Time to redefine prolonged third stage of labor? A systematic review and meta-analysis of the length of the third stage of labor and adverse maternal outcome after vaginal birth.

OBJECTIVES: (1) To assess the association between the duration of the third stage of labor and adverse maternal outcome after vaginal birth and (2) evaluate whether earlier manual placenta removal reduces this risk of adverse outcome. DATA SOURCES: PubMed/MEDLINE, EMBASE, ClinicalTrials.gov, Cochrane Library, Journals@Ovid and the WHO International Clinical Trials Registry from January 1st 2000-June 13th 2023. STUDY ELIGIBILITY CRITERIA: All studies that assessed adverse maternal outcome, defined as any maternal complication after vaginal birth, in relation to duration of the third stage of labor and timing of manual placenta removal. STUDY APPRAISAL AND SYNTHESIS METHODS: Included studies were evaluated according the COSMOS-E (Conducting Systematic Reviews and Meta-Analyses of Observational Studies of Etiology) methodology. Pooled odds ratios with 95% confidence intervals were calculated. We assessed heterogeneity (I2 test); performed subgroup analyses; and calculated 95% prediction intervals. RESULTS: To answer the first objective, 18 cohort studies were included. Assessed cut-offs of third stage were: 15, 30 and 60 minutes. Women with a third stage ≥15 minutes had an increased risk of postpartum hemorrhage compared to <15 minutes (Odds Ratio [OR] 5.55; 95%CI 1.74,17.72). For women without risk factors for postpartum hemorrhage, the OR was 2.20; 95%CI 0.75,6.49. Among women with a third stage ≥60 minutes versus <60 minutes, the OR was 3.72; 95%CI 2.36-5.89. Incidence of red blood cell transfusion was increased for a third stage ≥30 minutes versus <30 minutes (OR 3.23; 95%CI 2.26-4.61). Three studies assessed the timing of placenta removal and risk of adverse maternal outcome yet could not be pooled due to different outcome measures. One randomized controlled trial reported a significantly higher incidence of hemodynamic compromise in women with manual placenta removal at 15 versus 10 minutes (19.2%,30/156 6.4%,10/156) while two observational studies reported a lower risk of bleeding among women without manual placenta removal. CONCLUSION: Although the risk of adverse maternal outcome after vaginal birth increases when the third stage of labor exceeds 15 minutes, there is no convincing evidence supporting a reduction of the third stage of labor by earlier manual removal of the placenta to reduce the incidence of adverse maternal outcome.

Effects of uptake carrier blockers SK & F 89976-A and L-trans-PDC on in vivo release of amino acids in rat hippocampus.

This report describes the in vivo effects of the uptake carrier blockers 1-(4,4-diphenyl-3-butenyl)-3-piperidine carboxylic acid hydrochloride (SK & F 89976-A) and L-trans-pyrrolidine-2,4-dicarboxylate (L-trans-PDC) on basal and K(+)-evoked extracellular levels of gamma-aminobutyric acid (GABA), glutamate, aspartate and taurine in the hippocampus of anaesthetised rats, using the microdialysis technique. SK & F 89976-A increased extracellular GABA levels under K(+)-depolarised conditions and did not affect extracellular glutamate, aspartate and taurine levels, indicating its selective effect on GABA uptake L-trans-PDC dose dependently increased basal and K(+)-evoked extracellular glutamate levels, and did not affect extracellular GABA levels, but increased basal aspartate and taurine levels. The K(+)-evoked release of GABA and glutamate, measured in the presence of both SK & F 89976-A and L-trans-PDC, was Ca(2+)-dependent for about 50% and 65%, respectively. In contrast, the release of the putative amino acid transmitters aspartate and taurine was not Ca(2+)-dependent. These results indicate that (1) in rat hippocampus uptake carriers actively regulate extracellular GABA and glutamate levels, (2) the GABA and glutamate released by K+ was derived from both Ca(2+)-dependent (presumably vesicular) and Ca(2+)-independent (presumably cytosolic) pools, whereas aspartate and taurine release was exclusively from Ca(2+)-independent pools.

Developmental and comparative aspects of nonsynaptic release by the egg-laying controlling caudodorsal cells of basommatophoran snails.

In an immunoelectron microscope study the postembryonic development of the cerebral caudodorsal cells (CDC) in the freshwater snail Lymnaea stagnalis was studied as well as the development of similar neurons in other basommatophoran families. The CDC of adult L. stagnalis control egg-laying and associated behaviors by releasing various peptides, including the ovulation hormone CDCH. The CDC release peptides from neurohemal axon terminals and from nonsynaptic release sites of axon collaterals. During postembryonic development the collateral system develops synchronously with the neurohemal area. The first collaterals appear in the cerebral commissure of juvenile snails (10 mm shell height; S = 10). Up to S = 30 they gradually increase in size and length and eventually run through the entire inner compartment. Secretory granules in both collaterals and neurohemal axon terminals increase in size as well. Immunoelectron microscopy combined with the TARI-method for the demonstration of exocytosis indicates that CDCH-release from collaterals and neurohemal terminals occurs already in S = 10; exocytosis of immunoreactive granule contents takes place from nonsynaptic release sites, unspecialized areas of the axolemma of the collaterals. Release activity in the collaterals gradually increases up to S greater than or equal to 20. Neurohemal release activity shows a similar picture except for a steep increase in adult snails. A distinct glial sheath, separating the neurohemal area from the collateral system, appears around S = 15. Representatives of three families of Basommatophora, viz. the lymnaeid L. ovata, the planorbid Planorbis planorbis, and the bulinid Bulinus truncatus possess a well-developed collateral system showing many signs of exocytosis. A glial sheath separates the collaterals from the neurohemal area. Secretory granules of the CDC in L. ovata stain weakly positive with the anti-CDCH antiserum. Since the other Basommatophora did not show immunoreactivity, the chemical structure of egg laying peptides in Basommatophora seems to be genus specific. Apparently the secretory activity of both the neurohemal area and the collateral system is not only important in the sexually mature animal, being involved in the control of egg laying and egg-laying behavior, but also in the juvenile snail. The finding of a collateral system in representatives of three basommatophoran families strongly indicates the importance of the system for the control of reproduction in basommatophoran snails in general.