Induced Abortion and the Risk of Rh Sensitization.

Importance: While population-level data suggest Rh immunoglobulin is unnecessary before 12 weeks' gestation, clinical evidence is limited. Thus, guidelines vary, creating confusion surrounding risks and benefits of Rh testing and treatment. As abortion care in traditional clinical settings becomes harder to access, many people are choosing to self-manage and need to know if ancillary blood type testing is necessary. Objective: To determine how frequently maternal exposure to fetal red blood cells (fRBCs) exceeds the most conservative published threshold for Rh sensitization in induced first-trimester abortion. Design, Setting, and Participants: Multicenter, observational, prospective cohort study using high-throughput flow cytometry to detect circulating fRBCs in paired maternal blood samples before and after induced first-trimester abortion (medication or procedural). Individuals undergoing induced first-trimester abortion before 12 weeks 0 days' gestation were included. Paired blood samples were available from 506 participants who underwent either medical (n = 319 [63.0%]) or procedural (n = 187 [37.0%]) abortion. Exposure: Induced first-trimester abortion. Main Outcomes and Measures: The primary outcome was the proportion of participants with fRBC counts above the sensitization threshold (125 fRBCs/5 million total RBCs) after induced first-trimester abortion. Results: Among the 506 participants, the mean (SD) age was 27.4 (5.5) years, 313 (61.9%) were Black, and 123 (24.3%) were White. Three of the 506 participants had elevated fRBC counts at baseline; 1 of these patients had an elevated fRBC count following the abortion (0.2% [95% CI, 0%-0.93%]). No other participants had elevated fRBC counts above the sensitization threshold after induced first-trimester abortion. The median change from baseline was 0 fRBCs, with upper 95th and 99th percentiles of 24 and 35.6 fRBCs, respectively. Although there was a strong association between the preabortion and postabortion fRBC counts, no other baseline characteristic was significantly associated with postabortion fRBC count. Conclusions and Relevance: Induced first-trimester abortion is not a risk factor for Rh sensitization, indicating that Rh testing and treatment are unnecessary before 12 weeks' gestation. This evidence may be used to inform international guidelines for Rh immunoglobulin administration following first-trimester induced abortion.

Qualitative analysis of Doppler assessment used for surveillance of alloimmunized individuals.

OBJECTIVES: To summarize image quality variables for alloimmunized women at risk for fetal anemia. To investigate the association between image quality with the highest and median middle cerebral artery peak systolic velocity (MCA-PSV) at the last visit and fetal anemia based on hemoglobin. STUDY DESIGN: This study was a qualitative retrospective analysis of 192 Doppler ultrasound images used in the detection of fetal anemia in 26 alloimmunized women seen in a Minneapolis hospital over the past 3 years. Images were graded on seven criteria found in literature. RESULTS: Of the images analyzed, 23 (12.0%) of the 192 met all seven image quality criteria. Using the highest MCA-PSV value, the sensitivity, and specificity were 55.6% and 94.1%, respectively. Using the median MCA-PSV value, the sensitivity, and specificity were 44.4% and 94.1%, respectively. CONCLUSIONS: Only a minority of Doppler images meet all suggested image criteria. This could negatively impact the accuracy of the MCA-PSV measurements as indicated by the decreased sensitivity in our evaluations.

Following targeted routine antenatal anti-D prophylaxis, almost half of the pregnant women had undetectable anti-D prophylaxis at delivery.

