Why magnesium sulfate 'coverage' only is not enough to reduce eclampsia: Lessons learned in a middle-income country.

OBJECTIVES: Determine the eclampsia prevalence and factors associated with eclampsia and recurrent seizures in Suriname and evaluate quality-of-care indicator 'magnesium sulfate (MgSO4) coverage'. STUDY DESIGN: A two-year prospective nationwide cohort study was conducted in Suriname and included women with eclampsia at home or in a healthcare facility. MAIN OUTCOME MEASURES: We calculated the prevalence by the number of live births obtained from vital registration. Risk factor denominator data concerned hospital births. Descriptive statistics and multivariate regression analysis were performed. RESULTS: Seventy-two women with eclampsia (37/10.000 live births) were identified, including two maternal deaths (case-fatality 2.8%). Nulliparity, African-descent and adolescence were associated with eclampsia. Adolescents with eclampsia had significantly lower BPs (150/100 mmHg) than adult women (168/105 mmHg). The first seizure occurred antepartum in 54% (n = 39/72), intrapartum in 19% (n = 14/72) and postpartum in 26% (n = 19/72). Recurrent seizures were observed in 60% (n = 43/72). MgSO4 was administered to 99% (n = 69/70) of women; however 26% received no loading dosage and, in 22% of cases MgSO4 duration was <24 h, i.e. guideline adherence existed in only 43%. MgSO4 was ceased during CS in all women (n = 40). Stable BP was achieved before CS in 46%. The median seizure-to-delivery interval was 27 h, and ranged from four to 36 h. CONCLUSION: Solely 'MgSO4 coverage' is not a reliable quality-of-care indicator, as it conceals inadequate MgSO4 dosage and timing, discontinuation during CS, stabilization before delivery, and seizure-to-delivery interval. These other quality-of-care indicators need attention from the international community in order to reduce the prevalence of eclampsia.

Bottom-up development of national obstetric guidelines in middle-income country Suriname.

BACKGROUND: Obstetric guidelines are useful to improve the quality of care. Availability of international guidelines has rapidly increased, however the contextualization to enhance feasibility of implementation in health facilities in low and middle-income settings has only been described in literature in a few instances. This study describes the approach and lessons learned from the 'bottom-up' development process of context-tailored national obstetric guidelines in middle-income country Suriname. METHODS: Local obstetric health care providers initiated the guideline development process in Suriname in August 2016 for two common obstetric conditions: hypertensive disorders of pregnancy (HDP) and post partum haemorrhage (PPH). RESULTS: The process consisted of six steps: (1) determination of how and why women died, (2) interviews and observations of local clinical practice, (3) review of international guidelines, (4) development of a primary set of guidelines, (5) initiation of a national discussion on the guidelines content and (6) establishment of the final guidelines based on consensus. Maternal enquiry of HDP- and PPH-related maternal deaths revealed substandard care in 90 and 95% of cases, respectively. An assessment of the management through interviews and labour observations identified gaps in quality of the provided care and large discrepancies in the management of HDP and PPH between the hospitals. International recommendations were considered unfeasible and were inconsistent when compared to each other. Local health care providers and stakeholders convened to create national context-tailored guidelines based on adapted international recommendations. The guidelines were developed within four months and locally implemented. CONCLUSION: Development of national context-tailored guidelines is achievable in a middle-income country when using a 'bottom-up' approach that involves all obstetric health care providers and stakeholders in the earliest phase. We hope the descriptive process of guideline development is helpful for other countries in need of nationwide guidelines.

Frequency and characterization of RHD variants in serologically D- Surinamese pregnant women and D- newborns.

