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Progress in Neuro-psychopharmacology &... Jul 2024Increasing evidence suggests that the physiological changes of pregnancy may impact pharmacokinetics of antiseizure medications (ASM), and this may affect treatment... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Increasing evidence suggests that the physiological changes of pregnancy may impact pharmacokinetics of antiseizure medications (ASM), and this may affect treatment outcomes. The aim of this study was to quantify the pregnancy impact on the ASM pharmacokinetics.
METHODS
A systematic literature search was conducted in PubMed/EMBASE in November 2022 and updated in August 2023 for studies comparing levels of ASM in the same individuals during pregnancy and in the preconception/postpartum period. Alteration ratios between the 3rd trimester and baseline were estimated. We also performed a random-effects meta-analysis calculating between-timepoint differences in mean differences (MDs) and 95% confidence intervals (95%CIs) for dose-adjusted plasma concentrations (C/D ratios). Study quality was assessed using the ClinPK guidelines.
RESULTS
A total of 65 studies investigating 15 ASMs in 674 pregnancies were included. The largest differences were reported for lamotrigine, oxcarbazepine and levetiracetam (alteration ratio 0.42, range 0.07-2.45, 0.42, range 0.08-0.82 and 0.52, range 0.04-2.77 respectively): accordingly, C/D levels were lower in the 3rd trimester for lamotrigine, levetiracetam and the main oxcarbazepine metabolite monohydroxycarbazepine (MD = -12.33 × 10, 95%CI = -16.08 to -8.58 × 10 (μg/mL)/(mg/day), p < 0.001, MD = -7.16 (μg/mL)/(mg/day), 95%CI = -9.96 to -4.36, p < 0.001, and MD = -4.87 (μg/mL)/(mg/day), 95%CI = -9.39 to -0.35, p = 0.035, respectively), but not for oxcarbazepine (MD = 1.16 × 10 (μg/mL)/(mg/day), 95%CI = -2.55 to 0.24 × 10, p = 0.10). The quality of studies was acceptable with an average rating score of 11.5.
CONCLUSIONS
Data for lamotrigine, oxcarbazepine (and monohydroxycarbazepine) and levetiracetam demonstrate major changes in pharmacokinetics during pregnancy, suggesting the importance of therapeutic drug monitoring to assist clinicians in optimizing treatment outcomes.
Topics: Humans; Pregnancy; Anticonvulsants; Female; Pregnancy Complications; Levetiracetam; Lamotrigine; Epilepsy; Oxcarbazepine
PubMed: 38762161
DOI: 10.1016/j.pnpbp.2024.111030 -
BMC Pregnancy and Childbirth May 2024
PubMed: 38760768
DOI: 10.1186/s12884-024-06576-y -
Psychoneuroendocrinology Aug 2024Allopregnanolone (ALLO) is a metabolite of progesterone and a neuroactive steroid hormone. As a positive allosteric modulator of gamma-aminobutyric acid (GABA)...
BACKGROUND
Allopregnanolone (ALLO) is a metabolite of progesterone and a neuroactive steroid hormone. As a positive allosteric modulator of gamma-aminobutyric acid (GABA) receptors, ALLO seems to have antidepressant and anxiolytic effects, and was therefore approved as a specific medication for the treatment of postpartum depression in 2019. Despite the growing number of publications investigating ALLO levels, results on the biological and psychological correlates in the peripartum period remain inconsistent, possibly due to methodological challenges regarding measurement. To date, however, there is no systematic review examining the correlates, concentrations, and challenges in measuring ALLO in peripartum women.
METHOD
A systematic literature search of PubMed and PsycINFO was conducted in August 2023. Original research articles that measured ALLO concentrations in peripartum women were included. Reports were excluded if they were not original research, included non-human subjects, did not include peripartum women, did not include ALLO measurement as an outcome, included (pharmacological) interventions, constituted method validations, or used the same cohort as another study.
