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European Journal of Obstetrics,... Sep 2023A Cesarean Scar Pregnancy (CSP) is a variant of uterine ectopic pregnancy defined by full or partial implantation of the gestational sac in the scar of a previous... (Review)
Review
A Cesarean Scar Pregnancy (CSP) is a variant of uterine ectopic pregnancy defined by full or partial implantation of the gestational sac in the scar of a previous cesarean section. The continuous increase of Cesarean Deliveries is causing a parallel increase in CSP and its complications. Considering its high morbidity, the most usual recommendation has been termination of pregnancy in the first trimester; however, several cases progress to viable births. The aim of this systematic review is to evaluate the outcome of CSP managed expectantly and understand whether sonographic signs could correlate to the outcomes. An online-based search of PubMed and Cochrane Library Databases was used to gather studies including women diagnosed with a CSP who were managed expectantly. The description of all cases was analysed by the authors in order to obtain information for each outcome. 47 studies of different types were retrieved, and the gestational outcome was available in 194 patients. Out of these, 39 patients (20,1%) had a miscarriage and 16 (8,3%) suffered foetal death. 50 patients (25,8%) had a term delivery and 81 (41,8%) patients had a preterm birth, out of which 27 (13,9%) delivered before 34 weeks of gestation. In 102 (52,6%) patients, a hysterectomy was performed. Placenta Accreta Spectrum (PAS) was a common disorder among CSP and was linked to a higher rate of complications such as foetal death, preterm birth, hysterectomy, haemorrhagic morbidity and surgical complications. Some of the analysed articles showed that sonographic signs with specific characteristics, such as type II and III CSP classification, Crossover Sign - 1, "In the niche" implantation and lower myometrial thickness could be related to worse outcomes of CSP. This article provides a good understanding of CSP as an entity that, although rare, presents with a high rate of relevant morbidity. It is also understood that pregnancies with confirmed PAS had an even higher rate of morbidity. Some sonographic signs were shown to predict the prognosis of these pregnancies and further investigation is necessary to validate one or more signs so they can be used for a more reliable counselling of women with CSP.
Topics: Pregnancy; Infant, Newborn; Humans; Female; Cesarean Section; Premature Birth; Cicatrix; Watchful Waiting; Pregnancy, Ectopic; Pregnancy Outcome; Placenta Accreta; Fetal Death; Retrospective Studies
PubMed: 37421745
DOI: 10.1016/j.ejogrb.2023.06.030 -
Human Reproduction Update Jun 2022Uterine natural killer cells (uNK) are the most abundant lymphocytes found in the decidua during implantation and in first trimester pregnancy. They are important for... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Uterine natural killer cells (uNK) are the most abundant lymphocytes found in the decidua during implantation and in first trimester pregnancy. They are important for early placental development, especially trophoblast invasion and transformation of the spiral arteries. However, inappropriate uNK function has been implicated in reproductive failure, such as recurrent miscarriage (RM) or recurrent implantation failure (RIF). Previous studies have mainly focussed on peripheral NK cells (pNK), despite the well-documented differences in pNK and uNK phenotype and function. In recent years, there has been an explosion of studies conducted on uNK, providing a more suitable representation of the immune environment at the maternal-foetal interface. Here, we summarize the evidence from studies published on uNK in women with RM/RIF compared with controls.
OBJECTIVE AND RATIONALE
The objectives of this systematic review and meta-analysis are to evaluate: differences in uNK level in women with RM/RIF compared with controls; pregnancy outcome in women with RM/RIF stratified by high and normal uNK levels; correlation between uNK and pNK in women with RM/RIF; and differences in uNK activity in women with RM/RIF compared with controls.
SEARCH METHODS
MEDLINE, EMBASE, Web of Science and Cochrane Trials Registry were searched from inception up to December 2020 and studies were selected in accordance with PRISMA guidelines. Meta-analyses were performed for uNK level, pregnancy outcome and uNK/pNK correlation. Narrative synthesis was conducted for uNK activity. Risk of bias was assessed by ROBINS-I and publication bias by Egger's test.
