Is salivary uric acid, a putative biomarker of pre-eclampsia, of maternal, placental, or fetal origin?

OBJECTIVES: Increased salivary uric acid (sUA) represents a potential biomarker predictive of pre-eclampsia (PE), but its origin is unclear. The study explores whether sUA levels reflect maternal or feto-placental physiological stress and whether sUA levels in these cases correlate with amniotic fluid (fetal origin), maternal blood (maternal origin), or cord blood (fetal vs placental origin). STUDY DESIGN: Pregnant women (n = 39) undergoing amniotomy or caesarean section after 34 gestational weeks were designated into three groups of either maternal, feto-placental, or no signs of physiological stress: women (n = 15) in the established first phase of active labour and without any signs of fetal growth restriction (FGR) or PE were assigned to the maternal stress group, women (n = 6) with an ultrasound-based diagnosis of FGR, with or without PE, were assigned to the feto-placental stress group, and women (n = 18) not yet in active labour and without any signs of FGR or PE, were assigned to the control group. Uric acid levels in corresponding samples of amniotic fluid, saliva, maternal blood, and cord blood were compared between groups and between body compartments within each group. RESULTS: The feto-placental stress group showed increased UA levels in saliva (median, interquartile range [IQR]: 0.47 [0.38] mmol/L, P = 0.023) and maternal blood (0.42 [0.13] mmol/L, P = 0.032), but no differences in amniotic fluid or cord blood compared with the other groups. Within the control and maternal stress group, sUA levels were lower compared with maternal blood (0.20 [0.08] vs 0.25 [0.08] mmol/L, Pcontrol = 0.018; 0.20 [0.06] vs 0.26 [0.08] mmol/L, Pmaternal = 0.001) and highest in amniotic fluid (control group (0.49 [0.18] mmol/L): Pmaternal,blood = 0.001, Pumbilical,artery = <0.001, Pumbilical,vein = <0.001, Psaliva = <0.001) (maternal stress group (0.56 [0.23] mmol/L): Pmaternal,blood = 0.021, Pumbilical,artery = 0.006, Pumbilical,vein = 0.004, Psaliva = 0.003). Levels did not differ between compartments in the feto-placental stress group. CONCLUSIONS: Salivary and maternal blood UA levels were increased in the feto-placental stress group with salivary levels increasing more than blood levels compared with the maternal stress and control groups, whilst UA in amniotic fluid were not different between the groups, suggesting a placental origin and potential use of sUA as a biomarker of placental dysfunction, including FGR and severe PE.

Anterior quadratus lumborum catheters for elective cesarean section: A double-blind, randomized, placebo-controlled trial.

BACKGROUND: Optimizing pain management following cesarean section is crucial for the well-being of both mother and infant. Various types of quadratus lumborum blocks have exhibited reduced opioid consumption and pain scores after cesarean section. However, duration of block effect is relatively short. The aim of this study was to investigate the analgesic efficacy of the anterior quadratus lumborum catheters for cesarean section. METHODS: All 32 enrolled participants were allocated to postoperative bilateral ultrasound-guided anterior quadratus lumborum catheter placement with injection of 60 mL ropivacaine 0.375% after cesarean section. Randomization at 2 h resulted in either 60 mL ropivacaine 0.2% or 60 mL isotonic saline injected through the catheters, with subsequent 22-h infusion of either ropivacaine 0.2% or isotonic saline with an infusion rate of 4 mL h-1 per catheter. Participants in the active group received a total of 697 mg ropivacaine during the first 24 h. All participants received the standard postoperative multimodal pain regimen, and a final bilateral injection at 24-h post-catheter placement of 60 mL ropivacaine 0.375% in total. The primary outcome was time to first opioid administration. Secondary outcomes were pain scores, time to first ambulation, nausea and vomiting, accumulated opioid consumption, and catheter displacement rates. RESULTS: No significant intergroup differences were observed following the randomized intervention. Median time to first opioid (IQR) was (active vs. placebo) 414 (283, 597) vs. 428 (245, 552) minutes, with a median difference (CI) of -14 (-184 to 262) min, p = .32. CONCLUSION: Bilateral anterior quadratus lumborum catheters with continuous infusion did not prolong time to first opioid after elective cesarean section.

Investigations of leukocyte and inflammatory markers in pregnancies complicated by preeclampsia.

