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1.
Am J Obstet Gynecol ; 231(2): 259.e1-259.e10, 2024 08.
Article in English | MEDLINE | ID: mdl-38360449

ABSTRACT

BACKGROUND: The relationship between gestational diabetes mellitus and adverse outcomes in multifetal pregnancies is complex and controversial. Moreover, limited research has focused on the risk of gestational diabetes mellitus progression to type 2 diabetes mellitus specifically in multifetal pregnancies, resulting in conflicting results from existing studies. OBJECTIVE: This study aimed to assess the risk of gestational diabetes mellitus progression to type 2 diabetes mellitus between singleton and multifetal pregnancies in a large cohort of parturients with a 5-year follow-up. STUDY DESIGN: A retrospective study was conducted on a prospective cohort of pregnant individuals with pregnancies between January 1, 2017, and December 31, 2020, followed up to 5 years after delivery. Glucose levels during pregnancy were obtained from the Meuhedet Health Maintenance Organization laboratory system and cross-linked with the Israeli National Diabetes Registry. The cohort was divided into 4 groups: singleton pregnancy without gestational diabetes mellitus, singleton pregnancy with gestational diabetes mellitus, multifetal pregnancy without gestational diabetes mellitus, and multifetal pregnancy with gestational diabetes mellitus. Gestational diabetes mellitus was defined according to the American Diabetes Association criteria using the 2-step strategy. Univariate analyses, followed by survival analysis that included Kaplan-Meier hazard curves and Cox proportional-hazards models, were used to assess differences between groups and calculate the adjusted hazard ratios with 95% confidence intervals for progression to type 2 diabetes mellitus. RESULTS: Among 88,611 parturients, 61,891 cases met the inclusion criteria. The prevalence of type 2 diabetes mellitus was 6.5% in the singleton pregnancy with gestational diabetes mellitus group and 9.4% in the multifetal pregnancy with gestational diabetes mellitus group. Parturients with gestational diabetes mellitus, regardless of plurality, were older and had higher fasting plasma glucose levels in the first trimester of pregnancy. The rates of increased body mass index, hypertension, and earlier gestational age at delivery were significantly higher in the gestational diabetes mellitus group among patients with singleton pregnancies but not among patients with multifetal pregnancies. Survival analysis demonstrated that gestational diabetes mellitus was associated with adjusted hazard ratios of type 2 diabetes mellitus of 4.62 (95% confidence interval, 3.69-5.78) in singleton pregnancies and 9.26 (95% confidence interval, 2.67-32.01) in multifetal pregnancies (P<.001 for both). Stratified analysis based on obesity status revealed that, in parturients without obesity, gestational diabetes mellitus in singleton pregnancies increased the risk of type 2 diabetes mellitus by 10.24 (95% confidence interval, 6.79-15.44; P<.001) compared with a nonsignificant risk in multifetal pregnancies (adjusted hazard ratio, 9.15; 95% confidence interval, 0.92-90.22; P=.059). Among parturients with obesity, gestational diabetes mellitus was associated with an increased risk of type 2 diabetes mellitus for both singleton and multifetal pregnancies (adjusted hazard ratio, 3.66; [95% confidence interval, 2.81-4.67; P<.001] and 9.31 [95% confidence interval, 2.12-40.76; P=.003], respectively). CONCLUSION: Compared with gestational diabetes mellitus in singleton pregnancies, gestational diabetes mellitus in multifetal pregnancies doubles the risk of progression to type 2 diabetes mellitus. This effect is primarily observed in patients with obesity. Our findings underscore the importance of providing special attention and postpartum follow-up for patients with multifetal pregnancies and gestational diabetes mellitus, especially those with obesity, to enable early diagnosis and intervention for type 2 diabetes mellitus.


Subject(s)
Diabetes Mellitus, Type 2 , Diabetes, Gestational , Disease Progression , Obesity , Pregnancy, Multiple , Humans , Female , Pregnancy , Diabetes, Gestational/epidemiology , Diabetes Mellitus, Type 2/epidemiology , Adult , Retrospective Studies , Obesity/complications , Obesity/epidemiology , Pregnancy, Multiple/statistics & numerical data , Risk Factors , Body Mass Index , Proportional Hazards Models , Israel/epidemiology
2.
Isr Med Assoc J ; 26(6): 376-382, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38884311

