Complications of Preterm Birth-The Importance of Care for the Outcome: A Narrative Review.

Preterm-born children are susceptible to problems of adaptation in the early neonatal period, as well as the emergence of consequences due to the immaturity of the respiratory, cardiovascular, and especially cerebrovascular systems. The authors searched PubMed, Scopus, the Cochrane Library, and Web of Science for articles that were available in their entirety and published in English between 1990 and 2024 in peer-reviewed journals using keywords relevant to the manuscript topic. Analyzing the requested studies and manuscripts, adequate articles describing the stated problem were used. The last trimester of pregnancy is the most important period in brain development. Brain growth is at its most intense, and nerve cells are created, multiply, and migrate, creating numerous connections between them and receptors. During this period, the baby is protected from the influence of external environmental factors. When a baby is born, it leaves its protected environment and very often requires intensive treatment to survive. In these circumstances, the immature nervous system, which is in a sensitive stage of development, is overloaded with numerous external stimuli, continuous light, noise, inappropriate positioning, and repeated painful reactions due to necessary diagnostic and therapeutic procedures and the unavoidable absence of the mother and the family, which cause stress that threatens proper programmed development. Minimally invasive therapeutic procedures and the presence of parents during hospitalization play a significant role in reducing the consequences for a premature child.

The Importance of Metabolic and Environmental Factors in the Occurrence of Oxidative Stress during Pregnancy.

Metabolic changes in pregnant women begin in the first weeks after conception under the influence of placental hormones that affect the metabolism of all nutrients. An increased concentration of total lipids accompanies pregnancy and an increased accumulation of triglycerides in low-density lipoproteins (LDL) particles. Lipids in small dense LDL particles are more susceptible to oxidative modification than normal-density LDL particles. Unlike LDL high-density lipoproteins (HDL), lipoprotein particles have an atheroprotective role in lipid metabolism. The very growth of the fetus depends on the nutrition of both parents, so obesity is not only in the mother but also in the father. Nutritional programming of the offspring occurs through changes in lipid metabolism and leads to an increased risk for cardiometabolic diseases. Pregnancy is accompanied by an increased need for oxygen in the mitochondria of the placenta and a tendency to develop oxidative stress. Oxidative stress represents a disturbance in the balance of oxidation-reduction processes in the body that occurs due to the excessive production of free oxygen radicals that cellular homeostatic mechanisms are unable to neutralize. When the balance with the antioxidant system is disturbed, which happens when free oxygen radicals are in high concentrations, serious damage to biological molecules occurs, resulting in a series of pathophysiological and pathological changes, including cell death. Therefore, oxidative stress plays a significant role in the pathogenesis of many complications that can occur during pregnancy. The oxidative status of pregnant women is also influenced by socioeconomic living conditions, lifestyle habits, diet, smoking, and exposure to environmental air pollution. During a healthy pregnancy, the altered lipid profile and oxidative stress create an increased risk for premature birth and pregnancy-related diseases, and a predisposition to adult diseases.

Programming Factors of Neonatal Intestinal Dysbiosis as a Cause of Disease.

The intestinal microbiota consists of trillions of bacteria, viruses, and fungi that achieve a perfect symbiosis with the host. They perform immunological, metabolic, and endocrine functions in the body. The microbiota is formed intrauterine. Dysbiosis is a microbiome disorder characterized by an imbalance in the composition of the microbiota, as well as changes in their functional and metabolic activities. The causes of dysbiosis include improper nutrition in pregnant women, hormone therapy, the use of drugs, especially antibiotics, and a lack of exposure to the mother's vaginal microbiota during natural birth. Changes in the intestinal microbiota are increasingly being identified in various diseases, starting in the early neonatal period into the adult period. Conclusions: In recent years, it has become more and more obvious that the components of the intestinal microbiota are crucial for the proper development of the immune system, and its disruption leads to disease.

The Significance of COVID-19 Diseases in Lipid Metabolism Pregnancy Women and Newborns.

