Placental expression of glycophosphatidylinositol (GPI)-anchored proteins in paroxysmal nocturnal haemoglobinuria.

Paroxysmal nocturnal haemoglobinuria (PNH) is a clonal stem cell disorder in which a defect of glycophosphatidylinositol (GPI)-anchored proteins leads to higher morbidity and mortality because of intravascular haemolysis, haemoglobinuria, pancytopenia and an increased frequency of thrombotic events. We report here the clinical features of a pregnant woman with PNH and present an immunhistochemical analysis of complement regulators, leukocyte activation markers and placental alkaline phosphatase (PALP) on syncytiotrophoblasts and inflammatory cells in her placenta. Placental tissue from normal deliveries served as controls. The patient had severe PNH with haemolysis, thrombosis episodes and signs of bone marrow failure. Placental syncytiotrophoblasts and villous cells of fetal origin in both normal placentas and the placenta from the PNH patient expressed PALP and the complement regulators CD46, CD55 and CD59. Additionally, CD11b-positive leukocytes of presumed maternal origin were negative for CD15 in the PNH placenta, while they stained positive within the villous space and in normal placentas. These findings show that fetally derived cells in the PNH placenta expressed GPI-linked molecules that are known to be of importance for a successful pregnancy outcome.

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.

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.

[Suspected large fetus in the last period of pregnancy--a difficult problem]. / Mistanke om stort foster i siste del av svangerskapet--et vanskelig problem.

BACKGROUND: In pregnancy surveillance a large symphysis-to-fundus measure raises several questions concerning delivery. MATERIAL AND METHODS: We review various problems with large for gestation age foetuses, also called macrosomic foetuses. We have performed literature searches mainly through PuBMed, which includes the Medline database. The clinical problem is discussed from the primary care provider's point of view and from those of the patient and the obstetrician. RESULTS: Macrosomia is defined as foetal weight above the 90th percentile, birth weight above 4000 g or 4500 g, or birth weight over + 2 SD of the mean birthweight by age. The diagnosis is difficult, even with various sonographic procedures. Abdominal circumference alone appears to have the same diagnostic value as the use of a combination of biparietal diameter, femur length and abdominal circumference. INTERPRETATION: Based on the literature, labour should not be induced or caesarean section performed in non-diabetic pregnancies unless the estimated foetal weight is above 5000 g. A great number of caesarean sections would have to be performed to avoid a single case of plexus brachialis paresis due to difficult shoulder delivery. The best policy is to await spontaneous birth or to induce birth after the completion of 42 weeks. In pregnancies complicated by diabetes mellitus, there are reasons for selective induction of labour if macrosomia is suspected, and for caesarean section if the calculated birth weight is above 4000 g. As the problem of difficult shoulder delivery cannot be completely avoided, each department should have a strategy to handle such a situation. Various procedures for managing the difficult shoulder delivery are described.

[HELLP syndrome]. / HELLP-syndromet.

BACKGROUND: The HELLP syndrome (H = hemolysis, EL = elevated liver enzymes, LP = low platelets) is a pregnancy complication which affects 10-20% of cases of severe preeclampsia. MATERIAL AND METHODS: The article is a review of the literature. RESULTS: Approximately 70% of HELLP syndrome cases occur before delivery, 15% as early as in the second trimester, the remainder after delivery. The classical HELLP syndrome is characterised by abdominal pain, pathological liver tests and low platelets. However, some cases are atypical; hypertension and abdominal pain may both be absent. Genetic as well as immunologic factors are involved in the pathogenesis. There is an imbalance in the coagulation process in the placenta. Activated leukocytes and macrophages induce production of cytokines that may reach the general circulation and cause endothelial dysfunction. In the HELLP syndrome fibrin deposits are also found in the vessels and in the liver sinusoides. INTERPRETATION: A mother with a classic HELLP syndrome should be delivered after stabilisation of the clinical condition. A partial HELLP syndrome can be observed. Treatment with corticosteroids is beneficial.

[Pathophysiology and clinical manifestations in pre-eclampsia]. / Patofysiologi og kliniske manifestasjoner ved preeklampsi.

