occlusion time (OT), time needed to reach the occlusion pressure. METHODS AND FINDINGS: Sixty-one COVID-19 patients admitted to intensive, subintensive, and low intensive care were prospectively enrolled according to the time of admission: group A (up to 8 days) (n = 18); group B (from 9 to 21 days) (n = 19), and group C ( > 21 days) (n = 24). T-TAS measurements were performed at enrolment and after 7 days. Median OST was similar among groups. AUC was lower in group A compared to B (p = 0.001) and C (p = 0.033). OT was longer in group A compared to B (p = 0.001) and C (p = 0.028). Platelet count (PC) was higher in group B compared to A (p = 0.024). The linear regression showed that OT and AUC were independent from PC in group A (OT: 0.149 [95% confidence interval [CI]: -0.326 to 0.624], p = 0.513 and AUC: 0.005 [95% CI: -0.008 to 0.017], p = 0,447). In contrast, in group B, PC was associated with OT (-0.019 [-0.028 to 0.008], p = 0.023) and AUC (0.749 [0.358-1.139], p = 0,015), similarly to group C. Conversely, patients with different illness severity had similar T-TAS parameters. CONCLUSION: COVID-19 patients display an impaired platelet thrombus formation in the early phase of the disease compared to later stages and controls, independently from illness severity.

Evaluation of Rooming-in Practice for Neonates Born to Mothers With Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Italy.

Importance: The management of mother-infant dyads during the ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic constitutes a major issue for neonatologists. In mothers with SARS-CoV-2 infection, current recommendations suggest either to separate the dyad or encourage protected rooming-in under appropriate precautions. No data are available regarding the risk of mother-to-infant transmission of SARS-CoV-2 during rooming-in. Objective: To evaluate the risk of postnatal transmission of SARS-CoV-2 from infected mothers to their neonates following rooming-in and breastfeeding. Design, Setting, and Participants: A prospective, multicenter study enrolling mother-infant dyads from March 19 to May 2, 2020, followed up for 20 days of life (range, 18-22 days), was performed. The study was conducted at 6 coronavirus disease 2019 maternity centers in Lombardy, Northern Italy. Participants included 62 neonates born to 61 mothers with SARS-CoV-2 infection who were eligible for rooming-in practice based on the clinical condition of the mother and infants whose results of nasopharyngeal swabs were negative at birth. Exposures: Mothers with SARS-CoV-2 infection were encouraged to practice rooming-in and breastfeeding under a standardized protocol to minimize the risk of viral transmission. Main Outcomes and Measures: Clinical characteristics and real-time reverse transcriptase-polymerase chain reaction for SARS-CoV-2 on neonatal nasopharyngeal swabs at 0, 7, and 20 days of life. Results: Of the 62 neonates enrolled (25 boys), born to 61 mothers (median age, 32 years; interquartile range, 28-36 years), only 1 infant (1.6%; 95% CI, 0%-8.7%) was diagnosed as having SARS-CoV-2 infection at postbirth checks. In that case, rooming-in was interrupted on day 5 of life because of severe worsening of the mother's clinical condition. The neonate became positive for the virus on day 7 of life and developed transient mild dyspnea. Ninety-five percent of the neonates enrolled were breastfed. Conclusions and Relevance: The findings of this cohort study provide evidence-based information on the management of mother-infant dyads in case of SARS-CoV-2 maternal infection suggesting that rooming-in and breastfeeding can be practiced in women who are able to care for their infants.

SARS-CoV-2 infection and neonates: a review of evidence and unresolved questions.

SARS-CoV-2 infection in the neonatal period poses previously unmet challenges to obstetricians and neonatologists, but several key questions are yet to be answered. Few cases of presumed in utero vertical transmission of the virus from infected mothers to fetuses have been reported, but stronger evidence is needed, from larger datasets with multiple biospecimens rigorously analyzed. Whether acquired before or after birth, SARS-CoV-2 infection in neonates can be symptomatic, but our comprehension of neonatal immune response and the subsequent clinical characteristics of COVID-19 in early life are incomplete. Finally, the pandemic challenged several dogmas regarding the management of mother-infant dyads, and again more robust data are needed to support the formulation of evidence-based guidelines. Here, we briefly summarize existing evidence and key unresolved questions about SARS-CoV-2 infection and COVID-19 in the neonatal period.

Point of view of the Italians pediatric scientific societies about the pediatric care during the COVID-19 lockdown: what has changed and future prospects for restarting.

BACKGROUND: The coronavirus disease 2019 (COVID-19) is currently rare in children and they seem to have a milder disease course and better prognosis than adults. However, SARS-Cov-2 pandemic has indirectly caused problems in pediatric medical assistance. In view of this we wanted to draw a picture of what happened during health emergency and analyze future prospects for restarting. METHODS: We involved the Italian pediatric scientific societies institutionally collected in the Italian Federation of Associations and Scientific Societies of the Pediatric Area (FIARPED); We sent a questionnaire to all scientific societies about the pediatric care activity during the COVID-19 emergency and future perspectives for the phase of post-containment. RESULTS: The analysis of the questionnaires showed significant decrease of:admission, outpatient visits and specialist consultancy activities during the COVID-19 emergency, primarily linked to the fear of infection. Instead it was increased the serious degree of diseases admitted. Most of scientific societies maintained the relationship with chronic patients through some form of telemedicine, reporting a strong positive opinion about this modality. Finally showed the need to give life a new approach for hospitalizations and outpatient visits through a greater use of telemedicine, educational programs on families and a more decisive role of family pediatricians. CONCLUSIONS: Our study highlighted many aspects that can be improved in pediatric care. We think that It will be necessary a new shared strategy to improve the management and continuity of care for pediatric patients, primarily developing a network of collaboration between families, family pediatrician and hospitals and by enhancing the use of new methods of telecommunications.