Postponed pregnancies and risks of very advanced maternal age

QUESTIONS UNDER STUDY To evaluate pregnancy outcome in pregnant women aged ≥45 years, termed very advanced maternal age (VAMA). METHODS We retrospectively compared the outcome of pregnancies in VAMA patients with controls aged 30 years at time of delivery. Subgroups of singleton and multiple pregnancies were also analysed. Incidences of maternal and fetal adverse outcomes were measured. Statistical significance was set at p 7 days (37.8% vs 15.1%; OR 3.42) was found. Infant complications such as prematurity (44.9% vs 16.2%; OR 4.2) and low birthweight <5th percentile (11.0% vs 5.6%; OR 2.1) were also increased. CONCLUSION Pregnant women of very advanced maternal age (≥45 years) have significantly increased maternal and fetal risks. Women postponing pregnancy or planning a pregnancy in very advanced age should be informed about these risks, in particular before artificial reproductive technologies are applied or "social freezing"

Postpartum Blood Loss in Women Treated for Intrahepatic Cholestasis of Pregnancy

OBJECTIVE To evaluate postpartum blood loss in women with treated intrahepatic cholestasis of pregnancy. METHODS In a retrospective case-control study, 15,083 deliveries including 348 women with intrahepatic cholestasis of pregnancy (2.3%) were analyzed from 2004 to 2014. To adjust for differences in baseline characteristics, a propensity analysis was performed and women in the control group were matched to the women in the intrahepatic cholestasis of pregnancy group in a 5:1 ratio. Blood loss was analyzed by estimated blood loss and Δ hemoglobin (Hb, difference between prepartum and postpartum Hb). A subgroup analysis regarding severity of intrahepatic cholestasis of pregnancy based on maximum bile acid level (mild [less than 40 micromoles/L], moderate [40-99 micromoles/L], and severe intrahepatic cholestasis of pregnancy [100 micromoles/L or greater]) was performed. Differences in estimated blood loss, ΔHb, and meconium staining between subgroups were analyzed. A Spearman rank correlation was performed to evaluate the association of bile acid levels and blood loss within subgroups. RESULTS Estimated blood loss (median 400 [300-600] mL compared with 400 [300-600] mL, P=.22), ΔHb (14.0 [5.0-22.0] compared with 12.0 [4.0-21.0] g/L, P=.09), meconium staining (14.5% compared with 11.4%, P=.12), and number of stillbirths after 26 weeks of gestation (0.6% compared with 1.8%, P=.10) were not significantly different in the study compared with the control group. In moderate and severe intrahepatic cholestasis of pregnancy, meconium staining was observed significantly more often compared with that in a control group (23.0% and 32.3% compared with 11.4%, P<.01). There was no correlation between estimated blood loss or ΔHb and severity of intrahepatic cholestasis of pregnancy. CONCLUSIONS In our cohort of women with intrahepatic cholestasis of pregnancy who are treated with ursodeoxycholic acid and have planned delivery (induction of labor or planned cesarean delivery) at 38 weeks of gestation, no differences in postpartum blood loss were seen

Maternal and fetal outcomes after uterine fundal pressure in spontaneous and assisted vaginal deliveries

