Postnatal Treatment Research Articles

The Effect of Melatonin Supplementation on Dam Milking Traits and Calf Performance in Beef Cattle

Abstract Melatonin has been documented to alleviate compromised pregnancies and enhance livestock performance traits. The objective of this study was to determine the effect of melatonin supplementation on milking traits in beef cattle dams and subsequent influence on calf performance. Cows (n = 60) were blocked based on embryo transfer donor and sire, potential calf breed and embryo grade. At d190, 220 and 250 of gestation, dams were administered either 2 subdermal ear melatonin implants (preMEL) or no implants (preCON). After parturition, birth weights were recorded and calves randomly received either melatonin implants (posMEL) or none (posCON) on approximately d 0, 30, and 60. At approximately d 60 of lactation, a subset of dams (n = 32) were selected based on age, weight and calf sex for milk collection and analysis. At weaning, calf weight and morphometric data were collected and adjusted according to weaning age. Prenatal melatonin administration did not change calf birth weight (P = 0.956). Milk yield tended to decrease in the preMEL group (P = 0.054) at 2.368 kg ± 0.11 compared to preCON at 2.054 kg ± 0.11. Milk fat percent tended to decrease (P = 0.07) in preMEL at 3.25 ± 0.19 versus preCON at 3.92 ± 0.19. There were no differences in prenatal treatment in respect to milk protein, lactose, solid non-fats, somatic cell count, and urea nitrogen (P > 0.16). At weaning, calf head circumference decreased (P < 0.031) in the preMEL group at 77.92cm ± 0.42 versus preCON at 79.31cm ± 0.45. Otherwise, there were no prenatal or postnatal treatment differences in respect to weaning weight, crown-rump length, hip height and head length (P > 0.12). Previous studies show crown-to-rump length and ponderal index differences. Our lack of differences might be attributed to geographical locations that impact day length or endogenous melatonin status.

Postnatal Oxytocin Treatment Improves Survival and Improves Behavioral Outcomes in an Animal Model of Neonatal Abstinence Syndrome

Objective To investigate the therapeutic effect of the neuropeptide oxytocin in an animal model of neonatal abstinence syndrome. Hypothesis Prenatal exposure to drugs of abuse (eg. opioids and benzodiazepines) results in a severe withdrawal syndrome known as neonatal abstinence syndrome (NAS). NAS is a serious health problem with increasing prevalence. Standard of care pharmacological intervention consists of morphine, methadone, buprenorphine, clonidine, and phenobarbital. Safer and more effective treatments are urgently needed. The neuropeptide oxytocin has been shown to reverse drug and alcohol withdrawal syndromes in adult animals and humans. Here, we examined the effect of postnatal oxytocin treatment on survival and behavioral outcomes in neonatal rats prenatally exposed to opioids or benzodiazepines. Methods Pregnant Sprague-Dawley rats were injected subcutaneously with escalating doses of morphine (10-50 mg/kg/day) or diazepam (2-15 mg/kg/day) starting at gestational day seven through parturition. Upon delivery, rat pups received daily subcutaneous injections of 2 mg/kg oxytocin or saline for the first 10 postnatal days and survival was measured. A second cohort of morphine and diazepam exposed rat pups received injections of 0.3, 1, or 2 mg/kg oxytocin or saline for the first 10 postnatal days and survival was assessed for 30 days. Surviving animals were subjected to a battery of behavioral assessments between postnatal day 30 and 45 to determine how early life oxytocin treatment impacts neurocognitive outcomes. These assessments included a Locomotor Assay, Light-Dark Box Test, Passive Avoidance Task, and Social Interaction Test. Animals were then sacrificed, blood was collected and processed, and glucose oxidase, coritcosterone, and aldosterone was measured using Enzyme Immunoassay (EIA). Results In the first cohort of animals exposed to morphine prenatally, survival was significantly improved with 2 mg/kg oxytocin treatment compared to saline (100% vs 66.67%; P=0.008). The same pattern was observed with animals exposed to diazepam prenatally (100% vs 66.5%; P=0.0149). In the second cohort of animals exposed to morphine prenatally, all doses of oxytocin (0.3, 1, and 2 mg/kg) improved survival compared to saline (88.89%, 100%, 100% vs 50%, respectively; P<0.0001). A similar pattern of improved survival following the two highest doses of oxytocin, but not 0.3 mg/kg, was observed with animals exposed to diazepam prenatally (68.75%, 100%, 100% vs 62.5%, respectively; P=0.0176). Preliminary findings for improvements in learning and memory and social behavior were also observed. No differences in the measured biological outcomes was observed. Conclusions These findings provide insights in to the potential for oxytocin as a novel treatment option for NAS. Given the high unmet need in NAS and the established safety profile of oxytocin, clinical trials appear warranted.

