Recombinant erythropoietin for the treatment of iron deficiency anemia in pregnancy: A systematic review.

BACKGROUND: Treatment options for severe, refractory iron deficiency anemia are limited in pregnancy. OBJECTIVE: To review the available literature on the use of recombinant erythropoietin in the treatment of iron deficiency anemia in pregnancy. SEARCH STRATEGY: An electronic search of seven databases from inception to March 2022 was performed using a combination of keywords. SELECTION CRITERIA: We included all randomized controlled or observational studies of pregnant patients with iron deficiency anemia who received recombinant erythropoietin or control. The primary outcome was a change in hematologic parameters (hemoglobin or hematocrit) after treatment. Studies were appraised using the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions. DATA COLLECTION AND ANALYSIS: Data were summarized using narrative synthesis and descriptive statistics as appropriate. This study was registered with PROSPERO, CRD42022313328. MAIN RESULTS: Of 234 studies screened, five studies met the inclusion criteria and had sufficient data for analysis (n = 103 recombinant erythropoietin and n = 104 controls). All patients in the intervention group received iron supplementation (intravenous or oral) in addition to recombinant erythropoietin. All patients in the control group received iron supplementation (intravenous or oral) alone. As the result of variance between studies in inclusion criteria, the timing of repeat blood draws, and data reporting, a meta-analysis could not be performed. Three studies found that serial recombinant erythropoietin combined with iron supplementation was more effective at raising hematologic laboratory parameters (hemoglobin or hematocrit) than iron alone. One study reported no difference in hemoglobin or hematocrit levels between groups at day 28. However, patients in this study only received one dose of recombinant erythropoietin, whereas those in the other studies received serial doses. Another study also found no difference in hemoglobin levels by day 28, but patients in the recombinant erythropoietin group had lower hemoglobin levels at baseline and a more rapid rise in hemoglobin than iron alone. This is demonstrated by a more significant rise in hemoglobin at day 11 in the recombinant erythropoietin group than in the control group. CONCLUSIONS: Serial recombinant erythropoietin administration and iron supplementation may be more effective at treating refractory iron deficiency anemia in pregnancy than iron supplementation alone.

Pre- and postpregnancy platelet counts: evaluating accuracy of gestational thrombocytopenia and immune thrombocytopenia purpura diagnoses.

BACKGROUND: Given the overlapping clinical indicators and lack of diagnostic testing, misdiagnosis of immune thrombocytopenic purpura and gestational thrombocytopenia in pregnancy may be common. Current recommendations suggest utilizing platelet nadir during pregnancy to guide diagnosis. OBJECTIVE: This study aimed to assess the accuracy of gestational thrombocytopenia and immune thrombocytopenic purpura diagnoses using pre- and postpregnancy platelet counts. STUDY DESIGN: This was a retrospective cohort study of patients diagnosed with gestational thrombocytopenia and immune thrombocytopenic purpura from January 2017 to December 2019. Platelet counts were extracted from charts and evaluated at several time periods, namely prepregnancy (within 5 years), during pregnancy, and postpartum (>6 weeks to 5 years). A diagnosis of gestational thrombocytopenia was considered inaccurate if platelet counts were <150,000/µL pre- or postpregnancy with no other apparent causes or if the platelet nadir dropped below 100,000/µL during pregnancy. A diagnosis of immune thrombocytopenic purpura was deemed inaccurate if pre- or postpregnancy platelet counts were >150,000/µL. The primary outcome was accuracy of gestational thrombocytopenia and immune thrombocytopenic purpura diagnoses in patients. Secondary outcomes included mean platelet counts during pregnancy and difference in mean platelet counts for patients with an accurate vs inaccurate diagnosis of gestational thrombocytopenia. Outcomes were summarized with descriptive statistics and compared using Student t tests. RESULTS: A total of 116 patients met the inclusion criteria of which 111 (96%) and 5 (4%) had gestational thrombocytopenia and immune thrombocytopenic purpura diagnoses, respectively. Platelet counts outside of pregnancy were available for 91 (82%) of the patients, and 66 (57%) had prepregnancy platelet counts available. Of the 91 patients, the diagnosis was considered accurate in 61 (67%) and 5 (100%) patients with gestational thrombocytopenia and immune thrombocytopenic purpura, respectively. Conversely, 30 of 35 (86%) patients with immune thrombocytopenic purpura were found to be inaccurately diagnosed with gestational thrombocytopenia after application of platelet thresholds. Among these 30 patients, 10 had a prepregnancy platelet count <150,000/µL, 12 had a postpartum platelet count <150,000/µL, 3 had a platelet count nadir <100,000/µL during pregnancy, and 7 met more than 1 criterion. Pre- and postpregnancy platelet counts and platelet count nadir differed significantly for patients with an accurate vs inaccurate diagnosis of gestational thrombocytopenia (P<.001). CONCLUSION: When pre- and postpregnancy platelet counts were checked, one-third of cases of gestational thrombocytopenia met the criteria for immune thrombocytopenic purpura and were thus incorrectly diagnosed during pregnancy. Prepregnancy platelet counts, available for most patients, should be considered when diagnosing gestational thrombocytopenia vs immune thrombocytopenic purpura.

