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.
METHODS: All Rh D-negative pregnant individuals at risk for Rh D alloimmunization due to potential exposure to a paternally derived fetal Rh D antigen.
RESULTS: Routine postpartum and antepartum Rh D immunoprophylaxis reduces the risk of Rh D alloimmunization at 6 months postpartum and in a subsequent pregnancy.
RESULTS: 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.
METHODS: 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.
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).
UNASSIGNED: 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.
CONCLUSIONS: 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.
CONCLUSIONS: RECOMMENDATIONS.

OBJECTIVE: To provide recommendations for the prevention of Rh D alloimmunization in the first trimester of pregnancy.
METHODS: The quality of evidence of the literature was assessed following the GRADE methodology with questions formulated in the PICO format (Patients, Intervention, Comparison, Outcome) and outcomes defined a priori and classified according to their importance. An extensive bibliographic search was performed on Pubmed, Cochrane, EMBASE, and Google Scholar databases. The quality of evidence was assessed (high, moderate, low, very low) and a recommendation was formulated: (i) strong, (ii) weak, or (iii) no recommendation. The recommendations were reviewed in two rounds with reviewers from the scientific board of the French College of the OB/GYN (Delphi survey) to select the consensus recommendations.
RESULTS: The three recommendations from PICO questions reached agreement using the Delphi method. It is recommended not to administer Rh D immunoglobulin before 12 weeks of gestation to reduce the risk of alloimmunization in case of abortion or miscarriage, in RhD negative patients when the genitor is RhD positive or unknown (Weak recommendation. Very low-quality evidence). It is recommended not to administer Rh D immunoglobulin before 12 weeks of gestation to reduce the risk of alloimmunization in cases of bleeding in an ongoing intrauterine pregnancy (Weak recommendation. Very low-quality evidence). The literature data are insufficient in quality and quantity to determine if the injection of Rh D immunoglobulin reduces the risk of alloimmunization in the case of an ectopic pregnancy (No recommendation. Very low-quality evidence).
CONCLUSIONS: Even though the quality of evidence from the studies is very low, it is recommended not to administer Rh D immunoglobulin in case of abortion, miscarriage or bleeding before 12 weeks of amenorrhea. The quality of evidence was too low to issue a recommendation regarding ectopic pregnancy.

Historical evidence that fetal red blood cell (RBC) exposure during early spontaneous or induced abortion can cause maternal Rh sensitization is limited. A close reading of these studies indicates that forgoing Rh immunoglobulin administration before 12weeks gestation is highly unlikely to increase risk of Rh (D) antibody development, and recent studies indicate that fetal RBC exposure during aspiration abortion <12 weeks gestation is below the calculated threshold to cause maternal Rh sensitization, and the amount of fetomaternal hemorrhage during dilation and evacuation procedures up to 18weeks gestation is adequately treated with 100mcg of Rh immunoglobulin. We provide updated recommendations for Rh immunoglobulin administration based on this new evidence.

The introduction of anti-Rh(D) immunoglobulin more than 50 years ago has resulted in only a 50% decrease in Rhesus disease globally owing to a low uptake of this prophylactic approach. The International Federation of Gynecology and Obstetrics, International Confederation of Midwives, and Worldwide Initiative for Rhesus Disease Eradication have reviewed current evidence regarding the utility of anti-Rh(D) immunoglobulin. Taking into account the effectiveness anti-Rh(D), the new guidelines propose adjusting the dose for different indications and prioritizing its administration by indication.

