Contemporary fluid management, humidity, and patent ductus arteriosus management strategy for premature infants among 336 hospitals in Asia.

Objectives: The management of patent ductus arteriosus (PDA) is a critical concern in premature infants, and different hospitals may have varying treatment policies, fluid management strategies, and incubator humidity. The Asian Neonatal Network Collaboration (AsianNeo) collected data on prematurity care details from hospitals across Asian countries. The aim of this study was to provide a survey of the current practices in the management of PDA in premature infants in Asian countries. Methods: AsianNeo performed a cross-sectional international questionnaire survey in 2022 to assess the human and physical resources of hospitals and clinical management of very preterm infants. The survey covered various aspects of hospitals resources and clinical management, and data were collected from 337 hospitals across Asia. The data collected were used to compare hospitals resources and clinical management of preterm infants between areas and economic status. Results: The policy of PDA management for preterm infants varied across Asian countries in AsianNeo. Hospitals in Northeast Asia were more likely to perform PDA ligation (p < 0.001) than hospitals in Southeast Asia. Hospitals in Northeast Asia had stricter fluid restrictions in the first 24 h after birth for infants born at <29 weeks gestation (p < 0.001) and on day 14 after birth for infants born at <29 weeks gestation (p < 0.001) compared to hospitals in Southeast Asia. Hospitals in Northeast Asia also had a more humidified environment for infants born between 24 weeks gestation and 25 weeks gestation in the first 72 h after birth (p < 0.001). A logistic regression model predicted that hospitals were more likely to perform PDA ligation for PDA when the hospitals had a stricter fluid planning on day 14 after birth [Odds ratio (OR) of 1.70, p = 0.048], more incubator humidity settings (<80% vs. 80%-89%, OR of 3.35, p = 0.012 and <80% vs. 90%-100%, OR of 5.31, p < 0.001). Conclusions: In advanced economies and Northeast Asia, neonatologists tend to adopt a more conservative approach towards fluid management, maintain higher incubator humidity settings and inclined to perform surgical ligation for PDA.

Development of the Parental Experience with Care for Children with Serious Illnesses (PRECIOUS) quality of care measure.

BACKGROUND: Parent-reported experience measures are part of pediatric Quality of Care (QoC) assessments. However, existing measures were not developed for use across multiple healthcare settings or throughout the illness trajectory of seriously ill children. Formative work involving in-depth interviews with parents of children with serious illnesses generated 66 draft items describing key QoC processes. Our present aim is to develop a comprehensive parent-reported experience measure of QoC for children with serious illnesses and evaluate its content validity and feasibility. METHODS: For evaluating content validity, we conducted a three-round Delphi expert panel review with 24 multi-disciplinary experts. Next, we pre-tested the items and instructions with 12 parents via cognitive interviews to refine clarity and understandability. Finally, we pilot-tested the full measure with 30 parents using self-administered online surveys to finalize the structure and content. RESULTS: The Delphi expert panel review reached consensus on 68 items. Pre-testing with parents of seriously ill children led to consolidation of some items. Pilot-testing supported feasibility of the measure, resulting in a comprehensive measure comprising 56 process assessment items, categorized under ten subthemes and four themes: (1) Professional qualities of healthcare workers, (2) Supporting parent-caregivers, (3) Collaborative and holistic care, and (4) Efficient healthcare structures and standards. We named this measure the PaRental Experience with care for Children with serIOUS illnesses (PRECIOUS). CONCLUSIONS: PRECIOUS is the first comprehensive measure and has the potential to standardize assessment of QoC for seriously ill children from parental perspectives. PRECIOUS allows for QoC process evaluation across contexts (such as geographic location or care setting), different healthcare workers, and over the illness trajectory for children suffering from a range of serious illnesses.

PRECIOUS demonstrated satisfactory measurement properties for assessing the quality of care for children with serious illnesses.