RESULTS
The literature search yielded 234 articles, and two articles were identified from other sources. After full-text screening, 19 articles (N = 1401) met the inclusion criteria, of which seven focused on biological correlates of ALLO and 12 on mood correlates. Of the latter, six found no association between ALLO and mood, four found a negative association, and two found a positive association. Overall, the results show an increase in ALLO levels during pregnancy and a decrease after birth, with levels then remaining low until six months postpartum. ALLO was most commonly measured in blood plasma and by gas chromatography-mass spectrometry (GC-MS). A significant matrix effect was found for blood serum and a significant method effect for radioimmunoassays (RIAs). A significant effect of time of measurement was found.
CONCLUSION
ALLO measurement shows method and matrix effects. ALLO levels are higher when measured in serum compared to in plasma, and when measured using RIA compared to other methods. Time of measurement, study design, and standardization of measurement also influence the reliability of measurement and the interpretation of results.
Topics: Humans; Pregnanolone; Female; Peripartum Period; Pregnancy; Depression, Postpartum; Adult
PubMed: 38759520
DOI: 10.1016/j.psyneuen.2024.107081 -
BMC Medicine May 2024Mobile health (mHealth) technologies have been harnessed in low- and middle-income countries (LMICs) to address the intricate challenges confronting maternal, newborn,... (Review)
Review
BACKGROUND
Mobile health (mHealth) technologies have been harnessed in low- and middle-income countries (LMICs) to address the intricate challenges confronting maternal, newborn, and child health (MNCH). This review aspires to scrutinize the effectiveness of mHealth interventions on MNCH outcomes during the pivotal first 1000 days of life, encompassing the period from conception through pregnancy, childbirth, and post-delivery, up to the age of 2 years.
METHODS
A comprehensive search was systematically conducted in May 2022 across databases, including PubMed, Cochrane Library, Embase, Cumulative Index to Nursing & Allied Health (CINAHL), Web of Science, Scopus, PsycINFO, and Trip Pro, to unearth peer-reviewed articles published between 2000 and 2022. The inclusion criteria consisted of (i) mHealth interventions directed at MNCH; (ii) study designs, including randomized controlled trials (RCTs), RCT variations, quasi-experimental designs, controlled before-and-after studies, or interrupted time series studies); (iii) reports of outcomes pertinent to the first 1000 days concept; and (iv) inclusion of participants from LMICs. Each study was screened for quality in alignment with the Cochrane Handbook for Systematic Reviews of Interventions and the Joanne Briggs Institute Critical Appraisal tools. The included articles were then analyzed and categorized into 12 mHealth functions and outcome domain categories (antenatal, delivery, and postnatal care), followed by forest plot comparisons of effect measures.
RESULTS
From the initial pool of 7119 articles, we included 131 in this review, comprising 56 RCTs, 38 cluster-RCTs, and 37 quasi-experimental studies. Notably, 62% of these articles exhibited a moderate or high risk of bias. Promisingly, mHealth strategies, such as dispatching text message reminders to women and equipping healthcare providers with digital planning and scheduling tools, exhibited the capacity to augment antenatal clinic attendance and enhance the punctuality of child immunization. However, findings regarding facility-based delivery, child immunization attendance, and infant feeding practices were inconclusive.
CONCLUSIONS
This review suggests that mHealth interventions can improve antenatal care attendance and child immunization timeliness in LMICs. However, their impact on facility-based delivery and infant feeding practices varies. Nevertheless, the potential of mHealth to enhance MNCH services in resource-limited settings is promising. More context-specific implementation studies with rigorous evaluations are essential.
Topics: Humans; Telemedicine; Developing Countries; Infant, Newborn; Female; Pregnancy; Infant; Child Health; Infant Health; Maternal Health
PubMed: 38750486
DOI: 10.1186/s12916-024-03417-9 -
Revista de Saude Publica 2024To identify the prevalence of contamination by pesticides and their metabolites in the milk of lactating mothers in Latin America.
OBJECTIVE
To identify the prevalence of contamination by pesticides and their metabolites in the milk of lactating mothers in Latin America.
METHODS
In this systematic review, the PubMed, LILACS, Embase, and Scopus databases were searched up to January 2022 to identify observational studies. The Mendeley software was used to manage these references. The risk of bias assessment was evaluated according to the checklist for prevalence studies and writing design, by the Prisma guidelines.
