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This systematic review aims to assess the gestational age at birth and perinatal outcome [intrauterine demise (IUD), neonatal mortality and severe cerebral injury] in monochorionic twins with selective fetal growth restriction (sFGR), according to Gratacós classification based on umbilical artery Doppler flow patterns in the smaller twin. Seventeen articles were included. Gestational age at birth varied from 33.0 to 36.0 weeks in type I, 27.6-32.4 weeks in type II, and 28.3-33.8 weeks in type III. IUD rate differed from 0%-4% in type I to 0%-40% in type II and 0%-23% in type III. Neonatal mortality rate was between 0%-10% in type I, 0%-38% in type II, and 0%-17% in type III. Cerebral injury was present in 0%-2% of type I, 2%-30% of type II and 0%-33% of type III cases. The timing of delivery in sFGR varied substantially among studies, particularly in type II and III. The quality of evidence was moderate due to heterogenous study populations with varying definitions of sFGR and perinatal outcome parameters, as well as a lack of consensus on the use of the Gratacós classification, leading to substantial incomparability. Our review identifies the urgent need for uniform antenatal diagnostic criteria and definitions of outcome parameters. ispartof: PRENATAL DIAGNOSIS vol:42 issue:9 pages:1094-1110 ispartof: location:England status: published

Introduction: The aim of this study was to obtain expert consensus on the content of a curriculum for learning chorionic villus sampling (CVS) and amniocentesis (AC) and the items of an assessment tool to evaluate CVS and AC competence. Methods: We used a 3-round iterative Delphi process. A steering committee supervised all processes. Seven international collaborators were identified to expand the breadth of the study internationally. The collaborators invited fetal medicine experts to participate as panelists. In the first round, the panelists suggested content for a CVS/AC curriculum and an assessment tool. The steering committee organized and condensed the suggested items and presented them to the panelists in round 2. In the second round, the panelists rated and commented on the suggested items. The results were processed by the steering committee and presented to the panelists in the third round, where final consensus was obtained. Consensus was defined as support by more than 80% of the panelists for an item. Results: Eighty-six experts agreed to participate in the study. The panelists represented 16 countries across 4 continents. The final list of curricular content included 12 theoretical and practical items. The final assessment tool included 11 items, systematically divided into 5 categories: pre-procedure, procedure, post-procedure, nontechnical skills, and overall performance. These items were provided with behavioral scale anchors to rate performance, and an entrustment scale was used for the final overall assessment. Conclusion: We established consensus among international fetal medicine experts on content to be included in a CVS/AC curriculum and on an assessment tool to evaluate CVS/AC skills. These results are important to help transition current training and assessment methods from a time- and volume-based approach to a competency-based approach which is a key step in improving patient safety and outcomes for the 2 most common invasive procedures in fetal medicine.

Introduction Anti-D alloimmunization is the most common cause of severe hemolytic disease of the fetus and newborn (HDFN). The management of pregnancies affected by less frequent red blood cell (RBC) antibodies poses a challenge to clinicians, and perinatal outcomes are less well described. This study aimed to describe the frequency of clinically significant RBC antibodies in our pregnant population and analyze the risk of prenatal and postnatal treatment for HDFN in relation to our national risk classification system and management guidelines. Material and methods A retrospective cohort study in the population of all alloimmunized singleton pregnancies in the Stockholm region 1990-2016. Descriptive summaries of different RBC antibodies and pregnancy outcomes were presented, the risks of intrauterine blood transfusion (IUT) and neonatal treatment for HDFN were estimated by type of antibodies. Results Of the 1724 alloimmunized pregnancies, 1079 (63%) were at risk of HDFN and constituted our study cohort. Anti-D was detected in 492 (46%) pregnancies, followed by anti-E in 161 (15%), and anti-c in 128 (12%). Eighty-seven (8%) pregnancies had IUT, with the highest risk in pregnancies affected by anti-D combined with other antibodies. The maximum titer recorded before IUT was 64 or above, except for two pregnancies affected by anti-c, for which the maximum titers were 8 and 16. For the 942 (95%) live-born neonates from 992 alloimmunized pregnancies without IUT, the median gestational age at birth was 38+5 weeks compared with 35+5 weeks for those who had IUT. Neonatal treatment was most common in the anti-D alone and anti-D combined groups, with 136 (57%) and 21 (44%), respectively, treated with phototherapy and 35 (15%) and 9 (20%) receiving exchange transfusions, respectively. For pregnancies complicated by moderate- and low-risk antibodies, phototherapy was less frequent (32 [36%] and 21 [19%]) and exchange transfusion was rare (5 [6%] and 3 [3%]). Conclusions Anti-D, especially in combination with other antibodies, presents the highest risk of severe HDFN. The classification of less frequent and less well-known RBC antibodies into risk groups can help clinicians in assessing the risk of HDFN and counseling alloimmunized pregnant women regarding the risk of prenatal and postnatal treatments.