OBJECTIVES: To determine the measurement properties of PaRental Experience with care for Children with serIOUS illnesses (PRECIOUS), a parent-reported measure of Quality of Care for seriously ill children across care settings and illness trajectories. STUDY DESIGN AND SETTING: Parents self-administered baseline and 2-week follow-up surveys online. Exploratory Factor Analysis was used to determine PRECIOUS's factor structure and select items. Internal consistency was evaluated with Cronbach's α, test-retest reliability with intraclass correlation coefficients, and convergent validity with Spearman's correlations between PRECIOUS scales and subscales of Measure of Processes of Care and Quality of Children's Palliative Care Instrument. RESULTS: Of 152 parents [108 (71%) mothers, 44 (29%) fathers] who completed the baseline survey, 123 (81%) completed follow-up. Exploratory Factor Analysis grouped PRECIOUS into five scales: collaborative and goal-concordant care (12 items), caregiver support and respectful care (15 items), access to financial and medical resources (five items), reducing caregiving stressors (nine items), and hospitalization-specific processes (four items). Root Mean Square Error of Approximation was 0.040 and Comparative Fit Index was 0.980. Cronbach's α ranged from 0.85 to 0.96. Intraclass correlation coefficients ranged from 0.72 to 0.86. Significant correlations with Measure of Processes of Care and Quality of Children's Palliative Care Instrument confirmed convergent validity. The original 56-item tool was reduced to 45 items. CONCLUSION: PRECIOUS demonstrates satisfactory measurement properties for assessing Quality of Care for seriously ill children.

Short term Outcomes of COVID-19 Vaccines Among Lactating Mother and Child Dyads in Bangladesh: A Multi-centre, Cross-sectional Study.

INTRODUCTION: The aims of the study are to: (1) determine the short-term reactogenicity of WHO-approved COVID-19 vaccines (i.e., Pfizer-BioNTech, Moderna, Sinovac, Oxford-AstraZeneca, Johnson and Johnson, Covaxin) amongst lactating women and their children, and 2) evaluate lactation-related outcomes following the same vaccines in Bangladesh. METHODS: This was a multi-centre, self-reported, cross-sectional study of lactating woman-child dyads in Bangladesh. Demographics, past medical history, breastfeeding history and clinical outcomes of lactating woman-child dyads at least 7 days after the last dose of vaccine were determined through a structured questionnaire. RESULTS: There were 750 participants from four centres. The mean age of lactating women and children surveyed were 27.6 (SD ± 4.6) years and 10.3 (SD ± 6.7) months, respectively. Majority (81.2%; 608 of 750) received 2 doses of COVID-19 vaccinations while lactating. Almost all (99.9%; 749 of 750) vaccinated lactating women surveyed reported no change in human milk supply. More than half of the participants (56.9%; 373 of 656) reported no symptoms after both doses of COVID-19 vaccines. There were no serious adverse events such as anaphylaxis or hospital admission. Majority of the lactating women (98.9%; 742 of 750) reported that the children whom they breastfed had no symptoms such as fever or cough. DISCUSSION: This large study of lactating woman-child dyads in Bangladesh, who received a diverse range of WHO-approved COVID-19 vaccines, showed no serious short-term adverse effects.

A qualitative exploration of parental perspectives on quality of care for children with serious illnesses.

Introduction: Being responsive to end-users is essential to good care. Limited in-depth exploration of parental perspectives on care received by children over the course of serious illness has hindered the development of process measures to evaluate quality of care. Our objective was to identify the key process indicators prioritized by parents in the care of seriously ill young children and develop a framework to guide assessment of quality of care. Methods: This qualitative study followed Charmaz's Constructivist Grounded Theory. In-depth semi-structured interviews were conducted with parents of young children with serious illness in Singapore. Participants were sampled across various healthcare settings, children's ages, and illness categories. Theoretical sampling and constant comparative analysis were used to generate initial, focused, and theoretical codes, which informed construction of a conceptual framework. Results: 31 parents participated from July 2021 to February 2022. Initial and focused coding generated 64 quality of care indicators describing key care practices, interactions, and procedures. Indicators were categorized under four themes: (1) efficient healthcare structures and standards, (2) professional qualities of healthcare workers, 3. supporting parent-caregivers, and 4. collaborative and holistic care. Theoretical coding led to the development of the "PaRental perspectives on qualIty of care for Children with sErious iLlnESSes (PRICELESS)" framework which summarizes elements contributing to the parental perception of quality of care. Discussion: The identified process indicators will facilitate the development of standardised parent-reported measures for assessing service quality and benchmarking among providers. The framework provides overall guidance for conceiving quality improvement initiatives.

