Risk factors for RhD immunisation in a high coverage prevention programme of antenatal and postnatal RhIg: a nationwide cohort study.

OBJECTIVE: To evaluate which risk factors for RhD immunisation remain, despite adequate routine antenatal and postnatal RhIg prophylaxis (1000 IU RhIg) and additional administration of RhIg. The second objective was assessment of the current prevalence of RhD immunisations. DESIGN: Prospective cohort study. SETTING: The Netherlands. POPULATION: Two-year nationwide cohort of alloimmunised RhD-negative women. METHODS: RhD-negative women in their first RhD immunised pregnancy were included for risk factor analysis. We compared risk factors for RhD immunisation, occurring either in the previous non-immunised pregnancy or in the index pregnancy, with national population data derived from the Dutch perinatal registration (Perined). RESULTS: In the 2-year cohort, data from 193 women were eligible for analysis. Significant risk factors in women previously experiencing a pregnancy of an RhD-positive child (n = 113) were: caesarean section (CS) (OR 1.7, 95% CI 1.1-2.6), perinatal death (OR 3.5, 95% CI 1.1-10.9), gestational age >42 weeks (OR 6.1, 95% CI 2.2-16.6), postnatal bleeding (>1000 ml) (OR 2.0, 95% CI 1.1-3.6), manual removal of the placenta (MRP) (OR 4.3, 95% CI 2.0-9.3); these factors often occurred in combination. The miscarriage rate was significantly higher than in the Dutch population (35% versus 12.-5%, P < 0.001). CONCLUSION: Complicated deliveries, including cases of major bleeding and surgical interventions (CS, MRP), must be recognised as a risk factor, requiring estimation of fetomaternal haemorrhage volume and adjustment of RhIg dosing. The higher miscarriage rate suggests that existing RhIg protocols need adjustment or better compliance. TWEETABLE ABSTRACT: Complicated delivery (caesarean section, manual removal placenta, major bleeding) is the most valid risk factor for RhD immunization despite antenatal and postnatal RhIg.

Associations between road traffic noise exposure at home and school and ADHD in school-aged children: the TRAILS study.

Environmental noise may play a role in the manifestation and severity of attention deficit/hyperactivity disorder (ADHD) symptoms, but evidence is limited. We investigated the cross-sectional associations between residential and school road traffic noise exposure and ADHD symptoms and diagnosis. The sample included n = 1710, 10-12-year-old children from the TRAILS study in The Netherlands. ADHD symptoms were measured using a DSM-IV based subscale from the Child Behavior Checklist. Children with diagnosed ADHD originated from the clinic-referred cohort. Road traffic noise (Lden) was estimated at the residence and school level, by model calculation. Risk ratios for ADHD symptoms and ADHD diagnoses, and regression coefficients for symptom severity were estimated separately and simultaneously for residential and school road traffic noise. Adjusted multinomial models with residential road traffic noise showed that residential noise was not associated with ADHD symptoms, but was associated with lower risks for ADHD diagnosis (RR = 0.93; 95% CI 0.89, 0.97). Similar associations were observed for models including school road traffic noise and models including both exposures. No clear exposure response relationship was observed for associations between residential or school noise and ADHD symptom severity. We found no evidence for a harmful association between road traffic noise and ADHD. Associations between noise and lower risks for ADHD were observed only in referred cases with a confirmed ADHD diagnosis and may be due to residual confounding or selection bias. Future studies should focus on residential and school noise exposure, and study associations with ADHD symptoms and diagnosis over time.

Individual variation in temporal relationships between exposure to radiofrequency electromagnetic fields and non-specific physical symptoms: A new approach in studying 'electrosensitivity'.

