Article

Antenatal exposure to magnesium sulfate and the incidence of patent ductus arteriosus in extremely low birth weight infants

March 2007
Journal of Perinatology 27(3):154-7

DOI:10.1038/sj.jp.7211663

Source
PubMed

Authors:

Teresa del Moral

University of Miami

Silvia Vanbuskirk

University of Miami

Show all 5 authorsHide

Magnesium sulfate (MgSO(4)) is the most commonly used tocolytic agent in the US and is also employed as a prophylactic agent against seizures in pre-eclamptic women. MgSO(4) crosses the placenta and its concentration in the newborn usually exceeds that of maternal levels. The purpose of this study was to explore the relationship between antenatal exposure to MgSO(4) and the incidence of patent ductus arteriosus (PDA) in extremely low birth weight infants. A total of 954 neonates with birth weights between 500 and 1000 g, born at the University of Miami/Jackson Memorial Hospital between January 1995 and December 2004 and surviving for more than 3 days, were followed until death or discharge from the hospital. The incidence of PDA in infants exposed to MgSO(4) was compared with those not exposed and comparisons were also made between infants exposed to different maternal doses of MgSO(4). The incidence of PDA was significantly higher in the group of infants exposed to MgSO(4) compared with the unexposed control group (67 vs. 60%, P<0.018). When stratified by gestational age the differences were significant only in the group of infants with a gestational age of >or=26 weeks (58 vs. 49%, P<0.039). Logistic regression analysis to adjust for co-variables indicated an increased risk of PDA with higher doses of MgSO(4) (odds ratio 1.33 confidence interval (CI) 1.12 to 1.58, per 50 g of MgSO(4)). Antenatal exposure to MgSO(4) is associated with a higher risk of PDA in extremely low birth weight infants and this effect is more significant and dose-related in more mature infants.

Vasoactivity of magnesium sulfate in chicken ductus arteriosus

Article

Full-text available

Jan 2021
J PHYSIOL PHARMACOL

Prenatal treatment with magnesium sulfate (MgSO4) has neuroprotective effects in very preterm infants but its use has been associated with an increased rate of patent ductus arteriosus (DA). MgSO4 is a vasodilator and thus may exert a direct relaxant effect in the DA. We aimed to investigate the vasoactive effects of MgSO4 in the DA using the chicken embryo as experimental model. DA rings from 15-d (E15), 17-d (E17) and 19-d (E19) chicken embryos (total incubation: 21-d) were mounted in a wire myograph for isometric tension recordings. Exposure of DA rings to 21% O2 induced a tonic contraction which was relaxed by MgSO4 (2.4 – 7.2 mmol L–1) in a concentration-dependent manner (mean maximal relaxation E19:51.4%, SE 6.3; EC50: 3.5 mmol L–1, SE 0.7). The relaxation evoked by MgSO4 was not significantly different between E15, E17 and E19 DA and was not affected by removal of the endothelium or by the presence of the nitric oxide synthase inhibitor L-NAME, the soluble guanylate cyclase inhibitor ODQ, or the cyclooxygenase inhibitor indomethacin. In contrast, when the DA rings were incubated in Ca2+ -free solution, or in the presence of inhibitors of L-type Ca2+ channels (nifedipine), or large conductance Ca2+-activated K+ (BKCa) channels (iberiotoxin), MgSO4-induced relaxation was impaired. Preincubation of the DA rings with MgSO4 concentrations ranging from 0 to 6.0 mmol L–1 did not significantly affect O2-induced contraction that was only impaired by a concentration of 7.2 mmol L–1. In conclusion, MgSO4 induced endothelium-independent relaxation of chicken DA and this relaxation appeared to be mediated through stimulation of BKCa channels and blockade of transmembrane flux of extracellular Ca2+. However, O2-induced DA contraction was only impaired by suprapharmacological concentrations of MgSO4 (> 6.0 mmol L–1). Therefore, our data suggest that the higher incidence of patent DA in preterm infants exposed to MgSO4 is unlikely to be due to a direct pharmacological effect of the drug on the DA.

Antenatal magnesium sulphate and adverse neonatal outcomes: A systematic review and meta-analysis

Article

Full-text available

Dec 2019
PLOS MED

Background There is widespread, increasing use of magnesium sulphate in obstetric practice for pre-eclampsia, eclampsia, and preterm fetal neuroprotection; benefit for preventing preterm labour and birth (tocolysis) is unproven. We conducted a systematic review and meta-analysis to assess whether antenatal magnesium sulphate is associated with unintended adverse neonatal outcomes. Methods and findings CINAHL, Cochrane Library, LILACS, MEDLINE, Embase, TOXLINE, and Web of Science, were searched (inceptions to 3 September 2019). Randomised, quasi-randomised, and non-randomised trials, cohort and case–control studies, and case reports assessing antenatal magnesium sulphate for pre-eclampsia, eclampsia, fetal neuroprotection, or tocolysis, compared with placebo/no treatment or a different magnesium sulphate regimen, were included. The primary outcome was perinatal death. Secondary outcomes included pre-specified and non-pre-specified adverse neonatal outcomes. Two reviewers screened 5,890 articles, extracted data, and assessed risk of bias following Cochrane Handbook and RTI Item Bank guidance. For randomised trials, pooled risk ratios (RRs) or mean differences, with 95% confidence intervals (CIs), were calculated using fixed- or random-effects meta-analysis. Non-randomised data were tabulated and narratively summarised. We included 197 studies (40 randomised trials, 138 non-randomised studies, and 19 case reports), of mixed quality. The 40 trials (randomising 19,265 women and their babies) were conducted from 1987 to 2018 across high- (16 trials) and low/middle-income countries (23 trials) (1 mixed). Indications included pre-eclampsia/eclampsia (24 trials), fetal neuroprotection (7 trials), and tocolysis (9 trials); 18 trials compared magnesium sulphate with placebo/no treatment, and 22 compared different regimens. For perinatal death, no clear difference in randomised trials was observed between magnesium sulphate and placebo/no treatment (RR 1.01; 95% CI 0.92 to 1.10; 8 trials, 13,654 babies), nor between regimens. Eleven of 138 non-randomised studies reported on perinatal death. Only 1 cohort (127 babies; moderate to high risk of bias) observed an increased risk of perinatal death with >48 versus ≤48 grams magnesium sulphate exposure for tocolysis. No clear secondary adverse neonatal outcomes were observed in randomised trials, and a very limited number of possible adverse outcomes warranting further consideration were identified in non-randomised studies. Where non-randomised studies observed possible harms, often no or few confounders were controlled for (moderate to high risk of bias), samples were small (200 babies or fewer), and/or results were from subgroup analyses. Limitations include missing data for important outcomes across most studies, heterogeneity of included studies, and inclusion of published data only. Conclusions Our findings do not support clear associations between antenatal magnesium sulphate for beneficial indications and adverse neonatal outcomes. Further large, high-quality studies (prospective cohorts or individual participant data meta-analyses) assessing specific outcomes, or the impact of regimen, pregnancy, or birth characteristics on these outcomes, would further inform safety recommendations. PROSPERO: CRD42013004451.

Çok düşük doğum ağırlıklı prematürelerde antenatal magnezyum sülfat kullanımının patent duktus arteriozusa etkisi

Article

Full-text available

Aug 2019
J Harran Unv Med F

Amaç: Patent duktus arteriozus (PDA) sıklığı, gebelik haftası ve doğum ağırlığıyla ters orantılıdır ve birçok prematüre morbiditesine ve mortalitesine neden olabilir. Erken eyleminde tokolitik olarak kullanılan magnezyum sülfatın (MgSO4) PDA sıklığını artırdığıyla ilgili çelişkili sonuçlar vardır. Çalışmamızda çok düşük doğum ağırlıklı (ÇDDA; <1500g) prematürelerde antenatal MgSO4 uygulanmasının hemodinamik anlamlı PDA’nın (haPDA) üzerine etkisini belirlenmesi amaçlanmıştır. Materyal ve metod: Çalışmamızda Ocak 2013 ile Aralık 2016 tarihleri arasında ünitemizde izlenen, ÇDDA bebekler retrospektif olarak incelendi. Bebeklerin demografik ve klinik özellikleri kayıt edildi. Çalışmaya dahil edilen prematürelerin haPDA’sı olan ve olmayanlar olarak iki gruba ayrılarak, demografik, klinik özellikleri ve MgSO4 uygulanması açından karşılaştırıldı. Bulgular: Toplam 602 ÇDDA bebeğin dahil edildiği çalışmamızda, 257 bebekte (%42,7) haPDA saptandı ve 11 bebeğe (%1,8) PDA ligasyonu uygulandı. Hemodinamik anlamlı PDA grubunda antenatal MgSO4 uygulanma oranı %61,8 (n=159), haPDA olmayan gruptaki antenatal MgSO4 uygulanma oranına %31,6 (n=109) göre istatistiksel olarak anlamlı yüksek olarak tespit edildi (p<0,001). Sonuç: Çalışmamızda ÇDDA’lı bebeklerde haPDA grubunda antenatal MgSO4 kullanım oranı ve prematüre morbiditeleri daha yüksek olarak bulundu. Anahtar kelimeler: Hemodinamik anlamlı patent duktus arteriozus, prematüre, çok düşük doğum ağırlığı, magnezyum sülfat

Effects of antenatal magnesium sulfate therapy on cerebral and systemic hemodynamics in preterm newborns‏

Article

Jan 2010

Mohamed El Gergawi

The role of Magnetic Resonance Urography (MRU) and Computed Tomographic Urography (CTU) in Evaluation of Ureteric Diseases

Conference Paper

Apr 2012

Hosam Yousef

Antenatal magnesium sulfate and the postnatal response of the ductus arteriosus to indomethacin in extremely preterm neonates

Article

Full-text available

Jan 2011

The aim of this study is to evaluate the influence of antenatal magnesium sulfate (MgSO(4)) treatment on the clinical responsiveness of the ductus arteriosus to indomethacin prophylaxis and on that of symptomatic patent ductus arteriosus (sPDA) to indomethacin treatment in premature neonates. This is a retrospective study of 160 consecutively admitted neonates with a gestational age of <28 weeks (41 MgSO(4) exposed and 119 controls) who received indomethacin prophylaxis. Incidence of early closure of the ductus arteriosus was lower in the MgSO(4)-exposed neonates than in the control group (59 vs 84%, respectively; P=0.002), whereas incidence of an sPDA was higher (46 vs 24%, respectively; P=0.006). Response to indomethacin treatment was similar between the two groups. Logistic regression analysis indicated increased risk of failure of early ductus arteriosus closure following antenatal MgSO(4) treatment (odds ratio, 4.03; P=0.002). In extremely preterm neonates, antenatal MgSO(4) treatment reduces clinical responsiveness of the ductus arteriosus to indomethacin prophylaxis but not that of sPDA to indomethacin treatment.

Effects of antenatal magnesium sulfate therapy on cerebral and systemic hemodynamics in preterm newborns

Article

Jun 2010
ACTA OBSTET GYN SCAN

To investigate whether antenatal magnesium sulfate (MgSO(4)) exposure has an influence on cerebral blood flow and systemic hemodynamics in preterm infants during the first few days of life. Prospective case-control study. University affiliated referral hospital. A total of 48 women who delivered preterm (30-34 weeks) and their offspring. Mothers and newborns were divided into two groups based on maternal exposure to MgSO(4) (n = 28) or not (n = 20). Cerebral blood flow velocity measurements were obtained from the neonatal anterior cerebral artery and right and left middle cerebral arteries. Neonatal Doppler examinations of the brain circulation, heart rate, systemic blood pressure and echocardiographic assessment of ductus arteriosus shunting during the first week of life. Maternal MgSO(4) had a significant lowering effect on neonatal cerebral blood flow. Peak systolic velocity was significantly lower in anterior cerebral artery and right and left middle cerebral arteries (p = 0.031, 0.027 and 0.039, respectively), as was end-diastolic velocity (p = 0.035, 0.012 and 0.025, respectively) and mean velocity (p = 0.036, 0.024 and 0.003, respectively). The resistance index and relative vascular resistance in the three cerebral arteries showed no significant difference between the two studied groups. Antenatal MgSO(4) exposure before preterm birth has potent systemic vascular effects in the preterm offspring, which is reflected in decreased neonatal cerebral perfusion during the critical first few days of life. This is associated with an increased incidence of patent ductus arteriosus, which may require operative intervention.