AbstractAim: This study aimed to evaluate maternal and fetal outcomes after uterine fundal pressure (UFP) in spontaneous and assisted vaginal deliveries. Methods: In a retrospective cohort study, 9743 singleton term deliveries with cephalic presentation were analyzed from 2004 to 2013. Spontaneous and assisted vaginal deliveries were analyzed separately with and without the application of UFP. Odds ratios were adjusted in a multivariate logistic regression analysis. Results: Prevalence of UFP was 8.9% in spontaneous and 12.1% in assisted vaginal deliveries. UFP was associated with a higher incidence of shoulder dystocia in both spontaneous (adjusted odds ratio [adj. OR] 2.44, confidence interval [CI] 95% 1.23-4.84) and assisted vaginal deliveries (adj. OR 6.88 CI 95% 3.50-13.53). Fetal acidosis (arterial umbilical pH<7.2) was seen more often after the application of UFP in spontaneous vaginal deliveries (adj. OR 3.18, CI 95% 2.64-3.82) and assisted vaginal deliveries (adj. OR 1.59 CI 95% 1.17-2.16). The incidence of 5′-Apgar<7 (adj. OR 2.19 CI 95% 1.04-4.6) and 10′-Apgar<7 (adj. OR 3.04 CI 95% 1.17-7.88) was also increased after the application of UFP in spontaneous deliveries. A higher incidence of anal sphincter tears (AST) (adj. OR 46.25 CI 95% 11.78-181.6) in the UFP group of spontaneous deliveries was observed. Conclusions: UFP is associated with increased occurrence of shoulder dystocia and fetal acidosis. In spontaneous deliveries, the risk for lower Apgar scores after 5 and 10 min is increased, as well as the risk for AST

Maternal and fetal outcomes after uterine fundal pressure in spontaneous and assisted vaginal deliveries

AIM: This study aimed to evaluate maternal and fetal outcomes after uterine fundal pressure (UFP) in spontaneous and assisted vaginal deliveries. METHODS: In a retrospective cohort study, 9743 singleton term deliveries with cephalic presentation were analyzed from 2004 to 2013. Spontaneous and assisted vaginal deliveries were analyzed separately with and without the application of UFP. Odds ratios were adjusted in a multivariate logistic regression analysis. RESULTS: Prevalence of UFP was 8.9% in spontaneous and 12.1% in assisted vaginal deliveries. UFP was associated with a higher incidence of shoulder dystocia in both spontaneous (adjusted odds ratio [adj. OR] 2.44, confidence interval [CI] 95% 1.23-4.84) and assisted vaginal deliveries (adj. OR 6.88 CI 95% 3.50-13.53). Fetal acidosis (arterial umbilical pH<7.2) was seen more often after the application of UFP in spontaneous vaginal deliveries (adj. OR 3.18, CI 95% 2.64-3.82) and assisted vaginal deliveries (adj. OR 1.59 CI 95% 1.17-2.16). The incidence of 5'-Apgar<7 (adj. OR 2.19 CI 95% 1.04-4.6) and 10'-Apgar<7 (adj. OR 3.04 CI 95% 1.17-7.88) was also increased after the application of UFP in spontaneous deliveries. A higher incidence of anal sphincter tears (AST) (adj. OR 46.25 CI 95% 11.78-181.6) in the UFP group of spontaneous deliveries was observed. CONCLUSIONS: UFP is associated with increased occurrence of shoulder dystocia and fetal acidosis. In spontaneous deliveries, the risk for lower Apgar scores after 5 and 10 min is increased, as well as the risk for AST

Position at birth as an important factor for the occurrence of anal sphincter tears: a retrospective cohort study

Objective: This work aimed to analyze the association between maternal position at birth in spontaneous deliveries and the occurrence of anal sphincter tears (AST) given the lack of evidence related to the least traumatic birth position. Study design: A total of 7832 vaginal deliveries were included. Vaginal-operative deliveries and deliveries with fundal pressure were excluded. Birth positions on bed, in water, kneeling, and in a squatting position on a low stool were compared. Birth position on bed was considered as the reference group, and a logistic regression analysis adjusting for important fetomaternal parameters was performed. Results: The overall incidence of AST was 1.1%. AST rate was significantly increased in squatting (2.9%) and kneeling (2.1%) positions compared with birth position on bed (1.0%) or in water (0.9%). Logistic regression analysis revealed a significantly higher risk for ASTs in squatting (OR 2.92, CI 95% 1.04-8.18) and in kneeling positions (OR 2.14, CI 95% 1.05-4.37) compared with the reference group on bed. When adjusting for risk factors, birth in a kneeling position remained significantly associated with ASTs (adj. OR 2.21, CI 95% 1.07-4.54). Conclusions: Birth in squatting or in kneeling position is associated with an elevated risk for ASTs. Birth in water is not associated with an increased risk for AST. Based on the results, women should be informed about the association of certain birth positions with the occurrence of AST

