[Adds quotes from researcher in new paras 2 and 3, and adds "Dr. Maor and" to beginning of para 4, in story posted earlier today, October 24 2012, as 20121024epid002.]
NEW YORK (Reuters Health) – Assisted reproduction techniques (ART) are associated with an increased risk of idiopathic liver function test (LFT) abnormalities during pregnancy, a new study shows.
“Although our findings are preliminary, they clearly indicate a strong relationship between pregnancies achieved through ART and LFT elevation, especially idiopathic, in the third trimester,” coauthor Dr. Yaakov Maor told Reuters Health by email.
“As shown, idiopathic LFT abnormality may bear adversely on the outcomes of the mother and newborn,” he continued. “Our findings call for vigilance from GYN/OB specialists focusing on ART. We believe that women becoming pregnant through ART should be carefully monitored for LFT throughout their pregnancies and if such elevation occurs (particularly idiopathic) tight follow-up of the pregnancy and timely planning of the labor is warranted. The women with idiopathic LFT elevation should also monitored after delivery to detected yet unrecognized underlying chronic liver disease and the for elevated LFT during following pregnancies. Our paper also calls for attention in the part of opinion leaders in fertility on the widespread provision of ART especially in older women.
Dr. Maor and Dr. Uri Kopylov from Sheba Medical Center in Tel Hashomer, Israel and colleagues used an electronic database and patient files to investigate the prevalence, etiology, risk factors, and outcomes of liver abnormalities in pregnancy and to study the potential impact of ART on the incidence and outcome of pregnancy-related liver abnormality.
As reported October 11th online in Fertility and Sterility, they arbitrarily chose an alanine aminotransferase (ALT) level of 100 IU/L or higher to indicate significant liver abnormality.
Altogether they had data on LFT results in nearly 28,000 pregnant women. ALT was elevated at least 1.5 times the upper limit of normal during the third trimester in 440 (1.57%), and 228 (0.82%) had an ALT level above the threshold for significant abnormality.
ALT elevations at least 1.5 times the upper limit of normal were seen in 295 of 23,793 spontaneous pregnancies (1.2%), but in significantly more women with assisted pregnancies (145 of 4,520, 3.2%; p<0.0001).
Women with ART also had a higher rate of significant liver test abnormalities (78 of 4,520, or 1.7%) compared to women with spontaneous pregnancies (150 of 23,793, or 0.6%).
The etiologies of significant liver test abnormalities did not differ between women who conceived spontaneously and those who needed ART, except that HELPP (hemolysis, elevated liver enzymes, low platelet count) was more common in spontaneous pregnancies and ICP (intrahepatic cholestasis of pregnancy) was more common in ART pregnancies.
In multivariate analysis, ART increased the risk of significant liver test abnormalities by 6.5-fold (p<0.0001). Other factors independently associated with significant liver test abnormalities included age, number of fetuses/multiple embryos, gestational hypertension, and the need for prescription during pregnancy.
Liver test abnormalities were associated with a 2.3-fold increased rate of cesarean section and with an increased frequency of prematurity, low birth weight, and fetal/neonatal complications.
“Obviously, there is an unmet need for a uniform diagnostic definition and criteria for pregnancy-related liver abnormality, enabling adoption of algorithms for management of such women,” the researchers conclude. “Follow-up of those women without a certain diagnosis, particularly during subsequent pregnancies, can shed some light on the nature of this disorder.”
Dr. Jerry Kingham from Singleton Hospital, Swansea, UK told Reuters Health, “Retrospective studies of this nature should be interpreted with great caution.”
Dr. Kingham, who wasn’t involved in the study, added, “Although the authors state that no cause could be identified to explain the abnormal liver tests in almost 50% of cases, this should be interpreted as a defect of the methodology. In a prospective study, such as the one we undertook in South Wales a decade ago, we only failed to find a cause of the abnormal liver tests in 10% of cases.”
“Women unable to conceive spontaneously may be more likely to have underlying co-morbidity and be in receipt of medications for such co-morbidities, either or both of which could cause abnormal liver tests,” Dr. Kingham said. “In addition they will inevitably be on hormonal medication as part of the ART which could be a contributing factor.”
“With a pickup rate of around 1.5% of all third trimester pregnancies showing raised transaminase levels, it can be argued that a simple blood test to check liver function would be reasonable in all pregnancies,” Dr. Kingham continued. “The rate was 3.2% amongst those pregnancies resulting from ART so in health economics terms the benefit of checking liver function test results would be greater in that group.”
“Obstetricians, primary care physicians, and hospital-based physicians encountering pregnant patients in the emergency room should be aware that abnormal liver tests during pregnancy, particularly in the third trimester, are not uncommon,” Dr. Kingham concluded. “They sometimes herald severe and life threatening diseases and must not be ignored, even though in many cases there may be a relatively harmless cause. Advice should be sought from a hepatologist, particularly one with experience of obstetric liver disease. Ignorance about liver disease in pregnancy is still rife.”
Fertil Steril 2012.