Perinatal morbidity among women with a previous caesarean delivery (PRISMA trial): a cluster-randomised trial.

BACKGROUND: Women with a previous caesarean delivery face a difficult choice in their next pregnancy: planning another caesarean or attempting vaginal delivery, both of which are associated with potential maternal and perinatal complications. This trial aimed to assess whether a multifaceted intervention, which promoted person-centred decision making and best practices, would reduce the risk of major perinatal morbidity among women with one previous caesarean delivery. METHODS: We conducted an open, multicentre, cluster-randomised, controlled trial of a multifaceted 2-year intervention in 40 hospitals in Quebec among women with one previous caesarean delivery, in which hospitals were the units of randomisation and women the units of analysis. Randomisation was stratified according to level of care, using blocked randomisation. Hospitals were randomly assigned (1:1) to the intervention group (implementation of best practices and provision of tools that aimed to support decision making about mode of delivery, including an estimation of the probability of vaginal delivery and an ultrasound estimation of the risk of uterine rupture), or the control group (no intervention). The primary outcome was a composite risk of major perinatal morbidity. This trial was registered with ISRCTN, ISRCTN15346559. FINDINGS: 21 281 eligible women delivered during the study period, from April 1, 2016 to Dec 13, 2019 (10 514 in the intervention group and 10 767 in the control group). None were lost to follow-up. There was a significant reduction in the rate of major perinatal morbidity from the baseline period to the intervention period in the intervention group as compared with the control group (adjusted odds ratio [OR] for incremental change over time, 0·72 [95% CI 0·52-0·99]; p=0·042; adjusted risk difference -1·2% [95% CI -2·0 to -0·1]). Major maternal morbidity was significantly reduced in the intervention group as compared with the control group (adjusted OR 0·54 [95% CI 0·33-0·89]; p=0·016). Minor perinatal and maternal morbidity, caesarean delivery, and uterine rupture rates did not differ significantly between groups. INTERPRETATION: A multifaceted intervention supporting women in their choice of mode of delivery and promoting best practices resulted in a significant reduction in rates of major perinatal and maternal morbidity, without an increase in the rate of caesarean or uterine rupture. FUNDING: Canadian Institutes of Health Research (CIHR, MOP-142448).

Long-Term Consequences of COVID-19 in Predominantly Immunonaive Patients: A Canadian Prospective Population-Based Study.

Background: Lingering symptoms are frequently reported after acute SARS-CoV-2 infection, a condition known as post-COVID-19 condition (PCC). The duration and severity of PCC in immunologically naïve persons remain unclear. Furthermore, the long-term consequences of these chronic symptoms on work and mental health are poorly documented. Objective: To determine the outcome, the risk factors, and the impact on work and mental health associated with post-COVID-19 symptoms. Methods: This prospective population-based study assessed acute COVID-19 symptoms and their evolution for up to nine months following infection. Individuals aged 18 years and older with COVID-19 in three Canadian regions between 1 November 2020 and 31 May 2021 were recruited. Participants completed a questionnaire that was either administered by trained student investigators over the phone or self-administered online. Results: A total of 1349 participants with a mean age of 46.6 ± 16.0 years completed the questionnaire. Participants were mostly unvaccinated at the time of their COVID-19 episode (86.9%). Six hundred and twenty-two participants (48.0%) exhibited one symptom or more, at least three months post-COVID-19. Among participants with PCC, 23.0% to 37.8% experienced fatigue at the time of survey. Moreover, 6.1% expressed psychological distress. Risk factors for PCC and fatigue included female sex (OR = 1.996), higher number of symptoms (OR = 1.292), higher severity of episode (OR = 3.831), and having a mental health condition prior to the COVID-19 episode (OR = 5.155). Conclusions: In this multicenter cohort study, almost half (47%) of the participants reported persistent symptoms >3 months after acute infection. Baseline risk factors for PCC include female sex, number and severity of symptoms during acute infection, and a previous diagnosis of mental health disorder. Having PCC negatively impacted health-related quality of life and these patients were more likely to exhibit psychological distress, as well as fatigue.

Midtrimester Cervical Length in Low-Risk Nulliparous Women for the Prediction of Spontaneous Preterm Birth: Should We Consider a New Definition of Short Cervix?

