Intrauterine Drug Research Articles

Effectiveness of uterus sanitation in cows with oxytetracycline drugs after surgical separation of the placente

The article presents the results of studying the effectiveness of antimicrobial drugs for intrauterine use (foaming tablets) of domestic and foreign production based on the tetracycline antibiotic oxytetracycline when used for sanitation of the uterus of cows after operative treatment of retention placenta. Samples of uterine-vaginal secretions were taken for microbiological studies from cows, which were surgically separated from the dung. The sensitivity of the microflora of the biomaterial to this tetracycline antibiotic was confirmed by the method of diffusion in agar using standard disks with oxytetracycline (30 μg). Staphylococcus aureus, Streptococcus pyogenes, Escherichia coli and Pseudomonas aeruginosa bacteria were isolated and identified from the biomaterial using generally accepted microbiological methods. The minimum inhibitory concentrations (MIC) of oxytetracycline for bacterial isolates were determined by serial dilutions in a liquid nutrient medium. According to the obtained MIC values, a high level of bacteriostatic activity of the antibiotic was established against bacterial isolates, potential causative agents of postpartum endometritis in cows. All cows, which were manually separated placenta, were divided into three groups – two experimental and control – 8 cows in each. The animals of the experimental group were intrauterineally injected with antimicrobial drugs in the form of foaming tablets, the active substance of which is oxytetracycline, in the dose recommended by the manufacturer (2 tablets per animal twice with an interval of 48 hours). Cows of the control group were not given any intrauterine drugs. The use of intrauterine preparations based on oxytetracycline contributed to the prevention of the development of postpartum endometritis in cows and improved their reproductive characteristics.

Early neonatal outcomes in infants of mothers with organ transplantation under immunosuppressive treatment.

This study aimed to examine early clinical and laboratory findings in infants born to mothers who had organ transplants and received immunosuppressive treatment. Between 2016 and 2023, the study examined infants of mothers who underwent organ transplantation and were receiving immunosuppressive treatment, and followed at the Department of Neonatology at Akdeniz University. Demographic, clinical, and laboratory characteristics of mothers and infants were recorded. On the first day of life, complete blood count values were examined, as well as potassium levels on the first, third, and seventh days, and creatinine levels on the third and seventh days. The tacrolimus blood level was calculated by taking the average of the tacrolimus blood values of the mother measured during the pregnancy. The infants were evaluated for any potential morbidities caused by intrauterine immunosuppressive drug exposure. The study included 21 mothers (some with multiple pregnancies) and 27 infants. According to the findings of this study, 74% of these infants were born premature, 67% had low birth weight, and all were delivered via cesarean section. Prematurity was associated with the morbidities found in the infants. In the early period, lymphopenia was detected in 37%, neutropenia in 25.9%, thrombocytopenia in 11.1%, hyperkalemia in 18.5%, and creatinine elevation in 7.4%, all of which returned to normal within a few days. There was no significant relationship between maternal tacrolimus blood levels and infant potassium and creatinine levels. Apart from an increased risk of prematurity, low birth weight, and cesarean delivery, no effects were observed in these infants during the early period. However, long-term follow-up is necessary to monitor for any potential morbidities.