OUTCOMES
Our initial search yielded 4636 articles, of which 60 articles were included in our systematic review. Meta-analysis of CD56+ uNK level in women with RM compared with controls showed significantly higher levels in women with RM in subgroup analysis of endometrial samples (standardized mean difference (SMD) 0.49, CI 0.08, 0.90; P = 0.02; I2 88%; 1100 women). Meta-analysis of CD56+ uNK level in endometrium of women with RIF compared with controls showed significantly higher levels in women with RIF (SMD 0.49, CI 0.01, 0.98; P = 0.046; I2 84%; 604 women). There was no difference in pregnancy outcome in women with RM/RIF stratified by uNK level, and no significant correlation between pNK and uNK levels in women with RM/RIF. There was wide variation in studies conducted on uNK activity, which can be broadly divided into regulation and receptors, uNK cytotoxicity, cytokine secretion and effect of uNK on angiogenesis. These studies were largely equivocal in their results on cytokine secretion, but most studies found lower expression of inhibitory receptors and increased expression of angiogenic factors in women with RM.
WIDER IMPLICATIONS
The observation of significantly increased uNK level in endometrium of women with RM and RIF may point to an underlying disturbance of the immune milieu culminating in implantation and/or placentation failure. Further research is warranted to elucidate the underlying pathophysiology. The evidence for measuring pNK as an indicator of uNK behaviour is sparse, and of limited clinical use. Measurement of uNK level/activity may be more useful as a diagnostic tool, however, a standardized reference range must be established before this can be of clinical use.
Topics: Abortion, Habitual; Cytokines; Embryo Implantation; Endometrium; Female; Humans; Killer Cells, Natural; Placenta; Pregnancy; Uterus
PubMed: 35265977
DOI: 10.1093/humupd/dmac006 -
Ultrasound in Obstetrics & Gynecology :... Jan 2022To determine the diagnostic accuracy of ultrasound at 11-14 weeks' gestation in the detection of fetal cardiac abnormalities and to evaluate factors that impact the... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To determine the diagnostic accuracy of ultrasound at 11-14 weeks' gestation in the detection of fetal cardiac abnormalities and to evaluate factors that impact the detection rate.
METHODS
This was a systematic review of studies evaluating the diagnostic accuracy of ultrasound in the detection of fetal cardiac anomalies at 11-14 weeks' gestation, performed by two independent reviewers. An electronic search of four databases (MEDLINE, EMBASE, Web of Science Core Collection and The Cochrane Library) was conducted for studies published between January 1998 and July 2020. Prospective and retrospective studies evaluating pregnancies at any prior level of risk and in any healthcare setting were eligible for inclusion. The reference standard used was the detection of a cardiac abnormality on postnatal or postmortem examination. Data were extracted from the included studies to populate 2 × 2 tables. Meta-analysis was performed using a random-effects model in order to determine the performance of first-trimester ultrasound in the detection of major cardiac abnormalities overall and of individual types of cardiac abnormality. Data were analyzed separately for high-risk and non-high-risk populations. Preplanned secondary analyses were conducted in order to assess factors that may impact screening performance, including the imaging protocol used for cardiac assessment (including the use of color-flow Doppler), ultrasound modality, year of publication and the index of sonographer suspicion at the time of the scan. Risk of bias and quality assessment were undertaken for all included studies using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool.
