The conundrum of intestinal injury in preterm infants receiving mother's own milk.

"Necrotizing enterocolitis" ("NEC") is a heterogeneous group of intestinal injuries experienced primarily in preterm infants. Risk factors include among others preterm gut microbiome alterations. Maternal milk (MM), or otherwise parent milk, is protective for the developing intestine due to its constituents, which include bioactive antimicrobials, immunomodulatory molecules, human milk oligosaccharides (HMOs), secretory immunoglobulin A (sIgA), and microorganisms. However, some preterm infants receiving exclusively mother's own milk (MOM) develop intestinal injuries. Studies showed predisposition to increased risk for "NEC", when a decreased MM HMO, disialyllacto-N-tetraose, is combined with an altered infant's gut microbiome. The intestine may also become more prone to injury with a greater amount of bacteria not bound to IgA. Variations in MM composition may alter the offspring gut microbiome, depriving protection. The different "NEC" entities should be considered to play a role as to why, in many studies, MOM does not provide absolute protection against preterm intestinal injury.

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.

An Update on Lung Function of Extremely and Very Preterm Infants in Later Life: The Role of Early Nutritional Interventions.

Birth occurring at ≤32 weeks' gestation ("very preterm") or at ≤28 weeks' gestation ("extremely preterm") potentially poses considerable health problems for the neonate, including respiratory sequelae, not only during the immediate newborn period, but throughout childhood and into adulthood. With the progressive improvements in neonatal care, the survival of extremely preterm and very preterm neonates has improved substantially. However, a considerable percentage of these infants suffer dysfunctions that may trigger, at some stage later in life, the onset of respiratory morbidities. The interruption of the normal development of the respiratory tract caused by preterm birth, in combination with postnatal lung injury caused by various interventions, e.g., mechanical ventilation and oxygen therapy, increases the risk ofthe development of long-term respiratory deficits in survivors. Those infants that are most affected are those who develop chronic lung disease of prematurity (also called bronchopulmonary dysplasia, BPD), but impaired lung function can develop irrespective of BPD diagnosis. Apart from indicating abnormal lung function in survivors of extreme prematurity, recent long-term follow-up studies also emphasize the crucial role of early nutritional intake as an effective strategy, which promotes lung growth and repair. This article will update the associations between extremely/very preterm birth with long-term respiratory outcomes. It will also discuss the protective effect of nutritional interventions, focusing on recently published follow-up data.

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.

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.

European guidelines on perinatal care: corticosteroids for women at risk of preterm birth.

of recommendationsCorticosteroids should be administered to women at a gestational age between 24+0 and 33+6 weeks, when preterm birth is anticipated in the next seven days, as these have been consistently shown to reduce neonatal mortality and morbidity. (Strong-quality evidence; strong recommendation). In selected cases, extension of this period up to 34+6 weeks may be considered (Expert opinion). Optimal benefits are found in infants delivered within 7 days of corticosteroid administration. Even a single-dose administration should be given to women with imminent preterm birth, as this is likely to improve neurodevelopmental outcome (Moderate-quality evidence; conditional recommendation).Either betamethasone (12 mg administered intramuscularly twice, 24-hours apart) or dexamethasone (6 mg administered intramuscularly in four doses, 12-hours apart, or 12 mg administered intramuscularly twice, 24-hours apart), may be used (Moderate-quality evidence; Strong recommendation). Administration of two "all" doses is named a "course of corticosteroids".Administration between 22+0 and 23+6 weeks should be considered when preterm birth is anticipated in the next seven days and active newborn life-support is indicated, taking into account parental wishes. Clear survival benefit has been observed in these cases, but the impact on short-term neurological and respiratory function, as well as long-term neurodevelopmental outcome is still unclear (Low/moderate-quality evidence; Weak recommendation).Administration between 34 + 0 and 34 + 6 weeks should only be offered to a few selected cases (Expert opinion). Administration between 35+0 and 36+6 weeks should be restricted to prospective randomized trials. Current evidence suggests that although corticosteroids reduce the incidence of transient tachypnea of the newborn, they do not affect the incidence of respiratory distress syndrome, and they increase neonatal hypoglycemia. Long-term safety data are lacking (Moderate quality evidence; Conditional recommendation).Administration in pregnancies beyond 37+0 weeks is not indicated, even for scheduled cesarean delivery, as current evidence does not suggest benefit and the long-term effects remain unknown (Low-quality evidence; Conditional recommendation).Administration should be given in twin pregnancies, with the same indication and doses as for singletons. However, existing evidence suggests that it should be reserved for pregnancies at high-risk of delivering within a 7-day interval (Low-quality evidence; Conditional recommendation). Maternal diabetes mellitus is not a contraindication to the use of antenatal corticosteroids (Moderate quality evidence; Strong recommendation).A single repeat course of corticosteroids can be considered in pregnancies at less than 34+0 weeks gestation, if the previous course was completed more than seven days earlier, and there is a renewed risk of imminent delivery (Low-quality evidence; Conditional recommendation).

