RESUMO
BACKGROUND: In early-onset severe hemolytic disease of the fetus and newborn (HDFN), transplacental transfer of maternal antierythrocyte IgG alloantibodies causes fetal anemia that leads to the use of high-risk intrauterine transfusions in order to avoid fetal hydrops and fetal death. Nipocalimab, an anti-neonatal Fc receptor blocker, inhibits transplacental IgG transfer and lowers maternal IgG levels. METHODS: In an international, open-label, single-group, phase 2 study, we assessed treatment with intravenous nipocalimab (30 or 45 mg per kilogram of body weight per week) administered from 14 to 35 weeks' gestation in participants with pregnancies at high risk for recurrent early-onset severe HDFN. The primary end point was live birth at 32 weeks' gestation or later without intrauterine transfusions as assessed against a historical benchmark (0%; clinically meaningful difference, 10%). RESULTS: Live birth at 32 weeks' gestation or later without intrauterine transfusions occurred in 7 of 13 pregnancies (54%; 95% confidence interval, 25 to 81) in the study. No cases of fetal hydrops occurred, and 6 participants (46%) did not receive any antenatal or neonatal transfusions. Six fetuses received an intrauterine transfusion: five fetuses at 24 weeks' gestation or later and one fetus before fetal loss at 22 weeks and 5 days' gestation. Live birth occurred in 12 pregnancies. The median gestational age at delivery was 36 weeks and 4 days. Of the 12 live-born infants, 1 received one exchange transfusion and one simple transfusion and 5 received only simple transfusions. Treatment-related decreases in the alloantibody titer and IgG level were observed in maternal samples and cord blood. No unusual maternal or pediatric infections were observed. Serious adverse events were consistent with HDFN, pregnancy, or prematurity. CONCLUSIONS: Nipocalimab treatment delayed or prevented fetal anemia or intrauterine transfusions, as compared with the historical benchmark, in pregnancies at high risk for early-onset severe HDFN. (Funded by Janssen Research and Development; UNITY ClinicalTrials.gov number, NCT03842189.).
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Anticorpos Monoclonais Humanizados , Transfusão de Sangue Intrauterina , Eritroblastose Fetal , Imunoglobulina G , Humanos , Feminino , Gravidez , Recém-Nascido , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Adulto , Imunoglobulina G/sangue , Transfusão de Sangue Intrauterina/efeitos adversos , Nascido Vivo , Isoanticorpos/sangue , Receptores Fc , Idade Gestacional , Antígenos de Histocompatibilidade Classe IRESUMO
BACKGROUND: Artificial intelligence (AI) is becoming increasingly used in medical education, but our understanding of the validity of AI-based assessments (AIBA) as compared with traditional clinical expert-based assessments (EBA) is limited. In this study, the authors aimed to compare and contrast the validity evidence for the assessment of a complex clinical skill based on scores generated from an AI and trained clinical experts, respectively. METHODS: The study was conducted between September 2020 to October 2022. The authors used Kane's validity framework to prioritise and organise their evidence according to the four inferences: scoring, generalisation, extrapolation and implications. The context of the study was chorionic villus sampling performed within the simulated setting. AIBA and EBA were used to evaluate performances of experts, intermediates and novice based on video recordings. The clinical experts used a scoring instrument developed in a previous international consensus study. The AI used convolutional neural networks for capturing features on video recordings, motion tracking and eye movements to arrive at a final composite score. RESULTS: A total of 45 individuals participated in the study (22 novices, 12 intermediates and 11 experts). The authors demonstrated validity evidence for scoring, generalisation, extrapolation and implications for both EBA and AIBA. The plausibility of assumptions related to scoring, evidence of reproducibility and relation to different training levels was examined. Issues relating to construct underrepresentation, lack of explainability, and threats to robustness were identified as potential weak links in the AIBA validity argument compared with the EBA validity argument. CONCLUSION: There were weak links in the use of AIBA compared with EBA, mainly in their representation of the underlying construct but also regarding their explainability and ability to transfer to other datasets. However, combining AI and clinical expert-based assessments may offer complementary benefits, which is a promising subject for future research.
