Fetal Stress Research Articles

Role of Inflammation Markers and Osteopontin in the Prediction of Fetal Stress

Role of Inflammation Markers and Osteopontin in the Prediction of Fetal Stress

Maternal Obesity Alters Placental and Umbilical Cord Plasma Oxidative Stress, a Cross-Sectional Study.

Maternal obesity has been shown to impair the oxidative status in the placenta and newborns, potentially leading to adverse pregnancy outcomes and long-term effects on the programming of offspring metabolic status. This study aimed to investigate the impact of maternal obesity on maternal and umbilical cord plasma oxidative status, as well as placental oxidative adaptation. Maternal obesity (n = 20), defined as a pre-pregnancy BMI ≥ 25 kg/m2, and maternal leanness (n = 20), defined as a pre-pregnancy BMI < 23 kg/m2, were the group categories used in this study. Both groups were matched according to gestational age at delivery. Maternal blood, umbilical cord blood, and placental tissue were collected to assess nutritional content (cholesterol, triglyceride, and protein), oxidative stress markers (MDA and protein carbonyl), and antioxidant activity (SOD and catalase). Placental protein expression (SOD2, catalase, UCP2, and Nrf2) was evaluated using Western blot analysis. Catalase activity in maternal plasma significantly increased in the maternal obesity group (p = 0.0200), with a trend toward increased MDA and protein carbonyl levels. In umbilical cord plasma, triglyceride, protein carbonyl, and catalase activity were significantly elevated in the maternal obesity group compared with the lean controls (p = 0.0482, 0.0291, and 0.0347, respectively). Placental protein expression analysis revealed significantly decreased SOD2 (p = 0.0011) and catalase (p < 0.0001), along with Nrf2 downregulation (p < 0.0001). An increase in mitochondrial antioxidant UCP2 expression was observed (p = 0.0117). The neonatal protein carbonyl levels positively correlated with placental protein carbonyl (r = 0.7405, p < 0.0001) and negatively correlated with maternal catalase activity (r = -0.4332, p = 0.0052). This study thus provides evidence that maternal obesity is associated with placental and fetal oxidative stress, alongside a concurrent increase in placental antioxidant UCP2 expression.

Clinicopathological Insights to the Nerve Growth Factor NGF Associated Stress Response in Pregnancy and Therapeutic Potential in Fetal Neurodevelopment

The nerve growth factor has a significant role in fetal neurogenesis and sustaining pregnancy. Objectives: To investigate the effects of nerve growth factor in stress response during pregnancy on developing fetus to bring clinicopathological correlation on the role of nerve growth factor in maternal stress markers (cortisol levels, glucocorticoids, depression, anxiety, and brain-derived neurotrophic factor levels) and fetal brain development. Methods: Following PRISMA guidelines, this study was extracted from PubMed, ScienceDirect, Nature, and Google Scholar articles from January 2014 to April 2024. The examination of pregnant women in published research gave a possibility to understand the application of nerve growth factor as a suitable biomarker for brain stress and fetal neuronal development. To exclude studies with lower ranks, each of the selected studies was assessed for adherence to evidence-based research methodology. The studies were taken from China, Europe, America and South Asia (including Pakistan). Results: Increased nerve growth factor levels were associated with maternal stress reactions which caused changes in cortisol levels and the amygdaloidal complex area. However, the increased nerve growth factor level was linked to changes in the fetal brain such as the weight of the fetal brain and stress biomarkers in the amniotic fluid sample inferring a critical role in the modulation of maternal stress on the fetal neurodevelopmental spheres. Conclusions: It was concluded that it is important to note how stress and nerve growth factors interact during pregnancy to create effective interventions to reduce stress dependence for the better health of both the mother and child.