An assessment of oncofertility content on reproductive endocrinology and infertility clinic websites.

PURPOSE: To assess oncofertility content on fertility clinic websites as indicated by eight relevant keywords. Additionally, we sought to describe the relationship between oncofertility content and five predetermined clinic characteristics. METHODS: We examined 381 fertility clinic websites that are members of the Society for Associated Reproductive Technology (SART). Extracted data included clinic location, practice type (private vs academic), size (cycles/year), type of NCI designated center (cancer center vs comprehensive cancer center), and distance from the nearest NCI center. Additionally, we documented whether the clinic was located in a state mandating reproductive and infertility services and/or included fertility preservation for "iatrogenic infertility" as reported by the American Society for Reproductive Medicine (ASRM). Data were summarized using descriptive statistics and compared using chi-squared or t-test as appropriate. RESULTS: Of the 381 fertility clinic websites analyzed, 322 (85%) contained at least one oncofertility-related keyword. Most frequently used terms included cancer (79%) and fertility preservation (78%), while less frequently used terms included suppression (9.4%) and shielding (5.0%). Practices that initiated ≥ 501 cycles per year were more likely to mention one of the oncofertility keywords (OR 1.2; 95% CI 1.1-1.3). The associations of oncofertility website content with practice type, state-mandated fertility insurance coverage, and distance from an NCI-designated cancer center were not statistically significant. Large clinic size was the only predictive factor for inclusion of oncofertility website content. Further studies are required to evaluate whether inclusion of oncofertility content on clinic websites impacts the use of these services by patients with cancer. CONCLUSION: This is the first study correlating availability of oncofertility content on SART fertility clinic websites with consideration of geographic proximity to NCI designated cancer centers. Large clinic size was the only predictive factor for inclusion of oncofertility website content.

Etiology and Outcome of Isolated Fetal Ascites: A Systematic Review.