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Competência Clínica , Educação Médica , Humanos , Avaliação Educacional , Inteligência Artificial , Reprodutibilidade dos TestesRESUMO
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.
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Morte Perinatal , Gravidez de Gêmeos , Gravidez , Recém-Nascido , Feminino , Humanos , Lactente , Resultado da Gravidez/epidemiologia , Estudos Retrospectivos , Cuidado Pré-Natal , Parto , Idade Gestacional , Gêmeos MonozigóticosRESUMO
BACKGROUND AND OBJECTIVES: Anti-D prophylaxis, administered to RhD-negative women, has significantly reduced the incidence of RhD immunization. Non-invasive fetal RHD screening has been used in Stockholm for more than 10 years to identify women who will benefit from prophylaxis. The method is based on a single-exon approach and is used in early pregnancy. The aim of this study was to update the performance of the method. MATERIALS AND METHODS: The single exon assay from Devyser AB is a multiplex kit detecting both exon 4 of the RHD gene and the housekeeping gene GAPDH. Cell-free DNA was extracted from 1 ml of plasma from EDTA blood taken during early pregnancy, weeks 10-12. The genetic RHD results were compared with serological typing of newborns for a determination of sensitivity and specificity. RESULTS: In total, 4337 pregnancies were included in the study; 44 samples (1%) were inconclusive either due to maternal RHD gene variants (n = 34) or technical reasons (n = 10). Of the remaining 4293 pregnancies, a total number of nine discrepant results were found. False positive results (n = 7) were mainly (n = 4) due to RHD gene variants in the child. False-negative results were found in two cases, of which one was caused by a technical error. None of the false-negative cases was due to RHD gene variants. Overall, the sensitivity of the method was 99.93% and specificity 99.56%. CONCLUSION: The single-exon assay used in this study is correlated with high sensitivity and specificity.
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Ácidos Nucleicos Livres , Sistema do Grupo Sanguíneo Rh-Hr , Gravidez , Criança , Recém-Nascido , Feminino , Humanos , Sistema do Grupo Sanguíneo Rh-Hr/genética , Diagnóstico Pré-Natal/métodos , Éxons/genética , Sensibilidade e Especificidade , GenótipoRESUMO
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.
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Retardo do Crescimento Fetal , Gêmeos Monozigóticos , Doenças em Gêmeos , Feminino , Retardo do Crescimento Fetal/diagnóstico por imagem , Idade Gestacional , Humanos , Recém-Nascido , Gravidez , Gravidez de Gêmeos , Estudos Retrospectivos , Ultrassonografia Pré-Natal , Artérias Umbilicais/diagnóstico por imagemRESUMO
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<.001). Severe neonatal morbidity occurred in 33% (141 of 432) of twins with twin anemia polycythemia sequence and was similar for donors (32%; 63 of 196) and recipients (33%; 75 of 228) (P=.628). Independent risk factors for spontaneous perinatal mortality were donor status (odds ratio, 3.8; 95% confidence interval, 1.9-7.5; P<.001), antenatal twin anemia polycythemia sequence stage (odds ratio, 6.3; 95% confidence interval, 1.4-27.8; P=.016 [stage 2]; odds ratio, 9.6; 95% confidence interval, 2.1-45.5; P=.005 [stage 3]; odds ratio, 20.9; 95% confidence interval, 3.0-146.4; P=.002 [stage 4]), and gestational age at birth (odds ratio, 0.8; 95% confidence interval, 0.7-0.9; P=.001). Independent risk factors for severe neonatal morbidity were antenatal twin anemia polycythemia sequence stage 4 (odds ratio, 7.9; 95% confidence interval, 1.4-43.3; P=.018) and gestational age at birth (odds ratio, 1.7; 95% confidence interval, 1.5-2.1, P<.001). CONCLUSION: Spontaneous twin anemia polycythemia sequence can develop at any time in pregnancy from the beginning of the second trimester to the end of the third trimester. Management for twin anemia polycythemia sequence varies considerably, with laser surgery being the most frequent intervention. Perinatal mortality and severe neonatal morbidity were high, the former especially so in the donor twins.