RESULTS
The electronic search yielded 4108 citations. Following review of titles and abstracts, 223 publications underwent full-text review, of which 63 studies, reporting on 328 262 fetuses, were selected for inclusion in the meta-analysis. In the non-high-risk population (45 studies, 306 872 fetuses), 1445 major cardiac anomalies were identified (prevalence, 0.41% (95% CI, 0.39-0.43%)). Of these, 767 were detected on first-trimester ultrasound examination of the heart and 678 were not detected. First-trimester ultrasound had a pooled sensitivity of 55.80% (95% CI, 45.87-65.50%), specificity of 99.98% (95% CI, 99.97-99.99%) and positive predictive value of 94.85% (95% CI, 91.63-97.32%) in the non-high-risk population. The cases diagnosed in the first trimester represented 63.67% (95% CI, 54.35-72.49%) of all antenatally diagnosed major cardiac abnormalities in the non-high-risk population. In the high-risk population (18 studies, 21 390 fetuses), 480 major cardiac anomalies were identified (prevalence, 1.36% (95% CI, 1.20-1.52%)). Of these, 338 were detected on first-trimester ultrasound examination and 142 were not detected. First-trimester ultrasound had a pooled sensitivity of 67.74% (95% CI, 55.25-79.06%), specificity of 99.75% (95% CI, 99.47-99.92%) and positive predictive value of 94.22% (95% CI, 90.22-97.22%) in the high-risk population. The cases diagnosed in the first trimester represented 79.86% (95% CI, 69.89-88.25%) of all antenatally diagnosed major cardiac abnormalities in the high-risk population. The imaging protocol used for examination was found to have an important impact on screening performance in both populations (P < 0.0001), with a significantly higher detection rate observed in studies using at least one outflow-tract view or color-flow Doppler imaging (both P < 0.0001). Different types of cardiac anomaly were not equally amenable to detection on first-trimester ultrasound.
CONCLUSIONS
First-trimester ultrasound examination of the fetal heart allows identification of over half of fetuses affected by major cardiac pathology. Future first-trimester screening programs should follow structured anatomical assessment protocols and consider the introduction of outflow-tract views and color-flow Doppler imaging, as this would improve detection rates of fetal cardiac pathology. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
Topics: Female; Fetal Diseases; Fetal Heart; Gestational Age; Heart Defects, Congenital; Humans; Predictive Value of Tests; Pregnancy; Pregnancy Trimester, First; Prospective Studies; Retrospective Studies; Ultrasonography, Prenatal
PubMed: 34369613
DOI: 10.1002/uog.23740 -
Frontiers in Endocrinology 2023Glucagon-like peptide 1 (GLP-1) agonists and sodium-glucose co-transporter-2 (SGLT2) inhibitors are novel drugs which have recently seen rapid uptake in the treatment of... (Review)
Review
AIMS/HYPOTHESIS
Glucagon-like peptide 1 (GLP-1) agonists and sodium-glucose co-transporter-2 (SGLT2) inhibitors are novel drugs which have recently seen rapid uptake in the treatment of type 2 diabetes and obesity. The paucity of data regarding their safety during pregnancy and lactation causes a dilemma for the physician. The aim of the present study was to systematically review all available data on the offspring effects of GLP-1 agonists and SGLT2 inhibitors during pregnancy and lactation.
METHODS
We systematically searched PubMed, clinicaltrials.gov, FDA and EMA product information on GLP-1 agonists and SGLT2 inhibitors in pregnancy and lactation from inception up to 19 April 2022 without language restrictions. We approached both the Netherlands Pharmacovigilance Centre Lareb on January 17 2023 and the Teratology Information Service (TIS) of Switzerland on February 6 2023. Eligible studies investigating the safety (including congenital anomalies, fetal growth, perinatal demise) in animals or humans, or reporting the degree of transfer of these drugs to the fetus, breast milk or breastfed neonate. Two reviewers independently assessed and selected studies for inclusion and subsequently resolved discrepancies by discussion.