ABSTRACT

BACKGROUND: The prevalence of pregestational diabetes mellitus (PGDM) in women of reproductive age has surged globally, contributing to increased rates of adverse pregnancy outcomes. Hemoglobin A1c (HbA1c) is a crucial marker for diagnosing and monitoring PGDM, with periconceptional levels influencing the risk of congenital anomalies and complications. OBJECTIVES: To evaluate the association between periconceptional HbA1c levels and perinatal complications in pregnant women with poorly controlled PGDM. METHODS: We conducted a retrospective analysis of prospectively collected data of pregnancies between 2010 and 2019, HbA1c > 6% at 3 months prior to conception or during the first trimester. Outcomes of periconceptional HbA1c levels were compared. RESULTS: The cohort included 89 women: 49 with HbA1c 6-8%, 29 with HbA1c 8-10%, and 11 with HbA1c > 10%. Higher HbA1c levels were more prevalent in type 1 diabetics and were associated with increased end-organ damage risk. Women with elevated HbA1c levels tended toward unbalanced glucose levels during pregnancy. The cohort exhibited high rates of preterm delivery, hypertensive disorders, cesarean delivery, and neonatal intensive care unit admission. Overall live birth rate was 83%. While a significant correlation was found between HbA1c levels and preterm delivery, no consistent association was observed with other adverse outcomes. CONCLUSIONS: Periconceptional glycemic control in PGDM pregnancies is important. Elevated HbA1c levels are associated with increased risks of adverse outcomes. Beyond a certain HbA1c level, risks of complications may not proportionally escalate.


Subject(s)
Glycated Hemoglobin , Pregnancy Outcome , Pregnancy in Diabetics , Humans , Pregnancy , Female , Glycated Hemoglobin/analysis , Pregnancy Outcome/epidemiology , Adult , Retrospective Studies , Pregnancy in Diabetics/epidemiology , Pregnancy in Diabetics/blood , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 1/epidemiology , Premature Birth/epidemiology , Premature Birth/etiology , Infant, Newborn , Blood Glucose/analysis , Blood Glucose/metabolism , Cesarean Section/statistics & numerical data
3.
Gynecol Endocrinol ; 37(5): 428-432, 2021 May.
Article in English | MEDLINE | ID: mdl-32945210

ABSTRACT

OBJECTIVE: To evaluate the relationship between endometrial thickness measured before embryo transfer, and pregnancy outcomes in frozen-thawed embryo transfer (FET). METHODS: We retrospectively analyzed outcomes of all consecutive FET cycles, from January 2012 to August 2018. Based on ROC analysis for endometrial thickness, we found 8 mm was a reliable cutoff point to predict pregnancy prior to embryo transfer. Accordingly, the cycles were divided into Group A: cycles with endometrial thickness ≤ 8 mm and Group B: > 8 mm. RESULTS: Group A included 485 FET cycles and group B included 626 cycles. Compared with group A, Group B had significantly higher chemical and clinical pregnancy rates (30.3 vs. 24.6%; p = .046, and 24.0 vs. 18.6%; p = .036), respectively. In multivariate analysis, endometrial thickness and the protocols used were the only parameters influencing the chance to achieve pregnancy, with odds ratio 1.54 (95%CI 1.07-2.22, p = .019) for the endometrium and odds ratio 1.95 (95%CI 1.31-2.9; p = .001) to the protocol used. Endometrial thickness might predict crown-rump length (CRL) discordancy with odds ratio 4.61 (p = .001; 95% CI 1.42-14.92). Compared with group B, Group A had more cases of overt discordancy (13.3 vs. 4%; p = .016). CONCLUSIONS: For patients undergoing FET cycles, endometrial thickness and treatment protocol may predict the chemical and clinical pregnancy rates, as well as CRL discordancy. SUMMARY: Endometrial thickness and preparation improved pregnancy rate in FET cycles and significantly greater crown-rump length discordancy was observed with thinner endometria.


Subject(s)
Crown-Rump Length , Embryo Transfer/statistics & numerical data , Endometrium/physiology , Gestational Age , Pregnancy Rate , Adult , Cryopreservation , Embryo, Mammalian , Endometrium/anatomy & histology , Female , Humans , Pregnancy , Retrospective Studies
4.
J Obstet Gynaecol Can ; 43(10): 1159-1163, 2021 10.
Article in English | MEDLINE | ID: mdl-33621678

