An IL-10/DEL-1 axis supports granulopoiesis and survival from sepsis in early life.

The limited reserves of neutrophils are implicated in the susceptibility to infection in neonates, however the regulation of neutrophil kinetics in infections in early life remains poorly understood. Here we show that the developmental endothelial locus (DEL-1) is elevated in neonates and is critical for survival from neonatal polymicrobial sepsis, by supporting emergency granulopoiesis. Septic DEL-1 deficient neonate mice display low numbers of myeloid-biased multipotent and granulocyte-macrophage progenitors in the bone marrow, resulting in neutropenia, exaggerated bacteremia, and increased mortality; defects that are rescued by DEL-1 administration. A high IL-10/IL-17A ratio, observed in newborn sepsis, sustains tissue DEL-1 expression, as IL-10 upregulates while IL-17 downregulates DEL-1. Consistently, serum DEL-1 and blood neutrophils are elevated in septic adult and neonate patients with high serum IL-10/IL-17A ratio, and mortality is lower in septic patients with high serum DEL-1. Therefore, IL-10/DEL-1 axis supports emergency granulopoiesis, prevents neutropenia and promotes sepsis survival in early life.

Evaluation of various blood biomarkers associated with the outcomes of patients with COVID­19 treated in intensive care units.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (COVID-19) represented a global public health crisis and the most significant pandemic in modern times. Transmission characteristics, and the lack of effective antiviral treatment protocol and protective vaccines, pushed healthcare systems, particularly intensive care units (ICUs), to their limits and led to extreme quarantine measures to control the pandemic. It was evident from an early stage that patient stratification approaches needed to be developed to better predict disease progression. In the present study, the predictive value of clinical and blood biomarkers for the outcomes of patients with COVID-19 hospitalized in the ICU were investigated, taking age and sex into consideration. The present study analyzed blood samples from 3,050 patients with COVID-19 hospitalized in the ICU. The analysis revealed that the levels of procalcitonin, N-terminal pro-B-type natriuretic peptide, D-dimer, ferritin, liver enzymes, C-reactive protein and lactate dehydrogenase were increased and were associated with disease progression, resulting in a prolonged hospitalization period and severe COVID-19 related complications. Additionally, significant age and sex disparities among these biomarkers were documented and discussed in specific cases. On the whole, the results of the present study suggest a potential association of the demographic characteristics and blood biomarkers with prolonged hospitalization in the ICU and the mortality of patients with COVID-19.

Knowledge and attitudes of medical students about clinical aspects of congenital cytomegalovirus infection in newborns: A nationwide cross-sectional study in Greece.

Introduction: Cytomegalovirus (CMV) is the most frequent cause of congenital infection worldwide causing severe morbidity in newborns, infants, and children. Despite the clinical importance of congenital CMV (cCMV) infection, studies conducted so far indicate that there is limited awareness in the medical community in the field. The aim of this study was to assess Greek medical students' knowledge on cCMV infection. Methods: We performed a questionnaire-based nationwide cross-sectional study. A convenience sample of medical students from seven medical schools was enrolled. Results: Of the 562 respondents, 54,8% considered themselves undereducated on cCMV infection. However, almost half of the participants could correctly recognize some basic principles of cCMV infection including ways of transmission, diagnosis and treatment, while there were aspects of cCMV infection with knowledge deficit. The year of study had a positive impact on the level of knowledge with students of higher years of study being of more sufficient education on the specific topic. Conclusion: Overall, our study indicates a discrepancy between self-reported awareness and the level of knowledge among medical students in Greece. Further educational opportunities about cCMV should be offered, particularly in areas of the curriculum involving the care of women and children. Establishing medical students' solid background on the disease burden and educating them about preventative strategies for at-risk populations, should be the main pillars of such efforts in order to promote confidence in managing these cases in their future professional careers.

Telomere length as a predictive biomarker in osteoporosis (Review).

Telomeres are the ends of chromosomes that protect them from DNA damage. There is evidence to suggest that telomere shortening appears with advanced age. Since aging is a significant risk factor for developing age-related complications, it is plausible that telomere shortening may be involved in the development of osteoporosis. The present review summarizes the potential of telomere shortening as a biomarker for detecting the onset of osteoporosis. For the purposes of the present review, the following scientific databases were searched for relevant articles: PubMed/NCBI, Cochrane Library of Systematic Reviews, Scopus, Embase and Google Scholar. The present review includes randomized and non-randomized controlled studies and case series involving humans, irrespective of the time of their publication. In six out of the 11 included studies providing data on humans, there was at least a weak association between telomere length and osteoporosis, with the remaining studies exhibiting no such association. As a result, telomere shortening may be used as a biomarker or as part of a panel of biomarkers for tracking the onset and progression of osteoporosis.

