The present study described 32 cases of APIP with the aim to characterize the clinical correlates of this disease in China. In our cohort, most of the events (90.6%, 29/32) presented in the third trimester, which suggests an increased incidence with increasing gestational age. Gallstone is the most commonly reported etiology of AP among pregnant women in Europe and America, followed by idiopathic, alcohol abuse, and hypertriglyceridemia-induced AP[1,2,13−15]. In China, alcohol abuse is uncommon during pregnancy because of the excessive concern for pregnant women. However, most pregnant women in China tend to have high-fat diet due to local culture. Besides, the plasma lipid levels are liable to increase during pregnancy due to the effects of estrogen, progesterone, and human placental lactogen. Lipid levels in the first trimester are usually the same as the pre-pregnancy levels and significant changes in lipid metabolism are usually seen in the second and third trimesters. There is usually a two to four-fold rise in plasma triglyceride level during pregnancy. However, this is usually well-tolerated and does not affect the mother or fetus, but in some high-risk women, triglyceride levels may increase to abnormally high levels (more than 95th centile for the age) and in some cases up to severe level (>1000 mg/dL or 11.3 mmol/L). As expected, the most common cause of APIP in Chinese women in this study was hypertriglyceridemia (56.25%, 18/32). The results are in line with previous studies conducted in China. However, compared with the previously reported data, the proportion of APIP cases caused by hyperlipidemia was higher in our study[6, 7, 19]. We may speculate that the rising trend of obesity worldwide may have had a negative impact on the incidence of this disease. Many cases of APIP caused by hypertriglyceridemia were also reported in Japan and Korea[20–22]. Therefore, the etiological pattern of APIP appears to differ significantly between Asian and European women. Several studies have shown that patients with APIP caused by hypertriglyceridemia have an increased tendency to develop SAP and other complications[1, 7, 19, 23, 24]. We also observed a similar tendency in our study.
In our study, the initial diagnosis of 10 (31.2%) patients was different from the discharge diagnosis, and a delayed diagnosis of APIP was made for 12 (37.5%) patients. Several factors can explain this phenomenon. First of all, enlargement of the uterus displaces the pancreas posteriorly, and some APIP patients may not have the typical clinical manifestation of upper abdominal pain. The clinical manifestations of nausea and vomiting are similar to various physiological or pathological manifestations during pregnancy. Moreover, inflammation in the pancreas can induce uterine contraction; thus, the abdominal discomfort is liable to be mistaken for abdominal discomfort related to labor. Second, pregnancy will affect the changes and interpretation of various blood and biochemical indices. In our study, 25% (8/32) of patients had an increase in serum amylase less than three times the normal value, and the increase in serum amylase was not related to the severity of APIP. Studies have shown that compared with serum amylase, serum lipase has a higher sensitivity and a larger diagnostic window[25, 26]. In case of hyperlipidemic acute pancreatitis, lipase offers a better diagnostic accuracy (91.8%) than amylase (40.3%). Moreover, lipase may have an advantage over amylase in determining the severity of acute pancreatitis. Regrettably, serum lipase levels were not tested in most of the patients in this study. Thus, based on previous studies, we strongly recommend that serum lipase should be added to the routine biochemical examination of patients with abdominal pain during pregnancy to facilitate the diagnosis of APIP. Third, although ultrasound is still the first abdominal imaging method for APIP patients, the findings are greatly affected by gastrointestinal gas and the posture of pregnant women. Thus, use of ultrasound alone may not be adequate for accurate assessment of APIP. Magnetic resonance imaging (MRI) and Magnetic resonance cholangiopancreatography (MRCP) without iv contrast (gadolinium) should be considered in patients with indeterminate US findings.
In the present study, we found that the clinical management of APIP has remained almost the same in the past decade. Treatment of APIP requires multidisciplinary collaboration involving specialists from gastroenterology, radiology, obstetrics, general surgery, neonatology, and even intensive care departments to develop personalized treatment plans. Owing to the lack of standardized guidelines for APIP, the treatment is generally conservative and similar to that administered to non-pregnant patients with acute pancreatitis.
In our study, 55.5% of gallstone-induced APIP patients had a history of gallstones and 27.7% of hypertriglyceridemia-induced APIP patients had hyperlipidemia during pregnancy (one of which had a history of hyperlipidemia for two years before pregnancy). Therefore, we recommend primary prevention for high-risk patients (history of gallstones, hyperlipidemia or hyperlipidemia during pregnancy, and BMI ≥ 28 kg/m2) before and during pregnancy. For pregnant women with a history of gallstones, we recommend abdominal ultrasound examination during the pre-pregnancy counseling. Timely treatment of patients who are found to have gallstones can help prevent APIP. Patients with hyperlipidemia should stop taking lipid-lowering drugs during pregnancy owing to the lack of definitive evidence of their safety during pregnancy. However, they should be fully informed of the possible complications and treatment methods during pregnancy. It is recommended to improve their lifestyle including avoidance of excessive weight gain during pregnancy.
The management of APIP is complicated by the decision-making regarding the timing and route of termination of pregnancy (induction of labor or cesarean section or vaginal delivery). Pregnancy termination can also be regarded as a key to achieve cure of AP. In our study, pregnancy was terminated in 50% (9/18) of MAP patients and all MSAP and SAP patients (92.8%, 13/14), except for one patient who became ill at 23 weeks gestation. Based on the treatment of 32 patients, we have summarized some recommendations for termination of pregnancy: (1) Women who agree to the use of fetotoxic medication for pancreatitis treatment or voluntarily terminate their pregnancy; (2) stillbirth, fetal malformations, and severe fetal distress; (3) patients who are in the third trimester and whose condition deteriorates after 24-48 hours of treatment; (4) MSAP and SAP patients. If conditions permit, vaginal delivery should be preferred as it can help avoid infections associated with cesarean delivery. However, for APIP patients whose condition is still worsening after 24 to 48 hours of active treatment (e.g., no improvement in paralytic intestinal obstruction), cesarean delivery should be undertaken immediately to ensure maternal and fetal safety.
No maternal or fetal deaths occurred in our study. This observation is in agreement with previous studies[2, 6]. The good outcomes in our cohort are likely attributable to the improvement in maternal and neonatal intensive and supportive care that have occurred during the past decade in China.
Like all retrospective studies, this study has some limitations. First, because of de-identification of all personal information of patients, follow-up data of APIP patients after their discharge from the hospital were not available. Second, some laboratory indices (such as serum lipase level) were not assessed for all patients. Third, due to the low incidence of APIP, there were only 32 cases in our study. However, the study sample was drawn from a large dataset of pregnant women and so might add valuable practical information to the global knowledge of APIP.