A narrative review of in utero gene therapy: advances, challenges, and future considerations.

The field of in utero gene therapy (IUGT) represents a crossroad of technologic advancements and medical ethical boundaries. Several strategies have been developed for IUGT focusing on either modifying endogenous genes, replacing missing genes, or modifying gene transcription products. The list of candidate diseases such as hemoglobinopathies, cystic fibrosis, lysosomal storage disorders continues to grow with new strategies being developed as our understanding of their respective underlying molecular pathogenesis increases. Treatment in utero has several distinct advantages to postnatal treatment. Biologic and physiologic phenomena enable the delivery of a higher effective dose, generation of immune tolerance, and the prevention of phenotypic onset for genetic diseases. Therapeutic technology for IUGT including CRISPR-Cas9 systems, zinc finger nucleases (ZFN), and peptide nucleic acids (PNAs) has already shown promise in animal models and early postnatal clinical trials. While the ability to detect fetal diagnoses has dramatically improved with developments in ultrasound and next-generation sequencing, treatment options remain experimental, with several translational gaps remaining prior to implementation in the clinical realm. Complicating this issue, the potential diseases targeted by this approach are often debilitating and would otherwise prove fatal if not treated in some manner. The leap from small animals to large animals, and subsequently, to humans will require further vigorous testing of safety and efficacy.

Effect of Anesthesia Methods During Elective Cesareans on Neonates: Ordu Province Example

Objective: To research the short-term effects on neonates of different anesthesia methods administered for elective cesareans.Methods: Data obtained from files and electronic medical records of 157 singleton cesarean cases and neonates from January 2018 to December 2019 were retrospectively analyzed and 6 cases were excluded from the study. A total of 151 cases were divided into general anesthesia-propofol (n=30), spinal (n=100) and general anesthesia-pentothal (n=21) groups.Results: A total of 151 cesarean cases that meet the inclusion criteria in the date interval of the study were assessed. Of cases, 100 (66%) were in the spinal anesthesia group, 30 (20%) were in the general anesthesia-propofol group and 21 (14%) were in the general anesthesia-pentothal group. There was no significant difference between the study groups in terms of demographic data. The umbilical cord pCO2 value was significantly low in the spinal anesthesia group (43.60±5.52) compared to the general-pentothal group (47.38±5.71). The umbilical cord HCO3 value was lower in the spinal anesthesia group (22.69±1.62) compared to the general-pentothal (23.48±1.53) and general-propofol groups (23.49±1.83). There was a significant variation in postnatal treatment types according to anesthesia method (p=0.012). The rate not requiring treatment was lowest in the general-propofol group (46.7%), while the rate of balloon-valve mask use (46.7%) was highest compared to the other groups. In terms of 5th minute Apgar scores, there was a significant difference between the groups (p=0.024). Patients in the general-propofol group had significantly lower 5th minute Apgar scores compared to patients in the spinal group.Conclusion: The balloon-valve mask rate was highest for those with propofol general anesthesia. Additionally, it was identified that neonates in both general anesthesia groups had higher neonatal intensive care unit requirements compared to the spinal anesthesia group.