OBJECTIVE: The study aimed to estimate the predictive value of midtrimester cervical length (CL) and the optimal cut-off of CL that should be applied with asymptomatic nulliparous women for the prediction of spontaneous preterm birth (sPTB). STUDY DESIGN: This is a prospective cohort study of asymptomatic nulliparous women with a singleton gestation. Participants underwent CL measurement by transvaginal ultrasound between 20 and 24 weeks of gestation. The participants and their health care providers remained blinded to the results of CL measurement. The primary outcomes were sPTB before 35 weeks and sPTB before 37 weeks. Receiver operating characteristics (ROC) curve analyses were performed. Analyses were repeated by using multiples of median (MoM) of CL adjusted for gestational age. RESULTS: Of 796 participants, the mean midtrimester CL was 40 ± 6 mm with a 1st, 5th, and 10th percentile of 25, 29, and 32 mm, respectively. ROC curve analyses suggest that a cut-off of 30 mm was the optimal CL to predict sPTB before 35 weeks (area under the ROC curve [AUC]: 0.70, 95% confidence interval [CI]: 0.56-0.85) and before 37 weeks (AUC: 0.70, 95% CI: 0.59-0.80). Midtrimester CL <30 mm could detect 35% of all sPTB before 35 weeks at a false-positive rate of 5% (relative risk: 9.1, 95% CI: 3.5-23.5, p < 0.001). We observed similar results using a cut-off of CL <0.75 MoM adjusted for gestational age. CONCLUSION: A midtrimester CL cut-off of 30 mm (instead of 25 mm), or CL less than 0.75 MoM, should be used to identify nulliparous women at high risk of sPTB. KEY POINTS: · The optimal CL cut-off for the prediction of sPTB is 30 mm in nulliparous women.. · In nulliparous women, a midtrimester CL < 30 mm is highly associated with sPTB before 35 and 37 weeks.. · A midtrimester of CL <30 mm (5th percentile) should define a short cervix in asymptomatic nulliparous women..

The impact of levothyroxine exposure on delivery outcome in hypothyroid pregnant women (PETAL study): A five-year retrospective cohort study.

Background: Hypothyroidism affects 3% of pregnant women, and to date, no studies have addressed the impact levothyroxine-treated hypothyroidism on delivery outcome. Methods: This retrospective cohort study was conducted among 750 women with a singleton pregnancy who gave birth between 2015 and 2019. Delivery modes were compared between 250 hypothyroid women exposed to levothyroxine and 500 euthyroid control women. The aim of this study was to determine the impact of levothyroxine exposure on delivery outcome. Results: Multiple logistic regression showed no significant association between exposure to levothyroxine and the overall rate of caesarean delivery (aOR 1.1; 95% CI 0.8 to 1.6). Mean TSH concentrations were significantly higher throughout the pregnancy in hypothyroid women despite levothyroxine treatment. Maternal and neonatal outcomes in both groups were not different. Conclusion: Hypothyroidism treated with levothyroxine during pregnancy according to local guidelines is not a significant risk factor for caesarean delivery.

Survey of Mode of Delivery and Maternal and Perinatal Outcomes in Canada.

OBJECTIVE: To identify determinants of cesarean delivery (CD) and examine associations between mode of delivery (MOD) and maternal and perinatal outcomes. METHODS: We conducted a retrospective analysis of a Canadian multicentre birth cohort derived from provincial data collected in 2008/2009. Maternal and perinatal characteristics and outcomes were compared between vaginal and cesarean birth and between the following MOD subgroups: spontaneous vaginal delivery (VD), assisted VD, planned cesarean delivery (CD), and intrapartum CD. Multivariate regression identified determinants of CD and the effects of MOD and previous CD on maternal and perinatal outcomes. RESULTS: The cohort included 264 755 births (72.1% VD and 27.9% CD) from 91 participating institutions. Determinants of CD included maternal age, parity, previous CD, chronic hypertension, diabetes, urinary tract infection or pyelonephritis, gestational hypertension, vaginal bleeding, labour induction, pre-term gestational age, low birth weight, large for gestational age, malpresentation, and male sex. CD was associated with greater risk of maternal and perinatal morbidity and mortality. Subgroup analysis demonstrated higher risk of adverse pregnancy outcomes with assisted VD and intrapartum CD than spontaneous VD. Planned CD reduced the risk of obstetric wound hematoma and perinatal mortality but increased maternal and neonatal morbidity. Previous CD increased the risk of maternal and neonatal morbidity among multiparous women. CONCLUSIONS: The CD rate in Canada is consistent with global trends reflecting demographic and obstetric intervention factors. The risk of adverse pregnancy outcomes with CD warrants evaluation of interventions to safely prevent nonessential cesarean birth.

