[Newborn screening : the point of view of the paediatrician]. / Dépistage néonatal : le point de vue du pédiatre.

Newborn screening is a public health effort that has changed the prognosis of some congenital diseases. Newborn screening programmes differ between countries in which it is organized. Demographic, epidemiological or economic factors play a role in the choice of the screening panel. In the French Community of Belgium, the programme focuses on 13 metabolic and endocrine diseases, hearing loss and hemoglobinopathies (Brussels and Liege). Newborn screening is a complex process that requires the involvement of all stakeholders : parent information, blood sampling or testing, lab analysis, follow-up of the results, initiate adequate care in case of positive test and genetic counselling. Newborn screening programmes will evolve in the next years. New therapeutic and diagnostic methods will make other genetic diseases candidates for screening. Whole genome sequencing may be the next expansion; it will create new opportunities but will pose new ethical dilemmas. We must all prepare now for future challenges.

[Anemia in the elderly]. / L'anémie de la personne âgée.

Anaemia is a problem that affects almost 10% over 65 years and 20% over 85 years. There is no physiological anaemia in the elderly. Any anaemia expresses the existence of a pathological process, regardless of its severity. Anaemia in the elderly is always associated with a poor prognosis that is in terms of mortality, morbidity and risk of fragility. The diagnostic approach to anemia in the elderly is the same as in younger individual. There are many causes of anaemia; anaemia balance is a complex diagnostic process. Most anaemias are due to a deficiency, chronic inflammation or comorbidity. However, in the elderly, the etiology of anaemia is often multifactorial. In a number of cases remain unexplained anaemia. In a number of cases, anemia remain unexplained. Treatment of anaemia is the treatment of the cause, but specific therapeutic aspects to the elderly should be considered, as among other martial substitution or use of erythropoietin (EPO).

Early NT-proBNP is able to predict spontaneous closure of patent ductus arteriosus in preterm neonates, but not the need of its treatment.

The objective of this study was to establish the potential utility of N-terminal pro-brain natriuretic peptide (NT-proBNP) in the management of patent ductus arteriosus (PDA). This was a monocentric prospective blind study that was conducted in a referral neonatal intensive care unit. The patients were very low-birth-weight/gestational-age neonates. Babies with cardiac congenital anomaly other than PDA, life-threatening congenital malformation, severe asphyxia at birth, persistent pulmonary hypertension, and death within the first week of life were excluded. Plasma NT-proBNP concentrations were determined on days 2, 4, and 7 of life. Echocardiography was performed on days 4 and 7. Results were blinded to clinicians. Only echographic results were available upon request. Thirty-one infants were included. NT-proBNP levels were significantly correlated to ductal size and to left atrial-to-aortic diameter ratio. The median NT-proBNP on both days 2 and 4 was significantly higher in neonates with later treated or persistent PDA. A level above 10.000 pg/mL at 48 h of age yielded a 100% positive and a 87% negative predictive value to exclude spontaneous ductal closure. However, no NT-proBNP threshold could predict which PDA would be judged necessary to treat. It was concluded that early low NT-proBNP values can be used as a reliable independent marker to predict spontaneous ductal closure in preterm neonates. Yet, high NT-proBNP levels should not be used to guide the decision to treat PDA, the risk being of treating many bystanding PDAs.

[Qualitative analysis of the offer for prevention and caring of sickle cell anaemia in Brussels]. / Analyse qualitative de l'offre pour la prevention et la prise en charge de la drépanocytose à Bruxelles.

Sickle cell disease (SCD) is the first genetic disease in the world and remains largely ignored by the population but also by health professionals. SCD is characterized by a variable clinical expression, however most of the patients are at risk to develop acute and severe complications conducting to a fatal issue. This study develops a qualitative approach to analyze the adequacy between the services offered for those patients in Brussels and the sociocultural characteristics of the target population and more specifically of the migrant population originating of sub-saharan Africa which is the most concerned. To have a global vision of the preventive and care services provided for SCD in Brussels, semistructured interviews were conducted with health professionals and patients associations. The results were analyzed to determine if they match the expectations of health professionals and audiences across the voluntary sector. The results show the absence of a real recognition at the national level of sickle cell anaemia, a deficit in psychosocial care of patients and their families. SCD is often considered by the African community as a disease of the curse which has to be hidden. To the physical pain and multiple organ complications one must add a psychological distress that patients drive back into silence. The management of this disease therefore requires a dedicated approach. With the exception of newborn screening performed in all maternity hospitals in Brussels and Liège, there is no specific measure for the management of SCD in Belgium.

