Guideline No. 448: Prevention of Rh D Alloimmunization.

OBJECTIVE: This guideline provides recommendations for the prevention of Rh D alloimmunization (isoimmunization) in pregnancy, including parental testing, routine postpartum and antepartum prophylaxis, and other clinical indications for prophylaxis. Prevention of red cell alloimmunization in pregnancy with atypical antigens (other than the D antigen), for which immunoprophylaxis is not currently available, is not addressed in this guideline. TARGET POPULATION: All Rh D-negative pregnant individuals at risk for Rh D alloimmunization due to potential exposure to a paternally derived fetal Rh D antigen. OUTCOMES: Routine postpartum and antepartum Rh D immunoprophylaxis reduces the risk of Rh D alloimmunization at 6 months postpartum and in a subsequent pregnancy. BENEFITS, HARMS, AND COSTS: This guideline details the population of pregnant individuals who may benefit from Rho(D) immune globulin (RhIG) immunoprophylaxis. Thus, those for whom the intervention is not required may avoid adverse effects, while those who are at risk of alloimmunization may mitigate this risk for themselves and/or their fetus. EVIDENCE: For recommendations regarding use of RhIG, Medline and Medline in Process via Ovid and Embase Classic + Embase via Ovid were searched using both the trials and observational studies search strategies with study design filters. For trials, the Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Database of Abstracts of Reviews of Effects via Ovid were also searched. All databases were searched from January 2000 to November 26, 2019. Studies published before 2000 were captured from the grey literature of national obstetrics and gynaecology specialty societies, luminary specialty journals, and bibliographic searching. A formal process for the systematic review was undertaken for this update, as described in the systematic review manuscript published separately. VALIDATION METHODS: The authors rated the quality of evidence and strength of recommendations using the SOGC's modified GRADE approach. See Appendix A (Tables A1 for definitions and A2 for interpretations of strong and conditional [weak] recommendations). INTENDED AUDIENCE: The intended users of this guideline include prenatal care providers such as obstetricians, midwives, family physicians, emergency room physicians, and residents, as well as registered nurses and nurse practitioners. TWEETABLE ABSTRACT: An updated Canadian guideline for prevention of Rh D alloimmunization addresses D variants, cffDNA for fetal Rh type, and updates recommendations on timing of RhIG administration. SUMMARY STATEMENTS: RECOMMENDATIONS.

Canadian Association of Radiologists Obstetrics and Gynecology Diagnostic Imaging Referral Guideline.

The Canadian Association of Radiologists (CAR) Obstetrics and Gynecology Expert Panel consists of radiologists specializing in obstetrics and gynecology, obstetrics and gynecology physicians, a patient advisor, and an epidemiologist/guideline methodologist. After developing a list of 12 clinical/diagnostic scenarios, a systematic rapid scoping review was undertaken to identify systematically produced referral guidelines that provide recommendations for one or more of these clinical/diagnostic scenarios. Recommendations from 46 guidelines and contextualization criteria in the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) for guidelines framework were used to develop 68 recommendation statements across the 12 scenarios related to the evaluation of obstetrics and gynecology clinical and diagnostic scenarios. This guideline presents the methods of development and the imaging recommendations for a variety of obstetrical and gynecological conditions including pregnancy assessment, recurrent first trimester pregnancy loss, post-partum indications, disorders of menstruation, localization of intra-uterine contraceptive device, infertility assessment, assessment of adnexal mass, pelvic pain of presumed gynecological origin, and pelvic floor evaluation.

The Association between Intertwin Difference in First Trimester Crown-Rump Length, Nuchal Translucency, and Birth Weight Discordance in Twin Pregnancies: A Retrospective Cohort Study.

