Fetal Inflammatory Response Research Articles

How does fetal inflammatory response syndrome change fetalresponse to hypoxia? An experimental study in a fetal sheep model.

Fetal inflammatory response syndrome associated with acidosis during labor is a high-risk situation for the fetus. This study evaluated hemodynamic, gasometric, and heart rate variability changes during acute fetal inflammatory response syndrome associated with hypoxia, compared with isolated hypoxia. Acute fetal inflammatory response syndrome was obtained via anintravenously injection of lipopolysaccharide derived from Escherichia coli. Hypoxia was induced by repeated umbilical cord occlusions during three phases: mild, moderate, and severe umbilical cord occlusions. Two groups were created with chronically instrumented near-term fetal sheep: one group with isolated hypoxia, the other with hypoxia and fetal inflammatory response syndrome. Hemodynamic, gas parameters, and fetal heart rate variability were compared between the groups. The hypoxia and fetal inflammatory response syndrome group had a higher mortality rate (n = 4/9) compared with the hypoxia group (n = 0/9). Gasometric state was altered earlier in case of lipopolysaccharide injection (pH = 7.22 (7.12-7.24) vs 7.28 (7.23-7.34) p = 0.01; lactate = 10.3 mmol/L (9.4-11.0) vs 6.0 mmol/L (4.1-8.2) p < 0.001 after mild occlusions). After mild occlusions, the hypoxia and fetal inflammatory response syndrome group had higher values on seven heart rate variability parameters compared with the hypoxia group. After moderate occlusions, two parameters remained significantly higher. During fetal inflammatory response syndrome, fetal adaptation to hypoxia is impaired. In case of fetal infection, acidosis during labor is likely to become severe more rapidly, requiring closer fetal monitoring during labor.

Novel Biomarkers: Soluble Urokinase-Type Plasminogen Activator Receptor and Procalcitonin- and Histological Chorioamnionitis after Preterm Premature Rupture of Membranes

Fetal inflammatory response syndrome or infection after preterm premature rupture of membranes (PPROM) increases neonatal morbidity in preterm deliveries. Biochemical markers from the amniotic fluid (AF) have been used to evaluate possible intra-amniotic infection during the asymptomatic phase after PPROM. This study aimed to describe whether soluble urokinase-type plasminogen activator receptor (suPAR) or procalcitonin (PCT) from AF or maternal sera could reveal fetal inflammatory response or infection after PPROM. AF and maternal serum samples were collected weekly after PPROM (23+ 0 − 34+ 6 gestational weeks) until delivery from twenty women and two women with possible chorioamnionitis with intact membranes. Levels of suPAR, PCT, interleukin-6 (IL-6), glucose, lactate dehydrogenase (LDH), and bacterial PCR were determined from AF and suPAR and PCT and IL-6 from maternal sera. Fetal infection or inflammation response were determined by the histology of the placenta after delivery. AF glucose was significantly lower and AF LDH higher in the fetal site histologic chorioamnionitis (HCA) group, while AF suPAR concentrations tended to be higher in this group. AF suPAR correlated significantly with AF glucose and LDH. Based on receiver operating characteristic (ROC) analysis, AF glucose had the best predictability for fetal site histological chorioamnionitis. The findings of AF PCT were insignificant considering HCA. AF glucose had the highest accuracy in predicting fetal site histologic chorioamnionitis. AF suPAR may be a promising marker; however, our findings were limited by a small study population.

Latent profile analysis of newborn dried blood spot (DBS) cyto-and chemo-kines and growth factors and maternal and fetal acute inflammatory responses to amniotic fluid infection.

Latent profile analysis of newborn dried blood spot (DBS) cyto-and chemo-kines and growth factors and maternal and fetal acute inflammatory responses to amniotic fluid infection.