OBJECTIVES: Preeclampsia is a frequent and potentially fatal pregnancy complication. It can be challenging to make a timely diagnosis. Identifying clinically useful biochemical markers would be a remedying tool to support the diagnosis of preeclampsia. The aim was to investigate differential cell counts and acute phase reactants as diagnostic markers of preeclamptic third-trimester pregnancies and in relation to pregnancy term, gravidity and the severity of hypertension. METHODS: Based on a cohort of 421 pregnant women, we included 174 participants (case n = 84, control n = 90) during the third trimester. Peripheral blood was sampled to measure differential white blood cell counts and acute phase reactants on the day of inclusion. RESULTS: The neutrophil-to-lymphocyte ratio and plasma haptoglobin levels were significantly increased in healthy pregnancies compared with preeclamptic pregnancies. Plasma ferritin levels and albumin levels were respectively increased and decreased in cases of preeclampsia compared with controls. Albumin was specific among multigravida. Plasma transferrin and high-sensitivity C-reactive protein (hs-CRP) levels were significantly decreased and increased, respectively, in cases with preterm preeclampsia compared with term preeclampsia. CONCLUSION: Plasma ferritin and albumin levels reflected higher inflammation in cases with preeclampsia compared with healthy pregnancies; the same did plasma transferrin and hs-CRP levels in preterm versus term preeclampsia. When considering the normal ranges plasma albumin and hs-CRP levels identified preeclamptic from healthy third-trimester pregnancies and preterm from term preeclampsia cases, respectively, with near-acceptable diagnostic performances. Further validation of the diagnostic value will require larger sample-sized studies with paired plasma and serum samples.

Evidence for a shift in placental HLA-G allelic dominance and the HLA-G isoform profile during a healthy pregnancy and preeclampsia†.

Human leukocyte antigen (HLA)-G, which belongs to a nonclassical class Ib major histocompatibility complex gene family expressed by placental trophoblast cells, plays a central role in establishing tolerance to the semiallogeneic fetus and in placentation. HLA-G exists in different soluble or membrane-bound isoforms. Preeclampsia, a major cause of fetal and maternal morbidity and mortality, has been linked to insufficient placentation and an altered immune response in pregnancy, including altered HLA-G expression. The 14 bp insertion/deletion polymorphism in the 3' untranslated region of the gene and the isoform profile may affect HLA-G expression. The aim of the current pilot study was to characterize the expression patterns of HLAG mRNA, protein, and isoform profile in uncomplicated term pregnancies and in cases of preeclampsia. Maternal sHLA-G mRNA and protein levels were slightly reduced in preeclampsia. No difference was found for placental blood, and no correlation between peripheral and placental sHLA-G levels was found. We observed no association between neither fetal nor maternal HLA-G 14 bp insertion/deletion genotypes and preeclampsia, nor a significant difference in isoform profiles. However, in HLA-G 14 bp insertion/deletion heterozygous placental samples, we observed abundant HLA-G1 14 bp insertion allele expression in the term placentae, which is contrary to previous findings in first trimester trophoblast. Increased HLA-G1 14 bp insertion allele expression in the placenta was associated with reduced levels of placental sHLA-G and an altered isoform profile with increased relative levels of HLA-G1 and -G5 and reduced levels of HLA-G3. The results indicate that an allelic shift in heterozygous individuals could represent a novel regulatory pathway.

Maternal HLA Ib Polymorphisms in Pregnancy Allo-Immunization.

During pregnancy the formation of alloreactive anti-human leukocyte antigen (HLA) antibodies are a major cause of acute rejection in organ transplantation and of adverse effects in blood transfusion. The purpose of the study was to identify maternal HLA class Ib genetic factors associated with anti-HLA allo-immunization in pregnancy and the degree of tolerance estimated by IgG4 expression. In total, 86 primiparous women with singleton pregnancies were included in the study. Maternal blood samples and umbilical cord samples were collected at delivery. Clinical data were obtained. Maternal blood serum was screened for HLA class I and II antibodies, identification of Donor Specific Antibody (DSA), activation of complement measured by C1q and IgG4 concentrations. Mothers were genotyped for HLA class Ib (HLA-E, -F and -G). Anti-HLA class I and II antibodies were identified in 24% of the women. The maternal HLA-E*01:06 allele was significantly associated with a higher fraction of anti-HLA I immunization (20.0% vs. 4.8%, p = 0.048). The maternal HLA-G 3'-untranslated region UTR4-HLA-G*01:01:01:05 haplotype and the HLA-F*01:03:01 allele were significantly associated with a low anti-HLA I C1q activation (16.7% vs. 57.1%, p = 0.028; 16.7% vs. 50.0%, p = 0.046; respectively). Both HLA­G and HLA-F*01:03:01 showed significantly higher levels of IgG4 compared with the other haplotypes. The results support an association of certain HLA class Ib alleles with allo-immunization during pregnancy. Further studies are needed to elucidate the roles of HLA-E*01:06, HLA-F*01:03 and HLA­G UTR4 in reducing the risk for allo-immunization.