INTRODUCTION: In September 2016, a nationwide targeted routine antenatal anti-D prophylaxis program was implemented in Norway. The prophylaxis (anti-D immunoglobulin) aims to cover the whole third trimester and is administered in gestational week 28 to RhD-negative women who carry RhD-positive fetuses. However, in many women, antibody screening at delivery does not detect anti-D immunoglobulin. The goal of this study was to investigate the presumable role of dose and timing of antenatal anti-D immunoglobulin administration in non-detectable prophylaxis at the time of delivery. MATERIAL AND METHODS: In this retrospective observational study, RhD-negative pregnant women who gave birth at Oslo University Hospital and Akershus University Hospital between January 2017 and December 2019 were analyzed. Women who received antenatal anti-D immunoglobulin (1500 IU at Oslo University Hospital and 1250 IU at Akershus University Hospital) when fetal RHD genotyping at gestational week 24 predicted an RhD-positive fetus were included if an antibody screen at delivery was available. Data from the blood bank, maternity information systems, and electronic patient records were used. RESULTS: Analysis of the 984 RhD-negative women at the two hospitals revealed that 45.4% had non-detectable anti-D at delivery. A significant difference between the two hospitals was observed: 40.5% at Oslo University Hospital (n = 509) and 50.7% at Akershus University Hospital (n = 475) (p = 0.001). The proportion with non-detectable anti-D increased to 56.0 and 75.3%, respectively (p = 0.008) in the group of women who gave birth 12 weeks after routine antenatal anti-D prophylaxis. Significantly fewer women had detectable anti-D at delivery when the lower anti-D immunoglobulin dose (1250 IU) was administered antenatally. Multiple logistic regression indicated that the time interval between routine antenatal anti-D prophylaxis and delivery, in addition to anti-D dose, were significantly associated with detectable anti-D at delivery (p < 0.001). CONCLUSIONS: We do not know which RhD-negative pregnant women, despite antenatal anti-D prophylaxis, are at risk of RhD alloimmunization, when antibody screening is negative at delivery. Administration of antenatal prophylaxis should probably be moved closer to delivery, since the risk of fetomaternal hemorrhage is higher during the last weeks of the third trimester.

[Severe neonatal thrombocytopenia due to maternal alloimmunization: case report and literature review]. / Allo-immunisation fœto-maternelle sévère: à propos d´un cas et revue de la littérature.

Prior to 1970, maternal alloimmunization was the leading cause of perinatal death. Currently, it has become rarer thanks to screening and monitoring in high-risk pregnancies. The advent of transcranial doppler has been a turning point in the monitoring of these pregnancies, as it is a reliable, non-invasive method for the diagnosis of fetal anemia. This helps clinicians decide whether or not to perform intrauterine transfusion. Anti-D immunoprophylaxis has also played an important role in preventing fetal and neonatal hemolytic anemia and its administration is currently well codified. Adequate management helps to avoid the effects of alloimmunization on the fetus and newborn as well as to reduce the risks of alloimmunization in subsequent pregnancies. We here report a case of severe fetomaternal rhesus (Rh) alloimmunization during unmonitored pregnancy complicated by fetoplacental anasarca.

Rh Alloimmunisation: Current Updates in Antenatal and Postnatal Management.

In spite of advances in medical science, Rh alloimmunisation remains one of the leading causes of preventable neuro-morbidities and significant neonatal hyperbilirubinemia in lower-middle income countries. Despite availability of effective antenatal preventive strategy (Anti-D), its uptake in antenatal period is low due to ignorance. Further, once diagnosed, there is lack of adequate antenatal follow up in health care facility. Some of these cases even remain undiagnosed in antenatal period only to present as a case of severe hyperbilirubinemia and kernicterus in late neonatal period. Thus, there is an urgent need for creating awareness and educating health care professionals for early detection and timely management in both antenatal and postnatal period. Following two doses of anti-D prophylaxis (one in antenatal period and one in immediate postnatal period) the incidence of Rh alloimmunisation can reduce to <1%. It is recommended to follow all Rh alloimmunised pregnancies antenatally with serial indirect Coombs test titre (till critical titre is reached) followed by serial Doppler velocimetry of middle cerebral artery in a perinatal centre where facility for intrauterine transfusion as well as advanced neonatal care is available. Postnatal management of these infants comprises of confirmation of diagnosis, aggressive phototherapy and in selective cases, double volume exchange transfusion. With appropriate antenatal and postnatal management, the prognosis of Rh alloimmunised pregnancy remains favourable and long term outcome of Rh alloimmunised infants remain comparable with their normal counterparts.