Administration of RhD immunoglobulin (Ig) is important for RhD negative women throughout pregnancy and postnatally to prevent alloimmunisation and haemolytic disease of the fetus and newborn in subsequent pregnancies.
The aim of this audit was to understand compliance with the Australian guidelines on RhD Ig prophylaxis in pregnancy.
This was a retrospective audit of RhD negative pregnant women in Victoria, Northern Territory, Australian Capital Territory and Tasmania at maternity services of level 2 or higher care, between July 2017 and June 2018. Medical records were reviewed to identify how many RhD negative women received care compliant with the guidelines covering antibody testing, consent, administration of RhD Ig, and feto-maternal haemorrhage (FMH) quantification.
Analysis included 939 RhD negative women from 43 health services. Compliance with postnatal RhD Ig was high (98%); however, other practice was poor. Documented consent was obtained and recorded for 585 women (62%). Only 76% of eligible women received RhD Ig at the appropriate dose and time (28 and 34 weeks gestation). Similarly, management of potentially sensitising events was suboptimal with 78% receiving RhD Ig when recommended by guidelines. The results of our audit indicate a need for practice improvement across all aspects of care for women who need to receive RhD Ig. A major focus should be not just educating clinical staff, but also educating women to understand the importance of RhD Ig and the potential impact on subsequent pregnancies in order to improve guideline adherence and reduce risk.

OBJECTIVE:  The objective of this study was to compare national guidelines on the prevention of RhD alloimmunization.
METHODS:  We performed a review of four national guidelines on prevention of alloimmunization from the American Congress of Obstetricians and Gynecologists, Royal College of Obstetricians and Gynaecologists, Society of Obstetricians and Gynaecologists of Canada, and The Royal Australian and New Zealand College of Obstetricians and Gynaecologists. We compared the indications/contraindications, timing, dosing, formulation and route of anti-D immune globulin, and management of unique circumstances. The references were compared with regard to the number of randomized control trials, Cochrane Reviews, and systematic reviews/meta-analyses cited.
RESULTS:  Variation exists in recommendations on the timing and need for consent prior to routine antenatal anti-D immune globulin administration, prophylaxis for unique circumstances (e.g., threatened abortion < 12 weeks, complete molar pregnancy), and the use of cell-free fetal DNA testing for fetal RhD genotype.
CONCLUSIONS:  These variations in recommendations reflect the heterogeneity of the literature on the prevention of alloimmunization and highlight the need for synthesis of evidence to create an international guideline on prevention of alloimmunization. This may improve safety, quality, optimize outcomes, and stimulate future trials.

Events following which immunoglobulin (Ig) G anti-D should be given to all RhD negative women with no anti-D alloantibodies: First trimester indications (IgG anti-D sufficient dose of 50 μg*) - termination of pregnancy, spontaneous abortion followed by instrumentation, ectopic pregnancy, chorionic villus sampling, partial molar pregnancy; Second and third trimester indications (IgG anti-D sufficient dose of 100 μg*) - amniocentesis, cordocentesis, other invasive prenatal diagnostic or therapeutic procedures, spontaneous or induced abortion, intrauterine fetal death, attempt at external cephalic version of a breech presentation, abdominal trauma, obstetric hemorrhage; Antenatal prophylaxis at 28th weeks of gestation (IgG anti-D sufficient dose of 250 μg*); Delivery of an RhD positive infant** (IgG anti-D sufficient dose of 100 μg*); Minimal dose*: before 20 weeks gestation - 50 μg (250 IU), after 20 weeks gestation*** - 100 μg (500 IU); Timing: as soon as possible, but no later than 72 hours after the event. In cases where prevention of RhD alloimmunization is not performed within 72 hours of a potentially sensitising event, it is still reasonable to administer IgG anti-D within 13 days, and in special cases, administration is still recommended up to a maximum interval of 28 days postpartum; Legend: *administration of a higher dose of IgG anti-D is not a mistake, ** also if the D type is not known, *** simultaneous assessment of the volume of fetomaternal hemorrhage (FMH) to specify the dose is suitable; The FMH volume assessment - If the volume of fetal erythrocytes (red bood cells, RBCs) which entered maternal circulation is assessed, intramuscular administration of IgG anti-D in a dose of 10 μg per 0.5 mL of fetal RBCs or 1 mL of whole fetal blood is indicated. IgG anti-D in a dose of 10 μg administered intramuscularly should cover 0.5 mL of fetal RhD positive RBCs or 1mL of whole fetal blood. FMH is the fetal RBC volume; fetal blood volume is double (expected fetal hematocrit is 50%).

