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Pregnancy associated pancreatitis revisited
Clinics and Research in Hepatology and Gastroenterology (2013) 37, 177—181
Available online at
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ORIGINAL ARTICLE
Pregnancy associated pancreatitis revisited Osamuyimen Igbinosa ∗, Sameer Poddar , Capercomorin Pitchumoni Department of Medicine, Saint Peter’s University Hospital, 254, Easton avenue, New Brunswick, NJ 08901, United States Available online 7 September 2012
Summary Objectives: To evaluate the demographics, risk factors and outcomes of pregnancy associated pancreatitis (PAP). Study design: A retrospective chart review was done using ICD-9 Code 577.0 (acute pancreatitis) from January 2005 through December 2009. Women aged 18 to 45 years, who were pregnant and 6 months after delivery were considered for the study. For each case, two women of the same age (± 4 years) with no history of pancreatitis were matched as control. Demographics, etiology, diagnostic modality and intervention were obtained. Results: During the 5 years of study, 29 cases of PAP occurred among 25,600 total hospital deliveries, yielding prevalence of 0.001%: Hispanics 48%, Caucasians 24%, African Americans 17.2%, and Asian/Pacific Islanders 13% (P < 0.05). Sixty-five percent of those with pre-pregnancy body mass index (BMI) more than 30 kg/m2 had PAP, versus 24% with BMI between 25 and 30 kg/m2 and 10% with BMI less than 25 kg/m2 (P < 0.05). An increasing trend of PAP was seen with gestational age and number of pregnancy. Conclusion: Gallstone disease is the most frequent etiology for PAP and tends to occur more often in Hispanics in New Jersey. © 2012 Elsevier Masson SAS. All rights reserved.
Introduction Pregnancy associated pancreatitis (PAP) is rare with incidence of approximately one in 1000 to 10,000 birth [1]. There is a wide range of incidence, outcomes and risk factors reported in literature. Studies from 1970s to 1980s estimated maternal and perinatal mortality rates between 0 to 37% and 11 to 37% respectively [2—4].
∗ Corresponding author. Tel.: +1 732 745 8600; fax: +1 732 745 2980. E-mail address: [email protected] (O. Igbinosa).
Recent reports after 1999 demonstrated better maternal and fetal outcomes [1,5—10]. Management of PAP due to gallstones has improved significantly with newer therapeutic options. These developments include; abdominal ultrasound, magnetic resonance cholangiopancreatography (MRCP) endoscopic ultrasound (EUS), to evaluate the biliary system also, endoscopic retrograde cholangiopancreatography (ERCP) and sphinteroctomy for stone retraction. In the United States, early recognition, better supportive care in acute pancreatitis as well as improvement in maternal and perinatal care has improved across board. Thus, newer studies on maternal and fetal outcomes will likely be different compared to earlier series. At Saint-Peters university hospital, (SPUH) New Jersey USA; an academic
2210-7401/$ – see front matter © 2012 Elsevier Masson SAS. All rights reserved. http://dx.doi.org/10.1016/j.clinre.2012.07.011
178 Table 1
O. Igbinosa et al. Demographics and maternal clinical data. ALL PAP n = 29
PAP 1st trimester n=4
PAP 2nd trimester n=7
PAP 3nd trimester n = 14
Postpartum n=4
Control n = 58
Age mean ± sd (yrs)
28.7 ± 5.7
24.5
25.8
30.8
31
27.4 ± 4.8
Race H/AA/C/A (%)
48/13/24/13
50/50/0/0
42/0/14/4/2
50/14/28/7
50/0/50/0
31/14/41/12
# of pregnancy Gravida (mean ± sd) Parity
2.7 ± 1.6 1.7 ± 1.8
1.5 1
3.14 2.25
2.7 1.9
3.5 2
2.3 ± 3.2 1.5 ± 2.8
Cholethiasis on US (n)
21
3
6
8
4
0
Remote hx of pancreatits (n) Recurrent AP
2
0
0
1
1
0
2
0
0
1
1
0
History of GS
9
0
2
4
3
0
Dilated CBD on US
5
1
3
0
1
0
H/AA/C/A: Hispanic/African American/Caucasian/Asian; AP: acute pancreatitis; CBD: common bile duct; US: ultrasound; PAP: pregnancy associated pancreatitis.