Changes in Relative Counts of Different Leukocyte Subpopulations in Peripheral and Umbilical Cord Blood of Women With Preterm Prelabor Rupture of Membranes With Respect to Intraamniotic Inflammation and Fetal Inflammatory Response Syndrome

ABSTRACTObjectiveThe aim of this study was to evaluate changes in the relative counts of different leukocyte subsets in peripheral and umbilical cord blood in pregnancies complicated by preterm prelabor rupture of membranes (PPROM) with respect to the presence of intraamniotic inflammation (IAI) and fetal inflammatory response syndrome (FIRS).MethodsFifty‐two women with singleton pregnancies complicated by PPROM were included in this study. From samples of peripheral and umbilical cord blood, relative counts of these leukocyte subpopulations were determined using multicolor flow cytometry: granulocytes, monocytes, lymphocytes, T cells and their subpopulations, B cells and their subpopulations, and NK cells and their subpopulations. IAI was defined as increased concentrations of interleukin 6 in the amniotic fluid. Amniotic fluid samples were obtained by transabdominal amniocentesis.ResultsWomen with IAI had higher relative counts of monocytes (p = 0.04) in peripheral blood. There was an increased relative number of granulocytes (p = 0.003) and a decreased number of lymphocytes (p = 0.0048), helper CD4+ T cells (p = 0.019), NK cells (p = 0.0001) within leukocytes, NK cells within lymphocytes (p = 0.003) and CD16+ NK cells within NK cells (p = 0.005) in umbilical cord blood samples of women with FIRS. However, after adjusting the results for gestational age at sampling, all differences disappeared.ConclusionsThe presence of IAI or FIRS is not accompanied by significant changes in the relative counts of immune cells in peripheral blood or umbilical cord blood in pregnancies complicated by PPROM.

Two cases of Leukemoid reaction in premature infants caused by fetal inflammatory response syndrome

BackgroundFetal inflammatory response syndrome (FIRS) is a systemic inflammatory response caused by the activation of the fetal immune system. The serological diagnostic criterion for fetal inflammatory response syndrome is a cord blood interleukin-6 concentration that exceeds 11 pg/mL, while pathologic evidence indicates the presence of funisitis or chorionic vasculitis. It can affect all systems of the fetus. Alterations in patients’ hematopoietic system are primarily reflected by changes in peripheral blood leukocyte and neutrophil counts.Case presentationWe performed placental pathology to identify FIRS and showed two cases of neonatal leukemoid reaction caused by FIRS. These two babies’ alterations in hematopoietic system resolves spontaneously with the inflammation relief, without specific interventions. During the 16‑month and14- month follow‑up period, their motor and intellectual development was normal.Conclusions . Neonatal leukemoid reaction is a reactive disease characterized by abnormal blood parameters similar to those of leukemia, but not leukemia. It is an aberrant hematopoietic response that typically resolves spontaneously with cause relief without requiring specific interventions.

Diagnostic tests for the prediction of histological chorioamnionitis and funisitis in pregnant women with preterm premature rupture of membranes: A systematic review.

Infection of the amniotic cavity is an important driver and/or consequence of preterm prelabour rupture of membranes (PPROM). Prediction of infection is challenging, limiting guidance for interventions during the antenatal period. Infection typically triggers a host inflammatory response, and non-invasive indirect markers of the maternal or fetal inflammatory response have been reported in the context of PPROM and intra-amniotic infection. Some of these markers have also been tested in amniotic fluid (AF) samples. This study compared markers of the inflammatory response in women with PPROM against the outcome standard of histological chorioamnionitis (HCA) or funisitis (FUS). Searches were conducted for studies reporting diagnostic test sensitivity and specificity for proven HCA or FUS in pregnant women with PPROM after 20 weeks' gestation. Weighted mean pooled sensitivity (Se), specificity (Sp), positive predictive value, negative predictive value, diagnostic odds ratio and 95% confidence intervals were calculated for each of the selected diagnostic tests. Except ultrasonographic detection of fetal thymic involution, almost all index tests analysed showed relatively low sensitivity. Maternal white cell count, interleukin-6 (IL-6) and AF IL-6 had credible specificity. Testing of AF markers, while more consistent than serum markers, showed no clear diagnostic accuracy improvement. There is a clear lack of evidence for the reliability of any individual diagnostic test to assist in the detection of HCA or FUS in women with PPROM. Combining several markers into a predictive model for improved diagnosis may be worth investigating.

Neurodevelopmental outcomes in extremely preterm infants with placental pathologic evidence of fetal inflammatroy response.