Prevalence of sickle cell disease in a northeastern region of the Democratic Republic of Congo: what impact on transfusion policy?

Transfusion therapy may save the lives of patients with sickle cell disease (SCD), but it is also associated with a high risk of transmission of infection. The aims of this study were to determine the prevalence of SCD in a northeastern region of the Democratic Republic of Congo (DRC), and to define ways in which the procedures involved in the security of transfusions should be improved. During a 3-month period in 2006/2007, 520 samples of umbilical cord blood were obtained through neonatal screening in five health centres in Kisangani. The samples were analysed using an isoelectric focusing technique. The estimated prevalence of sickle cell trait and SCD in the population tested was 23.3 and 0.96%, respectively. These numbers will be presented for the attention of the health authorities in DRC with responsibility for SCD and they will be asked to consider improvements in treatment procedures for SCD, such as blood transfusions, as a public health priority.

Sickle cell disease from Africa to Belgium, from neonatal screening to clinical management.

AIM: To describe the severity of sickle cell disease (SCD) in newborns in Belgium and evaluate the impact of neonatal screening (NS) on clinical outcome. METHODS: Universal NS of umbilical cord blood for hemoglobinopathy was progressively deployed in Brussels and Liège starting in 1994. No particular population was targeted. Samples were analyzed initially using the isoelectric focusing technique and since 2008 the capillary electrophoresis technique. If a hemoglobin variant was suspected, further analysis was carried out using high performance liquid chromatography. Children presenting major hemoglobinopathy, especially SCD, were referred to a specialized centre for comprehensive management. Preventive measures included antipneumococcal prophylaxis immunization/antibiotic therapy, parental training to recognize severe anemia and splenic sequestration, and transcranial ultrasound recording for early detection of intracranial stenosis. A database was set up in Belgium to collect clinical and laboratory data including parental phenotype, diagnostic technique (neonatal screening or not), major clinical events (episodes of dactylitis, acute chest syndrome, severe anemia, infection, etc), number and duration of required hospitalizations, and treatment used. RESULTS: Screening of 222352 newborns in maternity units in Brussels led to diagnosis of SCD in 145 patients, Adequate data for analysis of clinical outcome was available for 96 of these children born before 2007. Median age in the study group was 4.2 years and the total duration of follow-up was 510 years. Most cases occurred in families from the Democratic Republic of Congo. (64/96 patients; 66.7%) and involved homozygous hemoglobin S disease (80/96 patients; 83.3%). Twenty-seven percent of patients (26/96) presented no severe clinical events during the study (17 SS, median age 2,1 years (0-13.1 years). Conversely 33% presented an episode of dactylitis and 47.9% (46/96) presented recurrent vasoocclusive crises. Severe anemia was observed in 39.6% (38/96) of cases. Six patients (6.3%) developed septicemia despite prophylactic antibiotic therapy and anti-pneumococcal immunization using heptavalent conjugate vaccine and polysaccharide vaccine, No penicillin-resistant strains were observed. The incidence of stroke was 2.1% (3/96). Two patients presenting homozygous hemoglobin S disease died due to septicemia due to non-compliance with antibiotic therapy in one case and severe anemia in one case. All episodes of septicemia and both deaths occurred at the beginning of the NS program. Hydroxyurea therapy was used in 30 patients (31.2%) including 7 in whom transcranial Doppler depicted blood flow abnormalities and 8 in whom allogeneic bone marrow transplantation was performed. CONCLUSIONS: Sickle cell disease is still associated with high morbidity and mortality but clinical care has improved and no death has occurred in the last 10 years. NS is an effective tool for early detection and management of SCD. Neonates with SCD diagnosed by NS in Belgium presented severe manifestations, but clinical outcomes were improved by comprehensive management.

[Hemoglobin sickle cell disease: experience of the Yalgado Ouedraogo University Hospital of Ouagadougou, Burkina Faso]. / Le syndrome drépanocytaire de type hémoglobine SC : expérience du CHU Yalgado Ouédraogo de Ouagadougou (Burkina Faso).

