PL.72 Risk Factors For Manual Removal of Placenta Across Parity

Abstract

Background Retained placenta is a complication of the third stage of labour that is associated with increased rates of post-partum haemorrhage. Previous research identified risk factors related to maternal demographics and delivery related variables, but both clinical practises and patient variables have since changed. This study re-examines risk factors for manual removal of placenta (MROP) across parity. Method This case-control study was conducted at the National Maternity Hospital in Dublin Ireland from January 2011 to Dec 2011. A chart review of all liveborn, singleton, vaginal deliveries was conducted to investigate maternal and delivery related variables in relation to retained placenta. Women were grouped based on the need for MROP as well as by parity. Statistical analysis was performed using chi square tests and odds ratios. Results 7163 deliveries met the study criteria and 190 (2.65%) required MROP. Risk factors that were identified were parity, two or more miscarriages, previous ERPC, gestation at delivery, and oxytocin to accelerate labour. When divided based on parity, increased maternal age was a significant risk factor for primiparous patients. For both groups, MROP was associated with greater blood loss. Conclusion These results show an increase in the rate of MROP as compared to earlier studies and identifies similar risk factors. Of note, maternal age in primiparous women and use of oxytocin are factors that have undergone change since earlier studies and may be contributing to the rise in the rates of MROP in the industrialised world.

Protein Arginine Deiminases (PADs): Biochemistry and Chemical Biology of Protein Citrullination

“…19 PADs 1, 3 and 4 also have K 0.5 values in the micromolar range (K 0.5(PAD1) = 140 µM; K 0.5(PAD3) = 550 µM; K 0.5(PAD4) = 560 µM) at pH 7.6 when using Nα-benzoyl arginine ethyl ester (BAEE) as the substrate. 20,21 Calcium activation is cooperative and the Hill coefficients are >1, consistent with the fact that multiple calcium ions must bind to generate active enzyme. The calcium binding sites are well conserved in PAD1, 2 and 4 (except Ca5, which is absent from PAD1, and Ca6, which is unique to PAD2).…”

“…Activation is calcium-specific because other metal ions, including barium, magnesium, manganese, strontium, samarium and zinc, do not promote catalysis. 20 BAEE, BAA and Nα-benzoyl arginine methyl ester (BAME) (Table 1) are often used model PAD-substrates. 1,17 Detailed substrate-specificity studies suggest that BAEE and BAME are preferred for PAD2 and PAD1, respectively, whereas BAA is the best substrate for both PAD1 and PAD4 (Table 1).…”

“…However, these arginine analogues are poor PAD3 substrates. [20][21][22] The structure of the PAD4C645A-BAA complex highlights how D350 and D473 stabilize the positively charged guanidinium group and place the central guanidinium carbon between C645, positioning it for nucleophilic attack, and H471, which acts as a general acid/ base in the first step of the reaction (Figure 2H). 17 The carbonyl groups in BAA form a bidentate H-bond with R374, conferring specificity toward peptidyl-arginine substrates over free arginine, which lacks these functionalities.…”

“…In addition to these benzoylated-arginines, we also evaluated the citrullination of histones H3 and H4, two physiological substrates. [20][21][22] The activity of PAD2 towards recombinant histone H3 (k cat /K m = 1200 M -1 s -1 ) is almost 10-fold lower than that observed with BAEE, the best small molecule PAD2 substrate (Table 1). 22 Similarly the activity of PAD1 is almost 5-fold lower for histone H4 than BAA.…”

“…Although hydrolysis of INT-3 could afford either ornithine and urea (as in the case of amidinotransferases, a structurally related enzyme family) or citrulline and ammonia, we unambiguously showed that PADs produce citrulline and ammonia in equimolar amounts. [20][21][22][23] Notably, mutation of any of these four key residues decreases k cat /K m by >5,000-fold, indicating that substratebinding, nucleophilic attack and general acid-base catalysis are highly cooperative processes. 23 To gain insights into the protonation states of C645 and H471, we measured PAD4-activity at pH values between 5.7 and 9.0.…”