Surveillance fœtale : limites actuelles et nouvelles pistes basées sur l’analyse du système nerveux autonome fœtal

ObjectiveCurrently, fetal monitoring during labor is based on visual analysis of the fetal heart rate (FHR). This test is imperfect, with high intra- and inter-observer variability and a moderate to poor prediction of the occurrence of neonatal acidosis or anoxic-ischaemic encephalopathy. In situations where there is an intermediate risk of acidosis, it is possible to use second-line tests such as blood scalp sampling (with pH or lactate measurement) or ST segment analysis of the fetal ECG. However, these invasive tests have many limitations and their place is debated. Some authors suggest a more physiological approach to FHR assessment. The main actor in maintaining fetal homeostasis is the autonomic nervous system (ANS). Its activity can be assessed by analysing heart rate variability (HRV). The aim is to assess whether HRV can be used to identify situations at risk of acidosis. Materials and methodsOur team has developed an index, the Fetal Stress Index, to measure HRV. To test it in a situation of acidosis, we used a pregnant ewe model. We also developed in parallel a human fetal ECG recording system. ResultsIn our experimental model, we have shown that this index reflects variations in the parasympathetic system and correlates with the onset of acidosis. As its use in clinical practice requires the acquisition of a beat-to-beat FHR signal, we have also developed an abdominal patch that allows highly accurate analysis of the fetal ECG. ConclusionThe future is therefore to validate the FSI as a marker of acidosis in a prospective cohort using the signal obtained from our patch. This could be a new tool for fetal monitoring during labor.

Gestational DNA methylation age as a marker for fetal development and birth outcomes: findings from the Boston Birth Cohort

BackgroundGestational DNA methylation age (GAmAge) has been developed and validated in European ancestry samples. Its applicability to other ethnicities and associations with fetal stress and newborn phenotypes such as inflammation markers are still to be determined. This study aims to examine the applicability of GAmAge developed from cord blood samples of European decedents to a racially diverse birth cohort, and associations with newborn phenotypes.MethodsGAmAge based on 176 CpGs (Haftorn GAmAge) was calculated for 940 children from a US predominantly urban, low-income, multiethnic birth cohort. Cord blood DNA methylation was profiled by Illumina EPIC array. Newborn phenotypes included anthropometric measurements and, for a subset of newborns (N = 194), twenty-seven cord blood inflammatory markers (sandwich immunoassays).ResultsGAmAge had a stronger correlation with GEAA in boys (r = 0.89, 95% confidence interval (CI) [0.87,0.91]) compared with girls (r = 0.83, 95% CI [0.80,0.86]), and was stronger among extremely preterm to very preterm babies (r = 0.91, 95% CI [0.81,0.96]), compared with moderate (r = 0.48, 95% CI [0.34,0.60]) and term babies (r = 0.58, 95% CI [0.53,0.63]). Among White newborns (N = 51), the correlation between GAmAge vs. GEAA was slightly stronger (r = 0.89, 95% CI [0.82,0.94]) compared with Black/African American newborns (N = 668; r = 0.87, 95% CI [0.85,0.89]) or Hispanic (N = 221; r = 0.79, 95% CI [0.74,0.84]). Adjusting for GEAA and sex, GAmAge was associated with anthropometric measurements, cord blood brain-derived neurotrophic factor (BDNF), and monocyte chemoattractant protein-1 (MCP-1) (p < 0.05 for all).ConclusionsGAmAge estimation is robust across different populations and racial/ethnic subgroups. GAmAge may be utilized as a proxy for GEAA and for assessing fetus development, indicated by inflammatory state and birth outcomes.

Effects of high-intensity resistance training associated with an obesogenic diet on placental and hepatic oxidative stress in fetuses and pregnant rats

Effects of high-intensity resistance training associated with an obesogenic diet on placental and hepatic oxidative stress in fetuses and pregnant rats

Biochemical analysis of catecholamine and cortisol for the evaluation of the fetal distress in third trimester stillbirths