Background: Discordant birth weight in twins is linked to poor outcomes and predicting this discrepancy may lead to enhanced screening and surveillance. Our purpose was to quantify the relationship between intertwin nuchal translucency (NT) and crown-rump length (CRL) discordance with birth weight discrepancies ≥ 20%. Methods: We conducted a retrospective cohort study of 887 live twin births delivering at a Canadian tertiary care center over a 7-year period who opted for integrated prenatal screening. Categorical data are presented as numbers and percentages, and continuous data are expressed as means and standard deviations. Chi-square tests, Fisher's Exact tests, or T-test were performed as appropriate. We then used published data and receiver operating curves to determine the optimal thresholds for predicting birth weight discordance based on first trimester intertwin NT differences. These values were used in multivariate logistic regression models accounting for known confounders. Results: Roughly 16% of twin pairs exhibited ≥ 20% difference in birth weight. Twin pairs with a CRL discordance greater than 10% have nearly a 4 times greater likelihood of having a birth weight discordance greater than 20% (OR 3.71, CI 2.24-6.14) while controlling for chorionicity, maternal age, gestational age at delivery, maternal body mass index (BMI), and parity. In these models, intertwin NT discordance ≥ 20% (OR 1.16, CI 0.77-1.77) and NT discordance ≥ 14% (OR 1.08, CI 0.73-1.60) were not statistically significant predictors of twin birth weight differences. However, when evaluating the effect of the larger intertwin NT value corresponding to the 95th percentile, an NT difference ≥ 0.9 mm was predictive of birth weight discordance ≥ 20% (OR 2.53, CI 1.21-5.29). Conclusion: Although intertwin CRL and NT discordance measured via ultrasound between 11-14 weeks gestation are related to birth weight discordance, there is uncertainty as to whether twin birth weight differences are related to adverse pregnancy outcomes in this population.

In Utero Enzyme-Replacement Therapy for Infantile-Onset Pompe's Disease.

Patients with early-onset lysosomal storage diseases are ideal candidates for prenatal therapy because organ damage starts in utero. We report the safety and efficacy results of in utero enzyme-replacement therapy (ERT) in a fetus with CRIM (cross-reactive immunologic material)-negative infantile-onset Pompe's disease. The family history was positive for infantile-onset Pompe's disease with cardiomyopathy in two previously affected deceased siblings. After receiving in utero ERT and standard postnatal therapy, the current patient had normal cardiac and age-appropriate motor function postnatally, was meeting developmental milestones, had normal biomarker levels, and was feeding and growing well at 13 months of age.

Does late second-trimester cervical length predict unscheduled preterm birth in asymptomatic triplet pregnancies?

OBJECTIVE: Multiple gestation increases the risk of unscheduled preterm birth (PTB), both spontaneous and indicated, leading to increased neonatal morbidity and additional healthcare costs. The purpose of this study was to determine whether cervical length (CL) assessment by 28 weeks could predict unscheduled PTB <34 weeks in triplet pregnancies. Secondary outcomes included prediction of PTB <30 weeks, prediction of PTB based on degree of cervical change and effect of ART-use on PTB. METHODS: This was a retrospective cohort of women with triplet pregnancies. The exposure variable of interest was short cervix < 25 and <20 millimeters (mm) by 28 weeks. Maternal characteristics were described. The distribution of CLs was analyzed by the primary outcome of unscheduled PTB < 34 weeks, and by PTB <30 weeks (secondary outcome). Gestational age at delivery was compared between women with and without a short cervix. Changes in CL were compared between the groups with unscheduled PTB and those delivering ≥34 and ≥30 weeks. Statistical analyses were performed using appropriate tests. RESULTS: Of 92 triplet pregnancies, 51 met the criteria, with 1233 total (411 shortest) CL measurements from 16 to 34 weeks' gestation. The overall rate of PTB <34 weeks was 31.4% and <30 weeks was 9.8%. The median gestational age at delivery was 32.7 (IQR 2.3) weeks. There were no statistically significant differences in rates of unscheduled PTB in women who had a short cervix and those that did not: PTB <34 weeks with CL <25 mm (p = .53) and CL <20 mm (p = .70); PTB <30 weeks with CL <25 mm (p = .38) and CL <20 mm (p = .26). The degree of cervical change from 18 to 28 weeks was not statistically significant for predicting unscheduled PTB <34 and <30 weeks. Of 70.6% of triplet pregnancies conceived by ARTs, 13.9% had unscheduled PTB <30 weeks, whereas no spontaneously-conceived pregnancies delivered <30 weeks (p = .14). CONCLUSION: Short cervix did not predict unscheduled spontaneous PTB <34 weeks nor <30 weeks in our triplet cohort, nor did the degree of cervical change by 28 weeks predict PTB. Triplets conceived by ARTs may have an increased risk of unscheduled PTB.

