Kjell Haram

BACKGROUND: The HELLP syndrome is a serious complication in pregnancy characterized by haemolysis, elevated liver enzymes and low platelet count occurring in 0.5 to 0.9% of all pregnancies and in 10-20% of cases with severe preeclampsia. The present review highlights occurrence, diagnosis, complications, surveillance, corticosteroid treatment, mode of delivery and risk of recurrence. METHODS: Clinical reports and reviews published between 2000 and 2008 were screened using Pub Med and Cochrane databases. RESULTS AND CONCLUSION: About 70% of the cases develop before delivery, the majority between the 27th and 37th gestational weeks; the remainder within 48 hours after delivery. The HELLP syndrome may be complete or incomplete. In the Tennessee Classification System diagnostic criteria for HELLP are haemolysis with increased LDH (> 600 U/L), AST (>or= 70 U/L), and platelets < 100 x 10(9)/L. The Mississippi Triple-class HELLP System further classifies the disorder by the nadir platelet counts. The syndrome is a progressive condition and serious complications are frequent. Conservative treatment (>or= 48 hours) is controversial but may be considered in selected cases < 34 weeks' gestation. Delivery is indicated if the HELLP syndrome occurs after the 34th gestational week or the foetal and/or maternal conditions deteriorate. Vaginal delivery is preferable. If the cervix is unfavourable, it is reasonable to induce cervical ripening and then labour. In gestational ages between 24 and 34 weeks most authors prefer a single course of corticosteroid therapy for foetal lung maturation, either 2 doses of 12 mg betamethasone 24 hours apart or 6 mg or dexamethasone 12 hours apart before delivery. Standard corticosteroid treatment is, however, of uncertain clinical value in the maternal HELLP syndrome. High-dose treatment and repeated doses should be avoided for fear of long-term adverse effects on the foetal brain. Before 34 weeks' gestation, delivery should be performed if the maternal condition worsens or signs of intrauterine foetal distress occur. Blood pressure should be kept below 155/105 mmHg. Close surveillance of the mother should be continued for at least 48 hours after delivery.

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 less than 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.

Preterm delivery is the leading factor causing neonatal mortality and morbidity. We have conducted a PubMed literature search to obtain an update on the etiology, diagnostic problems and therapeutic considerations of preterm delivery. Approximately 5-10% of all births are premature. Preterm labor is associated with preterm rupture of membranes, cervical incompetence, polyhydramnion, fetal and uterine anomalies, infections, social factors, stress, smoking, heavy work and other risk factors. The diagnosis is made on the patients presenting symptoms, clinical findings and of progressive effacement and dilatation of the cervix. Biochemical markers of preterm delivery are of minor importance in daily clinical work. Measurement of the cervix, however, is a practical and valuable tool to predict preterm delivery. Cervical cerclage can be useful in selected cases. Antibiotics may help to prevent preterm labor in cases of known etiologic agents (e.g. preterm rupture of membranes and urinary infection). The use of tocolytic agents such as beta-sympathetic receptor stimulators can be advocated for a few days. There is evidence that their long-term use is not beneficial and could even be harmful to the fetus. Calcium channel blockers (nifedipine) and a new selective oxytocin receptor antagonist, atosiban, appear to be as effective as beta-sympathomimetic drugs on uterine contractions with fewer side-effects. Prostaglandin synthetase inhibitors such as indomethacin may prevent uterine contractions and can be used prior to the 32nd week of pregnancy. A single course of corticosteroid treatment in two doses of 12 mg betamethasone or 6 mg of dexamethasone is important for the prevention of respiratory distress between the 24th and 34th weeks of pregnancy. Multiple doses may be harmful and should be avoided. In these cases management should depend on gestation age (fetal maturity). Uterine contractions after 34 weeks' gestation are not an indication for tocolytic treatment.

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.