Coronavirus disease (COVID-19) is an infectious disease caused by SARS-CoV-2. Elderly people, people with immunodeficiency, autoimmune and malignant diseases, as well as people with chronic diseases have a higher risk of developing more severe forms of the disease. Pregnant women and children can becomesick, although more often they are only the carriers of the virus. Recent studies have indicated that infants can also be infected by SARS-CoV-2 and develop a severe form of the disease with a fatal outcome. Acute Respiratory Distress Syndrome (ARDS) ina pregnant woman can affect the supply of oxygen to the fetus and initiate the mechanism of metabolic disorders of the fetus and newborn caused by asphyxia. The initial metabolic response of the newborn to the lack of oxygen in the tissues is the activation of anaerobic glycolysis in the tissues and an increase in the concentration of lactate and ketones. Lipid peroxidation, especially in nerve cells, is catalyzed by iron released from hemoglobin, transferrin and ferritin, whose release is induced by tissue acidosis and free oxygen radicals. Ferroptosis-inducing factors can directly or indirectly affect glutathione peroxidase through various pathways, resulting in a decrease in the antioxidant capacity and accumulation of lipid reactive oxygen species (ROS) in the cells, ultimately leading to oxidative cell stress, and finally, death. Conclusion: damage to the mitochondria as a result of lipid peroxidation caused by the COVID-19 disease can cause the death of a newborn and pregnant women as well as short time and long-time sequelae.

The Effect of Glucose Metabolism and Breastfeeding on the Intestinal Microbiota of Newborns of Women with Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) is a pregnancy complication in which women without previously diagnosed diabetes develop chronic hyperglycemia during gestation. The diet and lifestyle of the mother during pregnancy as well as lactation have long-term effects on the child's health and development. Detection of early risk markers of adult-age chronic diseases that begin during prenatal life and the application of complex nutritional interventions at the right time may reduce the risk of these diseases. Newborns adapt to the ectopic environment by developing intestinal immune homeostasis. Adequate initial colonization of bacteria is necessary for sufficient development of intestinal immunity. The environmental determinant of adequate colonization is breast milk. Although a developing newborn is capable of producing an immune response, the effector immune component requires bacterial stimulation. Breast milk stimulates the proliferation of a well-balanced and diverse microbiota, which initially influences the switch from an intrauterine TH2 predominant to a TH1/TH2 balanced response and the activation of T-regulatory cells by breast milk-stimulated specific organisms (Bifidobacteria, Lactobacillus, and Bacteroides). Breastfeeding in newborns of mothers with diabetes mellitus regulates the adequate immune response of the newborn and prevents diseases of the neonatal and postnatal period.

Neonatal Pneumothorax Outcome in Preterm and Term Newborns.

Background and Objectives: Pneumothorax implies the presence of air in the pleural space between the visceral and parietal pleura. The aim of this study was to investigate the incidence, clinical characteristics, risk factors, therapy and perinatal outcome in neonates with pneumothorax in a tertiary care center. Materials and Methods: A retrospective study based on a five-year data sample of neonates with pneumothorax was conducted in a Maternity Hospital with a tertiary NICU from 2015 to 2020. We included all neonates with pneumothorax born in our hospital and compared demographic characteristics, perinatal risk factors, anthropometric parameters, comorbidities, clinical course and method of chest drainage between term (≥37 GW) and preterm (<37 GW) neonates. Results: The study included 74 newborns with pneumothorax, of which 67.6% were male and 32.5% were female. The majority of women (59.5%) had no complications during pregnancy. Delivery was mainly performed via CS (68.9%). Delivery occurred on average in 34.62 ± 4.03 GW. Significantly more (p = 0.001) children with pneumothorax were born prematurely (n = 53; 71.6%) than at term (n = 21; 28.4%). Most of the neonates had to be treated with ATD (63.5%) and nCPAP (39.2%), but less often they were treated with surfactant (40.5%) and corticosteroids (35.1%). O2 therapy lasted an average of 8.89 ± 4.57 days. Significantly more (p = 0.001) neonates with pneumothorax had additional complications, pneumonia, sepsis, convulsions and intraventricular hemorrhage (68.9%). However, most children had a good outcome (83.8%) and were discharged from the clinic. Fatal outcomes occurred in six cases, while another six neonates had to be transferred to referral neonatal centers for further treatment and care. Conclusion: Significantly more children with pneumothorax were born prematurely than at term. With adequate therapy, even premature newborns can successfully recover from pneumothorax.

Neurological outcomes of antenatal corticosteroid therapy.