BACTERIAL ENDOMETRITIS OF COWS AND THE CURRENT STATUS ITS ETIOTROPIC THERAPY

In the article a literature review related to the etiology, epizootology, pathogenesis, clinical symptoms of endometritis in cows and modern means of its etiotropic therapy is provided. Postpartum endometritis is considered one of the most common diseases in cows, causing great economic losses to dairy operators, due to the increase in the number of unfertilized cows after repeated artificial insemination, the increase of the service period and the percentage of culled cows, treatment costs, decrease in milk yield, etc.
 The main role in the etiology of endometritis in cows in the postpartum period is assigned to bacterial opportunistic microflora. In the etiology of endometritis, the basic role is played by Staphylococcus spp., Streptococcus spp. and Escherichia coli. Other bacteria can cause endometritis in cows, such as: Actinomyces pyogenes, Fusobacterium necrophorum, Proteus mirabilis, Proteus vulgaris, Pseudomonas aeruginosa, Prevotella spp., Bacteroides spp. In many cases, acute postpartum endometritis in cows is caused by the association of microorganisms, especially Escherichia coli with streptococci and staphylococci.
 Microorganisms penetrate the mucous membrane of the uterus, their toxins and enzymes destroy nerve endings and capillaries, what leads to a reaction in the form of an inflammatory process, what is localized mainly in the surface layers of the endometrium and in the inter-glandular connective tissue. The development of endometritis depends on the immune response of the cow, as well as on the type and number of bacteria that colonize the endometrium.
 According to the kind of the inflammatory process, endometritis in cows are classified into: purulent; serous; catarrhal; serous-catarrhal; fibrinous; catarrhal-purulent. According to the passing of the disease, endometritis are acute, subacute, less often - chronic.
 Diagnosis of endometritis includes collection of anamnestic data, general clinical exploring of the animal and special gynecological (vaginal and rectal) testing.
 The basis of the treatment of endometritis in cows is etiotropic therapy, what involves by the use of antimicrobial drugs that affect the cause of the disease, and is used to stop the reproduction of opportunistic microflora in the uterine cavity and normalize the microbiocenosis. For the etiotropic therapy of endometritis in cows, drugs for intrauterine administration and drugs for systemic treatment in the form of a solution or suspension for injections are used.

Intrauterine Drug Exposure—What the Pediatrician Needs to Know

Intrauterine Drug Exposure—What the Pediatrician Needs to Know

Intrauterine Drug Exposure—What the Pediatrician Needs to Know. Part 1: General Overview, Transplacental Drug Transfer, Teratogenicity, and Fetal Alcohol Spectrum Disorder

Intrauterine Drug Exposure—What the Pediatrician Needs to Know. Part 1: General Overview, Transplacental Drug Transfer, Teratogenicity, and Fetal Alcohol Spectrum Disorder

The incidence of subclinical endometritis in repeat breeding dairy cows and the comparative efficacy of different antibiotics and herbal intrauterine therapy

The present research work was conducted to investigate the incidence of subclinical endometritis (SE) in repeat breeder dairy cattle, and to study the comparative efficacy of different antimicrobial and polyherbal intrauterine therapies. Repeat breeding crossbred cows (>90 days in milking) with clear cervico-vaginal mucous discharge in spontaneous estrus were examined for uterine cytology by the cytobrush technique. The cows with ≥ 4% polymorphonuclear cells (PMNs) in uterine cytology were considered to be affected with SE. These cows were randomly and equally divided (n=12/group) into 5 groups and treated with the intrauterine medicine Vodine-IU (T1), Metricare-IU (T2), Utriguard-IU (T3), Uraksha (polyherbal preparation) (T4), or left untreated (control/C). In the subsequent estrus, uterine cytology was repeated and the cows were inseminated. The cows that failed to conceive but showed estrus were re-inseminated. The pregnancy status was checked. The incidence of SE was observed to be 36.80% (60/163). The PMNs percentage significantly declined in all the treatment group cows in response to treatment. The highest conception rate was observed in the T4 group (Uraksha treated) cows. It was concluded that the uterine cytobrush technique can be used efficiently for diagnosis of SE in dairy cattle, and polyherbal intrauterine drugs may be a good alternative in intrauterine antimicrobial therapy.

Concentrations of penicillin and gentamicin following intrauterine administration of two compounded formulations