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Transfusão de Sangue Intrauterina , Terapias Fetais , Transfusão Feto-Fetal/terapia , Idade Gestacional , Terapia a Laser , Mortalidade Perinatal , Conduta Expectante , Aborto Induzido , Anemia/diagnóstico , Anemia/terapia , Peso ao Nascer , Infarto Cerebral/epidemiologia , Hemorragia Cerebral Intraventricular/epidemiologia , Estudos de Coortes , Parto Obstétrico , Permeabilidade do Canal Arterial/epidemiologia , Permeabilidade do Canal Arterial/terapia , Enterocolite Necrosante/epidemiologia , Feminino , Retardo do Crescimento Fetal/epidemiologia , Transfusão Feto-Fetal/diagnóstico , Humanos , Recém-Nascido , Internacionalidade , Leucomalácia Periventricular/epidemiologia , Masculino , Policitemia/diagnóstico , Policitemia/terapia , Gravidez , Redução de Gravidez Multifetal , Surfactantes Pulmonares/uso terapêutico , Respiração Artificial , Síndrome do Desconforto Respiratório do Recém-Nascido/epidemiologia , Síndrome do Desconforto Respiratório do Recém-Nascido/terapia , Retinopatia da Prematuridade/epidemiologia , Fatores de Risco , Índice de Gravidade de DoençaRESUMO
BACKGROUND AND OBJECTIVE: Routine antenatal anti-D prophylaxis (RAADP) to RhD-negative women is most often administered in gestational age (GA) 28-30 weeks with the next anti-D dose administered postpartum. The aim of this study was to analyse the proportion of RhD-negative women where RAADP is not detectable at term and in a pilot study to investigate whether RAADP administered in GA 28 and 38 results in detectable levels at term, post-term and post-delivery. MATERIALS AND METHODS: In a retrospective analysis, 4280 RhD-negative women carrying an RHD positive fetus were included and the proportion with a negative antibody screen at delivery was determined. In the second part, 39 pregnancies were included prospectively, a second dose of RAADP was administered in GA 38 weeks, and anti-D was quantified before the second dose and then weekly for 5 weeks. RESULTS: In the retrospective analysis, 20·5% (856/4280) with RAADP administered in GA 28 were negative in routine antibody screening at delivery. In the small prospective study, 18% (7/39) had a negative antibody screen and 26% (10/39) had levels below 0·005 IU/ml, in the quantification assay, in GA 38. Anti-D prophylaxis administered in GA 38 showed detectable levels of anti-D up to 30 days post-delivery, with concentration at delivery 0·060 ± 0·034 IU/ml (mean ± SD). CONCLUSION: Approximately 20% of the RhD-negative women show non-detectable levels of anti-D at term. A second dose of RAADP at GA 38 results in stable concentrations of anti-D at term, post-term and post-delivery, but with large interindividual variation.
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Isoimunização Rh , Feminino , Humanos , Lactente , Projetos Piloto , Gravidez , Resultado da Gravidez , Estudos Prospectivos , Estudos Retrospectivos , Sistema do Grupo Sanguíneo Rh-Hr , Imunoglobulina rho(D)RESUMO
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.
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Eritroblastose Fetal/diagnóstico , Eritrócitos/imunologia , Cuidado Pré-Natal , Transfusão de Sangue Intrauterina , Estudos de Coortes , Eritroblastose Fetal/terapia , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Isoanticorpos , Gravidez , Estudos RetrospectivosRESUMO
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.