Association of Prenatal Acetaminophen Exposure Measured in Meconium With Adverse Birth Outcomes in a Canadian Birth Cohort.

Background: The small number of studies examining the association of prenatal acetaminophen with birth outcomes have all relied on maternal self-report. It remains unknown whether prenatal acetaminophen exposure measured in a biological specimen is associated with birth outcomes. Objectives: To investigate the association of acetaminophen measured in meconium with birthweight, gestational age, preterm birth, size for gestational age, gestational diabetes, preeclampsia, and high blood pressure. Methods: This birth cohort from Sherbrooke, QC, Canada, included 773 live births. Mothers with no thyroid disease enrolled at their first prenatal care visit or delivery. Acetaminophen was measured in meconium for 393 children at delivery. We tested associations of prenatal acetaminophen with birthweight, preterm birth, gestational age, small and large for gestational age, gestational diabetes, preeclampsia, and high blood pressure. We imputed missing data via multiple imputation and used inverse probability weighting to account for confounding and selection bias. Results: Acetaminophen was detected in 222 meconium samples (56.5%). Prenatal acetaminophen exposure was associated with decreased birthweight by 136 g (ß = -136; 95% CI [-229, -43]), 20% increased weekly hazard of delivery (hazard ratio = 1.20; 95% CI [1.00, 1.43]), and over 60% decreased odds of being born large for gestational age (odds ratio = 0.38; 95% CI [0.20, 0.75]). Prenatal acetaminophen was not associated with small for gestational age, preterm birth, or any pregnancy complications. Conclusion: Prenatal acetaminophen was associated with adverse birth outcomes. Although unobserved confounding and confounding by indication are possible, these results warrant further investigation into adverse perinatal effects of prenatal acetaminophen exposure.

Evaluation of midtrimester cervical length thresholds for the prediction of spontaneous preterm birth.

INTRODUCTION: To estimate the optimal midtrimester cervical length (CL) threshold for the prediction of spontaneous preterm birth (sPTB) in asymptomatic pregnant women. MATERIAL AND METHODS: This is a prospective observational cohort study including asymptomatic women with singleton pregnancies who underwent CL measurement by transabdominal and/or transvaginal ultrasound between 19°/7 and 216/7 weeks of gestation. All CL ≤30 mm from transabdominal ultrasound were confirmed by transvaginal ultrasound. Primary outcomes were sPTB <35 and <37 weeks. RESULTS: Out of 3,449 participants, 28 (0.8%) had a sPTB before 35 weeks and 99 (2.9%) had a sPTB before 37 weeks. Receiver operating characteristics (ROC) curves suggest that a cut-off of 30 mm was the optimal CL to predict sPTB before 35 weeks (sensitivity: 43%; specificity: 97%) and sPTB before 37 weeks (sensitivity: 21%; specificity: 97%). While a CL <25 mm was an important risk factor for sPTB before 35 weeks (relative risk: 31; 95% confidence interval: 13-73), women with a CL between 25 and 30 mm were also at greater risk (relative risk: 12; 95% confidence interval: 4 - 35) compared to women with CL ≥30 mm. DISCUSSION: A midtrimester CL <30 mm should be considered to identify women at high-risk of sPTB.

In Utero Exposure to Persistent Organic Pollutants and Childhood Lipid Levels.

Animal studies have shown that developmental exposures to polybrominated diphenyl ethers (PBDE) permanently affect blood/liver balance of lipids. No human study has evaluated associations between in utero exposures to persistent organic pollutants (POPs) and later life lipid metabolism. In this pilot, maternal plasma levels of PBDEs (BDE-47, BDE-99, BDE-100, and BDE-153) and polychlorinated biphenyls (PCB-138, PCB-153, and PCB-180) were determined at delivery in participants of GESTation and Environment (GESTE) cohort. Total cholesterol (TCh), triglycerides (TG), low- and high-density lipoproteins (LDL-C and HDL-C), total lipids (TL), and PBDEs were determined in serum of 147 children at ages 6-7. General linear regression was used to estimate the relationship between maternal POPs and child lipid levels with adjustment for potential confounders, and adjustment for childhood POPs. In utero BDE-99 was associated with lower childhood levels of TG (p = 0.003), and non-significantly with HDL-C (p = 0.06) and TL (p = 0.07). Maternal PCB-138 was associated with lower childhood levels of TG (p = 0.04), LDL-C (p = 0.04), and TL (p = 0.02). Our data indicate that in utero exposures to POPs may be associated with long lasting decrease in circulating lipids in children, suggesting increased lipid accumulation in the liver, a mechanism involved in NAFLD development, consistent with previously reported animal data.

