Study of hemoglobin and red blood cell indices during first week of life in normal term neonates

Background: Transition from foetal to neonatal life is associated with major changes in hemogram due to homeostatic control. There are very wide ranges of hemogram levels that seem to be abnormally high or low in healthy term neonate at birth and during first week of life but these were actually normal for that neonatal period depending upon gestational and post-natal age.Method: Hemogram was studied in 100 normal term neonates born in RNT medical college during June 2009 to Dec 2009.Results: The ranges of various hemogram indices at birth, 24 hours, 48 hours and 7 days are as follows: Hemoglobin 12.2-23.2 gm/dl, 11.6-22.8 gm/dl, 11.5-21.3 gm/dl and 11.3-21.3 gm/dl respectively. Hematocrit 36.8-64.3%, 35.2-61.3%, 34.4-60.6% and 32.2-60.1% respectively. Mean corpuscular volume (MCV) 82.2-126.5 fl, 82.5-126.1 fl, 82.1-126.3 fl and 80.5-126.4 fl respectively. Mean corpuscular hemoglobin (MCH) 26.2-40.9 pg, 26.0-39.7 pg, 26-40.5 pg and 25.4-39.4 pg respectively. MCH concentration (MCHC) 29.6-38 g/dl, 28.5-37.7 g/dl, 28.4-38.6 g/dl and 28.4-38.5 g/dl respectively. Total red blood cell count (TRBC) 3.7-6.9×106/µl, 3.3-6.9×106/µl, 3.3-6.7×106/µl and 3.3-6.3×106/µl respectively.Conclusions: Hemoglobin level falls in early life in healthy term neonate. Also, there is wide range of RBC parameters in healthy term neonates. The normal values of hemogram in neonates are different from other age groups and it varies with postnatal age and gestational age. A reference range derived from large neonatal datasets of varied gestational and postnatal age should be used such as those presented here for healthy term neonates.

Identifying target sites for placental therapeutics through the comparison of normal term pregnancies and intrauterine growth restricted proteomes

A variety of pathologies, including intrauterine growth restriction (IUGR), have been linked to placental insufficiencies as important causal factors, however, little has been done to develop therapeutics that may improve placental development, structure and function. The placenta offers the opportunity to manipulate the in-utero environment without directly intervening with the fetus, accessible from the maternal circulation, a vital but temporary organ, the placenta is no longer required after birth. Developing therapeutics must involve multiple aspects of targeting and safety to ensure no off-target impact on the pregnant person or fetus as well as enhance efficiency of delivery. In addition to our studies on nanoparticle delivery to the placenta [1] we are developing targeting strategies to allow peripheral delivery via the maternal circulation. In this study we have performed the isolation of the microvillous membrane from human placental syncytiotrophoblast (the targeting cell) and via proteomic analysis identified potential targeting moieties, we have then compared this to publicly available data from pregnancies complicated by fetal growth restriction to ensure that we do not identify targets which would be reduced in FGR, resulting in less efficient targeting.

Lactic Acid Transport Mediated by Aquaporin-9: Implications on the Pathophysiology of Preeclampsia

Aquaporin-9 (AQP9) expression is significantly increased in preeclamptic placentas. Since feto-maternal water transfer is not altered in preeclampsia, the main role of AQP9 in human placenta is unclear. Given that AQP9 is also a metabolite channel, we aimed to evaluate the participation of AQP9 in lactate transfer across the human placenta. Explants from normal term placentas were cultured in low glucose medium with or without L-lactic acid and in the presence and absence of AQP9 blockers (0.3 mM HgCl2 or 0.5 mM Phloretin). Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and lactate dehydrogenase release. Apoptotic indexes were analyzed by Bax/Bcl-2 ratio and Terminal Deoxynucleotidyltransferase-Mediated dUTP Nick-End Labeling assay. Heavy/large and light/small mitochondrial subpopulations were obtained by differential centrifugation, and AQP9 expression was detected by Western blot. We found that apoptosis was induced when placental explants were cultured in low glucose medium while the addition of L-lactic acid prevented cell death. In this condition, AQP9 blocking increased the apoptotic indexes. We also confirmed the presence of two mitochondrial subpopulations which exhibit different morphologic and metabolic states. Western blot revealed AQP9 expression only in the heavy/large mitochondrial subpopulation. This is the first report that shows that AQP9 is expressed in the heavy/large mitochondrial subpopulation of trophoblasts. Thus, AQP9 may mediate not only the lactic acid entrance into the cytosol but also into the mitochondria. Consequently, its lack of functionality in preeclamptic placentas may impair lactic acid utilization by the placenta, adversely affecting the survival of the trophoblast cells and enhancing the systemic endothelial dysfunction.