BackgroundStress hormones like catecholamine and cortisol are thought to reflect the magnitude of physical stress in adults and were studied in relationship to the cause of death and agony time. Intrauterine distress, intrapartum events, and modes of delivery can affect the fetal endocrine stress response, as reflected by biochemical analyses. The aim of the present study was to evaluate the role of catecholamines and cortisol as markers of ante-mortem fetal distress. The role of cortisol as a marker of circadian timing of delivery was also assessed.MethodsA 2-year prospective cohort-comparison inclusion of stillbirths and newborns took place with collection of antemortem data, labor parameters, neonatal outcome, post-mortem data and blood samples. Stillbirths were classified as acute or chronic on the basis of a multidisciplinary evaluation. Heart blood of stillbirths and cord blood of newborns were analyzed by high pressure liquid chromatography (HPLC) for adrenaline and noradrenaline and by immunoassay for cortisol determination.ResultsFifteen stillbirths and 46 newborns, as a comparison group, delivered by spontaneous vaginal birth, elective, and emergency cesarean sections were included. Stillbirths’ main cause of death was cord thrombosis. Levels of adrenaline and noradrenaline (median: 14,188 pg/ml and 230.5 pg/ml, respectively) were significantly higher (p < 0.001) in stillbirths than in newborns and were also higher in acute compared to chronic distress. Cortisol levels were significantly higher (p < 0.05) in spontaneous vaginal delivery (median: 18.2 μg/dl) compared to elective cesarean sections (median: 3.8 μg/dl). No difference in cortisol concentrations was detected between newborns delivered at morning and at afternoon/evening.ConclusionOur results suggest that the biochemical measurement of adrenaline and noradrenaline levels might reflect a marked physical stress response during the process of death in stillbirths. On the contrary, the elevation of cortisol levels could mirror the elevation in maternal cortisol level during vaginal delivery. For the post-mortem evaluation of stillbirths, the analysis of CA levels could provide additional data on the duration of distress, useful to integrate the forensic diagnosis.

Clinical approach to a rare case of hydrallantois in bitch

AbstractThe present case describes the clinical, sonographic and histopathological findings of hydrallantois in bitch. After 55 days of the first mating, nulliparous Golden Retriever bitch was presented with a primary complaint of perceptible abdominal distension and dyspnoea for the last 3‒4 days. Ultrasonography revealed marked uterine distension with well appreciable anechoic to hypoechoic allantoic regions along with fetal stress. During caesarean section, a cumulative 2.75 L of placental fluid was recovered from allantoic portion with an altered electrolyte profile in comparison to maternal plasma. The histopathology examination of one fetal kidney corroborated tubular degeneration, suggesting nephrosis to be the concomitant aetiology. In conclusion, the clinical examination and ultrasonography provided provisional diagnosis of the condition; caesarean section proved to be an ideal option in order to prevent the dystocia or any other complication during whelping in a bitch even if none of the puppies survived. This approach, with supportive therapy ensures comprehensive care post‐treatment.

Does Pelvic Floor Muscle Exercise Change the Hemodynamic Responses of the Inferior Vena Cava in Pregnant Women? A Prospective-Controlled Study.

This study was aimed at exploring the immediate impacts of pelvic floor muscle exercises (PFMEs) on various maternal physiological parameters in pregnant women. The study included a total of 52 women, 26 pregnant (Pregnant group: 28.04±6.01 years; 26.83±3.81 kg/m2) and 26 nonpregnant (Control group: 29.42±5.73 years; 25.41±3.03 kg/m2) individuals. All women received PFME as follows: PFME was performed for 5 min (6-s holding contraction, 10 s of relaxation, 3 rapid PFM contractions). Evaluations were conducted before, immediately after, and 5 min post-exercise, with measurements including inferior vena cava (IVC) diameters and pulsatility index, blood pressure, oxygen saturation, and heart rates. Two-way analysis of variance was performed for group and time comparisons in repeated measurements. In both groups, the IVC collapsibility index values were lower 5 min after exercise, although this decrease, although clinically significant, did not reach statistical significance (p= 0.057). Post-exercise systolic blood pressure significantly decreased in both groups, whereas diastolic blood pressure decreased significantly in the pregnant group (p= 0.001, p= 0.023). The study found no statistically significant changes in the collapsibility index of the IVC after PFME but observed a clinically suggestive decrease. The clinical decrease in the collapsibility index can be interpreted as PFME in the supine position increasing venous return. Additionally, PFME was found not to alter maternal and fetal heart rates but contributed to the decrease in maternal systolic and diastolic blood pressure. Our study supports the view that the acute effects of PFME neither induce fetal stress nor pose maternal risks.