Implementation of high-throughput non-invasive prenatal testing for fetal RHD genotype testing in England: Results of a cross-sectional survey of maternity units and expert interviews.

BACKGROUND: Previously, routine antenatal anti-D prophylaxis (RAADP) was administered to all RhD-negative mothers to reduce the risk of sensitisation in the UK's National Health Service (NHS). If the baby is RhD-negative, RAADP is not required. In 2016, the UK National Institute for Health and Care Excellence (NICE) recommended non-invasive prenatal testing (NIPT) for fetal RHD genotype as a cost-effective option to guide RAADP. OBJECTIVES: To evaluate the implementation of high-throughput NIPT for fetal RHD genotype in maternity units in England by addressing research recommendations from the NICE. These were to reduce uncertainty around the resource use and cost of staff training, management of samples and results and record-keeping, as well as resultant changes to antenatal or post-partum care and performance of NIPT. METHODS: A cross-sectional survey was developed and sent to clinicians at 39 English NHS Trusts in May 2018. Qualitative interviews with seven individuals were conducted to explore missing or contraindicatory data. Qualitative findings were supplemented with NIPT test results (April 2017 to February 2019) from English hospitals. RESULTS: Staff reported that training took up to 30 minutes. There were no extra costs associated with sample management or additional appointments. Extra time required for record-keeping and management of test results was balanced later in the patient pathway. The antenatal pathway was not changed in the Trusts surveyed. The survey revealed that four post-partum scenarios were being used within English NHS Trusts. The frequency of inconclusive NIPT results was 4.3%. CONCLUSION: NIPT for fetal RHD genotype can be implemented without consuming substantial extra resources through incorporation into an existing patient pathway.

Targeted antenatal anti-D prophylaxis for RhD-negative pregnant women: a systematic review.

BACKGROUND: All non-sensitized Rhesus D (RhD)-negative pregnant women in Germany receive antenatal anti-D prophylaxis without knowledge of fetal RhD status. Non-invasive prenatal testing (NIPT) of cell-free fetal DNA in maternal plasma could avoid unnecessary anti-D administration. In this paper, we systematically reviewed the evidence on the benefit of NIPT for fetal RhD status in RhD-negative pregnant women. METHODS: We systematically searched several bibliographic databases, trial registries, and other sources (up to October 2019) for controlled intervention studies investigating NIPT for fetal RhD versus conventional anti-D prophylaxis. The focus was on the impact on fetal and maternal morbidity. We primarily considered direct evidence (from randomized controlled trials) or if unavailable, linked evidence (from diagnostic accuracy studies and from controlled intervention studies investigating the administration or withholding of anti-D prophylaxis). The results of diagnostic accuracy studies were pooled in bivariate meta-analyses. RESULTS: Neither direct evidence nor sufficient data for linked evidence were identified. Meta-analysis of data from about 60,000 participants showed high sensitivity (99.9%; 95% CI [99.5%; 100%] and specificity (99.2%; 95% CI [98.5%; 99.5%]). CONCLUSIONS: NIPT for fetal RhD status is equivalent to conventional serologic testing using the newborn's blood. Studies investigating patient-relevant outcomes are still lacking.

Red cell alloimmunization: A 2020 update.

Management of maternal red cell alloimmunization has been revolutionized over the last 60 years. Advances in the prevention, screening, diagnosis, and treatment of alloimmune-induced fetal anemia make this condition an exemplar for contemporary practice in fetal therapy. Since survival is now an expectation, attention has turned to optimization of long-term outcomes following an alloimmunized pregnancy. In this review, the current management of red cell alloimmunization is described. Current research and future directions are discussed with particular emphasis on later life outcomes after alloimmune fetal anemia.

Very Prolonged Anti-D: Confusion Surrounding Alloimmunization After Extra Rh Immunoglobulin: A Case Report.

