Antiphospholipid syndrome (APS) is an autoimmune disorder associated with thrombotic events and adverse obstetric outcomes, particularly in its obstetric form (OAPS). Affecting approximately 0.5% of the population, APS is a leading contributor to recurrent pregnancy loss (RPL), preeclampsia (PE), and fetal growth restriction ((FGR). Despite advancements in understanding its pathophysiology and management, optimal treatment strategies for APS in pregnancy remain challenging and require systematic evaluation. This review synthesizes current evidence on APS mechanisms, diagnostic criteria, and therapeutic interventions, with a focus on maternal and fetal outcomes in OAPS. A comprehensive search of PubMed, was conducted to identify studies exploring APS pathogenesis, diagnostic standards, and treatment efficacy in obstetric settings. Inclusion criteria prioritized randomized controlled trials, cohort studies, and systematic reviews with a clear focus on APS and pregnancy. The review confirmed that APS current accepted pathogenesis is governed by a “two-hit” model, where antiphospholipid antibodies (aPLs) initiate endothelial damage, culminating in thrombosis and placental insufficiency. Epidemiological analysis underscores the prevalence and severity of APS in obstetric contexts, with lupus anticoagulant (LA) emerging as a significant predictor of adverse outcomes. Evidence supports the use of low-dose aspirin (LDA) and heparin to reduce miscarriage rates, while adjunctive treatments, such as hydroxychloroquine (HCQ), have shown promise in improving live birth rates and reducing preterm delivery in high-risk cases. Emerging therapies, including tumoral necrosis factor (TNF-alpha) inhibitors and nitric oxide modulators, may offer additional benefits in refractory cases. APS remains a critical determinant of adverse pregnancy outcomes, necessitating precise diagnostic criteria and tailored management approaches. This systematic review emphasizes the importance of individualized therapeutic regimens to optimize maternal and fetal health in OAPS and highlights areas for future research, particularly regarding novel pharmacological approaches. Further studies are essential to refine treatment protocols and improve clinical guidelines for managing APS in pregnancy.

This meta-analysis assessed short-term outcomes after using human milk-derived fortifiers (HMFs) compared with bovine milk fortifiers (BMFs) in preterm infants fed an exclusive human milk (HM) diet, either mother’s own milk (MOM) or donor human milk (DHM). We searched PubMed, Embase, Google Scholar, CENTRAL and CINHAL between January 2015 and August 2023 for studies reporting outcomes in infants with ≤28 weeks gestation and/or birthweight ≤ 1500 g on an exclusive human milk diet fortified with HMF versus BMF. The primary outcomes were death and NEC (stage ≥ 2). Four studies with a total of 681 infants were included. Mortality was significantly lower in infants fed with an HM-HMFs diet (four studies, 681 infants; RR = 0.50, 95% CI = 0.26–0.94; p = 0.03; I² = 0%), NEC was similar between the two groups (four studies, 681 infants; RR = 0.48, 95% CI = 0.20–1.17; p = 0.11; I²= 39%). BPD was higher in the HM-BMFs group (four studies, 663 infants; RR = 0.83, 95% CI = 0.69–1.000; p = 0.05, I² = 0%), although not statistically significant. No differences were found for sepsis (RR = 0.97, 95% CI = 0.66–1.42; p = 0.96; I² = 26%) or combined ROP (four studies, 671 infants; RR = 0.64, 95% CI = 0.53–1.07; p = 0.28; I² = 69%). An HM-HMFs diet could possibly be associated with decreased mortality with no association with NEC, BPD, sepsis, or ROP. This meta-analysis was limited by the small number of studies included. However, the results should not be refuted for this reason as they provide an impetus for subsequent clinical trials to assess the observed associations.