A DIO2 missense mutation and its impact on fetal response to PRRSV infection

BackgroundPorcine reproductive and respiratory syndrome virus 2 (PRRSV-2) infection during late gestation substantially lowers fetal viability and survival. In a previous genome-wide association study, a single nucleotide polymorphism on chromosome 7 was significantly associated with probability of fetuses being viable in response to maternal PRRSV-2 infection at 21 days post maternal inoculation. The iodothyronine deiodinase 2 (DIO2) gene, located ~ 14 Kilobase downstream of this SNP, was selected as a priority candidate related to fetal susceptibility following maternal PRRSV-2 infection. Our objectives were to identify mutation(s) within the porcine DIO2 gene and to determine if they were associated with fetal outcomes after PRRSV-2 challenge. Sequencing of the DIO2, genotyping identified variants, and association of DIO2 genotypes with fetal phenotypes including DIO2 mRNA levels, viability, survival, viral loads, cortisol and thyroid hormone levels, and growth measurements were conducted.ResultsA missense variant (p.Asn91Ser) was identified in the parental populations from two independent PRRSV-2 challenge trials. This variant was further genotyped to determine association with fetal PRRS outcomes. DIO2 mRNA levels in fetal heart and kidney differed by the genotypes of Asn91Ser substitution with significantly greater DIO2 mRNA expression in heterozygotes compared with wild-type homozygotes (P < 0.001 for heart, P = 0.002 for kidney). While Asn91Ser did not significantly alter fetal viability and growth measurements, interaction effects of the variant with fetal sex or trial were identified for fetal viability or crown rump length, respectively. However, this mutation was not related to dysregulation of the hypothalamic-pituitary-adrenal and thyroid axis, indicated by no differences in circulating cortisol, T4, and T3 levels in fetuses of the opposing genotypes following PRRSV-2 infection.ConclusionsThe present study suggests that a complex relationship among DIO2 genotype, DIO2 expression, fetal sex, and fetal viability may exist during the course of fetal PRRSV infection. Our study also proposes the increase in cortisol levels, indicative of fetal stress response, may lead to fetal complications, such as fetal compromise, fetal death, or premature farrowing, during PRRSV infection.

Comparative Effects of Target-Controlled Infusion of Propofol Versus Spinal and Thiopental-Sevoflurane Anesthesia on Lipid Peroxidation in Elective Cesarean Section: A Prospective, Open-Label Study.

During pregnancy, physiological changes can increase oxidative stress (OS) in both mothers and fetuses. The use of anesthesia for cesarean sections (CSs) could exacerbate this stress due to its impact on the ischemia-reperfusion effect. Our study aimed to explore the effects of target-controlled infusion of propofol on OS during CSs, and to compare these effects with those of spinal and thiopental-sevoflurane anesthesia. The study included ninety parturients undergoing elective CS, allocated into three groups: Group S (spinal) (n = 30), Group P (propofol) (n = 30), and Group TS (thiopental-sevoflurane) (n = 30). Venous blood samples were taken from mothers at three time points, before, during, and after surgery, and one sample was taken from the umbilical vein after delivery. Blood samples were analyzed with the thiobarbituric acid reactive substances (TBARS) assay and blood gas analysis. A statistical comparison between groups was obtained by one-way analysis of variance (ANOVA) and the Wilcoxon test where appropriate. Levels of TBARS after the induction of anesthesia were lower in all groups compared to values preoperatively. In Group P, TBARS levels started to decrease in the first five minutes after the induction (1.90 ± 0.47; P < 0.001) and had significantly lower values compared to Group S (2.22 ± 0.21) and Group TS (2.40 ± 0.20). Two hours after surgery, TBARS values were the lowest in Group P (1.76 ± 0.15, P<0.001), compared to Group S (2.18 ± 0.24) and Group TS (2.41 ± 0.21). TBARS value in umbilical venous blood was significantly lower in Group P (1.56 ± 0.16, P < 0.001) compared to Group S (2.18 ± 0.17) and Group TS (2.09 ± 0.09). Umbilical cord venous blood gas values (pH, PCO2, HCO3, lactates, and base excess (BE)) were not different between the groups, except for PO2, which was significantly lower in Group S (20.5 ± 5.0; P < 0.001) compared to Group P (36.5 ± 19.2) and Group TS (33.5 ± 10.1). Target-controlled infusion of propofol anesthesia could beadvantageous for parturients with compromised oxidative status, especially those undergoing emergency CSs when general anesthesia is required.