ABSTRACT

OBJECTIVE: To assess the accuracy of sonographic estimation of fetal head circumference in twin gestations. METHODS: A retrospective analysis of sonographic evaluations of twin gestations >34 weeks, performed within 7 days of delivery, in a single university-affiliated medical centre. Sonographic head circumference was compared with neonatal head circumference. Measures of accuracy included systematic error, random error, proportion of estimates within 5% of neonatal head circumference, and reliability analysis. Accuracy of sonographic head circumference was compared between the first and second twin. RESULTS: Overall, 103 twin gestations were evaluated at a median of 4 days before delivery. The majority of twins were dichorionic-diamniotic (83%). Median gestational age at delivery was 37 weeks, with a median birth weight of 2645 grams for the first twin and 2625 grams for the second twin. For all fetuses, median sonographic head circumference was lower than the neonatal head circumference (first twin: 317.5 vs. 330 mm; second twin: 318.4 vs. 330 mm, P > 0.05 for both). Measures of accuracy showed no significant difference between first and second twin. There was no difference in the number of sonographic head circumference evaluations that were within 5% of the neonatal head circumference between fetuses (64% for both twins). Cronbach α value was higher for the second twin (0.746 vs. 0.613), suggesting higher accuracy for head circumference measurement for the second twin. CONCLUSION: In our cohort, sonographic head circumference underestimated postnatal head circumference. Accuracy measurements were not significantly different between the first and second twin.


Subject(s)
Pregnancy, Twin , Ultrasonography, Prenatal , Female , Gestational Age , Humans , Infant, Newborn , Pregnancy , Reproducibility of Results , Retrospective Studies
5.
J Perinat Med ; 49(2): 191-194, 2021 Feb 23.
Article in English | MEDLINE | ID: mdl-32918806

ABSTRACT

OBJECTIVES: To evaluate the association between extremely elevated alkaline phosphatase (ALKP) levels (above 1000 U/L) and adverse perinatal outcome. METHODS: A retrospective case series of all parturients with extremely elevated ALKP levels taken throughout pregnancy at a single university-affiliated medical center (2010-2018). Demographics and medical data were retrieved. Following literature review, previously reported similar cases were added to the cohort. We report perinatal outcome of our cohort as well as literature review. RESULTS: During study period 11 parturients with high ALKP were identified. Ten more cases were retrieved from PubMed search. Overall, median ALKP levels were 1880 (range 1052-4488 U/L). Reasons for evaluation were mostly nonspecific symptoms (pruritus, headache, abdominal pain) or routine obstetrical evaluation. In 10/12 (83%) cases, elevated ALKP levels were of placental origin; the rest had osteal origin. Median gestational age at delivery was 38 (range 35-41); four (19%) women had preterm delivery. Six patients (29%) had gestational diabetes mellitus and six (29%) had hypertensive disorders. Histopathology of the placenta was available in eight cases: three normal histology (38%) and five with different non-specific pathologies. CONCLUSIONS: We report the largest case series of extremely elevated levels of ALKP in pregnancy thus far. Our data suggest association with adverse perinatal outcome.


Subject(s)
Alkaline Phosphatase/blood , Isoenzymes/blood , Pregnancy Complications/blood , Pregnancy Outcome/epidemiology , Adult , Female , GPI-Linked Proteins/blood , Humans , Israel/epidemiology , Middle Aged , Pregnancy , Pregnancy Complications/epidemiology , Retrospective Studies , Young Adult
6.
Clin Diabetes ; 39(3): 313-319, 2021 Jul.
Article in English | MEDLINE | ID: mdl-34421208

ABSTRACT

Flat oral glucose tolerance test (OGTT) curve is characterized by low glucose levels, seemingly nonresponsive to glucose load. Few studies have explored flat OGTT during pregnancy and have yielded conflicting results, some suggesting risk for fetal growth restriction. This study evaluated the characteristics and perinatal outcomes of women with a flat OGTT during pregnancy. We found that a flat OGTT curve occurs in younger, leaner pregnant women. Also, flat OGTT curve was significantly associated with a male fetus and higher levels of pregnancy-associated plasma protein A at the first-trimester screening. Although flat OGTT can possibly reflect some degree of hyperinsulinemia, it is generally not associated with adverse maternal or neonatal outcomes.