community hospital with over 6000 deliveries annually, we have recognized a clinical entity — PAP (PAP). We defined PAP as acute pancreatitis complicating pregnancy from first trimester up to 6 months postpartum. PAP is associated with a set of distinct clinical features and risk. The etiological associations are similar to those in the general population and gallstone disease is believed to be responsible for more than 70% of cases [1]. The incidence of gallstone-related diseases including acute cholecystitis and biliary pancreatitis complicating pregnancy is between 0.05% and 0.8% [11]. Biliary etiology may still be a culprit even in patients with prior cholecystectomy since the prevalence of microlithiasis after cholecystectomy is 5% to 10% [12,13]. In this report, we describe the clinical presentation and outcome of 29 cases of acute pancreatitis in pregnant women and up to 6 months postpartum that presented to SPUH from January 2005 to December 2009. We postulated that outcomes in pregnant women with pancreatitis are likely to be poorer than for the overall cohort of pregnant women. The aim of this paper is to evaluate the demographics, risk factors and outcomes of PAP and calculate its prevalence in the community.
Material and methods Approval of institutional review board (IRB) was obtained from SPUH. Using international classification of disease9 (ICD) code of acute pancreatitis (577.9), we reviewed charts of women in child bearing age (18 through 45) from SPUH, New Jersey database from January 2005 through December 2009 and extracted information on patient demographics (maternal age, gestational age at presentation, gravity/parity and delivery, ethnicity); clinical presentation; diagnostic testing (amylase, lipase, triglycerides, calcium, ultrasound, EUS, ERCP); health outcomes in both mother and fetus. Total number of deliveries performed during study period was also obtained from hospital statistics.
To diagnose acute pancreatitis we used the scoring system developed by Sternby et al. [14]. Abdominal pain with serum amylase and lipase more than two times above upper limit of normal was the diagnostic indicator. Acute pancreatitis within 6 months of childbirth was considered postpartum in this study. For each case, we matched two women of the same age (± 4 years) with no history of acute pancreatitis that presented to SPUH outpatient clinic as control. The term PAP include acute pancreatitis during pregnancy and postpartum. Full-term pregnancy was defined as at least 37 completed weeks of gestation. First trimester was defined as weeks 1 through 14, second trimester as weeks 15 through 28, and the third trimester as 29 weeks up to delivery. Low birth weight was diagnosed when a newborn’s first weight was less than 2500 g. Upper limit of common bile duct size (CBD) was taken as 5 mm [15]. Calculation of body mass index (BMI) was done using weight in kilogram divided by height in meter square obtained on first obstetrical visit data.
Statistical analysis Numerical data were reported as number and percentage to characterize the patient population, study results, and outcomes. Categorical data were reported as mean with standard deviation for patient demographics. All analyses including chi-square were performed using SPSS version 20 statistical software (SPSS, Inc., Chicago, IL). P value < 0.05 was considered significant.
Results Demographics and maternal clinical data Over the study period, 29 cases of PAP occurred among 25,600 total hospital deliveries, yielding a prevalence of 0.001%. The race/ethnicity of patients with PAP was Hispanics 48%, Caucasians 24%, African Americans 13%,
Pregnancy associated pancreatitis revisited
179 Table 2
Figure 1 Number (%) of pregnancy associated pancreatitis (PAP) cases by gestational age.
Etiology of acute pancreatitis.
Etiology
Cases (n)
%
Gallstones associated Alcohol Hyperlipemia Hyperparathyroidism Idiopathic
21 1 0 1 7
72.4 3.4 0 3.4 24
Numbers do not add up because hyperparathyroidism was also associated with gallstones.
Discussion
Figure 2 Number (%) of pregnancy associated pancreatitis (PAP) cases by pre-pregnancy body mass index (BMI).
Asian/pacific islanders 13%, compared to those without PAP of 31%, 41%, 14%, and 12% respectively (Table 1). The average maternal age at presentation was 28.7 ± 5.7 years and they usually were multiparous; number of gestations (mean, 2.7 ± 1.6) and parity (mean, 1.7 ± 1.8). None of these patients were on medications known to be associated with either gallstones or pancreatitis. Pancreatitis occurred more frequently as pregnancy progressed 13% (four) in the first, 24% (seven) in the second, and 48% (14) in the third trimester and 13% (four) postpartum. Twenty-seven percent (eight) had a prior history of pancreatitis and 6% (two) had two episodes of acute pancreatitis during pregnancy and up to 6 months postpartum. Thirty-one percent (nine) had prior history of gallstones only 17% (five) had dilated CBD on transabdominal ultrasound at presentation. Choledocholithiasis was diagnosed in 34% (ten) of cases — five by ultrasound alone, additional three patients by MRCP. Two patients with CBD of 6 mm on ultrasound had EUS. The occurrence of acute pancreatitis was distributed across a range of gestational ages, with more cases presenting later in gestation: 13.7%, 24.1% and 48% in 1st, 2nd and 3rd trimesters respectively (Fig. 1). Fig. 2 shows 65% of cases with PAP had BMI more than 30 kg/m2 compared to 24% with BMI 25 to 30 kg/m2 and 10% with BMI less than 25 kg/m2 (P < 0.05) Therefore, cases were more likely to be obese prior to pregnancy.