BACKGROUND: Rh immunoglobulin (RhIg) is usually detectable a maximum of 12 to 14 weeks after administration. Positive antibodies beyond this time frame suggests alloimmunization. CASE: A woman had three pregnancies over a 6-month period, with two first-trimester losses. She received RhIg in the first pregnancy but not in the second. Two months after the second loss, in her third pregnancy, she received RhIg at week 6 due to first-trimester bleeding. She was subsequently anti-D antibody positive up to week 28 with antibodies too low to titre, leading to confusion about whether alloimmunization had occurred. CONCLUSION: Rh Ig administration led to positive anti-D antibodies lasting 22 weeks, suggesting keeping this differential diagnosis in mind when suspecting alloimmunization with positive antibodies at levels too low to titre.

Rhesus D alloimmunization in pregnancy from 1996 to 2015 in Iceland: a nation-wide population study prior to routine antenatal anti-D prophylaxis.

BACKGROUND: Rhesus D (RhD) incompatibility is still the most important cause of hemolytic disease of the fetus and newborn (HDFN) worldwide. The aim of this study was to investigate the incidence, causes, and consequences of anti-D alloimmunizations in pregnancy in Iceland, prior to implementation of targeted routine antenatal anti-D prophylaxis (RAADP) in 2018. STUDY DESIGN AND METHODS: This was a nation-wide cohort study of 130 pregnancies affected by RhD alloimmunization in Iceland in the period from 1996 through 2015. Data were collected from transfusion medicine databases, medical records, and the Icelandic Medical Birth Register. RESULTS: Of 130 RhD alloimmunizations, 80 cases (61.5%) represented new RhD immunization in the current pregnancy. Sensitization was discovered in the third trimester in 41 (51.3%) and occurred in the first pregnancy in 14 cases (17.5%). The most likely causative immunization event was the index pregnancy for 45 (56.25%), a previous pregnancy/birth for 26 (32.5%), abortion for 3 (3.75%), and unknown for 6 women (7.5%). Higher anti-D titers were associated with shorter gestational length, cesarean sections, positive direct antiglobulin test (DAT), and severe HDFN. Intrauterine transfusion (IUT) was performed in five pregnancies (3.8%), and 35 of 132 (26.5%) live-born neonates received treatment for HDFN; 32 received phototherapy (24.2%), 13 exchange transfusion (9.8%), and seven simple blood transfusion (5.3%). CONCLUSION: In about half of cases, RhD alloimmunization was caused by the index pregnancy and discovered in the third trimester. Thus, the newly implemented RAADP protocol should be effective in reducing the incidence of RhD immunization in Iceland in the future.

ACOG Practice Bulletin No. 192 Summary: Management of Alloimmunization During Pregnancy.

When any fetal blood group factor inherited from the father is not possessed by the mother, antepartum or intrapartum fetal-maternal bleeding may stimulate an immune reaction in the mother. Maternal immune reactions also can occur from blood product transfusion. The formation of maternal antibodies, or "alloimmunization," may lead to various degrees of transplacental passage of these antibodies into the fetal circulation. Depending on the degree of antigenicity and the amount and type of antibodies involved, this transplacental passage may lead to hemolytic disease in the fetus and neonate. Undiagnosed and untreated, alloimmunization can lead to significant perinatal morbidity and mortality. Advances in Doppler ultrasonography have led to the development of noninvasive methods of management of alloimmunization in pregnant women. Together with more established protocols, Doppler ultrasound evaluation may allow for a more thorough and less invasive workup with fewer risks to the mother and fetus. Prevention of alloimmunization is addressed in another Practice Bulletin ().

ACOG Practice Bulletin No. 192: Management of Alloimmunization During Pregnancy.

When any fetal blood group factor inherited from the father is not possessed by the mother, antepartum or intrapartum fetal-maternal bleeding may stimulate an immune reaction in the mother. Maternal immune reactions also can occur from blood product transfusion. The formation of maternal antibodies, or "alloimmunization," may lead to various degrees of transplacental passage of these antibodies into the fetal circulation. Depending on the degree of antigenicity and the amount and type of antibodies involved, this transplacental passage may lead to hemolytic disease in the fetus and neonate. Undiagnosed and untreated, alloimmunization can lead to significant perinatal morbidity and mortality. Advances in Doppler ultrasonography have led to the development of noninvasive methods of management of alloimmunization in pregnant women. Together with more established protocols, Doppler ultrasound evaluation may allow for a more thorough and less invasive workup with fewer risks to the mother and fetus. Prevention of alloimmunization is addressed in another Practice Bulletin ().