TO STUDY THE INCIDENCE AND RISK FACTORS OF RETINOPATHY OF PREMATURITY IN A TERTIARY CARE HOSPITAL IN NORTHERN INDIA

BACKGROUND: Retinopathy of prematurity (ROP) is a multifactorial retinal vaso-proliferative disorder which remains a leading cause of childhood blindness worldwide despite improvements in neonatal care and management guidelines. This study was conducted to determine the incidence of ROP among preterm neonates and to determine the risk factors. METHODS: All preterm infants with birth weight &lt;1750 gm and gestation &lt;34 weeks were screened for ROP at 4 weeks of birth for rst screening. Prenatal and postnatal risk factors, neonatal problems, treatment given, procedures and interventions done during stay in neonatal intensive care unit were recorded as per the proforma. The data from the study was systematically collected, compiled and statistically analyzed with SPSS Statistics-26 version to draw relevant conclusions. RESULTS: The incidence of ROP in 89 infants who were screened was 44%. The mean gestational age of babies with ROP was 32 weeks. In our study, pneumonia, apnea, sepsis, thrombocytopenia, NEC, shock, acidosis, IVH, BPD, the use of Bubble CPAP, Venti-CPAP and mechanical ventilator, the vasopressor use and blood transfusion were signicant risk factors. CONCLUSIONS: The incidence of ROP was signicantly higher in babies &lt;34 weeks. It was observed in our that lower the birth weight and lower the gestational age, higher is the risk for the development of ROP. Careful and timed retinal examination of all at risk infants will minimize the development of ROP and later on blindness.

Postnatal Management in Congenital Lower Urinary Tract Obstruction With and Without Prenatal Vesicoamniotic Shunt.

Purpose: Congenital lower urinary tract obstruction (cLUTO) includes a heterogeneous group of conditions caused by a functional or mechanical outlet obstruction. Early vesicoamniotic shunting (VAS) possibly reduces the burden of renal impairment. Postpartum, pediatric urologists are confronted with neonates who have a shunt in place and a potentially impassable urethra with a narrow caliber. Early management of these patients can be challenging. Here, we would like to share the approach we have developed over time.Materials and Methods: We conducted a single-center retrospective analysis from 2016 to 2020 and included all patients diagnosed with cLUTO. Data focusing on time point and type of intervention was collected. Furthermore, patients with temporary diversion via a percutaneous VAS were selected for a more detailed review.Results: In total, 71 cases of cLUTO were identified during the study period. Within this group, 31 neonates received postnatal management and surgical intervention in our center. VAS was performed in 55% of these cases (N = 17). The postnatal treatment varied between transurethral or suprapubic catheterization and early Blocksom vesicostomy. In five infants with VAS, the urinary drainage was secured through the existing VAS by inserting a gastric tube (N = 1) or a 4.8 Fr JJ-stent (N = 4). To our knowledge, this is the first report of a stent-in-stent scheme, which can remain indwelling until the definite treatment.Conclusion: Having a secure urine drainage through a VAS allows the often premature infant to grow until definite surgery can be performed. This avoids placing a vesicostomy, which requires anesthesia.

Prenatal Diagnosis and Postnatal Treatment in a Case of Abdominal Obstruction and Polyhydramnios Caused by Amniotic Band Sequence

Background: Amniotic band sequence (ABS) is a rare congenital disorder resulting from the entanglement of fetal parts by fibrous bands that may cause disruptions, deformations, or malformations that can range from mild to life threatening conditions. Prenatal diagnosis is usually based on ultrasounds visualization on amniotic bands attached to fetal parts, possibly causing fetal defects. Case Presentation: A 19-year-old woman with an unremarkable clinical history and a low-risk pregnancy was referred to our Fetal Therapy Unit for a suspected fetal clubfoot at 22 weeks gestational age. A chorioamniotic separation, together with unilateral clubfoot was diagnosed. Due to a high risk of premature rupture of membranes a decision was made not to perform amniocentesis for genetic investigation. At prenatal follow up progressive polyhydramnios developed with a preterm spontaneous rupture of the membranes at 34 weeks. After caesarean section – due to breech presentation – an amniotic band was observed at the abdominal level causing a circular skin lesion, constriction, and a sub-occlusive intestinal status. Moreover, a left clubfoot with amputation of distal phalanx of the second toe and a right foot amputation of 2nd and 3rd toes were evident. The neonate underwent abdominal plastic surgery on the second day of life with complete recovery. Following the postnatal diagnosis of ABS, we re-examined a stored fetal 3D ultrasound volume acquired at 22 weeks and, focusing on the fetal surface rendering, we could notice the deep abdominal skin furrow that was evident at birth. Discussion: This case represents an unusual antenatal presentation of an amniotic band sequence that escaped prenatal diagnosis with a progressive polyhydramnios as an indirect sign of fetal bowel obstruction caused by an abdominal constricting band. In the presence of chorioamniotic separation and additional ominous ultrasound findings, it is advisable to consider the possibility of an ABS.