OBJECTIVES: To evaluate the clinical features of children with hemoglobin sickle cell disease (HbSC) and compare them to children with sickle cell anemia (HbSS). POPULATION AND METHODS: This was a descriptive and retrospective study. New patients with sickle cell disease who consulted at the Yalgado Ouédraogo University Hospital's Pediatric Center in Ouagadougou, Burkina Faso, between May 2005 and June 2006, were included. They were free of any major disease unrelated to sickle cell disease. Clinical and laboratory results reported for these children were based on their health book and medical records. RESULTS: Sixty-one children were included in the study, 38 and 23 children were positive for HbSC and HbSS, respectively; there was no significant difference between the 2 groups in terms of sex ratio or mean age at inclusion. Mean age at diagnosis was 5 years and 2 years for HbSC and HbSS children, respectively. The first clinical event appeared at a significantly later age for HbSC than HbSS children (4 years versus 2 years). Painful episodes were equivalent in mean number per year and mean length per episode between the 2 groups; the median hemoglobin (Hb) level at inclusion was significantly higher for HbSC than for HbSS children, i.e., 95 g/l versus 70 g/l. CONCLUSION: At the Yalgado Ouédraogo University Hospital Pediatric Center, children with HbSC disease presented clinical and biological features very similar to those with HbSS.

[Major alpha-thalassemia: antenatal diagnosis, case report and literature review]. / Alpha-thalassémie majeure: à propos d'un cas de dépistage anténatal et revue de la littérature.

Homozygous alpha-thalassaemia or Bart's hydrops fetalis is a genetic disease with autosomal recessive transmission. The condition is lethal for the fetus because of hypoxia and anemia. For the mother there is an increased risk of the severe forms of preeclampsia and its complications. The diagnosis can be suspected in presence of suggestive ultrasonographic anomalies, where both parents come from South-East Asia or China. Confirmation is based on the identification of the typical deletions or mutation of the alpha globin gene by molecular genetics. We report a rare clinical case of Bart's hydrops fetalis diagnosed because of fetal growth retardation, fetal cardiomegaly and increased size of placenta on the 26 weeks fetal echography. This case underscores the need to include the alpha thalassemias in medical and midwifery education in countries where they were almost inexistent a generation ago.

[Sickle cell disease: an anonymous survey of physicians in Burkina Faso]. / Les syndromes drépanocytaires majeurs: une enquête anonyme auprès du corps médical au Burkina Faso.

The purpose of this survey was to evaluate the experience of physicians in Burkina Faso with haemoglobinopathy (particularly sickle cell disease). Survey findings showed that these pathologies were encountered in daily medical practice but that resources necessary to insure proper prevention, follow-up and treatment were insufficient. Practitioners expressed the need for better continuous medical education and for information campaigns to familiarize the public.

Hereditary spherocytosis veiled by anemia and iron deficiency.

Permanent significant hyperchromia, equivalent to hyperspherocytosis, the leading symptom of hereditary spherocytosis (HS), has become accessible to routine screening by hematologic automats using double angle laser technology. This has resulted in the discovery of a much higher incidence of this anomaly. In previous investigations we suggested the permanence of significant hyperchromia as obligate criterion for the diagnosis HS. Intercurrent normal percentages of hyperchromic RBC rather pointed to secondary, non-hereditary spherocytosis. Describing 6 typical cases, we demonstrate that occasional normal percentages of hyperchromic red blood cells occurring during phases of anemia and/or iron deficiency are compatible with the diagnosis of HS.

[Sickle cell disease: exotic disease or a Belgian public health problem?]. / La drépanocytose: une affection exotique ou un problème de santé publique en Belgique?

Sickle cell disease is a genetic disorder involving the haemoglobin designated as haemoglobin S, an autosomic recessive hereditary disease. It is the most frequent hereditary disease in sub-Saharan Africa, however epidemiological studies performed with a systematic neonatal screening in Brussels and Liège have proven that more than one neonate over 2.000 has a sickle cell disease. If this amount is significant, at the level of each physician the number of patient-contacts will be weak. Another aspect of the disease is the variability in its expression: some patients suffer from multiple and chronic organ alterations while other suffer also from acute events which might lead to death if not treated appropriately. The poor experience of each physician, the lack of the disease knowledge by the population, the symptoms complexity, and the socio-economical aspects of sickle cell disease explain that it can be considered as an "exotic" disease but also as a public health problem. A global and dedicated approach of the patient as a whole must be implemented. This is the reason for the existence of the "Réseau des Hémoglobinopathies": http://www.redcellnet.be/.

Distribution of lactate dehydrogenase isoenzymes in coelomic fluid and fetal adnexae.