Neonates born with fetal inflammatory response (FIR) are at increased risk for adverse neonatal outcomes. Our objective was to determine whether FIR and its severity is associated with neurodevelopmental impairment (NDI) at 2 years of age or death among preterm infants. A retrospective cohort study of prospectively collected data of all infants born <29 weeks gestational age (GA). FIR and its severity were diagnosed according to the Amsterdam Placental Workshop Group Consensus Statement. Neurodevelopmental outcomes among all participants were quantified according to Bayley III. Mothers of infants with FIR were significantly younger (P = 0.04) and had a greater prevalence of antenatal steroid use (P < 0.01), infection during pregnancy (P = 0.01), PPROM (P < 0.01), and clinical chorioamnionitis (P < 0.01). Infants with FIR had longer duration of hospitalization (P < 0.01), days on oxygen (P < 0.01), congenital pneumonia (P = 0.03), moderate/severe bronchopulmonary dysplasia (BPD; P < 0.01). Notably, infants with FIR were not at increased risk of NDI or death (primary outcome). Those with moderate to severe FIR (≥ stage 2 FIR) were at increased risk of developing motor & language impairment or death (P < 0.01). This is the first report demonstrating an association between the severity of FIR and subsequent NDI in preterm infants born. Fetal Inflammatory Response (FIR) is not associated Neurodevelopmental Impairement (NDI) or Death in preterm infants However, there is significant relationship between moderate to severe FIR and NDI at 2 years of age in preterm infants. This is the first study demonstrating the impact of progression and severity of FIR on NDI or Death in preterm infants. These observations provide additional insight into understanding the impact of intrauterine exposure to inflammation on the NDI or death in preterm infants.

Кореляція маркерів материнського та плодового запалення

Fetal inflammatory response syndrome (IFRS) is an inadequate reaction of the fetal immune system to the inflammatory process in the placenta, which is accompanied by an increase in neonatal mortality and morbidity. Aim - to assess the dependence of IFRS on the markers of the inflammatory process of the mother in premature births in different gestational periods to determine the date of delivery. Materials and methods. 405 mothers with premature singleton deliveries and their premature newborns were examined. The Spearman correlation method was used to calculate the relationship between IL-6 content in the umbilical cord blood of a newborn and laboratory markers of maternal inflammation in peripheral blood (containing leukocytes and rod-shaped neutrophils, C-reactive protein, procalcitonin, pro-inflammatory interleukins), amniotic fluid (glucose, secretory inhibitor of leukocyte proteinase (SILP) and pro-inflammatory interleukins) and cervical mucus (pro-inflammatory interleukins). Results. Between the indicators of the mother's peripheral blood circulation and the value of IL-6, only a moderate connection was found, and the content of IL-6 in the amniotic fluid shows a strong correlation with the concentration of IL-6 in the umbilical cord blood of extremely premature newborns. For SILP, a strong correlation with the laboratory marker SFZV was found. A negative correlation with IL-6 of umbilical cord blood was found in cervical mucus for SILP. Signs of infection in the newborn show a strong dependence on the concentration of C-reactive protein and procalcitonin in the peripheral blood of the mother, but this was not found for extremely premature newborns. A strong correlation was found between the concentration of glucose in the amniotic fluid and signs of infection in premature infants in both gestational categories. Conclusions. Among indicators of peripheral blood circulation of a pregnant woman, none shows a strong correlation with IFRS. The concentration of SILP in the amniotic fluid has a strong correlation with signs of fetal inflammation, regardless of gestational age. The content of SILP in the cervical mucus has a strong negative correlation with the criterion of IFRS in preterm infants against the background of intact fetal membranes. A strong correlation between the glucose content in the amniotic fluid and signs of infection in the premature infant was revealed. For extremely premature newborns, no indicator of the mother's peripheral blood correlates with signs of infection. The research was carried out in accordance with the principles of the Declaration of Helsinki. The research protocol was approved by the Local Ethics Committee of the institution mentioned in the work. Informed consent of the women was obtained for the research. The authors declare no conflict of interest.

Fetal inflammatory response syndrome predicts early-onset sepsis and cystic periventricular leukomalacia in preterm neonates: A retrospective study.