Cell-Free DNA: Screening for Single-Gene Disorders and Determination of Fetal Rhesus D Genotype.

The use of cell-free DNA (cfDNA) for screening and diagnosis of single-gene disorders is an evolving technology, and its application at this time is limited. Invasive testing is currently recommended for the diagnosis of single-gene disorders. The limitations of cfDNA technology are most notable in clinical settings involving X-linked and autosomal recessive conditions, in part because maternal mutant alleles greatly outnumber those of fetal origin. Examples of single-gene disorders for which cfDNA has been used include skeletal dyplasias, cystic fibrosis, congenital adrenal hyperplasia, ß-thalassemia, and muscular dystrophies.

Targeted antenatal anti-D prophylaxis program for RhD-negative pregnant women - outcome of the first two years of a national program in Finland.

INTRODUCTION: The aim of this study was to assess the accuracy of the non-invasive fetal RHD test at 24-26 weeks of gestation as part of the national antenatal screening program to target routine antenatal anti-D prophylaxis (RAADP) at 28-30 weeks at women carrying an RhD-positive fetus. MATERIAL AND METHODS: A prospective cohort study involving all maternity care centers and delivery hospitals in Finland between February 2014 and January 2016. Fetal RHD genotyping using cell-free fetal DNA in maternal plasma was performed with real-time polymerase chain reaction in a centralized setting. The results were systematically compared with the serological newborn RhD typing. The main outcome measure was the accuracy of the fetal RHD assay; the secondary variable was compliance with the newly introduced RAADP program. RESULTS: Fetal RHD was screened from 10 814 women. For the detection of fetal RHD, sensitivity was 99.99% [95% confidence interval (CI) 99.92-99.99] and specificity 99.81% (95% CI 99.60-99.92). One false-negative and seven false-positive results were reported by the delivery hospitals in two years. The negative predictive value of the test was 99.97% (95% CI 99.81-99.99). At the end of the study period, over 98% of the RhD-negative women participated in the new screening program. CONCLUSIONS: The targeted RAAPD program was implemented effectively in the national maternity care program in Finland. An accurate fetal RHD screening test allows discontinuation of newborn testing without risking the postnatal prophylaxis program. In the future, the main area to investigate will be the clinical effect of RAADP on subsequent pregnancies.

Sensitivity of fetal RHD screening for safe guidance of targeted anti-D immunoglobulin prophylaxis: prospective cohort study of a nationwide programme in the Netherlands.

OBJECTIVE:  To determine the accuracy of non-invasive fetal testing for the RHD gene in week 27 of pregnancy as part of an antenatal screening programme to restrict anti-D immunoglobulin use to women carrying a child positive for RHD DESIGN:  Prospectively monitoring of fetal RHD testing accuracy compared with serological cord blood typing on introduction of the test. Fetal RHD testing was performed with a duplex real time quantitative polymerase chain reaction, with cell-free fetal DNA isolated from 1 mL of maternal plasma The study period was between 4 July 2011 and 7 October 2012. The proportion of women participating in screening was determined. SETTING:  Nationwide screening programme, the Netherlands. Tests are performed in a centralised setting. PARTICIPANTS:  25 789 RhD negative pregnant women. MAIN OUTCOME MEASURES:  Sensitivity, specificity, false negative rate, and false positive rate of fetal RHD testing compared with serological cord blood typing; proportion of technical failures; and compliance to the screening programme. RESULTS:  A fetal RHD test result and serological cord blood result were available for 25 789 pregnancies. Sensitivity for detection of fetal RHD was 99.94% (95% confidence interval 99.89% to 99.97%) and specificity was 97.74% (97.43% to 98.02%). Nine false negative results for fetal RHD testing were registered (0.03%, 95% confidence interval 0.01% to 0.06%). In two cases these were due to technical failures. False positive fetal RHD testing results were registered for 225 samples (0.87%, 0.76% to 0.99%). Weak RhD expression was shown in 22 of these cases, justifying anti-D immunoglobulin use. The negative and positive predictive values were 99.91% (95% confidence interval 99.82% to 99.95%) and 98.60% (98.40% to 98.77%), respectively. More than 98% of the women participated in the screening programme. CONCLUSIONS:  Fetal RHD testing in week 27 of pregnancy as part of a national antenatal screening programme is highly reliable and can be used to target both antenatal and postnatal anti-D immunoglobulin use.