7.
J Perinat Med ; 47(7): 757-764, 2019 Sep 25.
Article in English | MEDLINE | ID: mdl-31373899

ABSTRACT

Objective To construct new reference values for biometrical measurements and sonographic estimated fetal weight (sEFW) in twin gestations and compare them to previously published normograms. Methods A retrospective analysis of sEFW evaluations of twin gestations was performed between 2011 and 2016 in a single university-affiliated medical center. sEFW was calculated using the Hadlock 1985 formula. To avoid selection bias, one evaluation per pregnancy was randomly selected. Following mathematical transformation to obtain normality of values, normograms were constructed using a best-fit regression model for estimation of mean and standard deviation at each gestational age (GA). Normograms were validated by applying all observations to ensure equal distribution at parallel percentiles. Our normograms were then compared to previously published sEFW normograms for twin gestations. Results A total of 864 sEFW evaluations were performed on 195 twin pregnancies at 22-39 gestational weeks. Of them, 390 entered the primary analysis. The rest were left for validation. Seventy percent of the cohort were dichorionic-diamniotic twins (136/195), 16% (32/195) were monochorionic-diamniotic twins and three (1.5%) were monochorionic-monoamniotic twins. Twenty-four fetuses lacked data on chorionicity. The rest were monochorionic twins or were of unknown chorionicity. Values corresponding to the 2.5th, 10th, 50th, 90th and 97.5th percentiles for sEFW are presented for every GA. Validation by applying all 864 evaluations on constructed normograms was achieved. Comparison to previously published twins' sEFW normograms demonstrated wide variation between curves. Conclusion New reference values for biometrical measurements and sEFW in twin gestations are presented for clinical and research use. Comparison to other curves demonstrates the wide variability and need for further investigation on twin's normal growth.


Subject(s)
Birth Weight , Fetal Weight , Pregnancy, Twin , Ultrasonography, Prenatal/methods , Biological Variation, Population , Biometry/methods , Dimensional Measurement Accuracy , Female , Gestational Age , Humans , Infant, Newborn , Israel , Pregnancy , Reference Values
8.
Harefuah ; 158(1): 30-34, 2019 Jan.
Article in Hebrew | MEDLINE | ID: mdl-30663290

ABSTRACT

INTRODUCTION: Epithelial ovarian cancer (EOC) is the principal cause of death from gynecologic cancer in developed countries. While surgery and chemotherapy can improve survival, the mortality and morbidity rates remain significantly high. The insulin-like growth factor (IGF) axis has been shown to play an important part in carcinogenesis of several human malignancies. Preclinical studies reported a significant anti-proliferative activity of IGF1 receptor (IGF1R) inhibitors in ovarian malignancies, however, clinical studies have shown variable response rates. Recent data indicate that immunotherapy could hold promise in improving EOC treatment. Dendritic cells (DCs) which are antigen presenting cells evoke a positive immune response. Moreover, a recent study shows that IGF treatment can inhibit DC maturation. AIMS: To investigate the involvement of IGF1R signaling in DCs and the effect of combined DCs and IGF1R inhibitor treatment on EOC cells growth. METHODS: HL-60 leukemic cells were differentiated to DCs and ligand induced phosphorylated IGF1R levels were measured by Western blotting. Next, inhibition of IGF1R in DCs was applied and the effect of this inhibition on EOC cell lines ES2 and SKOV3 was examined using the migration assay method. RESULTS: The differentiation of HL-60 into DCs was associated with decreased levels of both IGF1R phosphorylation and total IGF1R protein. In addition, in-vitro growth assays (scratch assay) demonstrated an increased growth of both ES2 and SKOV3 cells into the scratch zone when co-cultured with DCs which were not pre-treated with IGF1R inhibitor as compared to treated DCs. CONCLUSIONS: Preliminary data suggest that DC differentiation is associated with IGF1R signaling downregulation. Moreover, inhibition of IGF1R signaling in DCs might decrease EOC growth.


Subject(s)
Dendritic Cells , Ovarian Neoplasms , Somatomedins , Female , Humans , Ovarian Neoplasms/metabolism , Phosphorylation , Signal Transduction , Somatomedins/metabolism
10.
Isr Med Assoc J ; 19(8): 494-498, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28825768

ABSTRACT

BACKGROUND: The prevalence of major malformations in the general population is estimated at 5% of all live births. Prenatal diagnosis is an important scientific tool that allows reliable consultation and improves pregnancy outcome. In 2008, congenital malformations were the leading cause of death in Muslim infants and the second cause of death in Jewish infants in Israel. It is known that folic acid consumption prior to pregnancy decreases the rate of several fetal malformations. OBJECTIVES: To assess the folic acid consumption rate and to characterize variables associated with its use among pregnant women attending a rural medical center. METHODS: A cross-sectional observational study was conducted at our institution. Pregnant women in the second or third trimester of pregnancy or within 3 days postpartum were interviewed. The main variable measured was the use of folic acid. Demographic variables and the rate of prenatal testing were assessed. A secondary analysis of the population that reported no consumption of folic acid was carried out. RESULTS: Out of 382 women who participated in the study, 270 (71%) reported consumption of folic acid. Using a multivariate analysis model, we found that maternal education, planning of pregnancy, and low parity were independent predictors of folic acid consumption. Women who were not consuming folic acid tended to perform fewer prenatal tests during pregnancy. CONCLUSIONS: High maternal educational level, planning of pregnancy, and low parity are related to high consumption rates of folic acid. Women who were not taking folic acid performed fewer prenatal tests during pregnancy.