Prenatal Hypoxia Triggers a Glucocorticoid-Associated Depressive-like Phenotype in Adult Rats, Accompanied by Reduced Anxiety in Response to Stress.

Fetal hypoxia and maternal stress frequently culminate in neuropsychiatric afflictions in life. To replicate this condition, we employed a model of prenatal severe hypoxia (PSH) during days 14-16 of rat gestation. Subsequently, both control and PSH rats at 3 months old were subjected to episodes of inescapable stress to induce learned helplessness (LH). The results of the open field test revealed an inclination towards depressive-like behavior in PSH rats. Following LH episodes, control (but not PSH) rats displayed significant anxiety. LH induced an increase in glucocorticoid receptor (GR) levels in extrahypothalamic brain structures, with enhanced nuclear translocation in the hippocampus (HPC) observed both in control and PSH rats. However, only control rats showed an increase in GR nuclear translocation in the amygdala (AMG). The decreased GR levels in the HPC of PSH rats correlated with elevated levels of hypothalamic corticotropin-releasing hormone (CRH) compared with the controls. However, LH resulted in a reduction of the CRH levels in PSH rats, aligning them with those of control rats, without affecting the latter. This study presents evidence that PSH leads to depressive-like behavior in rats, associated with alterations in the glucocorticoid system. Notably, these impairments also contribute to increased resistance to severe stressors.

Analysis of Maternal and Fetal Oxidative Stress During Delivery with Epidural Analgesia

Childbirth is a stressful event for mothers, and labor epidural analgesia (LEA) may reduce mental stress. Mental stressors include labor pain, fear, and anxiety, which induce oxidative stress. In this study, we focused on oxidative stress during delivery and conducted a cross-sectional analysis of maternal and fetal oxidative stress. The participants included 15 women who received LEA (LEA group) and 15 who did not (No LEA group). Participants with a gestational age of < 37 weeks, BMI of ≥ 35 kg/m2, cerebrovascular or cardiovascular complications, multiple pregnancies, gestational hypertension, gestational diabetes, chronic hypertension, thyroid disease, birth weight of < 2,500 g, emergency cesarean section, or cases in which epidural anesthesia was re-administered during delivery were excluded from the study. Maternal blood was collected on admission, and immediately after delivery, and umbilical artery blood was collected from the fetus. The oxidative stress status was assessed by measuring diacron-reactive oxygen metabolite (an index of the degree of lipid peroxide oxidation), biological antioxidant potential (an index of antioxidant capacity) and calculating the ratio of BAP/d-ROMs (an index of the oxidative stress). The results showed that maternal oxidative stress immediately after delivery was lower in the LEA group than in the No LEA group. Moreover, the fetuses experienced less oxidative stress in the LEA group than in the No LEA group. Taken together, these results suggest that LEA may reduce maternal and fetal oxidative stress associated with childbirth.

Asparagine Synthetase Marks a Distinct Dependency Threshold for Cardiomyocyte Dedifferentiation.

Adult mammalian cardiomyocytes have limited proliferative capacity, but in specifically induced contexts they traverse through cell-cycle reentry, offering the potential for heart regeneration. Endogenous cardiomyocyte proliferation is preceded by cardiomyocyte dedifferentiation (CMDD), wherein adult cardiomyocytes revert to a less matured state that is distinct from the classical myocardial fetal stress gene response associated with heart failure. However, very little is known about CMDD as a defined cardiomyocyte cell state in transition. Here, we leveraged 2 models of in vitro cultured adult mouse cardiomyocytes and in vivo adeno-associated virus serotype 9 cardiomyocyte-targeted delivery of reprogramming factors (Oct4, Sox2, Klf4, and Myc) in adult mice to study CMDD. We profiled their transcriptomes using RNA sequencing, in combination with multiple published data sets, with the aim of identifying a common denominator for tracking CMDD. RNA sequencing and integrated analysis identified Asparagine Synthetase (Asns) as a unique molecular marker gene well correlated with CMDD, required for increased asparagine and also for distinct fluxes in other amino acids. Although Asns overexpression in Oct4, Sox2, Klf4, and Myc cardiomyocytes augmented hallmarks of CMDD, Asns deficiency led to defective regeneration in the neonatal mouse myocardial infarction model, increased cell death of cultured adult cardiomyocytes, and reduced cell cycle in Oct4, Sox2, Klf4, and Myc cardiomyocytes, at least in part through disrupting the mammalian target of rapamycin complex 1 pathway. We discovered a novel gene Asns as both a molecular marker and an essential mediator, marking a distinct threshold that appears in common for at least 4 models of CMDD, and revealing an Asns/mammalian target of rapamycin complex 1 axis dependency for dedifferentiating cardiomyocytes. Further study will be needed to extrapolate and assess its relevance to other cell state transitions as well as in heart regeneration.