Efficacy of Paracetamol in Closure of Ductus Arteriosus in Infants under 32 Weeks of Gestation

Article

Full-text available

Feb 2018

Background Standard medical treatment for patent ductus arteriosus (PDA) closure has been indomethacin/ibuprofen or surgical ligation. Up to date, new strategies have been reported with paracetamol. The aim of this study was to present our experience with intravenous paracetamol for closing PDA in preterm neonates presenting contraindication to ibuprofen or ibuprofen had failed and no candidates for surgical ligation because of huge instability.Materials and methodsWe conducted a retrospective case series study in a neonatal intensive care unit from a tertiary hospital. 9 preterm infants ≤32 weeks of gestational age with hemodynamically significant PDA (hsPDA) were enrolled. They received 15 mg/kg/6h intravenous paracetamol for ductal closure. Demographic data and transaminase levels before and after treatment were collected.Results30 preterm babies were diagnosed of hsPDA. 11/30 received ibuprofen with closure in 81.1%. 9 received intravenous paracetamol mainly due to bleeding disorders or thrombocytopenia. Successful closure on paracetamol was achieved in seven of nine babies (77.7%). There was a significant increase in transaminase levels in two patients. They required no treatment for normalization.Conclusion Paracetamol is an effective option in closure PDA. It should be a first-line therapeutic option when there are contraindications for ibuprofen treatment. Transaminases must be checked during treatment.

Antenatal Magnesium Sulfate Exposure and Acute Cardiorespiratory Events in Preterm Infants

Article

Jul 2014
AM J OBSTET GYNECOL

Objective: Antenatal magnesium (anteMg) is used for various obstetric indications including fetal neuroprotection. Infants exposed to anteMg may be at risk for respiratory depression and delivery room (DR) resuscitation. The study objective was to compare the risk of acute cardiorespiratory events among preterm infants who were and were not exposed to anteMg. Study design: This was a retrospective analysis of prospective data collected in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network's Generic Database from April 1, 2011, through March 31, 2012. The primary outcome was DR intubation or respiratory support at birth or on day 1 of life. Secondary outcomes were invasive mechanical ventilation, hypotension treatment, neonatal morbidities, and mortality. Logistic regression analysis evaluated the risk of primary outcome after adjustment for covariates. Results: We evaluated 1544 infants <29 weeks' gestational age (1091 in anteMg group and 453 in nonexposed group). Mothers in the anteMg group were more likely to have higher education, pregnancy-induced hypertension, and antenatal corticosteroids, while their infants were younger in gestation and weighed less (P < .05). The primary outcome (odds ratio [OR], 1.2; 95% confidence interval [CI], 0.88-1.65) was similar between groups. Hypotension treatment (OR, 0.70; 95% CI, 0.51-0.97) and invasive mechanical ventilation (OR, 0.54; 95% CI, 0.41-0.72) were significantly less in the anteMg group. Conclusion: Among preterm infants age <29 weeks' gestation, anteMg exposure was not associated with an increase in cardiorespiratory events in the early newborn period. The safety of anteMg as measured by the need for DR intubation or respiratory support on day 1 of life was comparable between groups.

Umbilical artery pH may be a possible confounder for neonatal adverse outcomes in preterm infants exposed to antenatal magnesium

Article

Full-text available

Oct 2012
J MATERN-FETAL NEO M

Objectives: To determine the normal range of ionized magnesium (IMg) levels in cord blood during preterm gestation and to investigate whether antenatal Mg administration affects neonatal intraventricular hemorrhage (IVH) or patent ductus arteriosus (PDA). Methods: In this retrospective case-control study, we reviewed 118 pregnant women with antenatal Mg administration and their infants after they gave birth at one tertiary care center between January 2006 and December 2010. Thirty-seven cases with IVH and/or PDA were compared to 81 controls by multiple logistic regression analysis. The normal range of IMg levels was determined by another 79 subjects without any tocolytic agents and possible confounders. Perinatal and neonatal characteristics were then compared between three groups divided by the IMg levels in cord serum. Results: The normal range of IMg levels in cord blood was determined to be 0.47 ± 0.07 mmol/L, regardless of gestational weeks. IMg level in cord serum could not be a risk factor for IVH or PDA. Elevation of IMg level in cord blood resulted in an increased incidence of IVH and a decreased incidence of PDA, but not significantly. IMg level in cord blood was inversely correlated with umbilical artery pH (p = 0.067). Conclusions: There was no significant relationship between the IMg levels in cord serum and neonatal IVH and PDA. Umbilical artery pH may be a possible confounder.

Fluid and electrolyte management in preterm infants with patent ductus arteriosus

Article

May 2022

Optimal fluid management of preterm babies with suspected or confirmed diagnosis of patent ductus arteriosus (PDA) is frequently challenging for neonatal care physician because of paucity of clinical trials. There is wide variation in practice across neonatal units, resulting in significant impact on outcomes in Extremely Low Birth Weight (ELBW) babies with hemodynamically significant PDA. A delicate balance is required in fluid management to reduce mortality and morbidity in this population. The purpose of this review is to lay out the current understanding about fluid and electrolyte management in ELBW babies with hemodynamically significant PDA and highlight areas for future research.

Effects of Antenatal Magnesium Sulfate on the Gut Function of Preterm (<32 weeks) Very Low Birth Weight Neonates: Experience from a Tertiary Institute in South India

Article

May 2021

Objective Antenatal magnesium sulfate (MgSO4) is found to have various adverse effects in newborn, but the effect on preterm gut is still unclear. This study aimed to evaluate the effects of antenatal MgSO4 on preterm gut function by assessing the clinical outcomes and mesenteric blood flow. Methods This was a prospective cohort study on all preterm very low birth weight (VLBW) neonates born at a tertiary care center in South India from November 2016 to August 2017. Neonates with antenatal magnesium (Mg) exposure were compared with those with no exposure for various neonatal outcome variables like time to reach full feeds, feed intolerance, necrotizing enterocolitis (NEC) and other preterm complications, serial serum Mg levels and superior mesenteric artery (SMA) Doppler velocity measurements at two time points (24–48 h and 4–5 days after birth). Results Out of 84 neonates, 56 neonates were exposed to antenatal Mg with a median cumulative maternal dose of 28 g and the rest 28 neonates had no exposure. The mean time to reach full feeds was the same in both groups (10.5 days). Feed intolerance episodes were similar in the first week of life between the exposed and unexposed groups (48.2% vs. 46.4%; p = 0.88). Univariate analysis revealed no difference between groups concerning rates of NEC (p = 0.17) or mortality (p = 0.39). There was no significant difference in SMA Doppler parameters and hypermagnesemia between the two groups. Conclusion Our study found no significant impact on postnatal feed tolerance and mesenteric blood flow among preterm VLBW neonates with antenatal MgSO4 exposure.

Effectiveness and safety of the surgical closure of permeable arteriosus conduct by the general pediatric surgeon: Clinical trial

Article

Full-text available

May 2021

Protective factors against preterm infants to develop significant patent ductus arteriosus

Article

Full-text available

Apr 2021

Background Identifying preterm infants with a higher likelihood of spontaneous patent ductus arteriosus (PDA) closure would be desirable. This study aimed to examine daily PDA status during the first week of life for very low birthweight (VLBW, <1500 g) preterm infants and to develop a scoring system to predict spontaneous PDA closure. Methods We enrolled VLBW infants admitted between January 2016 and January 2017 and performed daily echocardiographic screening for PDA existence. Oxygen index (OI, mean airway pressure X fraction of inspired oxygen/partial pressure of arterial oxygen) was applied to represent the respiratory condition. Results A total of 215 VLBW infants were enrolled, and the accumulative incidence of spontaneous PDA closure by age 1 week was 80%, 70%, and 34% for infants born of gestational age (GA) ≥30, 28–29, and ≤27 weeks, respectively. Of these 215 infants, 184 infants entered the second phase to establish the scoring system. Infants with spontaneous PDA closure were more mature (GA 29.2 ± 2.3 vs. 26.9 ± 2.3 weeks, p <0.001), had lower OI (2.8 ± 2.2 vs. 5.6 ± 5.3, p <0.001) and were less likely to need endotracheal intubation (23% vs. 68%, p <0.001). Using the receiver operating characteristics curve, OI <2.5 was determined favoring higher PDA closure incidence. The score was calculated based on the odds ratio generated in multiple regression: 4, 3 and 1 points for GA ≥30, 28–29 and ≤27 weeks, 2 and 1 points for OI <2.5 and ≥2.5, and 3 and 1 points for without and with endotracheal intubation. Using score ≥6 to predict PDA closure, the sensitivity and specificity were 0.77 and 0.72. Conclusion A score made up of GA, OI and need for intubation was proposed to predict spontaneous PDA closure by age 1 week, which could be helpful to clinicians in the management of PDA in preterm infants.

Eficacia y seguridad del cierre quirúrgico del conducto arterioso permeable por el cirujano pediatra general: ensayo clínico

Article

Full-text available

Feb 2021
Arch Cardiol Mex

Antecedentes: El conducto arterioso permeable (CAP) es un defecto cardiaco congénito y se considera un problema de salud pública. Se presenta en un alto porcentaje de recién nacidos y en algunos mayores de 1 mes. El cierre farmacológico es el tratamiento inicial preferido, ya que ha tenido excelentes resultados; sin embargo, en aquellos casos en los que no es posible, está indicado el cierre quirúrgico. Objetivo: Evaluar la eficacia y la seguridad del cierre quirúrgico del CAP por cirujanos pediatras sin especialidad en cirugía cardiovascular. Método: Ensayo clínico realizado en pacientes del Hospital General de Occidente, centro hospitalario público de segundo nivel, con diagnóstico de CAP, que requirieron corrección quirúrgica. Se revisaron en forma retrospectiva los expedientes de enero de 2001 a diciembre de 2018. Resultados: Se incluyeron 224 pacientes divididos en dos grupos: grupo I, con 184 (82%) recién nacidos, y grupo II, con 40 (18%) niños grandes de 2 meses a 8 años de edad. A todos se les realizó cierre quirúrgico: 3 por toracoscopía y 221 por toracotomía posterolateral izquierda. Presentaron complicaciones 36 pacientes, lo que representa el 16% del total; solo el 5.3% fueron complicaciones mayores. Fallecieron 24 pacientes en el posoperatorio, lo que representa una mortalidad del 10.7%; ninguno falleció por complicaciones transquirúrgicas. El CAP es un defecto cardíaco congénito que se presenta en alto porcentaje en pacientes prematuros. El cierre farmacológico es el principal tratamiento por tener excelentes resultados en recién nacidos; sin embargo, en aquellos casos en los que no sea posible está indicado el cierre quirúrgico. Todos los pacientes fueron operados por cirujanos pediatras generales, con una sobrevida global del 92%. Conclusiones: En los hospitales donde no hay cirujano cardiovascular pediátrico ni cardiólogo intervencionista, la corrección quirúrgica del CAP puede ser llevada a cabo por un cirujano pediatra. La técnica es reproducible, fácil de realizar y con mínimas complicaciones. Background: The Patent Ductus Arteriosus (PDA) is congenital heart defect and is considered a public health problem. It occurs in a high percentage of newborns and in some older than 1 month. Pharmacological closure is the preferred initial treatment, as it has had excellent results; however, in those cases where it is not possible, surgical closure is indicated. Objective: The objective is to evaluate the efficacy and safety of the surgical closure of the patent PDA when it is carried out by pediatric surgeons without specialization in cardiovascular surgery. Methods: This study was conducted at the West General Hospital, a 2nd level public hospital, with the diagnosis of patent ductus arteriosus that required surgical correction. For the collection of the information, the files from January 2001 to December 2018 were retrospectively reviewed. Results: 224 patients were included; divided into two groups: Group I: 184 (82%) “newborns” and Group II: 40 (18%) “big children” with ages from 2 months to 8 years. All had a surgical closure; 3 by thoracoscopy and 221 by left posterolateral thoracotomy. 36 patients presented complications representing 16% of the total of patients, only 5.3% were major complications. 24 patients died in the postoperative period, representing a mortality of 10.7%, none died due to trans-surgical complications. PDA is a congenital heart defect that occurs in a high percentage of premature patients. The pharmacological closure is the principal treatment because it has had excellent results in newborns; however, in those cases where it is not possible, surgical closure it´s indicated. All patients were operated by general pediatric surgeons, with a global survival of 92%. Conclusions: We conclude that in hospitals where there is no pediatric cardiovascular surgeon or interventional cardiologist, the surgical correction of the PDA can be carried out by a general pediatric surgeon. The technique is reproducible, easy to perform and with minimal complications.