BACKGROUND: Numerous RHD variant genes affect the expression of D on the red blood cell surface. In Suriname, 4.3% of pregnant women were D-, ranging from virtually zero to 7% among ethnic groups. Characterization of RHD variants, which are associated with a variable potential to induce anti-D, is of practical clinical importance especially in case of limited access to preventive measures. Here we report on the occurrence of RHD variant genes in Surinamese serologically D- pregnant women and their D- newborns from different ethnic groups. STUDY DESIGN AND METHODS: The RheSuN study is a cross-sectional cohort study in D- pregnant women and their newborns, who visited hospitals in Paramaribo, Suriname, during routine pregnancy care. The presence of RHD variants was investigated using quantitative polymerase chain reaction targeting RHD Exons 5 and 7 and RH-multiplex ligation-dependent probe amplification. RESULTS: Seven RHD variant genes were detected in 35 of 84 women and four RHD variant genes in 15 of 36 newborns. The RHD*03 N.01 and RHD*08 N.01 variants represented 87% of a total of 62 variant genes. Variants were comparably frequent among ethnicities. In four cases genotyping would have changed anti-D prophylaxis policy: one woman with a RHD*01EL.01 variant, not associated with anti-D formation and three D- newborns with RHD*09.01 and RHD*09.03.01 variants, potentially capable of inducing anti-D. CONCLUSION: RHD variants at risk for anti-D are common among serologic D- individuals from African descent in Suriname. While genotyping D- women has limited added value, it may be considered in newborns from D- women.

The golden hour of sepsis: An in-depth analysis of sepsis-related maternal mortality in middle-income country Suriname.

BACKGROUND: Sepsis was the main cause of maternal mortality in Suriname, a middle-income country. Objective of this study was to perform a qualitative analysis of the clinical and management aspects of sepsis-related maternal deaths with a focus on the 'golden hour' principle of antibiotic therapy. METHODS: A nationwide reproductive age mortality survey was performed from 2010 to 2014 to identify and audit all maternal deaths in Suriname. All sepsis-related deaths were reviewed by a local expert committee to assess socio-demographic characteristics, clinical aspects and substandard care. RESULTS: Of all 65 maternal deaths in Suriname 29 (45%) were sepsis-related. These women were mostly of low socio-economic class (n = 23, 82%), of Maroon ethnicity (n = 14, 48%) and most deaths occurred postpartum (n = 21, 72%). Underlying causes were pneumonia (n = 14, 48%), wound infections (n = 3, 10%) and endometritis (n = 3, 10%). Bacterial growth was detected in 10 (50%) of the 20 available blood cultures. None of the women with sepsis as underlying cause of death received antibiotic treatment within the first hour, although most women fulfilled the diagnostic criteria of sepsis upon admission. In 27 (93%) of the 29 women from which sufficient information was available, substandard care factors were identified: delay in monitoring in 16 (59%) women, in diagnosis in 17 (63%) and in treatment in 21 (78%). CONCLUSION: In Suriname, a middle-income country, maternal mortality could be reduced by improving early recognition and timely diagnosis of sepsis, vital signs monitoring and immediate antibiotic infusion (within the golden hour).

Maternal mortality audit in Suriname between 2010 and 2014, a reproductive age mortality survey.

BACKGROUND: The fifth Millennium Development Goal (MDG-5) aimed to improve maternal health, targeting a maternal mortality ratio (MMR) reduction of 75% between 1990 and 2015. The objective of this study was to identify all maternal deaths in Suriname, determine the extent of underreporting, estimate the reduction, audit the maternal deaths and assess underlying causes and substandard care factors. METHODS: A reproductive age mortality survey was conducted in Suriname (South-American upper-middle income country) between 2010 and 2014 to identify all maternal deaths in the country. MMR was compared to vital statistics and a previous confidential enquiry from 1991 to 1993 with a MMR 226. A maternal mortality committee audited the maternal deaths and identified underlying causes and substandard care factors. RESULTS: In the study period 65 maternal deaths were identified in 50,051 live births, indicating a MMR of 130 per 100.000 live births and implicating a 42% reduction of maternal deaths in the past 25 years. Vital registration indicated a MMR of 96, which marks underreporting of 26%. Maternal deaths mostly occurred in the urban hospitals (84%) and the causes were classified as direct (63%), indirect (32%) or unspecified (5%). Major underlying causes were obstetric and non-obstetric sepsis (27%) and haemorrhage (20%). Substandard care factors (95%) were mostly health professional related (80%) due to delay in diagnosis (59%), delay or wrong treatment (78%) or inadequate monitoring (59%). Substandard care factors most likely led to death in 47% of the cases. CONCLUSION: Despite the reduction in maternal mortality, Suriname did not reach MDG-5 in 2015. Steps to reach the Sustainable Development Goal in 2030 (MMR ≤ 70 per 100.000 live births) and eliminate preventable deaths include improving data surveillance, installing a maternal death review committee, and implementing national guidelines for prevention and management of major complications of pregnancy, childbirth and puerperium.

