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Archives of Gynecology and Obstetrics Jun 2024We aimed to perform a systematic review and meta-analysis addressing the efficacy of levothyroxine therapy in pregnant women with subclinical hypothyroidism considering... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
We aimed to perform a systematic review and meta-analysis addressing the efficacy of levothyroxine therapy in pregnant women with subclinical hypothyroidism considering most recent evidence and subgroups of interest for clinical practice.
METHODS
PubMed, Embase, and Cochrane Central were searched from inception for randomized controlled trials (RCTs) comparing levothyroxine with placebo or no intervention in pregnant women with subclinical hypothyroidism. We used a random-effects model and conducted subgroup analyses based on thyroid peroxidase antibody status, thyroid stimulating hormone levels, fertility treatment, and recurrent miscarriage.
RESULTS
We included 11 RCTs comprising 2,749 pregnant women with subclinical hypothyroidism. Patients treated with levothyroxine (1,439; 52.3%) had significantly lower risk of pregnancy loss (risk ratio 0.69; 95% confidence interval 0.52-0.91; p < 0.01; 6 studies). However, there was no significant association between levothyroxine and live birth (risk ratio 1.01; 95% confidence interval 0.99-1.03; p = 0.29; 8 studies). No statistically significant interaction was observed across subgroups (p > 0.05).
CONCLUSION
Levothyroxine replacement therapy for subclinical hypothyroidism during pregnancy may decrease pregnancy loss when early prescribed. Nevertheless, further investigation is needed in patients with thyroid stimulating hormone above four milliunits per liter, especially when associated with recurrent miscarriage or infertility.
Topics: Humans; Pregnancy; Female; Hypothyroidism; Thyroxine; Pregnancy Complications; Randomized Controlled Trials as Topic; Thyrotropin; Abortion, Habitual
PubMed: 38676741
DOI: 10.1007/s00404-024-07512-3 -
Cureus Oct 2023Primary hypothyroidism is a commonly encountered endocrine disorder and can be associated with pericardial effusion and cardiac tamponade in severe cases. Early...
Primary hypothyroidism is a commonly encountered endocrine disorder and can be associated with pericardial effusion and cardiac tamponade in severe cases. Early detection of hypothyroidism is key since it is a potentially treatable and reversible cause of pericardial effusions. A 53-year-old female was admitted following a fall. The clinical history was remarkable, with symptoms of persistent tiredness and fatigue for six months. She had no known medical conditions and was not taking any regular medications. Vital signs were stable. Physical examination revealed bilateral pitting pedal oedema and a tense abdomen with shifting dullness. Cardiovascular and respiratory examinations were normal. Notably, the patient exhibited delayed relaxation of deep-tendon reflexes bilaterally at the patellar and ankle sites. Pertinent laboratory findings showed an elevated thyroid-stimulating hormone (TSH) level of 151.69 milliunits/L, a low free thyroxine (fT4) level of <5.4 pmol/L, a haemoglobin level of 85 g/L, and a markedly high anti-thyroid peroxidase antibody level of 957.35 IU/mL. An electrocardiogram revealed a normal sinus rhythm with a low-voltage QRS complex. Chest X-ray findings indicated cardiomegaly suggestive of left heart failure. An emergent transthoracic echocardiography (TTE) demonstrated a large pericardial effusion measuring 5.4 cm posterior to the left ventricle. The most likely aetiology in this case was severe primary hypothyroidism. She initially received intravenous liothyronine 10 micrograms every four hours, followed by oral liothyronine 5 micrograms twice a day in conjunction with levothyroxine 100 micrograms once a day. The adrenal reserve assessment was satisfactory. An urgent pericardiocentesis was performed, draining a total of 900 mL of serosanguinous fluid. Serial echocardiograms demonstrated the absence of residual effusion. Hypothyroidism is a relatively uncommon cause of pericardial effusion. By ensuring early detection and appropriate treatment, we can optimise patient outcomes and prevent potential complications associated with untreated hypothyroidism.