Subject(s)
Dietary Supplements , Folic Acid/administration & dosage , Vitamin B Complex/administration & dosage , Cross-Sectional Studies , Female , Humans , Israel , Pregnancy , Pregnancy Outcome , Prenatal Care/statistics & numerical data , Rural Health
11.
J Perinat Med ; 44(7): 779-784, 2016 Oct 01.
Article in English | MEDLINE | ID: mdl-26124047

ABSTRACT

OBJECTIVE: To identify maternal characteristics independently associated with pregnancies resulting in intrauterine fetal demise (IUFD). STUDY DESIGN: This was a population-based cohort study of all births taking place at the McGill University Health Centre in Montreal, Canada, between 2001 and 2007, using the McGill University Obstetrics and Neonatal Database. Maternal characteristics were compared between pregnancies that resulted in IUFD and control pregnancies resulting in live newborns. A logistic regression analysis was constructed to identify parameters independently associated with IUFD. RESULTS: We identified 20,744 births during the study period, 87 of which were complicated by IUFD. Mothers with IUFD were more likely to be younger, with less formal education, higher rates of smoking during pregnancy, and more fetal anomalies (42.5% vs. 7.5%, P<0.001). After exclusion of pregnancies with congenital and/or chromosomal abnormalities, less formal education (7 vs. 13.6 school years, P<0.001) and smoking during pregnancy (24% vs. 7.7%, P<0.001) remained significantly more common in pregnancies resulting in IUFD. In the multivariable regression analysis both smoking and number of maternal school years were independently associated with IUFD pregnancies (OR 2.22 for smoking, P=0.007 and OR 0.865 for number of school years, P<0.001). CONCLUSION: Lower levels of education and smoking during pregnancy are independent predictors of IUFD.


Subject(s)
Fetal Death/etiology , Adult , Case-Control Studies , Cohort Studies , Educational Status , Female , Humans , Infant, Newborn , Logistic Models , Male , Pregnancy , Quebec/epidemiology , Risk Factors , Smoking/adverse effects , Young Adult
12.
Arch Gynecol Obstet ; 293(1): 75-80, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26054823

ABSTRACT

OBJECTIVE: The objective of this study was to estimate the influence of maternal body mass index (BMI) on progress and outcomes of labor induction using mechanical devices. METHODS: This study was a secondary analysis of data collected during the Cook Catheter vs. Foley Catheter study, a series of prospective randomized trials of women requiring cervical ripening for labor induction. The duration, characteristics, and outcomes of labor were analyzed after stratification by BMI categories. Outcomes assessed included time from device insertion to delivery, successful ripening, cesarean delivery rates, and any maternal and neonatal adverse events. RESULTS: One hundred and eighty-one patients were stratified according to BMI categories, with 102 study participants classified as normal weight (BMI ≤30) and 79 as obese (BMI >30). Maternal satisfaction from the induction process was significantly lower in the obese group compared to the normal weight group (5.95 ± 3.14 vs. 7.58 ± 2.7, respectively, in a 1-10 scale, p = 0.009). The cesarean delivery rate was similar in the normal weight and the obese groups (17.6 vs. 25.3 %, respectively, p = 0.27). No statistical differences were found in all other outcomes evaluated, including a sub-analysis of the different mechanical devices. CONCLUSIONS: During the process of mechanical cervical ripening, maternal satisfaction, but not objective obstetrical parameters, was influenced by increased maternal BMI. The trial is registered at ClinicalTrials.gov, no: NCT00604487. Trial registry name is "Induction of Labor in Patients with Unfavorable Cervical Conditions."