BACKGROUND: Everyday exposure to radiofrequency electromagnetic fields (RF-EMF) emitted from wireless devices such as mobile phones and base stations, radio and television transmitters is ubiquitous. Some people attribute non-specific physical symptoms (NSPS) such as headache and fatigue to exposure to RF-EMF. Most previous laboratory studies or studies that analyzed populations at a group level did not find evidence of an association between RF-EMF exposure and NSPS. OBJECTIVES: We explored the association between exposure to RF-EMF in daily life and the occurrence of NSPS in individual self-declared electrohypersensitive persons using body worn exposimeters and electronic diaries. METHODS: We selected seven individuals who attributed their NSPS to RF-EMF exposure. The level of and variability in personal RF-EMF exposure and NSPS were determined during a three-week period. Data were analyzed using time series analysis in which exposure as measured and recorded in the diary was correlated with NSPS. RESULTS: We found statistically significant correlations between perceived and actual exposure to wireless internet (WiFi - rate of change and number of peaks above threshold) and base stations for mobile telecommunications (GSM + UMTS downlink, rate of change) and NSPS scores in four of the seven participants. In two persons a higher EMF exposure was associated with higher symptom scores, and in two other persons it was associated with lower scores. Remarkably, we found no significant correlations between NSPS and time-weighted average power density, the most commonly used exposure metric. CONCLUSIONS: RF-EMF exposure was associated either positively or negatively with NSPS in some but not all of the selected self-declared electrohypersensitive persons.

Complications of intrauterine intravascular blood transfusion: lessons learned after 1678 procedures.

OBJECTIVE: Maternal alloimmunization to fetal red-blood-cell antigens is a major cause of fetal anemia, which can lead to hydrops and perinatal death if untreated. The cornerstone of management during pregnancy is intrauterine intravascular blood transfusion (IUT). Although this procedure is considered relatively safe, complications continue to occur. The aim of this study was to evaluate rates of procedure-related complications and perinatal loss following IUT, and their change over time, in order to identify factors leading to improved outcome. METHODS: This was a retrospective analysis of all IUTs for red-cell alloimmunization performed at the national referral center for fetal therapy in The Netherlands, from 1988 to 2015. Differences in complication rates and their associations with alterations in transfusion technique after 2001 were assessed. RESULTS: Between 1988 and 2015, 1678 IUTs were performed in 589 fetuses. For IUTs performed in 2001 and onwards, there was significant improvement in survival (88.6% vs 97.0%, P < 0.001) and a decline in procedure-related complications per fetus (9.8% vs 3.3%, P = 0.001) and per procedure (3.4% vs 1.2%, P = 0.003) compared with those performed before 2001. Procedure-related perinatal loss declined from 4.7% to 1.8% per fetus (P = 0.053). Beneficial changes in transfusion technique were routine use of fetal paralysis, increased use of intrahepatic transfusion and avoidance of arterial puncture. CONCLUSIONS: IUT has become an increasingly safe procedure in recent years when performed by experienced hands. The chosen technique should be fine-tuned according to the patient's individual situation. The declining complication rates are most likely related to center volume: this rare procedure is best performed in experienced fetal therapy centers. © 2016 Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

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

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

Increased perinatal loss after intrauterine transfusion for alloimmune anaemia before 20 weeks of gestation.

OBJECTIVES: To evaluate and compare perinatal outcome after intrauterine transfusions (IUT) performed before and after 20 weeks of gestation. To analyse contributing factors. DESIGN: Retrospective analysis. SETTING: The Dutch referral centre for fetal therapy. POPULATION: IUTs for fetal alloimmune anaemia. METHODS: Fetuses were divided into two groups: fetuses requiring the first IUT before 20 weeks of gestation (Group 1) and those in which the IUTs started after 20 weeks (Group 2). The cause of perinatal loss was classified as procedure-related (PR) or not procedure-related (NPR). The cohort was divided into two periods to describe the change of perinatal loss over time. MAIN OUTCOME MEASURES: Perinatal loss of fetuses requiring the first IUT before 20 weeks of gestation, compared with perinatal loss later in gestation. RESULTS: A total of 1422 IUTs were performed in 491 fetuses. Perinatal loss rate in Group 1 was higher (7/29 24% versus 35/462 8%, P = 0.002). Especially NPR was higher for IUTs performed before 20 weeks (4/37 11% versus 19/1385 1%, P < 0.001). Kell alloimmunisation was overrepresented in Group 1 (7/29 24% versus 52/462 11%, P = 0.04). In a multivariate regression analysis, only hydrops was independently associated with perinatal loss (P = 0.001). In recent years, a decline in total perinatal loss was found (36/224 16% versus 6/267 2%, P < 0.001), but perinatal loss in Group 1 did not decline (4/224 1.8% versus 3/267 1.1%, P = 0.5). CONCLUSIONS: Perinatal loss after IUT performed before 20 weeks of gestation is increased compared with loss after IUT performed later in gestation. In addition, we confirmed earlier observations that hydrops is a major contributor to adverse outcome. Early and timely detection and treatment may prevent hydrops and improve outcome.