PubMed: 38021716
DOI: 10.7759/cureus.46947 -
American Journal of Obstetrics and... Jun 2024The principal fetal energy source is glucose provided by the placental transfer of maternal glucose. However, the placenta's glucose consumption exhibits considerable...
BACKGROUND
The principal fetal energy source is glucose provided by the placental transfer of maternal glucose. However, the placenta's glucose consumption exhibits considerable variation. Hexokinase is the first and one of the rate-limiting enzymes of glycolysis that phosphorylates glucose to glucose-6-phosphate. The role of placental hexokinase activity in human placental glucose metabolism is unknown.
OBJECTIVE
This study aimed to test the hypothesis that placental hexokinase activity is related to maternal body mass index, placental glucose uptake and consumption, and birthweight.
STUDY DESIGN
Overall, 67 healthy pregnant participants at term were included in this study at Oslo University Hospital, Oslo, Norway. Placental hexokinase activity was measured by using a colorimetric assay. The mass of glucose taken up by the uteroplacental unit and the fetus was obtained by measuring arteriovenous glucose differences combined with Doppler assessment of uterine and umbilical blood flow. Blood samples were obtained from the maternal radial artery, uterine vein, and umbilical artery and vein. The uteroplacental glucose consumption constituted the difference between uteroplacental and fetal glucose uptakes. The Spearman rank correlation was performed for statistical analyses to study the correlation of placental hexokinase activity (milliunit per milligram of protein) with prepregnancy body mass index, maternal glucose and insulin, birthweight, uteroplacental glucose uptake and consumption, and fetal glucose uptake (micromole per minute). Partial rank correlation analysis was performed when controlling for hours of fasting or placental weight.
RESULTS
Hexokinase activity was detectable in all placental tissue samples. The mean activity was 19.6 (standard deviation, 4.64) mU/mg protein. Placental hexokinase activity correlated positively with prepregnancy body mass index (Spearman rho=0.33; P=.006). On controlling for hours of fasting, hexokinase activity showed positive correlations with both maternal glucose (r=0.30; P=.01) and insulin (r=0.28; P=.02). Hexokinase activity was positively correlated with uteroplacental glucose uptake (Spearman rho=0.31; P=.01) and consumption (Spearman rho=0.28; P=.02). Hexokinase activity did not correlate with fetal glucose uptake. On controlling for placental weight, hexokinase activity showed a positive correlation with birthweight (r=0.31; P=.01).
CONCLUSION
Our findings suggest that placental hexokinase, being crucial for uteroplacental retention of glucose for disposition, is related to both maternal body mass index and birthweight independent of placental weight. Placental hexokinase may play a central role in the relationship between maternal glucose dysregulation and fetal growth. Thus, the current study supports the need to develop clinically useful tools to assess the metabolic properties of the placenta.
Topics: Humans; Female; Hexokinase; Pregnancy; Placenta; Body Mass Index; Birth Weight; Adult; Glucose; Blood Glucose; Infant, Newborn
PubMed: 37925123
DOI: 10.1016/j.ajog.2023.10.043 -
BMC Pregnancy and Childbirth Mar 2023The reproductive hormone oxytocin facilitates labour, birth and postpartum adaptations for women and newborns. Synthetic oxytocin is commonly given to induce or augment...
Maternal and newborn plasma oxytocin levels in response to maternal synthetic oxytocin administration during labour, birth and postpartum - a systematic review with implications for the function of the oxytocinergic system.
BACKGROUND
The reproductive hormone oxytocin facilitates labour, birth and postpartum adaptations for women and newborns. Synthetic oxytocin is commonly given to induce or augment labour and to decrease postpartum bleeding.
AIM
To systematically review studies measuring plasma oxytocin levels in women and newborns following maternal administration of synthetic oxytocin during labour, birth and/or postpartum and to consider possible impacts on endogenous oxytocin and related systems.