Fetal inflammatory response syndrome (FIRS), the fetal equivalent of chorioamnionitis, is associated with poorer neonatal outcomes. FIRS is diagnosed through placental histology, namely by the identification of funisitis (inflammation of the umbilical cord) and chorionic vasculitis (inflammation of fetal vessels within the chorionic plate). The aim of this study was to identify and evaluate associations between FIRS and neonatal outcomes in preterm neonates. We performed a retrospective cohort study at a level III neonatal intensive care unit (NICU), from January 1st 2008 to December 31st 2022, involving all inborn neonates with a gestational age below 30 weeks. We compared preterm neonates based on whether their placental histology described funisitis with chorionic vasculitis (FCV) or not. The study included 113 preterms, 27 (23.9%) of those had FCV and 86 (76.1%) did not. After adjusting to gestational age, prolonged rupture of membranes and preeclampsia, FCV was independently associated with the development of early-onset sepsis (OR = 7.3, p = 0.021) and cystic periventricular leukomalacia (OR = 4.6, p = 0.004). The authors identified an association between FIRS and the development of early-onset sepsis and cystic periventricular leukomalacia, highlighting the importance of early detection and management of this condition in order to improve long-term neonatal outcomes.

Stage III Chorioamnionitis is Associated with Reduced Risk of Severe Retinopathy of Prematurity

ObjectiveTo identify whether histologically confirmed chorioamnionitis (hCAM) is associated with development of retinopathy of prematurity (ROP). Study designWe retrospectively analyzed two different cohorts. Cohort 1 was the national database of newborns in Japan born at ≤1500g or <32 weeks’ gestation (January 2003 through April 2021, n=38,013). Cohort 2 was babies born at <1500g from a single institution in Tsuchiura, Japan, (April 2015 through March 2018, n=118). ResultsFor Cohort1, after adjusting for potential confounders, stage III CAM (n=5,554) was associated with lower odds of severe ROP (stage ≥3 or required peripheral retinal ablation) by 14% (odds ratio [OR]: 0.86; 95% confidence interval [CI]: 0.78–0.94]. CAM of stage I (n=3,277) and II (N=4,319) was not associated with the risk of ROP. For Cohort 2, the odds of severe ROP were significantly reduced in moderate to severe hCAM groups (stage II, OR: 0.06, 95% CI: 0.05–0.82; stage III, OR: 0.10, 95% CI: 0.01-0.84). Neonates with funisitis, comorbidity of hCAM, and a finding of fetal inflammatory response had lower odds of severe ROP (OR: 0.11; 95% CI: 0.01–0.93). ConclusionsAfter adjusting for confounders, severe hCAM with fetal inflammatory response was associated with reduced risk of ROP.

Placental Histopathological Lesions and Adverse Neonatal Outcomes in Patients with Inflammatory Bowel Diseases- A retrospective Cohort Study.

Inflammatory bowel diseases (IBD) are significantly associated with adverse pregnancy and neonatal outcomes, though the pathomechanism is yet unknown. To investigate the relationship between IBD and adverse pregnancy outcomes by comparing neonatal outcomes and placental histopathology in two matched groups of patients with and without IBD. In this retrospective study, data of all patients who gave birth between 2008-2021 and were diagnosed with IBD were reviewed and compared to a control group matching two control cases for every IBD case. Neonatal outcomes and placental pathology were compared between the groups. Compared to the control group (n=76), the placentas of patients with IBD (n=36) were characterized by significantly lower placental weight (p < 0.001), and higher rates of maternal vascular malperfusion lesions (MVM, p < 0.001) and maternal and fetal inflammatory response lesions (p < 0.001). Neonates of patients with IBD were more frequently small for gestational age (SGA) (p=0.01), with increased rates of need for phototherapy (p = 0.03), respiratory morbidity and NICU admission (p < 0.001 for both outcomes). Multivariate logistic regression analyses adjusting for possible confounders (including maternal age, gestational age, chronic hypertension, smoking, and thrombophilia) confirmed the independent association between IBD and composite MVM lesions (aOR 4.31, p < 0.001), maternal inflammatory responses (aOR 40.22, p < 0.001) and SGA infants (aOR 4.31, p = 0.013). IBD is associated with increased rates of placental histopathological lesions and adverse pregnancy outcomes, including SGA infants. These novel findings imply the role of placental malperfusion and inflammatory processes in pregnancy complications of IBD patients, which should be followed accordingly. Approval of local ethics committee # WOMC-0219-20.