Background: Aetiology of preterm birth (PTB) is heterogeneous and preventive strategies remain elusive. Socio-environmental measures implemented as Ireland’s prudent response to the SARS-CoV-2 virus (COVID-19) pandemic represented, in effect, a national lockdown and have possibly influenced the health and wellbeing of pregnant women and unborn infants. Cumulative impact of such socio-environmental factors operating contemporaneously on PTB has never been assessed before. Methods: Regional PTB trends of very low birth weight (VLBW) infants in one designated health area of Ireland over two decades were analysed. Poisson regression and rate ratio analyses with 95% CI were conducted. Observed regional data from January – April 2020 were compared to historical regional and national data and forecasted national figures for 2020. Results: Poisson regression analysis found that the regional historical VLBW rate per 1000 live births for January to April, 2001-2019 was 8.18 (95% CI: 7.21, 9.29). During January to April 2020, an unusually low VLBW rate of just 2.17 per 1000 live births was observed. The rate ratio of 3.77 (95% CI: 1.21, 11.75), p = 0.022, estimates that for the last two decades there was, on average, 3.77 times the rate of VLBW, compared to the period January to April 2020 during which there is a 73% reduction. National Irish VLBW rate for 2020 is forecasted to be reduced to 400 per 60,000 births compared to the historical 500-600 range. Conclusion: An unprecedented reduction in PTB of VLBW infants was observed in one health region of Ireland during the COVID-19 lockdown. Potential determinants of this unique temporal trend reside in the summative socio-environmental impact of the COVID-19 dictated lockdown. Our findings, if mirrored in other regions that have adopted similar measures to combat the pandemic, demonstrate the potential to evaluate these implicated interdependent behavioural and socio-environmental modifiers to positively influence PTB rates globally. Key Questions: What is already known?: Premature birth is an important contributor for under-five mortality globally. Currently there is no broadly accepted and effective strategy to prevent the birth of premature very low birth weight infants. Impact of socio-environmental and maternal behavioural modifications on the incidence of preterm birth has not been assessed. What are the new findings?: COVID-19-triggered national lockdown in Ireland created an opportunity to study the cumulative influence of socio-environmental modifications on pregnant mothers. An unprecedented 73% reduction in the rate of very low birth weight deliveries was noted in one designated health region of Ireland during January to April of 2020 in comparison to the preceding 20 year timeframe. Our observations, if nationally mirrored, indicate that birth rate of very low birth weight premature infants in Ireland is forecasted to decrease considerably in 2020. What do the new findings imply?: Socially rooted modifiers such as family support, work related stress and commuting, environmental pollution, infection avoidance, sleep and nutritional support, adequate exercise, reduced exposure to tobacco and illicit drugs, avoidance of financial strain, all cumulatively could contribute to reduce preterm birth rate. Our observations, if reflected in other countries that adopted COVID-19-prompted lockdown measures, would redefine the antecedents that trigger the yet poorly understood pathways leading to preterm births. Prematurity rate would be the most important ‘ curve to bend ’ in the context of reducing infant mortality globally and thus promote the achievement of sustainable development goals for children.

Preterm birth is the leading cause of infant death worldwide, but the causes of preterm birth are largely unknown. During the early COVID-19 lockdowns, dramatic reductions in preterm birth were reported; however, these trends may be offset by increases in stillbirth rates. It is important to study these trends globally as the pandemic continues, and to understand the underlying cause(s). Lockdowns have dramatically impacted maternal workload, access to healthcare, hygiene practices, and air pollution - all of which could impact perinatal outcomes and might affect pregnant women differently in different regions of the world. In the international Perinatal Outcomes in the Pandemic (iPOP) Study, we will seize the unique opportunity offered by the COVID-19 pandemic to answer urgent questions about perinatal health. In the first two study phases, we will use population-based aggregate data and standardized outcome definitions to: 1) Determine rates of preterm birth, low birth weight, and stillbirth and describe changes during lockdowns; and assess if these changes are consistent globally, or differ by region and income setting, 2) Determine if the magnitude of changes in adverse perinatal outcomes during lockdown are modified by regional differences in COVID-19 infection rates, lockdown stringency, adherence to lockdown measures, air quality, or other social and economic markers, obtained from publicly available datasets. We will undertake an interrupted time series analysis covering births from January 2015 through July 2020. The iPOP Study will involve at least 121 researchers in 37 countries, including obstetricians, neonatologists, epidemiologists, public health researchers, environmental scientists, and policymakers. We will leverage the most disruptive and widespread “natural experiment” of our lifetime to make rapid discoveries about preterm birth. Whether the COVID-19 pandemic is worsening or unexpectedly improving perinatal outcomes, our research will provide critical new information to shape prenatal care strategies throughout (and well beyond) the pandemic.