Percutaneous umbilical blood sampling: current trends and outcomes.

OBJECTIVES: To report our contemporary experience with PUBS, including indications and complications, stratified by the presence of hydrops fetalis. STUDY DESIGN: All PUBS performed from 1988 to 2013 at a single tertiary care center were identified using a comprehensive ultrasound database. We recorded patient demographics, relevant obstetric, fetal and neonatal data, indication for and success of PUBS and any complications. Data were analyzed using SAS, version 9.3 (SAS Institute Inc., Cary, NC). RESULTS: 455 PUBS were performed on 208 pregnant women, 97.8% of which were successful. The average gestational age at the time of PUBS was 26.7 weeks (SD 5.1 weeks, range 17.5-41.3 weeks). Indications were available for 441: 245 (55.6%) isoimmunization, 77 (17.5%) non-immune hydrops fetalis (NIHF), 98 (22.2%) chromosomal diagnosis, and 21 (4.8%) other indications. Isoimmunization was a less common indication for PUBS in 2008-2013 as compared to 1988-1992 (51.7% vs 66.2%, p=0.07). Amongst PUBS performed in the setting of hydrops, isoimmunization was much less common in the later time period (61.1% vs 0%, respectively; p<0.01). The procedure complication rate (bradycardia or fetal demise at procedure) of 2.5% was stable over the study period and was most common with NIHF (2.0% without hydrops, 0% with immune hydrops and 6.3% with NIHF; p=0.04). Of the 208 women with a PUBS performed, 74 had more than one PUBS procedure (mean 2.2, max 18). Transfusions were performed in 233 of the 455 (51.2%). Overall, 10.2% of the pregnancies had an intrauterine fetal demise (IUFD) within 2 weeks of the procedure, which was most common in pregnancies with NIHF (3.2% without hydrops, 9.1% with immune hydrops and 31.7% with NIHF; p<0.01). The IUFD rate was 60% (3/5) in fetuses with parvovirus-mediated NIHF. CONCLUSIONS: PUBS has a high likelihood of success with a relatively low complication rate. The complication rate is highest in pregnancies with NIHF, and these pregnancies are also at a significantly higher risk of IUFD, particularly those patients with parvovirus-mediated NIHF. Our findings can be used when counseling patients who are considering PUBS for diagnostic or therapeutic purposes.

Third trimester screening for alloimmunisation in Rhc-negative pregnant women: evaluation of the Dutch national screening programme.