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Amniocentese , Amostra da Vilosidade Coriônica , Amostra da Vilosidade Coriônica/efeitos adversos , Consenso , Feminino , Humanos , GravidezRESUMO
BACKGROUND: Intrauterine transfusion for severe alloimmunization in pregnancy performed <20 weeks' gestation is associated with a higher fetal death rate. Intravenous immunoglobulins may prevent hemolysis and could therefore be a noninvasive alternative for early transfusions. OBJECTIVE: We evaluated whether maternal treatment with intravenous immunoglobulins defers the development of severe fetal anemia and its consequences in a retrospective cohort to which 12 fetal therapy centers contributed. STUDY DESIGN: We included consecutive pregnancies of alloimmunized women with a history of severe hemolytic disease and by propensity analysis compared index pregnancies treated with intravenous immunoglobulins (n = 24) with pregnancies managed without intravenous immunoglobulins (n = 28). RESULTS: In index pregnancies with intravenous immunoglobulin treatment, fetal anemia developed on average 15 days later compared to previous pregnancies (8% less often <20 weeks' gestation). In pregnancies without intravenous immunoglobulin treatment anemia developed 9 days earlier compared to previous pregnancies (10% more <20 weeks), an adjusted 4-day between-group difference in favor of the immunoglobulin group (95% confidence interval, -10 to +18; P = .564). In the subcohort in which immunoglobulin treatment was started <13 weeks, anemia developed 25 days later and 31% less <20 weeks' gestation (54% compared to 23%) than in the previous pregnancy. Fetal hydrops occurred in 4% of immunoglobulin-treated pregnancies and in 24% of those without intravenous immunoglobulin treatment (odds ratio, 0.03; 95% confidence interval, 0-0.5; P = .011). Exchange transfusions were given to 9% of neonates born from pregnancies with and in 37% without immunoglobulin treatment (odds ratio, 0.1; 95% confidence interval, 0-0.5; P = .009). CONCLUSION: Intravenous immunoglobulin treatment in mothers pregnant with a fetus at risk for hemolytic disease seems to have a potential clinically relevant, beneficial effect on the course and severity of the disease. Confirmation in a multicenter randomized trial is needed.
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Anemia Hemolítica/prevenção & controle , Eritroblastose Fetal/terapia , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Adulto , Anemia Hemolítica/terapia , Transfusão de Sangue Intrauterina , Progressão da Doença , Intervenção Médica Precoce , Transfusão Total/estatística & dados numéricos , Feminino , Doenças Fetais/terapia , Humanos , Hidropisia Fetal/prevenção & controle , Recém-Nascido , Masculino , Razão de Chances , Gravidez , Primeiro Trimestre da Gravidez , Segundo Trimestre da Gravidez , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de TempoRESUMO
BACKGROUND: The optimal strategy to monitor RhD-immunized pregnancies is not evident. Whether a quantitative analysis of anti-D antibodies adds valuable information to anti-D titre is unclear. The aim of this study was to evaluate the relevance of anti-D quantification in routine monitoring of RhD-immunized pregnancies. MATERIALS AND METHODS: In a retrospective study, 64 consecutive pregnancies in 61 immunized women with anti-D titre ≥128 at any time during pregnancy were included. According to routine, at titre ≥128, anti-D quantification was performed by flow cytometry and the peak systolic velocity in the middle cerebral artery was measured by ultrasound. Decisions for treatment with intrauterine blood transfusion were based on increased peak systolic velocity in the middle cerebral artery. RESULTS: Increasing anti-D concentrations correlated well to increasing anti-D titres, but at each titre value, there was a large interindividual variation, in the determined anti-D concentration. Intrauterine transfusions were initiated in 35 pregnancies according to algorithms based on ultrasound measurements, at anti-D concentrations of 2·4-619 IU/ml and titre 128-16 000. Sixty pregnancies resulted in a live-born child, three in miscarriage and one in termination of pregnancy. During the perinatal care in the neonatal intensive care unit, thirty-one of the neonates were treated with blood exchange transfusions and/or red cell transfusions and 47 were treated with phototherapy. CONCLUSION: Anti-D quantification does not add further information compared to anti-D titre, in defining a critical level to start monitoring RhD-immunized pregnancies with Doppler ultrasound.