Ultrasonographic Transabdominal Measurement of Uterine Cervical Length for the Prediction of a Midtrimester Short Cervix.

OBJECTIVE: This study was aimed to estimate the value of transabdominal (TA) ultrasound measurement of cervical length (CL), as an alternative of transvaginal (TV) ultrasound, for universal screening of short cervix in the midtrimester. STUDY DESIGN: We conducted a prospective cohort study of nulliparous women with singleton pregnancy at 20 to 24 weeks of gestation. All participants underwent TA ultrasound followed by TV ultrasound with acquisitions of images and videos of the uterine cervix. A second sonographer, blinded to the participants' data and pregnancy outcomes, measured the CL using TA and TV images and videos. Pearson's correlation test and receiver operating characteristic (ROC) curve analyses were performed. RESULTS: A total of 805 participants were recruited, including 780 (97%) where TA CL measurement was feasible. We observed a strong correlation of CL between TA and TV (correlation coefficient: 0.57; p < 0.0001) with a mean TA measurement being 4 mm (95% confidence interval [CI]: -6 to 14 mm) below the mean TV measurement (mean of differences: 5 ± 4 mm). We observed that a TA CL <30 mm was highly predictive of a short cervix defined as a TV CL ≤25 mm (area under the ROC curve: 0.97; 95% CI: 0.95-0.99; p < 0.0001) with a sensitivity of 100% and a false-positive rate of 22%. CONCLUSION: Universal short cervix screening in nulliparous women could be performed using TA ultrasound, which could allow the avoidance of TV ultrasound in more than three quarter of women. In low-risk population, TV ultrasound could be reserved to women with TA CL <30 mm. KEY POINTS: · Cervical length (CL) measurement with transabdominal (TA) ultrasound is feasible in most cases and is strongly correlated with CL measured with transvaginal (TV) ultrasound.. · Using a cut-off of 30 mm for TA ultrasound as a first-step screening of short cervix in nulliparous women, three-quarter of TV ultrasound could have been avoided.. · Use of TA CL screening could alleviate some of the logistical challenges of universal TV CL screening..

Intentional early delivery versus expectant management for preterm premature rupture of membranes at 28-32 weeks' gestation: A multicentre randomized controlled trial (MICADO STUDY).

OBJECTIVES: Preterm premature rupture of fetal membranes (PPROM) exposes the fetus to preterm birth, and optimal timing for delivery is controversial. The aim of this study was to compare intentional early delivery ("active management") with expectant management in very preterm birth (28-32 weeks). STUDY DESIGN: We conducted a prospective randomized controlled trial with intent-to-treat analysis, at 19 tertiary-care hospitals in France and 1 in Geneva, Switzerland. Inclusion criteria were women age ≥18 years, PPROM at 280/7 to 316/7 weeks' gestation, singleton pregnancy. Exclusion criteria were maternal/fetal indications for immediate delivery. All participants received prophylactic antibiotics (amoxicillin + gentamicin) and two doses of corticosteroids. Women in expectant management delivered at 34 weeks, sooner if medically indicated. Women in active management delivered 24 h after the second steroid dose. The primary outcome measure was a composite of neonatal death/severe adverse events: periventricular leukomalacia, intraventricular hemorrhage, sepsis, oxygen requirement at 36 weeks, and necrotizing enterocolitis. The secondary outcome was clinical chorioamnionitis. RESULTS: The trial was stopped prematurely, due to recruitment difficulties. Of 360 women assessed, 139 (40% of calculated sample size) were randomized: 70 to expectant management, 69 to active management. Mean gestational age at PPROM was similar in both groups (30 ± 1.3 vs. 30.2 ± 1.2 weeks, respectively). There were 35 cases of medical/suspected complications requiring delivery in expectant management vs. 4 in active management. Mean latency between PPROM and delivery was 11.7 ± 9.8 vs. 2.8 ± 0.6 days, respectively; P < 0.0001 (median 8.4 (1.8-44.2) vs. 2.7 (1.9-4.3)). There were more caesarean deliveries in active than expectant management (80% vs. 60%, respectively; P < 0.01). There were 2 chorioamnionitis cases, both in expectant management. One baby died in expectant management; 2 in active management (one with heart defect). There was no significant difference in sepsis rates. The combined neonatal death/severe adverse events measure was 12.9% for expectant management and 13.0% for active management (OR 0.98; 95% CI: 0.33-2.93, P = 0.97). CONCLUSION: For PPROM at 28-32 weeks, and with antenatal antibiotic and steroid therapy, there were no observed differences in neonatal health when comparing expectant management to early delivery. As expected, expectant management resulted in higher gestational age and birth weight. However, our study was underpowered to draw firm and reliable conclusions.

