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Literature Review and an Italian Hospital Experience about Post-Natal CMV Infection Acquired by Breast-Feeding in Very Low and/or Extremely Low Birth Weight Infants.
Garofoli, F, Civardi, E, Zanette, S, Angelini, M, Perotti, G, Zecca, M, Lombardi, G
Nutrients. 2021;(2)
Abstract
Breastfeeding is recommended for all neonates due to a known variety of beneficial effects, but infants can be infected by cell-associated bacteria and viruses from breast milk, such as cytomegalovirus (CMV). The majority of CMV-seropositive breastfeeding women have a viral, self-restricted reactivation, can shed the virus in the milk for about 12 weeks after delivery, and can transmit the infection to their offspring. Post-natal CMV-infected term infants are mainly asymptomatic, while very low birth weight (VLBW, <1500 g) and extremely low birth weight (ELBW, <1000 g) infants may present with severe disease, short-term sequelae ranging from abnormalities in laboratory indexes to sepsis-like syndrome, and long-term sequelae such as developmental problems. Thus, the use of thermally treated maternal milk for VLBW/ELBW infants may be indicated to prevent/reduce the risk of CMV transmission. Different techniques, with varying efficacy in eradicating CMV and maintaining the activity of biological compounds in milk are available: long/short pasteurization, freeze-thawing, the use of microwaves, and ultraviolet-C irradiation. In our NICU, the use of maternal raw milk is always strongly recommended for term/preterm infants, but to reduce risk of CMV transmission, freeze-thawing mother's own milk is used in neonates with GA ≤ 30 weeks or/and weight ≤ 1000 g, usually regardless of serological maternal condition, as CMV screening is not routinely offered to pregnant women and the milk of seroimmune mothers is not evaluated for CMV reactivation, as its rate is similar to seroprevalence. Over the last 4 years, we had 10 VLBW/ELBW newborns in our NICU with late-onset sepsis and negative cultures. In these cases, the research of CMV DNA in neonatal urine or saliva, for the diagnosis of post-natal symptomatic infection (once congenital transmission has been excluded) may be useful and not invasive. The take-home message we would like to share is that acquired CMV infection should be considered in VLBW/ELBW infants breastfed by seropositive mothers and presenting severe symptoms-particularly sepsis with negative cultures. This could allow pediatricians to make better-quality diagnoses, perform supportive therapy, provide antiviral treatment if needed, or establish a "pre-emptive" therapy for these high-risk neonates.
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Best Practices for Human Milk Collection for COVID-19 Research.
McGuire, MK, Seppo, A, Goga, A, Buonsenso, D, Collado, MC, Donovan, SM, Müller, JA, Ofman, G, Monroy-Valle, M, O'Connor, DL, et al
Breastfeeding medicine : the official journal of the Academy of Breastfeeding Medicine. 2021;(1):29-38
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Abstract
In addition to providing life-giving nutrients and other substances to the breastfed infant, human milk can also represent a vehicle of pathogen transfer. As such, when an infectious disease outbreak, epidemic, or pandemic occurs-particularly when it is associated with a novel pathogen-the question will naturally arise as to whether the pathogen can be transmitted through breastfeeding. Until high-quality data are generated to answer this question, abandonment of breastfeeding due to uncertainty can result. The COVID-19 pandemic, which was in full swing at the time this document was written, is an excellent example of this scenario. During these times of uncertainty, it is critical for investigators conducting research to assess the possible transmission of pathogens through milk, whether by transfer through the mammary gland or contamination from respiratory droplets, skin, breast pumps, and milk containers, and/or close contact between mother and infant. To promote the most rigorous science, it is critical to outline optimal methods for milk collection, handling, storage, and analysis in these situations, and investigators should openly share their methods in published materials. Otherwise, the risks of inconsistent test results from preanalytical and analytical variation, false positives, and false negatives are unacceptably high and the ability to provide public health guidance poor. In this study, we provide "best practices" for collecting human milk samples for COVID-19 research with the intention that this will also be a useful guide for future pandemics.
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Inositol and vitamin D may naturally protect human reproduction and women undergoing assisted reproduction from Covid-19 risk.