D antibodies in pregnant women in multiethnic Suriname: the observational RheSuN study.

BACKGROUND: Maternal antibodies against the D antigen are the most common cause of severe hemolytic disease of the fetus and newborn (HDFN). In high-income countries, the risk of D immunization has been reduced by routine antenatal and postpartum administration of RhIG from 13% to less than 0.5%. In less-resourced countries, such as Suriname, red blood cell (RBC) antibody screening during pregnancy and prophylactic RhIG administration are not routine. Accurate data on D immunization risk is not available. In the RheSuN (Rhesus Surinamese Neonates) study, the prevalence and the hemolytic potential of maternal D antibodies were investigated. STUDY DESIGN AND METHODS: A multicenter cross-sectional study in four major hospitals in Paramaribo, Suriname, covering 90% of approximately 10,000 births yearly in Suriname. Included were D- pregnant women of various ethnicities seeking routine prenatal care and/or their newborns. RESULTS: D antibodies were detected in 19 of 214 D- pregnancies (8.9%; 95% confidence interval, 5.1%-12.7%), in 2.0% of primigravid and 11.7% of multigravid women. The direct antiglobulin test was positive in 11 of 13 tested D+ newborns. Determination of D antibody titers and antibody-dependent cell mediated cytotoxicity (ADCC) assay revealed three newborns at high risk for HDFN (ADCC > 50%). CONCLUSION: D immunization risk in Suriname women is comparable to the pre-anti-D prophylaxis era in high-income countries. Recommended is free-of-charge routine RBC antibody screening and prophylactic RhIG administration for women at risk for D antibody formation as part of standard of ante- and postnatal care.

Prevalence of positive direct antiglobulin test and clinical outcomes in Surinamese newborns from D-negative women.

BACKGROUND: In low-resource countries, screening for D antibodies to detect pregnancies at risk for hemolytic disease of the newborn is not routine practice. Retrospective data showed that 5.5% of Surinamese newborns of D-negative women had a positive direct antiglobulin test (DAT), indicating the presence of maternal antibodies against fetal antigens. Here, the frequency and clinical relevance of DAT positivity is evaluated. STUDY DESIGN AND METHODS: Between April 2015 and June 2016, an observational, multicenter cohort study was undertaken among Surinamese newborns born to D-negative women. In newborns, the DAT was performed, and clinical outcomes between DAT-negative and DAT-positive newborns were compared. RESULTS: Of the 232 evaluable newborns, 19 (8.2%) had a positive DAT, of which 11 of 15 antibody-tested newborns had D antibodies. DAT-positive newborns had lower hemoglobin levels (p = 0.02) and a trend toward higher bilirubin concentrations (p = 0.09) in the first days of life compared with DAT-negative newborns. DAT-positive newborns were admitted more frequently (p = 0.02), needed phototherapy treatment almost four times as often as DAT-negative newborns (26% vs. 7%; p = 0.008), and therapy took 2 days longer (p = 0.01). Exchange transfusions were performed in two newborns with D antibodies, both complicated with sepsis. The hospital stay was 2.5 days longer for DAT-positive newborns (p = 0.007). Overall, the prevalence of hemolytic disease of the newborn requiring treatment was 2.2% among the whole cohort of newborns. CONCLUSION: We found a high prevalence of DAT positivity with substantial need for hyperbilirubinemia treatment in newborns in Suriname. These results stress the necessity for better management procedures in D-negative women.