Clinical guidelines for the treatment of congenital diaphragmatic hernia.

Congenital diaphragmatic hernia (CDH) is a birth defect of the diaphragm in which abdominal organs herniate through the defect into the thoracic cavity. The main pathophysiology is respiratory distress and persistent pulmonary hypertension because of pulmonary hypoplasia caused by compression of the elevated organs. Recent progress in prenatal diagnosis and postnatal care has led to an increase in the survival rate of patients with CDH. However, some survivors experience mid- and long-term disabilities and complications requiring treatment and follow-up. In recent years, the establishment of clinical practice guidelines has been promoted in various medical fields to offer optimal medical care, with the goal of improvement of the disease' outcomes, thereby reducing medical costs, etc. Thus, to provide adequate medical care through standardization of treatment and elimination of disparities in clinical management, and to improve the survival rate and mid- and long-term prognosis of patients with CDH, we present here the clinical practice guidelines for postnatal management of CDH. These are based on the principles of evidence-based medicine using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. The recommendations are based on evidence and were determined after considering the balance among benefits and harm, patient and society preferences, and medical resources available for postnatal CDH treatment.

Opioid withdrawal behavior in spiny mice: A novel preclinical model of neonatal opioid withdrawal syndrome (NOWS)

As the opioid epidemic continues to grow, opioid use among pregnant women is increasing significantly. This has led to a steady rise in the number of infants born with neonatal opioid withdrawal syndrome (NOWS). Although short-term withdrawal symptoms associated with NOWS are well characterized, there are many gaps in our understanding of the short and long-term effects of prenatal opioid exposure. Current animal models of NOWS are limited by shortened gestational periods, large litter sizes, and primary organogenesis occurring after birth. This often leads to postnatal treatment to mimic drug exposure during third-trimester development. Using the unique rodent species Acomys cahirinus, more commonly known as spiny mice, which have an extended 40-day gestation period, small litter sizes, and increased in utero organogenesis we aim to study the short-term effects of prenatal morphine exposure by assessing withdrawal behavior. To model maternal opioid use, dams were treated daily with morphine (10 and 30 mg/kg S.C.) beginning on gestation day 19 until the day of birth; this resulted in a cumulative exposure of 19–21 days. Withdrawal behaviors for each pup were recorded daily between postnatal days 0–7 (PND 0–7). Our study found that prenatal morphine exposure in spiny mice led to an increase in withdrawal behavior throughout the early postnatal period and validated the use of this species as a novel pre-clinical model of NOWS. We are hopeful this rodent model will further our understanding of the short and long-term consequences of prenatal opioid exposure on neurodevelopment and behavior.

The skeletal effect of post-natal treatment with N-acetylcysteine in a diastrophic dysplasia mouse model

The skeletal effect of post-natal treatment with N-acetylcysteine in a diastrophic dysplasia mouse model

Beneficial effects of melatonin on prostanoids pathways in pulmonary hypertensive neonates

Pulmonary arterial hypertension of the newborn (PAHN) is a syndrome caused by chronic hypoxia, characterized by decreased vasodilator function, a marked vasoconstrictor activity, proliferation of smooth muscle cells (SMC) and thickening of the extracellular matrix in the pulmonary circulation, among other characteristics. Prostaglandins are derived from the arachidonic acid (AA) metabolism and are important regulators of pulmonary vascular tone. Since hypoxia induces oxidative stress and has been related to PAHN, a postnatal treatment with melatonin has been proposed due to its antioxidant properties. Here, we determined the effects of melatonin on pulmonary vascular homeostasis given by prostanoids. Ten PAHN newborn lambs were divided in two groups and treated either with vehicle or melatonin. After 1 week of treatment, we assessed pulmonary vascular prostanoids function and expression by wire myography, RT-PCR, Western Blot and immunohistochemistry. Melatonin improved in vivo and ex vivo pulmonary vasodilation. This was associated with an increased function and expression of vasodilator prostanoids at the expense of vasoconstrictor prostanoids. Our study demonstrates for the first time that melatonin may enhance the vasodilator prostanoid pathway in PAHN.

