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Objective The aim of this study was to determine if mesenchymal stem cells (MSCs) would suppress the inflammatory response in human uterine cells in an in vitro lipopolysaccharide (LPS)-based preterm birth (PTB) model.Study Design Cocultures of human uterine smooth muscle cells (HUtSMCs) and MSCs were exposed to 5 μg/mL LPS for 4 hours and further challenged with 1 μg/mL LPS for a subsequent 24 hours. Key elements of the parturition cascade regulated by toll-like receptors (TLRs) through activation of mitogen-activated protein kinases (MAPKs) were quantified in culture supernatant as biomarkers of MSC modulation.Results Coculture with MSCs significantly attenuated TLR-4, p-JNK, and p- extracellular signal-regulated kinase 1/2 (ERK1/2) protein levels compared with HUtSMCs monoculture (p = 0.05). In addition, coculture was associated with significant inhibition of proinflammatory cytokines interleukin (IL)-6 and IL-8 (p = 0.0001) and increased production of anti-inflammatory cytokines IL-10 and transforming growth factor (TGF)-β1 (p = 0.0001).Conclusion MSCs appear to play a role in significantly attenuating LPS-mediated inflammation via alteration of down-stream MAPKs. MSCs may represent a novel, cell-based therapy in women with increased risk of inflammatory-mediated preterm birth.

Circulating hormones affect coagulopathy in pregnancy and after trauma. The hemostatic profile of pregnant women after injury has not been characterized. We hypothesized that injured pregnant females would present with an initial thrombelastography (TEG) reflecting a more hypercoagulable profile and a higher incidence of venous thromboembolic events (VTE) when compared with non-pregnant females and males.MethodsCohort study of adult trauma patients with TEG measured on arrival was performed from 2009 to 2018 with data extracted from medical records. Nearest-neighbor matching was used to match each pregnant patient by age, Injury Severity Score, prehospital transfusion, and arrival Glasgow Coma Scale with non-pregnant females and males, each in a maximum 1:4 ratio. Hypercoagulable profiles were defined as alpha (α) angle ≥76° and maximum amplitude (MA) ≥65 mm. Lysis at 30 minutes after MA (LY-30) was considered high if ≥3.0% and low if ≤0.8%. Univariate and multivariable analyses were performed.ResultsSeventy-six pregnant trauma patients were matched to 301 non-pregnant females and 301 males. Demographics were similar between groups, except pregnant females more frequently suffered blunt trauma. Pregnant females presented with a higher α angle, high MA and lower LY-30 than both control groups. Pregnant females met hypercoagulable criteria and had a low LY-30 more frequently than non-pregnant females and males. No pregnant patient versus 2% in each control group developed VTE. Transfusion requirements in the first 24 hours after admission and mortality were similar between groups. After adjustment, low MA and high LY-30 were associated with increased odds of mortality, regardless of sex or pregnancy. Hypocoagulable α angle was associated with pregnancy complications.ConclusionInjured pregnant females frequently presented with a profile that would be considered hypercoagulable under normal reference ranges. However, given the absence of VTE events, this profile may be non-pathologic.Level of evidenceIV.

Digital technologies offer many opportunities to improve mental healthcare management for women seeking pre- and-postnatal care. They provide a discrete, practical medium that is well-suited for the sensitive nature of mental health. Women who are more prone to experiencing peripartum depression (PPD), such as those of low-socioeconomic background or in high-risk pregnancies, can benefit the most from such technologies. However, current digital interventions directed towards this population provide suboptimal support, and their responsiveness to end user needs is quite limited. Our objective is to understand the digital terrain of information needs for low-socioeconomic status women with high-risk pregnancies, specifically within the management of their mental health. This qualitative study consists of semi-structured focus groups and interviews with a sample of nineteen patients. A total of eleven core themes emerged from participant comments. Resulting themes highlighted the need for digital technologies that promote personalized care, a sense of community, and improved provider communication.

Objective To determine whether basal insulin analogs reduce the rate of composite neonatal morbidity compared with neutral protamine Hagedorn (NPH) in women with type 2 diabetes mellitus (T2DM). Study Design This was a retrospective cohort study of women with T2DM and singleton pregnancy at a single tertiary center. Primary outcome was a composite neonatal morbidity of any of the following: shoulder dystocia, large for gestational age, neonatal intensive care unit admission, neonatal hypoglycemia, or respiratory distress syndrome. Secondary outcomes were rates of maternal hypoglycemic events, hypertensive disorders, preterm birth, and primary cesarean delivery. Adjusted relative risk (aRR) and 95% confidence intervals (CI) were calculated. Results Of 233 women with T2DM that met the inclusion criteria, 114 (49%) were treated with basal insulin analogs and 119 (51%) with NPH. The rate of composite neonatal morbidity was similar between groups (73 vs. 60%; aRR: 1.18; 95% CI: 0.92–1.51). There were no differences in the rates of maternal adverse outcomes between the groups. Basal insulin analog was associated with a lower rate of primary cesarean delivery as compared with NPH (21 vs. 36%; aRR: 0.44; 95% CI: 0.25–0.78). Conclusion Among pregnant women with T2DM managed with either basal or NPH insulin regimen, the rates of composite neonatal morbidity and maternal complications were similar.