RESULTS
We included 39 records (n=9 theoretical; based on drug properties, n=7 human; n=23 animal, including 76 human offspring, and an unknown number of animal offspring as these numbers could not be retrieved from the FDA and EMA product information). In animal studies, GLP1-agonists were associated with reduced fetal weight and/or growth, delayed ossification and skeletal variants, usually associated with a reduction in maternal weight gain and decreased food consumption. Exendin-4 (GLP1-agonist) was not transported across the maternal-fetal placental interface. In human studies, exenatide (GLP1-agonist) showed a fetal-to-maternal peptide concentration ratio of ≤ 0.017 in ex vivo human placental perfusion in a single placenta. Liraglutide (GLP1-agonist) showed no significant maternal to fetal transfer at least 3.5 hours after maternal exposure in a human study with one subject. In animal studies, GLP-1 agonists were excreted in breast milk; human data on excretion were not available. In animal studies, SGLT2 inhibitors were generally safe during the first trimester but exposure during postnatal day 21 to 90 in juvenile rats, a period coinciding with the late second and third trimester of human renal development, caused dilatation of the renal pelvis and tubules. Human data consisted of a pharmaceutical database of inadvertent pregnancies during SGLT2 inhibitor use, which found an increase in miscarriages and congenital malformations. In animal studies SGLT2 inhibitors were excreted in breast milk and affected neonatal growth, but human data are not available.
CONCLUSION/INTERPRETATION
We found evidence for adverse offspring effects of GLP-1 agonists and SGLT2 inhibitors also in human studies. Our findings broadly support the advice to discontinue GLP-1 agonists and SGLT2 inhibitors during pregnancy and lactation, and also support the ongoing registration of pregnancy outcomes in pharmacological databases since the amount of available data is scarce and mostly limited to animal studies.
REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=219877.
Topics: Female; Humans; Pregnancy; Rats; Animals; Sodium-Glucose Transporter 2 Inhibitors; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Breast Feeding; Placenta; Exenatide; Liraglutide; Lactation
PubMed: 37881498
DOI: 10.3389/fendo.2023.1215356 -
Annals of the New York Academy of... Aug 2019Maternal anemia is a well-recognized global health problem; however, there remain questions on specific hemoglobin (Hb) thresholds that predict health risk or protection... (Meta-Analysis)
Meta-Analysis
Maternal anemia is a well-recognized global health problem; however, there remain questions on specific hemoglobin (Hb) thresholds that predict health risk or protection for mother and child. We conducted a systematic review and meta-analysis to examine the associations of maternal Hb concentrations with a range of maternal and infant health outcomes, accounting for the timing of measurement (preconception, and first, second, and third trimesters), etiology of anemia, and cutoff category. The systematic review included 272 studies and the meta-analysis included 95 studies. Low maternal Hb (<110 g/L) was associated with poor birth outcomes (low birth weight, preterm birth, small-for-gestational-age (SGA), stillbirth, and perinatal and neonatal mortality) and adverse maternal outcomes (postpartum hemorrhage, preeclampsia, and blood transfusion). High maternal Hb (>130 g/L) was associated with increased odds of SGA, stillbirth, preeclampsia, and gestational diabetes. Relationships varied by the timing of measurement and cutoff category (stronger associations with lower cutoffs); limited data were available on anemia etiology. There were insufficient data for other maternal outcomes and long-term child health outcomes. Current data are insufficient for determining if revisions to current Hb cutoffs are required. Pooled high-quality individual-level data analyses, as well as prospective cohort studies, would be valuable to inform the reevaluation of Hb cutoffs.
Topics: Child Health; Female; Hemoglobins; Humans; Infant, Small for Gestational Age; Maternal Health; Obstetric Labor Complications; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Premature Birth
PubMed: 30994929
DOI: 10.1111/nyas.14093 -
Sexual and Reproductive Health Matters Dec 2019Guidelines can help healthcare practitioners manage syphilis in pregnancy and prevent perinatal death or disability. We conducted systematic reviews to locate guidance...
