Background/Objectives: Cardiac rhabdomyoma (CR), the most frequently occurring fetal cardiac tumor, is often an early marker of tuberous sclerosis complex (TSC). This study evaluates outcomes of fetuses with prenatally diagnosed cardiac tumors managed at a single tertiary center. Methods: Medical records of fetuses diagnosed with cardiac tumors between 2009 and 2024 were retrospectively reviewed. Results: Sixteen cases were identified, with a median follow-up of 6.7 years. TSC was confirmed in 14 cases (88%). Multiple tumors were observed in 13 cases (81%), while 3 cases (19%) had solitary tumors. Both non-TSC cases involved solitary tumors. Cardiac complications (arrhythmias, conduction disorders, and hemodynamic abnormalities) occurred in 38% of cases prenatally and 69% postnatally, with larger tumor diameters significantly associated with complications (p = 0.02). No fetal hydrops or mortality occurred; however, one child died at age five due to a seizure. Postnatal tumor regression occurred in 56% of cases and complete regression in 38% by a median age of 2.3 years (range: 0.6–4.4). One tumor remained stable. Brain MRI revealed TSC-related changes in all TSC-affected patients except one, who had a developmental brain anomaly. Most TSC patients experienced epilepsy (71%) and developmental delays. Conclusion: While CRs are typically benign and regress spontaneously, their strong association with TSC highlights the importance of early diagnosis and family counseling. TSC-related epilepsy and psychomotor delays significantly impair the quality of life. Early mTOR inhibitor therapy offers promise in mitigating TSC-related complications and improving outcomes.

ObjectiveTo examine whether variation of regional cerebral oxygen saturation (rScO2) within three days after delivery predicts development of brain injury (intraventricular/cerebellar hemorrhage or white matter injury) in preterm infants.Study designA prospective study of neonates <32 weeks gestational age with normal cranial ultrasound admitted between 2018 and 2022. All received rScO2 monitoring with near-infrared spectroscopy at admission up to 72 h of life. To assess brain injury a magnetic resonance imaging was performed at term-equivalent age. We assessed the association between rScO2 variability (short-term average real variability, rScO2ARV, and standard deviation, rScO2SD), mean rScO2 (rScO2MEAN), and percentage of time rScO2 spent below 60% (rScO2TIME<60%) during the first 72 h of life and brain injury.ResultsThe median [IQR] time from birth to brain imaging was 68 [59-79] days. Of 81 neonates, 49 had some form of brain injury. Compared to neonates without injury, in those with injury rScO2ARV was higher during the first 24 h (P = 0.026); rScO2SD was higher at 24 and 72 h (P = 0.029 and P = 0.030, respectively), rScO2MEAN was lower at 48 h (P = 0.042), and rScO2TIME<60% was longer at 24, 48, and 72 h (P = 0.050, P = 0.041, and P = 0.009, respectively). Similar results were observed in multivariable logistic regression. Although not all results were statistically significant, increased rScO2 variability (rScO2ARV and rScO2SD) and lower mean values of rScO2 were associated with increased likelihood of brain injury.ConclusionsIn preterm infants increased aberration of rScO2 in early postdelivery period was associated with an increased likelihood of brain injury diagnosis at term-equivalent age.