The objective of this study was to evaluate the distribution of lactate dehydrogenase isoenzymes in the human gestational sac. Total lactate dehydrogenase and its isoenzymes were measured in matched coelomic fluid and samples of villous and decidual tissues collected at the time of pregnancy termination in a group of 16 healthy women who were between 7 and 12 weeks of gestation. In addition intact secondary yolk sacs (n = 2) and fragments of fetal liver (n = 3) were collected. For comparison, samples of placental tissue, amniotic membrane and chorion obtained at term, were also investigated. In early pregnancy, H-type lactate dehydrogenase isoenzymes predominate in placental villous tissue and coelomic fluid, whereas M-type lactate dehydrogenase isoenzymes predominate in extracts of decidua, secondary yolk sac and fetal liver. These results highlight the important contribution of placental bioproducts to the constitution of the coelomic fluid. We observed also that placental patterns of lactate dehydrogenase isoenzymes change between the first and the third trimester of gestation, from the H-type to the M-type lactate dehydrogenase isoenzymes. We suggest that the lactate dehydrogenase pattern might be an indicator of proliferative or differentiative potential of the trophoblastic cells throughout pregnancy.

The human first trimester gestational sac limits rather than facilitates oxygen transfer to the foetus--a review.

Oxygen (O2) free radicals are a potential teratologic threat to the foetal tissues and are known to be involved in the pathophysiology of common human pregnancy disorders such as miscarriage and pre-eclampsia. During the first two months of human gestation, the placenta surrounds the whole gestational sac, the villi contain only a few capillaries located mainly within the centre of the mesenchymal core, the trophoblastic layer is twice the thickness it will be in the second trimester, the foetal red cells are nucleated and the exocoelomic cavity (ECC) occupies most of the space inside the gestational sac. The ECC contains no oxygen transport system, but anti-oxidant molecules that may provide additional protection to the embryo from oxidative damage are present. Ultrasound and anatomical studies have also demonstrated that the intervillous circulation starts in the periphery of the placenta at around 9 weeks of gestation, and that it becomes continuous and diffuse in the entire placenta only after 12 weeks. Overall, these anatomical features provide indirect evidence that the architecture of the human first trimester gestational sac limits foetal exposure to O2 to what is strictly necessary for its development. These results are in agreement with the concept that the placenta and foetus develop in a physiologically low O2 environment and that its metabolism must be essentially anaerobic. Because of these anatomical arrangements, different nutritional pathways to those operating during most of pregnancy must serve the first-trimester foetus. Up to 9 weeks of gestation, foetal nutrition appears to depend on uterine glandular secretions that are delivered into the intervillous space, supplemented by maternal plasma proteins and other molecules that may percolate through the trophoblastic shell. These molecules diffuse through, or are transported by, the trophoblast of the villi and the chorionic plate into the ECC. From here they are absorbed by the secondary yolk sac (SYS), in which the extraembryonic circulation is probably first established. At the end of the first trimester, the SYS and two-thirds of the placental mass degenerate, and the ECC is progressively obliterated by the enlarging amniotic cavity. The trophoblastic plugs occluding the utero-placental arteries are gradually dislocated, allowing maternal blood to flow into the intervillous space, and the uterine glands involute. These major anatomical transformations modify considerably the spatial relationships between the maternal tissues and the developing embryo, and, consequently, the materno-embryonic exchange pathways. Overall the comparison of morphological features with physiological findings reveals that the architecture of the human first trimester gestational sac is designed to limit foetal exposure to oxygen to that which is strictly necessary for its development, and that during early pregnancy alternative nutritional pathways are in use.

Normal and abnormal p21 h-ras posttranslational products in human neoplastic and nonneoplastic liver-tissues.

Using two-dimensional Western blot analysis with a pan-ras antibody, we previously defined conditions that allow to resolve the four post-translational p21-H-ras products expressed in normal mature rat tissues. Using the same approach, we conducted experiments that sometimes revealed deviations from the normal basal p21-H-ras pattern in primary human liver tumors. One type of alteration encountered was indicative of modifications in the relative rate of accomplishment of the different steps in the post-translational metabolisation of the protein, resulting in the accumulation of precursors of the fully-processed p21-H-ras product. This was also observed during ontogenesis and might thus be correlated with either cellular growth potential or differentiation. The second type of altered pattern is defined by the detection of abnormal spots and probably corresponds to the presence of mutant p21-ras products.

Immunodetection of the p21-ras products in human normal and preneoplastic tissues and solid tumors: a review.