Fetal and maternal complications There was no maternal and fetal mortality in this study. Of four patients who had ERCP, sphincterotomy was performed on three and none had post ERCP pancreatitis. There was no spontaneous or elective abortion and only one preterm pregnancy was recorded. No fetal malformation was observed. Average hospital stay was 5.87 ± 1.4 days in cohort of PAP.
Our retrospective study confirms observations from recent issues of pancreatitis in pregnancy, including prevalence, severity and outcome. Acute pancreatitis in pregnancy still being a cause for concern evidently has a good outcome. Acute pancreatitis during pregnancy in the United States was once thought to be rare now appears to be more frequently reported, with incidence between 0.1% and 0.008%. [1,3,16] Although the incidence is still rare, the potential complication is doubled compared with non-pregnant females, since it deals with two lives. The wide variation in the incidence is influenced by the prevalence of its most important etiological factor (gallstone disease). This is exemplified by the fact that biliary pancreatitis complicated one in 3300 pregnancies at a large public hospital in Dallas, Texas; [1] in southern California one in 1500 women [17]. In a series of 53 patients with acute pancreatitis during pregnancy published in the medical literature before 1951, [18] vast majority of diagnoses were made during surgery and/or on autopsy. The overall pancreatitis-related maternal mortality was 37% and was significantly higher than that in non-pregnant patients then: 12% to 33% [3]. Perinatal mortality was 38% and was related primarily to prematurity. Swisher et al. also demonstrated continued decline in maternal and perinatal mortality between 1970 and 1990 [6] although their study was relatively small. This improvement in all outcome measures is due to the advent of rapid assay methods for amylase and lipase, better supportive care of pancreatitis, newer therapeutic measures for gallstone pancreatitis and overall improvement in maternal and perinatal care. We have shown that maternal and perinatal mortality has continued to decline. The increasing incidence with gestational age observed in our study (Table 2) has been noted in other studies as well. [1,14,17]. Gallstone predominance for PAP (72.4%) in our study is similar to 65 to 100% noted in earlier studies. [1,7,19] PAP tends to occur more often in Hispanics in New Jersey (48% cases vs. 31% control), perhaps a reflection of high prevalence of gallstone disease. Hispanics make to 16% of total New Jersey population (Mexican origin 13%; Non Mexican origin 87%) [19]. Non-Mexicans are individuals from Latin American countries in central and South America. The prevalence rate of gallstones varies with ones ethnicity. Native American Indians, Latin Americans, Pima Indians and Mexicans have high incidence while the incidence is lower in Asian and African [10]. Obesity as a frequently co-morbid factor for gallstones [18] is made clear again. Obesity itself is also a marker of
180 Table 3
O. Igbinosa et al. Maternal and fetal complication. Case, n = 29 (%)
Control, n = 58 (%)
Fetal birth weight (kg) < 2.32 3—3.6 > 3.7
0 (0) 29 (100) 0 (0)
2 (3) 52 (89) 4 (6)
Preterm delivery (wks) < 35 36—40
1 (3.4) 28 (96.6)
2 (3) 56 (96.9)
Average hosp stay (days)
5.87 ± 1.4
3.21 ± 0.5
Type of delivery Vaginal Cesarean section
7 (24) 22 (75.8)
40 (69) 18 (31)
Maternal demise
0
0
Cesarean section is significantly more in pancreatitis patients.
Table 4
because of the relatively small sample. Further studies are therefore needed. We believe it is simply an institutional preference. However, on a wider view, it discerns unified approach to the management of gallstone pancreatitis and exposes controversies in management of PAP. Case report and anecdotal papers recommend cholecystectomy in 2nd trimester and postpartum if possible [5,20]. Some reports have also suggested that safety of laparoscopic cholestectomy at all stages of pregnancy [7,21]. Based on our findings, we are unable to determine the optimal management of PAP. Our good outcomes most likely reflect improvement in intensive and supportive care that has occurred over the past decade. It is notable that in-general, abdominal ultrasound examination performed by obstetricians was solely to evaluate the fetus and uterus and seldom paid attention to the gallbladder — an easy extension of examination to the liver would have added useful information especially in group considered high risk for gallstone pancreatitis. With newer approach to management of PAP a few issues remain:
Management and outcome.