AIM OF THE STUDY: The aim of the study was to investigate whether antenatal corticosteroid therapy (ACST) could impact neurological condition, as assessed through muscular tone, of prematurely born infants. METHODS: All 82 patients at risk of preterm delivery treated and delivered over 12 months were divided into two equal groups regarding the use of ACST. The investigated parameters were pregnancy complications, biophysical profile, Apgar score, gestational age of delivery and all postpartum complications. Neurological development and muscular tone were evaluated at the 1st, 3rd, 6th and 12th months of life using Vojta's method, which classifies muscular tone as good, hypotonic or hypertonic. RESULTS: After therapy, infants from the treated and control groups differed in biophysical profile, Apgar score, length of intensive care, occurrence of respiratory distress syndrome and intraventricular haemorrhage. During the follow-up, significantly more infants from the ACST group had good muscular tone when compared with those from the control group. Regression analysis showed that ASCT can significantly impact an infant's muscular tone. Still, the week of delivery and the complications such as diabetes mellitus, intrauterine growth restriction and respiratory distress syndrome, could change the association of ACST and infants' muscular tone. CONCLUSION: ACST was associated with the positive neurological outcomes of prematurely born infants when assessed through their muscular tone.

Free Fatty Acids of Newborns from Women with Gestational Diabetes Mellitus.

INTRODUCTION: Fetal macrosomia in gestational diabetes mellitus is contributed to by compensatory fetal mechanisms responding to alterations in maternal metabolism. OBJECTIVES: To compare FFA and blood glucose concentrations of newborns derived from healthy and hyperglycemic mothers. METHODS: Prospective study included two equal groups of term newborns (50) from GDM and healthy mothers. Blood was derived from umbilical and cubital vein of mothers immediately after birth. RESULTS: The mean FFA concentration of mothers did not differ whereas in infants of GDM mothers FFA were significantly lower. A significant correlation was found between FFA levels of healthy mothers and their newborns (p < 0.05). No such correlation was found in GDM group (p > 0.05). A significant correlation was found between mother's and newborn's glycemia (p < 0.05) in both groups. CONCLUSION: Suppression of FFA acids in newborn blood of mothers with GDM may represent the lipogenic and antilipolytic activity of the fetus.

Lipids and Adipokines in Cord Blood and at 72 h in Discordant Dichorionic Twins.

BACKGROUND: Intrauterine growth restriction (IUGR) is a risk factor for developing metabolic syndrome later in life. We explored whether adipokine concentrations in cord blood (CB) and on day 3 (D3) were related to impaired fetal growth and lipids in IUGR twins. PATIENTS AND METHODS: Thirty-six discordant (birth weight [BW] discordance ≥20% calculated in relation to the heavier co-twins) and 42 concordant (BW discordance ≤ 10%) twin pairs were included. RESULTS: In IUGR twins, both adiponectin/BW and triglyceride (TG) levels were significantly higher, while total cholesterol, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol were lower in CB. On D3, both leptin and HDL-C levels were significantly lower and TG levels were significantly higher in IUGR twins. In the discordant group, the alterations in lipids were not related to any adipokine. CONCLUSIONS: IUGR is related to lower leptin level and proatherogenic lipid profile (higher TG and lower HDL-C), which are not influenced by adipokine at birth.

Lipids on the Second Day in Ischemic and Normoxemic Term Neonates.

INTRODUCTION: In hypoxic newborns requiring oxygen, lipid peroxidation affects the peripheral blood lipids. OBJECTIVES: Determine the influence of perinatal oxygen therapy for hypoxia on serum lipid concentrations on the second day of life. MATERIALS AND METHODS: Our study included 50 newborns with perinatal hypoxia requiring oxygen and 50 healthy newborns without oxygen therapy. Arterialized capillary blood was taken for categorization of hypoxia (pO2) after birth in both groups. Lipid concentrations: total cholesterol (TC), high density lipoproteins (HDL), low density lipoproteins (LDL), and triglycerides (TG) were measured on day 2 in both groups. RESULTS: TC, LDL, HDL, TG, HC03 levels were statistically lower in the study group compared to the control one, while pCO2 and BE levels were statistically higher in newborns with perinatal hypoxia. CONCLUSION: Lower lipid levels in hypoxic newborns may suggest that circulating lipids are oxidized, peroxidized, and removed from the peripheral circulation.

Neonatal Outcome in Pregnancies with Autoimmune Myasthenia Gravis.