RESULTS
This study retrieved 1835 references and analyzed 49 studies. 69.38% of the analyzed studies found a 100% prevalence of breast milk contamination by pesticides among their sample. Main pesticides include dichlorodiphenyltrichloroethane (DDT) and its isomers (75.51%), followed by the metabolite dichlorodiphenyldichloroethylene (DDE) (69.38%) and hexachlorocyclohexane (HCH) (46.93%). This study categorized most (65.30%) studies as having a low risk of bias.
CONCLUSIONS
This review shows a high prevalence of pesticide contamination in the breast milk of Latin American women. Further investigations should be carried out to assess contamination levels in breast milk and the possible effects of these substances on maternal and child health.
Topics: Humans; Milk, Human; Female; Latin America; Lactation; Pesticides; Pesticide Residues; Prevalence; DDT; Maternal Exposure
PubMed: 38747867
DOI: 10.11606/s1518-8787.2024058005446 -
The Journal of Maternal-fetal &... Dec 2024Postpartum hemorrhage is a leading cause of maternal mortality and morbidity around the globe. The novel low-suction vacuum hemorrhage device (VHD) provides an... (Review)
Review
OBJECTIVE
Postpartum hemorrhage is a leading cause of maternal mortality and morbidity around the globe. The novel low-suction vacuum hemorrhage device (VHD) provides an alternative treatment option for cases of postpartum hemorrhage when first-line uterotonic agents fail. This systematic review aims to review current data evaluating the overall efficacy and safety of VHDs in treating postpartum hemorrhage.
METHODS
We searched CINAHL Ultimate, Academic Search Premier, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, MEDLINE with Full Text, and PubMed and reference lists of retrieved studies for eligible studies that included outcomes of effectiveness, efficacy, or safety. Two independent reviewers used Covidence.org to screen Titles and Abstracts for 69 studies of which six were included in the analysis. Secondary outcomes measured across studies included time to bleeding control, total device deployment time, and adverse effects.
RESULTS
Six nonrandomized trials ( = 1018 participants) included studies conducted in Indonesia, the United States, Switzerland, and Canada. The VHDs were found to have 90% effectiveness in achieving bleeding control across the studies. For most patients, this was achieved in <5 min and required a total device deployment time of 3 h. Reported adverse events were not considered life-threatening, including endometritis in 11 patients and red blood cell transfusions in 38% of patients.
CONCLUSION
VHDs have the potential to be used as a rapidly effective means for mechanical intervention of postpartum hemorrhage. The efficacy and safety of VHDs must be further studied at the randomized controlled trial level to determine their clinical usage.
Topics: Humans; Postpartum Hemorrhage; Female; Pregnancy
PubMed: 38735867
DOI: 10.1080/14767058.2024.2349957 -
The Journal of Maternal-fetal &... Dec 2024Although early evidence shows that epilepsy can increase the risks of adverse pregnancy, some outcomes are still debatable. We performed a systematic review and... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Although early evidence shows that epilepsy can increase the risks of adverse pregnancy, some outcomes are still debatable. We performed a systematic review and meta-analysis to explore the effects of maternal and fetal adverse outcomes in pregnant women with epilepsy.
METHODS
PubMed, Embase, Cochrane, and Web of Science were employed to collect studies that investigated the potential risk of obstetric complications during the antenatal, intrapartum, or postnatal period, as well as any neonatal complications. The search was conducted from inception to November 16, 2022. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of the included original studies. The odds ratio (OR) values were extracted after adjusting for confounders to measure the relationship between pregnant women with epilepsy and adverse maternal or fetal outcomes. The protocol for this systematic review is registered with PROSPERO ID CRD42023391539.
RESULTS
Of 35 articles identified, there were 142,577 mothers with epilepsy and 34,381,373 mothers without epilepsy. Our study revealed a significant association between pregnant women with epilepsy (PWWE) and the incidence of cesarean section, preeclampsia/eclampsia, gestational hypertension, induction of labor, gestational diabetes and postpartum hemorrhage compared with those without epilepsy. Regarding newborns outcomes, PWWE versus those without epilepsy had increased odds of preterm birth, small for gestational age, low birth weight (<2500 g), and congenital malformations, fetal distress. The odds of operative vaginal delivery, newborn mortality, and Apgar (≤ 7) were similar between PWWE and healthy women.