Thrombocytopenia at birth in neonates with red cell alloimmune haemolytic disease.

OBJECTIVE: To evaluate the incidence and severity of and risk factors for thrombocytopenia at birth in neonates with red cell alloimmunization. STUDY DESIGN: All neonates with haemolytic disease of the foetus/newborn (HDFN) due to red cell alloimmunization admitted to our centre between January 2000 and September 2010 were included in this retrospective study. We measured platelet counts at birth and determined the incidence of thrombocytopenia (platelet count<150×10(9)/l) and severe thrombocytopenia (platelet count<50×10(9)/l). Risk factors for thrombocytopenia at birth were evaluated. RESULTS: Thrombocytopenia was present in 26% (94/362) of included neonates with HDFN at birth. Severe thrombocytopenia was found in 6% (20/362) of neonates. Three risk factors were found to be independently associated with thrombocytopenia at birth: treatment with intrauterine red cell transfusion (IUT) (OR 3·32, 95% CI 1·67-6·60, P=0·001), small for gestational age (SGA) below the 10th percentile (OR 3·32, 95% CI 1·25-8·80, P=0·016) and lower gestational age at birth (OR 1·22/week, 95% CI 1·02-1·44, P=0·025). CONCLUSIONS: Thrombocytopenia at birth occurs in 26% of neonates with HDFN due to red cell alloimmunization and is independently associated with IUT treatment, SGA and lower gestational age at birth.

Exchange transfusions and top-up transfusions in neonates with Kell haemolytic disease compared to Rh D haemolytic disease.

OBJECTIVE: To evaluate neonatal outcome in Kell haemolytic disease compared to Rh D haemolytic disease. STUDY DESIGN: Retrospective study of all (near)-term neonates with Kell (n=34) and Rh D haemolytic disease (n=157) admitted to our centre between January 2000 and December 2008. We recorded the need for exchange transfusion and top-up transfusions up to 3 months of age. RESULTS: Neonates in the Kell group required less days of phototherapy than neonates in the Rh D group [2.4 vs. 4.1 days, respectively (P<0.01)]. The percentage of neonates requiring an exchange transfusion was lower in the Kell group than in the Rh D group [6% (2/34) and 62% (98/157), respectively (P<0.01)]. The percentage of neonates in the Kell group and Rh D group requiring a top-up transfusion was 62% (21/34) and 72% (113/157), respectively (P=0.20). The median number of top-up transfusions per neonate in the Kell group and Rh D group was 1 [interquartile range (IQR) 0-2] and 2(IQR 0-2), respectively (P=0.07). CONCLUSION: Neonates with Kell haemolytic disease require less phototherapy and less exchange transfusions compared to neonates with Rh D haemolytic disease, but an equal number of top-up transfusions.

Quantitative health impact assessment of transport policies: two simulations related to speed limit reduction and traffic re-allocation in the Netherlands.