Effects of Dichlorodiphenyltrichloroethane on the Female Reproductive Tract Leading to Infertility and Cancer: Systematic Search and Review.

Persistent Organic Pollutants (POPs) such as dichlorodimethyltrichloroethane (DDT) are present and ubiquitous in the environment due to their resilient nature. DDT is a prevalent endocrine disruptor still found in detectable amounts in organisms and the environment even after its use was banned in the 1970s. Medline and Google Scholar were systematically searched to detect all relevant animal and human studies published in the last 20 years (January 2003 to February 2023) in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. In total, 38 studies were included for qualitative synthesis. This systematic search and review indicated that exposure to DDT is associated with female reproductive health issues, such as reduced fecundability; increased risk of preterm/premature deliveries; increased periods of gestation; alterations in the synthesis of crucial reproductive hormones (Progesterone and Oxytocin) through ion imbalances and changes in prostaglandin synthesis, myometrial and stromal hypertrophy, and edema; and variations in uterine contractions through increased uterine wet weight. There was also limited evidence indicating DDT as a carcinogen sufficient to instigate reproductive cancers. However, this review only takes into account the in vitro studies that have established a possible pathway to understand how DDT impacts female infertility and leads to reproductive cancers. Links between the pathways described in various studies have been developed in this review to produce a summarized picture of how one event might lead to another. Additionally, epidemiological studies that specifically targeted the exposure to DDT of females belonging to various ethnicities have been reviewed to develop an overall picture of prevailing female reproductive health concerns in different nations.

The Impact of Estimated Energy and Protein Balances on Extrauterine Growth in Preterm Infants.

BACKGROUND: Nutritional support of preterm infants remains a field of debate in the literature and clinical practice varies significantly. Adequate nutrition should promote growth and aim for optimal later neurodevelopment. However, it is often impaired by prematurity-associated morbidity and the physiologic immaturity of preterm infants. This study assessed the impact of energy and macronutrient provision on growth velocity and outcome and explored differences attributed to the heterogeneity of the preterm population. METHODS: We retrospectively collected clinical and nutritional data from neonates hospitalized in two separate Neonatal Intensive Care Units (NICUs). Estimated energy and protein balance were calculated based on the ESPGHAN guidelines and their association with the growth outcome was explored. Growth assessment was based on somatometry Delta (Δ) z-scores at discharge. RESULTS: In total, 174 neonates were included in the study. By day 14, most preterm infants were exclusively enterally fed, whereas there were infants in the <28 and 28-31+6 subgroups fed exclusively parenterally. Energy balance was positive for all gestational age (GA) subgroups except for those born <28 weeks. Protein balance was consistently positive for extremely premature but negative for late preterms. Cumulative substrates provisions were strong predictors of a positive energy or protein balance in the <34 weeks GA preterms on days 14 (ROC analyses, p < 0.001) and 7 (p < 0.05). A higher GA (p = 0.013) and enteral nutrition (p = 0.005) were additional predictors of a positive energy balance. All GA subgroups had a negative Δ z-score of weight at discharge. In the <34 GA subcohorts, a positive protein balance on day 14 (p = 0.009) and a short time to regain birth weight (exp(B) 3.1 (p = 0.004)) were independently associated with a positive Δ z-score of weight at discharge. CONCLUSIONS: Early achievement of a positive energy and protein balance, based on the ESPGHAN guidelines, is crucial to ensure optimal postnatal growth and prevent extrauterine growth restriction, a relatively common occurrence in preterm infants.

The Prevalence of Small for Gestational Age and Extrauterine Growth Restriction among Extremely and Very Preterm Neonates, Using Different Growth Curves, and Its Association with Clinical and Nutritional Factors.