Cilj je ovog izvješća u proteklom trogodišnjem razdoblju (2019–2022) prikazati: 1) aktivnosti Referentnog centra, 2) postignute stručne rezultate i primjenu novih metoda, postupaka i unaprjeđenje struke, i 3) znanstvenu i stručnu suradnju s inozemnim ustanovama visoke razine. Rezultati: Referentni je centar jedino mjesto u Republici Hrvatskoj koje kontinuirano zbrinjava populaciju najugroženijih i najtežih bolesnika pedijatrijske dobi sa srčanom patologijom. Ima kontinuirano, 24 sata dostupnu kardiološku, kardiokiruršku, anesteziološku, neonatalnu i intenzivnu skrb za djecu sa složenim prirođenim i stečenim srčanim bolestima. Također su dostupne metode nadomještanja funkcije organa u zatajivanju (ECMO potpora, LVAD-BiVAD, Berlin-Heart pumpa, hemodijaliza, program transplantacije srca / drugih organa), a sve zahvaljujući timskom radu i suradnji tima nekoliko Zavoda. Izvode se složene kardiokirurške operacije u djece s prirođenim srčanim greškama uz jasan trend povećanja broja i složenosti operacija, te uz i dalje prihvatljivo nisku smrtnost. Danas smo u mogućnosti samostalno liječiti gotovo sve srčane bolesti u djece. Godišnje se izvede oko 200 kateterizacija srca u djece. Više od 40% čine intervencijske procedure, a više od 50% tih intervencija izvodi se u dojenačkom periodu. Tijekom protekle tri godine uvedeno je pet novih perkutanih intervencijskih metoda: liječenje nativne koarktacije i rekoarktacije umetanjem stenta, liječenje stenoze pulmonalnih grana umetanjem stenta, perkutano umetanje valvule na pulmonalnu poziciju, dilatacija postojećeg stenta te zatvaranje aortopulmonalnih kolaterala u djece s univentrikulskim srcem. Navedeni iskoraci učinjeni su kontinuiranim zalaganjem članova tima uz potporu i mentorstvo, odnosno kontinuiranu suradnju s inozemnim stručnjacima iz triju inozemnih ustanova (DeutschesHerzZentrum Muenchen, KinderherzZentrum Linz, Kids Heart Center Budapest). Zaključak: Naš centar stoji uz bok rijetkih centara u Europi koji su u mogućnosti izvesti navedene procedure. Navedene su aktivnosti rezultirale unaprjeđenjem kvalitete skrbi na razini RH i temelj su za daljnji planirani rast i razvoj struke u okvirima naše zemlje.

Aim To compare interleukin-2 levels (IL-2) and IL-2 gene site 1 methylation levels between preterm newborns (PN) and full-term newborns (FN) and investigate their association with the environmental exposure of their mothers during pregnancy. Methods IL-2 and IL-2 gene site 1 methylation levels were assessed in 50 PN and 56 FN. Newborns' mothers filled in questionnaires about their living and occupational environments, habits, diets, and hobbies. Results The mothers of PN were significantly more frequently agrarian/rural residents than the mothers of FN. PN had significantly higher IL-2 levels, and significantly lower methylation of IL-2 gene site 1 levels than FN. Conclusion IL-2 levels, hypomethylation of the IL-2 gene site 1, and the mother's rural residence (probably due to pesticide exposure) were predictive biomarkers for preterm birth. For the first time, we present the reference values for the methylation of IL-2 gene site 1 in PN and FN, which can be used in the clinical setting and biomonitoring.

Background:Kaposiform hemangioendothelioma (KHE) is a rare and aggressive, potentially life-threatening vascular tumor typically occurring in infancy.It is frequently associated with the Kasabach-Meritt syndrome (KMS), a serious consumptive coagulopathy with thrombocytopenia and hypofibrinogenemia.Because of this, morbidity rates are high.As of yet, no standardized guidelines exist for the treatment of KHE. Case presentation:In January 2019 a male full-term newborn presented to the neonatal intensive care unit (NICU) with a 14x10 cm tumor on the left side of the neck.The pregnancy itself was well-controlled and the male newborn was delivered by an elective C-section, with an Apgar score of 9/9.The tumor, purple in color and covered in petechiae and ecchymoses, was extending from the base of the neck towards the mandibula.Upon the transfer to the NICU, laboratory findings (platelets 9,000/μL, fibrinogen 0.8 g/L, Ddimer >10 mg/L, aPTT 37.1 s) showed significant thrombocytopenia and hypofibrinogenemia.Initial assessment (MRI and TOF angiography) showed a hypervascular, heterogeneous structure suggestive of hemangioma.The initial treatment strategy consisted of administering blood derivatives, DSA embolization of the tumor, propranolol, antifibrinolytics, and corticosteroids -but no clinical or laboratory improvement was noted.The MRI, laboratory findings, and the clinical course of the disease were all indicative of KHE, hence treatment with peroral sirolimus (an mTOR inhibitor) in combination with parenteral corticosteroids was started.In the following two months, complete resolution of KMS was noted with a progressive reduction in tumor size.The coagulation parameters turned normal.The patient is still on sirolimus and demonstrates nearly complete involution of the lesion with no apparent side effects. Conclusion:As there are no standardized guidelines for the treatment of KHE, this case strongly suggests the effectiveness of sirolimus treatment in severe KHE/KMS.

