Abstract Breast milk is the perfect nutrition for infants, a result of millions of years of evolution, finely attuning it to the requirements of the infant. Breast milk contains many complex ...proteins, lipids and carbohydrates, the concentrations of which alter dramatically over a single feed, as well as over lactation, to reflect the infant’s needs. In addition to providing a source of nutrition for infants, breast milk contains a myriad of biologically active components. These molecules possess diverse roles, both guiding the development of the infants immune system and intestinal microbiota. Orchestrating the development of the microbiota are the human milk oligosaccharides, the synthesis of which are determined by the maternal genotype. In this review, we discuss the composition of breast milk and the factors that affect it during the course of breast feeding. Understanding the components of breast milk and their functions will allow for the improvement of clinical practices, infant feeding and our understanding of immune responses to infection and vaccination in infants.
Breast milk is the perfect nutrition for infants, a result of millions of years of evolution. In addition to providing a source of nutrition, breast milk contains a diverse array of microbiota and ...myriad biologically active components that are thought to guide the infant's developing mucosal immune system. It is believed that bacteria from the mother's intestine may translocate to breast milk and dynamically transfer to the infant. Such interplay between mother and her infant is a key to establishing a healthy infant intestinal microbiome. These intestinal bacteria protect against many respiratory and diarrheal illnesses, but are subject to environmental stresses such as antibiotic use. Orchestrating the development of the microbiota are the human milk oligosaccharides (HMOs), the synthesis of which are partially determined by the maternal genotype. HMOs are thought to play a role in preventing pathogenic bacterial adhesion though multiple mechanisms, while also providing nutrition for the microbiome. Extracellular vesicles (EVs), including exosomes, carry a diverse cargo, including mRNA, miRNA, and cytosolic and membrane-bound proteins, and are readily detectable in human breast milk. Strongly implicated in cell-cell signaling, EVs could therefore may play a further role in the development of the infant microbiome. This review considers the emerging role of breast milk microbiota, bioactive HMOs, and EVs in the establishment of the neonatal microbiome and the consequent potential for modulation of neonatal immune system development.
Safety and effectiveness of COVID-19 vaccines during pregnancy is a particular concern affecting vaccination uptake by this vulnerable group. Here we evaluated evidence from 23 studies including ...117,552 COVID-19 vaccinated pregnant people, almost exclusively with mRNA vaccines. We show that the effectiveness of mRNA vaccination against RT-PCR confirmed SARS-CoV-2 infection 7 days after second dose was 89·5% (95% CI 69·0-96·4%, 18,828 vaccinated pregnant people, I
= 73·9%). The risk of stillbirth was significantly lower in the vaccinated cohort by 15% (pooled OR 0·85; 95% CI 0·73-0·99, 66,067 vaccinated vs. 424,624 unvaccinated, I
= 93·9%). There was no evidence of a higher risk of adverse outcomes including miscarriage, earlier gestation at birth, placental abruption, pulmonary embolism, postpartum haemorrhage, maternal death, intensive care unit admission, lower birthweight Z-score, or neonatal intensive care unit admission (p > 0.05 for all). COVID-19 mRNA vaccination in pregnancy appears to be safe and is associated with a reduction in stillbirth.
The COVID-19 pandemic has had a profound impact on health-care systems and potentially on pregnancy outcomes, but no systematic synthesis of evidence of this effect has been undertaken. We aimed to ...assess the collective evidence on the effects on maternal, fetal, and neonatal outcomes of the pandemic.
We did a systematic review and meta-analysis of studies on the effects of the pandemic on maternal, fetal, and neonatal outcomes. We searched MEDLINE and Embase in accordance with PRISMA guidelines, from Jan 1, 2020, to Jan 8, 2021, for case-control studies, cohort studies, and brief reports comparing maternal and perinatal mortality, maternal morbidity, pregnancy complications, and intrapartum and neonatal outcomes before and during the pandemic. We also planned to record any additional maternal and offspring outcomes identified. Studies of solely SARS-CoV-2-infected pregnant individuals, as well as case reports, studies without comparison groups, narrative or systematic literature reviews, preprints, and studies reporting on overlapping populations were excluded. Quantitative meta-analysis was done for an outcome when more than one study presented relevant data. Random-effects estimate of the pooled odds ratio (OR) of each outcome were generated with use of the Mantel-Haenszel method. This review was registered with PROSPERO (CRD42020211753).