"When in Doubt, Ask the Patient": A Quantitative, Patient-Oriented Approach to Formative Assessment of CanMEDS Roles.

Introduction: Since the introduction of competency-based frameworks into postgraduate medical curricula, educators have struggled to implement robust assessment tools that document the progression of necessary skills. The global movement towards competency-based medical education demands validated assessment tools. Our objective was to provide validity evidence for the Ottawa CanMEDS Competency Assessment Tool (OCCAT), designed to assess clinical performance in the communicator, professional, and health advocate CanMEDS roles. Methods: We developed the OCCAT, a 29-item questionnaire informed by specialty-specific Entrustable Professional Activities and consultation with stakeholders, including patients. Our sample included nine neonatal-perinatal medicine and maternal fetal medicine fellows rotating through antenatal high-risk clinics at the Ottawa Hospital. Following 70 unique encounters, the OCCAT was completed by patients and learners. Generalizability theory was used to determine overall reliability of scores. Differences in self and patient ratings were assessed using analyses of variance. Results: Generalizability analysis demonstrated that both questionnaires produced reliable scores (G-coefficient > 0.9). Self-scores were significantly lower than patient scores across all competencies, F(1, 6) = 13.9, p = .007. Variability analysis demonstrated that trainee scores varied across all competencies, suggesting both groups were able to recognize competencies as distinct and discriminate favorable behaviors belonging to each. Discussion: Our findings lend support to the movement to integrate self-assessment and patient feedback in formal evaluations for the purpose of enriched learner experiences and improved patient outcomes. We anticipate that the OCCAT will facilitate bridging to competency-based medical education.

Antenatal and postpartum prevention of Rh alloimmunization: A systematic review and GRADE analysis.

BACKGROUND: Existing systematic reviews of Rh immunoprophylaxis include only data from randomized controlled trials, have dated searches, and some do not report on all domains of risk of bias or evaluate the certainty of the evidence. Our objective was to perform an updated review, by including new trials, any comparative observational studies, and assessing the certainty of the evidence using the GRADE framework. METHODS: We searched MEDLINE, Embase and the Cochrane Library from 2000 to November 26, 2019. Relevant websites and bibliographies of systematic reviews and guidelines were searched for studies published before 2000. Outcomes of interest were sensitization and adverse events. Risk of bias was evaluated with the Cochrane tool and ROBINS-I. The certainty of the evidence was performed using the GRADE framework. RESULTS: Thirteen randomized trials and eight comparative cohort studies were identified, evaluating 12 comparisons. Although there is some evidence of beneficial treatment effects (e.g., at 6-months postpartum, fewer women who received RhIg at delivery compared to no RhIg became sensitized [70 fewer sensitized women per 1,000 (95%CI: 67 to 71 fewer); I2 = 73%]), due to very low certainty of the evidence, the magnitude of the treatment effect may be overestimated. The certainty of the evidence was very low for most outcomes often due to high risk of bias (e.g., randomization method, allocation concealment, selective reporting) and imprecision (i.e., few events and small sample sizes). There is limited evidence on prophylaxis for invasive fetal procedures (e.g. amniocentesis) in the comparative literature, and few studies reported adverse events. CONCLUSION: Serious risk of bias and low to very low certainty of the evidence is found in existing RCTs and comparative observational studies addressing optimal effectiveness of Rh immunoprophylaxis. Guideline development committees should exercise caution when assessing the strength of the recommendations that inform and influence clinical practice in this area.

Intrauterine Interventions for the Treatment of Twin Anemia-Polycythemia Sequence: A Systematic Review.