Molecular and Mechanical Mechanisms Regulating Ductus Arteriosus Closure in Preterm Infants

Article

Full-text available

Aug 2020

Fahri Ovalı

Failure of ductus arteriosus closure after preterm birth is associated with significant morbidities. Ductal closure requires and is regulated by a complex interplay of molecular and mechanical mechanisms with underlying genetic factors. In utero patency of the ductus is maintained by low oxygen tension, high levels of prostaglandins, nitric oxide and carbon monoxide. After birth, ductal closure occurs first by functional closure, followed by anatomical remodeling. High oxygen tension and decreased prostaglandin levels mediated by numerous factors including potassium channels, endothelin-1, isoprostanes lead to the contraction of the ductus. Bradykinin and corticosteroids also induce ductal constriction by attenuating the sensitivity of the ductus to PGE2. Smooth muscle cells of the ductus can sense oxygen through a mitochondrial network by the role of Rho-kinase pathway which ends up with increased intracellular calcium levels and contraction of myosin light chains. Anatomical closure of the ductus is also complex with various mechanisms such as migration and proliferation of smooth muscle cells, extracellular matrix production, endothelial cell proliferation which mediate cushion formation with the interaction of blood cells. Regulation of vessel walls is affected by retinoic acid, TGF-β1, notch signaling, hyaluronan, fibronectin, chondroitin sulfate, elastin, and vascular endothelial cell growth factor (VEGF). Formation of the platelet plug facilitates luminal remodeling by the obstruction of the constricted ductal lumen. Vasa vasorum are more pronounced in the term ductus but are less active in the preterm ductus. More than 100 genes are effective in the prostaglandin pathway or in vascular smooth muscle development and structure may affect the patency of ductus. Hemodynamic changes after birth including fluid load and flow characteristics as well as shear forces within the ductus also stimulate closure. Current pharmacological treatment for the closure of a patent ductus is based on the blockage of the prostaglandin pathway mainly through COX or POX inhibition, albeit with some limitations and side effects. Further research for new agents aiming ductal closure should focus on a clear understanding of vascular biology of the ductus.

No 376 - Recours au sulfate de magnésium aux fins de neuroprotection fœtale

Article

Apr 2019

Objectif: Fournir des directives sur l'administration prénatale de sulfate de magnésium visant à offrir une neuroprotection aux enfants prématurés. Options: L'administration prénatale de sulfate de magnésium aux fins de neuroprotection fœtale devrait être envisagée chez les femmes enceintes de 33+6 semaines ou moins étant sur le point d'accoucher prématurément; l'accouchement prématuré imminent est défini par une forte probabilité d'accouchement en raison d'un travail actif accompagné d'une dilatation du col d'au moins 4 cm, avec ou sans rupture prématurée des membranes avant le travail, ou comme un accouchement prématuré planifié pour des indications maternelles ou fœtales. Outre le sulfate de magnésium, aucun autre agent offrant une neuroprotection fœtale n'est connu. RéSULTATS: Les issues évaluées sont l'incidence de la paralysie cérébrale (PC) et du décès néonatal. DONNéES PROBANTES: La littérature publiée a été récupérée au moyen de recherches menées dans PubMed ou Medline, CINAHL et la Bibliothèque Cochrane en décembre 2017 à l'aide d'une terminologie et de mots-clés contrôlés (« magnesium sulphate », « cerebral palsy », « preterm birth »). Les résultats retenus provenaient de revues systématiques, d'essais cliniques randomisés et d'autres études observationnelles pertinentes. Aucune restriction de date ou de langue n'a été employée. Les recherches ont été refaites régulièrement, et les résultats ont été incorporés à la directive clinique jusqu'en décembre 2017. Nous avons également tenu compte de la littérature grise (non publiée) trouvée sur les sites Web d'organismes d'évaluation des technologies de la santé et d'autres organismes liés aux technologies de la santé, dans des collections de directives cliniques et dans des registres d'essais cliniques, et obtenue auprès d'associations nationales et internationales de médecins spécialistes. Valeurs: La qualité des données probantes a été évaluée au moyen des critères énoncés dans le rapport du Groupe d'étude canadien sur les soins de santé préventifs (tableau 1). AVANTAGES, DéSAVANTAGES ET COûTS: L'administration prénatale de sulfate de magnésium aux fins de neuroprotection fœtale réduit le risque de « décès ou PC » (risque relatif [RR] : 0,85; intervalle de confiance [IC] à 95 % : 0,74-0,98; 4 essais; 4 446 enfants), de « décès ou PC modérée ou grave » (RR : 0,85; IC à 95 % : 0,73-0,99; 3 essais; 4 250 enfants), de « PC de quelque gravité que ce soit » (RR : 0,71; IC à 95 % : 0,55-0,91; 4 essais; 4 446 enfants), de « PC modérée ou grave » (RR : 0,60; IC à 95 % : 0,43-0,84; 3 essais; 4 250 enfants) et de « dysfonctionnement important de la motricité globale » (incapacité à marcher sans aide) à l'âge de deux ans [RR : 0,60; IC à 95 % : 0,43-0,83; 3 essais; 4 387 femmes). Les conclusions allaient dans le même sens d'une étude et d'une méta-analyse à l'autre. Aucune augmentation significative des coûts liés aux soins de santé n'est attendue, puisque les femmes admissibles à l'administration prénatale de sulfate de magnésium seront celles dont l'accouchement prématuré est imminent. Validation: Une directive clinique australienne sur l'administration prénatale de sulfate de magnésium aux fins de neuroprotection fœtale a été publiée en mars 2010 par l'Antenatal Magnesium Sulphate for Neuroprotection Guideline Development Panel. On y recommande la même posologie que dans la présente directive, mais seulement chez les femmes enceintes de moins de 30 semaines, pour deux raisons : premièrement, aucun sous-groupe d'âge gestationnel n'a semblé bénéficier d'un avantage clair; et deuxièmement, en raison de cette incertitude, le comité a été d'avis qu'il valait mieux limiter les répercussions que pouvait avoir leur directive clinique sur la répartition des ressources. En mars 2010, l'American College of Obstetricians and Gynecologists a publié une opinion de comité sur l'administration de sulfate de magnésium aux fins de neuroprotection fœtale, dans laquelle on peut lire : « Les données probantes disponibles semblent indiquer que l'administration de sulfate de magnésium avant un accouchement prématuré anticipé réduit le risque de paralysie cérébrale chez les enfants survivants. » On n'y mentionne aucun seuil d'âge gestationnel, mais on recommande aux médecins de rédiger des lignes directrices sur les critères d'inclusions, la posologie, la tocolyse concomitante et la surveillance à exercer, selon les résultats d'un essai de grande envergure. De même, en 2015, l'Organisation mondiale de la Santé a également indiqué que l'administration de sulfate de magnésium aux fins de neuroprotection fœtale faisait partie des interventions recommandées pour améliorer les issues des grossesses prenant fin prématurément, mais a précisé que d'autres études portant sur la posologie et les traitements répétés étaient nécessaires. Commanditaire: Les Instituts de recherche en santé du Canada (IRSC). DéCLARATION SOMMAIRE: RECOMMANDATIONS.

Antenatal magnezyum ile prematüre morbiditelerindeki değişiklikler

Article

Full-text available

Jun 2019

Amaç: 34 gestasyonel haftadan once doğan bebeklerin annelerine yapılan antenatal magnesiyum sulfatın, bebeklerdeki intraventriküler kanama, beslenme intoleransı, retinopati ya da bronkopulmoner displazi gibi morbiditeler üzerine etkisi henüz tam açıklığa kavuşturulmamıştır. Biz antenatal uygulanan magnezyum sulfatın prematüre bebeklerde erken ve geç morbidite ve mortaliteye etkisini retrospektif olarak araştırmayı amaçladık.Gereç ve Yöntem: Antenatal magnesiyum alan 108 prematüre bebek Mg (+) grubu, ve antenatal magnesiyum almayan 172 prematüre bebek Mg(-) grubu,oluşturdu.Bulgular: Respiratuar Distres sendromu, intraventriküler kanama, ağır intraventriküler kanama (evre 3 ve 4), premature retinopatisi, bronkopulmoner displazi Mg (+) grupta daha düşük saptanmasına ragmen sadece Respiratuar Distres sendromu için istatistiksel olarak anlamlı idi.Sonuç: Bu retrospektif çalışmada antenatal magnezyum uygulamasının premature bebeklerde morbidite ve mortalite üzerine istatistiksel anlamlı bir yararı gösterilemedi.

Understanding the pathobiology in patent ductus arteriosus in prematurity—beyond prostaglandins and oxygen

Article

Apr 2019

The ductus arteriosus (DA) is probably the most intriguing vessel in postnatal hemodynamic transition. DA patency in utero is an active state, in which prostaglandin E2 (PGE2) and nitric monoxide (NO), play an important role. Since the DA gets programmed for postnatal closure as gestation advances, in preterm infants the DA frequently remains patent (PDA). PGE2 exposure programs functional postnatal closure by inducing gene expression of ion channels and phosphodiesterases and anatomical closure by inducing intimal thickening. Postnatally, oxygen inhibits potassium and activates calcium channels, which ultimately leads to a rise in intracellular calcium concentration consequently inducing phosphorylation of the myosin light chain and thereby vasoconstriction of the ductus arteriosus. Since ion channel expression is lower in preterm infants, oxygen induced functional vasoconstriction is attenuated in comparison with full term newborns. Furthermore, the preterm DA is more sensitive to both PGE2 and NO compared to the term DA pushing the balance toward less constriction. In this review we explain the physiology of DA patency in utero and subsequent postnatal functional closure. We will focus on the pathobiology of PDA in preterm infants and the (un)intended effect of antenatal exposure to medication on both fetal and neonatal DA vascular tone.

No. 376-Magnesium Sulphate for Fetal Neuroprotection

Article

Apr 2019

Objective: The objective is to provide guidelines for the use of antenatal magnesium sulphate for fetal neuroprotection of the preterm infant. Options: Antenatal magnesium sulphate administration should be considered for fetal neuroprotection when women present at ≤33 + 6 weeks with imminent preterm birth, defined as a high likelihood of birth because of active labour with cervical dilatation ≥4 cm, with or without preterm pre-labour rupture of membranes, and/or planned preterm birth for fetal or maternal indications. There are no other known fetal neuroprotective agents. Outcomes: The outcomes measured are the incidence of cerebral palsy (CP) and neonatal death. Evidence: Published literature was retrieved through searches of PubMed or Medline, CINAHL, and the Cochrane Library in December 2017, using appropriate controlled vocabulary and key words (magnesium sulphate, cerebral palsy, preterm birth). Results were restricted to systematic reviews, randomized controlled trials, and relevant observational studies. There were no date or language restrictions. Searches were updated on a regular basis and incorporated in the guideline to December 2017. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. Values: The quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care (Table 1). Benefits, harms, and costs: Antenatal magnesium sulphate for fetal neuroprotection reduces the risk of "death or CP" (relative risk [RR] 0.85; 95% confidence interval [CI] 0.74-0.98; 4 trials, 4446 infants), "death or moderate-severe CP" (RR 0.85; 95% CI 0.73-0.99; 3 trials, 4250 infants), "any CP" (RR 0.71; 95% CI 0.55-0.91; 4, trials, 4446 infants), "moderate-to-severe CP" (RR 0.60; 95% CI 0.43-0.84; 3 trials, 4250 infants), and "substantial gross motor dysfunction" (inability to walk without assistance) (RR 0.60; 95% CI 0.43-0.83; 3 trials, 4287 women) at 2 years of age. Results were consistent between trials and across the meta-analyses. There is no anticipated significant increase in health care-related costs because women eligible to receive antenatal magnesium sulphate will be judged to have imminent preterm birth. Validation: Australian National Clinical Practice Guidelines were published in March 2010 by the Antenatal Magnesium Sulphate for Neuroprotection Guideline Development Panel. Antenatal magnesium sulphate was recommended for fetal neuroprotection in the same dosage as recommended in these guidelines. However, magnesium sulphate was recommended only at <30 weeks gestation, based on 2 considerations. First, no single gestational age subgroup was considered to show a clear benefit. Second, in the face of uncertainty, the committee felt it was prudent to limit the impact of their clinical practice guidelines on resource allocation. In March 2010, the American College of Obstetricians and Gynecologists issued a Committee Opinion on magnesium sulphate for fetal neuroprotection. It stated that "the available evidence suggests that magnesium sulfate given before anticipated early preterm birth reduces the risk of cerebral palsy in surviving infants." No official opinion was given on a gestational age cut-off, but it was recommended that physicians develop specific guidelines around the issues of inclusion criteria, dosage, concurrent tocolysis, and monitoring in accordance with 1 of the larger trials. Similarly, the World Health Organization also strongly recommends use of magnesium sulphate for fetal neuroprotection in its 2015 recommendations on interventions to improve preterm birth outcomes but cites further researching on dosing regimen and re-treatment. Sponsors: Canadian Institutes of Health Research (CIHR). Summary statement: RECOMMENDATIONS.

