Kjell Haram

Iron requirement in normal pregnancy as assessed by serum ferritin, serum transferrin saturation and erythrocyte protoporphyrin determinations

Summary. Serum iron, serum iron‐binding capacity, serum ferritin and erythrocyte protoporphyrin were determined during uncomplicated pregnancy in 45 healthy women; 22 were given oral iron while the others were given a placebo. When iron was not given, 15 out of 23 women had exhausted iron stores and iron deficiency at term, as judged from low serum ferritin, low serum transferrin saturation and high erythrocyte protoporphyrin values. Only seven of them had a haemoglobin concentration between 10 and 11 g/dl at term but none had values < 10 g/dl. In the iron‐treated group (n=22) none of the women developed iron deficiency. Serum ferritin was the most sensitive and specific test of iron deficiency. A practical procedure to detect iron deficiency and to control iron supplementation in pregnancy is suggested.

Serum protein pattern in normal pregnancy with special reference to acute‐phase reactants

Summary. The concentrations of acute‐phase protein reactants, total protein, albumin and globulin fractions were measured throughout normal pregnancy in 27 women. α1‐Antitrypsin and caeruloplasmin concentrations increased gradually to reach their highest levels in the third trimester. Orosomucoid and haptoglobin showed similar patterns: higher levels in the first and third trimester with a decline around 24 weeks gestation. C‐Reactive protein showed levels similar to those of non‐pregnant healthy individuals (< 5 mg/1) throughout pregnancy. α1,‐, α2 and β‐Globulin concentrations increased from the first trimester towards term. γ‐Globulin concentration changed little during gestation. The data obtained provide reference ranges for serum proteins in healthy pregnancy.

Serum Urate as a Predictor of Fetal Outcome in Severe Pre‐Eclampsia

Abstract. Maternal serum urate levels were studied in 50 normal pregnancies and 72 cases of severe pre‐eclampsia. Markedly elevated levels of serum urate were found in severe pre‐eclampsia, compared with normal pregnancy. In severe pre‐eclampsia significantly higher levels were found prior to parturition in cases of growth retardation and perinatal distress, compared with patients whose newborns were of normal size and condition. Particularly high serum urate levels were found early in the third trimester in cases of perinatal death. A slight but significant correlation was found between the weight centile of the newborn and the last maternal urate level before parturition. A rapidly rising urate level reliably predicted perinatal distress. The last maternal serum urate before parturition was correlated with the hemoglobin and erythrocyte volume fraction values in the same blood sample.

Iron supplementation in pregnancy – evidence and controversies

Approximately 20% of women in industrialized countries have iron deficiency in pregnancy. This article focuses on the diagnostic problem of anemia and iron deficiency and discusses different strategies for iron supplementation in pregnancy. S‐ferritin is commonly used to diagnose empty iron stores and is considered useful early in pregnancy as a diagnostic tool. Mean cellular volume (MCV), s‐Fe and erythrocyte distribution width is too unspecific. Serum transferrin receptor (sTfR) is a relatively novel promising indicator of iron deficiency. Iron demands of the pregnant women are discussed as well as the dietary content of iron. Both beneficial and adverse effects of iron supplementation are outlined. It is not documented that supplementation has any substantial effect on birth weight or various complications in pregnancy. However, supplementation corrects the iron store and biochemical parameters of iron deficiency including hemoglobin concentration (Hb) and maintains the maternal iron stores in the puerperium. Recent literature also suggests that iron supply to the pregnant women may have beneficial effects on the iron content of neonates the first year of life.

Transplacental Passage of Ketamine after Intravenous Administration

This study was designed to measure how fast and at what concentrations ketamine would enter the foeto‐placental circulation, when administered intravenously to 10 healthy mothers immediately before forceps delivery, which was indicated by a delayed second stage of labour. It is shown that ketamine very rapidly passes the placenta, and that ketamine levels in cord blood exceed the levels in the maternal venous blood as early as 1 min 37 s after the injection. The ketamine levels in cord blood reach a maximum in the period 1 min 37 s to 2 min 5 s after the injection. Later they show a tendency to decline. A short‐lasting, marked elevation of blood pressure was produced by the ketamine anaesthesia. Two of the newborn showed low Apgar scores at 1 min. In one of them this was probably attributable to the anaesthesia.

Suspected big baby: a difficult clinical problem in obstetrics

Background. Large for gestational age fetuses, also called macrosomic fetuses, represent a continuing challenge in obstetrics.