OBJECTIVE: To describe the etiology of isolated fetal ascites and associated perinatal outcomes, and to assess the progression of isolated fetal ascites to fetal hydrops. DATA SOURCES: PubMed, Cochrane Library, Scopus, and ClinicalTrials.gov databases were searched using the following keywords: "fetus" OR "foetal" OR "fetal" OR "foetus" AND "ascites" from inception to February 2020. The search was limited to the English language. METHODS OF STUDY SELECTION: A total of 1,983 articles were identified through the search strategy. All studies containing five or more cases of isolated fetal ascites were included. TABULATION, INTEGRATION, AND RESULTS: Eleven studies, involving 315 cases of isolated fetal ascites, were eligible for inclusion in this systematic review. All included studies were evaluated using the tool for evaluating the methodologic quality of case reports and case series described by Murad et al. Data were summarized using narrative review and descriptive statistics. Two-tailed Fisher exact P values calculated from hypergeometric distribution were used to compare outcome by etiology. CIs were calculated with Clopper-Pearson exact binomial interval. The etiologies of isolated fetal ascites are genitourinary (24%), gastrointestinal (20%), viral or bacterial infections (9%), cardiac (9%), genetic disorders not otherwise categorized (8%), chylous ascites (6%), metabolic storage disorders (3%), other structural disorders (4%), other causes (4%) and idiopathic (13%). Survival is most favorable for cases of isolated fetal ascites as a result of chylous (100%), idiopathic (90%), gastrointestinal (77%) and genitourinary (77%) etiologies. Survival is least favorable for fetuses with isolated fetal ascites as a result of structural disorders (25%), cardiac etiology (32%) and metabolic storage disorders (33.3%). When pregnancy terminations were excluded, survival rates were similar between fetuses diagnosed at or after 24 weeks of gestation compared with those diagnosed at less than 24 weeks (74% vs 61%, P=.06). Progression of fetal ascites to fetal hydrops occurred in 6.6% (95% CI 3.6-9.6%) (17/259) of cases when pregnancies that were terminated were excluded. CONCLUSION: Isolated fetal ascites has a diverse etiology. Outcome is related to the etiology of isolated fetal ascites. In the majority of cases, fetal ascites does not progress to fetal hydrops. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42020213930.

The effect of music on anxiety in women undergoing cesarean delivery: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to evaluate the effect of music on anxiety in patients undergoing cesarean delivery. DATA SOURCES: An electronic search of PubMed, CINAHL, ClinicalTrials.gov, and the Cochrane Central Register of Controlled Trials was performed from inception to November 2020. STUDY ELIGIBILITY CRITERIA: Eligibility criteria included all randomized controlled trials of pregnant women undergoing cesarean delivery who were randomized to either the music intervention or control. Studies needed to measure preoperative, intraoperative, or postoperative anxiety via a visual analog scale, State-Trait Anxiety Inventory, or Zung Self-Rating Anxiety Scale, for inclusion. The primary outcome was intraoperative anxiety during cesarean delivery. Secondary outcomes included preoperative and postoperative anxiety, postoperative pain, postoperative opioid requirements, blood pressure, and heart rate. STUDY APPRAISAL AND SYNTHESIS METHODS: The methodologic quality of the included studies was evaluated using the Cochrane Handbook for Systematic Reviews of Interventions. A meta-analysis was performed using the random-effects model of DerSimonian and Laird to produce a summary of treatment effects in terms of mean difference with 95% confidence intervals. A prespecified subgroup analysis of patients undergoing a scheduled or an unscheduled cesarean delivery was carried out for the main outcomes. RESULTS: Of the 1296 studies screened, 15 met the inclusion criteria (n=613 music group vs n=748 controls). Three trials (n=217 music group vs n=215 controls) reported on intraoperative anxiety specifically. Among studies using a visual analog scale for anxiety assessment, women in the intervention group had lower intraoperative anxiety levels than the controls (mean difference, -0.54; 95% confidence interval, -0.87 to -0.20; I2=0%; n=2 studies). One trial used the State-Trait Anxiety Inventory and 1 trial used the Zung Self-Rating Anxiety Scale for intraoperative anxiety assessment. In both of these studies, music exposure was associated with lower anxiety levels when compared with the controls (State-Trait Anxiety Inventory: mean difference, -2.80; 95% confidence interval, -4.57 to -1.03; Zung Self-Rating Anxiety Scale: mean difference, -4.80; 95% confidence interval, -7.08 to -2.52). In the subgroup analyses, the same relationship persisted when the cesarean delivery was unscheduled and when the music was selected by the patient or by the study team. The effect of music on preoperative and postoperative anxiety varied depending on which anxiety assessment tool was used. Music was also associated with decreased opioid use (mean difference, -0.87; 95% confidence interval, -1.55 to -0.19; I2=0%). CONCLUSION: In patients undergoing a cesarean delivery, music is associated with decreased intraoperative anxiety.