Immunohistochemical detection of p21-ras to identify and characterize preneoplastic or neoplastic lesions in human tissues is reviewed. Information concerning the commercially available antibodies is presented. Antibodies DWP, Ras-10, Y13-259, YA6-172, NCC-001, and NCC-004 are fully documented with respect to their behavior in appropriate specificity tests and appear to be reliable reagents. After reviewing the data we have identified three groups of tissues or organs with respect to positive immunostaining for p21-ras as the significant criterion of malignancy. These three groups comprise (1) tissues for which no definite conclusion could be drawn (colon, lung, bladder, ovary, and neural and odontogenic tissues) despite occasional claims to the contrary, (2) tissues for which conclusions were negative (pancreas and stomach), and (3) tissues for which p21-ras staining positively discriminated malignant from normal tissues (liver, uterus, and salivary gland). Immunohistochemically detectable levels of products from a mutated ras gene could be demonstrated in a fraction of the samples from colon, lung, and bladder carcinomas, as well as in some histologically normal tissues adjacent to a colon carcinoma. The possibility that a higher relative intensity of the immunostaining reaction for p21-ras might discriminate malignant tissues from normal tissues or benign lesions in breast, pancreas, stomach, lung, uterus, or thyroid samples is suggested. Further studies now appear warranted and a strategy is proposed to validate the conclusions reached thus far.

Hydroxyurea treatment for sickle cell disease: impact on haematopoietic stem cell transplantation's outcome.

Since 1988, 24 children have undergone haematopoietic stem cell transplantation (HSCT) for severe sickle cell disease (SCD) in our unit, 13 being grafted after having been exposed to hydroxyurea (HU) to control SCD-related complications. Different pre-transplant conditioning regimens were given over time: Bu14/Cy200 in six patients (group 1), Bu16/Cy200/antithymocyte globulin (ATG) in five (group 2) and Bu16/Cy200/ATG with HU prior to HSCT in 13 (group 3). The aim of this study is to compare the outcome after HSCT of these groups of patients, which differ according to pre-transplant drug exposure. Overall, 20 of the 24 transplanted children had stable engraftment and have remained free of SCD-related symptoms after HSCT; 19 of them are currently alive and cured of SCD. In group 1 (HU-, ATG-), we observed one unexplainable late death, one absent engraftment, one late rejection and one mixed stable chimerism. In group 2 (HU-, ATG+), we observed the absence of engraftment in two patients and one early rejection. In group 3 (HU+, ATG+), we observed no cases of either absent engraftment, mixed stable chimerism or late rejection. In our experience, pre-transplant treatment with HU seems to be associated with a lower incidence of rejection/absent engraftment in severe SCD patients. These results need to be confirmed with a larger number of patients.

Fetal amino acid and enzyme levels with maternal smoking.

OBJECTIVE: To assess the influence of active maternal smoking on fetal amino acid and enzyme levels in early pregnancy. METHODS: The concentrations of 23 free amino acids and total protein, and the activity levels of four enzymes were measured in samples of maternal and fetal plasma from nine nonsmokers who were not exposed to tobacco smoke and nine long-term, heavy smokers matched for gestational age. To determine fetal exposure to smoking, cotinine levels were measured in maternal and fetal plasma and fetal liver samples from both groups. The pregnancies were between 12 and 17 weeks' gestation. RESULTS: In women who smoke, the median cotinine concentrations were 156 mg/mL in maternal plasma and 89 ng/mL in fetal plasma, but only one fetal liver sample contained detectable cotinine. Significantly lower concentrations of serine, proline, alpha-aminobutyric acid, leucine, and arginine were found in smokers compared with nonsmokers, with the lowest in arginine. Fetal plasma amylase activity was significantly higher in smokers than controls. There were no differences in concentrations of other amino acids or activity levels of other enzymes in the two groups. CONCLUSION: Maternal smoking affected placental and fetal protein metabolism and enzyme activity from at least 12 weeks' gestation. That finding indicates that high levels of tobacco exposure in the first trimester might cause irreversible changes in the cellular functions of the villous trophoblastic barrier.

Chronic maternal smoking and cord blood amino acid and enzyme levels at term.