Controlling fetal stress for preventing adverse health conditions in neonates and children.

Controlling fetal stress for preventing adverse health conditions in neonates and children.

The Relationship of Risk Factors with Preterm Labor at Ummi Bogor Hospital in 2022

Preterm labor causes abnormalities in the baby and perinatal death. The exact cause of preterm labor is not yet known, but maternal and pregnancy risk factors can cause it. This study analyzes the relationship between risk factors and preterm labor at Ummi Bogor Hospital Bogor in 2022. The research method uses an observational analytical design of retrospective case-control design. The population is all mothers at Ummi Bogor Hospital Bogor who gave birth prematurely in 2022, as many as 213 people. Bivariate analysis technique using chi-square test. Respondent characteristics were 64.8% of mothers aged 20-30 years, 60% multipara, 86.9% with singleton pregnancies, 82.2% with HAP, 71.4% with KPD, 75.5% with PEB, and 97.7% with fetal distress. The results of bivariate analysis used che square test of age p values (p = 0.846), p parity (p = 0.161), p game (0.118), p HAP (p = 0.354, p KPD (p = 0.861), p PEB (p = 0.404) and p Fetal distress (p = 0.252). In conclusion, there is no relationship between age, parity, gameli, HAP, KPD, PEB, and fetal stress factors for preterm labor at Ummi Bogor Hospital Bogor in 2022.

The effect of slow-release vaginal dinoprostone on maternal and fetal oxidative stress in term pregnancies complicated by oligohydramnios: Prospective cohort study.

To evaluate changes in oxidant status using thiol/disulfide homeostasis in mothers and fetuses after induction of labor with slow-release vaginal dinoprostone inserts. A total of 70 pregnant women were divided into two groups. Thirty-five women in whom labor was induced with slow-release vaginal dinoprostone inserts (10 mg of prostaglandin E2, group A) were compared before and after the administration. The other 35 women, who were followed up spontaneously during labor (group B), were included as a control group. Both groups were diagnosed with isolated oligohydramnios without signs of placental insufficiency. The thiol/disulfide homeostasis parameters were calculated before medical induction and after removal of the insert at the beginning of the active phase of labor. Maternal and cord blood values were measured in both groups. Although the balance shifted to the antioxidant side after the slow-release vaginal dinoprostone insert was applied, there was no significant difference in maternal oxidative load compared to the pre-application status (5.32 ± 014/5.16 ± 0.15, p = 0.491). Despite the shift toward the antioxidant side, maternal antioxidants were still significantly lower in the group that received slow-release vaginal dinoprostone at the beginning of the active phase of labor than in the control group (295.98 ± 13.03/346.47 ± 12.04, respectively, p = 0.009). There was no statistically significant difference in terms of oxidative balance or newborn Apgar score ( p > 0.05). Induction of labor with slow-release vaginal dinoprostone inserts in pregnancies with isolated oligohydramnios does not cause further oxidative stress and is safe for both mothers and neonates in terms of oxidant load by thiol/disulfide homeostasis.

Measurement of Calprotectin and PTH in the Amniotic Fluid of Early Second Trimester Pregnancies and Their Impact on Fetuses with Growth Disorders: Are Their Levels Related to Oxidative Stress?