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Monitorização Imunológica/métodos , Resultado da Gravidez/epidemiologia , Isoimunização Rh/sangue , Imunoglobulina rho(D)/sangue , Ultrassonografia Doppler/métodos , Adulto , Feminino , Humanos , Monitorização Imunológica/normas , Gravidez , Isoimunização Rh/diagnóstico por imagem , Isoimunização Rh/epidemiologia , Ultrassonografia Doppler/normasRESUMO
OBJECTIVE: To evaluate the management and outcome of a large international cohort of cases of pregnancies complicated by fetal and neonatal alloimmune thrombocytopenia (FNAIT). METHODS: This was an observational prospective and retrospective cohort study of all cases of FNAIT entered into the international multicentre No IntraCranial Haemorrhage (NOICH) registry during the period of 2001-2010. We evaluated human platelet antigen (HPA) specificity, the antenatal and postnatal interventions performed, and clinical outcome. RESULTS: A total of 615 pregnancies complicated by FNAIT from 10 countries were included. Anti-HPA-1a was the most commonly implicated antibody. Antenatal treatment was administered in 273 pregnancies (44%), varying from intrauterine platelet transfusion to maternal administration of immunoglobulins, steroids, or a combination of those. Intracranial haemorrhage was diagnosed in 23 fetuses or neonates (3.7%). Overall perinatal mortality was 1.14% (n = 7). CONCLUSION: This study presents the largest cohort of cases of FNAIT published. Our data show that antenatal treatment for FNAIT results in favourable perinatal outcome. Over time, in most centres, treatment for FNAIT changed from an invasive to a complete non-invasive procedure.
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Complicações na Gravidez/imunologia , Trombocitopenia Neonatal Aloimune/terapia , Feminino , Humanos , Imunoglobulinas/uso terapêutico , Recém-Nascido , Masculino , Transfusão de Plaquetas , Gravidez , Resultado da Gravidez , Estudos Retrospectivos , Esteroides/uso terapêutico , Resultado do TratamentoRESUMO
BACKGROUND: Intravenous immunoglobulins (IVIGs) are the cornerstone in the treatment of pregnancies at risk for fetal and neonatal alloimmune thrombocytopenia (FNAIT). The most commonly used dose is 1.0 g/kg/week, not based on any dose-finding study. IVIG is an expensive multidonor human blood product with dose-related side effects. Our aim was to describe the amount of severe thrombocytopenia according to two different doses of IVIG. STUDY DESIGN AND METHODS: We performed a cohort study, where two dosage regimes of IVIG were evaluated in the treatment of pregnant women suffering from FNAIT with a previous affected child without intracranial hemorrhage (ICH). Cases, treated with 0.5 or 1.0 g/kg/week, were selected from the international multicenter No IntraCranial Hemorrhage (NOICH) registry. Outcome was neonatal platelet (PLT) count at birth and amount of severe thrombocytopenia. Furthermore the appearance of ICH was analyzed. RESULTS: A total of 109 women were included in the study, 46 in the 0.5 IVIG group and 63 in the 1.0 IVIG group. There was no difference in PLT count at birth (mean, 112 vs. 119; crude difference, 7; confidence interval [CI], -37.4 to 23.7]) and incidence of severe thrombocytopenia (<30 × 10(9) /L; n = 7/46 vs. n = 7/63; odds ratio, 1.43 [CI, 0.46-4.42]). No ICH occurred. CONCLUSION: In pregnancies with FNAIT with a previous affected child without ICH, treatment with IVIG in a weekly dose of 0.5 or 1.0 g/kg results in comparable neonatal PLT count at birth and degree of thrombocytopenia.
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Doenças Fetais/tratamento farmacológico , Imunoglobulinas Intravenosas/administração & dosagem , Imunoglobulinas Intravenosas/uso terapêutico , Trombocitopenia Neonatal Aloimune/tratamento farmacológico , Trombocitopenia/tratamento farmacológico , Estudos de Coortes , Feminino , Humanos , Hemorragias Intracranianas/prevenção & controle , Gravidez , Resultado do TratamentoRESUMO
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 × 10(9)/l (range 8-269) in the 0.5 g/kg group versus 110 × 10(9)/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.
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Doenças Fetais/tratamento farmacológico , Imunoglobulinas Intravenosas/administração & dosagem , Hemorragias Intracranianas/prevenção & controle , Trombocitopenia Neonatal Aloimune/tratamento farmacológico , Adulto , Feminino , Doenças Fetais/diagnóstico , Doenças Fetais/epidemiologia , Humanos , Imunoglobulinas Intravenosas/efeitos adversos , Recém-Nascido , Internacionalidade , Hemorragias Intracranianas/diagnóstico , Hemorragias Intracranianas/epidemiologia , Gravidez , Trombocitopenia Neonatal Aloimune/diagnóstico , Trombocitopenia Neonatal Aloimune/epidemiologia , Adulto JovemRESUMO
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.