The HLA-DRB1*15 phenotype is associated with multiple red blood cell and HLA antibody responsiveness.

BACKGROUND: Once a patient has produced a red blood cell (RBC) antibody, there is an increased risk of additional antibody formation after subsequent RBC exposure. Recently, we observed that HLA-DRB1*15 was overrepresented in 379 multiple RBC antibody responders compared to controls or 562 patients with a single RBC antibody (odds ratio [OR], 1.7; 95% confidence interval [CI], 1.3-2.3). In this study we evaluated whether the HLA-DRB1*15 represents a responder phenotype against HLA and/or RBC antigens. STUDY DESIGN AND METHODS: HLA-DRB1*15 frequencies in single and multiple antibody responders were compared between three groups of individuals: 1) those with HLA antibodies, 2) those with RBC antibodies, and 3) those with both RBC and HLA antibodies. RESULTS: A total of 3959 immunized patients (female-to-male ratio, 2.3) had been HLA-DRB1 typed. Among the 3275 individuals with HLA antibodies, the frequency of the DRB1*15 phenotype differed significantly from 19.7% in patients with a panel reactivity (PRA) of not more than 20% to 26.9% in patients with PRA of more than 80% (OR, 1.5; 95% CI, 1.2-1.9). This association between DRB1*15 and multiresponsiveness was mainly due to pregnancy-induced HLA immunization. In the 257 individuals with RBC and HLA antibodies, the frequency of DRB1*15 was 4.2 times (95% CI, 1.1-16) higher in those with multiple RBC antibodies and HLA-PRA of more than 50% compared to only single RBC responders with PRA of less than 20%. CONCLUSION: The HLA-DRB1*15 phenotype is associated with broad RBC and HLA immunization.

RhD negativity among pregnant women in multiethnic Suriname.

BACKGROUND: RhD negativity is distributed unevenly among different ethnicities. In this study we explored the frequencies of RhD negativity in pregnant women in multiethnic Suriname, along with screening results for red blood cell (RBC) antibodies in these women and their offspring. Results may help identify women at risk for hemolytic disease of the fetus and newborn. STUDY DESIGN AND METHODS: A retrospective study was performed in pregnant women who delivered at three major hospitals in Suriname between January 1, 2013, and December 31, 2014. RESULTS: The overall prevalences of RhD negativity among 8686 women was 4.3%. The percentages of RhD negativity in Maroons, Creoles, and Hindustani women were 7.2, 5.4, and 3.7%, respectively. Chinese and Javanese women had very low prevalences of 0.8 and 0.5%, respectively, and Amerindians showed no RhD negativity. Antibody screening was positive in six D- (five Maroons and one Creole) women and weakly positive in three women (two Creoles and one Maroon), making overall antibody prevalence 4.4%. In 15 (5.5%; 10 Maroons, four Creoles, one Chinese) newborns from D- mothers antibody screening was positive. CONCLUSION: In the multiethnic Surinamese population RhD negativity among pregnant women varied between 0.0 and 7.2% between ethnic groups. RBC antibodies were detected during pregnancy and in newborns in 4.4 and 5.5%, respectively.

Fetal intracranial haemorrhages caused by fetal and neonatal alloimmune thrombocytopenia: an observational cohort study of 43 cases from an international multicentre registry.