The use of broad-spectrum antimicrobial therapy either by intrauterine or systemic route is commonplace in equine practice, however, much remains unknown about antibiotic efficacy in this environment. We recently demonstrated the activity of penicillin and gentamicin against common endometrial pathogens ex vivo.1 The objective of this study was to measure the concentration of gentamicin and penicillin in the uterine fluid of mares following intrauterine infusion of either a standard (PPGent) or long-acting (LA-PPGent) compounded formulation of procaine penicillin and gentamicin. We hypothesized that both drug formulations would result in therapeutic concentrations following administration, with total concentrations sustained for longer using the long-acting formulation (LA-PPGent). Ten reproductively sound mares in early estrus were administered 2378mg of procaine penicillin and 200mg of gentamicin via a single intrauterine infusion in either a standard (n=5) or a lyophilized formulation suspended in a slow-release matrix (n=5). Intrauterine fluid was collected at 0.5, 2, 4, 8, 24, 32, 48 and 72 h following infusion. A pre-weighed section of umbilical tape was introduced into the uterus through a double-guarded pipette for 30 seconds and then weighed to determine the absorbed fluid volume. Penicillin and gentamicin analyses were performed using high-performance liquid chromatography(HPLC) and ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS), respectively. Penicillin and gentamicin concentrations were assessed between groups and over time using a repeated measures analysis with treatment, time, and their interaction in the model statement with significance set at p<0.05. Mean intrauterine drug concentrations of PPGent peaked at 0.5 hours (Penicillin: 10,123.0 ± 4,298.0 µg/mL, Gentamicin: 3,397.3 ± 1,338.5 µg/mL), well above concentrations previously shown to inhibit bacterial growth ex vivo ([1] Von Dollen et al. J Equine Vet Sci 2019;79:121-26), and exceeded MIC for relevant organisms for 72 hours (Penicillin: 2.59 ± 6.34 µg/mL, Gentamicin: 2.14 ± 2.4 µg/mL). Mean concentrations of LA-PPG were lower at peak (Penicillin: 2,213.8 ± 967.8 µg/mL – p<0.05, Gentamicin: 1,859 ± 2,413 µg/mL) and exceeded MIC for 24h and 32h, respectively. These results support the use of procaine penicillin and gentamicin as intrauterine antimicrobial therapeutics. The long-acting formulation was not found to extend the time over MIC of antibiotics in the uterus of estrus mares. Acknowledgements: LA-PPGent was prepared by SR Veterinary Technologies LLC, Windsor CO using previously lyophilized PPGent. This research was supported by the Grayson-Jockey Club Research Foundation.

Hypertension in pregnancy: challenges in the management

Pregnancy is a cardiovascular and metabolic challenge to the human female body.During pregnancy, systemic vascular resistance and blood pressure decrease, whereas cardiac output and blood volume increase to safeguard an adequate circulation in the utero-placental arterial bed.Hypertensive disorders of pregnancy affect approximately from 5 to 10% of all pregnant women, and are the main contributors of maternal and neonatal morbidity and mortality worldwide. Hypertension in pregnancy includes a wide spectrum of conditions, including pre-eclampsia and eclampsia, pre-eclampsia superimposed on chronic hypertension, chronic hypertension, and gestational hypertension. Endothelial dysfunction, oxidative stress and an exaggerated inflammatory response are features related to hypertensive disorders. To reduce the risk of maternal and foetal complications due to haemodynamic maladaptation, the current management includes rest at home or in the hospital, closes monitoring of maternal and foetal signs and symptoms, early start of antihypertensive therapy, and timely delivery regarding maternal and foetal survival chances. Thresholds to initiate blood pressure lowering treatment during pregnancy are 160 mmHg systole or 110 mmHg diastole. Below these thresholds, treatment must be individualized because current evidence does not support aggressive medical interventions. Alpha-methyldopa and dihydropyridine calcium channel blockers are among the recommended antihypertensives. The major goal is to prevent maternal complications without compromising uteroplacental perfusion and fetal circulation. Before an antihypertensive agent is prescribed, the potential risk to the fetus from intrauterine drug exposure should be carefully reviewed. Bangladesh J Medicine 2023; Vol. 34, No. 2(1) Supplement: 186

Paenibacillus thiaminolyticus sepsis and meningoencephalitis in a 37-day old preterm infant

Introduction: The Paenibacillus genus consists of saprophytic organisms that are commonly associated with soil, water, plants, feces, and diseased insect larvae. Human infection is rare. This disease typically occurs in immunocompromised hosts, adults with a history of intravenous drug use, and hosts with prosthetic medical devices. There are a limited number of case reports describing Paenibacillus infections in neonates. This is the second published instance of pediatric meningoencephalitis caused by Paenibacillus thiaminolyticus in a preterm infant with intrauterine drug exposure. Case Report: A 37-day-old male infant with a history of prematurity of 33 weeks completed gestation presented to the Emergency Department for acute onset poor feeding, poor color, and unresponsiveness at home. Examination revealed cyanosis, apnea, and hypotonia. Vital signs were significant for hypotension and hypothermia. Initial labs revealed a metabolic acidosis, elevated C-reactive protein, normal complete white blood cell count, and a negative viral respiratory pathogen panel. Aerobic blood culture and cerebrospinal fluid (CSF) culture were positive for P. thiaminolyticus within 24 hours. Cranial ultrasound and magnetic resonance imaging revealed changes concerning for liquefactive meningoencephalitis. The infant was admitted to the neonatal intensive care unit (NICU) and ultimately discharged home on a “do not resuscitate/do not intubate” status and later died at 11 months of age. Conclusion: Paenibacillus species are common environmental organisms but can cause devastating disease in neonates. This is the second reported case of a preterm infant with P. thiaminolyticus infection and inutero drug exposure (IUDE), supporting that prematurity and IUDE may be risk factors for severe disease.