Objective Our primary objective was to determine whether biophysical profiles (BPP) performed on the antepartum unit result in changes in clinical decision making. Study Design A retrospective cohort chart review was performed among women who had a BPP during hospital admission. BPP status was categorized as normal (8/8 points) and abnormal (6/8 or less points). The primary outcome, clinical decision making, was the need for prolonged external fetal monitoring (defined as > 2 hours) or decision to proceed with delivery. Secondary outcomes included mode of delivery, indicated preterm delivery, birth weight, 5-minute Apgar's score Results Among our cohort (n = 186), 85.5% (n = 159) had a normal BPP. Delivery management was altered in one case (0.54%) by the BPP findings, and there were no BPPs that resulted in need for prolonged monitoring. Compared with women with normal BPP, women with abnormal BPPs were more likely to deliver at Conclusion In-hospital BPPs alter clinical decision making in less than 1% of cases.

Importance Maternal depression during pregnancy is associated with emotional and behavioral difficulties of offspring during childhood that can increase the risk of depression in adolescence and adulthood. Objective To investigate the association between perinatal maternal depression and an increased long-term risk of depression in their adolescent and adult offspring. Data Sources A systematic search of the electronic databases of PubMed and PsycINFO was conducted from May 2019 to June 2019. Study Selection A total of 6309 articles were identified, of which 88 articles were extracted for full-text review by 2 reviewers. Only articles reporting data from prospective longitudinal studies that assessed maternal depression during antenatal and/or postnatal periods and resulting offspring 12 years or older with measures of established psychometric properties were included. Exclusion criteria consisted of all other study designs, mothers with other medical and psychiatric comorbidities, and offspring younger than 12 years. Data Extraction and Synthesis Data were extracted by 2 independent reviewers, and discrepancies were mediated by an expert third reviewer. Meta-analysis was performed using Bayesian statistical inference and reported using Meta-analysis of Observational Studies in Epidemiology (MOOSE) guideline. The association of depression timing with the sex of offspring was explored using metaregression. Main Outcomes and Measures Offspring depression was evaluated using standardized depression scales or clinical interviews. Results Six studies with a total of 15 584 mother-child dyads were included in the meta-analysis, which found the offspring of mothers who experienced perinatal depression to have increased odds of depression (odds ratio [OR], 1.70; 95% credible interval [CrI], 1.60-2.65; posterior probability [PP] [OR >1], 98.6%). Although metaregression found no evidence for an overall association between perinatal depression timing and offspring depression (antenatal vs postnatal, PP [OR >1] = 53.8%), subgroup analyses showed slightly higher pooled odds for the antenatal studies (OR, 1.78; 95% CrI, 0.93-3.33; PP [OR >1] = 96.2%) than for the postnatal studies (OR, 1.66; 95% CrI, 0.65-3.84; PP [OR >1] = 88.0%). Female adolescent offspring recorded higher rates of depression in metaregression analyses, such that a 1% increase in the percentage of female (relative to male) offspring was associated with a 6% increase in the odds of offspring depression (OR, 1.06; 95% CrI, 0.99-1.14; τ2 = 0.31). Conclusions and Relevance In this study, maternal perinatal depression, especially antenatal depression, was associated with the risk of depression in adolescence and adulthood. More research into the mechanisms of depression risk transmission and assessments of postinterventional risk reduction could aid in the development of future strategies to tackle depressive disorders in pregnancy.