OBJECTIVE: To characterise pregnancies where the fetus or neonate was diagnosed with fetal and neonatal alloimmune thrombocytopenia (FNAIT) and suffered from intracranial haemorrhage (ICH), with special focus on time of bleeding onset. DESIGN: Observational cohort study of all recorded cases of ICH caused by FNAIT from the international No IntraCranial Haemorrhage (NOICH) registry during the period 2001-2010. SETTING: 13 tertiary referral centres from nine countries across the world. PARTICIPANTS: 37 mothers and 43 children of FNAIT pregnancies complicated by fetal or neonatal ICH identified from the NOICH registry was included if FNAIT diagnosis and ICH was confirmed. PRIMARY AND SECONDARY OUTCOME MEASURES: Gestational age at onset of ICH, type of ICH and clinical outcome of ICH were the primary outcome measures. General maternal and neonatal characteristics of pregnancies complicated by fetal/neonatal ICH were secondary outcome measures. RESULTS: From a total of 592 FNAIT cases in the registry, 43 confirmed cases of ICH due to FNAIT were included in the study. The majority of bleedings (23/43, 54%) occurred before 28 gestational weeks and often affected the first born child (27/43, 63%). One-third (35%) of the children died within 4 days after delivery. 23 (53%) children survived with severe neurological disabilities and only 5 (12%) were alive and well at time of discharge. Antenatal treatment was not given in most (91%) cases of fetal/neonatal ICH. CONCLUSIONS: ICH caused by FNAIT often occurs during second trimester and the clinical outcome is poor. In order to prevent ICH caused by FNAIT, at-risk pregnancies must be identified and prevention and/or interventions should start early in the second trimester.

Parenteral Pethidine for labour pain relief and substance use disorder: 20-year follow-up cohort study in offspring.

OBJECTIVE: To determine whether use of intrapartum Pethidine pain analgesia increases the risk for substance use disorder in adult offspring. DESIGN: Analysis of data from a cohort study. SETTING: Academic hospital in Leiden, the Netherlands. PARTICIPANTS: 133 cases and 164 control individuals, aged 18-20 years at follow-up. MAIN OUTCOME MEASURE: Incidence of substance use disorder or use of alcohol and tobacco. RESULTS: The lifetime use of addictive substances in children exposed to intrapartum Pethidine analgesia was 45% of 133 children versus 48% of 164 not-exposed subjects (adjusted OR=0.79, 95% CI 0.48 to 1.29). Recent use of alcohol, tobacco and hard drugs showed no statistical difference either. CONCLUSION: Pethidine for labour pain medication appears not to be associated with substance misuse or smoking in later life.

E-selectin is elevated in cord blood of South Asian neonates compared with Caucasian neonates.

OBJECTIVE: To test the hypothesis that the increased risk of type 2 diabetes mellitus and coronary artery disease in South Asian subjects could be caused by the presence of endothelial dysfunction in early life. We studied markers of endothelial dysfunction in umbilical cord blood of South Asian neonates and compared these with that of Caucasian control subjects. STUDY DESIGN: From South Asian (n = 57) and Caucasian (n = 21) neonates, cord blood was collected and levels of glucose, insulin, lipids, and markers of endothelial dysfunction (E-selectin, intercellular adhesion molecule 1, vascular cell adhesion molecule 1) and inflammation (C-reactive protein) were measured. RESULTS: Plasma E-selectin levels were significantly higher in South Asian neonates (46.7 versus 33.5 ng/mL, P < .001), and levels of intercellular adhesion molecule 1 and vascular cell adhesion molecule 1 did not differ. Furthermore, South Asian neonates had hyperinsulinemia (P = .043), dyslipidemia (with significantly higher triglyceride and lower high-density lipoprotein cholesterol levels), and higher C-reactive protein levels (75.7 versus 43.8 ng/mL, P = .009). CONCLUSIONS: South Asian newborns are characterized by elevated E-selectin levels in line with the hypothesis that endothelial dysfunction is present early in life. In addition, hyperinsulinemia, dyslipidemia, and inflammation are present. Because many pathogenic variables for coronary artery disease and type 2 diabetes are already present at birth in South Asian patients, the question arises whether rigorous childhood lifestyle intervention could be beneficial.