Costs and cost-effectiveness of management of possible serious bacterial infections in young infants in outpatient settings when referral to a hospital was not possible: Results from randomized trials in Africa.

Serious bacterial neonatal infections are a major cause of global neonatal mortality. While hospitalized treatment is recommended, families cannot access inpatient treatment in low resource settings. Two parallel randomized control trials were conducted at five sites in three countries (Democratic Republic of Congo, Kenya, and Nigeria) to compare the effectiveness of treatment with experimental regimens requiring fewer injections with a reference regimen A (injection gentamicin plus injection procaine penicillin both once daily for 7 days) on the outpatient basis provided to young infants (0-59 days) with signs of possible serious bacterial infection (PSBI) when the referral was not feasible. Costs were estimated to quantify the financial implications of scaleup, and cost-effectiveness of these regimens. Direct economic costs (including personnel, drugs and consumable costs) were estimated for identification, prenatal and postnatal visits, assessment, classification, treatment and follow-up. Data on time spent by providers on each activity was collected from 83% of providers. Indirect marginal financial costs were estimated for non-consumables/capital, training, transport, communication, administration and supervision by considering only a share of the total research and health system costs considered important for the program. Total economic costs (direct plus indirect) per young infant treated were estimated based on 39% of young infants enrolled in the trial during 2012 and the number of days each treated during one year. The incremental cost-effectiveness ratio was calculated using treatment failure after one week as the outcome indicator. Experimental regimens were compared to the reference regimen and pairwise comparisons were also made. The average costs of treating a young infant with clinical severe infection (a sub-category of PSBI) in 2012 was lowest with regimen D (injection gentamicin once daily for 2 days plus oral amoxicillin twice daily for 7 days) at US$ 20.9 (95% CI US$ 16.4-25.3) or US$ 32.5 (2018 prices). While all experimental regimens B (injection gentamicin once daily plus oral amoxicillin twice daily, both for 7 days), regimen C (once daily of injection gentamicin injection plus injection procaine penicillin for 2 days, thereafter oral amoxicillin twice daily for 5 days) and regimen D were found to be more cost-effective as compared with the reference regimen A; pairwise comparison showed regimen D was more cost-effective than B or C. For fast breathing, the average cost of treatment with regimen E (oral amoxicillin twice daily for 7 days) at US$ 18.3 (95% CI US$ 13.4-23.3) or US$ 29.0 (2018 prices) was more cost-effective than regimen A. Indirect costs were 32% of the total treatment costs. Scaling up of outpatient treatment for PSBI when the referral is not feasible with fewer injections and oral antibiotics is cost-effective for young infants and can lead to increased access to treatment resulting in potential reductions in neonatal mortality. The trial was registered with Australian New Zealand Clinical Trials Registry under ID ACTRN 12610000286044.

What is the Impact of Prenatal Counseling on Postnatal Cleft Treatment? Multidisciplinary Pathway for Prenatal Orofacial Cleft Care.

In the pediatric general surgery literature, it has been shown that prenatal diagnosis of a congenital anomaly is an independent predictor of parental psychological distress. Surgical prenatal counseling can decrease parental anxiety by helping families understand the surgical needs and potential outcomes of their infant. In this retrospective analysis (n = 440), the authors sought to present our care pathway for prenatally diagnosed cleft lip and palate (CL/P) and explore the impact of cleft lip and palate-specific prenatal counseling on patient care by comparing the timing of clinical and surgical care between a cohort of patients who received prenatal CL/P consultation and a cohort of patients only seen postnatally. The authors hypothesize that our multidisciplinary prenatal care intervention is associated with earlier postnatal clinic visits and surgical repair. The care of all patients whose mother's presented for prenatal CL/P consultation (prenatal cohort, n = 118) was compared to all new CL/P patients without prenatal consultation at our institution (postnatal cohort, n = 322) from January 2015 through August 2019. 81.4% (n = 96) of the prenatal cohort returned for care postnatally while 2 pregnancies were interrupted, four neonates died, and 15 patients did not return for care. Prenatal consultation was associated with earlier postnatal clinic appointments (P < 0.001) as well as a shorter time to CL repair in patients with CL only (P = 0.002) and CLP (P = 0.047). Our described pre- and postnatal CL/P pathway is a multidisciplinary model associated with high retention rates from the prenatal period through complete surgical repair.

