Search Results (50)

Newborn bloodspot screening for one or more lysosomal storage disorders (NBS-LSD) is currently performed by many public health NBS laboratories globally. The screening tests measure activities of selected lysosomal enzymes on dried blood spot (DBS) specimens collected from newborns by the heel stick method Because these assays measure enzyme activity, the quantitative results are dependent on the particular analytical method. DBS quality control (DBS QC) materials with assay-specific certified values that span the relevant range from typical to LSD-affected newborns are an important component of quality assurance in NBS laboratories. The Newborn Screening Quality Assurance Program (NSQAP) at the U.S. Centers for Disease Control and Prevention (CDC) provides public health NBS laboratories with DBS QC sets for NBS-LSD comprising four admixtures of pooled umbilical cord blood and a base pool made from leukodepleted peripheral blood and heat-inactivated serum. To evaluate the suitability of these materials for use with digital microfluidics fluorometry (DMF) assays which can currently measure the activity of four enzymes (acid α-galactosidase (GLA); acid β-glucocerebrosidase (GBA); acid α-glucosidase (GAA); and iduronidase (IDUA)), CDC collaborated with the Newborn Screening Unit at the Missouri State Public Health Laboratory (MSPHL). Using MSPHL criteria, we found that the certified results from each of two DBS QC lots collectively spanned the range from typical (screen negative) to enzyme deficient (screen positive) newborn DBS levels for each of the four lysosomal enzymes measured. The range included borderline results that would require repeat screening of the newborn under the MSPHL protocol. We conclude that these DBS QC preparations are suitable for use as external quality control materials for DMF assays used to detect LSDs in newborns. Full article

Background/Objectives: Neonatal early-onset sepsis (EOS) is a life-threatening condition, and numerous efforts have been invested in identifying the most promising biomarkers for its detection. In this prospective cohort study, we aimed to determine the diagnostic accuracy and optimal cut-off values of procalcitonin (PCT), presepsin, endocan, and interleukin (IL)-6 determined from the neonatal serum (0–12, 24–48, and 72–96 h), and umbilical blood cord for the diagnosis of EOS. Methods: A total of 122 patients were included in this study and were divided into two groups: group 1 (sepsis, n = 68 patients) and group 2 (without sepsis, n = 54 patients). Maternal and neonatal characteristics were assessed using descriptive statistics. Logistic regressions were used to evaluate the association between various biomarkers and the presence of EOS and to adjust for potential confounders. Using sensitivity analysis and Youden’s index from the ROC curve, the biomarkers’ diagnostic accuracy and optimal cut-off values were obtained. Results: PCT at 0–12 and 24–48 h of life exhibited the best diagnostic performance, with sensitivities (Ses) of 75% and 76.5% and specificities (Sps) above 74%. Presepsin demonstrated excellent performance at 24–48 h, with Ses of 68.42%, and Sps of 88.89%. IL-6 and endocan achieved modest results for the detection of EOS. Conclusions: PCT and presepsin measured at early neonatal timepoints demonstrated high diagnostic accuracy and favorable sensitivity–specificity balance for predicting EOS. Full article

Background: Thioredoxin-interacting protein (TXNIP) is a major inhibitor of the thioredoxin (TRX) antioxidant system and an important player in the development and aggravation of intracellular oxidative stress. Although first recognized as a metabolic regulator, recent studies have identified the multifaceted role of this protein in other molecular pathways involving inflammation, apoptosis, and glucose metabolism. Methods: This review aims to highlight the importance of TXNIP in diabetes-related pathophysiology and explore the existing evidence regarding TXNIP’s role in GDM-associated pathogenetic mechanisms, revealing common regulatory pathways. Results: Among other complex diseases, TXNIP has been found upregulated in diabetic pancreatic beta cells, thus contributing to diabetes pathogenesis and its related complications. In addition, depletion of TXNIP has been shown to decrease the negative consequences of excessive stress in various cellular systems and diseases, pointing towards a potential therapeutic target. In line with these findings, TXNIP has been investigated in the pathogenesis of Gestational Diabetes Mellitus (GDM), a common pregnancy complication affecting the mother and the neonate. Overexpression of TXNIP has been found in GDM placentas or trophoblast cell lines mimicking GDM conditions and has been associated with key dysregulated mechanisms of GDM pathophysiology, like oxidative stress, inflammation, apoptosis, impaired autophagy, altered trophoblast behavior, and placental morphology. Interestingly, TXNIP has been found upregulated in GDM maternal serum and downregulated in umbilical cord blood, indicating potential compensatory protective mechanisms to GDM-related oxidative stress. Conclusions: Due to its contribution to the regulation of critical cellular processes such as inflammation, metabolism, and apoptosis, TXNIP finds its place in the pathophysiology of gestational diabetes through a currently limited number of scientific reports. Full article