Objective To estimate the incidence of cholestasis in neonates with hemolytic disease of the fetus and newborn (HDFN) and investigate risk factors and long-term liver disease. Study design A population-based cohort study of all infants born with HDFN within the Stockholm region between 2006 and 2015. The study period was the first 90 days of life, and presence of any chronic liver disease was evaluated at two years of age. Results Cholestasis occurred in 7% (11/149). Median age at detection was 1.1 days. Intrauterine blood transfusions and maternal alloimmunization with multiple red blood cell antibodies including D-, c- or K-antibodies were independent risk factors for cholestasis. No infant had chronic liver disease at two years of age. Conclusions Infants with severe HDFN have increased risk for cholestasis, particularly those requiring multiple intrauterine transfusions. Early and repeated screening for conjugated hyperbilirubinemia in the first week of life is needed to ensure adequate management.

Purpose To retrospectively investigate perinatal outcome of monoamniotic twin pregnancies in a tertiary center during a 10 year period. Methods A retrospective analysis of all monoamniotic pregnancies managed at Karolinska University Hospital, Stockholm, Sweden 2010–2019 was performed. The primary outcomes were live birth rate, neonatal death and perinatal survival. The secondary outcomes were late miscarriage, gestational age at delivery and frequency of fetal complications. Results Twenty-two monoamniotic pregnancies, with 44 fetuses, were identified. Thirty-five of 44 fetuses (80%) were liveborn. Of 36 fetuses reaching 24 weeks gestation, 35 (97%) were liveborn. There were no neonatal deaths, thus the perinatal survival was 97%. The mean gestational age at birth was 32.5 weeks (SD ± 1.5). Conclusions The live birth rate and perinatal survival of monoamniotic pregnancies managed at Karolinska University Hospital was high and comparable to previously published data.

Background: Twin anemia polycythemia sequence is a chronic form of unbalanced fetofetal transfusion through minuscule placental anastomoses in monochorionic twins, leading to anemia in the donor and polycythemia in the recipient. Owing to the low incidence of twin anemia polycythemia sequence, data on diagnosis, management, and outcome are limited. Objective: This study aimed to investigate the diagnosis, management, and outcome in a large international cohort of spontaneous twin anemia polycythemia sequence. Study Design: Data from the international twin anemia polycythemia sequence registry, retrospectively collected between 2014 and 2019, were used for this study. A total of 17 fetal therapy centers contributed to the data collection. The primary outcomes were perinatal mortality and severe neonatal morbidity. Secondary outcomes included a risk factor analysis for perinatal mortality and severe neonatal morbidity. Results: A total of 249 cases of spontaneous twin anemia polycythemia sequence were included in this study, 219 (88%) of which were diagnosed antenatally and 30 (12%) postnatally. Twin anemia polycythemia sequence was diagnosed antenatally at a median gestational age of 23.7 weeks (interquartile range, 9.7–28.8; range, 15.1–35.3). Antenatal management included laser surgery in 39% (86 of 219), expectant management in 23% (51 of 219), delivery in 16% (34 of 219), intrauterine transfusion (with partial exchange transfusion) in 12% (26 of 219), selective feticide in 8% (18 of 219), and termination of pregnancy in 1% (3 of 219) of cases. Perinatal mortality rate was 15% (72 of 493) for the total group, 22% (54 of 243) for donors, and 7% (18 of 242) for recipients (P, SCOPUS: ar.j, info:eu-repo/semantics/published