Experiences of healthcare personnel with death in the neonatal intensive care unit: a systematic review of qualitative studies.

OBJECTIVE: To synthesise evidence from qualitative studies on the experiences of healthcare personnel (HCP) in the neonatal intensive care unit (NICU) caring for dying neonates. METHODS: We conducted a systematic search, in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PROSPERO: CRD42021250015), of four databases (PubMed, Embase, PsycINFO and CINAHL) from date of inception of the databases to 31 December 2021 using MeSH terms and related keywords. Data were analysed using three-step inductive thematic synthesis. Quality assessment of included studies was performed. RESULTS: Thirty-two articles were included. There were 775 participants, majority (92.6%) of whom were nurses and doctors. Quality of studies was variable. The narratives of HCP coalesced into three themes: sources of distress, coping methods and the way forward. Sources of distress encompassed HCP's discomfort with neonatal deaths; poor communication among HCP and with patient's family; lack of support (from organisations, peers and HCP's family) and emotional responses (guilt, helplessness and compassion fatigue). Methods of coping included setting emotional boundaries, support from colleagues, clear communication and compassionate care and well-designed end-of-life workflows. Steps taken by HCP to move forward and overcome the emotionally turbulent effects of NICU deaths included finding meaning in death, building deeper relationship with patients' families and the NICU team and embracing purpose and pride in work. CONCLUSION: HCP face several challenges when a death occurs in the NICU. HCP can provide better end-of-life care if their undesirable experiences with death are mitigated by better understanding and overcoming factors causing distress.

Birth anthropometry among three Asian racial groups in Singapore: proposed new growth charts.

OBJECTIVE: We analysed birth anthropometry of babies of Chinese, Malay and Indian ancestry living in Singapore with an aim to develop gestational age (GA) and gender-specific birth anthropometry charts and compare these with the widely used Fenton charts. DESIGN: Retrospective observational study. SETTING: Department of Neonatology, National University Hospital, Singapore. POPULATION: We report data from 52 220 infants, born between 1991-1997 and 2010-2017 in Singapore. METHODS: Anthropometry charts were built using smoothened centile curves and compared with Fenton's using binomial test. Birth weight (BW), crown-heel length and head circumference (HC) were each modelled with maternal exposures using general additive model. MAIN OUTCOME MEASURES: BW, crown-heel length and HC. RESULTS: There were 22 248 Chinese (43%), 16 006 Malay (31%) and 8543 Indian (16%) babies. Mean BW was 3103 g (95% CI 3096 to 3109), 3075 g (95% CI 3067 to 3083) and 3052 g (95% CI 3041 to 3062) for Chinese, Malays and Indians, respectively. When exposed to a uniform socioeconomic environment, intrauterine growth and birth anthropometry of studied races were almost identical. From our GA-specific anthropometric charts until about late prematurity, Asian growth curves mirrored that of Fenton's; thereafter, Asian babies showed a reduction in growth velocity. CONCLUSIONS: These findings suggest that Asian babies living in relatively uniform socioeconomic strata exhibit similar growth patterns. There is a slowing of growth among Asian babies towards term, prompting review of existing birth anthropometry charts. The proposed charts will increase accuracy of identification of true fetal growth restriction as well as true postnatal growth failure in preterm infants when applied to the appropriate population.

Quality of life of patients and caregivers affected by bronchopulmonary dysplasia: a systematic review.