CONCLUSION
Pregnant women affected by epilepsy encounter a higher risk of adverse obstetric outcomes and fetal complications. Therefore, it is crucial to develop appropriate prevention and intervention strategies prior to or during pregnancy to minimize the negative impacts of epilepsy on maternal and fetal health.
Topics: Humans; Pregnancy; Female; Epilepsy; Pregnancy Complications; Pregnancy Outcome; Infant, Newborn
PubMed: 38735863
DOI: 10.1080/14767058.2024.2351196 -
Journal of Diabetes Investigation May 2024Type 2 diabetes mellitus is a major metabolic disease that seriously endangers life and health, but women with gestational diabetes mellitus are at increased risk for...
AIMS/INTRODUCTION
Type 2 diabetes mellitus is a major metabolic disease that seriously endangers life and health, but women with gestational diabetes mellitus are at increased risk for developing type 2 diabetes mellitus. This study aimed to evaluate the effectiveness of postpartum lifestyle intervention on the prevention of type 2 diabetes mellitus, and the effect of lifestyle intervention on glycemic outcomes and anthropometric measures.
MATERIALS AND METHODS
We searched PubMed and other databases to retrieve articles published before May 21, 2023, on randomized controlled trials of postnatal lifestyle interventions (diet and/or physical activity) in women with gestational diabetes mellitus. We estimated the pooled odds ratios using fixed or random effects models and conducted a subgroup analysis of the different intervention methods to explore differences in the different lifestyle interventions.
RESULTS
The review included 17 randomized controlled trials. Overall, lifestyle changes started after a pregnancy complicated by gestational diabetes mellitus an 11% (RR = 0.89; 95% CI: 0.74-1.07) reduction in diabetes risk; significant differences were found for weight (MD = -1.33; 95% CI: [-1.76; -0.89], P < 0.00001) body mass index (MD = -0.53; 95% CI: [-0.74, -0.32], P < 0.00001), and waist circumference change (MD = -1.38; 95% CI: [-2.12; -0.64], P = 0.0002) but not for fasting glucose (MD = -0.06; 95% CI: [-0.19; 0.06], P = 0.32), 2 h glucose (MD = -0.12; 95% CI: [-0.30; 0.06], P = 0.19), and hemoglobin A1c (MD = -0.11; 95% CI: [-0.23; 0.02], P = 0.09). Subgroup analyses showed no significant differences in the effects of different lifestyle interventions on the incidence of type 2 diabetes, blood glucose levels, and anthropometric parameters.
CONCLUSION
Our comprehensive meta-analysis of lifestyle interventions can improve modifiable anthropometric measures in women with gestational diabetes. We need further research to provide more intensive lifestyle intervention, more scientific intervention methods, and to reduce the incidence of type 2 diabetes in patients with gestational diabetes.
PubMed: 38727771
DOI: 10.1111/jdi.14220 -
The Cochrane Database of Systematic... May 2024Magnesium sulphate is a common therapy in perinatal care. Its benefits when given to women at risk of preterm birth for fetal neuroprotection (prevention of cerebral... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Magnesium sulphate is a common therapy in perinatal care. Its benefits when given to women at risk of preterm birth for fetal neuroprotection (prevention of cerebral palsy for children) were shown in a 2009 Cochrane review. Internationally, use of magnesium sulphate for preterm cerebral palsy prevention is now recommended practice. As new randomised controlled trials (RCTs) and longer-term follow-up of prior RCTs have since been conducted, this review updates the previously published version.
OBJECTIVES
To assess the effectiveness and safety of magnesium sulphate as a fetal neuroprotective agent when given to women considered to be at risk of preterm birth.
SEARCH METHODS
We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) on 17 March 2023, as well as reference lists of retrieved studies.