OBJECTIVE: To assess the influence of chronic active maternal smoking on cord blood amino acid and enzyme levels at term. METHODS: The concentrations of 24 free amino acids, total protein, and five enzymes were measured in samples of maternal and fetal cord venous plasma from 24 nonsmokers who were not exposed to tobacco smoke and 24 chronic smokers. Cotinine levels were also measured in maternal plasma to evaluate fetal tobacco exposure. The pregnancies were between 37 and 40 weeks' gestation, were uncomplicated, and were delivered vaginally. RESULTS: Fetal weight was significantly (P <.01) lower in the smokers than in controls. A positive significant (P <.001) correlation was found between maternal and umbilical venous cotinine concentrations. Significantly lower concentrations of aspartic acid (P <.01), hydroxyproline (P <.05), threonine (P <.005), alanine (P <.05), alpha-aminobutyric acid (P <.001), methionine (P <.05), tyrosine (P <.001), phenylalanine (P <.01), and lysine (P <.05) were found in the venous cord plasma of the smokers compared with nonsmokers. The fetomaternal ratios were similar in both groups. The umbilical plasma alkaline phosphatase activity was significantly (P <.01) lower in the smokers than in the controls. CONCLUSION: Chronic maternal smoking is associated with alterations of protein metabolism and enzyme activity in fetal cord blood. These may be secondary to irreversible changes in the cellular functions of the trophoblast and may contribute to fetal growth restriction.

Maternal tobacco exposure and cotinine levels in fetal fluids in the first half of pregnancy.

OBJECTIVE: To evaluate the distribution of cotinine in fetal fluids and serum during the first half of pregnancy, and compare the fetal and maternal cotinine levels in passive and active smokers. METHODS: Maternal smoking status was determined by questionnaire in 85 pregnant women requesting abortion for psychosocial reasons between 7 and 17 weeks' gestation. Coelomic and amniotic fluid samples were collected between 7 and 11 weeks and fetal blood and amniotic fluid between 11 and 17 weeks. Cotinine levels were measured by radioimmunoassay. RESULTS: Women classified themselves as nonsmokers in 40 cases, passive smokers in 19 cases, and voluntary smokers in 26 cases. Five nonsmokers, 16 passive smokers, and all smokers had cotinine levels above the detection limit of the assay. Cotinine was invariably found in coelomic, amniotic, and fetal serum when maternal serum and urine cotinine levels exceeded 25 and 250 ng/mL, respectively. Higher cotinine levels were found in fetal fluids and serum than in maternal serum. Positive linear correlations were found between maternal urine and amniotic fluid cotinine concentrations (r = .75), between maternal urine cotinine concentration and number of cigarettes smoked per day (r = .66), and between maternal and fetal serum cotinine concentrations (r = .97). CONCLUSION: Cotinine accumulates in the fetal compartments as early as 7 weeks' gestation in both active and passive smokers. Women should be advised to give up smoking from conception and avoid environmental tobacco smoke exposure.

Distribution of iron and iron-binding proteins in first-trimester human pregnancies.

OBJECTIVE: To investigate the iron distribution between the maternal and embryonic compartments in the first trimester of pregnancy. METHODS: Coelomic and amniotic fluids (AF) and maternal serum were collected from 36 apparently normal pregnancies at 7-13 weeks of gestation. Iron, transferrin, ferritin, and lactoferrin were measured in all samples. Iron concentrations were also measured in placental villi, liver, gut, and brain samples collected from two embryos. RESULTS: Significantly (median value) lower iron and transferrin levels and higher levels of ferritin were found in the coelomic fluid (iron 4.8 mumol/L; transferrin 0.22 g/L) than in maternal serum (iron 21 mumol/L; transferrin 2.5 g/L). The AF contained significantly lower levels of iron and ferritin (iron less than 1.8 mumol/L; ferritin 2.0 micrograms/L) than both coelomic fluid (iron 4.8 mumol/L; ferritin 287 micrograms/L) and maternal serum (iron 21 mumol/L; ferritin 49 micrograms/L). Transferrin was undetectable (less than 0.08 g/L) in AF samples, and lactoferrin was undetectable (less than 2 micrograms/mL) in both embryonic fluids. The iron concentration in the coelomic fluid increased significantly (P < .001) with advancing gestation (iron at 7-9 weeks 3.8 mumol/L; 9.1-11 weeks 5.9 mumol/L). There was a nonsignificant correlation between coelomic fluid and maternal serum iron and iron-binding protein levels. The highest iron levels were found in the liver (52 mmol/kg dry weight) and brain (49 mmol/kg dry weight) tissues. CONCLUSIONS: The distribution of iron and iron-binding proteins between the maternal and embryo-placental compartments in the first trimester is comparable to that found later in gestation, suggesting that placental iron transfer may occur as early as tertiary villi are formed. The exocoelomic fluid is probably the main iron reservoir in early pregnancy, and the secondary yolk sac is probably the principal route of entry of iron to the embryo.