METHODS
Systematic searches of PubMed, CINAHL, PsycInfo and Scopus databases followed PRISMA guidelines, including all peer-reviewed studies in languages understood by the authors. Thirty-five publications met inclusion criteria, including 1373 women and 148 newborns. Studies varied substantially in design and methodology, so classical meta-analysis was not possible. Therefore, results were categorized, analysed and summarised in text and tables.
RESULTS
Infusions of synthetic oxytocin increased maternal plasma oxytocin levels dose-dependently; doubling the infusion rate approximately doubled oxytocin levels. Infusions below 10 milliunits per minute (mU/min) did not raise maternal oxytocin above the range observed in physiological labour. At high intrapartum infusion rates (up to 32 mU/min) maternal plasma oxytocin reached 2-3 times physiological levels. Postpartum synthetic oxytocin regimens used comparatively higher doses with shorter duration compared to labour, giving greater but transient maternal oxytocin elevations. Total postpartum dose was comparable to total intrapartum dose following vaginal birth, but post-caesarean dosages were higher. Newborn oxytocin levels were higher in the umbilical artery vs. umbilical vein, and both were higher than maternal plasma levels, implying substantial fetal oxytocin production in labour. Newborn oxytocin levels were not further elevated following maternal intrapartum synthetic oxytocin, suggesting that synthetic oxytocin at clinical doses does not cross from mother to fetus.
CONCLUSIONS
Synthetic oxytocin infusion during labour increased maternal plasma oxytocin levels 2-3-fold at the highest doses and was not associated with neonatal plasma oxytocin elevations. Therefore, direct effects from synthetic oxytocin transfer to maternal brain or fetus are unlikely. However, infusions of synthetic oxytocin in labour change uterine contraction patterns. This may influence uterine blood flow and maternal autonomic nervous system activity, potentially harming the fetus and increasing maternal pain and stress.
Topics: Infant, Newborn; Pregnancy; Female; Humans; Oxytocin; Parturition; Postpartum Period; Labor, Obstetric; Postpartum Hemorrhage
PubMed: 36864410
DOI: 10.1186/s12884-022-05221-w -
Obstetrics and Gynecology Feb 2023Despite lack of evidence for a safety threshold for oxytocin dose rate, many hospital protocols specify a maximum rate. We investigated whether exceeding 20... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
Despite lack of evidence for a safety threshold for oxytocin dose rate, many hospital protocols specify a maximum rate. We investigated whether exceeding 20 milliunits/min of oxytocin was associated with adverse outcomes.
METHODS
This is a secondary analysis of a double-blind, single-center, randomized controlled trial of nulliparous patients with singleton gestations at 36 weeks of gestation or later who presented in spontaneous labor randomized 1:1 to either a high-dose oxytocin titration regimen (initial-incremental rate of 6 milliunits/min) or standard-dose titration regimen (initial-incremental rate of 2 milliunits/min) for labor augmentation. A maximum oxytocin dose rate limit was not specified in the study protocol. For this secondary analysis, outcomes of participants who received oxytocin and exceeded a dose rate of 20 milliunits/min at any point in labor were compared with those whose rate remained at 20 milliunits/min or less. In addition, the cumulative proportions of labor and birth outcomes were calculated for each maximum dose rate of oxytocin reached among this study cohort.