Guidelines can help healthcare practitioners manage syphilis in pregnancy and prevent perinatal death or disability. We conducted systematic reviews to locate guidance documents describing management of syphilis in pregnancy, 2003-2017. We compared country and regional guidelines with current World Health Organization (WHO) guidelines. We found 64 guidelines with recommendations on management of syphilis in pregnancy representing 128 of the 195 WHO member countries, including the two WHO guidelines published in 2016 and 2017. Of the 62 guidelines, 16 were for countries in Africa, 21 for the Americas, two for Eastern Mediterranean, six for Europe and 17 for Asia or the Pacific. Fifty-seven (92%) guidelines recommended universal syphilis screening in pregnancy, of which 46 (81%) recommended testing at the first antenatal care visit. Also, 46 (81%) recommended repeat testing including 21 guidelines recommended this during the third pregnancy trimester and/or at delivery. Fifty-nine (95%) guidelines recommended benzathine penicillin G (BPG) as the first-line therapy for syphilis in pregnancy, consistent with WHO guidelines. Alternative regimens to BPG were listed in 42 (68%) guidelines, primarily from Africa and Asia; only 20 specified that non-penicillin regimens are not proven-effective in treating the fetus. We identified guidance recommending use of injectable penicillin in exposed infants for 112 countries. Most guidelines recommended universal syphilis testing for pregnant women, repeat testing for high-risk women and treatment of infected women with BPG; but several did not. Updating guidance on syphilis testing and treatment in pregnancy to reflect global norms could prevent congenital syphilis and save newborn lives.
Topics: Anti-Bacterial Agents; Female; Global Health; Guidelines as Topic; Humans; Infant; Infant Mortality; Pregnancy; Pregnancy Complications, Infectious; Syphilis; Syphilis, Congenital; World Health Organization
PubMed: 31884900
DOI: 10.1080/26410397.2019.1691897 -
Ultrasound in Obstetrics & Gynecology :... Jul 2019Primary studies and systematic reviews provide estimates of varying accuracy for different factors in the prediction of pre-eclampsia. The aim of this study was to...
OBJECTIVE
Primary studies and systematic reviews provide estimates of varying accuracy for different factors in the prediction of pre-eclampsia. The aim of this study was to review published systematic reviews to collate evidence on the ability of available tests to predict pre-eclampsia, to identify high-value avenues for future research and to minimize future research waste in this field.
METHODS
MEDLINE, EMBASE and The Cochrane Library including DARE (Database of Abstracts of Reviews of Effects) databases, from database inception to March 2017, and bibliographies of relevant articles were searched, without language restrictions, for systematic reviews and meta-analyses on the prediction of pre-eclampsia. The quality of the included reviews was assessed using the AMSTAR tool and a modified version of the QUIPS tool. We evaluated the comprehensiveness of search, sample size, tests and outcomes evaluated, data synthesis methods, predictive ability estimates, risk of bias related to the population studied, measurement of predictors and outcomes, study attrition and adjustment for confounding.
RESULTS
From 2444 citations identified, 126 reviews were included, reporting on over 90 predictors and 52 prediction models for pre-eclampsia. Around a third (n = 37 (29.4%)) of all reviews investigated solely biochemical markers for predicting pre-eclampsia, 31 (24.6%) investigated genetic associations with pre-eclampsia, 46 (36.5%) reported on clinical characteristics, four (3.2%) evaluated only ultrasound markers and six (4.8%) studied a combination of tests; two (1.6%) additional reviews evaluated primary studies investigating any screening test for pre-eclampsia. Reviews included between two and 265 primary studies, including up to 25 356 688 women in the largest review. Only approximately half (n = 67 (53.2%)) of the reviews assessed the quality of the included studies. There was a high risk of bias in many of the included reviews, particularly in relation to population representativeness and study attrition. Over 80% (n = 106 (84.1%)) summarized the findings using meta-analysis. Thirty-two (25.4%) studies lacked a formal statement on funding. The predictors with the best test performance were body mass index (BMI) > 35 kg/m , with a specificity of 92% (95% CI, 89-95%) and a sensitivity of 21% (95% CI, 12-31%); BMI > 25 kg/m , with a specificity of 73% (95% CI, 64-83%) and a sensitivity of 47% (95% CI, 33-61%); first-trimester uterine artery pulsatility index or resistance index > 90 centile (specificity 93% (95% CI, 90-96%) and sensitivity 26% (95% CI, 23-31%)); placental growth factor (specificity 89% (95% CI, 89-89%) and sensitivity 65% (95% CI, 63-67%)); and placental protein 13 (specificity 88% (95% CI, 87-89%) and sensitivity 37% (95% CI, 33-41%)). No single marker had a test performance suitable for routine clinical use. Models combining markers showed promise, but none had undergone external validation.