Intrauterine growth restriction.

This study reviewed the screening, diagnosis, prophylaxis, and treatment of intrauterine growth restriction using the PubMed database for key words and the Cochrane database for systematic reviews. Identification of risk factors and measurement of symphysis–fundus height are currently the screening standards. Diagnosis is verified by ultrasonography. Accuracy of diagnosis may be improved by using customized fetal growth curves, symphysis–fundus height charts, and 3‐dimensional ultrasonographic evaluation and measuring umbilical artery Doppler dimensional ultrasonographic evaluation measuring umbilical artery Doppler impedance. Prophylaxis with acetylsalicylic acid, started in the first or second trimester or combined with heparin before conception, may reduce the incidence of growth restriction in specific groups at high risk. Active management may reduce incidence in patients with mild to moderate asthma, and targeted treatment of infections may also be beneficial. Antenatal corticosteroid treatment also reduces the perinatal morbidity and mortality associated with IUGR. Bed rest has no demonstrated beneficial effects.

Paroxysmal nocturnal hemoglobinuria in pregnancy.

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hemolytic anemia in which a defect of glycophosphatidylinositol (GPI)‐anchored proteins in the cell membrane of bone marrow stem cells leads to increased sensitivity of the red cells to complement, causing intravascular hemolysis and hemoglobinuria. Other clinical features of this disease are cytopenia and an increased frequency of thrombotic events. We report a case of a pregnant woman with PNH on high‐dosage anticoagulation therapy, the follow‐up during the pregnancy, the delivery and the postpartum period. The obstetric literature on women with PNH is reviewed, the maternal and fetal risks are evaluated and the management of pregnancies and deliveries in such patients are discussed. During the pregnancy our patient was hypertransfused and used anticoagulation treatment. A healthy child was delivered in week 37 by cesarean section because of premature rupture of the membranes, unsuccessful induction and intrauterine infection. Because of bleeding problems a hysterectomy also had to be performed. In the postpartum period the patient developed her second episode of a liver vein thrombosis. She recovered gradually and 18 months after the delivery her disease is now in a stable phase. The literature shows a high maternal morbidity and mortality among pregnant PNH patients. Fetal wastage and prematurity rate are also high. Pregnancy in patients with PNH represents a high‐risk situation for both the mother and the child and should not be recommended. A pregnant PNH woman should be followed closely by both obstetricians and hematologists.

Haemoconcentration in severe pre‐eclampsia

Summary. The last maternal haemoglobin (Hb) concentration before delivery was related to the perinatal outcome in 87 non‐anaemic women suffering from severe pre‐eclampsia. Abnormally high Hb concentrations were found in most women with evidence of placental dysfunction. An inverse correlation was found between the centile weight of the newborn and the maternal Hb. Significantly higher Hb levels were found in pregnancies complicated by fetal growth retardation and perinatal distress compared with those in pregnancies with good outcomes. Particularly high levels were found in pregnancies that ended in perinatal deaths. The hypothesis is put forward that raised haemoconcentration during severe pre‐eclampsia causes increased maternal blood viscosity which predisposes to placental pathology and initiates a vicious circle.

Genetic Aspects of Preeclampsia and the HELLP Syndrome

Both preeclampsia and the HELLP syndrome have their origin in the placenta. The aim of this study is to review genetic factors involved in development of preeclampsia and the HELLP syndrome using literature search in PubMed. A familial cohort links chromosomes 2q, 5q, and 13q to preeclampsia. The chromosome 12q is coupled with the HELLP syndrome. The STOX1 gene, the ERAP1 and 2 genes, the syncytin envelope gene, and the −670 Fas receptor polymorphisms are involved in the development of preeclampsia. The ACVR2A gene on chromosome 2q22 is also implicated. The toll-like receptor-4 (TLR-4) and factor V Leiden mutation participate both in development of preeclampsia and the HELLP syndrome. Carriers of the TT and the CC genotype of the MTHFR C677T polymorphism seem to have an increased risk of the HELLP syndrome. The placental levels of VEGF mRNA are reduced both in women with preeclampsia and in women with the HELLP syndrome. The BclI polymorphism is engaged in development of the HELLP syndrome but not in development of severe preeclampsia. The ACE I/D polymorphism affects uteroplacental and umbilical artery blood flows in women with preeclampsia. In women with preeclampsia and the HELLP syndrome several genes in the placenta are deregulated. Preeclampsia and the HELLP syndrome are multiplex genetic diseases.