Green tea extracts containing epigallocatechin-3-gallate modulate facial development in Down syndrome

Trisomy of human chromosome 21 (Down syndrome, DS) alters development of multiple organ systems, including the face and underlying skeleton. Besides causing stigmata, these facial dysmorphologies can impair vital functions such as hearing, breathing, mastication, and health. To investigate the therapeutic potential of green tea extracts containing epigallocatechin-3-gallate (GTE-EGCG) for alleviating facial dysmorphologies associated with DS, we performed an experimental study with continued pre- and postnatal treatment with two doses of GTE-EGCG supplementation in a mouse model of DS, and an observational study of children with DS whose parents administered EGCG as a green tea supplement. We evaluated the effect of high (100 mg/kg/day) or low doses (30 mg/kg/day) of GTE-EGCG, administered from embryonic day 9 to post-natal day 29, on the facial skeletal development in the Ts65Dn mouse model. In a cross-sectional observational study, we assessed the facial shape in DS and evaluated the effects of self-medication with green tea extracts in children from 0 to 18 years old. The main outcomes are 3D quantitative morphometric measures of the face, acquired either with micro-computed tomography (animal study) or photogrammetry (human study). The lowest experimentally tested GTE-EGCG dose improved the facial skeleton morphology in a mouse model of DS. In humans, GTE-EGCG supplementation was associated with reduced facial dysmorphology in children with DS when treatment was administered during the first 3 years of life. However, higher GTE-EGCG dosing disrupted normal development and increased facial dysmorphology in both trisomic and euploid mice. We conclude that GTE-EGCG modulates facial development with dose-dependent effects. Considering the potentially detrimental effects observed in mice, the therapeutic relevance of controlled GTE-EGCG administration towards reducing facial dysmorphology in young children with Down syndrome has yet to be confirmed by clinical studies.

Perinatal risk factors for pediatric onset type 1 diabetes, autoimmune thyroiditis, juvenile idiopathic arthritis, and inflammatory bowel diseases

Type 1 diabetes mellitus (DM), autoimmune thyroiditis (AIT), juvenile idiopathic arthritis (JIA), and inflammatory bowel diseases (IBD) are common pediatric autoimmune diseases with unknown risk factors. Using nationwide registers, we searched for their perinatal risk factors. Our study followed up 11,407 children (born 2000–2005) for a median of 16.6 years (from birth to 2018). Of them, 2.15% received primary diagnosis and 0.08% also secondary: 0.89% had DM, 0.60% had AIT, 0.48% had JIA, and 0.25% had IBD. The incidences per 100,000 children/year were 106.1 for DM, 46.0 for AIT, 55.0 for JIA, and 23.7 for IBD. There were more preterm births (< 37 weeks) among children with studied autoimmune diseases compared with the rest of the cohort (8.6% vs. 5.3%, p = 0.035). Among those born preterm, children with studied autoimmune diseases received more postnatal antibiotics compared with other preterm children in the cohort (47.6% vs. 27.7%, p = 0.046). Children with IBD were born to older mothers compared with those without studied diagnoses (33.0 vs 30.2, p = 0.004).Conclusion: Preterm birth was a shared risk factor for autoimmune diseases in our study, especially when combined with postnatal antibiotic treatments. High maternal age was associated with IBD.What is Known:• Type 1 diabetes (DM), autoimmune thyroiditis (AIT), juvenile idiopathic arthritis (JIA), and inflammatory bowel diseases (IBD) are common pediatric autoimmune diseases• It is unclear whether these diseases have shared risk factors, since there are no previous simultaneous epidemiological nor follow-up studies on them in one cohort What is New:• Preterm births were more common in children with DM, AIT, JIA, or IBD compared with other children in the cohort, and preterm children who developed these diseases recieved more postnatal antibiotics compared with other preterm children• High maternal age was associated with IBD

Neonatal administration of erythropoietin attenuates cognitive deficits in adult rats following placental insufficiency.