Objective To investigate the antenatal management and outcome in a large international cohort of monochorionic twin pregnancies with spontaneous or post‐laser twin anemia–polycythemia sequence (TAPS). Methods This study analyzed data of monochorionic twin pregnancies diagnosed antenatally with spontaneous or post‐laser TAPS in 17 fetal therapy centers, recorded in the TAPS Registry between 2014 and 2019. Antenatal diagnosis of TAPS was based on fetal middle cerebral artery peak systolic velocity > 1.5 multiples of the median (MoM) in the TAPS donor and, This article's abstract has been translated into Spanish and Chinese. Follow the links from the abstract to view the translations. A video abstract of this article is available online here.

Problem Circulating B-cell numbers are lower during pregnancy compared with non-pregnant women, but the underlying reasons for this are unknown. Pregnancy-related hormones could influence B-cell lymphopoiesis in the bone marrow, but B cells may also be recruited to the placenta. To investigate the latter, we examined whether the proportions of total B cells and B cells at different maturational stages in placental intervillous blood (IVB) differ compared with peripheral blood (PB). Method of study From 23 paired samples of PB and IVB following full-term healthy pregnancies, total B cells and immature/transitional, mature/naive, and memory B cells were identified by flow cytometry. Chemokine levels in blood were analyzed using a Luminex assay. Placental explant-derived supernatant was assayed for B-cell chemotactic activity. Results The proportions of total B cells and mature/naive B cells were significantly higher in IVB relative to PB, while the fractions of immature/transitional cells and memory B cells were higher in PB. Multivariate factor analysis demonstrated that a specific chemokine profile in IVB, including CCL20, positively associated with higher proportions of mature/naive B cells in the intervillous space. All B cells expressed CCR6, the corresponding receptor for CCL20, but the intensity of CCR6 expression was significantly higher in mature/naive B cells relative to immature/transitional B cells. Migration assays showed that placental explant-derived supernatants attract B cells. Conclusion These results indicate that B cells, and mature/naive B cells in particular, are retained in the intervillous blood in response to certain chemokines produced by the placenta during late healthy pregnancy.

Objective To estimate the cost-effectiveness of first trimester non-invasive fetal RHD screening for targeted antenatal versus no routine antenatal anti-D prophylaxis (RAADP) or versus non-targeted RAADP. Design Model based on a population-based cohort study. Setting The Swedish health service. Population Intervention subjects in the underlying cohort study were RhD-negative pregnant women receiving first trimester fetal RHD screening followed by targeted anti-D in 2010–2011 (n = 6723). Historical comparators were RhD-negative women who delivered in 2008–2009 when standard care did not include RAADP (n = 7099). Methods Healthcare costs for the three strategies were included for the first and subsequent pregnancies. For the comparison with non-targeted RAADP, the immunisation rate was based on the observed rate for targeted therapy and adjusted downwards by removing the influence of false negatives. Main outcome measure Additional cost per RhD immunisation averted. Results Compared with RAADP, targeted prophylaxis was associated with fewer immunisations (0.19 versus 0.46% per pregnancy) and lower costs (cost-savings of €32 per RhD-negative woman). The savings were from lower costs during pregnancy and delivery, and lower costs of future pregnancies through fewer immunisations. Non-targeted anti-D was estimated to result in 0.06% fewer immunisations and an additional €16 in cost-savings per mother, compared with targeted anti-D. Conclusion Based on effect data from a population-based cohort study, targeted prophylaxis was associated with lower immunisation risk and costs versus no RAADP. Based on effect data from theoretical calculations, non-targeted RAADP was predicted to result in lower costs and immunisation risk compared with targeted prophylaxis. Tweetable abstract Fetal RHD screening and targeted prophylaxis resulted in lower immunisation risk and costs compared with no RAADP.