Down Syndrome or Trisomy 21 (T21) is a complex genetic disease characterized by the presence of an extra chromosome 21, which leads to multiple clinical features and manifestations that severely affect the patient’s quality of life. Various methods of prenatal screening have been developed over time, allowing informed decision-making. However, a common drawback of the current methods for detecting T21 is their invasive nature. Over the past years, mass-spectrometry-based omics technologies have become a key tool for discovering biomarkers for the prenatal screening of T21, particularly focusing on proteins, peptide sequences, or metabolites in samples, like amniotic fluid, umbilical cord blood, and others. Recently, there has been a noticeable shift towards using less invasive biological sample types (e.g., maternal serum, plasma, and urine) reflecting a growing interest in non-invasive methods for prenatal screening. These advances aim to improve the sensitivity and accuracy for T21 detection while reducing the risks associated with more invasive procedures. The first section of this paper offers an in-depth review of studies utilizing mass-spectrometry-based omics for the prenatal screening of T21. This part provides an overview of the methodologies employed and their key findings. Instead, the subsequent section offers a comprehensive examination of the differentially expressed proteins (DEPs) and metabolites (DEMs) reported in the literature in T21 prenatal screening. Additionally, pathway analysis is carried out to explore the biological pathways that these molecules are involved in and how they relate to the clinical features of the syndrome. These findings aim to guide future research in the field and foster the development of more advanced, less invasive prenatal screening techniques for T21. Full article

Background: The timing of delivery depends on the condition of the fetus and the mother’s body, which is reflected in both the incretion of enzymes in the pregnant woman’s body and their use by the developing fetus in the anabolic process. The aim: This work was aimed to analyze the activities of transaminases (aspartate aminotransferase (AST) and alanine aminotransferase (ALT)) and alkaline phosphatase (AlPh) in liquid media (blood serum, amniotic fluid, umbilical cord blood, and placental homogenate) in pregnant women in each trimester of pregnancy and in the postpartum period, considering the timing and type of delivery (term, premature or late delivery, or cesarean section). Methods: Data from studies in non-pregnant (n = 45) and pregnant (n = 193) women, including women in labor with different delivery timings (term, premature, and late) and types of delivery (natural birth or cesarean section), were analyzed. Amniotic fluid, umbilical cord blood, and the placental homogenate were collected during labor. The de Ritis coefficient (AST/ALT) was calculated. Alkaline phosphatase activity was determined using the standard constant-time method using Lahema diagnosticum biotests, and transaminase activity was determined using the colorimetric dinitrophenylhydrazine method, according to Reitman and Frenkel. Outcomes: The highest alkaline phosphatase activity was recorded in the placenta homogenate (6906.2 ± 208.1 U/mL) in pregnant women who gave birth at term. The highest transaminase activity was found in umbilical cord blood and, in particular, in the placenta in pregnant women with premature and late births. Conclusions: The significant role of transaminases and alkaline phosphatase in the transport functions of the histohematic barriers of the mother and fetus was established, which provides a mechanism for the constancy of enzyme levels in blood plasma. Full article

Background: Leptin, a protein predominantly produced by adipocytes, plays a crucial role in regulating energy balance, inflammation, immunity, and fetal growth. During pregnancy, maternal serum leptin levels increase, peaking in the second trimester, with placental production contributing to this rise. Leptin has also been identified in fetal tissues, and its concentration in umbilical cord blood correlates with birth weight. This study aimed to evaluate serum and umbilical cord blood leptin concentrations in rural Burundian women living in marginal nutritional conditions, and investigate potential gender differences in fetal leptin levels. Methods: We analyzed data from 38 healthy singleton pregnancies (20 male and 18 female newborns) delivered at Hôpital Autonome de Ngozi, Burundi. Leptin concentrations were measured in maternal and umbilical cord blood samples. Results: Our results revealed that neonatal leptin levels were significantly higher in female compared to male newborns, consistent with findings in other populations. Leptin concentrations in umbilical cord blood were positively correlated with neonatal birth weight and the Kaup index, while maternal leptin levels did not show such associations. Conclusions: Despite the challenging nutritional environment in this rural African setting, our findings suggest that leptin’s role in fetal growth regulation may transcend maternal nutritional status. The gender difference observed in leptin levels could be linked to genetic or epigenetic factors rather than fat content or reproductive hormones. This study supports the notion that leptin may be an important regulator of fetal development, even in malnourished populations, and underscores the need for further research to elucidate its mechanisms in pregnancy. Full article