Background: During the early stages of human fetal development, the fetal skeleton system is chiefly made up of cartilage, which is gradually replaced by bone. Fetal bone development is mainly regulated by the parathyroid hormone parathormone (PTH) and PTH-related protein, with specific calprotectin playing a substantial role in cell adhesion and chemotaxis while exhibiting antimicrobial activity during the inflammatory osteogenesis process. The aim of our study was to measure the levels of PTH and calprotectin in early second trimester amniotic fluid and to carry out a comparison between the levels observed among normal full-term pregnancies (control group) and those of the groups of embryos exhibiting impaired or enhanced growth. Methods: For the present prospective study, we collected amniotic fluid samples from pregnancies that underwent amniocentesis at 15 to 22 weeks of gestational age during the period 2021–2023. Subsequently, we followed up on all pregnancies closely until delivery. Having recorded fetal birthweights, we then divided the neonates into three groups: small for gestational age (SGA), appropriate for gestational age (AGA), and large for gestational age (LGA). Results: In total, 64 pregnancies, including 14 SGA, 10 LGA, and 40 AGA fetuses, were included in our study. Both substances were detected in early second trimester amniotic fluid in both groups. Concentrations of calprotectin differed significantly among the three groups (p = 0.033). AGA fetuses had a lower mean value of 4.195 (2.415–6.425) IU/mL, whereas LGA fetuses had a higher mean value of 6.055 (4.887–13.950) IU/mL, while SGA fetuses had a mean value of 5.475 (3.400–9.177) IU/mL. Further analysis revealed that only LGA fetuses had significantly higher calprotectin concentrations compared to AGA fetuses (p = 0.018). PTH concentration was similar between the groups, with LGA fetuses having a mean value of 13.18 (9.51–15.52) IU/mL, while SGA fetuses had a mean value of 14.18 (9.02–16.00) IU/mL, and AGA fetuses had similar concentrations of 13.35 (9.05–15.81) IU/mL. The differences in PTH concentration among the three groups were not statistically significant (p = 0.513). Conclusions: Calprotectin values in the amniotic fluid in the early second trimester were higher in LGA fetuses compared to those in the SGA and AGA categories. LGA fetuses can possibly be in a state of low-grade chronic inflammation due to excessive fat deposition, causing oxidative stress in LGA fetuses and, eventually, the release of calprotectin. Moreover, PTH concentrations in the amniotic fluid of early second trimester pregnancies were not found to be statistically correlated with fetal growth abnormalities in either LGA or SGA fetuses. However, the early time of collection and the small number of patients in our study should be taken into account.

Does Health-Care Consolidation Harm Patients? Evidence from Maternity Ward Closures

We study how closures of maternity wards affect maternal and neonatal health. Using data on all hospital births in Sweden between 1990 and 2004, we compare changes in birth-related outcomes across hospital catchment areas that were differently exposed to ward closures. Our findings show that the closures increased maternal obstetric trauma but also decreased fetal stress and infant trauma among newborns. Adverse maternal outcomes are mainly driven by ward overcrowding, whereas increases in travel distance have no distinguishable effects. Positive effects on infant health reflect a shift of births from smaller to larger wards of higher quality. (JEL D24, G34, I11, I12, I18, J13, J16)

EUROPEAN ASSOCIATION OF PERINATAL MEDICINE (EAPM) Position statement: Use of appropriate terminology for situations related to inadequate fetal oxygenation in labor

In high-resource countries, adverse perinatal outcomes are currently rare in term, non-malformed fetuses, undergoing labor, but they remain a leading cause of medico-legal dispute. Precise terminology is important to describe situations related to inadequate fetal oxygenation in labor, to ensure appropriate communication between healthcare professionals and adequate transmission of information to parents. This position statement provides consensus definitions from European perinatologists and midwives regarding the most appropriate terminology to describe situations related to inadequate fetal oxygenation in labor: suspected fetal hypoxia, severe newborn acidemia, newborn metabolic acidosis, and hypoxic-ischemic encephalopathy. It also identifies terms that are imprecise or nonspecific to this situation, and should therefore be avoided by healthcare professionals: fetal well-being, fetal stress, fetal distress, non-reassuring fetal state, and birth asphyxia.