Objective To evaluate the effect of a newly developed training curriculum on the performance of fetoscopic laser surgery for twin–twin transfusion syndrome (TTTS) using an advanced high-fidelity simulator model. Methods Ten novices were randomized to receive verbal instructions and either skills training using the simulator (study group; n = 5) or no training (control group; n = 5). Both groups were evaluated with a pre-training and post-training test on the simulator. Performance was assessed by two independent observers and comprised a 52-item checklist for surgical performance (SP) score, measurement of procedure time and number of anastomoses missed. Eleven experts set the benchmark level of performance. Face validity and educational value of the simulator were assessed using a questionnaire. Results Both groups showed an improvement in SP score at the post-training test compared with the pre-training test. The simulator-trained group significantly outperformed the control group, with a median SP score of 28 (54%) in the pre-test and 46 (88%) in the post-test vs 25 (48%) and 36 (69%), respectively (P = 0.008). Procedure time decreased by 11 min (from 44 to 33 min) in the study group vs 1 min (from 39 to 38 min) in the control group (P = 0.69). There was no significant difference in the number of missed anastomoses at the post-training test between the two groups (1 vs 0). Subsequent feedback provided by the participants indicated that training on the simulator was perceived as a useful educational activity. Conclusions Proficiency-based simulator training improves performance, indicated by SP score, for fetoscopic laser therapy. Despite the small sample size of this study, practice on a simulator is recommended before trainees carry out laser therapy for TTTS in pregnant women. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Objective. To describe the establishment of the fetoscopic guided laser occlusion (FLOC) technique for treatment of twin-to-twin transfusion syndrome (TTTS) and the initial results in a Swedish national center. Design. Retrospective, descriptive study. Setting. Tertiary level university hospital. Population. All referred and treated cases suffering significant TTTS. Methods. The present study includes all cases of FLOC for TTTS at the Center of Fetal Medicine at Karolinska University Hospital, Stockholm, Sweden from October 2001 until December 2009. Patients were referred from all over Sweden and a few from other Nordic countries. The patients were evaluated with ultrasound examination between gestational ages of 18 and 26 weeks. Data from patients were extracted from our electronic medical record system and, in addition, families were contacted and medical records requested from referring hospitals. Main outcome measures. Pregnancies with one or more surviving infants after FLOC treatment categorized according to stage of TTTS. Results. In 75% of pregnancies, one or more infant was born alive. At stage I, both infants survived in one pregnancy and one survived in the second. There was no significant difference between cases at stage II or III, i.e. 73 vs. 78% of pregnancies resulted in one or more surviving infant. At stage IV, 66% of pregnancies ended with one or more surviving infant. Conclusions. Treatment of TTTS is feasible in a rather small country like Sweden, with comparable results to other centers. There are strong arguments for centralization and further improvement of this kind of highly specialized treatment.

Objective We present a pharmacokinetic study evaluating a single intramuscular dose of 250 μg anti-D immunoglobulin in the third trimester of pregnancy. The aim of the study was to determine the kinetic profile and duration of detectable levels of anti-D. Design Prospective observational study. Setting Antenatal outpatient clinic. Population Healthy Rhesus D (RhD)-negative pregnant women with an RHD-positive fetus. Methods Serial plasma anti-D quantitations following antenatal administration of anti-D immunoglobulin were performed using flow cytometry. Kinetic profiles for anti-D levels were generated from the concentration values at predetermined sampling time points. The half-lives were calculated by linear regression analysis. Main outcome measures. Time vs. concentration profile, half-life and anti-D concentration ≥1 ng/mL close to term. Results The maximal plasma concentration of anti-D was usually seen at 3-10 days postinjection, with a median value of 25 ng/mL. The half-life varied between individuals, with a median of 23 days. We found detectable levels of anti-D IgG within two weeks of parturition in 11 of 12 women. Conclusions The preparation of anti-D immunoglobulin used in the present study, if administrated in pregnancy week 28-30, is associated with detectable levels of anti-D in most women at the time of delivery. Although the half-time is 23 days, it is uncertain whether all mothers have adequate anti-D concentrations at term. Alternative strategies may be evaluated in the future, with repeated administration of antenatal prophylaxis at term rather than conventional postpartum administration of anti-D.