Hands-and-knees posturing and fetal occiput anterior position: a systematic review and meta-analysis.

OBJECTIVE: Persistent occiput posterior and occiput transverse positions are associated with adverse maternal and neonatal outcomes. The objective of this study was to assess if the use of hands-and-knees posturing increased the rate of occiput anterior position immediately after posturing during the second stage of labor or at the time of birth. DATA SOURCES: An electronic search of PubMed, EMBASE, Clinicaltrials.gov, and Cochrane Central Register of Controlled Trials was performed from inception to September 2020. STUDY ELIGIBILITY CRITERIA: Eligibility criteria included all randomized controlled trials of singleton gestations at ≥36 weeks' gestation that were randomized to either the hands-and-knees posture group or control group. The primary outcome was a composite of occiput anterior positioning during the second stage of labor or at birth. Individual components of the composite were assessed as secondary outcomes. Additional secondary outcomes were a change to occiput anterior position immediately after the intervention, use of regional anesthesia, duration of labor, mode of delivery, third- or fourth-degree perineal laceration, neonatal birthweight, and Apgar score less than 7 at 5 minutes. METHODS: The methodological quality of all the included studies was evaluated using the Cochrane Handbook for Systematic Reviews of Interventions. A meta-analysis was performed using the random effects model of DerSimmonian and Laird to produce a summary of the treatment effects in terms of relative risk or mean difference with 95% confidence intervals. RESULTS: Of the 1079 studies screened, 5 met the inclusion criteria (n=1727 hands-and-knees posture vs n=1641 controls). When compared with the control group, patients who adopted the hands-and-knees posture had the same rate of occiput anterior positioning in the second stage of labor or at birth (81.2% vs 81.2%; relative risk, 1.03; 95% confidence interval, 0.92-1.14), as well as immediately after the intervention (34.1% vs 18.0%; relative risk, 1.60; 95% confidence interval, 0.88-2.90). On the basis of the post hoc subgroup analysis of patients with an ultrasound-diagnosed malposition before posturing, there was a higher rate of occiput anterior positioning immediately after the intervention (17.0% vs 10.3%; relative risk, 1.63; 95% confidence interval, 1.06-2.52), but this relationship did not persist at delivery. The remainder of the subgroup analyses and secondary outcomes were not significant. CONCLUSION: Adopting a hands-and-knees posture does not increase the rate of occiput anterior positioning at time of delivery.

Provider Knowledge and Attitudes About Female Genital Mutilation/Cutting in Philadelphia.

BACKGROUND: Due to an increase in immigration from African countries, U.S. healthcare professionals are encountering women affected by Female Genital Mutilation/Cutting (FGM/C). Little formal education exists in medical, nursing or midwifery schools. Additionally, very few studies assess attitudes and knowledge of U.S. providers to care for these women. In order to eventually offer FGM/C-affected women informed and culturally competent care, assessments of provider readiness and attitudes must guide future educational efforts. METHODS: A voluntary survey was administered to healthcare providers prior to thirteen separate education sessions on FGM/C at Philadelphia institutions. RESULTS: Of the 229 surveys distributed, 227 were returned > 50% complete. 61.2% reported encountering FGM/C at least once in the past 5 years, yet 13.7% of participants reported receiving formal training in FGM/C; 77.5% felt unprepared and 47.1% uncomfortable serving patients with FGM/C. 34.1% of participants knew the matriarchal influence on the custom. The majority of providers accurately identified the short and long-term clinical consequences of FGM/C, but 67.7% of participants denied familiarity with laws regarding FGM/C. Attitude assessment revealed beliefs that all types of FGM/C are harmful and a practice rooted in tradition. DISCUSSION: While most providers reported encountering patients with FGM/C, lack of formal training leaves them unprepared and uncomfortable serving them. Results demonstrate misunderstanding of the tradition and motives of FGM/C. Our findings support the need for expansion of provider education to provide culturally competent care for women affected by FGM/C.