Kaposiform hemangioendothelioma (KHE) is extremely rare, life-threatening vascular tumor with estimated incidence of 0.071 cases per 100.000 children. It is notably associated with Kasabach-Merritt phenomenon (KMP), a condition characterised by profound thrombocytopenia, hypofibrinogenemia, and elevated markers of coagulation activation (D-dimers or fibrin degradation products). Mortality is highly associated with degree of coagulopathy. Patients diagnosed prenatally appear to have increased disease severity. Optimal therapy for KHE is not known. Oral steroids and vincristine for patients with inoperable tumors is most commonly reported, but is associated with limited response and significant side effects. Sirolimus (rapamycin), a mammalian target of rapamycin (mTOR) inhibitor, is currently being tested in a prospective phase II clinical trial. Here we present a full-term newborn prenatally diagnosed with giant vascular tumor, affecting the lateral neck. He was delivered by elective C- section and initially presented with a firm, violaceous neck tumor 14x10 cm. Following the birth, he rapidly evolved to severe KMP. Despite endovascular embolisation performed immediately after birth, his coagulopathy worsened to life threatening hemorrhage (platelets 8,000/μL, fibrinogen 0.8 g/L, D-dimer >10 mg/L, PT-INR 1.36, aPTT 26 s, Hb 80 g/L, Hct 23%), necessitating aggressive blood products replacement to maintain hemostasis. MRI and laboratory investigations strongly suggested the diagnosis of KHE/KMP. Biopsy was not attempted because of the potential risk of hemorrhage. He was vitally endangered with rapidly enlarging tumor size compromising airway patency, as well as the worsening coagulopathy triggered by platelet entrapment. As there were no response to corticosteroid and propranolol therapy, we elected to start sirolimus (0.8 mg/m2 per dose twice daily) along with tapering parenteral corticosteroids. This therapeutic approach led to remarkable resolution of consumptive coagulopathy with stepwise regression of tumor size. After 14 months of follow-up he remains on sirolimus without toxicity, the tumor is barely visible, and MRI showed remarkable reduction in the tumor size. Currently, no standard treatment guidelines exist for KHE/KMP because of their rare nature and lack of prospective trials. Our experience adds to a growing body of evidence suggesting that sirolimus in the treatment of high-risk KHE/KMP patients might be an efficacious and safe treatment option.

Goal The purpose of this study was to characterize the population and evaluate risk factors, surgical treatments and short-term outcomes in preterm infants with surgical necrotizing enterocolitis (NEC). Methods We retrospectively evaluated premature infants with surgical NEC over a period of 5 years (2015-2019) in a Croatian tertiary referral centre. Data were extracted from medical records. Results This study included 23 outborns aged 23 to 36 weeks of gestation (27.7±3.7). The median age at surgery was 11 days (5-43 days). Male gender (83%) was overrepresented, whereas antenatal steroid exposure was low (61%). The majority of patients (n=15) had a primary laparotomy (65%); two patients had peritoneal drainage (PD) alone (9%) and six patients had PD followed by laparotomy (26%). All patients survived. After referral, the median length of hospitalization was 128 days (15-430 days), one patient developed short bowel syndrome, five (22%) were treated for sepsis, eight patients (35%) received laser photocoagulation due to retinopathy, and grade 3 to 4 intraventricular hemorrhages were diagnosed in seven (30%) patients. There were no differences in outcomes related to surgical approach. Conclusion NEC mortality in our cohort is lower than current literature suggests. Additionally, abdominal drainage seems to be equally successful treatment of NEC as explorative laparatomy and bowel resection in neonates who do not meet the criteria for the latter procedures. Neonates who underwent abdominal drainage do not show increased probability of complications or higher lethality.