PURPOSE: To synthesize evidence on the impact of bronchopulmonary dysplasia (BPD) on the Quality of Life (QoL) of affected individuals from three perspectives: (i) QoL of caregiver; (ii) caregiver's perception of BPD patient's QoL; and (iii) BPD patient's self-reported QoL. METHODS: Quantitative studies (case-control, cohort, and case series) on the QoL of BPD patients or their caregivers were considered. We conducted a systematic literature search of 6 databases (PubMed, Embase, World of Science, CINAHL, PsycINFO, and Chinese National Knowledge Infrastructure) for relevant studies. All databases were searched from the date of inception of the databases to 31 March 2022. Populations of interest were caregivers with preterm babies with BPD, or children/adults who were born premature and diagnosed with BPD. The main outcome measures were total and subdomain QoL scores, and factors affecting QoL. RESULTS: A total of 1078 articles were found; 10 were eligible for analysis, which included 247 caregivers and 1632 patients with BPD. The QoL of patients differed by domains-some were poorer or similar, but none of the QoL domains was better than QoL of healthy controls. Poor sleep and acute care needs of BPD patients negatively affected caregiver's QoL, while increasing illness acuity negatively affected the QoL of BPD patients. The QoL of BPD patients and their caregivers was most adversely affected during the immediate post-discharge period and tended to improve with time. The physical QoL of BPD patients was similar to that of preterm babies without BPD when assessed during late childhood and early adulthood. CONCLUSION: QoL assessment should be performed as an outcome measure and incorporated in the care plan for BPD patients and their caregivers. Systematic Review Registration PROSPERO CRD42021292253.

Immune and pathophysiologic profiling of antenatal coronavirus disease 2019 in the GIFT cohort: A Singaporean case-control study.

COVID-19 can be severe in pregnant women, and have adverse consequences for the subsequent infant. We profiled the post-infectious immune responses in maternal and child blood as well as breast milk in terms of antibody and cytokine expression and performed histopathological studies on placentae obtained from mothers convalescent from antenatal COVID-19. Seventeen mother-child dyads (8 cases of antenatal COVID-19 and 9 healthy unrelated controls; 34 individuals in total) were recruited to the Gestational Immunity For Transfer (GIFT) study. Maternal and infant blood, and breast milk samples were collected over the first year of life. All samples were analyzed for IgG and IgA against whole SARS-CoV-2 spike protein, the spike receptor-binding domain (RBD), and previously reported immunodominant epitopes, as well as cytokine levels. The placentae were examined microscopically. The study is registered at clinicaltrials.gov under the identifier NCT04802278. We found high levels of virus-specific IgG in convalescent mothers and similarly elevated titers in newborn children. Thus, antenatal SARS-CoV-2 infection led to high plasma titers of virus-specific antibodies in infants postnatally. However, this waned within 3-6 months of life. Virus neutralization by plasma was not uniformly achieved, and the presence of antibodies targeting known immunodominant epitopes did not assure neutralization. Virus-specific IgA levels were variable among convalescent individuals' sera and breast milk. Antibody transfer ratios and the decay of transplacentally transferred virus-specific antibodies in neonatal circulation resembled that for other pathogens. Convalescent mothers showed signs of chronic inflammation marked by persistently elevated IL17RA levels in their blood. Four placentae presented signs of acute inflammation, particularly in the subchorionic region, marked by neutrophil infiltration even though > 50 days had elapsed between virus clearance and delivery. Administration of a single dose of BNT162b2 mRNA vaccine to mothers convalescent from antenatal COVID-19 increased virus-specific IgG and IgA titers in breast milk, highlighting the importance of receiving the vaccine even after natural infection with the added benefit of enhanced passive immunity.

Antenatal corticosteroids in Singapore: A clinical and scientific assessment.

Preterm birth (PTB; delivery prior to 37 weeks' gestation) is the leading cause of early childhood death in Singapore today. Approximately 9% of Singaporean babies are born preterm; the PTB rate is likely to increase given the increased use of assisted reproduction technologies, changes in the incidence of gestational diabetes/high body mass index and the ageing maternal population. Antenatal administration of dexamethasone phosphate is a key component of the obstetric management of Singaporean women who are at risk of imminent preterm labour. Dexamethasone improves preterm outcomes by crossing the placenta to functionally mature the fetal lung. The dexamethasone regimen used in Singapore today affords a very high maternofetal drug exposure over a brief period of time. Drawing on clinical and experimental data, we reviewed the pharmacokinetic profile and pharmacodynamic effects of dexamethasone treatment regimen in Singapore, with a view to creating a development pipeline for optimising this critically important antenatal therapy.