RESULTS
Of the 1,003 participants in the parent trial, 955 (95.2%) received oxytocin, as planned, and were included, with 190 (19.9%) exceeding a maximum dose rate of 20 milliunits/min. Those who exceeded 20 milliunits/min were older and were more likely to have rupture of membranes as their trial entry indication, have hypertensive disorders of pregnancy, receive intrapartum magnesium sulfate infusion, and receive oxytocin for longer. Those whose maximum rates exceeded 20 milliunits/min underwent cesarean delivery more frequently, but the majority (74%) still delivered vaginally. In multivariable analyses, there were no significant associations between maximum oxytocin dose rates greater than 20 milliunits/min and cesarean delivery (adjusted odds ratio [aOR] 1.57, 95% CI 1.00-2.46), peripartum infection (aOR 0.69, 95% CI 0.41-1.19), postpartum hemorrhage (aOR 1.37, 95% CI 0.70-2.71), or neonatal intensive care unit (NICU) admission (aOR 1.72, 95% CI 0.89-3.31). Although 85% of spontaneous vaginal deliveries occurred at maximum oxytocin dose rates of 20 milliunits/min or less, vaginal deliveries continued to occur at higher maximum dose rates. The cumulative proportions of NICU admissions and composite severe neonatal morbidity and mortality cases increased with increasing oxytocin dose rates even with maximum oxytocin dose rates at 20 milliunits/min or less.
CONCLUSION
In multivariable analyses, there are no significant differences in maternal or perinatal adverse outcomes based on exceeding 20 milliunits/min of oxytocin. These data suggest that oxytocin dosing should be individualized to each patient and not be based on arbitrary thresholds.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov , NCT02487797.
Topics: Female; Humans; Infant, Newborn; Pregnancy; Cesarean Section; Delivery, Obstetric; Labor, Induced; Oxytocics; Oxytocin; Double-Blind Method
PubMed: 36649339
DOI: 10.1097/AOG.0000000000005058 -
SAGE Open Medical Case Reports 2022Treatment of neonates with persistent pulmonary hypertension of newborn includes optimization of ventilatory support, use of pulmonary vasodilators, and/or inotropic...
Treatment of neonates with persistent pulmonary hypertension of newborn includes optimization of ventilatory support, use of pulmonary vasodilators, and/or inotropic support. If refractory to this management, some may require extracorporeal membrane oxygenation. We describe a case series of 10 neonates with refractory persistent pulmonary hypertension of newborn treated with vasopressin in a single tertiary center. Mean initiation time of vasopressin was at 30 h of life with a dose ranging from 10 to 85 milliunits/kg/h. Oxygenation index decreased after 12 h of vasopressin exposure (25 to 11) and mean arterial pressure improved after 1 h (45 to 58 mm Hg). Extracorporeal membrane oxygenation was averted in 50% of the cases with transient hyponatremia as the only notable side effect. Although our findings are exploratory and further research is needed to establish safety and efficacy, our experience suggests that vasopressin may have rescue properties in the management of refractory persistent pulmonary hypertension of newborn.
PubMed: 35693924
DOI: 10.1177/2050313X221102289 -
Frontiers in Neurology 2022This study aimed to construct an animal model of intracranial arterial dolichoectasia (IADE) applying the modified modeling protocol.
BACKGROUND AND PURPOSE
This study aimed to construct an animal model of intracranial arterial dolichoectasia (IADE) applying the modified modeling protocol.
MATERIALS AND METHODS
Twenty five milliunits elastase and inactivated elastase were, respectively, injected into the cerebellomedullary cistern of 60 C57/BL6 mice which were divided into experimental group (EG, = 30) and control group (CG, = 30) by using a computer-based random order generator. The modified modeling protocol clarified these aspects including brain three-dimensional parameters of mouse head fixation, angle of head inclination, fixed position of taper ear, needle holding technique, needle entry depth, prevention of liquid drug back flow, and storage conditions of elastase. And it was observed for the following parts such as mortality, inflammatory factors, craniocerebral arteries scanning, vascular tortuosity index, artery diameter, pathology of the cerebrovascular.