Although rare, cardiac rhabdomyomas (CRs) are the most common fetal cardiac tumors. They may be the earliest manifestation of tuberous sclerosis complex (TSC). TSC is diagnosed in 75-80% cases of multiple fetal CRs and in 30% of single cases. We retrospectively reviewed the clinical outcome of fetal CR cases. All cases of prenatally diagnosed rhabdomyoma in a single tertiary centre from 2009 to 2019 were ascertained from medical records. We identified 14 fetuses with prenatally diagnosed CRs. Mean period of follow-up was 4 years (range 4m-9y). Two fetuses were twins (BC/BA), both affected by CR with family history of TSC, and one fetus of the dichorionic pair was not affected by rhabdomyoma. The mean GA at diagnosis was 29 weeks (range 21-35). There were eleven fetuses with multiple, and three with a solitary tumor. The right and left ventricle as well as the intraventricular septum were equally affected with a slight predominance of the left ventricle. The cardiac atrium was affected in two cases. The size ranged from small tumors of several mm in diameter up to dimensions of 20x20 mm. Sixty percent were <20 mm in diameter. Two of fetuses were affected by hemodynamically relevant cardiac obstruction (LVOT), and in four arrhythmias (SVES, VES, WPW syndrome, and AV block) were observed. No hydrops fetalis or fetal perinatal demise were observed. In 11 (79%) TSC was confirmed clinically or by mutational analysis. After birth, most rhabdomyomas demonstrated a stable (14%, n=2) or spontaneous regressive growth pattern (57%, n=8). In four children (29%) tumors entirely disappeared. No progression of tumor size or number was observed. After birth in five (36%) children the conduction abnormalities were confirmed by ECG and responded well to the anti-arrhythmic medication and two children were affected by LVOT obstruction. Cerebral manifestations (tubers and/or nodules) were detected by brain MRI in 9 patients (3 prenatally). Subependymal giant cell astrocytoma was diagnosed in 3 cases, 2 received treatment with mTOR inhibitor, and one child underwent VP shunt due to enlarging SEGA causing obstructive hydrocephalus. Six (55%) of the children with TSC suffered from epilepsy and psychomotoric development delay. Although CRs are benign from the cardiovascular standpoint, and have a natural history of spontaneous regression, their close association with TSC prompt for early prenatal diagnosis and family counselling regarding the dismal long-term prognosis. Recent literature suggests that early therapy with mTOR inhibitors may prevent the development of TS manifestations.

Estradiol (E), testosterone (T), and their ratio are crucial axis in life. Especially during intrauterine growth, they orchestrate the complex development of organs and their interaction, which have lifelong impact on health and an organism’s capacity to respond to environmental stressors. The aim of this study was to compare for the first time E, T, and their ratio levels with aromatase (CYP19) gene methylation levels between preterm newborns (PN) and full-term newborns (FN) with respect to their mother’s environmental exposure and diet. In this study, 56 FN of 37–42 weeks of gestation age (GA) and 46 PN at GA 27–36 weeks were analysed for E and T levels and CYP19A1 gene pI.3/II promoter region methylation. Results showed there was no difference in E levels between PN and FN, but there were significantly lower levels of T in PN than in FN (2.81 nmol vs. 3.76 nmol, respectively) and consequently a significantly higher E/T ratio in PN than in FN (5278.04 vs. 2891.23, respectively). CYP19A1 methylation was significantly lower in PN than in FN (86.04% vs. 90.04%, respectively). CYP19A1 methylation was significantly reduced in newborns whose mothers reported daily milk consumption. Our study is the first to provide referent values for CYP19A1 methylation levels in FN and PN and shows that PN and FN significantly differ in CYP19A1 methylation levels, T levels, and E/T ratio. Future research should further investigate the mechanisms involved in GA-dependent CYP19A1 methylation levels and mechanisms of sex hormone disturbances which may contribute to preterm birth.