Overexpression of Connexin 40 in the Vascular Endothelial Cells of Placenta with Acute Chorioamnionitis.

Connexins (Cx) 43 and 40 play a role in leukocytes recruitment in acute inflammation. They are expressed in the endothelial cells. They are also found in the placenta and involved in the placenta development. Acute chorioamnionitis is associated with an increased risk of adverse perinatal outcomes. The aim of this study was to determine the expressions of Cx43 and Cx40 in the placenta of mothers with acute chorioamnionitis, and to correlate their association with the severity of chorioamnionitis and adverse perinatal outcomes. This study comprised a total of 81 cases, consisting of 39 placenta samples of mothers with acute chorioamnionitis and 42 non-acute chorioamnionitis controls. Cx43 and Cx40 immunohistochemistry were performed on all cases and their expressions were evaluated on cytotrophoblasts, syncytiotrophoblasts, chorionic villi endothelial cells, stem villi endothelial cells, maternal endothelial cells and decidua of the placenta. Primigravida has a significantly higher risk of developing acute chorioamnionitis (p < 0.001). Neonates of mothers with a higher stage of fetal inflammatory response was significantly associated with lung complications (p = 0.041) compared to neonates of mothers with a lower stage. The expression of Cx40 was significantly higher in fetal and maternal vascular endothelial cells in acute chorioamnionitis (p < 0.001 and p = 0.037, respectively) compared to controls. Notably, Cx43 was not expressed in most of the types of cells in the placenta, except for decidua. Both Cx43 and Cx40 expressions did not have correlation with the severity of acute chorioamnionitis and adverse perinatal outcomes. Cx40 was overexpressed in the fetal and maternal vascular endothelial cells in the placenta of mothers with acute chorioamnionitis, and it may have a role in the development of inflammation in placenta.

Placental pathology and neonatal morbidity: exploring the impact of gestational age at birth

AimTo evaluate placental pathology in term and post-term births, investigate differences in clinical characteristics, and assess the risk of adverse neonatal outcome.MethodsThis prospective observational study included 315 singleton births with gestational age (GA) > 36 weeks + 6 days meeting the local criteria for referral to placental histopathologic examination. We applied the Amsterdam criteria to classify the placentas. Births were categorized according to GA; early-term (37 weeks + 0 days to 38 weeks + 6 days), term (39 weeks + 0 days to 40 weeks + 6 days), late-term (41 weeks + 0 days to 41 weeks + 6 days), and post-term births (≥ 42 weeks + 0 days). The groups were compared regarding placental pathology findings and clinical characteristics. Adverse neonatal outcomes were defined as 5-minute Apgar score < 7, umbilical cord artery pH < 7.0, admission to the neonatal intensive care unit or intrauterine death. A composite adverse outcome included one or more adverse outcomes. The associations between placental pathology, adverse neonatal outcomes, maternal and pregnancy characteristics were evaluated by logistic regression analysis.ResultsLate-term and post-term births exhibited significantly higher rates of histologic chorioamnionitis (HCA), fetal inflammatory response, clinical chorioamnionitis (CCA) and transfer to neonatal intensive care unit (NICU) compared to early-term and term births. HCA and maternal smoking in pregnancy were associated with adverse outcomes in an adjusted analysis. Nulliparity, CCA, emergency section and increasing GA were all significantly associated with HCA.ConclusionsHCA was more prevalent in late and post-term births and was the only factor, along with maternal smoking, that was associated with adverse neonatal outcomes. Since nulliparity, CCA and GA beyond term are associated with HCA, this should alert the clinician and elicit continuous intrapartum monitoring for timely intervention.

Histological chorioamnionitis and pathological stages on very preterm infant outcomes.