Monitoring the growth of neonates in the Neonatal Intensive Care Unit (NICU) using growth charts constitutes an essential part of preterm infant care. Preterm infants are at increased risk for extrauterine growth restriction (EUGR) due to increased energy needs and clinical complications. This retrospective study compares the prevalence of small for gestational age (SGA) at birth and EUGR at discharge in extremely and very preterm neonates hospitalized in the NICU of a tertiary hospital in Greece, using different growth curves, and it examines the associated nutritional and clinical factors. Fenton2013 and INTERGROWTH-21st growth curves were used to calculate z-scores of birth weight (BW) and weight, length, and head circumference at discharge. The study includes 462 newborns with a mean BW of 1341.5 g and mean GA of 29.6 weeks. At birth, 6.3% of neonates were classified as SGA based on Fenton2013 curves compared to 9.3% with INTERGROWTH-21st growth curves. At discharge, 45.9% of neonates were characterized as having EUGR based on the Fenton2013 weight curves and 29.2% were characterized based οn INTERGROWTH-21st curves. Nutritional factors such as the day of initiation, attainment of full enteral feeding, and the duration of parenteral nutrition were associated with EUGR by both curves. The prevalence of SGA and EUGR neonates differs between the two growth references. This shows that further evaluation of these charts is needed to determine the most appropriate way to monitor infant growth.

The effect of added filtration on radiation dose and image quality in digital radiography of newborns.

BACKGROUND: Repeated chest and/or abdomen radiographs are needed on mobile digital radiography (DR) units to assess infants' health status. Optimization of DR tube peak kilovoltage (kVp) and tube current time product (mAs) to derive images of diagnostic quality at as low as reasonably achievable radiation dose has been a challenging task. OBJECTIVE: To investigate the effect of exposure parameters and additional filtration on entrance skin dose and image quality in newborn DR imaging. MATERIALS AND METHODS: A physical anthropomorphic phantom that simulates the average full-term neonate was used. Chest and chest/abdomen DR images were acquired at the manufacturer's recommended kVp/mAs exposure parameters followed by a series of image acquisitions at different kVp/mAs and beam filtration combinations. Entrance skin dose (ESD) and signal difference to noise ratio (SdNR) for soft tissue, bone and feeding gastric tube were estimated in raw unprocessed images. A figure of merit (FOM) analysis provided the kVp/mAs and filtration that generated images of adequate quality at the lowest ESD. RESULTS: Signal difference increased with kVp and progressively decreased with increasing filtration. Compared to the manufacturer's recommended 53 kVp/1.6 mAs exposure parameters, ESD was reduced by 76% (47.61 µGy versus 11.3 µGy) in the chest and 66% (47.61 µGy versus 16.14 µGy) in the chest/abdomen when the exposure parameters and additional beam filtration provided by the FOM analysis were used. CONCLUSION: The results derived from this phantom study suggest that additional beam filtration along with the appropriate leverage of exposure parameters can lower ESD while maintaining image quality in full-term newborns.

Role of telomere length in human carcinogenesis (Review).

Cancer is considered the most important clinical, social and economic issue regarding cause­specific disability­adjusted life years among all human pathologies. Exogenous, endogenous and individual factors, including genetic predisposition, participate in cancer triggering. Telomeres are specific DNA structures positioned at the end of chromosomes and consist of repetitive nucleotide sequences, which, together with shelterin proteins, facilitate the maintenance of chromosome stability, while protecting them from genomic erosion. Even though the connection between telomere status and carcinogenesis has been identified, the absence of a universal or even a cancer­specific trend renders consent even more complex. It is indicative that both short and long telomere lengths have been associated with a high risk of cancer incidence. When evaluating risk associations between cancer and telomere length, a disparity appears to emerge. Even though shorter telomeres have been adopted as a marker of poorer health status and an older biological age, longer telomeres due to increased cell growth potential are associated with the acquirement of cancer­initiating somatic mutations. Therefore, the present review aimed to comprehensively present the multifaceted pattern of telomere length and cancer incidence association.

Endocrine-Disrupting Chemicals and Persistent Organic Pollutants in Infant Formulas and Baby Food: Legislation and Risk Assessments.

Human milk is the healthiest option for newborns, although, under specific circumstances, infant formula is a precious alternative for feeding the baby. Except for the nutritional content, infant formulas and baby food must be pollutant-free. Thus, their composition is controlled by continuous monitoring and regulated by establishing upper limits and guideline values for safe exposure. Legislation differs worldwide, although there are standard policies and strategies for protecting vulnerable infants. This work presents current regulations and directives for restricting endocrine-disrupting chemicals and persistent organic pollutants in infant formulas. Risk assessment studies, which are limited, are necessary to depict exposure variations and assess the health risks for infants from dietary exposure to pollutants.