To compare early neonatal health care outcomes in university hospitals (including university hospital centers) with outcomes in other health institutions in Croatia. An observational retrospective study of childbirth data from National Medical Birth Database was conducted. Outcomes (early neonatal mortality or survival rate) of all neonates of gestational age <32 completed weeks in the period 2009-2018 were studied with regard to birth settings (university hospitals and university hospital centers vs. other health institutions). The statistical significance of differences in average early neonatal mortality rates (ENM) was determined. In the period 2009-2018 there were 1,282 live-born children of gestational age 22-27 completed weeks in Croatia. Most (84.8%) were born in university hospitals (rate increasing over the studied period) and the rest (15.2%) in other health institutions. The respective average birth rates were 5.0/1,000 live births in university hospitals and 1.1/1,000 live births in other hospitals, with minor oscillations throughout the studied period (university hospitals: 4.0–6.3; other hospitals: 0.5-1.5). The average ENM rate in this gestational group was statistically significantly higher among neonates born in other hospitals (565.7/1,000 live births) compared to those born in university hospitals (373.7/1,000 live births), χ2=25,316, P<0.0001. Out of 2,148 live-born children of the gestational age 28-31 completed weeks most were born (87.8%) in university hospitals and the rest (12.3%) in other hospitals. The respective average birth rates were 8.6/1,000 in university hospitals (with an intermittently increasing rate) and 1.5/1,000 live births in other hospitals. The average ENM rate in this gestational group was higher in other hospitals (91.2/1,000 live births) compared to university hospitals (62.0/1,000 live births), but with no statistically significant difference; χ2=3.220, P=0.0727. The ENM rate in children of gestational age 22-27 completed weeks is higher in other hospitals than in university hospitals. Furthermore, the proportion of these children born in university hospitals in Croatia has increased over the studied 10-year period. As pre-term birth (before 32 weeks of gestation in particular) is closely related to perinatal outcome (i.e. high mortality or long-term impairment), analysis of their outcomes is important for planning and development of an appropriate neonatal intensive care unit network as well as to improve decision-making processes in health politics.

Vein of Galen aneurysmal malformation (VGAM) is a complex congenital cerebro-vascular malformation. Despite some controversy, the overall prognosis of VGAM has improved over time. We present a series of VGAM patients with hyper-dynamic heart failure during the neonatal period treated in our Department in the past 20 years. All cases diagnosed with chorioidal VGAM in a single tertiary centre between 2001 and 2020 were ascertained from medical records. All infants underwent postnatal cardiac ECHO, electroencephalogram and brain MRI, along with calculation of Bicetre severity score at admission. Embolization procedures were analysed based on timing and presence of peri- and post-procedural complications. Long-term survivors had standard neurocognitive assessment. For the purpose of outcome analysis we divided patients into two period cohorts: 2001-2010 and 2011-2020. Overall fourteen out-born neonates were diagnosed with chorioidal VGAM. Bicetre neonatal score were similar in both chronological sub-groups. First cohort comprised six neonates. Prenatal diagnosis of VGAM was obtained in one patient. Four newborns died owing to refractory heart failure without neuroembolization procedure. Two survivors underwent the intervention at fourth and eleventh day, respectively. Post-procedural analysis revealed minor intraventricular bleeding and neonatal seizures in one patient that eventually has been lost to follow up. Other survivor developed ischaemic lesions and hydrocephalus. Ventriculo-peritoneal drainage was performed. Severe neurodevelopmental delay and visual impairment were observed on follow-up. Second cohort comprised eight neonates, all prenatally diagnosed. Three patients died: at the age of five (intra-procedural rupture of aneurism), fifteen (multi-organ failure), and 205 days (pulmonary hypertension and congestive heart failure). All infants undergone the first embolization within the first ten days of life. Satisfactory immediate outcome including control of cardiac failure was achieved in six patients. Post-procedural analysis revealed minor intraventricular bleeding (n=2), ventriculomegaly (n=2), presence of ischaemic lesions (n=2), neonatal seizures (n=2) and abnormal encephalogram (n=2). Normal neurodevelopment was observed in four, and mild neuro-developmental delay was observed in one patient on follow-up. Given a small sample size it is difficult to quantify the difference between the two groups in a statistically relevant manner. However, the observed difference in survival and long-term outcome between the cohorts are most probably related to an overall improvement of prenatal diagnosis, intensive care management and embolization techniques. Early neuroembolization may decrease the risk of refractory cardiac failure and improve the long-term neurocognitive outcome.