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.

The COVID-19 pandemic and the "Plague of Athens": comparable features 25 centuries apart.

Motivated by the up to now disastrous outcomes of the COVID-19 pandemic, we attempted a flashback to the so-called "Plague of Athens," which indicated a serious contagious disease, having taken place between 430 and 426 BC. The ancient pandemic was meticulously described by the Athenian historian and general Thucydides. We compared, as much as possible, the following parameters: background conditions, spreading of the pandemics, preceded and concurrent adverse events, duration and waves of the pandemics, symptoms, implicated infectious agents/diseases and mental/psychosocial consequences. The current pandemic was preceded by a global economic crisis, which particularly affected deprived population groups, while the ancient one started on the second year of a catastrophic civil war. Rivalry and different political systems between now (US/China) and then (Athens/Sparta) superpowers were the basis for conspiracy scenarios, concerning origins of the pandemics, which resulted to huge numbers of deaths, particularly in overcrowded and poor areas/cities. Both pandemics not sparing any age, sex, nationality, social group, may have had a zoonotic component, besides being air-born. However, their spreading is/was remarkably rapid, presenting 3-4 waves and lasting for several years. Some somatic signs and symptoms of the diseases coincide. Although for COVID-19, SARS-CoV-2 has been identified as causing agent, the antique pandemic has most probably been attributed to typhoid fever, although this is still a matter of debate. Additionally, both pandemics affected mental health and psychosocial behavior in close similarity. It is noteworthy, that in both eras physicians and healthcare workers, despite physical and psychological exhaustion, in the majority, presented admirable resilience and willingness to help suffering fellow people, often at the expense of their own lives. The considerable number of comparable features between COVID-19 and the "Plague of Athens" confirms that pandemics may present over time important similarities in their origin, evolution and outcomes.

Intracytoplasmic sperm injection and fetal origins of autism spectrum disorder: an intriguing, though controversial association.

Latest knowledge assigns the origins of autism spectrum disorder (ASD)-currently affecting 1% of children- to intrauterine life, when fetal brain develops. Besides genetics, environmental factors, responsible for epigenetic changes contributed to its rising incidence. In vitro fertilization (IVF) and the most widely used intracytoplasmic sperm injection (ICSI) are implicated in epigenetic changes. A series of studies examined the impact of ICSI on ASD in the offspring. Results are usually conflicting, due to inherent problems of study design and power, mixed IVF/ICSI cases and not exclusively ASD diagnoses included. Furthermore, preterm birth, low birthweight infants, advanced parental age, hormonal disturbances, all associated with ICSI, are known factors affecting ASD. While solid data supporting ICSI contribution to currently alarming ASD increase are lacking, exploration of underlying molecular mechanisms would strengthen possible associations. In the meanwhile, ICSI use should be restricted to male-factor infertility cases.

Chorioamnionitis in utero, schizophrenia in adulthood: limited current evidence-future research focus?

Background: Developmental adaptive processes during gestation that are known to be involved in permanent changes in physiology and metabolism or "early life programming" can adversely affect fetal brain development, impacting both brain structure and function.Data: Emerging evidence strongly supports the developmental origin of schizophrenia, which may potentially be a result of prenatal exposure to a diversity of factors, especially infections, in genetically predisposed subjects. Structural and functional brain changes during development of schizophrenia are determined by genetic components, altered expression of schizophrenia risk genes and epigenetic dysregulation. However, the precise mechanisms underlying these relationships remain unclear. Findings from human and animal studies suggest that inflammatory-immune responses and activation of oxidative stress pathways are crucial in mediating intrauterine infection-induced neurodevelopmental and neuropsychiatric diseases.Aim: Considering the high prevalence of intrauterine inflammation in the context of chorioamnionitis during human pregnancy and the paucity of knowledge on fetal programming of schizophrenia, this mini review aims to exclusively consolidate the current evidence supporting a potential association between chorioamnionitis and schizophrenia.