Mentoring a surgical team towards procedural competence in the early learning curve for selective fetoscopic laser photocoagulation.

INTRODUCTION: Selective fetoscopic laser photocoagulation (SFLP) for twin-to-twin transfusion syndrome (TTTS) is challenging for new surgeons at the start of their learning curve. We described an approach utilising telementoring and team-based training to facilitate rapid attainment of the skills required for safe and efficient practice with a limited caseload. METHODS: We conducted a prospective observational study of SFLP performed by the novice primary surgical team in three stages: under direct on-site supervision from an expert mentor (Group 1), with remote tele-guidance from that mentor (Group 2) and independently (Group 3), at an academic tertiary hospital in Singapore. The primary team undertook regular training on high-fidelity tissue models to accelerate skills acquisition and complement the surgical performance. RESULTS: 9 patients diagnosed with Stage 2 TTTS were assessed for procedural characteristics, surgical outcomes and perinatal survival following SFLP. There were no significant differences in operative duration, anastomoses ablated, gestational age or birth weight at delivery. The complications observed were: recurrent TTTS (22.2% of pregnancies), twin anaemia polycythaemia sequence (33.3%), preterm prelabour membrane rupture (22.2%) and delivery at < 32 weeks (44.4%). ≥ 1 twin was live-born in 88.9% of cases, while postnatal survival to six months of ≥ 1 twin occurred in 77.8% of cases. CONCLUSION: Systematic mentoring and specialised skills training are useful in aiding new surgeons to negotiate the steep learning curve and achieve good outcomes at the start of a new practice, particularly in the setting of low patient numbers. This is best paired with dedicated model training to achieve and maintain surgical dexterity for this complex procedure.

Reactogenicity of mRNA- and Non-mRNA-Based COVID-19 Vaccines among Lactating Mother and Child Dyads.

The aims of the study are to: (a) Describe the reactogenicity of WHO-approved two mRNA (Pfizer-BioNTech, Moderna) and two non-RNA (Oxford-AstraZeneca, Sinovac) vaccines among lactating mother and child pairs, and (b) Compare and contrast the reactogenicity between mRNA and non-mRNA vaccines. A cross-sectional, self-reported survey was conducted amongst 1784 lactating women who received COVID-19 vaccinations. The most common maternal adverse reaction was a local reaction at the injection site, and the largest minority of respondents, 49.6% (780/1571), reported experiencing worse symptoms when receiving the second dose compared to the first dose. Respondents reported no major adverse effects or behavioural changes in the breastfed children for the duration of the study period. Among respondents who received non-mRNA COVID-19 vaccines, a majority reported no change in lactation, but those who did more commonly reported changes in the quantity of milk supply and pain in the breast. The more commonly reported lactation changes (fluctuations in breast milk supply quantity and pain in the breast) for the non-mRNA vaccines were similar to those of respondents who received mRNA vaccines. Our study, with a large, racially diverse cohort, further augments earlier reported findings in that the COVID-19 vaccines tested in this study did not cause any serious adverse events in our population for the duration of our survey period, although long-term effects are yet to be studied.

Effect of COVID-19 Pandemic on Influenza Vaccination Intention: A Meta-Analysis and Systematic Review.