BACKGROUND: Few quantitative health impact assessments (HIAs) of transport policies have been published so far and there is a lack of a common methodology for such assessments. OBJECTIVE: To evaluate the usability of existing HIA methodology to quantify health effects of transport policies at the local level. METHODS: Health impact of two simulated but realistic transport interventions - speed limit reduction and traffic re-allocation - was quantified by selecting traffic-related exposures and health endpoints, modelling of population exposure, selecting exposure-effect relations and estimating the number of local traffic-related cases and disease burden, expressed in disability-adjusted life-years (DALYs), before and after the intervention. RESULTS: Exposure information was difficult to retrieve because of the local scale of the interventions, and exposure-effect relations for subgroups and combined effects were missing. Given uncertainty in the outcomes originating from this kind of missing information, simulated changes in population health by two local traffic interventions were estimated to be small (<5%), except for the estimated reduction in DALYs by less traffic accidents (60%) due to speed limit reduction. CONCLUSIONS: Quantitative HIA of transport policies at a local scale is possible, provided that data on exposures, the exposed population and their baseline health status are available. The interpretation of the HIA information should be carried out in the context of the quality of input data and assumptions and uncertainties of the analysis.

Obstetric history and antibody titer in estimating severity of Kell alloimmunization in pregnancy.

OBJECTIVE: To evaluate the usefulness of the obstetric history and the maternal serum Kell antibody titer in the management of pregnancies with Kell alloimmunization. METHODS: In a retrospective cohort study of 41 pregnancies complicated by Kell alloimmunization, the obstetric history, divided into presence or absence of a previous Kell-positive child, and Kell antibody titers in the index pregnancy were correlated with the gestational age at the onset of fetal anemia. RESULTS: Women with a previous Kell-positive child had a lower gestational age at the first intrauterine transfusion compared with those without a previous Kell-positive child (P=.01). However, in two of 29 pregnancies in the latter group, severe fetal anemia requiring transfusion was detected before 20 weeks of gestation. In neither group were maternal Kell antibody titers significantly correlated with gestational age at first intrauterine transfusion (P=.62 and P=.72, respectively). In all but two pregnancies (1:2 and 1:4, respectively), antibody titers were at least 1:32 before the first intrauterine transfusion. CONCLUSION: For timely detection of all cases of severe fetal anemia, Kell-alloimmunized pregnancies with a Kell-positive fetus and titers greater than or equal to 1:2 should be closely monitored from 16 to 17 weeks of gestation onward.

Noise exposure and children's blood pressure and heart rate: the RANCH project.

BACKGROUND: Conclusions that can be drawn from earlier studies on noise and children's blood pressure are limited due to inconsistent results, methodological problems, and the focus on school noise exposure. OBJECTIVES: To investigate the effects of aircraft and road traffic noise exposure on children's blood pressure and heart rate. METHODS: Participants were 1283 children (age 9-11 years) attending 62 primary schools around two European airports. Data were pooled and analysed using multilevel modelling. Adjustments were made for a range of socioeconomic and lifestyle factors. RESULTS: After pooling the data, aircraft noise exposure at school was related to a statistically non-significant increase in blood pressure and heart rate. Aircraft noise exposure at home was related to a statistically significant increase in blood pressure. Aircraft noise exposure during the night at home was positively and significantly associated with blood pressure. The findings differed between the Dutch and British samples. Negative associations were found between road traffic noise exposure and blood pressure, which cannot be explained. CONCLUSION: On the basis of this study and previous scientific literature, no unequivocal conclusions can be drawn about the relationship between community noise and children's blood pressure.

Aircraft and road traffic noise and children's cognition and health: a cross-national study.