Preterm birth is a principal cause of neurological disability later in life, including cognitive and behavioral deficits. Notably, cognitive impairment has greater impact on quality of life than physical disability. Survivors of preterm birth commonly have deficits of executive function. Difficulties with tasks and planning complexity correlate positively with increasing disability. To overcome these barriers for children born preterm, preclinical and clinical studies have emphasized the importance of neurorestoration. Erythropoietin (EPO) is a endogenous cytokine with multiple beneficial mechanisms of action following perinatal brain injury. While most preclinical investigations have focused on pathology and molecular mechanisms, translational studies of repair using clinically viable biobehavioral biomarkers are still lacking. Here, using an established model of encephalopathy of prematurity secondary to placental insufficiency, we tested the hypothesis that administration of EPO in the neonatal period would attenuate deficits in recognition memory and cognitive flexibility in adult rats of both sexes. We assessed cognition and executive function in two ways. First, using the classic test of novel object recognition and second, using a touchscreen platform. Touchscreen testing allows for rigorous testing of cognition and executive function in preclinical and clinical scenarios. Data show that adult rats exhibit deficits in recognition memory and cognitive flexibility following in utero placental insufficiency. Notably, neonatal treatment of EPO attenuates these deficits in adulthood and facilitates functional repair. Together, these data validate EPO neurorestoration using a clinically relevant outcome measure and support the concept that postnatal treatment following in utero injury can improve cognition and executive function through adulthood.

Postnatal metformin treatment alters rat Sertoli cell proliferation and daily sperm production.

The direct correlation between Sertoli cell number and sperm production capacity highlights the importance of deciphering external factors that modify Sertoli cell proliferation. A growing body of evidence in vitro suggests that metformin, the main pharmacological agent for type 2 diabetes treatment in children, exerts anti-proliferative effects on Sertoli cells. The aims of this study were to investigate the effect of metformin administration during postnatal period on Sertoli cell proliferation and on cell cycle regulators expression and to analyze the impact of this treatment on the sperm production capacity in adulthood. Sprague Dawley rat pups were randomly divided into two groups: MET (receiving daily 200mg/kg metformin, from Pnd3 to Pnd7 inclusive) and control (receiving vehicle). BrdU incorporation was measured to assess proliferation. Gene expression analyses were performed in Sertoli cells isolated from animals of both groups. Daily sperm production and sperm parameters were measured in adult male rats (Pnd90) that received neonatal treatment. MET group exhibited a significant decrease in BrdU incorporation in Sertoli cells. Concordantly, MET group showed a reduction in cyclin D1 and E2 expression and an increase in p21 expression in Sertoli cells. In addition, metformin-treated animals displayed lower values of daily sperm production on Pnd90. These results suggest that metformin treatment may lead to a decrease in Sertoli cell proliferation, a concomitant altered expression of cell cycle regulators and ultimately, a reduction in daily sperm production in adult animals.

Sociodemographic Differences in Prenatal Diagnosis of Chromosomal Anomalies: A Population-Based Study.