Histological chorioamnionitis (HCA) is a condition linked to preterm birth and neonatal infection and its relationship with various pathological stages in extremely preterm neonates, and with their associated short- and long-term consequences, remains a subject of research. This study investigated the connection between different pathological stages of HCA and both short-term complications and long-term outcomes in preterm infants born at or before 32 weeks of gestational age. Preterm infants born at ≤ 32 weeks of gestation who underwent placental pathology evaluation and were followed-up at 18-24 months of corrected age were included. Neonates were classified based on their exposure to HCA and were further subdivided into different groups according to maternal inflammatory responses (MIR) and fetal inflammatory responses (FIR) stages. We compared short-term complications during their hospital stay between the HCA-exposed and -unexposed groups and examined the influence of HCA stages on long-term outcomes. The HCA group exhibited distinct characteristics such as higher rates of premature rupture of membranes > 18 h, reduced amniotic fluid, early-onset sepsis, bronchopulmonary dysplasia and intraventricular haemorrhage (IVH) grades III-IV (P < 0.05). The moderate-severe HCA group displayed lower gestational age, lower birth weight and higher incidence of IVH (grades III-IV) and preterm sepsis compared with the mild HCA group (P < 0.05). After adjusting for confounders, the MIR stages 2-3 group showed associations with cognitive impairment and cerebral palsy (P < 0.05), and the FIR stages 2-3 group also showed poor long-term outcomes and cognitive impairment (P < 0.05). Moderate-severe HCA was associated with increased early-onset sepsis, severe IVH and poor long-term outcomes, including cognitive impairment and cerebral palsy. Vigilant prevention strategies are warranted for severe HCA cases in order to mitigate poorer clinical outcomes.

Soluble urokinase plasminogen activator receptor in vaginally collected amniotic fluid predicting fetal inflammatory response syndrome: a prospective cohort study

BackgroundImproving noninvasive antenatal diagnosis of fetal inflammatory response syndrome (FIRS) can assist in the evaluation of prenatal risk and reduce perinatal outcomes. This study aimed to determine whether soluble urokinase-type plasminogen activator receptor (suPAR) in vaginally collected amniotic fluid is significant in identifying FIRS after preterm premature rupture of membranes before 34 weeks of gestation.MethodsThis was a prospective cohort study of 114 pregnant women and their newborns after preterm premature rupture of membranes at 22–34+6 weeks of gestation. SuPAR was evaluated using an enzyme-linked immunosorbent assay in vaginally collected amniotic fluid. Patients were classified according to the presence or absence of FIRS. FIRS was defined by umbilical cord blood interleukin-6 level > 11 pg/mL or histological funisitis. The data were analyzed using the R package (R–4.0.5).ResultsSuPAR was detected in all amniotic fluid samples with a median of 26.23 ng/mL (interquartile range (IQR), 15.19–51.14). The median level of suPAR was higher in the FIRS group than in the non-FIRS group, 32.36 ng/mL (IQR, 17.27–84.16) vs. 20.46 ng/mL (IQR, 11.49–36.63) (P = 0.01), respectively. The presence of histological chorioamnionitis significantly increased the suPAR concentration in the FIRS group (P < 0.001). The areas under the curve for FIRS and FIRS with histological chorioamnionitis were 0.65 and 0.74, respectively, with an optimum cutoff value of 27.60 ng/mL. Controlling for gestational age, the cutoff of suPAR more than 27.60 ng/mL predicted threefold higher odds for FIRS and sixfold higher odds for FIRS with histologic chorioamnionitis.ConclusionSoluble urokinase-type plasminogen activator receptor in vaginally obtained amniotic fluid may assist in evaluating prenatal risk of FIRS in patients after preterm premature rupture of membranes before 34 weeks of gestation.

Recognition of Chorioamnionitis on the Cardiotocograph (CTG): The role of the “Chorio Duck Score”