Poorer outcomes have been reported with COVID-19 and influenza coinfections. As the COVID-19 pandemic rages on, protection against influenza by vaccination is becoming increasingly important. This study examines how COVID-19 has influenced influenza vaccination intentions from a global perspective. A literature search was conducted on Embase, PubMed, and CNKI from 1 January 2019 to 31 December 2021 for articles reporting rates of influenza vaccination pre-COVID-19 (19/20 season), and intention and/or uptake of influenza vaccination post-COVID-19 (20/21 season). The changes in vaccination intention and reasons for changes were reported. Subgroup analyses were performed by region, gender, age, and occupation. Newcastle Ottawa Scale was used for quality assessment of the articles. Twenty-seven studies with 39,193 participants were included. Among 22 studies reporting intention to vaccinate in 20/21, there was increased intention to vaccinate (RR 1.50, 95% CI 1.32−1.69, p < 0.001) regardless of age, gender, and occupation. The remaining five studies reporting vaccination intention and uptake in 20/21 showed a similar increase (RR 1.68, 95%CI 1.20−2.36). Important determinants include historical vaccine acceptance, and perception of influenza severity and vaccine safety. The COVID-19 pandemic has increased intention to vaccinate against influenza internationally. The pandemic could be a window of opportunity to promote influenza vaccination and decrease vaccine hesitancy.

Human Milk Antibodies after BNT162b2 Vaccination Exhibit Reduced Binding against SARS-CoV-2 Variants of Concern.

SARS-CoV-2-specific antibody responses are engendered in human milk after BNT162b2 vaccination. However, the emergence of variants of concern (VOCs) raises concerns about the specificity of and potential cross-protection mediated by milk antibody responses, which are crucial for passive immunity transferred from breastfeeding mothers to their infants. In this study, we collected milk samples at three different time points pre- and post-vaccination, and measured milk IgA antibody binding to the receptor binding domain (RBD) of the original Wuhan-Hu-1 strain, and the four VOCs, namely Alpha, Beta, Gamma and Delta. We report a significant level of anti-RBD IgA in milk collected at 4-6 weeks after the second dose of vaccination compared to pre-vaccination. We observed around a 30% reduction in binding to most VOCs, including the major circulating Delta variant, compared to the original Wuhan-Hu-1 strain. As COVID-19 vaccines may take some time to be approved for infants, these individuals remain at risk for severe disease and rely mainly on transferred passive immunity. Our findings support the current recommendations for vaccinating lactating women with the aim of transferring mucosal immunity to breastfeeding infants.

Implementation research on kangaroo mother care, Bangladesh.

OBJECTIVE: To describe the implementation, coverage and performance of the national kangaroo mother care programme in Bangladesh. METHODS: Kangaroo mother care services for clinically stable babies with birth weight under 2000 g were set up in government-run health-care facilities in rural and urban areas of Bangladesh. Each facility provided counselling on kangaroo mother care, ensured adequate nutrition, and followed up mothers and babies. We studied implementation of the programme from January 2016 to March 2020 using data from the national database. We tracked the number of eligible babies enrolled and their outcomes, mortality and post-discharge follow-up. FINDINGS: The numbers of kangaroo mother care facilities increased from 16 in 2016 to 108 in 2020. Over the 4-year period 64 426 babies weighing under 2000 g were born in these facilities, 6410 of whom received kangaroo mother care. The quarterly percentage of eligible babies receiving kangaroo mother care increased from 4.7% (37/792) during the first quarter to 21.7% (917/4226) during the last five quarters of the programme. Deaths of babies receiving kangaroo mother care showed a downward trend over the study period. The overall mortality was 1.2% (77/6410), with large quarterly fluctuations in mortality. Post-discharge follow-up was low and only 15-20% of babies received four follow-up visits. CONCLUSION: Implementation of kangaroo mother care interventions is feasible in low-resource settings. Such care has the potential to reduce mortality among low-birth-weight and premature babies. Challenges include low coverage, expanding the programme to the community and strengthening the monitoring system.

Breastfeeding Mother and Child Clinical Outcomes After COVID-19 Vaccination.