RESULTS
Within differently surveyed stage, the total mortality of mice in EG was 20%. ELISA illustrated that the levels of matrix metalloproteinase-9 (MMP-9) and tumor necrosis factor α (TNF-α) in peripheral blood were increased significantly after modeling. Angiography indicated that 100% of IADE in EG were observed and the diameter and tortuosity index of the basilar artery were significantly increased ( < 0.01). EVG histological processing and staining showed the disrupted internal elastic lamina, the atrophied muscle layer, and the hyalinized connective tissue of the basilar artery with the vascular wall tunica media in EG. Micro-computed tomography reported that the craniocerebral arteries of the mice in EG were outstandingly elongated, tortuous, and dilated.
CONCLUSION
The modified modeling protocol can reduce the mortality, improve the success rate, and provide a stable animal model for IADE.
PubMed: 35518204
DOI: 10.3389/fneur.2022.860541 -
Pediatric Cardiology Dec 2021The use of vasopressin has been increased in recent years in children after congenital heart surgery. However, there is limited information regarding its effects on...
The use of vasopressin has been increased in recent years in children after congenital heart surgery. However, there is limited information regarding its effects on cardiac output, systemic oxygen delivery, and myocardial energetics. The purpose of this study is to characterize the effects of vasopressin infusions on hemodynamics and systemic oxygen delivery in children with congenital heart disease. A retrospective, single-center study of patients with congenital heart disease who received vasopressin infusions in a pediatric cardiac intensive care unit between January 2019 and May 2020. The measured values collected for study were systolic and diastolic blood pressure, heart rate, arterial oxygen saturation as determined by pulse oximetry, arterial pH, arterial partial pressure of oxygen, arterial partial pressure of carbon dioxide, serum lactate, serum sodium, and renal and cerebral oximetry based on near-infrared spectroscopy. The calculated values for this study were the difference between arterial and NIRS oximetry, the reno-cerebral near-infrared spectroscopy gradient and the vasoinotrope score. A Wilcoxon signed-rank test was utilized to compare values of paired continuous variables before and after initiation of the vasopressin infusion. Correlations were assessed using Spearman correlation analyses and stepwise regressions were completed. A total of 26 vasopressin infusions among 20 unique patients were included in the final analyses. Of these 26 vasopressin infusions, 18 were in patients with biventricular circulation and 8 were in patients with functionally univentricular circulation. The median vasopressin infusion dose at initiation was 0.4 (0.1-1) milliunits/kg/min. For the entire cohort 2 h after the initiation of vasopressin, systolic blood pressure increased to 8.4 mmHg, p < 0.01, but no significant correlation was found to markers of systemic oxygen delivery. Similar results were obtained when only those with biventricular circulation were considered. Those with functionally univentricular circulation were not found to have any statistically significant rise in blood pressure. Vasopressin infusions appear to statistically significantly increase systolic blood pressure in children with congenital heart disease who have a biventricular but not functionally univentricular circulation. Even when an increase in systolic blood pressure is present, systemic oxygen delivery did not improve.
Topics: Arginine; Blood Pressure; Cerebrovascular Circulation; Child; Heart Defects, Congenital; Hemodynamics; Humans; Oximetry; Oxygen; Retrospective Studies; Vasopressins
PubMed: 34181038
DOI: 10.1007/s00246-021-02667-1 -
EFSA Journal. European Food Safety... Apr 2021Pasteurisation of raw milk, colostrum, dairy or colostrum-based products must be achieved using at least 72°C for 15 s, at least 63°C for 30 min or any equivalent...