Pre-eclampsia Educational Tool Impact on Knowledge, Anxiety, and Satisfaction in Pregnant Women: A Randomized Trial.

OBJECTIVE: This study aimed to evaluate the impact of educational tools concerning pre-eclampsia on knowledge, anxiety, and women's satisfaction. METHODS: The investigators conducted a randomized controlled trial from March to July 2014 at the Centre Hospitalier Universitaire de Sherbrooke (Sherbrooke, QC) by comparing ambulatory pregnant women (20-32 weeks of gestation) who were receiving educational tools on pre-eclampsia with control patients who received routine care. Tools consisted of an informative pamphlet, a video, and a pictographic magnet, all validated by a multidisciplinary team. The primary outcome was global knowledge (number of correct answers on 35 items) about the disease after 1 month, as assessed by questionnaire. Secondary outcomes included anxiety regarding pre-eclampsia and satisfaction concerning the different tools (a 1-6 Likert scale was used). RESULTS: Among 362 pregnant women approached for the research, 269 were randomized. After 1 month, 247 questionnaires (92%) were filled and analyzed: 122 from the control group and 125 from the intervention group. Baseline characteristics were similar between the groups. Patients who received the tools scored significantly higher on global knowledge (70.1% ± 19.2% compared with 51.1% ± 23.4%; mean difference of 19.0%; P < 0.001). Anxiety scores regarding pre-eclampsia were similar between the groups, with a mean of 2.40 out of 6 for the control group and 2.53 out of 6 for the intervention group (equivalence test, P < 0.001). High score levels of satisfaction for the pamphlet and video were found: 5.1 out of 6 and 5.2 out of 6, respectively. CONCLUSION: These well-received educational tools for pregnant women increased their knowledge about pre-eclampsia without increasing their anxiety about it. Women reported the highest satisfaction for the tools.

[Spontaneous preterm birth and the maternal microbiome]. / La prématurité spontanée et le microbiote maternel.

Preterm birth is the leading cause of perinatal mortality and morbidity. Despite the efforts spent over the past 40 years to solve the physiopathological processes involved in the triggering of prematurity, efficient therapeutics are still lacking. Recently, growing body of evidence suggests that the maternal microbiome is a major player for a normal pregnancy and that dysbiosis is associated with preterm birth. The vaginal microbiome and its commensal Lactobacillus species may protect the uterus of ascending dissemination of pathogens. The uterus can also be contaminated with oral bacteria by the blood stream. Thus, the maternal microbiome can play both a protective role or a causal role in the triggering of preterm birth.

The Canadian Preterm Birth Network: a study protocol for improving outcomes for preterm infants and their families.

BACKGROUND: Preterm birth (birth before 37 wk of gestation) occurs in about 8% of pregnancies in Canada and is associated with high mortality and morbidity rates that substantially affect infants, their families and the health care system. Our overall goal is to create a transdisciplinary platform, the Canadian Preterm Birth Network (CPTBN), where investigators, stakeholders and families will work together to improve childhood outcomes of preterm neonates. METHODS: Our national cohort will include 24 maternal-fetal/obstetrical units, 31 neonatal intensive care units and 26 neonatal follow-up programs across Canada with planned linkages to provincial health information systems. Three broad clusters of projects will be undertaken. Cluster 1 will focus on quality-improvement efforts that use the Evidence-based Practice for Improving Quality method to evaluate information from the CPTBN database and review the current literature, then identify potentially better health care practices and implement identified strategies. Cluster 2 will assess the impact of current practices and practice changes in maternal, perinatal and neonatal care on maternal, neonatal and neurodevelopmental outcomes. Cluster 3 will evaluate the effect of preterm birth on babies, their families and the health care system by integrating CPTBN data, parent feedback, and national and provincial database information in order to identify areas where more parental support is needed, and also generate robust estimates of resource use, cost and cost-effectiveness around preterm neonatal care. INTERPRETATION: These collaborative efforts will create a flexible, transdisciplinary, evaluable and informative research and quality-improvement platform that supports programs, projects and partnerships focused on improving outcomes of preterm neonates.