Introduction: We present a review of all cases of intravascular transfusions in red cell alloimmunization over a time span of 20 years in Stockholm. The aim of the study is to compare our results with published results from larger centers and to identify areas that can be further improved. Material and Methods: A retrospective cohort study was conducted of all women treated with intrauterine transfusions due to erythrocyte immunization in our hospital between June 1990 and June 2010. Primary outcome variables were fetal and neonatal survival, procedure-related complications and gestational age at delivery. Results: A total of 284 intrauterine transfusions were performed in 84 pregnancies, with an overall survival rate of 91.8%. Procedure-related and fatal complications occurred in the present study in 4.9 and 1.4% of fetuses or neonates, respectively. Procedure-related complications were significantly more common in free-loop transfusions than in transfusions in the intrahepatic part of the umbilical vein (OR: 5.4, p = 0.025). There was no significant difference between the intrahepatic and the placental cord insertion route (p = 0.83). Gestational age at first transfusion was significantly associated with an increased risk of a procedure-related complication (OR: 0.8, p = 0.019). Of the live-born infants, 24% of the neonates were born before gestational week 34. Discussion: Our study confirms previous studies demonstrating favorable results with intravascular transfusions.

BACKGROUND: Intrauterine transfusion for severe alloimmunization in pregnancy performed

Objective To determine pregnancy outcomes of patients who present with Stage I twin-to-twin transfusion syndrome (TTTS). Methods This was a retrospective review of all patients with TTTS referred to our institution between January 2005 and December 2006. Quintero criteria were used for staging. Laser ablation was not offered to patients with Stage I disease. Results A total of 155 twin pregnancies were evaluated for TTTS during this period. Forty-two met the criteria for Stage I and were included in the analysis. The overall survival to discharge was 82%. The mean gestational age at the time of consultation was 20.9 ± 0.4 weeks. A total of 23 cases (54.8%) underwent amnioreduction. Progression of TTTS requiring invasive therapy occurred in four cases. The mean gestational age at delivery was 32.5 ± 0.62 weeks. When divided according to use of amnioreduction, there were no statistically significant differences between the groups for gestational age at delivery or for birth weight. Those Stage I cases with a CHOP cardiovascular score of 5 or higher delivered almost 3 weeks earlier than the remainder of the cohort. Conclusions Progression of TTTS beyond Stage I occurred in only 9.5% of the cohort. Mean gestational age at delivery and survival to discharge did not differ between Stage I patients and those treated with placental laser ablation for more advanced stages of TTTS. Copyright © 2010 ISUOG. Published by John Wiley & Sons, Ltd.

Fetal stem-cell transplantation is an attractive approach to the treatment of a variety of hematological, metabolic and immunological diseases before birth. The possibility of delivering a large number of cells in an early stage of life, and of taking advantage of normal fetal stem-cell migration and development, is promising. During fetal life, the capacity to mount an immune response to allogeneic cells is impaired compared with adult life. This provides an opportunity to induce tolerance to alloantigens without the need for myeloablation, although there are possible immune barriers to foreign cells in the fetus.