[Suspected toxoplasmosis in pregnancy].

Primary infection with Toxoplasma gondii in pregnant women can lead to vertical transmission of the parasites resulting in congenital toxoplasmosis. The frequency of foetal infection increases with gestational age at maternal infection, but the risk of developing clinical sequelae decreases. Data on antiparasitic treatment suggest, that maternal treatment reduces the risk of serious neurological sequelae or death in congenitally infected offspring. Aspects of diagnosis and antimicrobial treatment of T. gondii infection during pregnancy are summarised in this review.

Ultrasound-guided transmuscular quadratus lumborum block for elective cesarean section significantly reduces postoperative opioid consumption and prolongs time to first opioid request: a double-blind randomized trial.

BACKGROUND: Elective cesarean section (ECS) can cause moderate to severe pain that often requires opioid administration. To enhance maternal recovery, and promote mother and baby interaction, it is important to reduce postoperative pain and opioid consumption. Various regional anesthesia techniques have been implemented to improve postoperative pain management following ECS. This study aimed to investigate the efficacy of bilateral ultrasound-guided transmuscular quadratus lumborum (TQL) block on reducing postoperative opioid consumption following ECS. METHODS: A randomized double-blind trial with concealed allocation was conducted in 72 parturients who received bilateral TQL block with either 30 mL ropivacaine 0.375% or saline. TQL block injectate was deposited in the interfascial plane between the quadratus lumborum and psoas major muscles, posterior to the transversalis fascia. Primary outcome was opioid consumption, which was recorded electronically. Pain scores and time to first opioid request were also evaluated. RESULTS: Opioid consumption (oral morphine equivalents, OME) was significantly reduced in group ropivacaine (GRO) in the first 24 hours compared with group saline (65 mg OME vs 94 mg OME) with a mean difference of 29 mg OME; 95% CI 3 to 55, p<0.03. Time to first opioid request was significantly prolonged in GRO, p<0.003. Numerical rating scale pain scores were significantly lower in GRO in the first 6 hours after surgery, p<0.03. CONCLUSIONS: Bilateral TQL block significantly reduced 24 hours' opioid consumption. Further, we observed significant prolongation in time to first opioid, and significant reduction of pain during the first 6 postoperative hours.

Prevalence of polyhydramnios at a Danish hospital--a population-based study.

BACKGROUND: The purpose of this study was to determine the incidence of polyhydramnios, the related maternal and perinatal morbidity, and to estimate the association between perinatal outcome and the degree of polyhydramnios in a Danish population. METHODS: The study population consisted of 168 women with singleton pregnancies and polyhydramnios diagnosed by ultrasound as a largest two-diameter pocket of > 50 cm2. Mild polyhydramnios defined as > 50 and < 100 cm2, and severe polyhydramnios defined as > or = 100 cm2. The background population consisted of 8,347 pregnant women from the same hospital. Outcome measures were compared using chi2 test or Fisher's exact test. RESULTS: The incidence of polyhydramnios was 2%, with 66.7% of cases mild, and 33.3% were severe polyhydramnios. The study population had an increased risk of emergency (19 versus 10.5%, p<0.001) and elective (11.3 versus 5.0%, p<0.001) caesarean section, as well as perinatal death (1.2 versus 0.3%, p<0.05) compared to the background population. In cases of severe polyhydramnios, there was an increased risk of caesarean section (44.6 versus 23.1%, p<0.005), birth weight > 4,000 g (28.6 versus 14.3%, p<0.05), and need for neonatal care (8.9 versus 0.9%, p<0.01) compared to mild cases. Apgar score < 7, perinatal death and structural malformations only occurred in women with severe polyhydramnios. CONCLUSION: It is reasonable to distinguish between mild and severe polyhydramnios regarding special attention and follow-up, as caesarean section and perinatal morbidity and mortality are related to the degree of polyhydramnios. A two-diameter pocket > or = 100 cm2 could be used to separate mild from severe cases.