Outcome of 45,X fetuses with cystic hygroma: A systematic review.

This objective of this systematic review was to estimate live birth rate and explore prognostic indicators in fetuses with 45,X karyotype and a posterior cystic hygroma (CH). Electronic databases were searched and studies reporting pregnancy outcomes (termination, spontaneous abortion, demise, or live birth) for fetuses with 45,X karyotype and a CH diagnosed on ultrasound were included. For cases of survival, CH characteristics, presence of hydrops fetalis, or concomitant anomalies, delivery details, and postnatal outcomes were summarized. A total of 95 studies, including 535 cases, met inclusion criteria: 285 (53.3%) pregnancies were terminated, 72 (13.5%) had spontaneous abortion or demise, 164 (30.7%) had unspecified pregnancy failure, and 14 (2.6%) were live births. Among live births with data available, all CH measured 2-7 cm, more than half were septate, and almost all regressed in size or eventually disappeared. Hydrops fetalis was noted in five cases. Of the eight live births with neonatal outcomes available, three neonates died shortly after birth and five survived past the neonatal period. This review suggests that diagnosis of CH in a 45,X fetus is associated with an estimated live birth rate of 2.6%, but only 1% survive to infancy. Prognosis appears to improve with CH regression.

The effect of transvaginal ultrasound, vaginal examination, or coitus on fetal fibronectin results: individual participant data from 6 cohort studies.

OBJECTIVE: This study aimed to determine whether recent cervical manipulation via transvaginal ultrasound, sterile vaginal examination, or coitus affects the accuracy of fetal fibronectin results. DATA SOURCES: An electronic search was performed in PubMed, Scopus, Embase, Ovid MEDLINE, ClinicalTrials.gov, Cochrane Library, and CINAHL using a combination of pertinent key words from inception to June 2019. STUDY ELIGIBILITY CRITERIA: We included all observational studies that provided individual-level data on fetal fibronectin results after recent transvaginal ultrasound, sterile vaginal examination, or coitus. STUDY APPRAISAL AND SYNTHESIS METHODS: Studies were appraised using the Newcastle-Ottawa Quality Assessment Scale for cohort studies. Individual participant data from the included studies were pooled for each intervention. The primary outcome was agreement between pre- and postmanipulation swabs, estimated using proportion agreement and kappa statistics with 95% confidence intervals. Secondary outcomes included frequency in which the fetal fibronectin result changed after cervical manipulation and percentage of discordant pairs. Baseline fetal fibronectin swabs were not obtained in studies examining coitus; therefore, the results of these articles were examined separately. Outcome data were combined to estimate the relative risk of a positive qualitative fetal fibronectin result after coitus and differences in the concentration of quantitative fetal fibronectin. RESULTS: Of 807 studies identified, 6 were included. Three studies assessed the effect of transvaginal ultrasound (n=346 specimen pairs), 2 of sterile vaginal examination (n=122 specimen pairs), and 2 of coitus (n=262 specimen pairs) on fetal fibronectin results, with 1 study assessing the effect of more than 1 intervention. The proportion agreement between specimen pairs before and after transvaginal ultrasound and sterile vaginal examination was 93.4% (kappa, 0.69; 95% confidence interval, 0.57-0.81) and 88.5% (kappa, 0.69; 95% confidence interval, 0.54-0.84), respectively. For both transvaginal ultrasound and sterile vaginal examination, discordance with a positive preintervention fetal fibronectin and negative postintervention fetal fibronectin occurred more frequently than the converse. Patients reporting coitus within 24 to 48 hours were more likely to have a positive fetal fibronectin result than controls (39.7% vs 7.1%; relative risk, 5.6; 95% confidence interval, 3.0-10.6). CONCLUSION: Cervical manipulation via transvaginal ultrasound or sterile vaginal examination does not significantly affect fetal fibronectin results; therefore, its use after these exposures is clinically acceptable. Conversely, the use of fetal fibronectin in the setting of recent coitus should continue to be discouraged.