CONCLUSIONS
This review of reviews calls into question the need for further aggregate meta-analysis in this area given the large number of published reviews subject to the common limitations of primary predictive studies. Prospective, well-designed studies of predictive markers, preferably randomized intervention studies, and combined through individual-patient data meta-analysis are needed to develop and validate new prediction models to facilitate the prediction of pre-eclampsia and minimize further research waste in this field. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.
Topics: Adult; Biomarkers; Body Mass Index; Female; Humans; Mass Screening; Meta-Analysis as Topic; Placenta Growth Factor; Pre-Eclampsia; Predictive Value of Tests; Pregnancy; Pregnancy Complications; Prospective Studies; Pulsatile Flow; Risk Factors; Sensitivity and Specificity; Ultrasonography; Uterine Artery
PubMed: 30267475
DOI: 10.1002/uog.20117 -
Expert Opinion on Drug Metabolism &... May 2020: Pregnancy-related physiological changes exert a crucial impact on the pharmacokinetics of antidepressants; however, the current evidence presents inconsistencies. A... (Meta-Analysis)
Meta-Analysis
: Pregnancy-related physiological changes exert a crucial impact on the pharmacokinetics of antidepressants; however, the current evidence presents inconsistencies. A clearer understanding of pregnancy-related effects on antidepressant disposition may facilitate the development of guidelines for appropriate dose adjustments during the course of pregnancy based on therapeutic drug monitoring.: We systematically reviewed studies comparing antidepressant levels in the same individuals during pregnant and non-pregnant states. Using dose-adjusted plasma concentration measurements, we estimated alteration ratios between the 3rd trimester and baseline (before or after pregnancy). Additionally, we performed a meta-analysis for changes in dose-adjusted concentrations to estimate mean differences.: Data for several antidepressants display clear alteration patterns during pregnancy. On the basis of the alteration ratios trimipramine, fluvoxamine, and nortriptyline show a prominent decrease in dose-adjusted levels, especially in the 3rd trimester. Clomipramine, imipramine, citalopram, and paroxetine show smaller decreases in dose-adjusted concentrations in the third trimester. For escitalopram, venlafaxine and fluoxetine, changes are considered negligible. For sertraline, there was a tendency toward increased dose-adjusted concentrations in pregnancy. Available evidence suffers from major limitations and factors affecting pharmacokinetics have been insufficiently addressed. Further research is required to promote knowledge on pregnancy effects on antidepressant pharmacokinetics.
Topics: Antidepressive Agents; Depression; Dose-Response Relationship, Drug; Female; Humans; Pregnancy; Pregnancy Complications; Pregnancy Trimester, Third
PubMed: 32238008
DOI: 10.1080/17425255.2020.1750598 -
The Cochrane Database of Systematic... Sep 2017During pregnancy, fetal cells suitable for genetic testing can be obtained from amniotic fluid by amniocentesis (AC), placental tissue by chorionic villus sampling... (Review)
Review
BACKGROUND
During pregnancy, fetal cells suitable for genetic testing can be obtained from amniotic fluid by amniocentesis (AC), placental tissue by chorionic villus sampling (CVS), or fetal blood. A major disadvantage of second trimester amniocentesis is that the results are available relatively late in pregnancy (after 16 weeks' gestation). Earlier alternatives are chorionic villus sampling (CVS) and early amniocentesis, which can be performed in the first trimester of pregnancy.
OBJECTIVES
The objective of this review was to compare the safety and accuracy of all types of AC (i.e. early and late) and CVS (e.g. transabdominal, transcervical) for prenatal diagnosis.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (3 March 2017), ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP; 3 March 2017), and reference lists of retrieved studies.
SELECTION CRITERIA
All randomised trials comparing AC and CVS by either transabdominal or transcervical route.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. The quality of the evidence was assessed using the GRADE approach.