Multiple intestinal atresia (MIA) is a congenital malformation disorder in which atresia occurs at multiple levels throughout the gastrointestinal tract, most commonly small bowel. Frequently it presents as an isolated anomaly, but also as a part of a complex inherited disorder caused by homozygous or compound heterozygous mutation in tetratricopeptide repeat domain 7A (TTC7A) gene. These patients usually have associated mild or severe combined immunodeficiency. Herein we report an infant with MIA and associated combined immunodeficiency (CID). The female child was born at term by vaginal delivery to a 26-year-old G5P3 mother. The parents are healthy, non-consanguineous couple of Albanian origin. Pregnancy was complicated by polyhydramnios. Fetal ultrasound at 19 weeks of gestation revealed dilated bowel loops. Postpartal abdominal X-ray showed signs of gastric atresia. Surgery revealed widespread atresias, extending from stomach to cecum, and atrophic microcolon. Multiple small bowel resections with end-to-end anastomosis, and ileostomy were done. Histopathological examination showed pseudostratification of the epithelium, increased enterocyte apoptosis, inflammatory eosinophilic infiltrate in lamina propria, decreased small bowel villi, and disrupted apical-basal polarity. At two weeks of age GI obstruction recurred, and she underwent jejunal resection with end ileostomy. The residual small bowel length measured 45cm. Immunological investigation revealed CID: T cell lymphopenia affecting all subsets with lower B cell, natural killer cell count and impaired mitogen response. She experienced several septic episodes. At two months, allogeneic bone marrow transplantation was successfully performed. MIA-CID was suspected and genetic testing confirmed homozygous pathogenic variant in the TTC7A gene (c.315_318del/c.315_318del) causing premature translational stop signal that result with absent protein production. She is now 4 months old, has failure to thrive and parenteral nutrition-induced cholestasis and continues to be dependent on parenteral nutrition for a short gut. MIA-CID is a rare hereditary disease with about 50 reported patients in literature. Abundant expression of TTC7A gene in thymus and colon and its critical role in intestinal and immune homeostasis can explain this severe phenotype and almost invariably poor prognosis. Clinical course may be more favourable if the bone marrow transplantation is done in the first three months of life. Therefore, immunological and genetic testing should be performed in every neonate born with MIA.