BACKGROUND: Exposure to environmental stressors can impair children's health and their cognitive development. The effects of air pollution, lead, and chemicals have been studied, but there has been less emphasis on the effects of noise. Our aim, therefore, was to assess the effect of exposure to aircraft and road traffic noise on cognitive performance and health in children. METHODS: We did a cross-national, cross-sectional study in which we assessed 2844 of 3207 children aged 9-10 years who were attending 89 schools of 77 approached in the Netherlands, 27 in Spain, and 30 in the UK located in local authority areas around three major airports. We selected children by extent of exposure to external aircraft and road traffic noise at school as predicted from noise contour maps, modelling, and on-site measurements, and matched schools within countries for socioeconomic status. We measured cognitive and health outcomes with standardised tests and questionnaires administered in the classroom. We also used a questionnaire to obtain information from parents about socioeconomic status, their education, and ethnic origin. FINDINGS: We identified linear exposure-effect associations between exposure to chronic aircraft noise and impairment of reading comprehension (p=0.0097) and recognition memory (p=0.0141), and a non-linear association with annoyance (p<0.0001) maintained after adjustment for mother's education, socioeconomic status, longstanding illness, and extent of classroom insulation against noise. Exposure to road traffic noise was linearly associated with increases in episodic memory (conceptual recall: p=0.0066; information recall: p=0.0489), but also with annoyance (p=0.0047). Neither aircraft noise nor traffic noise affected sustained attention, self-reported health, or overall mental health. INTERPRETATION: Our findings indicate that a chronic environmental stressor-aircraft noise-could impair cognitive development in children, specifically reading comprehension. Schools exposed to high levels of aircraft noise are not healthy educational environments.

The severity of immune fetal hydrops is predictive of fetal outcome after intrauterine treatment.

OBJECTIVE: This study was undertaken to test the hypothesis that the degree of immune fetal hydrops predicts outcome in red blood cell-alloimmunized pregnancies. STUDY DESIGN: In an 11-year period, 213 fetuses received 599 intrauterine transfusions. The outcome of 208 pregnancies, including two pairs of twins, was analyzed in a retrospective study. Eighty fetuses demonstrated ultrasonographic signs of hydrops at the start of treatment; 42 of these were classified as mildly hydropic and 38 were classified as severely hydropic. Reversal of hydrops as a result of treatment, survival, and neonatal morbidity was studied. RESULTS: The overall survival rate of fetuses with hydrops was 78%. Of the fetuses with mild hydrops, 98% survived, whereas in cases of severe hydrops the survival rate was 55%. Intrauterine reversal of hydrops occurred in 65% of the fetuses with hydrops. The reversal rate was 88% in fetuses with mild hydrops and 39% in fetuses classified as severely hydropic. After reversal of hydrops, almost all of the fetuses survived (98%), whereas in cases of persistent hydrops outcome was unfavorable, with a survival rate of 39% for all fetuses and 26% for fetuses classified as severely hydropic. CONCLUSION: In contrast with severe hydrops, there is a high rate of reversal of mild hydrops after adequate treatment. In our study 98% of fetuses survived after reversal of hydrops. To improve the outcome of red blood cell-alloimmunized pregnancies, early diagnosis of fetal anemia and referral to a specialized center are important; these steps enable the start of intrauterine treatment when hydrops is absent or still mild.

Clinical value of an antibody-dependent cell-mediated cytotoxicity assay in the management of Rh D alloimmunization.

OBJECTIVE: The aim of this study was to evaluate the clinical value of an antibody-dependent cell-mediated cytotoxicity assay relative to the indirect antiglobulin test titer in the management of Rh D-alloimmunized pregnancies. STUDY DESIGN: Data from 172 Rh D-alloimmunized pregnancies were analyzed retrospectively. The accuracies of the highest antibody titer and of the highest antibody-dependent cell-mediated cytotoxicity assay result during pregnancy to predict fetal and neonatal Rh disease, defined as the need for intrauterine (n = 30) or neonatal (n = 37) blood transfusion, respectively, were assessed. RESULTS: At different cutoff levels with equal sensitivities the antibody-dependent cell-mediated cytotoxicity assay consistently showed a higher specificity than the antibody titer for the prediction of fetal disease. No difference was found between the receiver operating characteristic curves of the 2 tests for the prediction of neonatal disease. CONCLUSIONS: Selection of patients for referral and invasive testing for Rh D alloimmunization may be improved with the use of an antibody-dependent cell-mediated cytotoxicity assay.

Benefits and risks of fetal red-cell transfusion after 32 weeks gestation.