Objective To describe the outcome of children prenatally diagnosed with omphalocele, exstrophy of the cloaca, imperforate anus and spinal defects (OEIS). Method A retrospective study identified six fetuses diagnosed with OEIS from 2001 to 2007 and data were collected from pre- and postnatal charts. Results Prenatal findings included an infraumbilical wall defect, omphalocele, no visible bladder and spinal defects. Abnormalities of the upper urinary tract were seen in all cases and ambiguous genitalia in four. Four women continued the pregnancy after prenatal counseling and these fetuses were liveborn at a mean gestational age of 36 weeks. Postnatal evaluation confirmed the prenatal findings in the neonates. The children have required multiple surgeries. Common complications are recurrent urinary tract infections and failure to thrive. Neurodevelopment and motor function are normal in all children, except for one child with lower extremity paralysis and global developmental delay. Conclusion Prenatal diagnosis of OEIS is reliable and no significant differences in pre- and postnatal findings in the children were found. Correct diagnosis of abnormalities of external and internal genitalia remains a challenge and abnormalities of the upper urinary tract are common. Postnatal survival is good but associated with considerable morbidity and psychosocial consequences. Copyright © 2008 John Wiley & Sons, Ltd.

Background. This is a descriptive study of the management and outcome of 18 cases of fetomaternal alloimmune thrombocytopenia (FMAIT) treated from 1991 to 2001. Material and methods. Management of the disease changed over the years from cordocentesis in the 20-24th week of gestation, platelet transfusions and immunoglobulin to a less invasive management consisting of only blind administration of immunoglobulin and predelivery cordocentesis. Results. Three of the fetuses were treated with intrauterine platelet transfusions. Two of these were delivered by emergency cesarean section due to failed transfusions and the third fetus died as a result of the procedure. Nine mothers were treated with immunoglobulin intravenously. Four of these delivered thrombocytopenic children. Three women did not want to undergo any treatment, and all newborns had low platelet counts. Two fetuses died, one in conjunction with a platelet transfusion and the other in utero before treatment was commenced. All the other children did...

Objective: Pregnancies at risk of fetal and neonatal alloimmune thrombocytopenia (FNAIT) are commonly treated using weekly intravenous immunoglobulin (IVIG) at 1 g/kg maternal weight. IVIG is an expensive multidonor human blood product with dose-related side effects. Our aim was to evaluate the effectiveness of IVIG at a lower dose, i.e. 0.5 g/kg. Methods: This was a randomized controlled multicenter trial conducted in Sweden, the Netherlands and Australia. Pregnant women with human platelet antigen alloantibodies and an affected previous child without intracranial hemorrhage (ICH) were enrolled. The participants were randomized to IVIG at 0.5 or 1 g/kg per week. The analyses were per intention to treat. The primary outcome was fetal or neonatal ICH. Secondary outcomes were platelet count at birth, maternal and neonatal IgG levels, neonatal treatment and bleeding other than ICH. Results: A total of 23 women were randomized into two groups (low dose: n = 12; standard dose: n = 11). The trial was stopped early due to poor recruitment. No ICH occurred. The median newborn platelet count was 81 × 109/l (range 8-269) in the 0.5 g/kg group versus 110 × 109/l (range 11-279) in the 1 g/kg group (p = 0.644). Conclusion: The risk of adverse outcomes in FNAIT pregnancies treated with IVIG at 0.5 g/kg is very low, similar to that using 1 g/kg, although our uncompleted trial lacked the power to conclusively prove the noninferiority of using the low dose.