BACKGROUND: Twin anemia-polycythemia sequence (TAPS) is a complication of monochorionic, multiple gestation pregnancies in which blood shunting through placental anastomoses results in chronic anemia in one fetus and chronic polycythemia in another. The outcomes of different treatment modalities for TAPS are not well known. OBJECTIVE: To determine the outcomes of the intrauterine interventions used to treat TAPS. STUDY DESIGN: A systematic literature search of MEDLINE, EMBASE, and CENTRAL was performed in June 2016. Primary outcomes were mortality, morbidity, and adverse perinatal outcomes. Data were summarized in the form of weighted means, and statistical difference was determined. RESULTS: Twenty-one articles were identified for inclusion in this review and were composed of 105 cases of TAPS. In the cases presented in the literature, there was no statistically significant difference in mortality, morbidity, or emergent Caesarean section rates between expectant management, intrauterine transfusion (IUT), and laser ablation therapy. Laser ablation therapy and IUT were found to have a significantly lower rate of adverse perinatal outcomes when compared to expectantly managed cases. CONCLUSIONS: The literature looking into the treatment of TAPS is very limited, with no randomized controlled trials and only one includable comparative study. Based on the data in the case report and case study literature, there is no mortality difference between any of the treatment modalities. Expectant management may be associated with an increase in adverse perinatal outcomes when compared to laser therapy and IUT. More comparative studies are needed to assist clinicians in adopting an evidence-based approach to the treatment of TAPS.

Oocyte donation pregnancies and the risk of preeclampsia or gestational hypertension: a systematic review and metaanalysis.

The purpose of this study was to determine whether pregnancies that were achieved via oocyte donation, compared with pregnancies achieved via other assisted reproductive technology methods or natural conception, demonstrate increased risk of preeclampsia or gestational hypertension. Comparative studies of pregnancies that were achieved with oocyte donation vs other methods of assisted reproductive technology or natural conception with preeclampsia or gestational hypertension were included as 1 of the measured outcomes. Abstracts and unpublished studies were excluded. Two reviewers independently selected studies, which were assessed for quality with the use of methodological index for non-randomized studies, and extracted the data. Statistical analysis was conducted. Of the 523 studies that were reviewed initially, 19 comparative studies met the predefined inclusion and exclusion criteria and were included in the metaanalysis, which allowed for analysis of a total of 86,515 pregnancies. Our pooled data demonstrated that the risk of preeclampsia is higher in oocyte-donation pregnancies compared with other methods of assisted reproductive technology (odds ratio, 2.54; 95% confidence interval, 1.98-3.24; P < .0001) or natural conception (odds ratio, 4.34; 95% confidence interval, 3.10-6.06; P < .0001). The risk of gestational hypertension was also increased significantly in oocyte donation pregnancies in comparison with other methods of assisted reproductive technology (odds ratio, 3.00; 95% confidence interval, 2.44-3.70; P < .0001) or natural conception (odds ratio, 7.94; 95% confidence interval, 1.73-36.36; P = .008). Subgroup analysis that was conducted for singleton and multiple gestations demonstrated a similar risk for preeclampsia and gestational hypertension in both singleton and multiple gestations. This metaanalysis provides further evidence that supports that egg donation increases the risk of preeclampsia and gestational hypertension compared with other assisted reproductive technology methods or natural conception.

The importance of a late first trimester placental sonogram in patients at risk of abnormal placentation.

Background. Placenta accreta is a potentially life-threatening obstetrical condition and is responsible for many emergency Caesarean hysterectomies. Early prenatal diagnosis may help minimize maternal morbidity and mortality. This report highlights risk factors, early diagnostic findings and complications associated with placenta accreta, and the role of first trimester sonography in diagnosis. Case. A 38-year-old pregnant woman, G2P1L1 with history of one previous Caesarean section, presented with vaginal bleeding at 13 weeks' gestation. Ultrasound examination was highly suspicious of placenta previa with accreta. During an earlier 12-week scan for nuchal translucency measurement, the placenta was suboptimally visualized. She was counselled regarding potential maternal and fetal complications as well as management options. At 33 weeks' gestation Caesarean hysterectomy was performed due to vaginal bleeding. Conclusion. Early ultrasound screening in high-risk patients may be advantageous in order to identify placenta accreta and conduct appropriate patient counseling regarding risks and management options.

Three new high-prevalence antigens in the Cromer blood group system.