Policies Affecting Pregnant Women with Substance Use Disorder

Policies Affecting Pregnant Women with Substance Use Disorder

Utilizing 4D Printing to Design Smart Gastroretentive, Esophageal, and Intravesical Drug Delivery Systems.

The breakthrough of 3D printing in biomedical research has paved the way for the next evolutionary step referred to as four dimensional (4D) printing. This new concept utilizes the time as the fourth dimension in addition to the x, y, and z axes with the idea to change the configuration of a printed construct with time usually in response to an external stimulus. This can be attained through the incorporation of smart materials or through a preset smart design. The 4D printed constructs may be designed to exhibit expandability, flexibility, self-folding, self-repair or deformability. This review focuses on 4D printed devices for gastroretentive, esophageal, and intravesical delivery. The currently unmet needs and challenges for these application sites are tried to be defined and reported on published solution concepts involving 4D printing. In addition, other promising application sites that may similarly benefit from 4D printing approaches such as tracheal and intrauterine drug delivery are proposed.

Prevalence and Impact of Adverse Childhood Experiences in an Interdisciplinary, School-Based Pediatric Clinic.

This study's purpose was to ascertain the prevalence of adverse childhood experiences (ACEs) in a pediatric population and their connection to other health history information. Using health history data, a retrospective, descriptive study was undertaken with 1,028 children seen at a school-based, interprofessional clinic over 1 academic year. Nearly 58% of children had at least one ACE, and 9.5% had four or more, similar to the prevalence of ACEs in adults reported in the original study by Felitti et al. (1998). With increasing ACEs, children had higher rates of intrauterine drug exposure, intensive care on delivery, homelessness, substance abuse, behavioral problems, mental illness, learning difficulties, and weight issues. Because ACEs are prevalent among children, pediatric providers should use trauma-informed care principles and teach and model a loving and supportive adult presence in children's lives.

Incidence of Neonatal Abstinence Syndrome (NAS) in Castilla y Leon (Spain).

Introduction: Neonatal Abstinence Syndrome (NAS) is considered a Public Health problem that is defined as a group of symptoms that appear in the newborn due to withdrawal from intrauterine drug exposure. Objective: The aim of this study was to analyze the incidence of NAS in Castilla y León from 2000 to 2019. Methodology: Data of NAS cases in Castilla y León from 2000 to 2019 were obtained. NAS incidence per 1000 births was calculated and the correlation among data from different provinces and years was analyzed. Results: The cumulative incidence of NAS in Castilla y León per 1000 births between 2000-2019 was 0.91‰, with great interprovincial variability. The provinces of Zamora and Palencia stand out, with high incidence rates of NAS despite their low birth rates. The temporal trend points towards a decrease in incidence from 2000 to 2019. Opioids such as methadone, cannabis, benzodiazepines and poly-drug use are the most prevalent drugs causing NAS, and it has also been observed that methadone is being replaced by cannabis as the major cause of NAS cases at the University Hospital in Salamanca in recent years. Conclusions: The incidence of NAS in Castilla y León decreased in 2004 and remained constant until 2019, but it shows great interprovincial variability. It is necessary to implement a national NAS Registry to obtain comprehensive information regarding its incidence.

Cerebral perfusion and neurological examination characterise neonatal opioid withdrawal syndrome: a prospective cohort study

ObjectiveTo test the hypothesis that cerebral blood flow (CBF) assessed with arterial spin labelling (ASL) MRI is increased and standardised neurological examination is altered in infants with neonatal opioid withdrawal...

Neonatal outcome and adaption after in utero exposure to antidepressants: A systematic review and meta-analysis.