Comprehensive Morphological Assessment of Cord Blood: Normal Values and the Prevalence of Morphologically Aberrant Leukocytes

Introduction: Cord blood (CB) is becoming a valuable source for stem cells utilized in a variety of cell therapy applications, as well as for newborn diagnostics. Some parameters of the CB cellular components can be provided by automated analyzers, while others, such as immature or aberrant cells, require blood film morphological assessment. The objectives of the study were to establish normal CB morphology, and to determine the prevalence of morphologically aberrant leukocytes in CB. Methods: We performed a comprehensive morphological analysis of 100 CB samples taken from healthy term and appropriate-for-gestational-age neonates born to healthy mothers, preterm neonates, neonates of diabetic mothers, and small-for-gestational-age neonates. Blood counts were assessed, and manual morphological analyses were performed by laboratory specialists. Results: The manual differential count of normal CB samples established the following values: 47.8±10.7% neutrophils, 31.2±9.8% lymphocytes, 10.0±4.0% monocytes, and 3.0±2.5% eosinophils, with no significant sex-related differences. Blasts were observed in 44/100 samples with an average of 0.5±0.7% per sample, and only a minor left shift was observed. There were significant populations of large granular lymphocytes (19.1±10.6% of the total lymphocytes) and morphologically aberrant lymphocytes (12.4±5.4% of the total lymphocytes) in the samples, irrespective of neonatal status. The differentials of preterm CB samples differ significantly from normal term CB samples, including the reverse of neutrophils/lymphocytes ratio, and the lack of basophils. Conclusions: Normal values and unique morphological features in the CB of neonates are described. The abundant morphologically aberrant lymphocytes in CB may represent an immature state of the immune system at birth.

Molecular Mechanism and Pathways of Normal Human Parturition in Different Gestational Tissues: A Systematic Review of Transcriptome Studies

Objective: Genome-wide transcriptomic studies on gestational tissues in labor provide molecular insights in mechanism of normal parturition. This systematic review aimed to summarize the important genes in various gestational tissues around labor onset, and to dissect the underlying molecular regulations and pathways that trigger the labor in term pregnancies.Data sources: PubMed and Web of Science were searched from inception to January 2021.Study Eligibility Criteria: Untargeted genome-wide transcriptomic studies comparing the gene expression of various gestational tissues in normal term pregnant women with and without labor were included.Methods: Every differentially expressed gene was retrieved. Consistently expressed genes with same direction in different studies were identified, then gene ontology and KEGG analysis were conducted to understand molecular pathways and functions. Gene-gene association analysis was performed to determine the key regulatory gene(s) in labor onset.Results: A total of 15 studies, including 266 subjects, were included. 136, 26, 15, 7, and 3 genes were significantly changed during labor in the myometrium (seven studies, n = 108), uterine cervix (four studies, n = 64), decidua (two studies, n = 42), amnion (two studies, n = 44) and placenta (two studies, n = 41), respectively. These genes were overrepresented in annotation terms related to inflammatory and immune responses. TNF and NOD-like receptor signaling pathways were overrepresented in all mentioned tissues, except the placenta. IL6 was the only gene included in both pathways, the most common reported gene in all included studies, and also the gene in the central hub of molecular regulatory network.Conclusions: This systematic review identified that genes involved in immunological and inflammatory regulations are expressed in specific gestational tissues in labor. We put forward the hypothesis that IL6 might be the key gene triggering specific mechanism in different gestational tissues, eventually leading to labor onset through inducing uterine contraction, wakening fetal membranes and stimulating cervical ripening.Systematic Review Registration: Identifier [CRD42020187975].

Reduced Placental CD24 in Preterm Preeclampsia Is an Indicator for a Failure of Immune Tolerance

Introduction: CD24 is a mucin-like glycoprotein expressed at the surface of hematopoietic and tumor cells and was recently shown to be expressed in the first trimester placenta. As it was postulated as an immune suppressor, CD24 may contribute to maternal immune tolerance to the growing fetus. Preeclampsia (PE), a major pregnancy complication, is linked to reduced immune tolerance. Here, we explored the expression of CD24 in PE placenta in preterm and term cases. Methods: Placentas were derived from first and early second trimester social terminations (N = 43), and third trimester normal term delivery (N = 67), preterm PE (N = 18), and preterm delivery (PTD) (N = 6). CD24 expression was determined by quantitative polymerase chain reaction (qPCR) and Western blotting. A smaller cohort included 3–5 subjects each of term and early PE, and term and preterm delivery controls analyzed by immunohistochemistry. Results: A higher expression (2.27-fold) of CD24 mRNA was determined in the normal term delivery compared to first and early second trimester cases. The mRNA of preterm PE cases was only higher by 1.31-fold compared to first and early second trimester, while in the age-matched PTD group had a fold increase of 5.72, four times higher compared to preterm PE. The delta cycle threshold (ΔCt) of CD24 mRNA expression in the preterm PE group was inversely correlated with gestational age (r = 0.737) and fetal size (r = 0.623), while correlation of any other group with these parameters was negligible. Western blot analysis revealed that the presence of CD24 protein in placental lysate of preterm PE was significantly reduced compared to term delivery controls (p = 0.026). In immunohistochemistry, there was a reduction of CD24 staining in villous trophoblast in preterm PE cases compared to gestational age-matched PTD cases (p = 0.042). Staining of PE cases at term was approximately twice higher compared to preterm PE cases (p = 0.025) but not different from normal term delivery controls. Conclusion: While higher CD24 mRNA expression levels were determined for normal term delivery compared to earlier pregnancy stages, this expression level was found to be lower in preterm PE cases, and could be said to be linked to reduced immune tolerance in preeclampsia.