OBJECTIVE: To evaluate the effect of red blood cell (RBC) antibody screening in the 27th week of pregnancy in Rhc-negative women, on detection of alloimmunisation, undetected at first trimester screening ('late' alloimmunisation), and subsequent haemolytic disease of the fetus and newborn (HDFN), to assess risk factors for late alloimmunisation. DESIGN: Prospective cohort and nested case-control study. SETTING: The Netherlands. POPULATION: Two-year nationwide cohort. METHODS: Prospective inclusion of Rhc-negative women with negative first trimester screening and of screen-negative controls. Assessment of incidence and numbers needed to screen (NNS) of late alloimmunisation and HDFN; logistic regression analysis to establish risk factors for late alloimmunisation. MAIN OUTCOME MEASURES: Late alloimmunisation, HDFN. RESULTS: Late alloimmunisation occurred in 99 of 62 096 (0.159%) Rhc-negative women; 90% had c/E antibodies and 10% non-Rhesus antibodies. Severe HDFN (fetal/neonatal transfusion) occurred in two of 62 096 (0.003%) of Rhc-negative women and 2% of late alloimmunisations; moderate HDFN (phototherapy) occurred in 20 children [22.5%; 95% confidence interval (CI), 13.8-31.1%]. Perinatal survival was 100%. The NNS to detect one HDFN case was 2823 (31 048 for severe, 3105 for moderate HDFN). Significant risk factors were former blood transfusion [odds ratio (OR), 10.4; 95% CI, 1.14-94.9], parity (P-1: OR, 11.8; 95% CI, 3.00-46.5; P > 1: OR, 7.77; 95% CI, 1.70-35.4) and amniocentesis/chorionic villus sampling during current pregnancy (OR, 9.20; 95% CI, 1.16-72.9). CONCLUSIONS: Additional screening of Rhc-negative women improved the detection of late alloimmunisation and HDFN, facilitating timely treatment, with a NNS of 2823. Independent risk factors for late alloimmunisation were blood transfusion, parity and chorionic villus sampling/amniocentesis in the current pregnancy. The occurrence of most factors before the current pregnancy suggests a secondary immune response explaining most late alloimmunisations. TWEETABLE ABSTRACT: Third trimester screening for alloimmunisation in Rhc-neg women improves detection and treatment of severe HDFN.

Enfermedad hemolítica perinatal causada por anticuerpos anti-M y tratada con inmunoglobulinas intravenosas fetales / Hemolytic disease of the fetus due to anti-M antibodies treated with fetal intravenous immunoglobulin therapy

Presentamos el caso de una mujer de 28 años, con 2 abortos tardíos previos causados por anticuerpos anti-M. En la actual gestación es tratada desde la semana 23 hasta la semana 34 con inmunoglobulinas intravenosas fetales, con resultado satisfactorio. Aunque no hay estudios randomizados y controlados que indiquen que las inmunoglobulinas fetales son efectivas en el manejo de la isoinmunización, pequeñas series de casos sugieren resultados prometedores (AU)

We present the case of a 28-year-old woman with two prior late miscarriages caused by anti-M antibodies, leading to alloimmunization of her previous pregnancies. During this pregnancy, she was successfully treated with intravenous immunoglobulins administered from the 23th to the 34th week of pregnancy. There are no randomized trials to indicate whether the antenatal use of intravenous immunoglobulin is effective in the management of fetal red blood cell alloimmunization. Several case series suggest a beneficial role in preventing severe fetal anemia (AU)

Non-invasive prenatal diagnosis of fetal RhD by using free fetal DNA.

OBJECTIVE: Anti-D immunoglobulin is applied to all pregnant women having RhD incompatibility to prevent hemolytic disease of the newborn. The aim of this study is to determine fetal RhD status in the Rh incompatible pregnancies with an non-invasive technique; free fetal DNA isolation from maternal circulation. In the case of Rh incompatibility especially with a history of previous fetal anemia, it can be beneficial to know Rh status antenatally in terms of monitoring fetuses with Rh positive [RhD(+)] status consciously. MATERIALS AND METHODS: Total free DNA was isolated in 50 Rh negative [RhD(-)] pregnant women, who had RhD alloimmunisation with their husbands. The gene in isolated DNA was investigated with TagMan prob and real time PCR by using primers belonging to exon 7 of the RhD gene. RESULTS: The authors analyzed 50 RhD(-) women by using quantitative real time PCR technique. Five of them were RhD(-) and the rest of them were found to be RhD(+). After birth one of the infants who were analyzed as RhD(+) were found to be RhD(-). CONCLUSION: The detection of fetal RhD status by using a non-invasive method from maternal circulation was found to be possible. Assessing fetal RhD status non-invasively by using free fetal DNA in maternal blood will be cost-efficient, avoiding unnecessary indirect Coombs test and unnecessary Rhogam applications that is used in RH incompatible pregnancies. This study will throw a fresh light on prenatal diagnosis.