Comparing Full and Pre-Term Neonates' Heart Rate Variability in Rest Condition and during Spontaneous Interactions with Their Parents at Home.

BACKGROUND: Preterm neonates show decreased HRV compared to those at full-term. We compared HRV metrics between preterm and full-term neonates in transfer periods from neonate rest state to neonate-parent interaction, and vice versa. METHODS: Short-term recordings of the HRV parameters (time and frequency-domain indices and non-linear measurements) of 28 premature healthy neonates were compared with the metrics of 18 full-term neonates. HRV recordings were performed at home at term-equivalent age and HRV metrics were compared between the following transfer periods: from first rest state of the neonate (TI1) to a period in which the neonate interacted with the first parent (TI2), from TI2 to a second neonate rest state (TI3), and from TI3 to a period of neonate interaction with the second parent (TI4). RESULTS: For the whole HRV recording period, PNN50, NN50 and HF (%) was lower for preterm neonates compared to full-terms. These findings support the reduced parasympathetic activity of preterm compared to full-term neonates. The results of comparisons between transfer period simply a common coactivation of SNS and PNS systems for both full and pre-term neonates. CONCLUSIONS: Spontaneous interaction with the parent may reinforce both full and pre-term neonates' ANS maturation.

Giving Birth in Unpredictable Conditions: Association between Parents' COVID-19 Related Concerns, Family Functioning, Dyadic Coping, Perceived Social Support and Depressive Symptoms.

BACKGROUND: The way postpartum parents' COVID-19-related concerns are associated with the family environment, support resources and depressive symptoms areunder-investigated. METHODS: Two hundred and forty-three new parents (132 mothers, 111 fathers) completed self-report questionnaires within an 8-week period after birth. Parental concerns for COVID-19-related life changes were assessed with the COVID-19 Questionnaire, perceived social support with the Multidimensional Scale of Perceived Social Support, perceived family functioning with the Family Adaptability and Cohesion Evaluation Scales IV Package, dyadic coping behaviors with the Dyadic Coping Inventory and maternal/paternal postnatal depression with the Edinburgh Postnatal Depression Scale. RESULTS: (a) Higher levels of COVID-19-related concerns about daily life were associated with lower levels of family communication, satisfaction and increased depressive symptomatology in both parents, and with lower levels of family functioning in mothers; (b) Maternal health care COVID-19-related concerns were linked with lower levels of family communication, lower perceived social support and with an increase in maternal depressive symptoms; and (c) COVID-19-related concerns about neonate hospitalization were associated with increased maternal depressive symptoms. CONCLUSION: Τhese findings suggest that COVID-19-related concerns had a common negative effect on both postpartum mothers' and fathers' mental health and on certain aspects of family functioning.

Mild coronary artery dilatation developed in some children with mild COVID-19 but completely regressed within 3 months.

AIM: We studied the incidence and time course of any coronary artery changes in children up to 2 years of age who were hospitalised with mild COVID-19. METHODS: This was a single-centre prospective study of 29 children (19 males) with a median age of 3 months and interquartile range (IQR) of 1.6-4.3 months. They were admitted to a Greek University hospital for mild COVID-19 from 1 March to 30 December 2021. Three echocardiographic evaluations were performed at a median (IQR) of 19 (16-24) days, 82 (75-89) days and 172 (163-197) after the first symptoms. The prevalence of coronary artery dilation, regression, and changes was documented. RESULTS: Coronary artery dilation was present in 3 (10.3%) cases at the first evaluation, with complete regression at the second. Regression was observed in 18/24 (75%) cases with follow-up data and 9 (31%) demonstrated significant z-score changes of >2. Coronary artery changes in any segment at any time were documented in 18/29 (62%) of the patients. CONCLUSION: Cases of transient and very mild coronary artery dilatation following mild COVID-19 completely regressed within 3 months. Large-scale studies are needed to document the extent and time course of coronary artery dilation following paediatric COVID-19.

COVID-19 Pandemic-Related Restrictions: Factors That May Affect Perinatal Maternal Mental Health and Implications for Infant Development.

This review aims to discuss the factors that may affect maternal mental health and infant development in COVID-19 pandemic condition. Toward this direction, the two objectives of this review are the following: (a) to discuss possible factors that may have affected negatively perinatal mental health through the pandemic-related restrictions; and (b) to present the implications of adversely affected maternal emotional wellbeing on infant development. We conclude that the pandemic may has affected maternal mental health with possible detrimental effects for the infants of the COVID-19 generation. We highlight the need for evidence-based interventions to be integrated within the health system for prenatal and postpartum care in an effort to promote maternal mental health and infant development.