Pilot study of EEG in neonates born to mothers with gestational diabetes mellitus.

BACKGROUND: The goal was to evaluate whether there was neurodevelopmental deficits in newborns born to mothers with gestational diabetes mellitus (GDM) compared to control newborns born to healthy mothers. METHODS: Forty-six pregnant women (21 controls and 25 GDM) were recruited. Electroencephalogram (EEG) was recorded in the newborns within 48 h after birth. The EEG signal was quantitatively analyzed using power spectral density (PSD); coherence between hemispheres was calculated in paired channels of frontal, temporal, central and occipital regions. RESULTS: The left centro-occipital PSD in control newborns was 12% higher than in GDM newborns (p = 0.036) but was not significant after adjustment for gestational age. While coherence was higher in the frontal regions compared to the occipital regions (p < 0.001), there was no difference between the groups for the fronto-temporal, frontal-central, centro-occipital and tempo-occipital regions. CONCLUSION: Our results support that EEG differences between groups were mainly modified by gestational age and less by GDM status of the mothers. However, there is a need to confirm this result with a higher number of mother-newborns. Quantitative EEG in GDM newborns within 48 h after birth is feasible. This study emphasizes the importance of controlling blood glucose during GDM to protect infant brain development.

Impact of tamsulosin and nifedipine on contractility of pregnant rat ureters in vitro.

OBJECTIVES: To evaluate the in vitro effect of tamsulosin and nifedipine on the contractility of pregnant rat ureters and to perform quantitative analysis of the pharmacological effects. Medical expulsive therapy (MET) is commonly used to treat urolithiasis. However, this treatment is seldom used in pregnant women since no studies support this practice. METHODS: This was an in vitro study on animal tissue derived from pregnant Sprague-Dawley rats. A total of 124 ureteral segments were mounted in an organ bath system and contractile response to methacholine (MCh) was assessed. Tamsulosin or nifedipine were added at cumulative concentrations (0.001-1 µM). The area under the curve (AUC) from isometric tension measurements was calculated. The effect of pharmacological agents and the respective controls were assessed by calculating the AUC for each 5-min interval. Statistical analyses were performed using the Mann-Whitney-Wilcoxon nonparametric test. RESULTS: Both drugs displayed statistically significant inhibitory activity at concentrations of 0.1 and 1 µM for tamsulosin and 1 µM for nifedipine when calculated as the AUC as compared to DMSO controls. CONCLUSION: Tamsulosin and nifedipine directly inhibit MCh-induced contractility of pregnant rat ureters. Further work is needed to determine the clinical efficacy of these medications for MET in pregnancy.

Phorbol 12,13-dibutyrate-induced protein kinase C activation triggers sustained contracture in human myometrium in vitro.

BACKGROUND: Although physiologic transition from rhythmic contractions to uterine retraction postpartum remains a poorly understood process, it has been shown that the latter is essential in the prevention of hemorrhage and its negative consequences. OBJECTIVE: To investigate the transition from oscillatory contractions to tonic contracture in human myometrium after delivery, a mechanism purported to facilitate postpartum hemostasis. Protein kinase C (PKC) plays a key regulatory role in human uterine contractions because it can prevent dephosphorylation of regulatory proteins and sensitize the contractile machinery to low Ca2+. Thus, activation of PKC by phorbol 12,13-dibutyrate (PDBu) may act as a strong uterotonic agent. STUDY DESIGN: Uterine biopsies were obtained from consenting women undergoing elective caesarian delivery at term without labor (N = 19). Isometric tension measurements were performed on uterine strips (n = 114). The amplitudes and area under the curve of phasic contractions and tonic responses were measured and compared. A total of 1 µM PDBu was added to the isolated organ baths, and maximal tension of the uterine contracture was determined in the absence and presence of either 1 µM of staurosporine, 100 nM nifedipine, or 10 µM cyclopiazonic acid to assess the role of PKC and calcium sensitivity on uterine contractility. RESULTS: On the addition of PDBu on either basal or oxytocin-induced activity, consistent contractures were obtained concomitant with complete inhibition of phasic contractions. After a 30-minute incubation period, the mean amplitude of the PDBu-induced tone represented 65.3% of the amplitude of spontaneous contraction. Staurosporine, a protein kinase inhibitor, induced a 91.9% inhibition of PDBu contractures, a process not affected by nifedipine or cyclopiazonic acid, thus indicating that this mechanism is largely Ca2+ independent. CONCLUSION: Pharmacologic activation of PKC leads to a significant contracture of the myometrium. Together, these data suggest that the up-regulation of PKC plays a physiologic role in the modulation of uterine contracture after delivery. A switch from phasic to strong tonic contractions potentially may facilitate postpartum hemostasis.

