The microbiome in pregnancy and early life-Highlights from the 11th Maria Delivoria-Papadopoulos Perinatal Symposium.

This review was based on a symposium that examined novel aspects of the microbiome during pregnancy and early life and explored papers published by the lecturers. For example, it showed that bacterial extracellular vesicles derived from the microbiome harboured in various maternal niches, carried bacterial deoxyribonucleic acid, were isolated from the placenta and may have confounded placental microbiome studies. Maternal diet was responsible for the composition and diversity of breast milk microbiota, and may have shaped the offspring's microbiome and influenced their immune components. Probiotics and antibiotics administered perinatally may have had beneficial but also long-lasting adverse effects on offspring.

Advanced parental age affects cardiometabolic risk in offspring.

Advanced age at conception usually refers to human mothers aged 35 years plus and fathers aged 40 years plus. Advanced parental age may be responsible for genetic and/or epigenetic alterations and may affect the health of offspring. Limited epidemiological and experimental studies have addressed the effect of advanced parental age on cardio-metabolic functions in human and rodent offspring. This mini review aimed to present the knowledge by focusing on adverse and favourable outcomes related to sex-specific risks and intergenerational inheritance. The outcomes identified by this review were mainly negative, but there were also some positive results.

Evidence, hints and assumptions for late pregnancy in the Ancient Mediterranean and Near East.

Ancient women, who survived childhood mortality, received good and adequate nutrition, did not work hard and escaped death during childbirth could live fairly long lives. Girls started procreation after marriage, usually at 15 years, had on average seven children, childbearing lasted 14-21 or more years and could happen at the age of 35 or more years. Breastfeeding, usually with contraceptive effect, continued for 2-3 years. Limited actual facts, written evidence and findings, but several hints, assumptions and logical conclusions from secular texts, sacred books, narratives and myths suggest the possibility of late childbearing in the Mediterranean and Near-Eastern ancient world, particularly for the Jews.

Breastfeeding provides a protective hug and the benefits have outweighed the risks during the COVID-19 pandemic.

Mothers have been very hesitant about breastfeeding when they have COVID-19 infection or vaccinations. Maternal milk protects neonates through its high biological value, immune factors and anti-infectious molecules and this review shows that the virus that causes COVID-19 is not transmitted through breast milk. COVID-19 vaccines induce anti-spike antibodies with neutralising capacity, and phagocytosis, and no vaccine particles or messenger ribonucleic acid have been detected in breast milk. Most drugs used for maternal COVID-19 infections are safe for breastfed infants. CONCLUSION: The clear benefits of breastfeeding by far outweigh the very low risk of infant infections from COVID-19.

Paid leave to support parenting-A neglected tool to improve societal well-being and prosperity.

Cohesive families and stimulating and caring environments promoting attachment to caregivers is fundamental for a child's physical and psychosocial growth and development. Parental care, supporting early years development, presupposes the presence and involvement of parents in children's daily life with activities that include breastfeeding, playing, reading and storytelling. However, parents have to balance their child's well-being against employment, career progression and gender equality. Universally accessible and equitably available parental leave addresses this challenge. CONCLUSION: Distinct from compulsory maternity leave, leave at full or nearly full pay for both parents benefits not only families but also societal well-being and prosperity.

Valuing maternal, newborn, child and adolescent health for societal progress - Going beyond the economic orthodoxy of gross domestic product.

AIM: In view of the long-standing recognition that gross domestic product (GDP) does not capture the unremunerated work largely conducted by women upon which societal well-being depends, to discuss the implications for GDP of maternal, newborn, child and adolescent health (MNCAH), and its influences on health, well-being and prosperity across the life course and across generations. METHODS: A wide-ranging discussion of the informal think-tank The Venice Forum was held over two days, with inputs from invited experts in person and online. RESULTS: There was consensus that a strong case could be made for inclusion of unremunerated work largely conducted by women as a positive contribution to GDP in view of its impact on future health and prosperity, and conversely exclusion from GDP of outputs from industries which harm health. CONCLUSION: Taken with the current challenges from COVID, climate change and conflict, there is a compelling need to redefine economic progress through equitable models and metrics that incorporate short-/medium-/long-term societal value of activities that improve MNCAH.

Action is needed to tackle the clinical, psychological and socioeconomic impact of perinatal COVID-19.