OBJECTIVE: To compare the outcome after intrauterine transfusion (IUT) between fetuses treated before and those treated after 32 weeks gestation. SETTING: National referral center for intrauterine treatment of red-cell alloimmunization in The Netherlands. STUDY DESIGN: Retrospective evaluation of an 11 year period, during which 209 fetuses were treated for alloimmune hemolytic disease with 609 red-cell IUTs. We compared fetal and neonatal outcome in three groups: fetuses only treated before 32 weeks gestation (group A, n=46), those treated both before and after 32 weeks (group B, n=117), and those where IUT was started at or after 32 weeks (group C, n=46). RESULTS: Survival rate was 48% in group A, 100% in group B, and 91% in group C. Moreover, fetuses in group A were hydropic significantly more often. Short-term perinatal loss rate after IUT was 3.4% in the 409 procedures performed before 32 weeks and 1.0% in the 200 procedures performed after 32 weeks gestation. CONCLUSION: Perinatal losses were much more common in fetuses only treated before 32 weeks gestation. Two procedure-related perinatal losses in 200 IUT after 32 weeks remain a matter of concern because of the good prospects of alternative extrauterine treatment.

[Blood group immunization: results of treatment of fetal anemia with intra-uterine intravascular blood transfusion in the Netherlands, 1987-1995]. / Bloedgroepimmunisatie: resultaten van behandeling van foetale anemie met intra-uteriene intravasculaire bloedtransfusie in Nederland, 1987-1995.

OBJECTIVE: To evaluate outcome of red cell alloimmunized pregnancies treated with intravascular intrauterine blood transfusions. DESIGN: Retrospective. METHODS: Medical records of all women and neonates treated with intrauterine transfusions in the period March 1987-December 1995, were reviewed. Survival rates of the infants were analysed in relation to both gestational age and the presence or absence of hydrops at the time of the first transfusion. RESULTS: In 153 pregnancies 155 foetuses underwent 462 transfusions (median: 3; range: 1-7). Patients were immunized against RhD in 88%. Kell in 7% and Rhe in 5% of the cases. Overall survival rate was 83%. No difference in survival rate was found between children with the first transfusion early (< or = 26 weeks) or late (> 26 weeks) in pregnancy. Survival rate for foetuses without hydrops was significantly higher than for those with hydrops (90% versus 73%). The mildly hydropic foetuses had a significantly higher survival rate than the severely hydropic foetuses (94% versus 53%). Absence of intrauterine reversal of hydrops was associated with a bad outcome. CONCLUSION: Intravascular transfusion is an effective and safe procedure for correction of foetal anaemia provided it is performed by an experienced multidisciplinary team. In contrast to gestational age at first transfusion severity of hydrops is predictive for successful treatment, so timely institution of treatment is of paramount importance.

Blood gas and pH in the human fetus with severe anemia.

Leiden University Hospital is the national referral center for the management of fetal isoimmunization in The Netherlands. In this observational study, blood gas and acid-base measurements from 286 pretransfusion samples and 214 paired posttransfusion samples of 113 fetuses were analyzed. In umbilical arterial blood, we found a significant positive correlation between the degree of anemia and pH, as well as a significant negative correlation between degree of anemia and pO2. However, umbilical venous blood gas and pH remained virtually unchanged even in severe anemia. During intrauterine transfusion with unbuffered adult red cells, there was a small but statistically significant decrease of pH and pO2 in fetal blood. We conclude that severe fetal anemia is associated with decreased umbilical arterial pH, but that umbilical venous pH remains normal until shortly before death.

Outcome for children treated with fetal intravascular transfusions because of severe blood group antagonism.