Long-term neurodevelopmental outcome after intrauterine transfusion for hemolytic disease of the fetus/newborn: the LOTUS study.

OBJECTIVE: To determine the incidence and risk factors for neurodevelopmental impairment (NDI) in children with hemolytic disease of the fetus/newborn treated with intrauterine transfusion (IUT). STUDY DESIGN: Neurodevelopmental outcome in children at least 2 years of age was assessed using standardized tests, including the Bayley Scales of Infant Development, the Wechsler Preschool and Primary Scale of Intelligence, and the Wechsler Intelligence Scale for Children, according to the children's age. Primary outcome was the incidence of neurodevelopmental impairment defined as at least one of the following: cerebral palsy, severe developmental delay, bilateral deafness, and/or blindness. RESULTS: A total of 291 children were evaluated at a median age of 8.2 years (range, 2-17 years). Cerebral palsy was detected in 6 (2.1%) children, severe developmental delay in 9 (3.1%) children, and bilateral deafness in 3 (1.0%) children. The overall incidence of neurodevelopmental impairment was 4.8% (14/291). In a multivariate regression analysis including only preoperative risk factors, severe hydrops was independently associated with neurodevelopmental impairment (odds ratio, 11.2; 95% confidence interval, 1.7-92.7). CONCLUSION: Incidence of neurodevelopmental impairment in children treated with intrauterine transfusion for fetal alloimmune anemia is low (4.8%). Prevention of fetal hydrops, the strongest preoperative predictor for impaired neurodevelopment, by timely detection, referral and treatment may improve long-term outcome.

Long-Term follow up after intra-Uterine transfusionS; the LOTUS study.

BACKGROUND: The Leiden University Medical Center (LUMC) is the Dutch national referral centre for pregnancies complicated by haemolytic disease of the fetus and newborn (HDFN) caused by maternal alloimmunization. Yearly, 20-25 affected fetuses with severe anaemia are transfused with intra-uterine blood transfusions (IUT). Mothers of whom their fetus has undergone IUT for HDFN are considered high responders with regard to red blood cell (RBC) antibody formation. Most study groups report high perinatal survival, resulting in a shift in attention towards short- and long-term outcome in surviving children. METHODS/DESIGN: We set up a large long-term observational follow-up study (LOTUS study), in cooperation with the Sanquin Blood Supply Foundation and the LUMC departments of Obstetrics, Neonatology and ImmunoHematology & Bloodtransfusion.The first part of this study addresses several putative mechanisms associated with blood group alloimmunization in these mothers. The second part of this study determines the incidence of long-term neurodevelopment impairment (NDI) and associated risk factors in children treated with IUT. All women and their life offspring who have been treated with IUT for HDFN in the LUMC from 1987-2008 are invited to participate and after consent, blood or saliva samples are taken. RBC and HLA antigen profile and antibodies are determined by serologic or molecular techniques. Microchimerism populations are tested by real time polymerase chain reaction (RT PCR).All children are tested for their neurological, cognitive and psychosocial development using standardised tests and questionnaires. The primary outcome is neurodevelopmental impairment (NDI), a composite outcome defined as any of the following: cerebral palsy, cognitive or psychomotor development < 2 standard deviation, bilateral blindness and/or bilateral deafness. DISCUSSION: The LOTUS study includes the largest cohort of IUT patients ever studied and is the first to investigate post-IUT long-term effects in both mother and child. The results may lead to a change in transfusion policy, in particular future avoidance of certain incompatibilities. Additionally the LOTUS study will provide clinicians and parents better insights in the long-term neurodevelopmental outcome in children with HDFN treated with IUTs, and may improve the quality of antenatal counselling and long-term guidance.

Association between colonization with Group B Streptococcus and preterm delivery: a systematic review.