The COVID-19 pandemic has turned perinatal healthcare into a worldwide public health challenge. Although initial data did not demonstrate pregnancy as a more susceptible period to adverse outcomes of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, an increasing number of reports now certify maternal illness as a high-risk condition for the development of maternal-fetal complications. Despite the rarity of SARS-CoV-2 vertical transmission, severe maternal illness might induce adverse perinatal and neonatal outcomes. Additionally, perinatal COVID-19 data may raise concerns about long-term harmful consequences to the offspring in the framework of non-communicable diseases. The World Health Organisation, as well as scientific literature, consider the protection of the maternal-fetal dyad against COVID-19 as a critical issue and, therefore, strongly promote and encourage the vaccination of pregnant and lactating women. Furthermore, the pandemic has triggered an unprecedented recession, leading to historic levels of unemployment and deprivation, while health, societal, economic and gender inequities particularly affecting low-income and middle-income countries, have increased. This mini-review provides an updated brief report on historical, clinical, psychological and socioeconomic aspects of the COVID-19 pandemic based on 10 lectures presented at the 9th Maria-Delivoria-Papadopoulos Perinatal Symposium, held virtually on 19 March 2022.

Recommendations of Ancient Greek and Byzantine physicians and philosophers on perinatal nutrition and care.

This mini-narrative historical review presents views and recommendations of Ancient Greek and Byzantine physicians and philosophers, concerning the nutrition and lifestyle, collectively referred in antiquity as 'diet', of pregnant and breastfeeding women, and the nutrition of the foetus and neonate. Pregnant and breastfeeding women in these eras were cared for with regard to their nutrition and well-being, in addition to their clothing, physical exercise and mental health. A number of ancient scholars taught that the foetus was fed through the umbilical cord. Breastfeeding by mothers was warmly recommended, but wet nurses and baby bottles were also available. Relevant information is found in preserved texts of well-known antique physicians and philosophers, who had studied medicine, or discussed medical issues.

The jury is still out on the existence of a placental microbiome.

The human microbiome is crucial for regulating normal development, but the exact point when it is established remains unknown. A sterile placenta was traditionally considered a prerequisite for a healthy pregnancy, but studies have revealed that the placenta harbours microbial communities, even under normal conditions. However, reports have failed to provide evidence for the consistent presence of bacteria in the normal human placenta, challenging the in utero colonisation hypothesis. This mini review examines our understanding of the potential placental microbial colonisation in normal healthy pregnancies. This may impact the metabolic and immune functions of the growing foetus and have long-term consequences.

Adipokines and Metabolic Regulators in Human and Experimental Pulmonary Arterial Hypertension.

Pulmonary hypertension (PH) is associated with meta-inflammation related to obesity but the role of adipose tissue in PH pathogenesis is unknown. We hypothesized that adipose tissue-derived metabolic regulators are altered in human and experimental PH. We measured circulating levels of fatty acid binding protein 4 (FABP-4), fibroblast growth factor -21 (FGF-21), adiponectin, and the mRNA levels of FABP-4, FGF-21, and peroxisome proliferator-activated receptor γ (PPARγ) in lung tissue of patients with idiopathic PH and healthy controls. We also evaluated lung and adipose tissue expression of these mediators in the three most commonly used experimental rodent models of pulmonary hypertension. Circulating levels of FABP-4, FGF-21, and adiponectin were significantly elevated in PH patients compared to controls and the mRNA levels of these regulators and PPARγ were also significantly increased in human PH lungs and in the lungs of rats with experimental PH compared to controls. These findings were coupled with increased levels of adipose tissue mRNA of genes related to glucose uptake, glycolysis, tricarboxylic acid cycle, and fatty acid oxidation in experimental PH. Our results support that metabolic alterations in human PH are recapitulated in rodent models of the disease and suggest that adipose tissue may contribute to PH pathogenesis.

Perinatal biomarkers implying 'Developmental Origins of Health and Disease' consequences in intrauterine growth restriction.