Trimester
Intervention
Outcome
I
n=4 ERCP: 1 EUS: 0 None: 2 1 lap chole (25%)
4 FTD
II
n=7 ERCP: 1 EUS: 1 None: 5 2 lap chole (28%)
7 FTD
n = 14
1 preterm delivery at 35 wks 13 FTD
III
ERCP: 2 EUS: 2 None: 4 Open chole 2 (14%) Postpartum
n=4 Lap chole 4 (100%)
• the safety of MRCP in the first trimester; • the safety of laparoscopic cholecystectomy in 2nd trimester, however newer reports indicate safety in all trimester; • the use of antibiotics remain controversial; • the risk of bleeding, perforation, pancreatitis, fetal radiation associated with ERCP/EUS is of concern.
Conclusions This study confirms the following:
Maternal demise 0
Lap chole: laparoscopic cholecystectomy; FTD: full-term delivery; ERCP: endoscopic retrograde cholangiopancreatography; EUS: endoscopic ultrasound.
severe pancreatitis. Cases were more likely to be obese prior to pregnancy than control. Sixty-five percent of cases had pre-pregnancy BMI of more than 30 vs. 24% control (Fig. 2). Fetal and maternal mortality in this study (0%) is consistent with literature [1,7—10]. As shown in Table 3, overall rate of preterm delivery in this study, 3.4% cases of PAP vs. 3% (P > 0.5) in patients without PAP. One interesting finding in this study was a higher trend of cholecystectomy in women who developed acute pancreatitis in late trimesters (Table 4); 25% in first trimester, versus 28% in second trimester, 50% in third trimester (mostly in early third trimester) and 100% postparturm. Unfortunately, we do not have a good explanation for this finding
• • • • •
the prevalence of PAP in New Jersey is 0.001%; gallstone disease is the most significant etiology for PAP; ethnicity determines the incidence of PAP; obesity is a frequently co-morbid factor in PAP; this pilot study did not reveal a significant fetal or maternal mortality; • cesarean section is frequently utilized in delivery of fetus.
On the basis of this study, we would like to extend our recommendations to screen Hispanic obese (BMI > 30 kg/m2 ) pregnant women for cholelithiasis by extending the routinely performed ultrasonography during pregnancy to include the gallbladder in the same setting without extra diagnostic cost. This will help identify patients at high risk for PAP who may benefit from elective cholecystectomy during second trimester or before subsequent pregnancy.
Study limitations There two major limitation regarding this study. The first is the small sample size of cases, which reflects the rarity of PAP. Second, it is a single center study, so broad generalization beyond the cases studied should be made with great caution.
Pregnancy associated pancreatitis revisited
Disclosure of interest The authors declare that they have no conflicts of interest concerning this article.
References [1] Ramin KD, Ramin SM, Richey SD, Cunningham FG. Acute pancreatitis in pregnancy. Am J Obstet Gynecol 1995;173(1):187—91. [2] Montgomery WH, Miller FC. Pancreatitis and pregnancy. Obstet Gynecol 1970;35:658—64. [3] Wilkinson EJ. Acute pancreatitis in pregnancy: a review of 98 cases and a report of 8 new cases. Obstet Gynecol Surv 1973;28:281—303. [4] McKay AJ, O’Neill J, Imrie CW. Pancreatitis, pregnancy and gallstones. Br J Obstet Gynaecol 1980;87:47—50. [5] Legro RS, Laifer SA. First trimester pancreatitis: maternal and neonatal outcome. J Reprod Med 1995;40:689—95. [6] Swisher SG, Hunt KK, Schmit PJ, Hiyama DT, Bennion RS, Thompson JE. Management of pancreatitis complicating pregnancy. Am Surg 1994;60(10):759—92. [7] Hernandez A, Petrov MS, Brooks DC, Banks PA, Ashley SW, Tavakkolizadeh A. Acute pancreatitis and pregnancy: a 10-year single center experience. J Gastrointestinal Surg 2007;11(12):1623—7. [8] Chen CP, Wang KG, Su TH, Yang YC. Acute pancreatitis in pregnancy. Acta Obstet Gynecol Scand 1995;74(8):607—10. [9] Chang C, Hsieh Y, Tsai H, Yang T, Yeh L, Hsu T. Acute pancreatitis in pregnancy. Chin Med J 1998;61:85—92. [10] Pitchumoni CS, Yegneswaran B. Acute pancreatitis in pregnancy. World J Gastroenterol 2009;15(45):5641—6.