Subject(s)
Catheterization/instrumentation , Cervical Ripening , Labor, Induced/instrumentation , Obesity , Adult , Body Mass Index , Catheters , Cesarean Section/statistics & numerical data , Delivery, Obstetric , Female , Humans , Infant, Newborn , Labor, Induced/methods , Mechanical Phenomena , Obesity/complications , Pregnancy , Prospective Studies
13.
Fetal Diagn Ther ; 40(3): 161-173, 2016.
Article in English | MEDLINE | ID: mdl-27160748

ABSTRACT

OBJECTIVE: To investigate whether isolated oligohydramnios at term is associated with increased rates of perinatal morbidity and mortality and whether induction of labor in term pregnancies with isolated oligohydramnios is superior to conservative management in reducing perinatal morbidity and mortality. STUDY DESIGN: We searched databases from inception to May 2015. We included studies that evaluated isolated oligohydramnios at term and perinatal outcome. Each outcome was analyzed separately, performing a comparative analysis between the study and control groups. RESULTS: Twelve studies were included with 35,999 women: 2,414 (6.7%) with isolated oligohydramnios and 33,585 (93.29%) with normal amniotic fluid index. Patients with isolated oligohydramnios had significantly higher rates of labor induction [odds ratio (OR) 7.56, confidence interval (CI) 4.58-12.48] and Cesarean sections (OR 2.07, CI 1.77-2.41). There were higher rates of an Apgar score <7 at 1 and 5 min (OR 1.53, CI 1.03-2.26, and OR 2.01, CI 1.3-3.09, respectively) and admission to the neonatal intensive care unit (OR 1.47, CI 1.17-1.84). There were no significant differences in cord pH <7.1 and meconium-stained amniotic fluid. In the single randomized trial comparing induction of labor with expectant management, no differences were found in any significant maternal or neonatal outcomes. CONCLUSION: Isolated oligohydramnios at term is associated with significantly higher rates of labor induction, Cesarean sections, and short-term neonatal morbidity.


Subject(s)
Labor, Induced , Oligohydramnios/diagnostic imaging , Adult , Amniotic Fluid , Cesarean Section , Delivery, Obstetric , Female , Humans , Odds Ratio , Oligohydramnios/mortality , Pregnancy , Pregnancy Outcome , Pregnancy Trimester, Third , Term Birth
14.
Am J Obstet Gynecol ; 213(6): 851.e1-8, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26232507

ABSTRACT

OBJECTIVE: Maternal chorioamnionitis is associated with newborn neurologic injury. Recent evidence suggests that maternal administration of magnesium sulphate (MG) may protect fetuses from white matter injury. Previously we demonstrated evidence by magnetic resonance imaging that MG may prevent maternal inflammation-induced gray matter injury of offspring. Thus, we sought to determine the potential of maternal inflammation to induce fetal neurological/behavioral deficits and assess whether maternal MG attenuates these effects. STUDY DESIGN: Pregnant rats at day 18 received injections of intraperitoneal lipopolysaccharide (LPS) or saline. Dams were treated with subcutaneous saline/MG (270 mg/kg followed by 27 mg/kg every 20 minutes) for 2 hours before and following LPS/saline injections. Pups were delivered spontaneously. At 1 and 3 months of age, 11-12 offspring of each group (saline, LPS, MG, LPS-MG) underwent a 2-way shuttle box avoidance testing. The shuttle box is divided in half and the animal moves between compartments to avoid an electric shock in response to an auditory stimulus. RESULTS: Control offspring demonstrated significantly improved learning and memory abilities from age 1 to 3 months. At 1 month, LPS-treated dams' offspring were similar to controls with no improvement in learning abilities at 3 months. MG treatment of LPS dams significantly improved offspring learning at 3 months, to equal or better than that of controls. CONCLUSION: LPS-stimulated inflammation during pregnancy impairs offspring learning ability and memory, which is ameliorated by maternal MG treatment. These results suggest that maternal MG therapy may prevent white and gray matter injuries associated with maternal infection/inflammation.


Subject(s)
Avoidance Learning/drug effects , Magnesium Sulfate/administration & dosage , Memory, Short-Term/drug effects , Neuroprotective Agents/administration & dosage , Animals , Animals, Newborn , Chorioamnionitis/drug therapy , Escape Reaction/drug effects , Female , Injections, Subcutaneous , Lipopolysaccharides/adverse effects , Pregnancy , Rats, Sprague-Dawley
15.
Pharm Res ; 32(2): 403-13, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25079390