Bezerra Espinola, MS, Bertelli, M, Bizzarri, M, Unfer, V, Laganà, AS, Visconti, B, Aragona, C
Journal of reproductive immunology. 2021;:103271
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Abstract
In late 2019, the new Coronavirus has been identified in the city of Wuhan then COVID-19 spreads like wildfire in the rest of the world. Pregnant women represent a risk category for increased abortion rates and vertical transmission with adverse events on the newborns has been recently confirmed. The scientific world is struggling for finding an effective cure for counteracting symptomatology. Today, there are many therapeutic proposes but none of them can effectively counteract the infection. Moreover, many of these compounds show important side effects not justifying their use. Scientific literature reports an immune system over-reaction through interleukins-6 activation. In this regard, the possibility to control the immune system represents a possible strategy for counteracting the onset of COVID-19 symptomatology. Vitamin D deficiency shows increased susceptibility to acute viral respiratory infections. Moreover, Vitamin D seems involved in host protection from different virus species by modulating activation and release of cytokines. Myo-inositol down-regulates the expression of IL-6 by phosphatidyl-inositol-3-kinase (PI3K) pathway. Furthermore, myo-inositol is the precursor of phospholipids in the surfactant and it is applied for inducing surfactant synthesis in infants for treating respiratory distress syndrome (RDS). This review aims to summarize the evidence about COVID-19 infection in pregnant women and to encourage the scientific community to investigate the use of Vitamin D and Myo-inositol which could represent a possible preventive treatment for pregnant women or women undergoing assisted reproductive technologies (ART).
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Presence of Ebola virus in breast milk and risk of mother-to-child transmission: synthesis of evidence.
Medina-Rivera, M, Centeno-Tablante, E, Finkelstein, JL, Rayco-Solon, P, Peña-Rosas, JP, Garcia-Casal, MN, Rogers, L, Ridwan, P, Martinez, SS, Andrade, J, et al
Annals of the New York Academy of Sciences. 2021;(1):33-43
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To help inform global guidelines on infant feeding, this systematic review synthesizes evidence related to the presence of the Ebola virus (EBOV) in breast milk and its potential risk of viral transmission to the infant when breastfeeding. We relied on a comprehensive search strategy to identify studies including women with suspected, probable, or confirmed EBOV infection, intending to breastfeed or give breast milk to an infant. Our search identified 10,454 records, and after deduplication and screening, we assessed 148 full texts. We included eight studies reporting on 10 breastfeeding mothers and their children (one mother with twins), who provided breast milk samples for assessment. EBOV was detected via RT-PCR or viral culture in seven out of ten breast milk samples. Four out of the five-breastfed infants with EBOV-positive breast milk were found positive for EBOV infection, and all of these EBOV-positive infants died. Since previous reports have detected EBOV in tears, saliva, sweat, and contaminated surfaces, with the current evidence, it is not possible to conclude with certainty that breast milk was the main route of EBOV transmission.
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Impact of COVID-19 on pregnancy and delivery - current knowledge.
Krupa, A, Schmidt, M, Zborowska, K, Jorg, D, Czajkowska, M, Skrzypulec-Plinta, V
Ginekologia polska. 2020;(9):564-568
Abstract
The World Health Organization announced on 12 March 2020 a global pandemic of the new SARS-CoV-2 coronavirus causing COVID-19 disease associated with pneumonia and acute respiratory failure. SARS-CoV-2 has caused so far over 6.66 million recorded cases, of which 393,000 ended in death (as of June 1, 2020). Despite the demographic statistics of incidence, there is no current recording of cases in the group of pregnant or perinatal women. Changes occurring in the female body system during pregnancy also affect and alter the immune system, and as studies based on other viral respiratory infections have shown, the population of pregnant women is at risk of having a severe course of the disease. The aim of the study is to summarize current reports on the course of COVID-19 disease in a group of pregnant women and the possible impact of SARS-CoV-2 on the foetus and vertical transmission, taking into account changes occurring in the woman's immune system during pregnancy. Available advice and recommendations for antenatal and perinatal care of pregnant women during the pandemic period are also included.