181 [11] Ko CW. Risk factors for gallstone-related hospitalization during pregnancy and the postpartum. Am J Gastroenterol 2006;101:2263—8. [12] Okoro N, Patel A, Goldstein M, Narahari N, Cai Q. Ursodeoxycholic acid treatment for patients with postcholecystectomy pain and bile microlithiasis. Gastrointest Endosc 2008;68:69—74. [13] Quallich LG, Stern MA, Rich M, Chey WD, Barnett JL, Elta GH. Bile duct crystals do not contribute to sphincter of oddi dysfunction. Gastrointest Endosc 2002;55:163—6. [14] Sternby B, O’Brien JF, Zinsmeister AR, DiMagno EP. What is the best biochemical test to diagnose acute pancreatitis? A prospective clinical study. Mayo Clin Proc 1996;71:1138—44. [15] Mintz MC, Grumbach K, Arger PH, Coleman BG. Sonographic evaluation of bile duct size during pregnancy. AJR 1985;145.3:575—8. [16] Nesbitt TH, Kay HH, McCoy MC, Herbert WNP. Endoscopic management of biliary disease during pregnancy. Obstet Gynecol 1996;87:806—9. [17] Uomo G, Manes G, Picciotto FP, Rabitti PG. Endoscopic treatment of acute biliary pancreatitis in pregnancy. J Clin Gastroenterol 1994;18(3):250—2. [18] Cortlett RC, Mishell DR. Pancreatitis in pregnancy. Am J Obstet Gynecol 1972;113:281. [19] Swisher SG, Schmit PJ, Hunt KK, Hiyama DT, Bennion RS, Swisher EM, et al. Biliary disease during pregnancy. Am J Surg 1994;168:576—9 [discussion 580—581]. [20] Friedman RL, Friedmen IH. Acute cholecystitis with calculous biliary duct obstruction in the gravid patient. Surg Endosc 1995;9:910—3. [21] Cosenza CA, Saffari B, Jabbour N, et al. Surgical management of biliary gallstone disease during pregnancy. Am J Surg 1999;178:545—8.
Available online at
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ORIGINAL ARTICLE
Pregnancy associated pancreatitis revisited Osamuyimen Igbinosa ∗, Sameer Poddar , Capercomorin Pitchumoni Department of Medicine, Saint Peter’s University Hospital, 254, Easton avenue, New Brunswick, NJ 08901, United States Available online 7 September 2012
Summary Objectives: To evaluate the demographics, risk factors and outcomes of pregnancy associated pancreatitis (PAP). Study design: A retrospective chart review was done using ICD-9 Code 577.0 (acute pancreatitis) from January 2005 through December 2009. Women aged 18 to 45 years, who were pregnant and 6 months after delivery were considered for the study. For each case, two women of the same age (± 4 years) with no history of pancreatitis were matched as control. Demographics, etiology, diagnostic modality and intervention were obtained. Results: During the 5 years of study, 29 cases of PAP occurred among 25,600 total hospital deliveries, yielding prevalence of 0.001%: Hispanics 48%, Caucasians 24%, African Americans 17.2%, and Asian/Pacific Islanders 13% (P < 0.05). Sixty-five percent of those with pre-pregnancy body mass index (BMI) more than 30 kg/m2 had PAP, versus 24% with BMI between 25 and 30 kg/m2 and 10% with BMI less than 25 kg/m2 (P < 0.05). An increasing trend of PAP was seen with gestational age and number of pregnancy. Conclusion: Gallstone disease is the most frequent etiology for PAP and tends to occur more often in Hispanics in New Jersey. © 2012 Elsevier Masson SAS. All rights reserved.
Introduction Pregnancy associated pancreatitis (PAP) is rare with incidence of approximately one in 1000 to 10,000 birth [1]. There is a wide range of incidence, outcomes and risk factors reported in literature. Studies from 1970s to 1980s estimated maternal and perinatal mortality rates between 0 to 37% and 11 to 37% respectively [2—4].
∗ Corresponding author. Tel.: +1 732 745 8600; fax: +1 732 745 2980. E-mail address: [email protected] (O. Igbinosa).