Chorioamnionitis refers to the inflammation of the chorion and amnion by the bacteria and their toxins as well as by the inflammatory cytokines. Therefore, it is a fetal disease with the bacteria, their toxins as well as the fetal immunological responses involving inflammatory cytokines (interleukins, interferons, and tumour necrosis factor-alpha) exerting their detrimental effects within the fetal compartment (i.e., amniotic fluid, fetal membranes, the placenta, and fetal tissues and organs). The vast majority of fetal inflammation occurs as a result of an ascending infection (i.e., entry of the bacteria from the maternal genital tract through the cervix). Therefore, maternal signs (tachycardia and pyrexia) may not be observed until the late stages of the disease. Cardiotocograph (CTG) trace was introduced into clinical practice in the 1960s as a tool to timely recognise ongoing fetal hypoxic stress so that immediate action could be taken to avoid hypoxic ischaemic encephalopathy (HIE) and/ or intrapartum hypoxia-related perinatal deaths. Unfortunately, the CTG was introduced into clinical practice without any prior randomised controlled trials, which resulted in panicking and reacting to the observed morphology of fetal heart rate decelerations, which reflect an ongoing fetal compensatory response to reduce the myocardial workload. A sudden and reflex reduction of the heart rate in response to ongoing intermittent hypoxic stress (i.e., repetitive compression of the umbilical cord or interruptions in uteroplacental oxygenation due to uterine contractions) would ensure a reduction in myocardial oxygen demand and maintenance of aerobic metabolism to avoid the onset of anaerobic metabolism and production of lactic acid within the myocardium. Lack of understanding of fetal compensatory responses resulted in the illogical approach of grouping arbitrary features into different categories and then randomly combining them to classify the CTG traces into “Normal, Suspicious, and Pathological”. The same parameters were used in fetuses with chorioamnionitis with an alternative, inflammatory pathway of neurological injury. The international consensus guidelines of physiological interpretation of CTG produced by 44 CTG experts from 14 countries in 2018 ensured a paradigm shift and recommended classification of CTG traces based on the type of fetal hypoxia and fetal response to stress, by applying the knowledge of fetal physiology whilst interpreting CTG traces. During the last 5 years, research has highlighted CTG features in fetal neuro-inflammation, which include an absence of fetal heart rate cycling, the ZigZag Pattern, and sinusoidal patterns. The proposed “Chorio Duck Score” is a scoring system based on recently published scientific evidence on CTG features in subclinical and clinical chorioamnionitis to enable timely diagnosis of fetal systemic inflammatory response syndrome (FIRS). This will help avoid the continuation of super-imposed hypoxic stress (i.e., progressive increasing frequency, duration, and strength of uterine contractions) on the background fetal inflammation, to prevent fetal neurological injury.

Prenatal exposure to intra-amniotic infection with Ureaplasma species increases the prevalence of bronchopulmonary dysplasia

Objectives The present study investigated the relationship between bronchopulmonary dysplasia (BPD) and intra-amniotic infection with Ureaplasma species. Methods This was a single-center, retrospective cohort study. Patients with singleton pregnancies who underwent inpatient management at our department for preterm premature rupture of membranes (PPROM), preterm labor, cervical insufficiency, and asymptomatic cervical shortening at 22–33 gestational weeks were included. Amniocentesis was indicated for patients with PPROM or an elevated maternal C-reactive protein level (≥0.58 mg/dL). Patients with an amniotic fluid IL-6 concentration ≥3.0 ng/mL were diagnosed with intra-amniotic inflammation, while those with positive aerobic, anaerobic, M. hominis, and Ureaplasma spp. cultures were diagnosed with microbial invasion of the amniotic cavity (MIAC). Patients who tested positive for both intra-amniotic inflammation and MIAC were considered to have intra-amniotic infection. An umbilical vein blood IL-6 concentration >11.0 pg/mL indicated fetal inflammatory response syndrome (FIRS). The maternal inflammatory response (MIR) and fetal inflammatory response (FIR) were staged using the Amsterdam Placental Workshop Group Consensus Statement. Results Intra-amniotic infection with Ureaplasma spp. was diagnosed in 37 patients, intra-amniotic infection without Ureaplasma spp. in 28, intra-amniotic inflammation without MIAC in 58, and preterm birth without MIR/FIR and FIRS in 86 as controls. Following an adjustment for gestational age at birth, the risk of BPD was increased in patients with intra-amniotic infection with Ureaplasma spp. (adjusted odds ratio: 10.5; 95% confidence interval: 1.55–71.2), but not in those with intra-amniotic infection without Ureaplasma spp. or intra-amniotic inflammation without MIAC. Conclusion BPD was only associated with intra-amniotic infection with Ureaplasma species.

Prevalence of Fetal Inflammatory Response Syndrome and Villitis of Unknown Etiology in the Placenta of Saudi Women and Their Association with Baby Sex.