Maternal obesity is increasingly recognized as a risk factor for adverse fetal outcomes, primarily through its association with heightened oxidative stress. This study aimed to evaluate oxidative stress markers in umbilical cord blood of neonates born to obese mothers. Sixty-three pregnant women, who were of normal weight at the start of pregnancy but classified as obese at term, were included. Umbilical cord blood samples were collected immediately post-delivery and analyzed for serum oxidative stress markers (total oxidant status (TOS), total antioxidant status (TAS), paraoxanase (PON), aryl esterase, thiol, and catalase activities). Protein interaction networks were generated using Cytoscape (v3.10.3), and the overlapping proteins were further analyzed for functional annotations with ShinyGO (0.80). The top ten significantly enriched pathways were identified with a false discovery rate (FDR) threshold of <0.05. Significant associations were found between maternal BMI change and paraoxonase 1 (PON1) levels in umbilical cord blood, while no correlation was observed with other oxidative (total oxidant status) and antioxidant markers (total antioxidant status, aryl esterase, thiol, and catalase). Additionally, the correlation analysis showed a significant relationship between BMI change and fetal gestational age, but not with other demographic or clinical features. A total of 24 common protein interactors associated with PON1, obesity, and oxidative stress were identified. Functional annotation analysis revealed significant enrichment in antioxidant and oxidoreductase activities, along with pathways involved in insulin resistance, AGE-RAGE signaling, and atherosclerosis. Maternal obesity may specifically affect PON1 activity, potentially serving as a compensatory response to oxidative stress in neonates, suggesting PON1 as a possible biomarker for oxidative stress-related metabolic disturbances in neonates of obese mothers, with implications for monitoring and managing pregnancy outcomes in obese populations. Full article

Preterm birth (PTB) forms a heterogeneous group with possible genetic predisposition. 25(OH)-vitamin D3 plays a significant role during implantation, placentation, and the maintenance of normal pregnancy. The aim of our research was to examine whether FokI, Cdx2, and ApaI VDR gene variants, as well as serum concentrations of 25-hydroxy25(OH)-vitamin D3 in women and their newborns, might be predisposing factors for idiopathic spontaneous preterm birth. The patient group consisted of 44 pairs of women with ISPTB and their children, and the control group consisted of 44 pairs of women who delivered at term and their children. At the time of delivery, peripheral blood was collected from every woman, and after newborn delivery, umbilical cord blood was collected. For genotyping of the rs2228570 C/T, rs11568820 G/A, and rs7975232 T/G SNPs, a combination of polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) was used. Serum concentrations of 25(OH)-vitamin D3 were determined using high-performance liquid chromatography (HPLC). There were no statistically significant differences in the frequencies of VDR genotypes and alleles between women with ISPTB and control women. There was a statistically significant difference in the distribution of VDR Cdx-2 (rs11568820) genotypes between preterm-born children and controls, with the GG genotype and G allele being more prevalent among patients than controls (p < 0.001). There were no statistically significant differences in mean values between women with ISPTB and control women, nor between preterm and full-term newborns, although the 25(OH)-vitamin D3 concentrations in preterm-born children were lower than in controls. Furthermore, there was a statistically significant correlation in 25(OH)-vitamin D3 concentrations between mothers and children both in the patient and in the control groups (b = 0.771, p < 0.001). The results of our study demonstrate a notable association between the VDR Cdx2 gene polymorphism and idiopathic spontaneous preterm birth (ISPTB) in a Caucasian population, but because of the small number of participants, further research is needed. Full article