The intrauterine-growth-restricted (IUGR) state, particularly the asymmetric one, has been associated with 'Developmental Origins of Health and Disease' (DOHaD) consequences later in life. Several environmental factors, acting during the phase of foetal developmental plasticity interact with genotypic variation, 'programme' tissue function and change the capacity of the organism to cope with its environment. They may be responsible for chronic illness risk in adulthood. Detection of possible future DOHaD consequences at a very early age, by applying relevant biomarkers, is of utmost importance. This review focuses on biomarkers possibly predicting consequences from bone, psychoneural system and lung. Although no concrete biomarker has been identified for bone disorders in adulthood, reduced brain-derived neurotrophic factor (BDNF) concentrations in cord blood and BDNF DNA methylation might predict schizophrenia and possibly depression, bipolar disorder and autism. High surfactant protein D (SP-D) concentrations in cord blood of IUGR foetuses/neonates could point to structural lung immaturity, resulting to asthma and chronic obstructive pulmonary disease in adult life.

Impact of economic crises on offspring health and the developmental origins of health and disease concept.

There is emerging evidence that economic crises may impact long-term health. Furthermore, adversity experienced by women and their offspring might be transmitted to next generations. The Developmental Origins of Health and Disease (DOHaD) approach emphasises the importance of early life events for the state of health and risk for disease later in life. In this review, we discuss current evidence on the possible impact of economic crises on offspring health through the DOHaD framework and highlight the importance of critical periods of development for future disease risk. Therefore, successful interventions should prioritise strategies that address early life risk factors.

Preadipocyte factor-1 in maternal, umbilical cord serum and breast milk: The impact of fetal growth.

BACKGROUND/OBJECTIVE: To study the concentrations of preadipocyte factor-1 (Pref-1) -an inhibitor of adipocyte differentiation, implicated in adipose tissue metabolism, late metabolic disorders and fetal growth- in maternal and umbilical cord serum, as well as maternal milk and correlate above concentrations with intrauterine growth and other perinatal parameters. MATERIAL AND METHODS: Pref-1 concentrations were determined by ELISA in antepartum maternal and umbilical cord serum, as well as day 3 to 4 postpartum breast milk, deriving from 80 women, who delivered 40 appropriate (AGA), 20 large for gestational age (LGA) and 20 intrauterine growth restricted (IUGR) neonates, classified by the use of customized birth-weight standards adjusted for significant determinants of fetal growth. RESULTS: Umbilical cord serum Pref-1 concentrations were significantly higher than antepartum maternal ones (p < 0.001), while breast milk concentrations were the lowest (p < 0.001 concerning umbilical serum, p < 0.001 concerning maternal serum). Umbilical cord serum Pref-1 concentrations were significantly lower in the LGA group than in the AGA one (p = 0.044). Breast milk and maternal serum Pref-1 concentrations did not differ between the three intrauterine growth groups. Maternal serum and breast milk Pref-1 concentrations did not correlate with maternal age, body mass index before and after gestation, birth weight, body length, and customized centile. A positive weak correlation was recorded between maternal serum and milk Pref-1 concentrations (r = 0.238, p = 0.034). CONCLUSIONS: Pref-1 concentrations in umbilical cord serum are higher than in antepartum maternal serum, probably pointing to its fetal origin and role in intrauterine growth. Breast milk concentrations, being extremely low, and possibly implying infant protection from metabolic disorders, positively correlate with maternal serum ones, conceivably suggesting a transfer of the substance from the circulation to the breast. Umbilical cord serum Pref-1 concentrations were lower in LGA fetuses/neonates, as compared to respective AGA ones.

Cord blood fatty acid-binding protein-4 levels are upregulated at both ends of the birthweight spectrum.

AIM: Fatty acid-binding protein-4 (FABP4) is an adipokine associated with obesity and signs of the metabolic syndrome. We aimed to investigate at birth in term neonates with normal and abnormal intrauterine growth concentrations of FABP4 and associate them with various perinatal parameters. METHODS: Serum cord blood FABP4 levels were prospectively determined by ELISA in 80 singleton term appropriate-for-gestational-age (AGA), intrauterine growth-restricted (IUGR) and large-for-gestational-age (LGA) neonates. RESULTS: Compared to the AGA group, cord blood FABP4 levels were increased in the IUGR and LGA groups. Additionally, they were higher in early-term than full-term neonates. A significant U-shaped correlation was recorded between serum FABP4 levels and birthweight. A significant negative correlation between cord blood FABP4 and gestational age in the whole study population was noted. CONCLUSION: Cord blood FABP4 levels were significantly higher at the extremes of foetal growth at term and negatively correlated with gestational age, being increased in early-term versus full-term neonates. Further longitudinal studies with larger sample sizes are required to elucidate FABP4 implication in foetal growth and its association with future adverse cardiometabolic outcomes in the offspring.