Up to 36% of pregnant women are colonized with Group B Streptococcus (GBS). Preterm delivery in colonized mothers is a risk factor for early onset neonatal GBS disease, but whether maternal GBS genital colonization is related to preterm delivery is unclear. The objective of this review was to determine the relationship between maternal colonization with GBS and preterm delivery. Pubmed searches and reference lists of all selected publications were used to find studies reporting on the relationship between maternal GBS colonization and preterm delivery. Study characteristics were abstracted, and validity scores were performed. To assess the relationship between GBS colonization and pregnancy outcome, four-fold prognostic tables were constructed for each study. Out of more than 60 full-text articles, 16 follow-up studies and four case control studies were included in this review. Follow-up studies were divided into 'cohort studies,' in which cultures were taken early in pregnancy and which reported on pregnancy outcome, and 'cross-sectional studies', in which cultures were collected during delivery. Studies differed widely in methods, validity score, and GBS prevalence. The combined estimate from a random effect meta-analysis of the 11 cohort studies was 1.06 (95% confidence intervals (CI) 0.95-1.19) and for the five cross-sectional studies 1.75 (95% CI 1.43-2.14). For the case control studies, the pooled odds ratio was 1.59 (95% CI 1.03-2.44). This systematic review did not show an association between maternal GBS colonization during pregnancy and preterm delivery. However, in case of preterm delivery, there is an increased risk of subsequent maternal GBS colonization.

Long-term neurodevelopmental outcome after fetal arrhythmia.

OBJECTIVE: The purpose of this study was to determine the long-term neurodevelopmental outcome in fetuses with severe tachy- or bradyarrhythmia. STUDY DESIGN: This was a follow-up study to assess the neurologic, mental, and psychomotor development in cases with fetal cardiac arrhythmia. RESULTS: A total of 44 fetuses were diagnosed with fetal tachy- or bradyarrhythmia: 28 fetuses had supraventricular tachycardia (SVT); 7 fetuses had atrial flutter (AF), and 9 fetuses had atrioventricular block (AVB). The mortality rate was low (6%; 2/35 fetuses) in the SVT and AF groups and high in the AVB group (78%; 7/9 fetuses). Six patients were lost to follow-up evaluation (14%). Neurodevelopmental outcome was normal in all survivors in the SVT and AF groups, except for 1 patient who experienced plexus brachialis injury because of shoulder dystocia. Two of the 3 survivors in the AVB group had severe developmental delay. CONCLUSION: The mortality rate and neurodevelopmental impairment in infants with SVT and AF are low, but the mortality rate in infants with AVB is elevated.

Differential immunomodulatory effects of fetal versus maternal multipotent stromal cells.

Protective mechanisms are likely to be present at the fetomaternal interface because fetus-specific alloreactive T cells present in the decidua do not harm the fetus. We tested the immunosuppressive capacity of maternal and fetal multipotent stromal cells (MSC). Single cell suspensions were made from second-trimester amnion, amniotic fluid, and decidua. Culture-expanded cells were identified as MSC based on phenotype and multilineage potential. Coculture of MSC in a primary mixed lymphocyte culture of unrelated responder-stimulator combinations resulted in a dose-dependent inhibition of proliferation. Fetal MSC demonstrated a significantly higher inhibition compared with maternal MSC. This stronger inhibition by fetal MSC was even more prominent in a secondary mixed lymphocyte reaction (MLR) with primed alloreactive T cells. Analysis of cytokine production revealed that fetal MSC produced significantly more interleukin (IL)-10 and vascular endothelial growth factor than maternal MSC. Cell-cell contact is needed for part of the inhibitory effects of MSC. In addition, soluble factors play a role because blocking experiments with anti-IL-10 revealed that the inhibition of the MLR response by fetal MSC is mainly mediated by IL-10. For maternal MSC, other soluble factors seem to be involved. Fetal MSC derived from the fetomaternal interface have a stronger inhibitory effect on naive and antigen-experienced T cells compared with maternal MSC, which is probably related to their higher IL-10 production.