Major depressive disorder (MDD) and anxiety disorders are both common and especially challenging during pregnancy. Considering possible risks of intrauterine drug exposure of the child, the role of psychopharmacological treatment is ambiguous and various negative obstetric outcomes were inconsistently associated with medication. Consequently, a critical examination of peri- and postnatal phenomena associated with intrauterine exposure to antidepressants based on serotonin reuptake inhibition (SRI) and subsumed under the term "poor neonatal adaptation syndrome" (PNAS) is urgently called for. A comprehensive literature search was conducted, revealing a total number of 33 relevant studies and 69 individual outcomes among 3025 screened studies. Seventeen outcomes allowed meta-analytic evaluation (random effects model). Measures for heterogeneity (I2 ) and contour-enhanced funnel plots were generated. Single studies showed increased risks for deficits in neurological functioning and autonomous adaptation in SRI exposed infants. Meta-analytical evaluation showed increased symptom occurrence or severity in exposed neonates for low APGAR scores, birth weight, size for gestational age, preterm delivery, neuromuscular and autonomous regulation, and higher rates of admission to specialized care. Mostly, increased risk after SRI exposure was supported by comparison to unexposed infants born to mothers diagnosed with depression. Whereas statistically significant evidence for various effects of intrauterine exposure to SRI was found, the clinical relevance remains unresolved because of inherently low data quality in this research domain and insufficiently defined samples and outcomes. More systematic research under ethical considerations is required to improve multiprofessional counseling in the many women dealing with MDD during pregnancy and the peripartum.

Intrauterine drug exposure as a risk factor for cerebral palsy.

To determine whether infants with intrauterine drug exposure (IUDE) are similarly at risk for cerebral palsy (CP) as other high-risk populations, whether CP classification differs based on IUDE status, and describe the association of CP with specific substances among exposed infants. This was a retrospective analysis of infants in a high-risk follow-up program (n=5578) between January 2014 and February 2018 with a history of IUDE or who received a CP diagnosis. CP rates were compared using two-sample z-tests. CP classification was assessed using Fisher's exact, Cochran-Armitage, and Wilcoxon rank-sum tests. Models for CP risk were assessed using multivariable logistic regression. Among all infants with IUDE (n=1086), 53.8% were male with a mean (SD) birth gestational age of 36.8 (3.6) weeks. Among unexposed infants with CP (n=259), 54.4% were male with a mean (SD) birth gestational age of 29.9 (5.7) weeks. Opioids were the most common exposure (93.7%) of all infants with IUDE. The CP rate in the IUDE (5.2%) and unexposed (5.7%) high-risk populations were not significantly different (p=0.168), nor were there differences in CP typology, topography, or severity between exposed (n=57) and unexposed (n=259) infants (all p>0.05). In patients with IUDE and after controlling for established CP risk factors, the observed odds of CP varied among substances. We suggest that IUDE should be considered a 'newborn-detectable risk' in the guidelines for the early detection of CP.

International Adoption: A Review and Update.

1. Judith Kim Eckerle, MD*,† 2. Megan Marie Bresnahan, OTR/L† 3. Maria Kroupina, PhD, LP*,† 4. Dana Ernest Johnson, MD, PhD*,† 5. Cynthia Ruth Howard, MD, MPHTM*,† 1. *Department of Pediatrics, University of Minnesota, Minneapolis, MN 2. †MHealth Fairview University of Minnesota Masonic Children’s Hospital, Minneapolis, MN * Abbreviations: Ab : : antibody ACE : : adverse childhood experience CDC : : Centers for Disease Control and Prevention CXR : : chest radiography IA : : international adoptee TB : : tuberculosis 1. Key information for accurate assessment of the preadoption referral. 2. Determining immunization status and planning catch-up strategy. 3. Updated screening protocol for and treatment of latent tuberculosis infection. 4. Evaluation of developmental delays in the context of international adoption. 5. Screening for risk factors indicating the need for referral to child mental health and developmental specialists. After completing this article, readers should be able to: 1. Review the basic components of an adoption referral file and know when to consult an international adoption medicine expert. 2. Perform the initial medical assessment of a newly arrived international adoptee, including evaluation of the efficacy of previous immunizations and planning of catch-up immunization based on new recommendations. 3. Screen for tuberculosis and treat latent tuberculosis infection based on recent Centers for Disease Control and Prevention (CDC) guidelines. 4. Understand the multiple areas of a developmental baseline of adopted children and assess for catch-up needs. 5. Identify the child with multiple risk factors and/or parental or family stressors who needs a referral to an adoption-competent mental health specialist. Although interest in intercountry adoption continues to be high, the numbers of international adoptions have changed dramatically since the peak in 2004 when 45,483 international adoptees (IAs) were placed in families worldwide. By 2017, the number dropped 79% to 9,387. In the United …

What Should We Do When the Kids Grow Up? Studying the Long-Term Cognitive Effects of In-Utero Anti-Seizure Medication Exposure.