BACKGROUND: The Cromer blood group system consists of nine high-prevalence and three low-prevalence antigens carried on decay-accelerating factor (DAF). This report describes three new Cromer high-prevalence antigens, named ZENA, CROV, and CRAM. STUDY DESIGN AND METHODS: Sequence analyses were performed on DNA from three probands whose serum samples each contained an alloantibody to a high-prevalence antigen in the Cromer blood group system. Polymerase chain reaction-restriction fragment length polymorphism analysis to detect the mutation encoding the CROV- phenotype was performed on 100 Croatian donors. To map the respective epitopes, DAF deletion mutants were tested by immunoblotting with eluates containing the antibodies. RESULTS: In each proband, sequence analysis revealed a single-nucleotide substitution in DAF: ZENA, 726T>G mutation, predicted change His242Gln; CROV, 466G>A mutation, predicted change Glu156Lys; and CRAM, 740A>G mutation, predicted change Gln247Arg. By analysis of DAF deletion mutants, the CROV antigenic determinant mapped to the complement control protein (CCP) domain 2, which is encoded by exon 3, whereas ZENA and CRAM mapped to CCP4, which is encoded by exon 6. CONCLUSION: This study describes three novel high-prevalence antigens in the Cromer blood group system each characterized by a predicted single-amino-acid substitution. The antigens have been assigned the following International Society of Blood Transfusion (ISBT) numbers: ZENA is CROM13, CROV is CROM14, and CRAM is CROM15.

Relationship between intertwin delivery interval and metabolic acidosis in the second twin.

This study sought to assess the relationship between intertwin delivery interval (ITDI) and metabolic acidosis in the second twin at birth using a retrospective twin delivery cohort from a tertiary-level teaching hospital. Twin births were identified from an obstetrical database during a 10-year period from 1994 to 2004. Mean arterial cord pH and base deficit among different ITDIs were compared by analysis of variance. Logistic regression models were used to estimate effects of ITDI on metabolic acidosis. The incidence of metabolic acidosis in the second twin was defined as pH < 7.0, and base deficit was defined as >or= 12 mmol/L at birth. After excluding those pregnancies with both twins delivered by cesarean section, birthweight less than 750 g of either twin, antepartum death of either twin, or second twins with missing cord arterial pH, we had 310 twin pairs left for final analysis. Mean pH was significantly lower and base deficit significantly higher for second twin after ITDI exceeded 60 minutes. The incidence of metabolic acidosis increased with increasing ITDI (chi2 test for linear trend, P = 0.02) and the risk of metabolic acidosis (odds ratio, 22.6; 95% confidence interval, 2.5 to 494.1) was increased in the second twins with ITDI longer than 60 minutes compared with those with ITDI less than 15 minutes. The incidence of metabolic acidosis increases with increasing ITDI and there is a statistically significant increased risk of neonatal acidosis after longer than 60 minutes compared with less than 15 minutes of ITDI.

Impacts of operative delivery for the first twin on neonatal outcomes in the second twin.

We assess the impacts of operative delivery for the first twins with vertex presentation on neonatal outcomes in second twins using the 1995 to 1997 twin registry data of the United States. A total of 102,554 eligible twin pairs with vertex presentation for the first twin were included in the analysis. Of these, 50,748 (49.5%) first twins had a normal vaginal delivery, 43,504 (42.4%) were delivered by cesarean section, and 8302 (8.1%) were delivered by vaginal operation (vacuum extraction or forceps). In term twins, the risks of asphyxia-related mortality (odds ratio [OR], 3.08; 95% CI, 1.07 to 8.45), newborn injury (OR, 2.10; 95% 1.39 to 3.12), low Apgar score at 5 minutes (OR, 1.49; 95% 1.24 to 1.78), and mechanical ventilation use (OR, 1.34; 95% 1.20 to 1.51) were increased in the second twins whose co-twins were delivered by vaginal operation compared with those whose co-twins who had normal vaginal delivery. In contrast, the risks of asphyxia-related mortality (OR, 0.55; 95% 0.17 to 1.57), newborn injury (OR, 0.20; 95% 0.11 to 0.34), low Apgar score at 5 minutes (OR, 0.51; 95% 0.44 to 0.60), and mechanical ventilation use (OR, 0.77; 95% 0.71 to 0.83) were decreased in the second twins whose co-twins were delivered by cesarean section compared with those whose co-twins had a normal vaginal delivery. In conclusion, vaginal operative delivery for the first twins is related to the adverse neonatal outcomes of their co-twins, whereas cesarean delivery for the first twins is associated with the beneficial neonatal outcomes of their co-twins.

Neonatal mortality and morbidity rates in term twins with advancing gestational age.