BACKGROUND: Preeclampsia is a progressive, multisystem disorder characterised by hypertension and proteinuria. A body of evidence suggest a genetic basis; it is generally accepted that the underlying pathological processes are in the placenta. MATERIAL AND METHODS: This article is a review of the pathophysiology of preeclampsia based on literature mainly obtained through PubMed and Medline searches. RESULTS: A poorly perfused placenta, secondary to defective placental invasion of the spiral arteries, may lead to hypoxia and insufficient perfusion and cause release of cytokines which damage endothelial cells and cause dysfunction. Women with preeclampsia have markedly elevated concentrations of triglyceride-rich lipoproteins. Lipid peroxidation also causes endothelial dysfunction and thus contributes to preeclampsia. Placenta is one source of the lipid peroxides. Antioxidant deficiency is also a predisposing factor. Hyperhomocysteinaemia, protein S and protein C deficiency, and activated protein C resistance appear to be involved in the pathophysiology of severe preeclampsia and early onset preeclampsia. INTERPRETATION: The new information about mechanisms for development of preeclampsia gives a basis for new treatment modalities.

[Pre-eclampsia--a review]. / Preeklampsi--en oversikt.

BACKGROUND: Preeclampsia is characterized by hypertension and proteinuria with or without oedema. MATERIAL AND METHODS: The authors highlight some aspects of preeclampsia: epidemiology, classification, clinical evaluation and treatment. RESULTS: The condition may be classified as light or severe. Preeclampsia can induce damage to the placenta, liver, kidneys and brain, in addition to complications like the HELLP syndrome, placental abruption and eclampsia. Thrombocyte activation may cause activation of the coagulation system and thrombocytopenia. Early onset preeclampsia (< 34 weeks) is often associated with placental infarcts and reduced fetal growth. INTERPRETATION: We focus on early signs and close clinical surveillance. The diastolic blood pressure should be estimated with Korotkoffs' phase V. Patients with early onset preeclampsia should be hospitalized, as should women with hypertension and newly developed proteinuria. Antihypertensive treatment is discussed. Cases with reduced fetal growth and those with severe preeclampsia should in most cases be delivered preterm. Vaginal delivery is preferable. Labour may be induced by oxtocin, following cervical prostaglandin stimulation as indicated. In such cases cardiotocography surveillance during labour should be performed. Caesarean section may be performed in selected cases. Patients with mild preeclampsia can await spontaneous vaginal delivery at term, but delivery should be induced if they proceed past term.

[Deep venous thrombosis in pregnant women]. / Dyp venetrombose hos gravide.

The main risk factors for deep vein thrombosis in pregnancy and after delivery are preeclampsia, operative delivery, adiposity, prolonged bed rest, and haemostatic defects (antithrombin, protein C and protein S deficiencies), activated protein C resistance, lupus anticoagulant/antiphospholipid antibodies. Hyperhomocystinaemia is a general risk factor for deep vein thrombosis. The clinical diagnosis of deep vein thrombosis is difficult and must be confirmed by imaging techniques. Positive D-dimer has high sensitivity, but low specificity to detect acute thrombosis. Standard treatment is unfractionated heparin intravenously for 7-10 days, followed by subcutaneous injections. Anticoagulant treatment is prolonged for 6-12 weeks after delivery, usually with warfarin. During pregnancies associated with high risk of thrombosis, low molecular heparin prophylaxis is given during pregnancy and 6-12 weeks after delivery. Thrombosis in pregnancy must be followed by adequate investigation for an underlying thrombotic predisposition.

[Weight and weight gain in pregnancy]. / Vekt og vektøkning hos gravide.

This article reviews different aspects of maternal weight before and during pregnancy and weight gain in pregnancy, e.g. causes of undernourishment (hyperemesis, anorexia nervosa and bulimia nervosa). Physiological weight gain during pregnancy is normally between 10 and 16 kg, representing 20% of the body weight before pregnancy. The increase in weight is usually lowest during the 1st trimester and greatest between the 17th and the 24th week of pregnancy. Low maternal weight at conception may cause low birthweight. Undernourishment may cause premature delivery or low birthweight, or both. There is an increased risk of gestational diabetes and macrosomia, as well as preterm delivery and hypertension in pregnant women who are overweight. There is also an increased risk of complications arising during general anaesthesia and operative delivery in severely overweight women. These women should be offered heparin or dextran as thrombosis prophylaxis where a caesarean section is to be performed. They should also be given antibiotic prophylaxis. A weight gain of between 7 and 12 kg reduces the risk of complications in overweight patients.