Kidney-synthesized erythropoietin is the main source for the hypoxia-induced increase in plasma erythropoietin in adult humans

Purpose: Erythropoietin (EPO) is mainly synthesized within renal peritubular fibroblasts, and also other tissues such as the liver possess the ability. However, to what extent non-kidney produced EPO contributes to the hypoxia-induced increase in circulating EPO in adult humans remains unclear. Methods: We aimed to quantify this by assessing the distribution of EPO glycoforms which are characterized by posttranslational glycosylation patterns specific to the synthesizing cell. The analysis was performed on samples obtained in seven healthy volunteers before, during and after 1month of sojourn at 3,454m altitude. Results: Umbilical cord (UC) plasma served as control. As expected a peak (p<0.05) in urine (2.3±0.5-fold) and plasma (3.3±0.5-fold) EPO was observed on day 1 of high-altitude exposure, and thereafter the concentration decreased for the urine sample obtained after 26days at altitude, but remained elevated (p<0.05) by 1.5±0.2-fold above the initial sea level value for the plasma sample. The EPO glycoform heterogeneity, in the urine samples collected at altitude, did not differ from values at sea level, but were markedly lower (p<0.05) than the mean percent migrated isoform (PMI) for the umbilical cord samples. Conclusion: Our studies demonstrate (1) UC samples express a different glycoform distribution as compared to adult humans and hence illustrates the ability to synthesis EPO in non-kidney cells during fetal development (2) as expected hypoxia augments circulating EPO in adults and the predominant source here for remains being kidney derived

Minimally invasive, imaging guided virtual autopsy compared to conventional autopsy in foetal, newborn and infant cases: study protocol for the paediatric virtual autopsy trial

BACKGROUND: In light of declining autopsy rates around the world, post-mortem MR imaging is a promising alternative to conventional autopsy in the investigation of infant death. A major drawback of this non-invasive autopsy approach is the fact that histopathological and microbiological examination of the tissue is not possible. The objective of this prospective study is to compare the performance of minimally invasive, virtual autopsy, including CT-guided biopsy, with conventional autopsy procedures in a paediatric population. METHODS/DESIGN: Foetuses, newborns and infants that are referred for autopsy at three different institutions associated with the University of Zurich will be eligible for recruitment. All bodies will be examined with a commercial CT and a 3 Tesla MRI scanner, masked to the results of conventional autopsy. After cross-sectional imaging, CT-guided tissue sampling will be performed by a multifunctional robotic system (Virtobot) allowing for automated post-mortem biopsies. Virtual autopsy results will be classified with regards to the likely final diagnosis and major pathological findings and compared to the results of conventional autopsy, which remains the diagnostic gold standard. DISCUSSION: There is an urgent need for the development of alternative post-mortem examination methods, not only as a counselling tool for families and as a quality control measure for clinical diagnosis and treatment but also as an instrument to advance medical knowledge and clinical practice. This interdisciplinary study will determine whether virtual autopsy will narrow the gap in information between non-invasive and traditional autopsy procedures. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01888380

Kidney-synthesized erythropoietin is the main source for the hypoxia-induced increase in plasma erythropoietin in adult humans