INTRODUCTION: Acquired autoimmune myasthenia gravis (MG) is an autoimmune process in which antibodies (AB) directed against the acetylcholine nicotinic receptor (AChR) cause weakness and fatigue of striated muscles. OBJECTIVES: The objective of this study was to determine the range of clinical manifestations in newborns with transient neonatal myasthenia (TNM). METHODS: 62 newborns with mothers who had autoimmune MG were followed by: anthropometric parameters, gestational age, gender, type of delivery completion, Apgar score (AS) in the first and fifth minute, and the emergence of TNM symptoms. RESULTS: For fourteen consecutive years, from a total of 98,000 infants, 62 (0.06%) were born to mothers with autoimmune MG. Four of them (6.4%) had symptoms of TNM. CONCLUSION: Newborns of mothers with MG manifest clinical features of TNM relative to stage of mother's illness. These newborns need monitoring until the seventh day of life.

Importance of Staphylococcus epidermidis findings in the blood and cerebrospinal fluid of a full-term newborn: a case report.

Methicillin-resistant Staphylococcus epidermidis (MRS) predominantly colonizes the skin and mucous membranes of humans and other animals. We describe the case of a male newborn of gestational age 39 weeks whose primary and repeated blood cultures and cerebrospinal fluid samples isolated MRS. The choice and duration of antibiotic therapy were determined by the clinical presentation, infection parameters, and results of bacteriological analyses of blood and cerebrospinal fluid samples obtained from the newborn on the day 5 of life. After 28 days of antibiotic therapy for sepsis accompanied by meningitis, the newborn was discharged home without sequelae.

Gestational Diabetes Mellitus and Antenatal Corticosteroid Therapy-A Narrative Review of Fetal and Neonatal Outcomes.

BACKGROUND: There, we review the pathogenesis of gestational diabetes mellitus (GDM), its influence on fetal physiology, and neonatal outcomes, as well as the usage of antenatal corticosteroid therapy (ACST) in pregnancies complicated by GDM. METHODS: MEDLINE and PubMed search was performed for the years 1990-2022, using a combination of keywords on such topics. According to the aim of the investigation, appropriate articles were identified and included in this narrative review. RESULTS: GDM is a multifactorial disease related to unwanted pregnancy course and outcomes. Although GDM has an influence on the fetal cardiovascular and nervous system, especially in preterm neonates, the usage of ACST in pregnancy must be considered taking into account maternal and fetal characteristics. CONCLUSIONS: GDM has no influence on neonatal outcomes after ACST introduction. The ACST usage must be personalized and considered according to its gestational age-specific effects on the developing fetus.

Neurological impairments in hypoxic neonates and lactate levels.

INTRODUCTION: Metabolic acidosis with increasing lactate concentration develops due to the lack of oxygen in the tissues. OBJECTIVES: The effect of lactic acidosis on neurological development in the first year of life. MATERIALS AND METHODS: Our study included 50 newborns with perinatal hypoxia requiring oxygen therapy and 50 healthy newborns. pH, pCO2, pO2, base excess (BE) and lactates from arterialized capillary blood were determined in both groups of newborns, in the first and second hours after birth, and neurological development in the first year of life was estimated. RESULTS: pH, pCO2, pO2, BE and lactates differed significantly between the groups in the first and second hours after birth p < 0.01. Hypotonia was recorded in 20/50 cases and hypertonia was recorded in 10/50 cases in the first year of life. CONCLUSION: Lactate concentration may be an indicator of neurological damage in neonates with perinatal hypoxia.

Leptin and adiponectin levels in discordant dichorionic twins at 72 hours of age-associations with anthropometric parameters and insulin resistance.

BACKGROUND: Insulin resistance (IR) in adults has been associated with intrauterine growth restriction (IUGR). Leptin and adiponectin correlations with anthropometric parameters and IR at 72 h in discordant twins were tested. METHODS: We included 24 discordant (birth weight discordance ≥20% in relation to the heavier cotwin) and 30 concordant (birth weight discordance ≤10%) twins. RESULTS: A correlation between leptin (but not adiponectin) level and birth weight (BW), birth length and head circumference in IUGR twins was recorded (p<0.05). Insulin sensitivity (IS) and homeostatic model assessment (HOMA)-IR in IUGR twins were similar to appropriate-for-gestational-age cotwins and unrelated to adipokines. In IUGR twins, adiponectin and insulin associated positively. In larger concordant twins' leptin level correlated with HOMA-IR and insulin. CONCLUSIONS: Leptin, but not adiponectin, levels correlate positively with anthropometric parameters in IUGR twins. IR in IUGR twins is unrelated to adipokines in the first few days of life.