The search identified 3592 citations, of which 40 studies were included. We identified significant increases in stillbirth (pooled OR 1·28 95% CI 1·07–1·54; I2=63%; 12 studies, 168 295 pregnancies during and 198 993 before the pandemic) and maternal death (1·37 1·22–1·53; I2=0%, two studies both from low-income and middle-income countries, 1 237 018 and 2 224 859 pregnancies) during versus before the pandemic. Preterm births before 37 weeks' gestation were not significantly changed overall (0·94 0·87–1·02; I2=75%; 15 studies, 170 640 and 656 423 pregnancies) but were decreased in high-income countries (0·91 0·84–0·99; I2=63%; 12 studies, 159 987 and 635 118 pregnancies), where spontaneous preterm birth was also decreased (0·81 0·67–0·97; two studies, 4204 and 6818 pregnancies). Mean Edinburgh Postnatal Depression Scale scores were higher, indicating poorer mental health, during versus before the pandemic (pooled mean difference 0·42 95% CI 0·02–0·81; three studies, 2330 and 6517 pregnancies). Surgically managed ectopic pregnancies were increased during the pandemic (OR 5·81 2·16–15·6; I2=26%; three studies, 37 and 272 pregnancies). No overall significant effects were identified for other outcomes included in the quantitative analysis: maternal gestational diabetes; hypertensive disorders of pregnancy; preterm birth before 34 weeks', 32 weeks', or 28 weeks' gestation; iatrogenic preterm birth; labour induction; modes of delivery (spontaneous vaginal delivery, caesarean section, or instrumental delivery); post-partum haemorrhage; neonatal death; low birthweight (<2500 g); neonatal intensive care unit admission; or Apgar score less than 7 at 5 min.
Global maternal and fetal outcomes have worsened during the COVID-19 pandemic, with an increase in maternal deaths, stillbirth, ruptured ectopic pregnancies, and maternal depression. Some outcomes show considerable disparity between high-resource and low-resource settings. There is an urgent need to prioritise safe, accessible, and equitable maternity care within the strategic response to this pandemic and in future health crises.
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Group B
(GBS) causes a high burden of neonatal and infant disease globally. Implementing a vaccine for pregnant women is a promising strategy to prevent neonatal and infant GBS disease and has been ...identified as a priority by the World Health Organisation (WHO). GBS serotype-specific polysaccharide - protein conjugate vaccines are at advanced stages of development, but a large number of participants would be required to undertake Phase III clinical efficacy trials. Efforts are therefore currently focused on establishing serocorrelates of protection in natural immunity studies as an alternative pathway for licensure of a GBS vaccine, followed by Phase IV studies to evaluate safety and effectiveness. Protein vaccines are in earlier stages of development but are highly promising as they might confer protection irrespective of serotype. Further epidemiological, immunological and health economic studies are required to enable the vaccine to reach its target population as soon as possible.
We aimed to provide the first comprehensive estimates of the burden of group B Streptococcus (GBS), including invasive disease in pregnant and postpartum women, fetal infection/stillbirth, and ...infants. Intrapartum antibiotic prophylaxis is the current mainstay of prevention, reducing early-onset infant disease in high-income contexts. Maternal GBS vaccines are in development.
For 2015 live births, we used a compartmental model to estimate (1) exposure to maternal GBS colonization, (2) cases of infant invasive GBS disease, (3) deaths, and (4) disabilities. We applied incidence or prevalence data to estimate cases of maternal and fetal infection/stillbirth, and infants with invasive GBS disease presenting with neonatal encephalopathy. We applied risk ratios to estimate numbers of preterm births attributable to GBS. Uncertainty was also estimated.