MAIN RESULTS
We included a total of 16 randomised studies, with a total of 33,555 women, 14 of which were deemed to be at low risk of bias. The number of women included in the trials ranged from 223 to 4606.Studies were categorized into six comparisons: 1. second trimester AC versus control; 2. early versus second trimester AC; 3. CVS versus second trimester AC; 4. CVS methods; 5. Early AC versus CVS; and 6. AC with or without ultrasound.One study compared second trimester AC with no AC (control) in a low risk population (women = 4606). Background pregnancy loss was around 2%. Second trimester AC compared to no testing increased total pregnancy loss by another 1%. The confidence intervals (CI) around this excess risk were relatively large (3.2% versus 2.3 %, average risk ratio (RR) 1.41, 95% CI 0.99 to 2.00; moderate-quality evidence). In the same study, spontaneous miscarriages were also higher (2.1% versus 1.3%; average RR 1.60, 95% CI 1.02 to 2.52; high-quality evidence). The number of congenital anomalies was similar in both groups (2.0% versus 2.2%, average RR 0.93, 95% CI 0.62 to 1.39; moderate-quality evidence).One study (women = 4334) found that early amniocentesis was not a safe early alternative compared to second trimester amniocentesis because of increased total pregnancy losses (7.6% versus 5.9%; average RR 1.29, 95% CI 1.03 to 1.61; high-quality evidence), spontaneous miscarriages (3.6% versus 2.5%, average RR 1.41, 95% CI 1.00 to 1.98; moderate-quality evidence), and a higher incidence of congential anomalies, including talipes (4.7% versus 2.7%; average RR 1.73, 95% CI 1.26 to 2.38; high-quality evidence).When pregnancy loss after CVS was compared with second trimester AC, there was a clinically significant heterogeneity in the size and direction of the effect depending on the technique used (transabdominal or transcervical), therefore, the results were not pooled. Only one study compared transabdominal CVS with second trimester AC (women = 2234). They found no clear difference between the two procedures in the total pregnancy loss (6.3% versus 7%; average RR 0.90, 95% CI 0.66 to 1.23, low-quality evidence), spontaneous miscarriages (3.0% versus 3.9%; average RR 0.77, 95% CI 0.49 to 1.21; low-quality evidence), and perinatal deaths (0.7% versus 0.6%; average RR 1.18, 95% CI 0.40 to 3.51; low-quality evidence). Transcervical CVS may carry a higher risk of pregnancy loss (14.5% versus 11.5%; average RR 1.40, 95% CI 1.09 to 1.81), but the results were quite heterogeneous.Five studies compared transabdominal and transcervical CVS (women = 7978). There were no clear differences between the two methods in pregnancy losses (average RR 1.16, 95% CI 0.81 to 1.65; very low-quality evidence), spontaneous miscarriages (average RR 1.68, 95% CI 0.79 to 3.58; very low-quality evidence), or anomalies (average RR 0.68, 95% CI 0.41 to 1.12; low-quality evidence). We downgraded the quality of the evidence to low due to heterogeneity between studies. Transcervical CVS may be more technically demanding than transabdominal CVS, with more failures to obtain sample (2.0% versus 1.1%; average RR 1.79, 95% CI 1.13 to 2.82, moderate-quality evidence).Overall, we found low-quality evidence for outcomes when early amniocentesis was compared to transabdominal CVS. Spontaneous miscarriage was the only outcome supported by moderate-quality evidence, resulting in more miscarriages after early AC compared with transabdominal CVS (2.3% versus 1.3%; average RR 1.73, 95% CI 1.15 to 2.60). There were no clear differences in pregnancy losses (average RR 1.15, 95% CI 0.86 to 1.54; low-quality evidence), or anomalies (average RR 1.14, 95% CI 0.57 to 2.30; very low-quality evidence).We found one study that examined AC with or without ultrasound, which evaluated a type of ultrasound-assisted procedure that is now considered obsolete.