Recent reports after 1999 demonstrated better maternal and fetal outcomes [1,5—10]. Management of PAP due to gallstones has improved significantly with newer therapeutic options. These developments include; abdominal ultrasound, magnetic resonance cholangiopancreatography (MRCP) endoscopic ultrasound (EUS), to evaluate the biliary system also, endoscopic retrograde cholangiopancreatography (ERCP) and sphinteroctomy for stone retraction. In the United States, early recognition, better supportive care in acute pancreatitis as well as improvement in maternal and perinatal care has improved across board. Thus, newer studies on maternal and fetal outcomes will likely be different compared to earlier series. At Saint-Peters university hospital, (SPUH) New Jersey USA; an academic
2210-7401/$ – see front matter © 2012 Elsevier Masson SAS. All rights reserved. http://dx.doi.org/10.1016/j.clinre.2012.07.011
178 Table 1
O. Igbinosa et al. Demographics and maternal clinical data. ALL PAP n = 29
PAP 1st trimester n=4
PAP 2nd trimester n=7
PAP 3nd trimester n = 14
Postpartum n=4
Control n = 58
Age mean ± sd (yrs)
28.7 ± 5.7
24.5
25.8
30.8
31
27.4 ± 4.8
Race H/AA/C/A (%)
48/13/24/13
50/50/0/0
42/0/14/4/2
50/14/28/7
50/0/50/0
31/14/41/12
# of pregnancy Gravida (mean ± sd) Parity
2.7 ± 1.6 1.7 ± 1.8
1.5 1
3.14 2.25
2.7 1.9
3.5 2
2.3 ± 3.2 1.5 ± 2.8
Cholethiasis on US (n)
21
3
6
8
4
0
Remote hx of pancreatits (n) Recurrent AP
2
0
0
1
1
0
2
0
0
1
1
0
History of GS
9
0
2
4
3
0
Dilated CBD on US
5
1
3
0
1
0
H/AA/C/A: Hispanic/African American/Caucasian/Asian; AP: acute pancreatitis; CBD: common bile duct; US: ultrasound; PAP: pregnancy associated pancreatitis.
community hospital with over 6000 deliveries annually, we have recognized a clinical entity — PAP (PAP). We defined PAP as acute pancreatitis complicating pregnancy from first trimester up to 6 months postpartum. PAP is associated with a set of distinct clinical features and risk. The etiological associations are similar to those in the general population and gallstone disease is believed to be responsible for more than 70% of cases [1]. The incidence of gallstone-related diseases including acute cholecystitis and biliary pancreatitis complicating pregnancy is between 0.05% and 0.8% [11]. Biliary etiology may still be a culprit even in patients with prior cholecystectomy since the prevalence of microlithiasis after cholecystectomy is 5% to 10% [12,13]. In this report, we describe the clinical presentation and outcome of 29 cases of acute pancreatitis in pregnant women and up to 6 months postpartum that presented to SPUH from January 2005 to December 2009. We postulated that outcomes in pregnant women with pancreatitis are likely to be poorer than for the overall cohort of pregnant women. The aim of this paper is to evaluate the demographics, risk factors and outcomes of PAP and calculate its prevalence in the community.
Material and methods Approval of institutional review board (IRB) was obtained from SPUH. Using international classification of disease9 (ICD) code of acute pancreatitis (577.9), we reviewed charts of women in child bearing age (18 through 45) from SPUH, New Jersey database from January 2005 through December 2009 and extracted information on patient demographics (maternal age, gestational age at presentation, gravity/parity and delivery, ethnicity); clinical presentation; diagnostic testing (amylase, lipase, triglycerides, calcium, ultrasound, EUS, ERCP); health outcomes in both mother and fetus. Total number of deliveries performed during study period was also obtained from hospital statistics.
To diagnose acute pancreatitis we used the scoring system developed by Sternby et al. [14]. Abdominal pain with serum amylase and lipase more than two times above upper limit of normal was the diagnostic indicator. Acute pancreatitis within 6 months of childbirth was considered postpartum in this study. For each case, we matched two women of the same age (± 4 years) with no history of acute pancreatitis that presented to SPUH outpatient clinic as control. The term PAP include acute pancreatitis during pregnancy and postpartum. Full-term pregnancy was defined as at least 37 completed weeks of gestation. First trimester was defined as weeks 1 through 14, second trimester as weeks 15 through 28, and the third trimester as 29 weeks up to delivery. Low birth weight was diagnosed when a newborn’s first weight was less than 2500 g. Upper limit of common bile duct size (CBD) was taken as 5 mm [15]. Calculation of body mass index (BMI) was done using weight in kilogram divided by height in meter square obtained on first obstetrical visit data.
Statistical analysis Numerical data were reported as number and percentage to characterize the patient population, study results, and outcomes. Categorical data were reported as mean with standard deviation for patient demographics. All analyses including chi-square were performed using SPSS version 20 statistical software (SPSS, Inc., Chicago, IL). P value < 0.05 was considered significant.