Worldwide in 2015, we estimated 205000 (uncertainty range UR, 101000-327000) infants with early-onset disease and 114000 (UR, 44000-326000) with late-onset disease, of whom a minimum of 7000 (UR, 0-19000) presented with neonatal encephalopathy. There were 90000 (UR, 36000-169000) deaths in infants <3 months age, and, at least 10000 (UR, 3000-27000) children with disability each year. There were 33000 (UR, 13000-52000) cases of invasive GBS disease in pregnant or postpartum women, and 57000 (UR, 12000-104000) fetal infections/stillbirths. Up to 3.5 million preterm births may be attributable to GBS. Africa accounted for 54% of estimated cases and 65% of all fetal/infant deaths. A maternal vaccine with 80% efficacy and 90% coverage could prevent 107000 (UR, 20000-198000) stillbirths and infant deaths.
Our conservative estimates suggest that GBS is a leading contributor to adverse maternal and newborn outcomes, with at least 409000 (UR, 144000-573000) maternal/fetal/infant cases and 147000 (UR, 47000-273000) stillbirths and infant deaths annually. An effective GBS vaccine could reduce disease in the mother, the fetus, and the infant.
The virus subsequently spread rapidly throughout China and other countries worldwide, and on March 11, 2020, the outbreak was declared a pandemic. Since March 11, 2020, the virus has continued to ...spread, causing substantial morbidity and mortality in many countries. A systematic review and meta-analysis of mainly small case series reported that a high proportion of women with confirmed COVID-19 infection had preterm birth (<37 weeks 22%) and caesarean delivery (48%).5 Estimated rates of admission to the intensive care unit among pregnant women (7%) were higher than those of non-pregnant women (4%) and around 1·9% of infants born to these women tested positive for SARS-CoV-2.5 Thus far, the literature has focused on symptomatic women with confirmed infection, however, this might underestimate the rates of admission, since many individuals are asymptomatic.6 Many important questions remain unanswered, including the extent of asymptomatic or mild infection and the effect of COVID-19 on miscarriage, intrauterine fetal growth restriction, congenital anomalies, long-term growth, and neurodevelopmental outcomes. The need for intensive care support among patients with COVID-19 is of particular concern for pregnant women who reside in low-income and middle-income countries.5 These factors suggest that pregnant women should be considered as candidates for preventative measures, of which vaccination is the gold standard. Since the immune responses to vaccination in pregnant women cannot be assumed from that of non-pregnant women and because the assessment of safety of vaccination in pregnancy is unique, pregnant women should be included in appropriately designed vaccine trials.
Synopsis
Post‐licensure studies of a Group B streptococcal vaccines for pregnant women in low and middle‐income countries will require investment in electronic health records.
The COVID-19 pandemic has had a profound impact on healthcare systems globally, with a worrying increase in adverse maternal and foetal outcomes. We aimed to assess the changes in maternity ...healthcare provision and healthcare-seeking by pregnant women during the COVID-19 pandemic.
We performed a systematic review and meta-analysis of studies of the effects of the pandemic on provision of, access to and attendance at maternity services (CRD42020211753). We searched MEDLINE and Embase in accordance with PRISMA guidelines from January 1st, 2020 to April 17th 2021 for controlled observational studies and research letters reporting primary data comparing maternity healthcare-seeking and healthcare delivery during compared to before the COVID-19 pandemic. Case reports and series, systematic literature reviews, and pre-print studies were excluded. Meta-analysis was performed on comparable outcomes that were reported in two or more studies. Data were combined using random-effects meta-analysis, using risk ratios (RR) or incidence rate ratios (IRR) with 95% confidence intervals (CI).
Of 4743 citations identified, 56 were included in the systematic review, and 21 in the meta-analysis. We identified a significant decrease in the number of antenatal clinic visits (IRR 0614, 95% CI 0486–0776, P<00001, I2=54.6%) and unscheduled care visits (IRR 0741, 95% CI 0602–0911, P = 00046, I2=00%) per week, and an increase in virtual or remote antenatal care (IRR 4656 95% CI 7762–2794, P<00001, I2=90.6%) and hospitalisation of unscheduled attendees (RR 1214, 95% CI 1118–1319, P<00001, I2=00%). There was a decrease in the use of GA for category 1 Caesarean sections (CS) (RR 0529, 95% CI 0407–0690, P<00001, I2=00%). There was no significant change in intrapartum epidural use (P = 00896) or the use of GA for elective CS (P = 079)
Reduced maternity healthcare-seeking and healthcare provision during the COVID-19 pandemic has been global, and must be considered as potentially contributing to worsening of pregnancy outcomes observed during the pandemic.
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