Manijeh Kamyar

Magnesium sulfate, chorioamnionitis, and neurodevelopment after preterm birth.

To assess the neuroprotective effect of magnesium sulfate (MgSO4) in preterm children exposed to chorioamnionitis.

Antenatal Magnesium Sulfate, Necrotizing Enterocolitis, and Death among Neonates < 28 Weeks Gestation

Objective This study aims to examine the relationship between antenatal magnesium sulfate (MgSO4) and neonatal death and/or severe necrotizing enterocolitis (NEC) among infants < 28 weeks. Methods Secondary analysis of a multicenter randomized trial of antenatal MgSO4 versus placebo administered to women to prevent death and cerebral palsy. Neonates < 28 weeks were included. The primary outcome was neonatal death before NICU discharge, and/or severe NEC (Bell criteria stage II/III). Neonates with and without death/severe NEC were compared. Results A total of 697 neonates met the criteria. Out of which 150 (21.5%) died and/or were diagnosed with severe NEC. Antenatal MgSO4 exposure was not associated with death/severe NEC in infants < 28 weeks. In a subgroup analysis of neonates < 26 weeks, treatment group assignment to antenatal MgSO4 was associated with an increased odds of death/severe NEC (adjusted odds ratio: 1.90, 95% confidence interval: 1.12–3.22, p = 0.017). Conclusions Among neonates < 26 weeks, antenatal MgSO4 was associated with death and severe NEC. Further prospective study in larger populations is needed.

Epilepsy in pregnancy.

Over 25,000 epileptic women deliver viable pregnancies each year in the United States. Although medical management is the first line of treatment, many physiological changes associated with pregnancy can make optimal treatment challenging. Medication dosage is adjusted based on side effects and seizure frequency, with the goal being no seizures with the lowest medication dosage(s) and side-effect profile possible. Whenever possible, monotherapy is preferred. Many antiepileptic drugs have teratogenic potential, so preconceptional optimization of medication dosage(s) is recommended. Epilepsy has associated neurological comorbidities, the most common being migraines and sleep disorders.

Intrapartum Magnesium Sulfate and the Potential for Cardiopulmonary Drug-Drug Interactions

Background: This study sought to determine the frequency of possible cardiopulmonary drug–drug interactions among pregnant women who received intrapartum magnesium sulfate (MgSO4). Methods: Pregnant women admitted to an Intermountain Healthcare facility between January 2009 and October 2011 were studied, if they received 1 or more doses of MgSO4. Concomitant medications were electronically queried from an electronic health records system. Adverse events were identified using administrative discharge codes. The frequency of cardiopulmonary drug–drug interactions was compared among women who did, and did not, receive aminoglycoside antibiotics, antacids/laxatives, calcium channel blockers, corticosteroids, diuretics, neuromuscular blocking agents, and vitamin D analogs, all of which were contraindicated for patients receiving MgSO4. Results: Overall, 683 women received intrapartum MgSO4 during the study period. A total of 219 MgSO4 potentially interacting drugs were identified among 155 (23%) unique patients. The most commonly identified potentially interacting agents included calcium channel blockers (26%), diuretics (25%), and antacids/laxatives (19%). Longer hospital stays were significantly associated with increasing numbers of MgSO4 interacting drugs (P < 0.001). Three of 53 (6%) women who received furosemide experienced a cardiac arrest, compared with 0 of 618 (0%) women who did not receive furosemide (Fisher exact test, P < 0.001). Conclusions: Intrapartum administration of drugs that interact with MgSO4 is common and associated with prolonged hospital stays and potentially cardiopulmonary drug–drug interactions. Caution is warranted when prescribing MgSO4 in combination with known interacting medications.

Therapeutic Drug Monitoring in Pregnancy

Abstract During pregnancy, important physiologic changes occur that affect pharmacokinetics and ultimately drug management. These include changes to renal and liver function, changes in serum protein levels, and the addition of a pharmacokinetic compartment (the infant and placenta) that is not present in the broader population. In addition, postpartum return to baseline physiology can further complicate drug management. This chapter examines therapeutic drug monitoring issues associated with pregnancy, including specific examples such as management of antidepressants.

Authors' reply re: Magnesium sulphate, chorioamnionitis, and neurodevelopment after preterm birth

Sir, The article by Kamyar et al. on magnesium sulphate, chorioamnionitis and neurodevelopment after preterm birth made an interesting read. Kamyar et al. concluded that among children who were exposed to chorioamnionitis, antenatal administration of magnesium sulphate was not associated with improved neurodevelopmental outcome. The general expectation is that magnesium sulphate confers neuroprotection by mitigating the inflammatory cytokine production in preterm infants. The authors quite correctly did not recommend any changes to the current practice guidelines, based on their study. It is worth mentioning the possibility for nonimprovement in neurodevelopmental outcome in the present study with the presence of infection. One explanation would be the random error and the small sample size. Another possibility is that the anti-inflammatory effect of magnesium sulphate may not be sufficient to overcome the inflammationmediated injury associated with chorioamnionitis, as suggested by the authors. There might be alternative mechanisms of neuronal injury for which magnesium sulphate is insufficient to abrogate the inflammatory insult and which need alternative neuromodulators. It is known that pathogens responsible for chorioamnionitis produce ‘bacterial biofilms’ that resist the actions of antibiotic therapy. Perhaps a similar mechanism may be in operation, to overcome the actions of magnesium sulphate, in the presence of chorioamnionitis. Another possibility is that the investigation of fetal neuroprotection is limited because cerebral palsy tends to be the sole clinical outcome studied. There are many subtle neurological impairments related to prematurity such as sensory neural hearing loss, visual impairments, and attention, cognitive and academic impairments. So the effects of magnesium, sulphate may be underestimated and this needs to be considered when considering the overall effect. It is clear that there remain gaps in our knowledge on preterm labour, neurodevelopmental impairments and the effects of magnesium sulphate. However, the study by Kamyar et al. has improved our existing body of evidence on the effects of magnesium sulphate and neurodevelopmental outcomes in preterm labour.&