Background/Objectives: The folate Recommended Daily Allowance (RDA) for pregnant women is 600 μg/day dietary folate equivalents, which is equivalent to approximately 400 μg folic acid. Many prenatal supplements contain much higher doses of folic acid. The body’s ability to reduce synthetic folic acid to the metabolically active form may be exceeded with high levels of supplementation. The objective of this double-blinded randomized controlled intervention trial was to determine changes in unmetabolized folic acid and other biomarkers of folate and one-carbon metabolism in maternal and cord blood in response to a folic acid dose commonly found in prenatal supplements (800 μg/day) compared to the dose equivalent of the RDA (400 μg/day). Methods: Healthy pregnant women were randomized and provided supplements from their first prenatal visit (<12 weeks gestation) through delivery. Maternal blood was collected at baseline and delivery. Umbilical cord blood from the mothers was collected at delivery. Results: A repeated measures analysis of variance revealed that there was a significant group supplemental dose effect (p = 0.0225) on serum unmetabolized folic acid concentration in mothers but no difference in cord blood unmetabolized folic acid concentrations between groups. Mixed effects analysis found a significant overall effect of pre-pregnancy BMI (p = 0.0360) and length of previous folic acid supplementation (p = 0.0281) on serum folate concentrations. No treatment effect was seen in RBC folate concentrations. Choline concentrations were higher in cord blood from the 800 μg/day group compared to the 400 μg/day group, but there was no group effect in maternal choline concentrations. Conclusions: The results indicate that folic acid dose during pregnancy affects certain folate and one-carbon biomarkers, and these effects are not consistent between maternal and cord blood. Potential long-term effects of these results on both mothers and offspring are unknown and merit further investigation. Full article

Background and Objectives: Human umbilical cord blood serum (HUCBS) stands out as a potent adjunct to conventional therapies for ocular surface disorders (OSDs) caused by, among many, autoimmune systemic syndromes. By expediting ocular surface regeneration and fostering epithelial integrity, HUCBS not only enhances subjective patient experiences but also improves objective clinical indicators. This makes it particularly useful in patients with corneal ulcers through ocular surface regeneration and anti-inflammatory activity. This study aims to explore the efficacy of HUCBS in patients who had previously received other treatments unsuccessfully. Materials and Methods: This study was a prospective, non-comparative, interventional case series study involving 49 patients (30 females and 19 males) aged 15–82 years with severe OSDs who were unresponsive to standard treatments. The study was conducted at the San Marco Hospital, Catania, Italy. Patients were categorized into four groups based on the etiology of their severe OSDs: Group I consisted of twenty four patients with filamentary keratitis and corneal ulcers associated with rheumatologic diseases such as Sjogren’s syndrome and systemic sclerosis; Group II comprised thirteen patients with graft-versus-host disease; Group III consisted of nine patients with corneal neurotrophic ulcers; and Group IV included three patients with Steven–Johnson syndrome. The outcomes were evaluated before and after treatment using the following assessments: OSDI (Ocular Surface Disease Index) and SANDE (Symptom Assessment in Dry Eye) questionnaires, VAS (Visual Analog Scale), Slit Lamp Examination, Esthesiometry, Lissamine Green Staining, NIBUT (Non-Invasive Break-Up Time), BUT (Break-Up Time), Fluorescein Staining with Photography and Oxford Classification, The Schirmer Test, Best-Corrected Visual Acuity (BCVA), and Meibography. Results: We observed a significant improvement in the outcomes from the SANDE, VAS, and OSDI questionnaires, The Schirmer Test, BUT, BCVA, and Oxford Classification, after treatment with UCBS. Clinical variables, such as corneal inflammation, conjunctivalization, corneal neovascularization, and pain, were also considered individually. Nevertheless, pain and inflammation reduced markedly over time until complete healing was achieved in all cases. Conclusions: Our pilot study highlights the substantial efficacy of HUCBS in patients with systemic autoimmune diseases who have shown inadequate responses to prior treatments for dry eye. This underscores the need for further comprehensive investigations in this field. Full article