It is estimated that about two thirds of newborns will appear clinically jaundiced during their first weeks of life. As newborns and their mothers spend fewer days in the hospital after birth, the number of infants readmitted yearly in the United States for neonatal jaundice over the last 10 years has increased by 160%. A portion of these infants present to the emergency department, requiring a careful history and physical examination assessing them for the risk factors associated with pathologic bilirubin levels. Although the spectrum of illness may be great, the overwhelming etiology of neonatal jaundice presenting to an emergency department is physiologic and not due to infection or isoimmunization. Therefore, a little more than a good history, physical examination, and indirect/direct bilirubin levels are needed to evaluate an otherwise well-appearing jaundiced newborn. The American Academy of Pediatrics\' 2004 clinical practice guidelines for \"Management of Hyperbilirubinemia in the Newborn Infant 35 or More Weeks of Gestation\" are a helpful and easily accessible resource when evaluating jaundiced newborns (available at http://aappolicy.aappublications.org/cgi/content/full/pediatrics;114/1/297). There are several exciting developments on the horizon for the diagnosis and management of hyperbilirubinemia including increasing use of transcutaneous bilirubin measuring devices and medications such as tin mesoporphyrin and intravenous immunoglobulin that may decrease the need for exchange transfusions.

BACKGROUND: Evidence-based guidelines have been issued for ectopic pregnancy (EP), covering both diagnostic and therapeutic management. In general, guidelines aim to reduce practice variation and to improve quality of care. To assess the guideline adherence in the management of EP, we developed guideline-based quality indicators and measured patient care in various hospitals.
METHODS: A panel of experts and clinicians developed quality indicators based on recommendations from the Dutch guideline on EP management, using the systematic RAND-modified Delphi method. With these indicators, patient care was assessed in six Dutch hospitals between January 2003 and December 2005. For each quality indicator, a ratio for guideline adherence was calculated. Overall adherence was reported, as well as adherence per hospital type, i.e. academic, teaching and non-teaching hospitals.
RESULTS: Out of 30 guideline-based recommendations, 12 quality indicators were selected covering procedural, structural and outcome aspects of care. For 317 women surgically treated for EP, these aspects were assessed. Overall adherence to the guideline was 75%. The highest adherence (98%) was observed for performing transvaginal sonography during the diagnostic workup. The lowest adherence (21%) was observed for performing salpingotomy in case of contra-lateral tubal pathology. Wide variance in adherence (0-100%) existed between academic, teaching and non-teaching hospitals.
CONCLUSIONS: The overall guideline adherence was reasonable, with ample room for improvement in various aspects of care. Further research should focus on the barriers for guideline dissemination and adherence, to further improve the management of EP.

Events following which anti-D immunoglobulin should be given to all RhD negative women with no anti-D antibodies: First trimester indications (50 microg)--termination of pregnancy, spontaneous abortion followed by instrumentation, ectopic pregnancy, chorionic villus sampling, partial molar pregnancy; Second and third trimester indications (100 microg)--amniocentesis, cordocentesis, other invasive prenatal diagnostic or therapeutic procedures, spontaneous or induced abortion, intrauterine fetal death, attempt at external cephalic version of a breech presentation, abdominal trauma, obstetric haemorrhage; Antenatal prophylaxis at 28th weeks of gestation (250 microg); Delivery of an RhD positive infant * (100 microg); Minimal dose: before 20 weeks gestation--50 microg (250 IU), after 20 weeks gestation **--100 microg (500 IU); Timing: as soon as possible, but no later than 72 hours after the event. In cases where prevention of RhD alloimmunization is not performed within 72 hours of a potentially sensitising event, it is still reasonable to administer anti-D immunoglobulin (IgG anti-D) within 13 days, and in special cases, administration is still recommended up to a maximum interval of 28 days postpartum.; FMH (fetomaternal haemorrhage)--If the amount of fetal erythrocytes which entered the maternal circulation is quantitatively determined, administration of 10 microg IgG anti-D per 0.5 ml of fetal erythrocytes or 1 ml of whole blood is indicated. *also if the RhD type of the infant has not been determined or is in doubt, **in conjunction with a test to assess the volume of any fetomaternal hemorrhage.