BACKGROUND: Pre-approval clinical trials of the Pfizer/BioNTech messenger RNA COVID-19 vaccine, BNT162b2 did not include participants who were breastfeeding. Therefore, there is limited evidence about outcomes of breastfeeding mother-child dyads and effects on breastfeeding after vaccination. RESEARCH AIMS: To determine: (1) solicited adverse effects (e.g., axillary lymphadenopathy, mastitis, and breast engorgement), which are unique to lactating individuals; and (2) systemic and local adverse effects of COVID-19 mRNA vaccine on mothers and potential effects on their breastfed infants. METHOD: This was a prospective cohort study of lactating healthcare workers (N = 88) in Singapore who received two doses of BNT162b2 vaccination (Pfizer/BioNTech). The outcomes of mother-child dyads within 28 days after the second vaccine dose were determined through a participant-completed questionnaire. RESULTS: Minimal effects related to breastfeeding were reported by this cohort; three of 88 (3.4%) participants had mastitis, one (1.1%) participant experienced breast engorgement, five of 88 (5.7%) participants reported cervical or axillary lymphadenopathy. There was no change in human milk supply after vaccination. The most common side effect was pain/redness/swelling at the injection site, which was experienced by 57 (64.8%) participants. There were no serious adverse events of anaphylaxis or hospital admissions. There were no short-term adverse effects reported in the infants of 67 lactating participants who breastfed within 72 hr after BNT162b2 vaccination. CONCLUSIONS: BNT162b2 vaccination was well tolerated in lactating participants and was not associated with short-term adverse effects in their breastfed infants. STUDY PROTOCOL REGISTRATION: The study protocol was registered at clinicaltrials.gov (NCT04802278).

Guidance for the clinical management of infants born to mothers with suspected/confirmed COVID-19 in Singapore.

In this paper, we provide guidance to clinicians who care for infants born to mothers with suspected/confirmed COVID-19 during this current pandemic. We reviewed available literature and international guidelines based on the following themes: delivery room management; infection control and prevention strategies; neonatal severe acute respiratory syndrome coronavirus 2 testing; breastfeeding and breastmilk feeding; rooming-in of mother-infant; respiratory support precautions; visiting procedures; de-isolation and discharge of infant; outpatient clinic attendance; transport of infant; and training of healthcare staff. This guidance for clinical care was proposed and contextualised for the local setting via consensus by members of this workgroup and was based on evidence available as of 31 July 2020, and may change as new evidence emerges.

Titres and neutralising capacity of SARS-CoV-2-specific antibodies in human milk: a systematic review.

OBJECTIVE: Synthesise evidence on production of SARS-CoV-2 antibodies in human milk of individuals who had COVID-19, and antibodies' ability to neutralise SARS-CoV-2 infectivity. DESIGN: A systematic review of studies published from 1 December 2019 to 16 February 2021 without study design restrictions. SETTING: Data were sourced from PubMed, MEDLINE, Embase, CNKI, CINAHL and WHO COVID-19 database. Search was also performed through reviewing references of selected articles, Google Scholar and preprint servers. Studies that tested human milk for antibodies to SARS-CoV-2 were included. PATIENTS: Individuals with COVID-19 infection and human milk tested for anti-SARS-CoV-2 neutralising antibodies. MAIN OUTCOME MEASURES: The presence of neutralising antibodies in milk samples provided by individuals with COVID-19 infection. RESULTS: Individual participant data from 161 persons (14 studies) were extracted and re-pooled. Milk from 133 (82.6%) individuals demonstrated the presence of anti-SARS-CoV-2 immunoglobulin A (IgA), IgM and/or IgG. Illness severity data were available in 146 individuals; 5 (3.4%) had severe disease, 128 (87.7%) had mild disease, while 13 (8.9%) were asymptomatic. Presence of neutralising antibodies in milk from 20 (41.7%) of 48 individuals neutralised SARS-CoV-2 infectivity in vitro. Neutralising capacity of antibodies was lost after Holder pasteurisation but preserved after high-pressure pasteurisation. CONCLUSION: Human milk of lactating individuals after COVID-19 infection contains anti-SARS-CoV-2-specific IgG, IgM and/or IgA, even after mild or asymptomatic infection. Current evidence demonstrates that these antibodies can neutralise SARS-CoV-2 virus in vitro. Holder pasteurisation deactivates SARS-CoV-2-specific IgA, while high-pressure pasteurisation preserves the SARS-CoV-2-specific IgA function.