Magnesium Sulphate for Fetal Neuroprotection

Article

May 2011

To provide guidelines for the use of antenatal magnesium sulphate (MgSO4) for fetal neuroprotection of the preterm infant.

Pharmacokinetics and Placental Transfer of Magnesium Sulfate in Pregnant Women

Article

Jan 2016

Background: Magnesium sulfate is one of the most commonly prescribed intravenous medications in obstetrics. Despite widespread use, there are limited data about magnesium pharmacokinetics, and magnesium is prescribed empirically without dose adjustment for different indications. Objective: The aim of this study was to characterize the pharmacokinetics and placental transfer of magnesium sulfate in pregnant women, and to determine key covariates which impact the pharmacokinetics. Study design: This is a prospective pharmacokinetic cohort study of pregnant women prescribed magnesium sulfate for preeclampsia, preterm labor or extreme prematurity. Women received 4g loading dose and 2g/hr maintenance dose as clinically indicated. Maternal blood samples were obtained prior to and at multiple time points during and after magnesium administration. Cord blood was also sampled at delivery. A population pharmacokinetic approach using nonlinear mixed-effects modeling was used to characterize magnesium disposition. Results: Pharmacokinetic profiles of 111 pregnant women were analyzed. Magnesium clearance was 3.98 L/h in preeclamptic women and 5.88 L/h non-preeclamptic women. Steady state concentration of magnesium was 7.2 mg/dL in preeclamptic women compared to 5.1 mg/dL in non-preeclamptic women. Maternal weight significantly impacted time to steady-state. The ratio of the mean umbilical vein magnesium level to the mean maternal serum magnesium level at the time of delivery was 0.94 + 0.15. Conclusions: The study accurately characterizes the pharmacokinetics of magnesium administered to pregnant women. Preeclamptic status and maternal weight significantly impact serum magnesium levels. This pharmacokinetic model could be applied to larger cohorts to help tailor magnesium treatment and account for these covariates.

Experiencia en el cierre quirúrgico de ducto arterioso permeable en la Unidad de Cuidados Intensivos Neonatales (UCIN) de un hospital de segundo nivel en Guadalajara, Jalisco, México

Article

Full-text available

Apr 2010

Background: Patent ductus arteriosus (PDA) is the most common congenital cardiac defect affecting 80% of very low birth weight preterm newborns (<1 000 g) and is considered an important public health issue. The aim was to demonstrate that it is possible to perform surgical closure of PDA on premature newborns in a second-level hospital.

Effect of Antenatal Magnesium Sulfate Exposure on Patent Ductus Arteriosus in Premature Infants

Article

Feb 2024

Objective Magnesium sulfate (MgSO4) provides effective fetal neuroprotection. However, there is conflicting evidence regarding the association between antenatal MgSO4 exposure and patent ductus arteriosus (PDA). Thus, herein, we aimed to evaluate the association between antenatal MgSO4 exposure and PDA. Study Design Preterm infants born between 240/7 and 316/7 weeks of gestation were included in this retrospective study. Infants who died within the first 72 hours of life and those with significant congenital anomalies were excluded from the study. Echocardiographic and clinical assessment parameters were used to define PDA and hemodynamically significant PDA (hsPDA). Treatments were planned according to the standard protocols of the unit. The following data were collected from hospital medical records: perinatal characteristics, neonatal outcomes, detailed PDA follow-up findings, and maternal characteristics including MgSO4 exposure and doses. Results Of the 300 included infants, 98 (32.6%) were exposed to antenatal MgSO4. hsPDA rates were similar in the infants exposed and not exposed to antenatal MgSO4, when adjusted for antenatal steroid administration, gestational age, and birth weight (OR: 1.6, 95% CI: 0.849–3.118, p = 0.146). The rates of PDA ligation and open PDA at discharge were similar between the groups. A cumulative MgSO4 dose of >20 g was associated with an increased risk of hsPDA (crude OR: 2.476, 95% CI: 0.893–6.864, p = 0.076; adjusted OR: 3.829, 95% CI: 1.068–13.728, p = 0.039). However, the cumulative dose had no effect on the rates of PDA ligation or open PDA at discharge. Rates of prematurity-related morbidities and mortality were similar between the groups. Conclusion Although antenatal MgSO4 exposure may increase the incidence of hsPDA, it may not affect the rates of PDA ligation or open PDA at discharge. Further studies are required to better evaluate the dose-dependent outcomes and identify the MgSO4 dose that not only provides neuroprotection but also has the lowest risk of adverse effects. Key Points

Maternal Magnesium Sulfate Administration Increases Early-Onset Hyperkalemia Risk in Premature Infants: A Propensity Score-Matched, Case-Control Study.

Article

Full-text available

Sep 2022

Background Magnesium sulfate (MgSO4) is a common substance administered to pregnant women with preeclampsia or eclampsia to prevent and treat seizures or gestational hypertension. This study aimed to evaluate whether administering maternal magnesium sulfate increased the risk of early-onset hyperkalemia in preterm infants. Methods This single-center, propensity score-matched, case-control study examined preterm infants born within 24–36 weeks of gestation using electronic medical records between January 2015 and June 2019, in the Saitama City Hospital, Japan. We categorized infants according to their maternal MgSO4 administration status. After adjusting for perinatal information and maternal treatment, we compared the incidence of the variables, including neonatal hyperkalemia, within 24 h after birth between the matched cohorts. All infants in Model 1 were analyzed separately, while in Model 2 infants with birth weight of less than 1000 g were excluded. Results We enrolled 421 infants (maternal MgSO4 group, 124; control group, 297). Ninety-five infants in Model 1 and 86 in Model 2 were matched in each group using propensity scores, respectively. In the matched cohorts of both models, infants in the maternal MgSO4 group had a higher hyperkalemia incidence than did those in the control group (42.1% vs. 7.4% in Model 1, 44.2% vs. 5.8% in Model 2, respectively; p <0.0001). However, there was no relationship between the duration of intrauterine exposure to MgSO4 and early-onset neonatal hyperkalemia incidence. Conclusion Our study demonstrated that maternal MgSO4 administration, even for a short period of time, may increase the risk of early-onset hyperkalemia in preterm infants. Accordingly, physicians should be cautious when administering serum potassium to infants born to mothers administered MgSO4, especially within 24 h after birth.

Effects of antenatal magnesium sulfate use for neuroprotection on cardiorespiratory complications during the early neonatal period in preterm infants

Article

Sep 2021

Background/Aim: Antenatal magnesium sulfate (MgSO4) treatment is widely used for fetal neuroprotection in women at risk of preterm delivery. Possible adverse effects of MgSO4 include respiratory depression and delay in closure of ductus arteriosus by antagonism of calcium channels. The aim of this study was to investigate the effects of antenatal MgSO4 exposure on cardiorespiratory complications during the early neonatal period in premature infants. Methods: A retrospective cohort study was performed on 340 preterm infants born between 23 and 32 weeks of gestational age. Patients were divided into two groups according to antenatal MgSO4 exposure: The MgSO4 group (n=186) and the no-MgSO4 group (n=154). Outcomes were acute cardiorespiratory events (intubation at birth, respiratory support, and hypotension in first day of life), and hemodynamically significant patent ductus arteriosus (HsPDA). Results: Mothers in the MgSO4 group were more likely to have preeclampsia and antenatal steroid treatment, while their infants were younger in gestation and weighed less (P

Patent Ductus Arteriosus and the Lung

Chapter

Jan 2019

The ductus arteriosus plays a vital role in fetal life but failure to constrict and close postnatally, particularly in a premature infant, can result in systemic to pulmonary shunting. As a result of this shunting, a significant patent ductus arteriosus (PDA) can have both systemic (reduced systemic blood flow) and pulmonary (increased pulmonary blood flow) consequences and potential for lung injury. Despite the experimental and epidemiologic evidence supporting the role of the PDA in the pathogenesis of chronic lung injury, there are scarce data from more recent prospective clinical trials to confirm this association or demonstrate that treatment of the PDA has any effect on chronic lung injury. The need for treatment of the PDA is increasingly controversial because of a high rate of spontaneous closure, only moderate efficacy of the treatment options, and a risk of adverse effects. Both medical and surgical PDA treatment options are associated with lung injury. Until further evidence becomes available, the decision on management of PDA must balance the consequences of ductal patency that are closely related to its hemodynamic significance, versus the side effects of the interventions to close it. More data are needed to define the impact of a more conservative approach toward the PDA on respiratory, cardiovascular and neurologic outcomes.

Genetic Basis of Patent Ductus Arteriosus

Chapter

Jan 2019

The ductus arteriosus (DA) is an important fetal vessel required for normal in utero cardiovascular development. Many physiologic and pharmacologic investigations have characterized DA closure, but genetic studies of persistent patency of the DA are relatively recent. The identification of specific genes associated with patent ductus arteriosus (PDA) is lagging behind that of many other conditions for several reasons, including the lack of large, well-phenotyped biorepositories for the preterm population. Viewing PDA as a developmentally influenced disease with both genetic and environmental risk factors has resulted in successes in recent genetic studies. Several genetic approaches have been successful in identifying polymorphisms associated with other diseases and are currently investigating PDA. Discovering further genetic variations causing PDA may identify pathways to manipulate for the more rational use of current and future therapies.

Patent Ductus Arteriosus: A Practical Approach to Neonatal Diseases

Chapter

Oct 2018

Bart Van Overmeire

Patent Ductus Arteriosus in the Preterm Infant

Chapter

Dec 2017

Ronald I. Clyman

Experience in the surgical closure of patent ductus arteriosus in the Neonatal Intensive Care Unit of a second-level hospital in Guadalajara, Jalisco, Mexico

Article

Apr 2010

Background: Patent ductus arteriosus (PDA) is the most common congenital cardiac defect affecting 80% of very low birth weight preterm newborns (

Mechanisms Regulating Closure of the Ductus Arteriosus

Chapter

Jan 2017

Ronald I. Clyman

Risk factors for patent ductus arteriosus in early preterm infants: A case-control study

Article

Jan 2016
Chin J Contemp Pediatr

Objective: To investigate the risk factors for the occurrence of patent ductus arteriosus (PDA) and to provide a clinical basis for reducing the occurrence of PDA in early preterm infants. Methods: A total of 136 early preterm infants (gestational age≤32 weeks) who were hospitalized between January 2013 and December 2014 and diagnosed with hemodynamicalhy significant PDA (hs-PDA) were enrolled as the case group. Based on the matched case-control principle, 136 early preterm infants without hs-PDA were selected among those who were hospitalized within the same period at a ratio of 1:1 and enrolled as the control group. The two groups were matched for sex and gestational age. The basic information of neonates and maternal conditions during the pregnancy and perinatal periods were collected. Logistic regression analysis was performed to identify the risk factors for the development of PDA. Results: Univariate analysis showed that neonatal infectious diseases, neonatal respiratory distress syndrome, decreased platelet count within 24 hours after birth, and low birth weight were associated with the development of hs-PDA (P<0.05). Multivariate conditional logistic regression analysis revealed that neonatal infectious diseases (OR=2.368) and decreased platelet count within 24 hours after birth (OR=0.996) were independent risk factors for hs-PDA. Conclusions: Neonatal infectious diseases and decreased platelet count within 24 hours after birth increase the risk of hs-PDA in early preterm infants.