Single versus double-layer uterine closure at cesarean: impact on lower uterine segment thickness at next pregnancy.

BACKGROUND: Uterine rupture is a potential life-threatening complication during a trial of labor after cesarean delivery. Single-layer closure of the uterus at cesarean delivery has been associated with an increased risk of uterine rupture compared with double-layer closure. Lower uterine segment thickness measurement by ultrasound has been used to evaluate the quality of the uterine scar after cesarean delivery and is associated with the risk of uterine rupture. OBJECTIVE: To estimate the impact of previous uterine closure on lower uterine segment thickness. STUDY DESIGN: Women with a previous single low-transverse cesarean delivery were recruited at 34-38 weeks' gestation. Transabdominal and transvaginal ultrasound evaluation of the lower uterine segment thickness was performed by a sonographer blinded to clinical data. Previous operative reports were reviewed to obtain the type of previous uterine closure. Third-trimester lower uterine segment thickness at the next pregnancy was compared according to the number of layers sutured and according to the type of thread for uterine closure, using weighted mean differences and multivariate logistic regression analyses. RESULTS: Of 1613 women recruited, with operative reports available, 495 (31%) had a single-layer and 1118 (69%) had a double-layer closure. The mean third-trimester lower uterine segment thickness was 3.3 ± 1.3 mm and the proportion with lower uterine segment thickness <2.0 mm was 10.5%. Double-layer closure of the uterus was associated with a thicker lower uterine segment than single-layer closure (weighted mean difference: 0.11 mm; 95% confidence interval [CI], 0.02 to 0.21 mm). In multivariate logistic regression analyses, a double-layer closure also was associated with a reduced risk of lower uterine segment thickness <2.0 mm (odd ratio [OR], 0.68; 95% CI, 0.51 to 0.90). Compared with synthetic thread, the use of catgut for uterine closure had no significant impact on third-trimester lower uterine segment thickness (WMD: -0.10 mm; 95% CI, -0.22 to 0.02 mm) or on the risk of lower uterine segment thickness <2.0 mm (OR, 0.95; 95% CI, 0.67 to 1.33). Finally, double-layer closure was associated with a reduced risk of uterine scar defect (RR, 0.32; 95% CI, 0.17 to 0.61) at birth. CONCLUSION: Compared with single-layer closure, a double-layer closure of the uterus at previous cesarean delivery is associated with a thicker third-trimester lower uterine segment and a reduced risk of lower uterine segment thickness <2.0 mm in the next pregnancy. The type of thread for uterine closure has no significant impact on lower uterine segment thickness.

Reduction of total labor length through the addition of parenteral dextrose solution in induction of labor in nulliparous: results of DEXTRONS prospective randomized controlled trial.