OBJECTIVE: The purpose of this study was to identify the gestational age with the lowest morbidity and mortality rates for twin pregnancies that reach term. STUDY DESIGN: A retrospective cohort study carried out with 60,443 twin pairs from the United States (1995-1997). Analysis was restricted to pregnancies that had reached at least 37 weeks of gestation; groups were created on the basis of the gestational ages of 37, 38, 39, and > or = 40 weeks. The incidence of death and morbidity were calculated; multiple logistic regression models were used to estimate the independent effect of gestational age for twin A and B. RESULTS: The neonatal mortality rate increased significantly after 40 weeks of gestation (twin A: odds ratio, 3.47 [95% CI, 2.29, 5.38]; twin B, odds ratio, 2.52 [95% CI, 1.75, 3.67]). There was also an increased risk of neonatal morbidity in the > or = 40 weeks of gestation group for twin A and B (Apgar score, < or = 3; odds ratio, 1.88 [95% CI, 1.18, 3.02], 1.74 [95% CI, 1.21, 2.52], respectively). There was a decreased risk of assisted ventilation in the 38 and 39 weeks of gestation group for twin A (odds ratio, 0.86 [95% CI, 0.77, 0.97], odds ratio, 0.83 [95% CI, 0.72, 0.95], respectively) and a decreased risk in the 39 and > or = 40 weeks of gestation groups for twin B (assisted ventilation: odds ratio, 0.83 [95% CI, 0.73, 0.93], odds ratio, 0.81 [95% CI, 0.72, 0.92], respectively). CONCLUSION: This study suggests that the optimal date of delivery for twins should be <40 weeks of gestation; there was no compelling evidence for delivering at <38 weeks of gestation.

The distribution of intra-twin birth weight discordance and its association with total twin birth weight, gestational age, and neonatal mortality.

OBJECTIVE: To determine an appropriate cutoff value to differentiate physiologic and pathologic birth weight discordance, to determine the prevalence of birth weight discordance > or =25% among twin pregnancies in different sub-populations, and to examine its clinical significance. STUDY DESIGN: Historical cohort study of 147,262 twin sets registered in the United States between 1995 and 1997. RESULTS: The prevalence of birth weight discordance > or =25% among twin pregnancies was 8.6%. The prevalence of birth weight discordance > or =25% was significantly decreased with increasing total twin birth weight deciles, was more frequently found in twins with discordant gender (9.1%) than in those twins with concordant gender (8.3%) and in mothers whose age was 30 years or older (9.1%) than those of younger mothers (8.1%). Birth weight discordance > or =25% was associated with earlier gestational age at delivery (35.0 weeks versus 36.0 weeks) and higher neonatal mortality (5.4% versus 2.3%) as compared to twins with lower birth weight discordance. CONCLUSIONS: The prevalence of birth weight discordance > or =25% among twin pregnancies was 8.6%, which is associated with lower gestational age at delivery and higher neonatal mortality rates, and may represent a pathologic process.

Neonatal death and morbidity in vertex-nonvertex second twins according to mode of delivery and birth weight.

OBJECTIVE: The purpose of this study was to assess the risk of neonatal death and morbidity in vertex-nonvertex second twins according to the mode of delivery and birth weight. STUDY DESIGN: Data from a retrospective cohort study that was based on all twin births in the United States (1995-1997) were used. RESULTS: A total of 15,185 vertex-nonvertex second twins were classified into 3 groups: (1) both twins were delivered by cesarean delivery (37.7%), (2) both twins were delivered vaginally (46.8%), and (3) the second twin was delivered by cesarean delivery after vaginal delivery of the first twin (15.5%). The risk of asphyxia-related neonatal deaths and morbidity was increased in the group in which both twins were delivered vaginally and the group in which both twins were delivered by cesarean delivery. The increase in neonatal death in the group in which both twins were delivered vaginally was stronger in the birth weight of < 1500 g. In contrast, in the group in which both twins were delivered vaginally and the group in which the second twin was delivered by cesarean delivery after the first twin was delivered vaginally, the increase in neonatal morbidity was greater in the group in which the birth weight was 1500 to 4000 g. CONCLUSION: The risk of neonatal death and morbidity in second-born twins is higher in the group in which both twins were delivered vaginally and the group in which the second twin was delivered by cesarean delivery after the first twin was delivered vaginally compared with the group in which both twins were delivered by cesarean delivery.