Severe fetal thrombocytopenia in Rhesus D alloimmunized pregnancies.

OBJECTIVE: The objective of the study was to evaluate the incidence of fetal thrombocytopenia and association with hydrops in Rhesus D alloimmunization. STUDY DESIGN: The study was a retrospective chart review of 914 intrauterine transfusions in 314 pregnancies performed between 1988 and 2005 in a single institution. The incidence of thrombocytopenia and severity of hydrops at cordocentesis were assessed and correlated with perinatal mortality. RESULTS: Thrombocytopenia (less than 150 x 10(9)/L) was found in 241 of 914 (26%) and severe thrombocytopenia (less than 50 x 10(9)/L) in 25 of 914 (3%) cordocentesis. Twenty-three percent of severely hydropic fetuses had severe thrombocytopenia, compared with 3% and 1% of mildly hydropic and nonhydropic fetuses, respectively. Thrombocytopenia was an independent risk factor for perinatal mortality. Mortality in fetuses that were severely thrombocytopenic and severely hydropic was 67%. CONCLUSION: Thrombocytopenia is common in hydropic anemic fetuses. Severe thrombocytopenia is associated with a poor prognosis, irrespective of the presence of hydrops. The option of platelet transfusion in severely hydropic anemic fetuses needs further study.

Implementation of routine screening for Kell antibodies: does it improve perinatal survival?

BACKGROUND: In 1998 a national program for first-trimester screening for red cell (RBC) antibodies in all pregnant women was implemented. The aim of our study was to assess the impact on perinatal mortality caused by Kell alloimmunization STUDY DESIGN AND METHODS: Prospectively collected data on all pregnant women referred to our center from 1988 until 2005 for intrauterine transfusion (IUT) for fetal anemia due to Kell alloantibodies were analyzed. The cohort was divided into two groups, those treated before 1998 and those treated after 1998. The primary outcome was fetal and neonatal survival. Secondary outcome variables were gestational age, fetal hemoglobin (Hb) levels at first IUT, severity of hydrops, and total number of IUTs per pregnancy. Causes for mortality were analyzed in detail. RESULTS: A total of 43 pregnancies were included, 18 before introduction of screening and 25 thereafter. Perinatal survival increased from 61 percent in the first period to 100 percent after introduction of screening. After 1998, fetal hydrops was generally less severe at first IUT, while gestational age and fetal Hb levels at first IUT were similar. CONCLUSION: Implementation of routine screening for Kell antibodies in pregnancy was associated with an increased referral rate for suspected fetal anemia, more timely referrals, and a higher perinatal survival rate after intrauterine treatment.

Pediatric outcome in Rhesus hemolytic disease treated with and without intrauterine transfusion.

OBJECTIVE: To study the short-term morbidity in Rhesus hemolytic disease of infants treated either with or without intrauterine transfusions (IUT). STUDY DESIGN: All term and near term infants (gestational age > or = 36 weeks) with neonatal Rhesus hemolytic disease admitted to our center between January 2000-March 2005 were retrospectively included in the study. We recorded the duration of phototherapy, the need of exchange transfusions, and the need of top-up red blood cell transfusions until 6 months of age. RESULTS: A total of 89 infants were included, of whom 52 received at least one IUT. Duration of phototherapy in the IUT and no-IUT group was 3.8 and 5.1 days, respectively (P = .01). The percentage of infants requiring an exchange transfusion in the IUT group was 71% compared to 65% in the no-IUT group (P = .64). The percentage of infants requiring a top-up transfusion in the IUT and no-IUT group was 77% and 26.5%, respectively (P < .01). CONCLUSION: Infants with Rhesus hemolytic disease treated with IUT required less days of phototherapy and more top-up red blood cell transfusions than neonates without IUT. However, the need for exchange transfusion was similar in both groups.