Enduring Language Deficits in Children of Women With Epilepsy and the Potential Role of Intrauterine Exposure to Antiepileptic Drugs Unnikrishnan G, Jacob NS, Salim S, et al. Epilepsia. 2020;61(11):2442-2451. doi:10.1111/epi.16685Objective:Exposure to certain intrauterine antiepileptic drugs (AEDs) can negatively influence the language skills and intelligence of young children. It remains unanswered whether these deficits are transient or persist as children grow up. This study aims to evaluate the language function of children of women with epilepsy (CWE) aged 9 to 13 years in comparison with their peers, and its relationship with intrauterine AED exposure.Methods:We included 191 CWE in our study from the Kerala Registry of Epilepsy and Pregnancy. Children in the same age group (n = 144) and without maternal epilepsy or antenatal AED exposure served as controls. We used Clinical Examination for Language Function version IV to assess language in both groups. Relevant data related to maternal epilepsy and AED use were obtained from the registry records.Results:The average Core Language Scaled Score (CLSS) was significantly lower in CWE as compared to controls (83.19 vs 90.18, P = .001). Similarly, the mean scaled scores in other language parameters were also significantly lower in CWE. In the multivariate analysis, compared to control children, the average CLSS in CWE was 4.5 units lower (95% CI = −8.8 to −0.2, P = .04) with AED monotherapy exposure and 7.3 units lower with exposure to AED polytherapy (95% CI = −13.8 to −0.8, P = .03). Intrauterine exposure to phenobarbitone (n = 61) and valproate (n = 55) as either monotherapy or polytherapy showed a negative effect on CLSS in CWE as compared to control children. However, carbamazepine (n = 75) and phenytoin (n = 37) use was not associated with significant variation of CLSS. In head-to-head comparisons between AED monotherapies in CWE, phenobarbitone showed a negative effect on CLSS (−14.7, 95% CI = −23.1 to −6.4, P = .001) as compared to carbamazepine.Significance:Intrauterine exposure to phenobarbitone and valproate impairs language development in CWE, with effects persisting into the second decade.

Neonatal Abstinence Syndrome and Preterm Infants: A Look at Current Practice.

Intrauterine opioid drug exposure is associated with an increased risk of preterm birth. Preterm infants may not exhibit the same withdrawal symptoms as term infants diagnosed with neonatal abstinence syndrome (NAS). There are no current standards for how to screen, assess, or treat NAS in preterm infants. This study explored the current state of practice for preterm infants born at less than 34 weeks of gestational age exposed to intrauterine opioids. This was a descriptive cross-sectional study of NAS practice in preterm infants born at less than 34 weeks of gestational age in neonatal intensive care units (NICUs) in the United States and Canada. The study was conducted May through September 2018. All respondents cared for preterm infants born at less than 34 weeks of gestational age exposed to intrauterine drugs. There were 70 respondents representing 67 hospitals in the United States and 1 in Canada. Level III NICUs represented 69% of respondents. Ninety-three percent reported neonatal triggers for further evaluation. Review of maternal history and maternal urine testing was the most consistent practice across NICUs. A modified Finnegan scoring tool was used for both preterm and term infants. Morphine was reported as the most common first-line drug used for treatment. Great variability in NAS practice for preterm infants born at less than 34 weeks of gestational age across the multiple NICUs supports the need for a validated preterm infant assessment tool and development of appropriate treatment strategies. Future research describing the NAS symptomatology of preterm infants born at less than 34 weeks of gestational age exposed to intrauterine opioids is warranted.

Adverse effects of maternal rheumatoid arthritis during pregnancy on children.

Adverse effects of maternal rheumatoid arthritis during pregnancy on children.