Background: In Europe, about 76% of cases of chromosomal anomalies are prenatally diagnosed. Prenatal diagnosis allows more efficient planning of postnatal treatment and helps parents for an informed decision about the continuation of pregnancy. The main aim of this study was to evaluate whether the sociodemographic maternal characteristics affect the probability of prenatal diagnosis of chromosomal anomalies.Methods: Cases of chromosomal anomalies in the period 2005–2017 came from the population-based registry of congenital anomalies of Tuscany (Italy). Differences in the proportion of cases prenatally diagnosed were investigated through the following maternal characteristics: education, geographic origin and occupation. The association between cases of termination of pregnancy after prenatal diagnosis and maternal characteristics was also analysed. Odds Ratios (OR) adjusted by maternal age were calculated using logistic regression models. Results were provided for all cases of chromosomal anomalies and for Down syndrome cases.Results: A total of 1,419 cases were included in the study. Cases prenatally diagnosed were 1,186 (83.6%). We observed a higher proportion of cases not prenatally diagnosed among cases with low maternal education compared to those with high maternal education (OR = 2.16, p < 0.001) and in women from high migratory outflow countries, compared to the Italian ones (OR = 2.85, p < 0.001). For prenatally diagnosed Down syndrome cases, we observed a higher proportion of termination of pregnancy for women with low education level (OR = 4.36, p = 0.023).Conclusions: In our study evidence of differences in the probability of prenatal diagnosis of chromosomal anomalies associated with maternal education and geographic origin was found. Population-based studies investigating sociodemographic disparities can provide essential information for targeted public health programs. Further studies are recommended to monitor the impact of the increasing availability of non-invasive screening tests.

Improvement of the skeletal phenotype in a mouse model of diastrophic dysplasia after postnatal treatment with N-acetylcysteine

Diastrophic dysplasia (DTD) is a recessive chondrodysplasia caused by mutations in the SLC26A2 gene encoding for a sulfate/chloride transporter. When SLC26A2 is impaired intracellular level of sulfate is reduced leading to the synthesis of undersulfated proteoglycans. In normal chondrocytes, the main source of intracellular sulfate is the extracellular uptake through SLC26A2, but a small amount comes from the catabolism of sulfur-containing amino acids and other thiols. Here N-acetylcysteine (NAC), an extensively used drug, is proposed as alternative source of intracellular sulfate in an animal model of DTD (dtd mouse). Mutant and wild type mice were treated twice a day with hypodermic injections of 250 mg NAC/kg body weight for one week after birth. At the end of the treatment, an improvement trend in cartilage proteoglycan sulfation and in the skeletal phenotype of treated dtd mice were observed. Thus, a longer treatment lasted three weeks starting from birth was performed. Treated mutant mice showed a significant increase of cartilage proteoglycan sulfation and a relevant improvement of the skeletal phenotype based on measurements of several bony elements and bone quality by DEXA and micro CT. Moreover, the amelioration of the overall growth plate morphology in treated dtd mice suggested a partial rescue of the endochondral ossification process. Overall, the results prove that NAC is an effective source of intracellular sulfate for dtd mice in the postnatal period. This finding paves the way for a potential pharmacological treatment of DTD patients taking advantage from a drug repositioning strategy.

Association of Fetal Atrial Flutter with Neonatal Atrioventricular Re-entry Tachycardia Involving Accessory Pathway: A Link to be Remembered.

To investigate prenatal and postnatal outcomes of atrial flutter and its association with the development of a second tachycardia, following restoration of sinus rhythm, in the fetus or newborn. This study is a retrospective review of all fetuses that presented with atrial flutter from January 2001 to December 2019 at the University Hospital of Wales, Cardiff, UK. The specific type of arrhythmia, its time of appearance and clinical characteristics, echocardiographic findings, medical management, and postnatal outcomes were evaluated. Sixteen fetuses were diagnosed with atrial flutter (AFL). Thirteen fetuses had persistent AFL and three fetuses had intermittent AFL. Seven patients had hydrops, of which one had Ebstein's anomaly and the other six had normal hearts. Three of the fetuses that presented with AFL were diagnosed at 20, 21, and 23 weeks' gestation and the remainder were diagnosed in the third trimester. Thirteen patients with AFL received antiarrhythmic drugs and three were delivered without any treatment. Five fetuses with AFL developed atrioventricular reciprocating tachycardia following DC cardioversion after birth, and four of them exhibited pre-excitation on the ECG. These five patients (31.3%) required postnatal antiarrhythmic treatment for up to 2years. Pre-excitation disappeared in two patients during follow-up and two asymptomatic patients with neonatal pre-excitation required accessory pathway ablation. Fetal atrial flutter has a strong association with atrioventricular reciprocating tachycardia and ventricular pre-excitation in the neonatal period. Therefore, electrocardiograms should be carefully reviewed in newborns following the initial resolution of atrial flutter.