Long-term health consequences are influenced by circumstances that occur during pregnancy. The convergence of the maternal and fetal circulations occurs in the placenta, which is the first organ to develop. Placental pathology provides an accurate diagnosis of amniotic sac inflammation, and pathological alterations in preterm placentas provide evidence for the causes of numerous perinatal pathologies, including spontaneous preterm births. This retrospective study aimed to re-examine placentas regarded as normal by the Obstetrics and Gynecology Department at our institution. Thirty-seven male and forty-seven female placentas were collected following full-term delivery, and the grading and staging of any evident inflammatory responses were evaluated and correlated with the babies' sex. Full-thickness placental samples that were considered normal and not sent to the histopathology department were obtained from the central and marginal regions of placental discs. Morphological examination of the fresh placenta was conducted, and fetal and maternal inflammatory response syndromes were assessed. In addition, placental villitis of unknown etiology (VUE) and chronic deciduitis were evaluated. Immunohistochemistry was performed to evaluate the patterns of inflammation in the placenta using anti-CD8 and anti-CD68 antibodies. The correlation between silent pathologies and clinical complications or the development of fetal inflammatory response syndrome was measured. In this study, 17 (20%) maternal and 10 (12%) fetal samples showed inflammatory responses. The frequencies of chronic deciduitis and VUE were higher among pregnant Saudi women than previously reported, probably because fetal inflammatory response syndrome goes unnoticed in Saudi Arabia. In addition, the prevalence of fetal and maternal inflammatory responses was higher in the placentas of the mothers of males than in those of females, suggesting that differences occur in the inflammatory response in the placenta depending on the sex of the newborn. Grading placental inflammation (in cases of VUE) typically predicts the degree of maternal anti-fetal cellular rejection; therefore, increasing the number of placental samples sent for microscopic inspection may be preferable because of their significance in identifying the causes of chronic disorders.

Risk Factors and Mortality in Newborns with Persistent Pulmonary Hypertension: A Six-Year Single-Center Experience.

Persistent pulmonary hypertension (PPHT) of the newborn is a disorder of circulatory transition resulting in high pulmonary vascular resistance with extrapulmonary right-to-left shunts causing hypoxemia. In this study, our aim was to evaluate the risk factors, administered treatments, and mortality of patients followed in our neonatal intensive care unit (NICU) due to PPHT over the past six years. Patients diagnosed with PPHT and followed in the NICU between January 2017 and November 2022 were included in the study. The sociodemographic characteristics, diagnoses that could lead to pulmonary hypertension, the presence of congenital anomalies, the duration of respiratory support treatment and hospital follow-up, treatments administered for PPHT, and mortality rates were evaluated. Out of 21 patients diagnosed with persistent pulmonary hypertension, 9 of them (42.9%) were male. The mean gestational age of the patients was 37.6±3.7 weeks, and their birth weight was 3006±819grams. The APGAR scores at 1 and 5 minutes were 4(2-7) and 6(3-8), respectively. Risk factors during the antenatal period included fetal distress (38.1%), oligohydramnios (23.8%), intrauterine growth restriction (23.8%), gestational diabetes (14.3%), preeclampsia (4.8%), and chorioamnionitis (4.8%). The median duration of invasive mechanical ventilation for cases requiring respiratory support was 20.1 days, while the median duration of non-invasive ventilation was 3.7 days. Patients with a diagnosis of persistent pulmonary hypertension were treated with inhaled nitric oxide (iNO) in 76.2% of cases, milrinone in 66.7% of cases, sildenafil in 52.4% of cases, and iloprost in 14.3% of cases. The length of hospital stay for patients was 38.4 days, and 9 (42.9%) patients died. The patients who died had severe PPHT along with fetal inflammatory response syndrome (FIRS), congenital heart disease, pulmonary hypoplasia, pneumothorax, hypoxic-ischemic encephalopathy (HIE), and congenital anomalies. Persistent pulmonary hypertension, characterized by severe hypoxemia, is a neonatal emergency that necessitates early intervention, effective treatment of the underlying cause to prevent potential short-term and long-term morbidities and mortality. Effective treatment of the underlying cause in patients diagnosed with PPHT could reduce morbidity and mortality. It is inevitable to avoid the loss of patients with major abnormalities, severe comorbidities, and unpreventable organ dysfunctions.

Fetal inflammatory response spectrum: mapping its impact on severity of necrotising enterocolitis.

Fetal inflammatory response spectrum: mapping its impact on severity of necrotising enterocolitis.