Results Demographics and maternal clinical data Over the study period, 29 cases of PAP occurred among 25,600 total hospital deliveries, yielding a prevalence of 0.001%. The race/ethnicity of patients with PAP was Hispanics 48%, Caucasians 24%, African Americans 13%,
Pregnancy associated pancreatitis revisited
179 Table 2
Figure 1 Number (%) of pregnancy associated pancreatitis (PAP) cases by gestational age.
Etiology of acute pancreatitis.
Etiology
Cases (n)
%
Gallstones associated Alcohol Hyperlipemia Hyperparathyroidism Idiopathic
21 1 0 1 7
72.4 3.4 0 3.4 24
Numbers do not add up because hyperparathyroidism was also associated with gallstones.
Discussion
Figure 2 Number (%) of pregnancy associated pancreatitis (PAP) cases by pre-pregnancy body mass index (BMI).
Asian/pacific islanders 13%, compared to those without PAP of 31%, 41%, 14%, and 12% respectively (Table 1). The average maternal age at presentation was 28.7 ± 5.7 years and they usually were multiparous; number of gestations (mean, 2.7 ± 1.6) and parity (mean, 1.7 ± 1.8). None of these patients were on medications known to be associated with either gallstones or pancreatitis. Pancreatitis occurred more frequently as pregnancy progressed 13% (four) in the first, 24% (seven) in the second, and 48% (14) in the third trimester and 13% (four) postpartum. Twenty-seven percent (eight) had a prior history of pancreatitis and 6% (two) had two episodes of acute pancreatitis during pregnancy and up to 6 months postpartum. Thirty-one percent (nine) had prior history of gallstones only 17% (five) had dilated CBD on transabdominal ultrasound at presentation. Choledocholithiasis was diagnosed in 34% (ten) of cases — five by ultrasound alone, additional three patients by MRCP. Two patients with CBD of 6 mm on ultrasound had EUS. The occurrence of acute pancreatitis was distributed across a range of gestational ages, with more cases presenting later in gestation: 13.7%, 24.1% and 48% in 1st, 2nd and 3rd trimesters respectively (Fig. 1). Fig. 2 shows 65% of cases with PAP had BMI more than 30 kg/m2 compared to 24% with BMI 25 to 30 kg/m2 and 10% with BMI less than 25 kg/m2 (P < 0.05) Therefore, cases were more likely to be obese prior to pregnancy.
Fetal and maternal complications There was no maternal and fetal mortality in this study. Of four patients who had ERCP, sphincterotomy was performed on three and none had post ERCP pancreatitis. There was no spontaneous or elective abortion and only one preterm pregnancy was recorded. No fetal malformation was observed. Average hospital stay was 5.87 ± 1.4 days in cohort of PAP.
Our retrospective study confirms observations from recent issues of pancreatitis in pregnancy, including prevalence, severity and outcome. Acute pancreatitis in pregnancy still being a cause for concern evidently has a good outcome. Acute pancreatitis during pregnancy in the United States was once thought to be rare now appears to be more frequently reported, with incidence between 0.1% and 0.008%. [1,3,16] Although the incidence is still rare, the potential complication is doubled compared with non-pregnant females, since it deals with two lives. The wide variation in the incidence is influenced by the prevalence of its most important etiological factor (gallstone disease). This is exemplified by the fact that biliary pancreatitis complicated one in 3300 pregnancies at a large public hospital in Dallas, Texas; [1] in southern California one in 1500 women [17]. In a series of 53 patients with acute pancreatitis during pregnancy published in the medical literature before 1951, [18] vast majority of diagnoses were made during surgery and/or on autopsy. The overall pancreatitis-related maternal mortality was 37% and was significantly higher than that in non-pregnant patients then: 12% to 33% [3]. Perinatal mortality was 38% and was related primarily to prematurity. Swisher et al. also demonstrated continued decline in maternal and perinatal mortality between 1970 and 1990 [6] although their study was relatively small. This improvement in all outcome measures is due to the advent of rapid assay methods for amylase and lipase, better supportive care of pancreatitis, newer therapeutic measures for gallstone pancreatitis and overall improvement in maternal and perinatal care. We have shown that maternal and perinatal mortality has continued to decline. The increasing incidence with gestational age observed in our study (Table 2) has been noted in other studies as well. [1,14,17]. Gallstone predominance for PAP (72.4%) in our study is similar to 65 to 100% noted in earlier studies. [1,7,19] PAP tends to occur more often in Hispanics in New Jersey (48% cases vs. 31% control), perhaps a reflection of high prevalence of gallstone disease. Hispanics make to 16% of total New Jersey population (Mexican origin 13%; Non Mexican origin 87%) [19]. Non-Mexicans are individuals from Latin American countries in central and South America. The prevalence rate of gallstones varies with ones ethnicity. Native American Indians, Latin Americans, Pima Indians and Mexicans have high incidence while the incidence is lower in Asian and African [10]. Obesity as a frequently co-morbid factor for gallstones [18] is made clear again. Obesity itself is also a marker of
180 Table 3
O. Igbinosa et al. Maternal and fetal complication. Case, n = 29 (%)
Control, n = 58 (%)
Fetal birth weight (kg) < 2.32 3—3.6 > 3.7
0 (0) 29 (100) 0 (0)
2 (3) 52 (89) 4 (6)
Preterm delivery (wks) < 35 36—40
1 (3.4) 28 (96.6)
2 (3) 56 (96.9)
Average hosp stay (days)
5.87 ± 1.4
3.21 ± 0.5
Type of delivery Vaginal Cesarean section
7 (24) 22 (75.8)
40 (69) 18 (31)
Maternal demise
0
0
Cesarean section is significantly more in pancreatitis patients.