Patent Ductus Arteriosus

Chapter

Jan 2012

Bart Van Overmeire

Patent ductus arteriosus (PDA) is the most common cardiac abnormality of the preterm infant. Its incidence is inversely related to gestational age, such that it affects almost 60% of infants less than 28 weeks’ gestation. Data published in 2007 demonstrated that spontaneous closure of the ductus occurs in 30% of infants with birthweights below 1500 g (very low birth weight [VLBW]) [1]. It is obvious that percentages are decreasing for each lower birthweight category (Table 80.1), but also that a markedly wide variation exists among centers. This may reflect the influence of varying factors on the closure of the ductus.

Necesidad de reanimación en prematuros menores de 32 semanas expuestos a sulfato de magnesio para neuroprotección fetal

Article

Jan 2016
Rev Chil Pediatr

Introduction: Magnesium sulphate administration is recommended for foetal neuroprotection in pregnant women at imminent risk of early preterm birth. Objective: To evaluate the relationship between intrapartum magnesium sulphate for foetal neuroprotection and delivery room resuscitation of preterm infants less 32 weeks. Patients and method: A prospective observational study was conducted on preterm infants less 32 weeks exposed to magnesium sulphate for neuroprotection, and a comparison made with another historic group immediately before starting this treatment. Cases in both groups that had not reached lung maturity with corticosteroids were rejected. The rates of resuscitation, morbidity and mortality for each of the groups were analysed and compared. Results: There was a total of 107 preterm, with 56 exposed to magnesium sulphate. Rate of advanced resuscitation were similar between the two groups. There were no other differences in mortality, invasive mechanical ventilation, time to first stool, and other comorbidities. Conclusions: Intrapartum magnesium sulphate for foetal neuroprotection was not associated with an increased need for intensive delivery room resuscitation and other morbidities in these cohorts of less than 32 weeks preterm infants.

Effects of Antenatal Magnesium Exposure on Intestinal Blood Flow and Outcome in Preterm Neonates

Article

Mar 2015
AM J PERINAT

Objective This study aims to investigate the effects of antenatal magnesium sulfate on intestinal blood flow in preterm neonates. Study Design In this prospective case-match study, 25 preterm neonates exposed to magnesium sulfate antenatally were included (study group). Overall, 25 gestational age-matched neonates who had no exposure to magnesium constituted the control group. Serial daily Doppler flow measurements of superior mesenteric artery (SMA) were performed. The time to reach full feeds, first meconium passage were assessed. Presence of feeding intolerance or necrotizing enterocolitis was recorded. Results Blood flow velocities of SMA were not different between the groups during the first five postnatal days. However, SMA blood flow showed an increasing trend in the control group unlike the study group (control group, p < 0.001; study group, p = 0.29). There was no significant difference between the two groups regarding the time to reach full feeds or first meconium passage and presence of feeding intolerance. No case of necrotizing enterocolitis was seen. Conclusion Antenatal magnesium does not significantly affect intestinal blood flow, but it seems to attenuate the increasing trend of the intestinal blood flow in the early postnatal days. However, this study failed to show any impact of this finding on clinical outcomes. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Influence of Antenatal Magnesium Sulfate Exposure on Perinatal Outcomes in VLBW Infants with Maternal Preeclampsia

Article

Full-text available

Jan 2013

Magnesium sulfate (MgSO4) is a commonly used drug for eclampsia prophylaxis and the first choice tocolytic agent for preterm labor. Recently it has been reported to have a fetal neuroprotective effect. This study was aimed to evaluate the influence of antenatal magnesium sulfate exposure on perinatal outcomes in very low birth weight infants (VLBWIs) with maternal preeclampsia.

Management of Patent Ductus Arteriosus in Premature Infants

Article

Dec 2014

Patency of the ductus arteriosus is required for fetal survival in utero. In infants born prematurely, ductus fails to close and shunt reverses from left to right. Incidence of patent ductus arteriosus (PDA) is inversely proportional to the gestational age. A large PDA (>1.5 mm diameter) with left to right shunt in very low birth weight infants can cause pulmonary edema, congestive heart failure, pulmonary hemorrhage and increase the risk for bronchopulmonary dysplasia. Attempts to prevent or close the duct by pharmacological or surgical methods have not changed the morbidity or the long term outcome. Pharmacological treatment with indomethacin or ibuprofen is successful in 75 to 80 % of infants but its use also exposes these infants to undesirable side effects like gastrointestinal bleeding, perforation and necrotizing enterocolitis. Prophylactic therapy with indomethacin or ibuprofen to prevent PDA has not altered the morbidity or long term outcome. Currently, there is a dilemma as to how to treat, when to treat and whom to treat. Recent literature suggests a trial of conservative management during the first week followed by selective use of anti-inflammatory drugs. Surgical ligation is reserved for infants who fail medical therapy and still remain symptomatic. Spontaneous closure of the PDA has been reported in up to 40-67 % of very low birth weight (VLBW) infants by 7 d. In this review authors discuss these controversies and propose a more rational approach.

Association of ionized magnesium, total magnesium, gestational age, and intraventricular hemorrhage in preterm babies

Article

Full-text available

Jan 2009

The pathophysiology of magnesium, the second highest common compound in humans, is still unclear, especially in preterm babies. We accessed the association between total magnesium (tMg), ionized Mg (iMg), and gestational age (GA) and that between serum magnesium (sMg) and intraventricular hemorrhage (IVH) in preterm babies.

Primer consenso clínico de SIBEN: enfoque diagnóstico y terapéutico del ductus arterioso permeable en recién nacidos pretérmino

Article

Nov 2008

Objective To report the process and results of the first neonatal clinical consensus of the Ibero-American region. Design and methods Two recognized experts in the field (Clyman and Van Overmeire) and 45 neonatologists from 23 countries were invited for active participation and collaboration. We developed 46 questions of clinical-physiological relevance in all aspects of patent ductus arteriosus (PDA). Guidelines for consensus process, literature search and future preparation of educational material and authorship were developed, reviewed and agreed by all. Participants from different countries were distributed in groups, and assigned to interact and work together to answer 3-5 questions, reviewing all global literature and local factors. Answers and summaries were received, collated and reviewed by 2 coordinators and the 2 experts. Participants and experts met in Granada, Spain for 4.5 h (lectures by experts, presentations by groups, discussion, all literature available). Results 31 neonatologists from 16 countries agreed to participate. Presentations by each group and general discussion were used to develop a consensus regarding: general management, availability of drugs (indometacine vs. ibuprofen), costs, indications for echo/surgery, etc. Many steps were learnt by all present in a collaborative forum. Conclusions This first consensus group of Ibero-American neonatologists SIBEN led to active and collaborative participation of neonatologists of 16 countries, improved education of all participants and ended with consensus development on clinical approaches to PDA. Furthermore, it provides recommendations for clinical care reached by consensus. Additionally, it will serve as a useful foundation for future SIBEN Consensus on other topics and it could become valuable as a model to decrease disparity in care and improve outcomes in this and other regions.

Role of Dynamin-Related Protein 1 (Drp1)-Mediated Mitochondrial Fission in Oxygen Sensing and Constriction of the Ductus Arteriosus

Article

Jan 2013
CIRC RES

Rationale: Closure of the ductus arteriosus (DA) is essential for the transition from fetal to neonatal patterns of circulation. Initial PO2-dependent vasoconstriction causes functional DA closure within minutes. Within days a fibrogenic, proliferative mechanism causes anatomic closure. Though modulated by endothelial-derived vasodilators and constrictors, O2 sensing is intrinsic to ductal smooth muscle cells and oxygen-induced DA constriction persists in the absence of endothelium, endothelin, and cyclooxygenase mediators. O2 increases mitochondrial-derived H2O2, which constricts ductal smooth muscle cells by raising intracellular calcium and activating rho kinase. However, the mechanism by which oxygen changes mitochondrial function is unknown. Objective: The purpose of this study was to determine whether mitochondrial fission is crucial for O2-induced DA constriction and closure. Methods and results: Using DA harvested from 30 term infants during correction of congenital heart disease, as well as DA from term rabbits, we demonstrate that mitochondrial fission is crucial for O2-induced constriction and closure. O2 rapidly (<5 minutes) causes mitochondrial fission by a cyclin-dependent kinase- mediated phosphorylation of dynamin-related protein 1 (Drp1) at serine 616. Fission triggers a metabolic shift in the ductal smooth muscle cells that activates pyruvate dehydrogenase and increases mitochondrial H2O2 production. Subsequently, fission increases complex I activity. Mitochondrial-targeted catalase overexpression eliminates PO2-induced increases in mitochondrial-derived H2O2 and cytosolic calcium. The small molecule Drp1 inhibitor, Mdivi-1, and siDRP1 yield concordant results, inhibiting O2-induced constriction (without altering the response to phenylephrine or KCl) and preventing O2-induced increases in oxidative metabolism, cytosolic calcium, and ductal smooth muscle cells proliferation. Prolonged Drp1 inhibition reduces DA closure in a tissue culture model. Conclusions: Mitochondrial fission is an obligatory, early step in mammalian O2 sensing and offers a promising target for modulating DA patency.

Patent Ductus Arteriosus: Are Current Neonatal Treatment Options Better or Worse Than No Treatment at All?

Article

Apr 2012

Although a moderate-sized patent ductus arteriosus (PDA) needs to be closed by the time a child is 1-2 years old, there is great uncertainty about whether it needs to be closed during the neonatal period. Although 95% of neonatologists believe that a moderate-sized PDA should be closed if it persists in infants (born before 28 weeks) who still require mechanical ventilation, the number of neonatologists who treat a PDA when it occurs in infants who do not require mechanical ventilation varies widely. Both the high likelihood of spontaneous ductus closure and the absence of randomized controlled trials, specifically addressing the risks and benefits of neonatal ductus closure, add to the current uncertainty. New information suggests that early pharmacologic treatment has several important short-term benefits for the preterm newborn. By contrast, ductus ligation, while eliminating the detrimental effects of a PDA on lung development, may create its own set of morbidities that counteract many of the benefits derived from ductus closure.

Effects of Maternal Magnesium Sulfate Administration on Intestinal Blood Flow Velocity in Preterm Neonates

Article

Jun 2011

Antenatal MgSO4 administration is used extensively as a tocolytic agent and to treat preeclampsia. Various effects on the fetus and newborn have been reported, and MgSO4 has well-documented vasoactive effects. To determine if antenatal MgSO4 administration affects intestinal blood flow velocity in newborn preterm infants. Peak, mean and end-diastolic velocities in the superior mesenteric artery were measured on day 1 of life. Maternal medical records were reviewed to identify infants whose mothers had been administered MgSO4 for preterm labor or preeclampsia within 24 h of delivery. Fifty-six infants were studied: 27 were exposed and 29 were not exposed to antenatal MgSO4. Mean birth weight (1,371 ± 349 and 1,401 ± 469 g, respectively), gestational age (29.7 ± 2.0 and 30.0 ± 2.9 weeks, respectively) and infant hemodynamic and clinical variables (other than clinical indication for antenatal MgSO4 administration) were similar between groups. There were no significant differences between the exposed and unexposed groups in intestinal blood flow velocities. For the exposed group, however, there was a significant negative correlation between mean velocity and the number of hours from birth to the time superior mesenteric artery blood flow velocity measurements were made (p = 0.002); there was no correlation for the unexposed group (p = 0.852). Group mean values indicate that antenatal exposure to MgSO4 does not significantly affect intestinal blood flow velocity in newborn preterm infants. However, the significant negative relationship between mean blood flow velocity and time from birth to blood flow velocity measurement in exposed infants suggests that there may be measurable effects of MgSO4 exposure within the hours immediately after birth. Trials that prospectively evaluate the development of intestinal blood flow velocities are needed to further clarify potential effects of antenatal MgSO4 on the gastrointestinal tract of preterm infants.