[Hemoglobin, iron deficiency and anemia in pregnant women. Diagnostic aspects]. / Hemoglobin, jernmangel og anemi hos gravide. Diagnostiske aspekter.

Normal haemoglobin concentration in the trimesters of pregnancy can be considered to be 11-13 g/100 ml, 10-13 g/100 ml and 11-14 g/100 ml, respectively. High and low haemoglobin levels both indicate important pathophysiological changes. The authors discuss the use of serum-ferritin (S-ferritin), mean corpuscular volume (MCV) and erythrocyte protoporphyrin as diagnostic tools. S-ferritin, which is a reliable indicator of the iron status in the first trimester, becomes less reliable after the 20th week due to the physiological dilution of the plasma and a concurrent fall in haemoglobin and S-ferritin. Erythrocyte protoporphyrin is not influenced by the plasma dilution and can be used as a supplement to S-ferritin to assess iron deficiency. MCV can also be used to characterise the iron status. Decreases in MCV take time, however, which makes clinical interpretation difficult. S-ferritin measurement early in pregnancy is a reliable parameter for judging whether iron supplementation is necessary. Even if S-ferritin is influenced by the plasma dilution, a concentration below 15 microgram/l indicates iron deficiency in all stages of pregnancy.

[New aspects on preventive iron supplementation in normal pregnancy]. / Nyere syn på profylaktisk jerntilskudd i normale svangerskap.

The paper gives an overview of iron metabolism and supplementation in pregnancy. Pregnancy leads to an increased demand for iron which is not normally met by the iron content in food in Norway and other western countries. The authors discuss the possible advantages of supplementation, as well as adverse reactions. Iron supplementation may have beneficial effects on cerebral function in neonates. High doses should not be given because of possible adverse effects. Low doses of iron (50-100 mg a day) should be offered from the beginning of the 20th week to pregnant women with an S-ferritin concentration between 20 micrograms/l and 60 micrograms/l. Approximately 20% of all pregnant women have large enough stores of iron to make supplementation unnecessary. S-ferritin measurement early in pregnancy is recommended to determine therapeutic strategies.

[Diabetes mellitus in pregnancy]. / Diabetes mellitus hos gravide.

The authors highlight some aspects of diabetes mellitus that complicate pregnancy. Several complications, e.g. hypoglycaemia, hyperglycaemia and macrosomia are described briefly. Macrosomia can be diagnosed by ultrasound examination, which should be performed every other week from the 24th week of gestation. Accelerated abdominal circumference (> or = 1.2 cm/week) between 32 and 39 weeks and excess thickness of soft tissue over the proximal humerus of the foetus after the 32nd week (> 13 mm at term) may imply development of macrosomia. The elevated risk related to adiposity and poor metabolic control can be avoided by intensive treatment. Intensive metabolic treatment can also reduce the frequency of preeclampsia and polyhydramnion. Ketoacidosis and intrauterine foetal death may be consequences of poor diabetic control. The authors discuss infectious problems, some aspects of treatment, e.g. risk of preterm delivery, dietary treatment and insulin, indications for delivery and various neonatal problems.

[Pregnancy in diabetes]. / Svangerskapsdiabetes.

The authors review various aspects of gestational diabetes, including definition, screening, diagnostic procedures, complications (hypertension, macrosomia), clinical evaluation (ultrasound, non-stress test), treatment (diet, insulin), indications for delivery and neonatal aspects (hypoglycaemia, hypocalcaemia). Complications can be reduced by intensive dietary treatment and insulin. If the gestational diabetes is regulated well the woman can wait for spontaneous birth at term. In the case of pregnant women with less than optimal regulated diabetes, however, or with complications such as hypertension, macrosomia, previous stillbirth, labour can be induced preterm by local administration of prostaglandin or infusion of oxytocin. Physical training and weight reduction should be instituted to avoid later development of type II diabetes mellitus. There is still some uncertainty about different aspects of gestational diabetes.

