Syed et al. BMC Public Health 2011, 11(Suppl 3):S2 http://www.biomedcentral.com/1471-2458/11/S3/S2 Page 8 of 12 Experimental Control Odds Ratio Study or Subgroup Events Total Events Total Weight IV, Fixed, 95% CI 1.1.1 Randomized Controlled Trials Carta 1986 2 14 0 15 23.1% 6.20 [0.27, 141.32] Coustan 1986 0 11 0 11 Not estimable Nosari 1993 2 16 1 16 36.0% 2.14 [0.17, 26.33] Subtotal (95% CI) 41 42 59.1% 3.25 [0.46, 22.98] Total events 4 1 Heterogeneity: Chi² = 0.27, df = 1 (P = 0.60); I² = 0% Test for overall effect: Z = 1.18 (P = 0.24) 1.1.2 Quasi Randomized Controlled Trials Botta 1986 1 5 0 Burkart 1988 1 48 0 Subtotal (95% CI) 53 Total events 2 0 Heterogeneity: Chi² = 0.02, df = 1 (P = 0.89); I² = 0% Test for overall effect: Z = 0.93 (P = 0.35) 5 41 46 19.2% 21.7% 40.9% 3.67 [0.12, 113.73] 2.62 [0.10, 66.10] 3.07 [0.29, 32.23] Odds Ratio IV, Fixed, 95% CI Total (95% CI) 94 88 100.0% 3.17 [0.71, 14.28] Total events 6 1 Heterogeneity: Chi² = 0.29, df = 3 (P = 0.96); I² = 0% 0.01 0.1 1 10 Test for overall effect: Z = 1.50 (P = 0.13) Favours experimental Favours control Test for subgroup differences: Chi² = 0.00, df = 1 (P = 0.97), I² = 0% 100 Figure 5 Continuous SC insuline pump versus conventional mulitiple insuline injections. Outcome: pooled stillbirth/IUFD. insulin aspart versus human insulin on stillbirths did not show significant effect on the risk of stillbirth (RR=1.05, 95%CI 0.07-16.7).However, there were only 322 subjects in this trial. Persson et al. 2002 [22] studied the effects of insulin Lispro versus regular insulin. There were no stillbirths or neonatal deaths reported in this compari- son. A single observational study by Aydin et al.2008 [78] assessed the comparison of insulin lispro versus regular human insulin and did not report a significant difference in on the risk of stillbirth (RR=2.14, 95% CI 0.14-33.03). Whereas the other prospective cohort [63] compared the effects of glargine versus NPH insulin. There were two stillbirths reported in the group of preg- estational diabetics using NPH insulin and none in the glargine utilizing group (p-value=0.028). (8) Oral hypoglycemic agents and metformin use in diabetic pregnancies Five observational studies [39,46,48,51,65] focused on the impact of using oral hypoglycemic agents or metfor- min versus diet alone or insulin. Of these studies Holt et al. 2008 [48] compared the effect of glibenclamide versus insulin in a population of women with GDM. No significant difference was seen on risk of stillbirth (RR= 3.07, 95%CI 0.13-73.31). A retrospective cohort study by Ekpebegh et al 2007 [39]compared women treated with oral glucose-lowering agents (OGLA-metformin and glibenclamide) alone (group 1) and women converted from OGLA to insulin (group 2) with women who were treated with insulin alone and women converted from diet to insulin (group 3). There was a significant differ- ence in perinatal mortality rates between group the three groups; perinatal mortality rates (per 1000 births): 125, 28 and 33 (p-value=0.003). At least one group dif- fered significantly from another (p-value=0.003). It is clear that the PNM rate for those on OGLA alone, 125 per 1000, was much higher than for the other two groups. The majority of all perinatal deaths were still- births: eight of 11 in the OGLA alone group and five of seven in the OGLA to insulin group. A study by Hughes et al 2006 [51] compared use of metformin versus none in type 2 diabetics. No signifi- cant difference was observed in perinatal loss (p-value =0.65). Another retrospective cohort study Rayburn et al 2006 [65] compared pregnancies requiring oral hypogly- cemic drugs with those controlled with diet alone. A single stillbirth was reported in the diet controlled group with none in the treatment group and the results were not significant. Hellmuth et al. 2007 compared metformin with sulphonylureas in pregnant diabetic patients and a reference group treated with insulin. (9) Pregestational and gestational DM versus normal pregnancy Our literature search also yielded studies which assessed the risk of stillbirth in the above mentioned comparison. Twelve observational studies assessing the risk of stillbirth in pre-gestational and gestational diabetes versus normal pregnancies [82-93] were identified. Of these, five studies [82-86] could be pooled to assess risk of stillbirth in women with diabetic pregnancy versus normal women. Pooled data from these studies displayed a significant effect on stillbirth risk in the fixed effects model (RR 2.17, 95% CI 1.45-3.25). Due to considerable heterogeneity