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A review of newborn outcomes during the COVID-19 pandemic.
Kyle, MH, Glassman, ME, Khan, A, Fernández, CR, Hanft, E, Emeruwa, UN, Scripps, T, Walzer, L, Liao, GV, Saslaw, M, et al
Seminars in perinatology. 2020;(7):151286
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Abstract
As the COVID-19 pandemic continues to spread worldwide, it is crucial that we determine populations that are at-risk and develop appropriate clinical care policies to protect them. While several respiratory illnesses are known to seriously impact pregnant women and newborns, preliminary data on the novel SARS-CoV-2 Coronavirus suggest that these groups are no more at-risk than the general population. Here, we review the available literature on newborns born to infected mothers and show that newborns of mothers with positive/suspected SARS-CoV-2 infection rarely acquire the disease or show adverse clinical outcomes. With this evidence in mind, it appears that strict postnatal care policies, including separating mothers and newborns, discouraging breastfeeding, and performing early bathing, may be more likely to adversely impact newborns than they are to reduce the low risk of maternal transmission of SARS-CoV-2 or the even lower risk of severe COVID-19 disease in otherwise healthy newborns.
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Breastfeeding and coronavirus disease-2019: Ad interim indications of the Italian Society of Neonatology endorsed by the Union of European Neonatal & Perinatal Societies.
Davanzo, R, Moro, G, Sandri, F, Agosti, M, Moretti, C, Mosca, F
Maternal & child nutrition. 2020;(3):e13010
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The recent COVID-19 pandemic has spread to Italy with heavy consequences on public health and economics. Besides the possible consequences of COVID-19 infection on a pregnant woman and the fetus, a major concern is related to the potential effect on neonatal outcome, the appropriate management of the mother-newborn dyad, and finally the compatibility of maternal COVID-19 infection with breastfeeding. The Italian Society on Neonatology (SIN) after reviewing the limited scientific knowledge on the compatibility of breastfeeding in the COVID-19 mother and the available statements from Health Care Organizations has issued the following indications that have been endorsed by the Union of European Neonatal & Perinatal Societies (UENPS). If a mother previously identified as COVID-19 positive or under investigation for COVID-19 is asymptomatic or paucisymptomatic at delivery, rooming-in is feasible, and direct breastfeeding is advisable, under strict measures of infection control. On the contrary, when a mother with COVID-19 is too sick to care for the newborn, the neonate will be managed separately and fed fresh expressed breast milk, with no need to pasteurize it, as human milk is not believed to be a vehicle of COVID-19. We recognize that this guidance might be subject to change in the future when further knowledge will be acquired about the COVID-19 pandemic, the perinatal transmission of SARS-CoV-2, and clinical characteristics of cases of neonatal COVID-19.
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Guidance on breastfeeding during the Covid-19 pandemic.
Calil, VMLT, Krebs, VLJ, Carvalho, WB
Revista da Associacao Medica Brasileira (1992). 2020;(4):541-546
Abstract
OBJECTIVE These recommendations aim to provide guidance on breastfeeding for mothers with suspected or confirmed Covid-19. METHODS We performed a review of the recent medical literature on breastfeeding mothers with suspected or confirmed Covid-19, focusing on the neonatal period. RESULTS We analyzed 20 recent publications on breastfeeding, Covid-19, and its transmission through breastmilk. We presented possible options for breastfeeding and their consequences for the mother and the child. CONCLUSION All maternal decisions in relation to breastfeeding are justifiable since the infection by Covid-19 is still poorly known. However, puerperal women and their families must be very well informed to make a conscious choice based on the information available in the literature so far.
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Impact of breastfeeding, maternal antiretroviral treatment and health service factors on 18-month vertical transmission of HIV and HIV-free survival: results from a nationally representative HIV-exposed infant cohort, South Africa.