[Nasoenteral tube feeding in hyperemesis gravidarum. An alternative to parenteral nutrition]. / Nasoenteral sondeernaering ved hyperemesis gravidarum. Et alternativ til parenteral ernaering.

A severe form of hyperemesis gravidarum involving maternal weight loss greater than 5% of the prepregnant weight occurs in up to 0.1-0.2% of all pregnancies and may lead to retarded foetal growth. Treatment consists of hospitalisation, antiemetics and correction of fluid and electrolyte deficiencies. If severe vomiting and weight loss continues, the mother must receive supplementary nutrition, usually parenteral. Nasoenteral tube feeding is a well documented method of nutrition for other patients. A gastroscopically placed nasojejunal tube as part of the treatment of hyperemesis gravidarum has not been reviewed before. Seven women with severe hyperemesis gravidarum were treated with nasojejunal tube feeding. The tube was positioned gastroscopically. Enteral feeding continued for up to 41 days, leading to reasonable weight gain. The tube was tolerated well by most patients and no serious adverse effects were seen. Nasoenteral nutrition ought to be considered as an alternative to parenteral nutrition for treatment of hyperemesis gravidarum.

[Premature rupture of fetal membranes and chorioamnionitis]. / For tidlig fostervannsavgang og korioamnionitt.

The article presents a survey of preterm rupture of the amniotic membranes at term (more than 1 hour prior to uterine contractions) and preterm (< 37 weeks). The diagnosis of rupture can be suspected from the history alone in 90% of the cases, and confirmed by inspection. In doubtful cases the pH in fluid from the posterior fornix of the vagina is determined and microscopy is performed. Amniotic fluid is alkaline. Microscopy of a dried specimen shows "ferning" when amniotic fluid is present (crystallization test). Staining with Nil blue will reveal orange foetal cells in fresh specimens, usually only late in pregnancy (after the 38 week). The crystallization test is useful, however, in all three trimesters. The cause of membrane rupture and of chorioamnionitis may be infection. Chorioamnionitis is a serious clinical condition, but can be subclinical and may occur with intact membranes. It can lead to preterm delivery. It is important that chorioamnionitis be diagnosed (maternal fever, tachycardia, uterine contractions, abdominal pain, foul smelling vaginal discharge and elevated C-reactive protein). The condition is treated with antibiotics and labour must be induced.

Osteopenia caused by heparin treatment in pregnancy.

A case is reported of severe osteopenia caused by heparin treatment of thrombosis in the eleventh week of pregnancy followed by heparin prophylaxis (5000 IU three times daily) during pregnancy and lactation. The mother complained of back pain during the last two weeks of pregnancy. Six weeks post partum, generalized osteopenia in the skeleton was diagnosed and a compression fracture of the body of the sixth thoracic vertebra. During pregnancy the mother had relatively low serum concentrations of 1,25(OH)2D, the active metabolite of vitamin D, and six weeks after delivery the serum concentration had fallen to about 50% of the lowest reference level. Eight and fourteen weeks after delivery, when heparin treatment had been discontinued, the serum concentrations of 1,25(OH)2D were within the reference range for non-pregnant adults.

Calcium homeostasis in pregnancy and lactation.

This paper discusses different aspects of calcium homeostasis in pregnancy: the calcium demands of the mother, regulation mechanisms and the risk factors for demineralization. Special care should be paid to patients lying in bed for long periods and patients given heparin prophylaxis. One to two grams of calcium and 400 IU of vitamin D daily should be given orally to patients who are being treated for deep vein thrombosis. In addition, bone density should be checked to detect osteoporosis. The period of heparin prophylaxis must be as short as possible and bed rest must not be unnecessarily prolonged.

[Prenatal prevention of respiratory distress syndrome in newborn infants]. / Prenatal forebygging av åndenødssyndrom hos nyfødte.

This article reviews the embryology, pathophysiology, clinical aspects and prophylactic treatment of respiratory distress syndrome (RDS). Prenatal prophylaxis with corticosteroids is indicated for gestational ages between 24 and 32 weeks, even if the effect of prophylaxis is uncertain before the 28th week. Prophylactic treatment is less important between the 32nd and 34th gestational week. Hypertension is not considered a contraindication, but premature rupture of the membranes is a relative contraindication. Corticosteroid treatment may be given, however, in combination with antibiotic prophylaxis.