Background: The aim of this study was to compare for the first time IL-6 (Interleukin 6), testosterone (T) and estradiol (E) levels, their ratio (E/T), micronucleus (MN), and nuclear bridge (NB) frequency between newborns with regard to their mother's residency and diet. Our results should enable an assessment of the possible environmental endocrine effects and interaction between biomarkers, pointing to possible associated health risks. Methods: Fifty full-term newborns of both sexes, whose mothers were healthy and not occupationally exposed to any known carcinogen, were analyzed. All of the mothers filled in a detailed questionnaire. Results: The results showed significantly higher levels of E in newborns of mothers with agricultural residency than those born by mothers with urban residency. Significantly, lower levels of E were measured in newborns of mothers who drank milk and carbonated beverages more frequently. Testosterone was significantly higher in boys of mothers with agricultural residency than from mothers with urban residency. Residence and other parameters had no impact on the difference in MN frequency. IL-6 levels were higher in newborns of mothers with agricultural residency. NB levels were significantly associated with E. A significant association between E levels and IL-6 was found. Conclusion: Our results were the first to show a significant impact of the mother's agricultural residency and diet on their newborns' sex hormone and IL-6 levels and their association.

Conjoined twining is a rare medical phenomenon, with an overall prevalence of 1.47 per 100 000 births. This report describes a successful separation of xypho-omphalopagus conjoined twins complicated by unbalanced blood shunting through the porto-systemic anastomoses within the shared liver parenchyma. Significant extrauterine twin-twin transfusion syndrome caused by unbalanced shunting is an extremely rare, and probably under-recognized, hemodynamic complication in conjoined twins necessitating urgent separation. Progressive deterioration with a poor outcome can be prevented if the condition is recognized in a timely manner.

Introduction. In neonatology, various illness severity scores have been developed to predict mortality and morbidity risk in neonates. The aim of our study was to validate the ability of the 'Clinical Risk Index for Babies' (CRIB) II score to predict mortality in neonates born before 32 weeks' gestation in a level 3 neonatal intensive care unit (NICU), setting.Materials and Methods. Prospective birth cohort study including all live-born neonates of 32 weeks' gestation or less.. CRIB II score was calculated and the predicted mortality was compared with the observed mortality. Discrimination (the ability of the score to correctly predict survival or death) was assessed by calculating the receiver operating characteristic curve (ROC curve) and its associated area under the curve (AUC).Results. The ROC curve analysis in our study showed that the AUC was 0.9008 suggesting that mortality prediction was 90% accurate for all infants. Sensitivity and specificity were 77% and 88% respectively. In our study population, the CRIB II score appears to be more accurate than gestational age and birth weight in predicting mortality.Conclusions. The CRIB II scoring system is a useful tool for predicting mortality and morbidity in NICUs, and also a useful tool for evaluating the variations in mortality and other outcomes seen between different NICUs.

Introduction: Long-lasting respiratory symptoms have a huge impact on the quality of life in prematurely born children. The aim was to investigate paths of assumed causality leading from foetal inflammatory response syndrome (FIRS) to asthma symptoms in preterms. Methods: Demographic, antenatal, delivery and outcome data were collected from 262 infants with less than 32 completed weeks of gestational age over a 10-year period in a prospective cohort study. The presence of symptoms of asthma beyond the age of 5 years was the primary outcome measure. The causal effect of FIRS on childhood asthma was tested with three different logistic regression models and two structural equation models (SEM). Results: FIRS (OR = 4.7) and subsequent chronic lung disease of prematurity (OR = 7.7) and early childhood wheezing (OR = 9.5) are the most important risk factors for development of asthma symptoms in children born with less than 32 weeks of gestational age. The path analysis showed that FIRS has a large direct (0.59), medium indirect (0.11) and large overall (0.70) effect on CLD; large negative direct effect on ECW (-0.34) and a large positive indirect effect (0.74), mediated by CLD. On the occurrence of asthma symptoms, FIRS has a medium negative direct effect (-0.18) and a medium positive indirect effect (0.26), mediated by CLD and ECW. Conclusion: Prenatal inflammation plays an important role in the development of chronic respiratory disturbances in preterm infants. This influence is mainly related to structural and developmental lung abnormalities initiated in utero as consequences of FIRS, resulting in CLD of prematurity, and overcoming the protective mechanisms of chorioamnionitis.