SELECTION CRITERIA
We included RCTs and cluster-RCTs of women at risk of preterm birth that assessed prenatal magnesium sulphate for fetal neuroprotection compared with placebo or no treatment. All methods of administration (intravenous, intramuscular, and oral) were eligible. We did not include studies where magnesium sulphate was used with the primary aim of preterm labour tocolysis, or the prevention and/or treatment of eclampsia.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed RCTs for inclusion, extracted data, and assessed risk of bias and trustworthiness. Dichotomous data were presented as summary risk ratios (RR) with 95% confidence intervals (CI), and continuous data were presented as mean differences with 95% CI. We assessed the certainty of the evidence using the GRADE approach.
MAIN RESULTS
We included six RCTs (5917 women and their 6759 fetuses alive at randomisation). All RCTs were conducted in high-income countries. The RCTs compared magnesium sulphate with placebo in women at risk of preterm birth at less than 34 weeks' gestation; however, treatment regimens and inclusion/exclusion criteria varied. Though the RCTs were at an overall low risk of bias, the certainty of evidence ranged from high to very low, due to concerns regarding study limitations, imprecision, and inconsistency. Primary outcomes for infants/children: Up to two years' corrected age, magnesium sulphate compared with placebo reduced cerebral palsy (RR 0.71, 95% CI 0.57 to 0.89; 6 RCTs, 6107 children; number needed to treat for additional beneficial outcome (NNTB) 60, 95% CI 41 to 158) and death or cerebral palsy (RR 0.87, 95% CI 0.77 to 0.98; 6 RCTs, 6481 children; NNTB 56, 95% CI 32 to 363) (both high-certainty evidence). Magnesium sulphate probably resulted in little to no difference in death (fetal, neonatal, or later) (RR 0.96, 95% CI 0.82 to 1.13; 6 RCTs, 6759 children); major neurodevelopmental disability (RR 1.09, 95% CI 0.83 to 1.44; 1 RCT, 987 children); or death or major neurodevelopmental disability (RR 0.95, 95% CI 0.85 to 1.07; 3 RCTs, 4279 children) (all moderate-certainty evidence). At early school age, magnesium sulphate may have resulted in little to no difference in death (fetal, neonatal, or later) (RR 0.82, 95% CI 0.66 to 1.02; 2 RCTs, 1758 children); cerebral palsy (RR 0.99, 95% CI 0.69 to 1.41; 2 RCTs, 1038 children); death or cerebral palsy (RR 0.90, 95% CI 0.67 to 1.20; 1 RCT, 503 children); and death or major neurodevelopmental disability (RR 0.81, 95% CI 0.59 to 1.12; 1 RCT, 503 children) (all low-certainty evidence). Magnesium sulphate may also have resulted in little to no difference in major neurodevelopmental disability, but the evidence is very uncertain (average RR 0.92, 95% CI 0.53 to 1.62; 2 RCTs, 940 children; very low-certainty evidence). Secondary outcomes for infants/children: Magnesium sulphate probably reduced severe intraventricular haemorrhage (grade 3 or 4) (RR 0.76, 95% CI 0.60 to 0.98; 5 RCTs, 5885 infants; NNTB 92, 95% CI 55 to 1102; moderate-certainty evidence) and may have resulted in little to no difference in chronic lung disease/bronchopulmonary dysplasia (average RR 0.92, 95% CI 0.77 to 1.10; 5 RCTs, 6689 infants; low-certainty evidence). Primary outcomes for women: Magnesium sulphate may have resulted in little or no difference in severe maternal outcomes potentially related to treatment (death, cardiac arrest, respiratory arrest) (RR 0.32, 95% CI 0.01 to 7.92; 4 RCTs, 5300 women; low-certainty evidence). However, magnesium sulphate probably increased maternal adverse effects severe enough to stop treatment (average RR 3.21, 95% CI 1.88 to 5.48; 3 RCTs, 4736 women; moderate-certainty evidence). Secondary outcomes for women: Magnesium sulphate probably resulted in little to no difference in caesarean section (RR 0.96, 95% CI 0.91 to 1.02; 5 RCTs, 5861 women) and postpartum haemorrhage (RR 0.94, 95% CI 0.80 to 1.09; 2 RCTs, 2495 women) (both moderate-certainty evidence). Breastfeeding at hospital discharge and women's views of treatment were not reported.