AUTHORS' CONCLUSIONS
Second trimester amniocentesis increased the risk of pregnancy loss, but it was not possible to quantify this increase precisely from only one study, carried out more than 30 years ago.Early amniocentesis was not as safe as second trimester amniocentesis, illustrated by increased pregnancy loss and congenital anomalies (talipes). Transcervical chorionic villus sampling compared with second trimester amniocentesis may be associated with a higher risk of pregnancy loss, but results were quite heterogeneous.Diagnostic accuracy of different methods could not be assessed adequately because of incomplete karyotype data in most studies.
Topics: Amniocentesis; Chorionic Villi Sampling; Congenital Abnormalities; Female; Humans; Pregnancy; Pregnancy Trimester, First; Pregnancy Trimester, Second; Randomized Controlled Trials as Topic
PubMed: 28869276
DOI: 10.1002/14651858.CD003252.pub2 -
The American Journal of Psychiatry Jan 2020Uncertainty surrounds the risks of lithium use during pregnancy in women with bipolar disorder. The authors sought to provide a critical appraisal of the evidence... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Uncertainty surrounds the risks of lithium use during pregnancy in women with bipolar disorder. The authors sought to provide a critical appraisal of the evidence related to the efficacy and safety of lithium treatment during the peripartum period, focusing on women with bipolar disorder and their offspring.
METHODS
The authors conducted a systematic review and random-effects meta-analysis assessing case-control, cohort, and interventional studies reporting on the safety (primary outcome, any congenital anomaly) or efficacy (primary outcome, mood relapse prevention) of lithium treatment during pregnancy and the postpartum period. The Newcastle-Ottawa Scale and the Cochrane risk of bias tools were used to assess the quality of available PubMed and Scopus records through October 2018.
RESULTS
Twenty-nine studies were included in the analyses (20 studies were of good quality, and six were of poor quality; one study had an unclear risk of bias, and two had a high risk of bias). Thirteen of the 29 studies could be included in the quantitative analysis. Lithium prescribed during pregnancy was associated with higher odds of any congenital anomaly (N=23,300, k=11; prevalence=4.1%, k=11; odds ratio=1.81, 95% CI=1.35-2.41; number needed to harm (NNH)=33, 95% CI=22-77) and of cardiac anomalies (N=1,348,475, k=12; prevalence=1.2%, k=9; odds ratio=1.86, 95% CI=1.16-2.96; NNH=71, 95% CI=48-167). Lithium exposure during the first trimester was associated with higher odds of spontaneous abortion (N=1,289, k=3, prevalence=8.1%; odds ratio=3.77, 95% CI=1.15-12.39; NNH=15, 95% CI=8-111). Comparing lithium-exposed with unexposed pregnancies, significance remained for any malformation (exposure during any pregnancy period or the first trimester) and cardiac malformations (exposure during the first trimester), but not for spontaneous abortion (exposure during the first trimester) and cardiac malformations (exposure during any pregnancy period). Lithium was more effective than no lithium in preventing postpartum relapse (N=48, k=2; odds ratio=0.16, 95% CI=0.03-0.89; number needed to treat=3, 95% CI=1-12). The qualitative synthesis showed that mothers with serum lithium levels <0.64 mEq/L and dosages <600 mg/day had more reactive newborns without an increased risk of cardiac malformations.
CONCLUSIONS
The risk associated with lithium exposure at any time during pregnancy is low, and the risk is higher for first-trimester or higher-dosage exposure. Ideally, pregnancy should be planned during remission from bipolar disorder and lithium prescribed within the lowest therapeutic range throughout pregnancy, particularly during the first trimester and the days immediately preceding delivery, balancing the safety and efficacy profile for the individual patient.
Topics: Abnormalities, Drug-Induced; Abortion, Spontaneous; Bipolar Disorder; Female; Humans; Lithium Compounds; Postpartum Period; Pregnancy; Treatment Outcome
PubMed: 31623458
DOI: 10.1176/appi.ajp.2019.19030228