Immune response (IgG) following full inoculation with BNT162b2 COVID­19 mRNA among healthcare professionals.

Soon after the beginning of the severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2) pandemic in December, 2019, numerous research teams, assisted by vast capital investments, achieved vaccine development in a fraction of time. However, almost 8 months following the initiation of the European vaccination programme, the need for prospective monitoring of the vaccine­induced immune response, its determinants and related side­effects remains a priority. The present study aimed to quantify the immune response following full vaccination with the BNT162b2 coronavirus disease 2019 (COVID­19) mRNA vaccine by measuring the levels of immunoglobulin G (IgG) titers in healthcare professionals. Moreover, common side­effects and factors associated with IgG titers were identified. For this purpose, blood samples from 517 individuals were obtained and analysed. Blood sampling was performed at a mean period of 69.0±23.5 days following the second dose of the vaccine. SARS­CoV­2 IgG titers had an overall mean value of 4.23±2.76. Females had higher titers than males (4.44±2.70 and 3.89 ±2.84, respectively; P=0.007), while non­smokers had higher titers than smokers (4.48±2.79 and 3.80±2.64, respectively; P=0.003). An older age was also associated with lower antibody titers (P<0.001). Moreover, the six most prevalent adverse effects were pain at the injection site (72.1%), generalized fatigue (40.5%), malaise (36.3%), myalgia (31,0%), headache (25.8%) and dizziness/weakness (21.6%). The present study demonstrated that the immune response after receiving the BNT162b2 COVID­19 mRNA vaccine is dependent on various modifiable and non­modifiable factors. Overall, the findings of the present study highlight two key aspects of the vaccination programs: First, the need for prospective immunosurveillance studies in order to estimate the duration of immunity, and second, the need to identify those individuals who are at a greater risk of developing low IgG titers in order to evaluate the need for a third dose of the vaccine.

Mexiletine Treatment for Neonatal LQT3 Syndrome: Case Report and Literature Review.

Background: Early diagnosis of long QT type 3 (LQT3) syndrome during the neonatal period is of paramount clinical importance. LQT3 syndrome results in increased mortality and a mutation-specific response to treatment compared to other more common types of LQT syndrome. Mexiletine, a sodium channel blocker, demonstrates a mutation-specific QTc shortening effect in LQT3 syndrome patients. Case Presentation: A neonate manifested marked QTc prolongation after birth. An electrocardiogram (ECG) recording was performed due to positive family history of genetically confirmed LQT3 syndrome (SCN5A gene missense mutation Tyr1795Cys), and an association with sudden cardiac death was found in family members. The mexiletine QTc normalizing effect (QTc shortening from 537 to 443 ms), practical issues related to oral mexiletine treatment of our young patient, along with a literature review regarding identification and mexiletine treatment in infants with LQT3 syndrome are presented. Conclusions: Mexiletine could be considered in the treatment of high-risk LQT3 patients already in the neonatal period in addition to b-blocker therapy. Availability of standardized commercial mexiletine pediatric formulas, serum mexiletine level analyses, and future prospective studies are needed to evaluate the potential beneficial effect of early mexiletine treatment on the incidence of future acute cardiac events in these high-risk LQT syndrome patients.

Cyclopia: The Face Predicts the Future.

The most extreme form of holoprosencephaly (HPE) is cyclopia and appears with a single characteristic midline diamond-shaped orbital structure and various facial, brain, and extrafacial features. We aimed to report a case of a cyclopic fetus diagnosed at the 22 weeks of the gestational age and further we reviewed the recent literature in order to highlight the etiopathogenesis and set goals for approaching such future pregnancies. Following the first-trimester assessment, in a 27-year-old pregnant woman, who underwent in vitro fertilization, the pregnancy was associated with a low risk for aneuploidies and a high risk for pre-eclampsia. On the anomaly scan, due to severe fetal brain maldevelopment and microcephale, HPE was suspected. Furthermore, three-dimensional ultrasound confirmed a common orbit in the midline of the face. Although the parents did not opt for amniocentesis and further postnatal management, parental karyotyping test did not detect any pathology. The pregnancy was terminated and the macroscopic examination of the aborted specimen revealed cyclopia, synophalmia, fussed eyelids with a proboscis on the upper midline of the face, and a malpositioned left ear. To conclude, cyclopia is not widely manifested, and different cyclo-pian disorders could still occur. Although this rare congenital abnormality is incompatible with life, the awareness of the spectrum of sonographic features and the appropriate genetic counseling can determine the outcome of current and forthcoming pregnancies.