Inadvertent Relaxation of the Ductus Arteriosus by Pharmacologic Agents that are Commonly Used in the Neonatal Period

Article

Jun 2010

Premature birth and disruption of the normal maturation process leave the immature ductus arteriosus unable to respond to postnatal cues for closure. Strategies that advocate conservative management of the patent ductus arteriosus (PDA) in premature infants are dependent on identification of the symptomatic PDA and understanding the risk factors that predispose to PDA. Exposure of premature infants to unintended vasodilatory stimuli may be one of the risk factors for PDA that is under recognized. In this article, we summarize the clinical factors that are associated with PDA and review commonly used neonatal drugs for their vasodilatory properties. Data demonstrating relaxation of the ductus arteriosus by gentamicin and other aminoglycoside antibiotics, by cimetidine and other H2 receptor antagonists, and by heparin are provided as examples of neonatal therapies that have unanticipated effects that may promote PDA.

Fetal Reversed Constrictive Effect of Indomethacin and Postnatal Delayed Closure of the Ductus Arteriosus following Administration of Transplacental Magnesium Sulfate in Rats

Article

Apr 2009

Magnesium sulfate (MgSO4) is used therapeutically for eclampsia and tocolysis. Some reports have suggested a relationship between therapeutic MgSO4 and patent ductus arteriosus (DA) in preterm infants. To clarify patent DA induction by MgSO4 in preterm infants, we studied the increase in serum Mg concentrations and fetal dilatation and postnatal delayed closure of the ductus, using transplacental MgSO4 in rats. Fetal and neonatal ductus diameters were measured with a microscope and a micrometer after rapid whole-body freezing. In the postnatal study, 21-day pregnant dams were administered a subcutaneous injection of MgSO4 1-3 h before delivery, and the ductus was studied 0, 15, 30, 60 and 120 min after birth. In the fetal study, MgSO4 (1 g/kg) and indomethacin (10 mg/kg) were simultaneously administered to 21-day dams and the fetal ductus was studied 1, 2 and 4 h later. Serum Mg concentration was measured in the dams and newborns. Neonatal Mg concentrations increased from 3.8 to 4.7 and 5.8 mg/dl at 1 and 3 h after maternal administration of MgSO4. Following MgSO4 administration 3 h before birth, closure of the neonatal DA was delayed. The ductus diameter was 0.88 mm (0.80 mm in control) at 0 min, and 0.26 mm (0.08 mm in the control) at 60 min after birth. In the fetal study, MgSO4 initially reversed and later attenuated the ductus-constricting effect of indomethacin. Hypermagnesemia induced by transplacental MgSO4 attenuates the fetal ductus-constricting effects of indomethacin, and delays postnatal ductal closure in rats.

First SIBEN clinical consensus: Diagnostic and therapeutic approach to patent ductus arteriosus in premature newborns

Article

Dec 2008

To report the process and results of the first neonatal clinical consensus of the Ibero-American region. Two recognized experts in the field (Clyman and Van Overmeire) and 45 neonatologists from 23 countries were invited for active participation and collaboration. We developed 46 questions of clinical-physiological relevance in all aspects of patent ductus arteriosus (PDA). Guidelines for consensus process, literature search and future preparation of educational material and authorship were developed, reviewed and agreed by all. Participants from different countries were distributed in groups, and assigned to interact and work together to answer 3-5 questions, reviewing all global literature and local factors. Answers and summaries were received, collated and reviewed by 2 coordinators and the 2 experts. Participants and experts met in Granada, Spain for 4.5 h (lectures by experts, presentations by groups, discussion, all literature available). 31 neonatologists from 16 countries agreed to participate. Presentations by each group and general discussion were used to develop a consensus regarding: general management, availability of drugs (indomethacin vs. ibuprofen), costs, indications for echo/surgery, etc. Many steps were learnt by all present in a collaborative forum. This first consensus group of Ibero-American neonatologists SIBEN led to active and collaborative participation of neonatologists of 16 countries, improved education of all participants and ended with consensus development on clinical approaches to PDA. Furthermore, it provides recommendations for clinical care reached by consensus. Additionally, it will serve as a useful foundation for future SIBEN Consensus on other topics and it could become valuable as a model to decrease disparity in care and improve outcomes in this and other regions.

Calcium-dependent and calcium-sensitizing pathways in the mature and immature ductus arteriosus

Article

Nov 2007

Studies performed in sheep and baboons have shown that after birth, the normoxic muscle media of ductus arteriosus (DA) becomes profoundly hypoxic as it constricts and undergoes anatomic remodeling. We used isolated fetal lamb DA (pretreated with inhibitors of prostaglandin and nitric oxide production) to determine why the immature DA fails to remain tightly constricted during the hypoxic phase of remodeling. Under normoxic conditions, mature DA constricts to 70% of its maximal active tension (MAT). Half of its normoxic tension is due to Ca(2+) entry through calcium L-channels and store-operated calcium (SOC) channels. The other half is independent of extracellular Ca(2+) and is unaffected by inhibitors of sarcoplasmic reticulum (SR) Ca(2+) release (ryanodine) or reuptake [cyclopiazonic acid (CPA)]. The mature DA relaxes slightly during hypoxia (to 60% MAT) due to decreases in calcium L-channel-mediated Ca(2+) entry. Inhibitors of Rho kinase and tyrosine kinase inhibit both Ca(2+)-dependent and Ca(2+)-independent DA tension. Although Rho kinase activity may increase during gestation, immature DA develop lower tensions than mature DA, primarily because of differences in the way they process Ca(2+). Calcium L-channel expression increases with advancing gestation. Under normoxic conditions, differences in calcium L-channel-mediated Ca(2+) entry account for differences in tension between immature (60% MAT) and mature (70% MAT) DA. Under hypoxic conditions, differences in both calcium L-channel-dependent and calcium L-channel-independent Ca(2+) entry, account for differences in tension between immature (33% MAT) and mature (60% MAT) DA. Stimulation of Ca(2+) entry through reverse-mode Na(+)/Ca(2+) exchange or CPA-induced SOC channel activity constrict the DA and eliminate differences between immature and mature DA during both hypoxia and normoxia.

Effect of Magnesium Sulfate Given for Neuroprotection Before Preterm Birth

Article

Full-text available

Jan 2003

Context Prenatal magnesium sulfate may reduce the risk of cerebral palsy or death in very preterm infants. Objective To determine the effectiveness of magnesium sulfate given for neuro- protection to women at risk of preterm birth before 30 weeks' gestation in preventing pediatric mortality and cerebral palsy. Design, Setting, and Patients Randomized controlled trial at 16 tertiary hospi- tals in Australia and New Zealand with stratification by center and multiple preg- nancy. A total of 1062 women with fetuses younger than 30 weeks' gestation for whom birth was planned or expected within 24 hours were enrolled from February 1996 to September 2000 with follow-up of surviving children at a corrected age of 2 years. Interventions Women were randomly assigned to receive a loading infusion of 8 mL (4 g (16 mmol) of 0.5 g/mL of magnesium sulfate solution or isotonic sodium chlo- ride solution (0.9%)) for 20 minutes followed by a maintenance infusion of 2 mL/h for up to 24 hours. Main Outcome Measures Rates of total pediatric mortality, cerebral palsy, and the combined outcome of death or cerebral palsy at a corrected age of 2 years. Results Data were analyzed for 1047 (99%) 2-year survivors. Total pediatric mor- tality(13.8%vs17.1%;relativerisk(RR),0.83;95%confidenceinterval(CI),0.64-1.09), cerebral palsy in survivors (6.8% vs 8.2%; RR, 0.83; 95% CI, 0.54-1.27), and com- bined death or cerebral palsy (19.8% vs 24.0%; RR, 0.83; 95% CI, 0.66-1.03) were less frequent for infants exposed to magnesium sulfate, but none of the differences were statistically significant. Substantial gross motor dysfunction (3.4% vs 6.6%; RR, 0.51; 95% CI, 0.29-0.91) and combined death or substantial gross motor dysfunc- tion (17.0% vs 22.7%; RR, 0.75; 95% CI, 0.59-0.96) were significantly reduced in the magnesium group. Conclusions Magnesium sulfate given to women immediately before very preterm birth may improve important pediatric outcomes. No serious harmful effects were seen. JAMA. 2003;290:2669-2676 www.jama.com

A calcium channel blocker verapamil inhibits the spontaneous closure of the ductus arteriosus in newborn rats

Article

Full-text available

Sep 1994

Newborn rats delivered by caesarean section were given subcutaneously verapamil hydrochloride (VER), a Ca-channel blocker, (1) immediately or (2) 180 min after delivery. The diameter of the ductus arteriosus (DA) of the newborn pups was calibrated at 30, 60 and 90 min after the VER-administration. (1) The DA calibers of the pups given 0.1, 1.0 mg/kg VER immediately after delivery remained significantly larger than those of control pups in a dose-dependent manner for 30 min after treatment. In the 1 mg/kg group, the enlargement of the DA was prolonged until 90 min after treatment. (2) In untreated pups, the DA completely closed by 180 min after caesarean delivery. The closed DA was not affected after 1 mg/kg VER was given at 3 hours after delivery. It was concluded that, VER inhibits the spontaneous constriction of the DA, suggesting that the increase of intracellular Ca2+ concentration may play an important role on the spontaneous closure of the DA in newborn rats.

Magnesium Sulfate in Labor and Risk of Neonatal Brain Lesions and Cerebral Palsy in Low Birth Weight Infants

Article

Full-text available

Jun 1997
Pediatrics

We tested the hypothesis that administration of magnesium sulfate in labor protects against the development of neonatal brain lesions and cerebral palsy (CP) in low birth weight infants. Magnesium exposure was ascertained in a population-based cohort of 1105 infants weighing 2000 g or less through review of medical records of maternal magnesium sulfate administration and, where available, elevated maternal serum magnesium levels. Neonatal germinal matrix/intraventricular hemorrhage and parenchymal brain lesions were ascertained by a prospective, timed ultrasound scanning protocol in the first week of life. CP was ascertained at 2 years of age by clinical examination in 80% of survivors and by interview and medical record review in another 6% and was classified as disabling or nondisabling. No significant reduction in risk of nondisabling CP (adjusted odds ratio [OR], 1.00; 95% confidence interval [CI], 0.53 to 1.88) or disabling CP [DCP] (adjusted OR, 0.63; 95% CI, 0.32 to 1.24) CP with magnesium exposure was found in a logistic regression model that controlled for gestational age, fetal growth, gender, multiple birth status, mode of delivery, amnionitis, and hypertensive disorders. In a small subset of infants, those with onset of parenchymal lesions at 7 days of age or later (n = 29), magnesium exposure was associated with a significantly reduced risk of DCP (OR, 0.10; 95% CI, 0.02 to 0.65). Magnesium sulfate exposure was not associated with germinal matrix/intraventricular hemorrhage (adjusted OR, 0.89; 95% CI, 0.64 to 1.25) or with parenchymal brain lesions (adjusted OR, 0.83; 95% CI, 0.53 to 1.30). The hypothesis that magnesium sulfate use reduces the risk of neonatal brain lesions or CP in low birth weight infants was not statistically supported in this study, although a modest reduction in risk of DCP cannot be excluded. The data further suggest that magnesium exposure may be associated with reduction in risk of CP in low birth weight infants who have late-onset brain lesions, but this unpredicted observation requires confirmation in another data set.

Developmental change in magnesium sulfate-induced relaxation of rabbit pulmonary arteries

Article

Full-text available

Dec 1999

Magnesium causes a variety of vascular smooth muscle to relax. The present study was designed to determine whether there is a developmental change in the magnesium-induced response of pulmonary vasculature. Isolated pulmonary arteries (PA) of newborn (1- to 3-day-old) and juvenile (4- to 6-wk-old) rabbits were suspended in organ chambers filled with modified Krebs-Ringer bicarbonate solution (95% O(2)-5% CO(2), 37.0 degrees C), and their isometric tension was recorded. In arteries preconstricted with endothelin-1 to a similar tension level, MgSO(4) caused greater relaxation of juvenile rabbit PA than that of the newborn rabbit PA. Verapamil, a voltage-dependent Ca(2+) channel blocker, attenuated magnesium-induced relaxation in juvenile rabbit PA but not in newborn PA. The uptake of Ca(2+) of juvenile rabbit PA was inhibited by MgSO(4), and the inhibition was attenuated by verapamil. The uptake of Ca(2+) of newborn rabbit PA was smaller than that of the juvenile PA and was not significantly affected by MgSO(4) and verapamil. These results demonstrate that there is a developmental increase in the dilator effect of MgSO(4) in rabbit PA. In newborn rabbit PA, an incomplete maturation of the voltage-dependent Ca(2+) channels may contribute to the smaller vasodilation induced by MgSO(4).