ABSTRACT

PURPOSE: The purpose of this research was to evaluate the effect of ultrasound on mass transport across fetal membrane for direct fetal drug delivery and sensing of the amniotic fluid in a noninvasive manner. METHODS: Post-delivery human fetal membranes (chorioamnion) were used for in vitro experiments, in which the effect of ultrasound on transport across fetal membrane of fluorescent model molecule (250 kDa) was evaluated. Ex vivo experiments were carried out on a whole rat amniotic sac. The model molecule or alpha-fetoprotein was injected into the amniotic sac through the placenta. Transport of these molecules across pre- and post-insonation of the amniotic sac was evaluated. The ultrasound enhancement's mechanism was also assessed. RESULTS: The greatest enhancement in mass transport (43-fold) in vitro was achieved for 5 min of insonation (20 kHz, 4.6 W/cm(2), 5 mm distance). Ex vivo results showed a rapid increase (23-fold) in mass transport of the model molecule and also for alphafetoprotein following 30 s of insonation (20 kHz, 4.6 W/cm(2), 5 mm distance). CONCLUSIONS: Mass transport across fetal membranes was enhanced post-insonation both in vitro and ex vivo in a reversible and transient manner. We suggest that exterior (to the amniotic sac) ultrasound-induced cavitation is the main mechanism of action.


Subject(s)
Dextrans/metabolism , Drug Delivery Systems/methods , Extraembryonic Membranes/metabolism , Extraembryonic Membranes/radiation effects , Fluorescein-5-isothiocyanate/analogs & derivatives , Sound , Animals , Biological Transport/physiology , Biological Transport/radiation effects , Female , Fluorescein-5-isothiocyanate/metabolism , Humans , Pregnancy , Rats , Rats, Sprague-Dawley
16.
J Perinat Med ; 43(5): 553-8, 2015 Sep.
Article in English | MEDLINE | ID: mdl-25389984

ABSTRACT

OBJECTIVE: To evaluate a possible dose-response relationship between active maternal smoking during pregnancy and adverse perinatal outcome. DESIGN: Retrospective cohort study. SETTING: Population-based in Montreal, Quebec, Canada. POPULATION: Women who gave birth to a liveborn or stillborn infant during the period of January 2001 to December 2007. METHODS: Active smokers of different daily cigarette consumption (n=1646) were identified through maternal self-reporting. The reference group comprised 19,292 non-smoking women who delivered during the same period. MAIN OUTCOME MEASURES: Birth weight, preterm delivery rate, fetal and neonatal mortality and morbidity, and congenital malformations. RESULTS: Preterm delivery rate was significantly higher in the smoking group compared with controls (22.2% vs. 12.4%, P<0.05), as was intrauterine fetal demise (1.4% vs. 0.3%, P<0.05). Newborns of active smokers were more likely to weigh less (3150±759 g vs. 3377±604 g, P<0.05), suffer from respiratory distress syndrome (2.5% vs. 1.3%, P<0.05), suffer from a cardiac malformation (1.5% vs. 0.8%, P<0.05), and die (neonatal death 1.2% vs. 0.6%, P<0.05). A dose-response relationship was demonstrated between levels of daily cigarette smoking and several adverse outcomes. Using multiple regression models, smoking was found to be an independent predictor of preterm delivery (odds ratios (OR) 1.9, 95% confidence intervals (95%CI) 1.6-2), and intrauterine fetal demise (OR 2.4, 95%CI 1.4-4.2). CONCLUSION: Any amount of daily smoking appears to harm the fetus and newborn. As pregnancy may be a "window of opportunity" for behavioural changes, efforts to promote smoking cessation should be encouraged.


Subject(s)
Prenatal Exposure Delayed Effects/etiology , Smoking/adverse effects , Birth Weight , Cohort Studies , Congenital Abnormalities/etiology , Female , Humans , Infant , Infant Mortality , Infant, Newborn , Odds Ratio , Pregnancy , Pregnancy Outcome , Premature Birth , Quebec/epidemiology , Respiratory Distress Syndrome, Newborn/etiology , Retrospective Studies , Risk Factors , Stillbirth
17.
Am J Obstet Gynecol ; 210(1): 73.e1-7, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24055577