Extremely Preterm Infant Admissions Within the SafeBoosC-III Consortium During the COVID-19 Lockdown.

Objective: To evaluate if the number of admitted extremely preterm (EP) infants (born before 28 weeks of gestational age) differed in the neonatal intensive care units (NICUs) of the SafeBoosC-III consortium during the global lockdown when compared to the corresponding time period in 2019. Design: This is a retrospective, observational study. Forty-six out of 79 NICUs (58%) from 17 countries participated. Principal investigators were asked to report the following information: (1) Total number of EP infant admissions to their NICU in the 3 months where the lockdown restrictions were most rigorous during the first phase of the COVID-19 pandemic, (2) Similar EP infant admissions in the corresponding 3 months of 2019, (3) the level of local restrictions during the lockdown period, and (4) the local impact of the COVID-19 lockdown on the everyday life of a pregnant woman. Results: The number of EP infant admissions during the first wave of the COVID-19 pandemic was 428 compared to 457 in the corresponding 3 months in 2019 (-6.6%, 95% CI -18.2 to +7.1%, p = 0.33). There were no statistically significant differences within individual geographic regions and no significant association between the level of lockdown restrictions and difference in the number of EP infant admissions. A post-hoc analysis based on data from the 46 NICUs found a decrease of 10.3%in the total number of NICU admissions (n = 7,499 in 2020 vs. n = 8,362 in 2019). Conclusion: This ad hoc study did not confirm previous reports of a major reduction in the number of extremely pretermbirths during the first phase of the COVID-19 pandemic. Clinical Trial Registration: ClinicalTrial.gov, identifier: NCT04527601 (registered August 26, 2020), https://clinicaltrials.gov/ct2/show/NCT04527601.

Autonomic Nervous System Maturation and Emotional Coordination in Interactions of Preterm and Full-Term Infants With Their Parents: Protocol for a Multimethod Study.

BACKGROUND: There is limited knowledge on the physiological and behavioral pathways that may affect the developmental outcomes of preterm infants and particularly on the link between autonomic nervous system maturation and early social human behavior. Thus, this study attempts to investigate the way heart rate variability (HRV) parameters are related to emotional coordination in interactions of preterm and full-term infants with their parents in the first year of life and the possible correlation with the developmental outcomes of infants at 18 months. OBJECTIVE: The first objective is to investigate the relationship between emotional coordination and HRV in dyadic full-term infant-parent (group 1) and preterm infant-parent (group 2) interactions during the first postpartum year. The second objective is to examine the relationship of emotional coordination and HRV in groups 1 and 2 in the first postpartum year with the developmental outcomes of infants at 18 months. The third objective is to investigate the effect of maternal and paternal postnatal depression on the relation between emotional coordination and HRV in the two groups and on developmental outcomes at 18 months. The fourth objective is to examine the effect of family cohesion and coping on the relation between emotional coordination and HRV in the two groups and on developmental outcomes at 18 months. METHODS: This is an observational, naturalistic, and longitudinal study applying a mixed method design that includes the following: (1) video recordings of mother-infant and father-infant interactions at the hospital, in the neonatal period, and at home at 2, 4, 6, 9, and 12 months of the infants' life; (2) self-report questionnaires of parents on depressive symptoms, family cohesion, and dyadic coping of stress; (3) infants' HRV parameters in the neonatal period and at each of the above age points during and after infant-parent video recordings; and (4) assessment of toddlers' social and cognitive development at 18 months through an observational instrument. RESULTS: The study protocol has been approved by the Research Ethics Committee of the University of Crete (number/date: 170/September 18, 2020). This work is supported by the Special Account for Research Funds of the University of Crete (grant number: 10792-668/08.02.2021). All mothers (with their partners) of full-term and preterm infants who give birth between March 2021 and January 2022 at the General University Hospital of Crete (northern Crete, Greece) will be invited to participate. The researcher will invite the parents of infants to participate in the study 1 to 2 days after birth. Data collection is expected to be completed by March 2023, and the first results will be published by the end of 2023. CONCLUSIONS: Investigating the regulatory role of HRV and social reciprocity in preterm infants may have implications for both medicine and psychology. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/28089.