PURPOSE Erythropoietin (EPO) is mainly synthesized within renal peritubular fibroblasts, and also other tissues such as the liver possess the ability. However, to what extent non-kidney produced EPO contributes to the hypoxia-induced increase in circulating EPO in adult humans remains unclear. METHODS We aimed to quantify this by assessing the distribution of EPO glycoforms which are characterized by posttranslational glycosylation patterns specific to the synthesizing cell. The analysis was performed on samples obtained in seven healthy volunteers before, during and after 1 month of sojourn at 3,454 m altitude. RESULTS Umbilical cord (UC) plasma served as control. As expected a peak (p < 0.05) in urine (2.3 ± 0.5-fold) and plasma (3.3 ± 0.5-fold) EPO was observed on day 1 of high-altitude exposure, and thereafter the concentration decreased for the urine sample obtained after 26 days at altitude, but remained elevated (p < 0.05) by 1.5 ± 0.2-fold above the initial sea level value for the plasma sample. The EPO glycoform heterogeneity, in the urine samples collected at altitude, did not differ from values at sea level, but were markedly lower (p < 0.05) than the mean percent migrated isoform (PMI) for the umbilical cord samples. CONCLUSION Our studies demonstrate (1) UC samples express a different glycoform distribution as compared to adult humans and hence illustrates the ability to synthesis EPO in non-kidney cells during fetal development (2) as expected hypoxia augments circulating EPO in adults and the predominant source here for remains being kidney derived

Maternal and perinatal outcomes following pre-Delta, Delta, and Omicron SARS-CoV-2 variants infection among unvaccinated pregnant women in France and Switzerland: a prospective cohort study using the COVI-PREG registry.

BACKGROUND SARS-CoV-2 positive pregnant women are at higher risk of adverse outcomes, but little evidence is available on how variants impact that risk. We aim to evaluate maternal and perinatal outcomes among unvaccinated pregnant women that tested positive for SARS-CoV-2, stratified by pre-Delta, Delta, and Omicron periods. METHODS This prospective study enrolled women from March 2020 to September 2022. Exposure to the different SARS-CoV-2 variants was defined by their periods of predominance. The primary outcome was severe maternal adverse outcome defined as either intensive care unit admission, acute respiratory distress syndrome, advanced oxygen supplementation, or maternal death. The secondary outcomes were preterm birth and other perinatal outcomes. FINDINGS Overall, 1402, 262, and 391 SARS-CoV-2 positive pregnant women were enrolled during the pre-Delta, Delta, and Omicron periods respectively. Severe maternal adverse outcome was reported in 3.4% (n = 947/1402; 95% confidence intervals (95%CI) 2.5-4.5), 6.5% (n = 7/262; 95%CI 3.8-10.2), and 1.0% (n = 4/391; 95%CI 0.3-2.6) of women during the pre-Delta, Delta, and Omicron periods. The risk of severe maternal adverse outcome was higher during the Delta vs pre-Delta period (adjusted risk ratio (aRR) = 1.8; 95%CI 1.1-3.2) and lower during the Omicron vs pre-Delta period (aRR = 0.3; 95%CI, 0.1-0.8). The risks of hospitalization for COVID-19 were 12.6% (n = 176/1402; 95%CI 10.9-14.4), 17.2% (n = 45/262; 95%CI 12.8-22.3), and 12.5% (n = 49/391; 95%CI 9.4-16.2), during the pre-Delta, Delta, and Omicron period, respectively. Pregnancy complications occurred after SARS-CoV-2 exposure in 30.0% (n = 363/1212; 95%CI 27.4-32.6), 35.2% (n = 83/236; 95%CI 29.1-41.6), and 30.3% (n = 105/347; 95%CI 25.5-35.4) of patients during the pre-Delta, Delta, and Omicron periods, respectively. Stillbirths were reported in 0.5% (n = 6/1159; 95%CI 0.2-1.1), 2.8% (n = 6/210; 95%CI 1.0-6.0), and 0.9% (n = 2/213; 95%CI 0.1-3.4) or patients during the pre-Delta, Delta, and Omicron periods respectively. INTERPRETATION The Delta period was associated with a higher risk of severe maternal adverse outcome and the Omicron period with a lower risk of severe adverse outcome compared to pre-Delta era. The reported risk of hospitalization was high during the Omicron period and should not be trivialized. FUNDING Swiss Federal Office of Public Health, Fondation CHUV