Pasteurisation of raw milk, colostrum, dairy or colostrum-based products must be achieved using at least 72°C for 15 s, at least 63°C for 30 min or any equivalent combination, such that the alkaline phosphatase (ALP) test immediately after such treatment gives a negative result. For cows' milk, a negative result is when the measured activity is ≤ 350 milliunits of enzyme activity per litre (mU/L) using the ISO standard 11816-1. The use and limitations of an ALP test and possible alternative methods for verifying pasteurisation of those products from other animal species (in particular sheep and goats) were evaluated. The current limitations of ALP testing of bovine products also apply. ALP activity in raw ovine milk appears to be about three times higher and in caprine milk about five times lower than in bovine milk and is highly variable between breeds. It is influenced by season, lactation stage and fat content. Assuming a similar pathogen inactivation rate to cows' milk and based on the available data, there is 95-99% probability (extremely likely) that pasteurised goat milk and pasteurised sheep milk would have an ALP activity below a limit of 300 and 500 mU/L, respectively. The main alternative methods currently used are temperature monitoring using data loggers (which cannot detect other process failures such as cracked or leaking plates) and the enumeration of Enterobacteriaceae (which is not suitable for pasteurisation verification but is relevant for hygiene monitoring). The inactivation of certain enzymes other than ALP may be more suitable for the verification of pasteurisation but requires further study. Secondary products of heat treatment are not suitable as pasteurisation markers due to the high temperatures needed for their production. More research is needed to facilitate a definitive conclusion on the applicability of changes in native whey proteins as pasteurisation markers.
PubMed: 33968255
DOI: 10.2903/j.efsa.2021.6576 -
Obstetrics and Gynecology Jun 2021To evaluate whether a high-dose oxytocin regimen reduces the risk for primary cesarean birth and other obstetric morbidities when compared with standard dosing. (Comparative Study)
Comparative Study
OBJECTIVE
To evaluate whether a high-dose oxytocin regimen reduces the risk for primary cesarean birth and other obstetric morbidities when compared with standard dosing.
METHODS
In a double-blind randomized clinical trial of nulliparous women at or beyond 36 weeks of gestation who were undergoing augmentation of labor, participants were assigned to high-dose (initial and incremental rates of 6 milliunits/min) or standard-dose (initial and incremental rates of 2 milliunits/min) oxytocin regimens. The primary outcome was cesarean birth. Prespecified secondary outcomes included labor duration, clinical chorioamnionitis, endometritis, postpartum hemorrhage, Apgar score 3 or less at 5 minutes, umbilical artery acidemia, neonatal intensive care unit admission, perinatal death, and a severe perinatal morbidity composite. A sample size of 501 per group (n=1,002) was planned to detect a 6.6% absolute reduction in rate of the primary outcome, from 20% in the standard-dose group to 13.4% in the high-dose group with 80% power.
RESULTS
From September 2015 to September 2020, 1,003 participants were randomized-502 assigned to high-dose and 501 assigned to standard dosing. The majority of participants were of White race, were married or living as married, and had commercial insurance. Baseline characteristics between groups were similar. The primary outcome occurred in 14.5% of those receiving high-dose compared with 14.4% of those receiving standard-dose oxytocin (relative risk, 1.01; 95% CI 0.75-1.37). The high-dose group had a significantly shorter mean labor duration (9.1 vs 10.5 hours; P<.001), and a significantly lower chorioamnionitis incidence (10.4% vs 15.6%; relative risk, 0.67; 95% CI 0.48-0.92) compared with standard dosing. Umbilical artery acidemia was significantly less frequent in the high-dose group in complete case analysis, but this finding did not persist after multiple imputation (relative risk, 0.55; 95% CI 0.29-1.04). There were no significant differences in other secondary outcomes.
CONCLUSION
Among nulliparous participants who were undergoing augmentation of labor, a high-dose oxytocin regimen, compared with standard dosing, did not affect the cesarean birth risk but significantly reduced labor duration and clinical chorioamnionitis frequency without adverse effects on perinatal outcomes.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov, NCT02487797.
Topics: Acidosis; Adult; Apgar Score; Cesarean Section; Chorioamnionitis; Double-Blind Method; Female; Fetal Blood; Humans; Infant, Newborn; Intensive Care Units, Neonatal; Labor, Obstetric; Male; Oxytocics; Oxytocin; Parity; Patient Admission; Pregnancy; Time Factors; Umbilical Arteries
PubMed: 33957657
DOI: 10.1097/AOG.0000000000004399