Background and Objective: The effects of neonatal hypoglycemia on the developing brain are well known, resulting in poor neurological outcomes. We aimed to perform an updated meta-analysis on neonatal hypoglycemia, the severity of hypoglycemia, and the associated neurodevelopmental outcomes from infancy to adulthood. Methods: A systematic literature search was conducted from inception until March 2024, using the PubMed, CINAHL, Embase, and the CENTRAL databases. Randomized/quasi-randomized trials and observational studies that evaluated at least one of the pre-specified outcomes were included. A random-effects model meta-analysis was performed to yield the pooled OR and its 95% CI for each outcome due to the expected heterogeneity in the studies. The study findings were reported as per the PRISMA guidelines. Neurodevelopmental impairment (NDI), cognitive impairment, and visual-motor or visual impairment were the primary outcomes. Results: A total of 17 studies (19 publications) were included in the final analysis. NDI, as defined by authors, was significantly higher in early- (OR = 1.16; 95% CI = 1.11–1.43) and mid-childhood (OR = 3.67; 95%CI = 1.07–12.2) in infants with neonatal hypoglycemia. ‘Any cognitive impairment’ was significantly more common in infants with neonatal hypoglycemia (OR = 2.12; 95%CI = 1.79–2.52). Visual-motor impairment (OR = 3.33; 95%CI = 1.14–9.72) and executive dysfunction (OR = 1.99; 95%CI = 1.36–2.91) were also more common in the hypoglycemic group. No difference in the incidence of epilepsy, motor impairment, emotional-behavioral problems, or hearing impairment were noted. Certainty of evidence was adjudged as ‘low’ to ‘very low’ for most outcomes. The severity of hypoglycemia was studied at different intervals, with NDI more common with a blood glucose interval between 20 and 34 mg/dL (1.1–1.9 mmol/L). Conclusions: Low-quality evidence from large observational studies finds a significant association with hypoglycemia in the early neonatal period and long-term neurodevelopmental problems. Additional studies with long enough follow-up are paramount to determine the cut-off concentration and to quantify the impact beyond the infancy period.

Background: Neonatal encephalopathy is a complex syndrome in infants that predominantly affects the brain and other organs. The leading cause is a lack of oxygen in the blood reaching the brain. Neonatal encephalopathy can result in mortality or complications later in life, including seizures, movement disorders and cerebral palsy. Treatment options for neonatal encephalopathy are limited mainly to therapeutic hypothermia, although other potential treatments are emerging. However, evaluations of the effectiveness of treatments are challenging because of heterogeneity and inconsistency in outcomes measured and reported between trials. In this paper, we detail how we will develop a core outcome set to standardise outcomes measured and reported upon for interventions for the treatment of neonatal encephalopathy. Methods: We will systematically review the literature to identify outcomes reported previously in randomised trials and systematic reviews of randomised trials. We will identify outcomes important to parents or caregivers of infants diagnosed with and who have received treatment for neonatal encephalopathy. We will do this by conducting in person or by video teleconferencing interviews with parents or caregivers in high-income and low- to middle-income countries. Stakeholders with expertise in neonatal encephalopathy (parents/caregivers, healthcare providers and researchers) will rate the importance of identified outcomes in an online Delphi survey using either a three-round Delphi survey or a “Real-Time” Delphi survey to which stakeholders will be allocated at random. Consensus meetings will take place by video conference to allow for an international group of stakeholder representatives to discuss and vote on the outcomes to include in the final core outcome set (COS). Discussion: More research is needed on treatments for neonatal encephalopathy. Standardising outcomes measured and reported in evaluations of the effectiveness of interventions for the treatment of neonatal encephalopathy will improve evidence synthesis and improve results reported in systematic reviews and meta-analysis in this area. Overall, this COS will allow for improved treatments to be identified, heterogeneity in research to be reduced, and overall patient care to be enhanced. Trial registration: This study is registered in the Core Outcome Measures for Effectiveness (COMET) database http://www.comet-initiative.org/Studies/Details/1270.