BACKGROUND: Prolonged labor is a significant cause of maternal and fetal morbidity and very few interventions are known to shorten labor course. Skeletal muscle physiology suggests that glucose supplementation might improve muscle performance in case of prolonged exercise and this situation is analogous to the gravid uterus during delivery. Therefore, it seemed imperative to evaluate the impact of adding carbohydrate supplements on the course of labor. OBJECTIVE: We sought to provide evidence as to whether intravenous glucose supplementation during labor induction in nulliparous women can reduce total duration of active labor. STUDY DESIGN: We performed a single-center prospective double-blind randomized controlled trial comparing the use of parental intravenous dextrose 5% with normal saline to normal saline in induced nulliparous women. The study was conducted in a tertiary-level university hospital setting. Participants, caregivers, and those assessing the outcomes were blinded to group assignment. Inclusion criteria were singleton pregnancy at term with cephalic presentation and favorable cervix. Based on blocked randomization, patients were assigned to receive either 250 mL/h of intravenous dextrose 5% with normal saline or 250 mL/h of normal saline for the whole duration of induction, labor, and delivery. The primary outcome studied was the total length of active labor. Secondary outcomes included duration of the active phase of second stage of labor, the mode of delivery, Apgar scores, and arterial cord pH. RESULTS: In all, 100 patients were randomized into each group. A total of 193 patients (96 in the dextrose with normal saline group and 97 in the normal saline group) were analyzed in the study. The median total duration of labor was significantly less in the dextrose with normal saline group (499 vs 423 minutes, P = .024) than in the normal saline group. The probabilities of a woman being delivered at 200 minutes and 450 minutes were 18.8% and 77.1% in the dextrose with normal saline group vs 8.2% and 59.8% in the normal saline group (Kolmogorov-Smirnov test P value = .027). There was no difference in the rate of cesarean delivery, instrumented delivery, Apgar score, or arterial cord pH. CONCLUSION: Glucose supplementation significantly reduces the total length of labor without increasing the rate of complication in induced nulliparous women. Given the low cost and the safety of this intervention, glucose should be used as the default solute during labor.

Neuroprotective effects of antenatal magnesium sulfate under inflammatory conditions in a Sprague-Dawley pregnant rat model.

OBJECTIVE: Antenatal magnesium sulfate (MgSO4) is recommended for fetal neuroprotection. The aim of this animal study was to assess the neuroprotective effect of in utero exposure to MgSO4, under inflammatory conditions. METHODS: Timed pregnant Sprague-Dawley (SD) rats (n = 29) received four intra-peritoneal (IP) injections of lipopolysaccharides (LPS; 200 µg/kg), combined with increasing concentrations of MgSO4 (25, 50 or 100 mg/kg, n = 19) or saline solution (SS; n = 10). In the second set of experiments, animals (n = 8) received a single IP injection of i) LPS (500 µg/kg), MgSO4 (50 mg/kg) and SS (n = 4) or ii) LPS (500 µg/kg), MgSO4 (50 mg/kg) and IL-6 (12 µg/kg) (n = 4). Neurodevelopmental outcomes of surviving pups (n = 212) were assessed by the open field and the rotarod tests. RESULTS: Pups' average weight at postnatal day (P) 25 was 75.77 g and 89.08 g in MgSO4 and control groups, respectively (p = 0.02). Pups in MgSO4 group have traveled a shorter distance and have shown reduced motor balance and coordination (p < 0.01). Average weight of pups receiving (LPS + MgSO4+ IL-6) was 92.26 g at P25, compared to 75.86 g in (LPS + MgSO4+SS) group (p < 0.05). CONCLUSIONS: In our model, MgSO4 induces pup's growth retardation and motor deficits, which may partly be related to a lower IL-6 circulating concentration.

Fatty acid profile in cord blood of neonates born to optimally controlled gestational diabetes mellitus.

OBJECTIVE: To evaluate the fatty acid profile of cord blood phospholipids (PL), cholesteryl esters (CE), triglycerides (TG) and non-esterified fatty acids (NEFA) in neonates born to mothers with gestational diabetes mellitus (GDM) compared to non-diabetic mothers. METHODS: The offspring of 30 pregnant women (15 non-diabetic controls, 15 with diet- or insulin-controlled GDM) were recruited before delivery. Cord blood was collected. After lipid extraction, PL, CE, TG and NEFA were separated by thin layer chromatography and analysed by gas chromatography. RESULTS: In GDM vs. control mothers, maternal glycated haemoglobin (A1C, mean±SD) was not different between groups: 5.3±0.5% vs. 5.3±0.3% (p=0.757), respectively. Cord plasma fatty acids were not different in TG, CE and NEFA between GDM and non-diabetic mothers. However, in PL, levels of palmitate, palmitoleate, oleate, vaccinate and di-homo-gamma-linolenate were significantly lower, with a trend for lower arachidonate (p=0.078), in neonates born to GDM mothers compared to controls. CONCLUSION: In contrast to other studies on cord blood docosahexaenoic acid (DHA) levels in GDM mothers, we did not found lower levels of DHA in cord PL, CE, TG or NEFA in neonates born to GDM compared to non-diabetic mothers.