Background: Graft-versus-host disease (GvHD) is an overactive systemic inflammatory response that can arise following allogeneic hematopoietic stem cell transplantation (HSCT). This condition occurs when the transplanted donor immune cells recognize the recipient’s tissues as foreign and trigger an immune response against them. The ocular surface (eyelids, conjunctiva, meibomian glands, lacrimal glands, and cornea) is particularly involved in GvHD, and its response to existing treatments, including potent immunosuppressants and new targeted therapies, is undesirable, with such treatments often being ineffective. Human allogeneic umbilical cord blood platelet lysate stands out as a potent adjunct to conventional therapies for ocular surface disorders related to severe Dry Eye Disease. This study aimed to evaluate the safety and efficacy of umbilical cord blood platelet lysate eyedrops for the treatment of severe ocular surface disorders in graft-versus-host disease patients who have received previous unsuccessful treatments. Methods: This study was a prospective, non-comparative, interventional case series study involving 22 patients (10 females and 12 males) aged 25–46 years with severe ocular surface disorders that were unresponsive to standard treatments. The GvHD patients were categorized based on the severity of their ocular surface disorders into three groups: Group I: five patients with severe Dry Eye Disease and filamentary keratitis; Group II: eight patients suffering from severe blepharo-kerato-epitheliopathy; Group III: nine patients with corneal ulcers. Fresh umbilical cord blood (UCB) was obtained from healthy donors and subjected to centrifugation using a novel PRP preparation kit provided by Sciacca (AG) Cord blood bank, Italy in a one-step process. In all groups, the outcomes before and after treatment were evaluated by means of the OSDI (Ocular Surface Disease Index), SANDE (Symptom Assessment in Dry Eye) questionnaire, VAS (Visual Analogue Scale), slit lamp examination, Esthesiometry, Lissamine Green Staining, the NIBUT (Non-Invasive Break-Up Time) and BUT, fluorescein staining with digital photography and Oxford classification, the Schirmer Test, the Best Corrected Visual Acuity (BCVA), and Meibography. In Group III at each evaluation time, the size of the ulcer and its relative reduction compared to the baseline size were recorded. Clinical variables, such as corneal inflammation, conjunctivalization, corneal neovascularization, or pain, were also considered individually. Results: We observed a significant improvement in the SANDE, VAS, and OSDI scores; Schirmer Test; BUT; BCVA; and Oxford classification after treatment with allogeneic cord blood serum eyedrops. Nevertheless, pain and inflammation reduced markedly over time until complete healing in all cases. The mean reduction in the ulcer surface area (compared to baseline values) was significantly higher at all assessment points (p = 0.001 for day 7 and p < 0.001 for subsequent time points every 30 days for 90 days). At the last check-up (after 90 days of treatment), the number of ulcers (Group III, nine patients) with a reduction in size of greater than 50% was eight (88.8%), of which seven ulcers were completely healed. None of the patients experienced treatment-related local or systemic adverse events. In this study, using a relatively large number of cases, we demonstrated that the use of umbilical cord blood platelet lysate eyedrops is a safe, feasible, and effective curative approach for severe ocular surface disease in patients with GvHD. Conclusions: Our pilot study highlights the remarkable effectiveness of allogeneic cord blood serum eyedrops in patients with severe ocular surface disorders following GvHD who have shown an inadequate response to the usual treatments. It is mandatory to design future studies on the efficacy of this therapeutic approach for acute ocular, mucosal, and cutaneous GvHD. Full article

Background and Objectives: This study aimed to assess the impact of monopolar electrocautery on the fetus during cesarean section. Materials and methods: A retrospective analysis was conducted with 552 patients delivered by cesarean section. Patients were grouped based on usage of monopolar electrocautery. In 272 patients, monopolar electrocautery was used to separate the tissues before the delivery. In 280 patients, no electrocautery was used. Newborn vital signs, Apgar scores, umbilical cord blood parameters, newborn serum parameters collected within 6th postpartum hour, and rate of newborn intensive care unit admission were compared. Results: The 1st and 5th minute Apgar scores were significantly higher in the electrocautery group; however, this difference lost its significance at the 10th minute. The median newborn pulse rate (148 (7) vs. 146 (6) beats per minute, p = 0.026), umbilical cord blood pH, and partial oxygen pressure were significantly higher in the electrocautery group compared to the no-electrocautery group (7.34 ± 0.06 vs. 7.31 ± 0.06, p < 0.001, and 25.5 (14.77) vs. 23 (16.08) mmHg, p = 0.025, respectively). The median umbilical cord blood serum calcium level was 1.51 (0.64) mmol/L in the electrocautery group, which was significantly lower than 1.9 (0.82) mmol/L in the no-electrocautery group (p = 0.002). The incidence of hypoglycemia was significantly lower in the electrocautery group than in the no-electrocautery group (2.2% vs. 5.7%, p = 0.035). Conclusions: Monopolar electrocautery during cesarean section affects the fetus, but it is safe to use it. Electrocautery is independently associated with umbilical cord blood pH and calcium level. Electrocautery may be associated with a lower incidence of hypoglycemia. Full article