Effect of Magnesium Sulfate Given for Neuroprotection Before Preterm Birth: A Randomized, Controlled Trial

Article

Full-text available

Dec 2003
J Am Med Assoc

Prenatal magnesium sulfate may reduce the risk of cerebral palsy or death in very preterm infants. To determine the effectiveness of magnesium sulfate given for neuroprotection to women at risk of preterm birth before 30 weeks' gestation in preventing pediatric mortality and cerebral palsy. Randomized controlled trial at 16 tertiary hospitals in Australia and New Zealand with stratification by center and multiple pregnancy. A total of 1062 women with fetuses younger than 30 weeks' gestation for whom birth was planned or expected within 24 hours were enrolled from February 1996 to September 2000 with follow-up of surviving children at a corrected age of 2 years. Women were randomly assigned to receive a loading infusion of 8 mL (4 g [16 mmol] of 0.5 g/mL of magnesium sulfate solution or isotonic sodium chloride solution [0.9%]) for 20 minutes followed by a maintenance infusion of 2 mL/h for up to 24 hours. Rates of total pediatric mortality, cerebral palsy, and the combined outcome of death or cerebral palsy at a corrected age of 2 years. Data were analyzed for 1047 (99%) 2-year survivors. Total pediatric mortality (13.8% vs 17.1%; relative risk [RR], 0.83; 95% confidence interval [CI], 0.64-1.09), cerebral palsy in survivors (6.8% vs 8.2%; RR, 0.83; 95% CI, 0.54-1.27), and combined death or cerebral palsy (19.8% vs 24.0%; RR, 0.83; 95% CI, 0.66-1.03) were less frequent for infants exposed to magnesium sulfate, but none of the differences were statistically significant. Substantial gross motor dysfunction (3.4% vs 6.6%; RR, 0.51; 95% CI, 0.29-0.91) and combined death or substantial gross motor dysfunction (17.0% vs 22.7%; RR, 0.75; 95% CI, 0.59-0.96) were significantly reduced in the magnesium group. Magnesium sulfate given to women immediately before very preterm birth may improve important pediatric outcomes. No serious harmful effects were seen.

The Risks of Extending the Controversial Use of Tocolytic Magnesium Sulfate for the Purpose of Neuroprotection in Preterm Labor

Article

Full-text available

Aug 2004
J PERINATOL

Prenatal Magnesium Sulfate Exposure and the Risk for Cerebral Palsy or Mental Retardation Among Very Low-Birth-Weight Children Aged 3 to 5 Years

Article

Dec 1996

Diana E. Schendel

Objective. —To examine the relationship between prenatal magnesium sulfate exposure and the risk for cerebral palsy (CP) or mental retardation (MR) among very low-birth-weight (VLBW; <1500 g) children. Secondarily, to investigate the effect of prenatal magnesium sulfate exposure on VLBW infant mortality.Design. —Cohort study with follow-up to 1 year of age; a subset followed up to 3 to 5 years.Setting. —Twenty-nine Georgia counties, including the 5-county Atlanta metropolitan area.Participants. —All VLBW births (N=1097) occurring during 2 years (1986-1988); all metropolitan Atlanta VLBW neonates who survived infancy (N=519).Main Outcome Measures. —Infant mortality as determined from vital statistics records. Development of CP or MR by 3 to 5 years of age among metropolitan Atlanta VLBW survivors as determined from the Metropolitan Atlanta Developmental Disabilities Surveillance Program.Results. —For the entire cohort, there was no association between prenatal magnesium sulfate exposure and infant mortality (adjusted rate ratio, 1.02; 95% confidence interval [CI], 0.83-1.25). Among Atlanta-born survivors, those exposed to magnesium sulfate had a lower prevalence of CP or MR than those not exposed (CP: magnesium sulfate, 0.9%, no magnesium sulfate, 7.7%, crude odds ratio [OR], 0.11, 95% CI, 0.02-0.81; MR: magnesium sulfate, 1.8%, no magnesium sulfate, 5.8%, crude OR, 0.30,95% CI, 0.07-1.29). Multivariable adjustment had no appreciable effect on the ORs for CP or MR, but the CIs included 1.0.Conclusions. —A reduced risk for CP, and possibly MR, among VLBW children is associated with prenatal magnesium sulfate exposure. The reduced risk for childhood CP or MR does not appear to be due to selective mortality of magnesium sulfate—exposed infants.

Randomized investigation of magnesium sulfate for prevention of preterm birth

Article

Oct 1990
AM J OBSTET GYNECOL

One hundred fifty-six women with preterm labor between 24 and 34 weeks' gestation were randomized to receive either intravenous magnesium sulfate or no tocolytic therapy. Magnesuim sulfate infusions of up to 3 gm/hr were used in 76 pregnancies and resulted in a mean serum magnesium concentration of 5.5 +/- 1.4 mEq/L (mean +/- SEM). Compared with 80 control pregnancies, magnesium sulfate tocolysis had no significant effect on duration of gestation, birth weight, neonatal morbidity, and perinatal mortality. We conclude that clinically safe infusions of magnesium sulfate are ineffective when used to prevent preterm birth.

Maternal-fetal transfer of ionized serum magnesium during the stress of labor and delivery: A human study

Article

Aug 1995

The purpose of this study was to compare levels and fractions of ionized magnesium in maternal venous serum with those in umbilical venous and arterial serum and to determine whether the maternal levels and fractions change during the stress of labor. Utilizing an ion-selective electrode, we determined levels and fractions of ionized magnesium (IMg2+) and levels of ionized calcium (ICa2+) in the maternal venous serum (MVS) of 12 parturients on admission and at the end of labor, as well as in the umbilical venous (UVS) and umbilical arterial serum (UAS) at delivery. A paired-sample study design was used. Whereas mean levels of ICa2+ did not change significantly (p > 0.05) during labor, the mean (+/- SE) MVS levels of IMg2+ and total magnesium (TMg) fell from 0.50 +/- 0.01 and 0.80 +/- 0.02 mmol/L, respectively, on admission to 0.46 +/- 0.01 and 0.68 +/- 0.01 mmol/L (p < 0.01 and p < 0.001, respectively) at delivery. The ionized fraction, expressed as a percent (IMg2+/TMg x 100), increased from 62.8 +/- 2.1% to 67.8 +/- 1.2% (p < 0.05). In the UVS, the mean IMg2+ level (0.52 +/- 0.02 mmol/L) and the mean ionized fraction (73.6 +/- 1.7%) were higher than in MVS on admission or at delivery (p < 0.05 for all comparisons). The mean IMg2+ level in UAS (0.50 +/- 0.02 mmol/L) was lower than in UVS (p < 0.05), but higher than in MVS at delivery (p < 0.01). Finally, there were significant positive correlations between levels of magnesium (Mg) in MVS and in the UAS or UVS. The observation that UAS levels of IMg2+ and TMg were similar to the MVS levels on admission despite the fall in maternal levels during labor points to the presence of homeostatic mechanisms in the fetus and placenta. It is possible that the presence of a higher fraction of unbound, free magnesium in UVS enhances magnesium transport to the fetus and thus homeostasis. Finally, we hypothesize that the fall in the levels of the biologically active form of Mg during labor may be yet another manifestation of the known stress responses to labor.

Prenatal magnesium sulfate exposure and the risk for cerebral palsy or mental retardation among very low-birth-weight children aged 3−5 years

Article

Dec 1996

To examine the relationship between prenatal magnesium sulfate exposure and the risk for cerebral palsy (CP) or mental retardation (MR) among very low-birth-weight (VLBW; <1500 g) children. Secondarily, to investigate the effect of prenatal magnesium sulfate exposure on VLBW infant mortality. Cohort study with follow-up to 1 year of age; a subset followed up to 3 to 5 years. Twenty-nine Georgia counties, including the 5-county Atlanta metropolitan area. All VLBW births (N=1097) occurring during 2 years (1986-1988); all metropolitan Atlanta VLBW neonates who survived infancy (N=519). Infant mortality as determined from vital statistics records. Development of CP or MR by 3 to 5 years of age among metropolitan Atlanta VLBW survivors as determined from the Metropolitan Atlanta Developmental Disabilities Surveillance Program. For the entire cohort, there was no association between prenatal magnesium sulfate exposure and infant mortality (adjusted rate ratio, 1.02; 95% confidence interval [CI], 0.83-1.25). Among Atlanta-born survivors, those exposed to magnesium sulfate had a lower prevalence of CP or MR than those not exposed (CP: magnesium sulfate, 0.9%, no magnesium sulfate, 7.7%, crude odds ratio [OR], 0.11, 95% CI, 0.02-0.81; MR: magnesium sulfate, 1.8%, no magnesium sulfate, 5.8%, crude OR, 0.30, 95% CI, 0.07-1.29). Multivariable adjustment had no appreciable effect on the ORs for CP or MR, but the CIs included 1.0. A reduced risk for CP, and possibly MR, among VLBW children is associated with prenatal magnesium sulfate exposure. The reduced risk for childhood CP or MR does not appear to be due to selective mortality of magnesium sulfate-exposed infants.

Prevalence of Overweight Among Preschool Children in the United States, 1971 Through 1994

Article

May 1997
Pediatrics

To examine the prevalence of overweight among US preschool children 2 months through 5 years of age between the years 1971 through 1974 and 1988 through 1994. Nationally representative cross-sectional surveys with a physical examination, including measurement of stature, length, and weight. Between 1200 and 7500 children younger than 6 years were examined in each of four different surveys during 1971 through 1974 (first National Health and Nutrition Examination Survey [NHANES I]), 1976 through 1980 (NHANES II), 1982 through 1984 (Hispanic Health and Nutrition Examination Survey), and 1988 through 1994 (NHANES III). The prevalence of overweight increased among some sex and age groups of preschool children between 1971 through 1974 and 1988 through 1994. More than 10% of 4- and 5-year-old girls were overweight in 1988 through 1994 compared with 5.8% in 1971 through 1974. However, there was no change during this period in the prevalence of overweight among 1- and 2- to 3-year-old children. During 1988 through 1994, the prevalence of overweight among children 2 months through 5 years of age was consistently higher in girls than boys. Mexican-American children had a higher prevalence of overweight than non-Hispanic black and non-Hispanic white children. These results parallel what has been reported for older children and adults in the United States. These results show that in the last 20 years the prevalence of overweight has increased among 4- and 5-year-old children but not among younger children. These findings suggest that efforts to prevent overweight, including encouragement of physical activity and improved diets, should begin in early childhood.

Serum levels of magnesium at birth related to complications of immaturity

Article

Oct 1997

Magnesium is a natural calcium channel blocker inhibiting vasoconstriction in numerous vascular beds. Magnesium sulphate given prior to birth to pre-eclamptic mothers and mothers in preterm labour has in retrospect been found to be associated with a decreased incidence of both intraventricular haemorrhage and cerebral palsy. Little is known about the effect of normal variations of serum magnesium in the very preterm baby, where morbidity is closely related to rapid vascular changes. We have analysed the absolute levels and normal variations of magnesium concentration in cord blood and during the first 3 weeks after birth for 69 infants born before 32 gestational weeks of age. The results show an inverse relation between serum magnesium at birth and gestational age. Higher levels of serum magnesium at birth within normal variations were associated with a delayed closure of the ductus arteriosus, and mild but not severe peri- and intraventricular haemorrhage.