Objective To estimate the incidence of RhD immunisation after implementation of first trimester non-invasive fetal RHD screening to select only RhD negative women carrying RHD positive fetuses for routine antenatal anti-D prophylaxis (RAADP). Materials and Methods We present a population-based prospective observational cohort study with historic controls including all maternity care centres and delivery hospitals in the Stockholm region, Sweden. All RhD negative pregnant women were screened for fetal RHD genotype in the first trimester of pregnancy. Anti-D immunoglobulin (250–300 µg) was administered intramuscularly in gestational week 28–30 to participants with RHD positive fetuses. Main outcome measure was the incidence of RhD immunisation developing during or after pregnancy. Results During the study period 9380 RhD negative women gave birth in Stockholm. Non-invasive fetal RHD genotyping using cell-free fetal DNA in maternal plasma was performed in 8374 pregnancies of which 5104 (61%) were RHD positive and 3270 (39%) RHD negative. In 4590 pregnancies with an RHD positive test the women received antenatal anti-D prophylaxis. The incidence of RhD immunisation in the study cohort was 0.26 percent (24/9380) (95% CI 0.15–0.36%) compared to 0.46 percent (86/18546) (95% CI 0.37 to 0.56%) in the reference cohort. The risk ratio (RR) for sensitisation was 0.55 (95% CI 0.35 to 0.87) and the risk reduction was statistically significant (p = 0.009). The absolute risk difference was 0.20 percent, corresponding to a number needed to treat (NNT) of 500. Conclusions Using first trimester non-invasive antenatal screening for fetal RHD to target routine antenatal anti-D prophylaxis selectively to RhD negative women with RHD positive fetuses significantly reduces the incidence of new RhD immunisation. The risk reduction is comparable to that reported in studies evaluating the outcome of non selective RAADP to all RhD negative women. The cost-effectiveness of this targeted approach remains to be studied.

Objective To analyze the timing of Rhesus D (RhD) immunization in pregnancy and the consequences for the index pregnancy and for subsequent pregnancies to be able to optimize the design of antenatal screening and prevention programs. Design Retrospective cohort study. Setting Stockholm county, Sweden. Population All RhD immunized pregnant women 1990–2008 before the introduction of routine antenatal anti-D prophylaxis. Methods Data were collected from transfusion medicine registers and databases, medical records, the Swedish Medical Birth Register and the National Perinatal Quality Register and entered into a standardized database before analysis. Main outcome measures The order of pregnancy and trimester when immunization occurred and treatment of hemolytic disease of the fetus and newborn. Results A total of 290 RhD immunized women were included in the study. In 147/290 (51%) of the women, sensitization occurred with their first-born child and in 96/290 (33%) it occurred with their second-born child. Anti-D antibodies developed during the second or third trimester in 212/290 (73%) and in 61/290 (21%) at term or after delivery. In subsequent pregnancies 56% (144/259) of the neonates required treatment for hemolytic disease of the fetus and newborn. Conclusions Based on our study, at least half of the cases could potentially have been avoided by routine antenatal anti-D prophylaxis in the beginning of the third trimester. To optimize the beneficial effects of new prevention programs, we propose providing anti-D prophylaxis in gestational week 28–30 selectively to all RhD-negative women with RhD-positive fetuses.

OBJECTIVE: To develop a simple and robust assay suitable for fetal RHD screening in first-trimester pregnancy and to estimate the sensitivity and specificity of the test after its implementation in an unselected pregnant population. METHODS: Pregnant women attending their first antenatal visit were included, and fetal RHD determination was performed for all women who typed RhD-negative by routine serology. DNA was extracted by an automated system and quantitative polymerase chain reaction was done by an assay based on exon 4. Reporting criteria were simple and strict. RESULTS: Four thousand one hundred eighteen pregnancies, with a median gestational age of 10 weeks, were included. After 211 (5.1%) reanalyses, fetal RHD was reported positive in 2,401 (58.3%), negative in 1,552 (37.7%), and inconclusive in 165 (4.0%) based on the first sample. After a second sample in 147 of 165, only 14 remained inconclusive, all resulting from a weak or silent maternal RHD gene. Using blood group serology of the newborns as the gold standard, the false-negative rate was 55 of 2,297 (2.4%) and the false-positive rate was 15 of 1,355 (1.1%). After exclusion of samples obtained before gestational week 8, the false-negative rate was 23 of 2,073 (1.1%) and the false-positive rate was 14 of 1,218 (1.1%). Both sensitivity and specificity were close to 99% provided samples were not collected before gestational week 8. From gestational week 22, sensitivity was 100%. CONCLUSION: : Fetal RHD detection in early pregnancy using a single-exon assay in a routine clinical setting is feasible and accurate. LEVEL OF EVIDENCE: : I. (Less)