Table 4
because of the relatively small sample. Further studies are therefore needed. We believe it is simply an institutional preference. However, on a wider view, it discerns unified approach to the management of gallstone pancreatitis and exposes controversies in management of PAP. Case report and anecdotal papers recommend cholecystectomy in 2nd trimester and postpartum if possible [5,20]. Some reports have also suggested that safety of laparoscopic cholestectomy at all stages of pregnancy [7,21]. Based on our findings, we are unable to determine the optimal management of PAP. Our good outcomes most likely reflect improvement in intensive and supportive care that has occurred over the past decade. It is notable that in-general, abdominal ultrasound examination performed by obstetricians was solely to evaluate the fetus and uterus and seldom paid attention to the gallbladder — an easy extension of examination to the liver would have added useful information especially in group considered high risk for gallstone pancreatitis. With newer approach to management of PAP a few issues remain:
Management and outcome.
Trimester
Intervention
Outcome
I
n=4 ERCP: 1 EUS: 0 None: 2 1 lap chole (25%)
4 FTD
II
n=7 ERCP: 1 EUS: 1 None: 5 2 lap chole (28%)
7 FTD
n = 14
1 preterm delivery at 35 wks 13 FTD
III
ERCP: 2 EUS: 2 None: 4 Open chole 2 (14%) Postpartum
n=4 Lap chole 4 (100%)
• the safety of MRCP in the first trimester; • the safety of laparoscopic cholecystectomy in 2nd trimester, however newer reports indicate safety in all trimester; • the use of antibiotics remain controversial; • the risk of bleeding, perforation, pancreatitis, fetal radiation associated with ERCP/EUS is of concern.
Conclusions This study confirms the following:
Maternal demise 0
Lap chole: laparoscopic cholecystectomy; FTD: full-term delivery; ERCP: endoscopic retrograde cholangiopancreatography; EUS: endoscopic ultrasound.
severe pancreatitis. Cases were more likely to be obese prior to pregnancy than control. Sixty-five percent of cases had pre-pregnancy BMI of more than 30 vs. 24% control (Fig. 2). Fetal and maternal mortality in this study (0%) is consistent with literature [1,7—10]. As shown in Table 3, overall rate of preterm delivery in this study, 3.4% cases of PAP vs. 3% (P > 0.5) in patients without PAP. One interesting finding in this study was a higher trend of cholecystectomy in women who developed acute pancreatitis in late trimesters (Table 4); 25% in first trimester, versus 28% in second trimester, 50% in third trimester (mostly in early third trimester) and 100% postparturm. Unfortunately, we do not have a good explanation for this finding
• • • • •
the prevalence of PAP in New Jersey is 0.001%; gallstone disease is the most significant etiology for PAP; ethnicity determines the incidence of PAP; obesity is a frequently co-morbid factor in PAP; this pilot study did not reveal a significant fetal or maternal mortality; • cesarean section is frequently utilized in delivery of fetus.
On the basis of this study, we would like to extend our recommendations to screen Hispanic obese (BMI > 30 kg/m2 ) pregnant women for cholelithiasis by extending the routinely performed ultrasonography during pregnancy to include the gallbladder in the same setting without extra diagnostic cost. This will help identify patients at high risk for PAP who may benefit from elective cholecystectomy during second trimester or before subsequent pregnancy.
Study limitations There two major limitation regarding this study. The first is the small sample size of cases, which reflects the rarity of PAP. Second, it is a single center study, so broad generalization beyond the cases studied should be made with great caution.
Pregnancy associated pancreatitis revisited
Disclosure of interest The authors declare that they have no conflicts of interest concerning this article.
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