Is tocolytic magnesium sulphate associated with increased paediatric mortality

Article

Dec 1997

Maternal Magnesium Sulfate and the Development of Neonatal Periventricular Leucomalacia and Intraventricular Hemorrhage

Article

Apr 1999
OBSTET GYNECOL

Neonatal periventricular leucomalacia and intraventricular hemorrhage are strong correlates of cerebral palsy. Our objective was to evaluate the effect of maternal magnesium sulfate exposure on the incidence and severity of periventricular leucomalacia and intraventricular hemorrhage in preterm neonates. Nine hundred eighteen consecutive inborn neonates with birth weights from 500 to 1750 g were divided primarily into two groups on the basis of maternal exposure to magnesium sulfate. The groups were divided secondarily into two clinical groups, a physician-initiated group, which consisted of neonates delivered for maternal or fetal indications, and a preterm delivery group, which included neonates delivered as a result of preterm labor or preterm premature rupture of membranes. These clinical groups were stratified further into magnesium sulfate-exposed and -unexposed subgroups. Neonatal neurosonograms were performed on days 3 and 7 of life and described as normal or abnormal. Abnormal sonograms included any periventricular leucomalacia or intraventricular hemorrhage. Severe lesions included periventricular leucomalacia, periventricular leucomalacia with intraventricular hemorrhage, or grades 3 or 4 intraventricular hemorrhage. The magnesium sulfate groups and the clinical groups with their magnesium sulfate strata were compared for the incidence and severity of abnormal sonograms. They also were compared for maternal and neonatal characteristics. Maternal magnesium sulfate exposure was not associated with reduction in the incidence of abnormal sonograms when compared with the unexposed group (27% compared with 33%, P = .06). However, fewer severe lesions were observed in the exposed group (14% compared with 21%, P = .004). When clinical groups were examined, magnesium sulfate was not associated with a decrease in abnormal sonograms (adjusted odds ratio [OR] 1.09, 95% confidence interval [CI] 0.78, 1.52, P = .40) or severe lesions (adjusted OR 1.11, 95% CI 0.73, 1.68, P = .42). Logistic regression analyses of magnesium sulfate exposure within clinical groups controlling for the confounding effects of maternal and neonatal characteristics revealed no protective effect of magnesium sulfate exposure on the incidence of abnormal sonograms (adjusted OR 1.01, 95% CI 0.70, 1.44, P = .97) or severe lesions (adjusted OR 1.01, 95% CI 0.70, 1.74, P = .69). Within clinical groups, the preterm delivery group exhibited an increased risk for abnormal sonograms (adjusted OR 1.63, 95% CI 1.01, 2.67, P = .05) and severe lesions (adjusted OR 9.79, 95% CI 3.27, 29.29, P = .001) when compared with the physician-initiated delivery group, independent of maternal magnesium sulfate exposure. Maternal magnesium sulfate exposure had no protective effect on the incidence or severity of periventricular leucomalacia and intraventricular hemorrhage in preterm neonates. The prevalence of these lesions was correlated better with the clinical group of origin and indication for its use.

Perinatal Death and Tocolytic Magnesium Sulfate

Article

Sep 2000
OBSTET GYNECOL

To determine whether there is a significant association between perinatal mortality and exposure to total doses of tocolytic magnesium sulfate larger than 48 g. We did a case-control study in which cases were defined as neonates or fetuses who died after being exposed to tocolytic magnesium sulfate and controls were those who survived exposure. The study included fetuses and neonates who weighed between 700 and 1249 g and whose mothers had received tocolytic magnesium sulfate at Chicago Lying-in Hospital between January 1, 1986, and March 31, 1999. We excluded women who received prophylactic magnesium sulfate for preeclampsia or preeclampsia superimposed on chronic hypertension, and fetuses or neonates with major congenital anomalies. Data were analyzed by Fisher exact test, chi(2) test, Student t test, Mann-Whitney U test, multivariable logistic regression, and Cochrane-Armitage trend test. Controlling for birth weight or gestational age, year of delivery, receipt of betamethasone, acute maternal disease, and maternal race in a multivariable model, we found that exposure to total doses of tocolytic magnesium sulfate exceeding 48 g was significantly associated with increased perinatal mortality (adjusted odds ratio 4. 7; 95% confidence interval 1.1, 20.0; P =.035). Using the Cochrane-Armitage trend test, we found that a significant dose response was present (P =.03), but one that was most consistent with a threshold effect. Our findings support the hypothesis that high doses of tocolytic magnesium sulfate are associated with increased perinatal mortality among fetuses and neonates weighing 700-1249 g.

Fetal cardiovascular function during prolonged magnesium sulfate tocolysis

Article

Jan 2000

The purpose of this study was to evaluate the fetal cardiovascular function during prolonged magnesium sulfate tocolysis. We performed a fetal ultrasonographic examination in 15 patients (Mg group) during magnesium sulfate tocolysis for the treatment of preterm labor. The maternal serum magnesium concentration was 5.7 +/- 0.5 mg/dl at the time of the examination. Sixteen fetuses in normal pregnancies at similar gestational ages were used as the control group. The fetal heart rate and the middle cerebral artery pulsatility index in the Mg group were lower than in the control group (p < 0.01). Fractional shortening (FS) of the right ventricle in the Mg group was lower (p < 0.01), while FS of the left ventricle was higher (p < 0.01) than in the controls. The calculated blood flow through the tricuspid orifice in the Mg group was lower than in the control group (p < 0.01). In contrast, the blood flow through the mitral orifice in the Mg group was higher than in the control group (p < 0.01). In conclusion, in spite of the fact that the right ventricular function is depressed, the fetus maintains its cardiac output during prolonged hypermagnesemia by increasing its left ventricular function. These results indicate the different fetal intracardiac and peripheral circulation, especially in the brain, from normal fetuses.

Hypocarbia during the First 24 Postnatal Hours and White Matter Echolucencies in Newborns ≤28 Weeks Gestation

Article

Apr 2001

The purpose of the present study was to test the hypothesis that newborns < or = 28 wk gestation who have a PCO(2) measurement in the lowest gestational age-specific quartile (hypocarbia) on the first day of life are not at increased risk for ultrasonographic white matter echolucency (EL) after adjustment for confounders. The sample consisted of 799 infants < or = 28 wk gestation born during 1991-1993. Forty-eight infants with EL were classified as cases and compared with 751 controls, i.e. those without EL. We performed univariable comparisons, stratified analyses, and multivariable logistic regression. In the univariable analyses, hypocarbia on the first day of life was associated with an increased EL risk. The odds ratios for the hypocarbia-EL relationship were prominently elevated in the strata of infants who did not have other major risk factors for EL (e.g. gestational age 26-28 wk, normothyroxinemia, no characteristics of antenatal infection). In the multivariable analyses, the association diminished after adjustment with a hypocarbia propensity score (odds ratio = 1.7; 95 % confidence interval, 0.8-3.2) or with potential confounders.

Magnesium sulfate as a tocolytic agent

Article

Sep 2001
SEMIN PERINATOL

Although magnesium sulfate is widely used as a tocolytic agent in the hope of preventing spontaneous preterm birth, there is a paucity of data from large well-designed randomized clinical studies demonstrating the efficacy of magnesium sulfate therapy. Given the potential for untoward side effects and the inherent risks of magnesium sulfate therapy, a thorough understanding of the potential risks and benefits of this agent is needed. To accomplish this understanding we have provided a detailed review the history, pharmacology, physiology, maternal/fetal side effects, and tocolytic efficacy of magnesium sulfate.

Association between maternal serum ionized magnesium levels at delivery and neonatal intraventricular hemorrhage

Article

Jun 2002
J Pediatr

To determine whether magnesium sulfate (MgSO(4)) exposure is associated with a reduced risk for neonatal intraventricular hemorrhage (IVH). In a randomized, controlled trial, women in preterm labor were randomly assigned to receive MgSO(4), "other" tocolytic, or saline control. At delivery, we collected maternal antecubital and umbilical cord blood for determination of serum ionized magnesium levels. Neonatal IVH was diagnosed by cranial ultrasonogram. Among 144 infants, 24 were diagnosed with IVH. Using crude intention-to-treat analysis, we found that 18% (13/74) of survivors exposed after birth to MgSO(4) had IVH compared with 16% (11/70) of babies who were not exposed. Infants who had IVH were more likely to have been delivered by mothers with higher serum ionized magnesium (Mg) levels (0.75 vs 0.56 mmol/L) (P =.01). Using multivariable logistic regression, we confirmed that higher Mg levels are a significant predictor of neonatal IVH (adjusted odds ratio, 15.8; 95% CI, 1.4-175.0) even when adjusted for birth weight, gestational age, antenatal hemorrhage, and neonatal glucocorticoid exposure. In mothers with preterm labor, our data indicate that antenatal MgSO(4) exposure may be associated with an increased risk for IVH among their newborns.

Effects of magnesium on prostacyclin synthesis and intracellular free calcium concentration in vascular cells

Article

Apr 2004

This study investigated the effects of extracellular magnesium concentration ([Mg2+]e; 0.3-3 mM) on intracellular free calcium concentration ([Ca2+]i) and prostacyclin (PGI2) production in cultured human umbilical vein endothelial cells (HUVEC) and vascular smooth muscle cells from rats (VSMC) under basal and agonist-stimulated conditions. We used histamine as agonist which increases [Ca2+]i and PGI2 production in HUVEC, norepinephrine in VSMC. [Mg2+]e dose-dependently increased basal and agonist-stimulated PGI2 production in both cells. [Mg2+]e dose-dependently reduced basal [Ca2+]i in VSMC, but did not influence in HUVEC. In both cells, increasing [Mg2+]e reduced agonist-stimulated [Ca2+]i responses. Furthermore, [Mg2+]e dose-dependently reduced agonist-stimulated [Ca2+]i in Ca(2+)-free buffer, indicating intracellular Ca2+ release. In VSMC, 10(-6) M diltiazem and 10(-7) M nifedipine, Ca2+ channel blockers, reduced agonist-stimulated [Ca2+]i as well as 3 mM Mg2+, but did not affect PGI2 production. [Mg2+]e amplified dose-dependently arachidonic acid-induced PGI2 production in both cells, suggesting the activation of cyclooxygenase and/or PGI2 synthetase. Our results suggest that [Mg2+]e influences intracellular Ca2+ mobilization of not only vascular smooth muscle cells but also endothelial cells by inhibiting both Ca2+ influx and intracellular Ca2+ release. [Mg2+]e enhances PGI2 production in both types of cells, although the mechanism is likely to be independent from Ca2+ mobilization.

Magnesium sulfate as a tocolytic agent retardation among very low-birth weight children aged 3–5 years

Jan 1996
236-247

Ps Ramsey
Dj Rouse

Ramsey PS, Rouse DJ. Magnesium sulfate as a tocolytic agent. Semin Perinatol 2001; 25(4): 236–247. retardation among very low-birth weight children aged 3–5 years. JAMA 1996; 276: 1805–1810.

Magnesium sulfate for preventing preterm birth in threatened preterm labour. Cochrane pregnancy and childbirth group

C A Crowther
J E Hiller
L W Doyle

Crowther CA, Hiller JE, Doyle LW. Magnesium sulfate for preventing preterm birth in threatened preterm labour. Cochrane pregnancy and childbirth group. Cochrane Database of Systematic Reviews, 4 2006.

In utero magnesium exposure: effects on ELBW infants at 18 months of age

Jan 2001
388A

J A Lemons
B R Vorh
D K Stevenson
K Poole
A Das
C R Bauer
JA Lemons

Lemons JA, Vorh BR, Stevenson DK, Poole K, Das A, Bauer CR et al. In utero magnesium exposure: effects on ELBW infants at 18 months of age. Pediatr Res 2001; 49: 388A.

Cord-blood ionized magnesium (iMg) exceeds maternal levels in both untreated and tocolytic magnesium sulfate treated preterm neonates

Jan 1999
S50

P G Pryde
M J Borg
R Mittendorf
R J Elin
PG Pryde

Pryde PG, Borg MJ, Mittendorf R, Elin RJ. Cord-blood ionized magnesium (iMg) exceeds maternal levels in both untreated and tocolytic magnesium sulfate treated preterm neonates. Am J Obstet Gynecol 1999; 184: S50.

Antenatal exposure to magnesium sulfate and the incidence of patent ductus arteriosus in extremely low birth weight infants

Abstract

No full-text available

Recommended publications

Serial Echocardiography in Very Preterm Infants: A Pilot Randomized Trial

Serum Endocan Level as a Predictive Marker for Hemodynamically Significant Patent Ductus Arteriosus...

Ligation of patent ductus arteriosus in low birth weight premature infants: Timing for intervention...

1154 Spontaneous Closure of Patent Ductus Arteriosus is Presumable in Very Low Birth Weight Infants