The Uterocervical Angle Combined with Bishop Score as a Predictor for Successful Induction of Labor in Term Vaginal Delivery

The objective of this study was to determine the value of uterocervical angle (UCA) in predicting successful induction of labor (IOL) in singleton pregnant women compared to the Bishop score and cervical length (CL). A total of 205 normal term, singleton labor-induction cases were analyzed. Successful IOL was defined as the onset of active labor of induction. A comparative analysis was performed to evaluate the effectiveness of UCA, Bishop score, and CL in predicting IOL. Compared to the non-successful IOL group, the women in the successful IOL group had significantly wider UCA (p = 0.012) and higher Bishop score (p = 0.001); however, the CL was not significantly different (p = 0.130). UCA alone did not perform better than the Bishop score when predicting successful IOL. However, UCA combined with the Bishop score showed higher performance in predicting IOL (combined UCA > 108.4° and favorable Bishop score as sensitivity of 44.6%, specificity of 96.0%, PPV of 96.2%, and NPV of 43.6; combined UCA > 108.4° or favorable Bishop score as sensitivity of 85.7%, specificity of 50.0%, PPV of 78.7%, and NPV of 61.9). In conclusion, UCA combined with Bishop score may be an effective sonographic method for predicting successful IOL.

Establishment of a personalized fetal growth curve model

BACKGROUND: Fetal weight is one of the important indicators for judging whether fetal growth and development are normal. Fetal weight exceeding the normal range may lead to poor delivery outcomes. OBJECTIVE: We aimed to establish a personalized fetal growth curve in order to effectively monitor fetal growth during pregnancy. Fetal weight can be monitored while fetal growth and development are assessed. METHODS: This study retrospectively analyzed the birth weight and ultrasound database of 3,093 newborns delivered at normal term. The personalized fetal growth curve model was generated based on the birth weight formula established by Gardosi combined with the proportional weight equation. RESULTS: (1) The average birth weight of the single fetus at normal term was 3,457g. (2) According to the regression results of the proportion of fetal weight in full-term pregnancy and gestational week, the proportional weight equation is Weight% = 500.9 - 51.60GA + 1.727GA2- 0.01718GA3 (GA is gestational week), R2 is 98%, P< 0.001. CONCLUSIONS: In this study, the normal birth weight of newborns and normal range of fetal weight can be estimated by using the personalized fetal growth curve model.

Assessment of perinatal outcomes of pregnant women with severe versus simple malaria

Objective Malaria in pregnancy is associated with adverse perinatal outcomes. The objective was to compare outcomes of simple and severe malaria and to determine whether they vary by trimester or severity of infection. Methods Prospective cohort study performed in 3 hospitals in Rwanda. Both hospitalized and non-hospitalized pregnant patients with confirmed malaria were enrolled and followed until 7 days postpartum. Demographic, clinical manifestations and perinatal outcomes were recorded. Results There were 446 pregnant women with confirmed malaria and outcome data; 361 (80.9%) had simple malaria. Severe malaria was more common as pregnancy progressed; out of 85 with severe malaria, 12.9%, 29.4% and 57.6% were in the 1st, 2nd and 3rd trimesters (p<0.0001). Overall, a normal term delivery occurred in 57.6%, with preterm delivery in 24.9% and abortion in 13.5%. Adverse perinatal outcomes increased with trimester of infection (p<0.0001). Eight of the 9 early neonatal deaths had 3rd trimester infection (p<0.0001). There were 27 stillbirths; 63.7% were associated with 3rd trimester infection. A significant difference in perinatal outcomes between simple and severe malaria was seen: 64% of women with simple malaria had a normal term delivery as compared to 30.6% with severe malaria (p<0.0001). All complications were significantly greater with severe malaria. Conclusion Overall poor outcomes are seen in malaria with significant differences in perinatal outcomes between simple and severe malaria and by trimester of infection. In addition to vector control and exposure prevention, efforts need to be made in screening, treatment education and monitoring pregnancies affected by malaria.

Bilateral scrotoshisis a rare entity: case report

Background Scrotoschisis is a rare anomaly in which the testis is lying outside scrotum congenitally. Only few cases have been reported in literature under different names most of which are unilateral. We have found only one case of bilateral scrotoschisis in literature. Case presentation Newborn presented to us after normal term twin delivery as a case of bilateral scrotoschisis in which both testes were lying outside the scrotum congenitally. Baby underwent uneventful bilateral orchiopexy and was discharged home the next day. Conclusion Scrotoschisis is a very rare genital anomaly with only a few cases reported in literature. This report would add to the literature which would help in studying the exact mechanism and embryopathogenesis of this anomaly which is not known yet.