AUTHORS' CONCLUSIONS
The currently available evidence indicates that magnesium sulphate for women at risk of preterm birth for neuroprotection of the fetus, compared with placebo, reduces cerebral palsy, and death or cerebral palsy, in children up to two years' corrected age, and probably reduces severe intraventricular haemorrhage for infants. Magnesium sulphate may result in little to no difference in outcomes in children at school age. While magnesium sulphate may result in little to no difference in severe maternal outcomes (death, cardiac arrest, respiratory arrest), it probably increases maternal adverse effects severe enough to stop treatment. Further research is needed on the longer-term benefits and harms for children, into adolescence and adulthood. Additional studies to determine variation in effects by characteristics of women treated and magnesium sulphate regimens used, along with the generalisability of findings to low- and middle-income countries, should be considered.
Topics: Female; Humans; Infant, Newborn; Pregnancy; Bias; Cerebral Palsy; Magnesium Sulfate; Neuroprotective Agents; Premature Birth; Randomized Controlled Trials as Topic; Tocolytic Agents
PubMed: 38726883
DOI: 10.1002/14651858.CD004661.pub4 -
Frontiers in Neuroscience 2024Current treatment modalities for Major Depressive Disorder have variable efficacies and a variety of side effects. To amend this, many trials for short term, well...
BACKGROUND
Current treatment modalities for Major Depressive Disorder have variable efficacies and a variety of side effects. To amend this, many trials for short term, well tolerated monotherapies are underway. One such option is Zuranolone (SAGE-217), which is a recent FDA approved antidepressant for depression (PPD) and is undergoing clinical trials for PPD, major depressive disorder (MDD) and essential tremors (ET).
OBJECTIVES
Pool currently available data that compare Zuranolone to Placebo for the treatment of Major Depressive Disorder and evaluate its efficacy and safety profile.
METHODS
We retrieved data from PUBMED and SCOPUS from inception to July 2023. We included articles comparing Zuranolone or SAGE 217 with placebo in patients suffering from Major Depressive Disorder. Review Manager 5.4 was used to analyze the outcomes including changes in the Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A) and Montgomery-Åsberg Depression Rating Scale (MADRS) scores from baseline as well as any treatment emergent adverse events (TEAEs) and severe adverse events.
RESULTS
Our review analyzed 4 trials and the data of 1,357 patients. Patients treated with Zuranolone indicated a statistically significant effect in the change from baseline in HAM-D score ( = 0.0009; MD [95% CI]: -2.03 [-3.23, -0.84]) as well as in MADRS score ( = 0.02; MD [95% CI]: -2.30[-4.31, -0.30]) and HAM-A score ( = 0.03; MD [95% CI]: -1.41[-2.70, -0.11]) on 15th day when compared to the Placebo group. Zuranolone was also significantly associated with a higher response rate ( = 0.0008; OR [95% CI]: 1.63[1.14, 2.35]) and higher remission rate ( = 0.03; OR [95% CI]: 1.65[1.05, 2.59]) when compared with the placebo. As for safety, Zuranolone was significantly associated with 1 or more TEAE ( = 0.006; RR [95% CI]: 1.14[1.04, 1.24]) but an insignificant association with side effects that lead to drug discontinuation ( = 0.70; RR [95% CI]: 1.18[0.51, 2.76]) and serious adverse events ( = 0.48; RR [95% CI]: 1.46 [0.52, 4.10]) when compared with placebo.
CONCLUSION
Zuranolone is an effective and safe drug for short course major depressive disorder monotherapy. It shows results in 14 days (compared to 2-4 weeks that SSRI's take) and has anti-anxiolytic effects as well. However, only 4 trials have been used for the analysis and the sample size was small. The trials reviewed also cannot determine the long-term effects of the drug. More trials are needed to determine long term effects.
PubMed: 38726035
DOI: 10.3389/fnins.2024.1361692