OBJECTIVE: To describe the outcome for 92 fetuses treated between May 1987 and January of 1993 with intrauterine (intravascular) transfusions for severe hemolytic disease in comparison with a high-risk and a healthy control group. STUDY DESIGN: Information on the perinatal period was obtained from the patient records. The children regularly attended the outpatient clinic, and a general pediatric examination was performed on each visit. The psychometer development of the child until age 4 1/2 years was assessed according to Gesell. At the age of 5 years, the adaptation part of the Denver Developmental Screening Test and a Dutch-language test were used. A neurologic examination was performed according to Touwen. RESULTS: In our study, 77 (83.7%) of 92 fetuses were born alive after intravascular transfusions. The overall survival rate was 79.3%. The follow-up group included 69 infants, with an age range of 6 months to 6 years. Correlation between antenatal and perinatal features showed a significant negative relationship between the number of intrauterine transfusions and the duration of phototherapy (p = 0.002). The probability that neurologic abnormalities would occur was significantly greater when perinatal asphyxia had been present (p < 0.05) and with a lower cord hemoglobin level at birth (p = 0.03). The total number of children with disabilities was 10.1% (7/69). CONCLUSIONS: The neurodevelopmental outcome for the group of survivors compared favorably with a group of high-risk, very low birth weight infants (10.1% to 18%), and less favorably with a healthy control group (10.1% to 6%).

The disappearance of fetal and donor red blood cells in alloimmunised pregnancies: a reappraisal.

OBJECTIVE: To determine the proportional reduction per day in the number of fetal and donor red blood cells from the fetal circulation after intrauterine intravascular transfusions. DESIGN: A retrospective study of 302 transfusions in 101 fetuses. SETTING: The Department of Obstetrics and Gynaecology of the University Medical Centre Leiden, The Netherlands. METHODS: We measured the haematocrit in fetal samples both before and after repeated intravascular intrauterine transfusion in fetuses with alloimmune disease. The percentage of fetal erythrocytes was determined in Kleihauer-Betke stained smears. The decline of fetal, donor and mixed red blood cells was calculated by dividing the proportional decrease of the haematocrit values of the number of days between transfusions, also after correction for changes in fetoplacental volumes. Results (given as mean [SD]) are derived from the proportional changes of haematocrit per day. RESULTS: The interval between the first and second transfusion (15.5 days [SD 5.2]) was shorter than between subsequent transfusions (means ranging from 21.4 to 21.9 days; P < or = 0.0001). The decline per day of mixed, and of donor red blood cells, calculated without corrections for volume changes did not differ from those corrected for volume changes resulting from the transfusion and from fetal growth (correction factor 1.1 [SD 0.4]). Since the coefficient of variance is smaller for the uncorrected decline values, this type of calculation is preferable for clinical purposes. The disappearance of fetal erythrocytes after the first transfusion (6.1%/day [SD 2.9]) was faster than that of mixed fetal and donor red blood cells (3.2%/day [SD 1.2]; P < 0.0001) and of donor cells alone (1.4%/day [SD 1.6]; P < 0.0001). The decline of the mixed red blood cell population became the same as that of the donor cells (2.2%/day [SD 0.8]) after the second transfusion. This decline of donor cells was higher than after the first transfusion (1.4%/day [SD 1.6]; P < 0.05). After the first transfusion the fetal erythrocytes disappeared faster after transplacental puncture of the umbilical cord (6.6%/day [SD 2.8]) than after transamniotic punctures (5.4%/day [SD 2.7]; P = 0.05). The mixed red blood cell also decreased faster (3.5%/day [SD 1.3] versus 2.8%/day [SD 0.9]; P < 0.01). CONCLUSION: The fast disappearance of fetal erythrocytes, especially after transplacental punctures, shows that the interval between the first and second transfusion needs to be shorter than that for intervals between subsequent transfusions. The number of donor erythrocytes declines by approximately 2% per day.

Body wall defects in two sibs.

We describe 2 sibs, a male fetus with an unusual lumbar hernia and spina bifida occulta, and a female fetus with a median abdominoschisis. The first fetus had some signs of lumbocostovertebral syndrome (LCVS), which consists of a congenital lumbar hernia and associated abnormalities such as absent or hypoplastic ribs, hemivertebrae, and scoliosis. Abdominoschisis has not been described in LCVS, and the given abnormalities in the 2 sibs have not been published to date. One can hypothesize that vascular disruption of a somite or a group of somites may result in the described abdominal wall defects. We conclude that these abnormalities could be coincidental in the 2 sibs or could have a related, probably multifactorial, cause.