Assuntos
Eritroblastose Fetal/prevenção & controle , Cuidado Pré-Natal , Isoimunização Rh/prevenção & controle , Imunoglobulina rho(D)/uso terapêutico , Adulto , Feminino , Humanos , Recém-Nascido , Gravidez , Complicações Hematológicas na Gravidez/prevenção & controle , Terceiro Trimestre da Gravidez , Diagnóstico Pré-Natal , Sistema de Registros , Estudos RetrospectivosRESUMO
Background: Triplet pregnancies carry a high risk of pregnancy-related complications. The primary aim of this study was to describe maternal, pregnancy, and neonatal outcomes in expectantly managed triplet pregnancies in Sweden. The secondary aim was to compare outcomes in expectantly managed triplet pregnancies with triplet pregnancies where fetal reduction had been performed with the only indication to reduce the number of fetuses. Methods: Nationwide cohort study based on linkage of data from three national Swedish registers. Triplet pregnancies with delivery at gestational age ≥ 22+0 weeks between 2014 and 2019 were included. Results: In the main cohort of expectantly managed triplet pregnancies (n = 106), 98% (312/318) of infants were liveborn with a mean gestational age at birth of 32+3 weeks and a mean birthweight of 1,726 g. Nine percent (n = 29) suffered from severe neonatal morbidity, and 4% (n = 12) died during the neonatal period. In the reduced cohort (n = 13 pregnancies), all infants were liveborn (n = 22). Mean gestational age at birth (36+0 weeks) and mean birthweight (2,444 g) were higher than in the expectantly managed cohort (P < 0.01 for both comparisons). There were no cases of severe neonatal morbidity (P = 0.24) or mortality (P = 1.00). Conclusion: Overall neonatal survival from 22+0 weeks of gestation in expectantly managed triplet pregnancies in Sweden was high. Nine out of 10 infants did not suffer from severe neonatal morbidity. Fetal reduction was performed in only a very small number of cases and was associated with higher gestational age at birth and higher birth weight.
Assuntos
Complicações na Gravidez , Gravidez de Trigêmeos , Gravidez , Recém-Nascido , Feminino , Humanos , Lactente , Resultado da Gravidez , Peso ao Nascer , Suécia/epidemiologia , Estudos de Coortes , Complicações na Gravidez/epidemiologia , Estudos RetrospectivosRESUMO
During pregnancy, maternal blood circulates through the intervillous space of the placenta and the reciprocal interactions between foetal tissues and maternal immune cells makes the intervillous space a unique immunological niche. Labour is characterised by a proinflammatory response in the myometrium, but the relationship between local and systemic changes during the onset of labour remains elusive. We here aimed to investigate how the systemic and intervillous circulatory systems are affected during labour from an immunological point of view. We report that the proportion of monocytes is dramatically higher in peripheral (PB), intervillous blood (IVB) and decidua in labouring (n = 14) compared to non-labouring women (n = 15), suggesting that labour leads to both a systemic and local mobilisation of monocytes. Labour was associated with a relative increase of effector memory T cells in the intervillous space compared to the periphery, and MAIT cells and T cells showed an elevated expression of activation markers both in PB and IVB. Intervillous monocytes consisted to a higher degree of CD14+CD16+ intermediate monocytes compared to peripheral monocytes, independently of mode of delivery, and displayed an altered phenotypic expression pattern. A proximity extension assay analysis of 168 proteins revealed that several proteins associated to myeloid cell migration and function, including CCL2 and M-CSF, were upregulated in IVB plasma in labouring women. Thus, the intervillous space could be a bridging site for the communication between the placenta and the periphery, which contribute to monocyte mobilisation and generation of inflammatory reactions during spontaneous labour.
Assuntos
Trabalho de Parto , Células T Invariantes Associadas à Mucosa , Gravidez , Feminino , Humanos , Monócitos , Fatores Quimiotáticos , PlacentaRESUMO
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.