Goga, AE, Lombard, C, Jackson, D, Ramokolo, V, Ngandu, NK, Sherman, G, Puren, A, Chirinda, W, Bhardwaj, S, Makhari, N, et al
Journal of epidemiology and community health. 2020;(12):1069-1077
Abstract
BACKGROUND We analysed the impact of breastfeeding, antiretroviral drugs and health service factors on cumulative (6 weeks to 18 months) vertical transmission of HIV (MTCT) and 'MTCT-or-death', in South Africa, and compared estimates with global impact criteria to validate MTCT elimination: (1) <5% final MTCT and (2) case rate ≤50 (new paediatric HIV infections/100 000 live births). METHODS 9120 infants aged 6 weeks were enrolled in a nationally representative survey. Of 2811 HIV-exposed uninfected infants (HEU), 2644 enrolled into follow-up (at 3, 6, 9, 12, 15 and 18 months). Using Kaplan-Meier analysis and weighted survey domain-based Cox proportional hazards models, we estimated cumulative risk of MTCT and 'MTCT or death' and risk factors for time-to-event outcomes, adjusting for study design and loss-to-follow-up. RESULTS Cumulative (final) MTCT was 4.3% (95% CI 3.7% to 5.0%); case rate was 1290. Postnatal MTCT (>6 weeks to 18 months) was 1.7% (95% CI 1.2% to 2.4%). Cumulative 'MTCT-or-death' was 6.3% (95% CI 5.5% to 7.3%); 81% and 62% of cumulative MTCT and 'MTCT-or-death', respectively, occurred by 6 months. Postnatal MTCT increased with unknown maternal CD4-cell-count (adjusted HR (aHR 2.66 (1.5-5.6)), undocumented maternal HIV status (aHR 2.21 (1.0-4.7)) and exclusive (aHR 2.3 (1.0-5.2)) or mixed (aHR 3.7 (1.2-11.4)) breastfeeding. Cumulative 'MTCT-or death' increased in households with 'no refrigerator' (aHR 1.7 (1.1-2.9)) and decreased if infants used nevirapine at 6 weeks (aHR 0.4 (0.2-0.9)). CONCLUSIONS While the <5% final MTCT target was met, the case rate was 25-times above target. Systems are needed in the first 6 months post-delivery to optimise HEU health and fast-track ART initiation in newly diagnosed mothers.
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Pharmacokinetics of HIV-Integrase Inhibitors During Pregnancy: Mechanisms, Clinical Implications and Knowledge Gaps.
van der Galiën, R, Ter Heine, R, Greupink, R, Schalkwijk, SJ, van Herwaarden, AE, Colbers, A, Burger, DM
Clinical pharmacokinetics. 2019;(3):309-323
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Abstract
Prevention of mother-to-child transmission of HIV and optimal maternal treatment are the most important goals of antiretroviral therapy in pregnant women with HIV. These goals may be at risk due to possible reduced exposure during pregnancy caused by physiological changes. Limited information is available on the impact of these physiological changes. This is especially true for HIV-integrase inhibitors, a relatively new class of drugs, recommended first-line agents and hence used by a large proportion of HIV-infected patients. Therefore, the objective of this review is to provide a detailed overview of the pharmacokinetics of HIV-integrase inhibitors in pregnancy. Second, this review defines potential causes for the change in pharmacokinetics of HIV-integrase inhibitors during pregnancy. Despite increased clearance, for raltegravir 400 mg twice daily and dolutegravir 50 mg once daily, exposure during pregnancy seems adequate; however, for elvitegravir, the proposed minimal effective concentration is not reached during pregnancy. Lower exposure to these drugs may be caused by increased hormone levels and, subsequently, enhanced drug metabolism during pregnancy. The pharmacokinetics of bictegravir and cabotegravir, which are under development, have not yet been evaluated in pregnant women. New studies need to prospectively assess whether adequate exposure is reached in pregnant women using these new HIV-integrase inhibitors. To further optimize antiretroviral treatment in pregnant women, studies need to unravel the underlying mechanisms behind the changes in the pharmacokinetics of HIV-integrase inhibitors during pregnancy. More knowledge on altered pharmacokinetics during pregnancy and the underlying mechanisms contribute to the development of effective and safe antiretroviral therapy for HIV-infected pregnant women.