Galectin-3 belongs to a family of soluble glycan-binding proteins, which are increasingly recognized as modulators of pregnancy-associated processes, including proper placental development. Gestational hypertension and preeclampsia are significant complications of pregnancy, affecting millions of women annually. Despite their prevalence, the underlying pathophysiological mechanisms remain poorly understood. Several theories have been proposed, including inflammation, placental insufficiency, disturbed placental invasion, and angiogenesis. The Scopus and PubMed/MEDLINE databases were utilized until the end of May 2024. In total, 11 articles with 1011 patients, with 558 in the control group and 453 in the preeclampsia group, were included. Seven articles investigated the expression of galectin-3 (Gal-3) in placental tissue samples, eight studies calculated the serum levels of Gal-3 in maternal blood samples, while one study referred to the possible correlation of galectin-3 levels in umbilical cord blood. The results were inconsistent in both the placental tissue and maternal serum; Gal-3 placental expression was found to be statistically increased in five studies compared to that in women without gestational hypertensive disorders, while two studies either mentioned decreased expression or no difference. Similarly, the Gal-3 maternal serum levels, compared to those in women without gestational hypertensive disorders, were found to be statistically increased in five studies, while three studies did not find any statistical difference. Gal-3 can play a crucial role in the pathogenesis of preeclampsia, and its expression is influenced by gestational age and placental insufficiency. A further investigation ought to be conducted to enlighten the correlation of Gal-3 with gestational hypertension and preeclampsia development. Full article

The present study aimed to determine the effects of dietary Lonicera flos and Sucutellaria baicalensis mixed extract (LSE) supplementation during the late-pregnancy period on the reproductive performance, umbilical cord blood hematological parameters, umbilical cord serum biochemical parameters, immune indices, hormone levels, colostrum ingredients, and immunoglobulin contents of sows. A total of 40 hybrid pregnant sows were randomly assigned to the control group (CON; sows fed a basal diet) and LSE group (LSE; sows fed a basal diet supplemented with 500 g/t PE). The results indicated that dietary LSE supplementation significantly increased (p < 0.05) the number of alive and healthy piglets and the litter weight at birth, and significantly increased (p < 0.05) the platelet counts in umbilical cord blood. Dietary LSE supplementation significantly increased (p < 0.05) the levels of prolactin (PRL) and growth hormone (GH), and the content of interleukin 2 (IL-2) in umbilical cord serum. Moreover, immunoglobulin A (IgA) and immunoglobulin M (IgM) in the colostrum were increased with PE supplementation (p < 0.05). In conclusion, dietary LSE supplementation in late-pregnancy sows could improve reproductive performance and colostrum quality, and could also regulate the levels of reproductive hormone in umbilical cord serum. Full article

Fetal programming is a process initiated by intrauterine conditions, leaving a lasting impact on the offspring’s health, whether they manifest immediately or later in life. It is believed that children born to mothers with gestational diabetes mellitus (GDM) and excessive gestational weight gain (EGWG) may be at an increased risk of developing type 2 diabetes mellitus (T2DM) and obesity later in their adult lives. Substance P is a neurotransmitter associated with obesity development and impairment of insulin signaling. Dysregulation of substance P could lead to several pregnancy pathologies, such as preeclampsia and preterm birth. Our study aimed to compare substance P concentrations in serum and umbilical cord blood in patients with GDM, EGWG, and healthy women with a family history of gestational weight gain. Substance P levels in umbilical cord blood were significantly higher in the GDM group compared to the EGWG and control groups. Substance P levels in serum and umbilical cord blood were positively correlated in all groups and the GDM group. A very interesting direction for future research is the relationship between the concentration of substance P in newborns of diabetic mothers and the occurrence of respiratory distress syndrome as a complication of impaired surfactant synthesis. To our knowledge, it is the first study assessing substance P concentration in GDM and EGWG patients. Full article