ABSTRACT

OBJECTIVE: Immature myeloid cells (IMCs) are bone marrow-derived cells that normally differentiate into granulocytes, macrophages, and dendritic cells (DCs) but expand in pathological conditions such as malignancy. DCs are antigen-presenting cells that regulate the immune response. Both IMCs and DCs were shown to take part in angiogenesis; however, little is known of their function in the placenta. We sought to determine whether alterations in DC and IMC populations in the placenta precede the onset of delivery. STUDY DESIGN: Experiments were performed on 6-8 week old C57Bl/6 female mice. Placentas from pregnant mice that were killed on designated days, immunostained using fluorescently labeled anti-CD11b, Gr-1, CD11c, major histocompatibility II (MHCII), and CD45, and analyzed by flow cytometry and immunofluorescent microscopy. RESULTS: Throughout the latter part of pregnancy toward labor and delivery, the CD45(+)CD11b(+)Gr1(+)-IMC population decreased 29 ± 9.1% (day 12) and 30 ± 9.9% (day 15), vs 21 ± 8.1% (day18, n = 21, 15, and 27; P = .006 and P = .004, respectively), whereas the CD45(+)CD11c(+)MHCII(+)-DC population increased 0.87 ± 0.3% (day 12) and 0.70 ± 0.3% (day 15) vs 1.81 ± 1.3% (day 18, n = 21, 15, and 27, P = .002 and P = .001, respectively). Both myeloid cell populations were localized adjacent to CD31(+) endothelial cells in sites of placental angiogenesis. CONCLUSION: Labor and delivery are preceded by proangiogenic-myeloid cell alterations, reflected by a decrease in IMCs and an increase in DCs populating the mouse placenta. The intriguing possibility that delivery is preceded by the maturation of IMCs in part into DCs warrants further studies.


Subject(s)
Dendritic Cells/physiology , Labor Onset/physiology , Myeloid Cells/physiology , Neovascularization, Physiologic/physiology , Placenta/cytology , Animals , Female , Flow Cytometry , Fluorescent Antibody Technique , Mice , Mice, Inbred C57BL , Placenta/physiology , Pregnancy
18.
Am J Obstet Gynecol ; 211(5): 446-52, 2014 Nov.
Article in English | MEDLINE | ID: mdl-24858198

ABSTRACT

In spite of the recognized occurrence of cesarean-attributable adhesions, its clinical significance is uncertain. The presence of adhesions during a repeat cesarean section can make fetal extraction lengthy and the procedure challenging and may increase the risk of injury to adjacent organs. Two methods for adhesion prevention are discussed, peritoneal closure and use of adhesion barriers. Peritoneal closure appears to be safe in the short term. In the long term, conflicting evidence arise from reviewing the literature for possible adhesion reduction benefits. A systematic review of the literature on the use of adhesion barriers in the context of cesarean section yielded only a few studies, most of which are lacking in methodology. For now, it appears that the available evidence does not support the routine use of adhesion barriers during cesarean delivery.


Subject(s)
Abdominal Wound Closure Techniques , Cesarean Section/methods , Peritoneal Diseases/prevention & control , Peritoneum/surgery , Uterine Diseases/prevention & control , Cesarean Section, Repeat/methods , Female , Humans , Pregnancy , Tissue Adhesions/prevention & control
20.
Article in English | MEDLINE | ID: mdl-38864262

ABSTRACT

OBJECTIVE: Impaired fasting glucose is a prediabetic condition defined as glucose levels of 100-125 mg/dL and is considered a risk factor for type 2 diabetes. However, this definition does not confer to pregnancy. The significance of first-trimester fasting glucose and future progression to diabetes is not well defined. Therefore, we aimed to evaluate the progression to type 2 diabetes according to first- trimester fasting plasma glucose levels, as compared with gestational diabetes, a well-established risk factor for diabetes, in up to 5-year follow-up postpartum. METHODS: A retrospective analysis of 69 001 parturients, evaluating fasting plasma glucose levels measured during the first trimester. The primary outcome was the incidence of type 2 diabetes within 5 years post-delivery. Fasting plasma glucose levels were categorized in 10 mg/dL increments. Receiver operating characteristic-area under the curve (ROC-AUC) statistics and the Youden index were employed to identify the optimal fasting plasma glucose cutoff for progression to type 2 diabetes. Survival analysis was applied to calculate the adjusted hazard ratios (aHRs) for type 2 diabetes progression with further stratification to maternal obesity status. RESULTS: The identified fasting plasma glucose cutoff for progression to type 2 diabetes was 86.5 mg/dL. This cut-off demonstrated superior performance compared with gestational diabetes diagnosis. Stratification by maternal obesity revealed enhanced predictive capabilities for type 2 diabetes, particularly among patients without obesity. CONCLUSIONS: Increased first-trimester fasting plasma glucose levels are associated with progression to type 2 diabetes, at least as gestational diabetes. For patients without obesity, first-trimester fasting plasma glucose has a more pronounced impact on progression to diabetes.

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