Background Insulin detemir, being used increasingly during pregnancy, may have pharmacologic benefits compared with neutral protamine Hagedorn. Objective We evaluated the probability that compared with treatment with neutral protamine Hagedorn, treatment with insulin detemir reduces the risk for adverse neonatal outcome among individuals with type 2 or overt type 2 diabetes mellitus (gestational diabetes mellitus diagnosed at Study Design We performed a multiclinic randomized controlled trial (September 2018 to January 2020), which included women with singleton gestation with type 2 or overt type 2 diabetes mellitus who sought obstetrical care at ≤21 weeks’ gestation. Participants were randomized to receive either insulin detemir or neutral protamine Hagedorn by a clinic-stratified scheme. The primary outcome was a composite of adverse neonatal outcomes, including shoulder dystocia, large for gestational age, neonatal intensive care unit admission, respiratory distress (defined as the need of at least 4 hours of respiratory support with supplemental oxygen, continuous positive airway pressure or ventilation at the first 24 hours of life), or hypoglycemia. The secondary neonatal outcomes included gestational age at delivery, small for gestational age, 5-minute Apgar score of 75% probability of any reduction in the primary outcome, assuming 80% power and a hypothesized effect of 33% reduction with insulin detemir. All analyses were intent to treat under a Bayesian framework with neutral priors (a priori assumed a 50:50 likelihood of either intervention being better; National Clinical Trial identifier 03620890). Results There were 108 women randomized in this trial (57 in insulin detemir and 51 in neutral protamine Hagedorn), and 103 women were available for analysis of the primary outcome (n=5 for pregnancy loss before 24 weeks’ gestation). Bayesian analysis indicated an 87% posterior probability of reduced primary outcome with insulin detemir compared with neutral protamine Hagedorn (posterior adjusted relative risk, 0.88; 95% credible interval, 0.61–1.12). Bayesian analyses for secondary outcomes showed consistent findings of lower adverse maternal outcomes with the use of insulin detemir vs neutral protamine Hagedorn: for example, maternal hypoglycemic events (97% probability of benefit; posterior adjusted relative risk, 0.59; 95% credible interval, 0.29–1.08) and hypertensive disorders (88% probability of benefit; posterior adjusted relative risk, 0.81; 95% credible interval, 0.54–1.16). Conclusion In our comparative effectiveness trial involving individuals with type 2 or overt type 2 diabetes mellitus, use of insulin detemir resulted in lower rates of adverse neonatal and maternal outcomes compared with neutral protamine Hagedorn.

To estimate whether antenatal corticosteroids before 34 weeks of gestation are associated with reduced incidence of respiratory distress syndrome (RDS) and composite neonatal morbidity in preterm twins.This was a secondary analysis of a multicenter randomized trial for the prevention of preterm birth in multiple gestations. All liveborn, nonanomalous twins delivered between 24 0/7 and 36 6/7 weeks of gestation were included. Neonatal outcomes were compared between women who received antenatal corticosteroids and those who did not. The primary outcome was the incidence of RDS. The secondary outcome was the incidence of serious composite neonatal morbidity. Multivariable log Poisson regression with correlation adjustment between twins born to the same mother was performed for confounder control. Adjusted relative risks (RRs) are reported for study outcomes. Based on a post hoc power analysis, this study was powered to detect an RR less than 0.63 for RDS and greater than 1.43 for composite neonatal morbidity outcomes.A total of 432 women (850 neonates) were included. Only 300 (35%) neonates were born to women receiving antenatal corticosteroids. After multivariable regression, antenatal corticosteroids were not associated with a reduced incidence of RDS (81 [27%] compared with 92 [17%] neonates, adjusted RR 1.28, 95% confidence interval [CI] 0.97-1.71) or composite neonatal morbidity (87 [29%] compared with 108 [20%] neonates, adjusted RR 1.21, 95% CI 0.93-1.56). However, antenatal corticosteroids were associated with increased rates of neonatal intensive care unit admissions (235 [78%] compared with 322 [59%] neonates, adjusted RR 1.22, 95% CI 1.09-1.36) and mechanical ventilation (70 [23%] compared with 66 [12%] neonates, adjusted RR 1.52, 95% CI 1.12-2.09). Focusing analysis to newborns delivered before 34 weeks of gestation (n=311), 161 (52%) received antenatal corticosteroids. Similarly, no differences in the rate of RDS (66 [41%] compared with 68 [45%] neonates, adjusted RR 1.01, 95% CI 0.76-1.34) or composite neonatal morbidity (72 [45%] compared with 81 [54%] neonates, adjusted RR 0.95, 95% CI 0.74-1.22) were noted.In this cohort of preterm twins, antenatal corticosteroid administration was not associated with a reduced incidence of RDS and composite neonatal morbidity.

The objective of this study was to elucidate the possible toxic effects on the fetal tissues after exposure to two clinically relevant concentrations of granisetron. Primary cells were isolated from human fetal organs of 16-19 weeks gestational age and treated with 3 ng/mL or 30 ng/mL of granisetron. Cell cycle progression was evaluated by flow cytometry. ELISA was used to detect alterations in major apoptotic proteins. Up to 10% apoptosis in cardiac tissue was observed following treatment with 30 ng/mL granisetron. Neither concentration of granisetron caused alteration in cell cycle progression or alterations in apoptotic proteins in any of the other tissues. At 30 ng/mL granisetron concentration had the potential to induce up to 10% apoptosis in cardiac tissue; clinical significance needs further evaluation. At granisetron 3 ng/mL there was no detectable toxicity or on any fetal tissue in this study. Further research is needed to confirm these preliminary findings and determine if clinically significant.

Stercoral perforation of the colon, though rare, is associated with high mortality. Review of the literature identified only three prior cases reported during pregnancy. We report a case on a multiparous female presenting at 31 weeks of gestation with acute abdominal pain. Computed tomography suggested a sigmoid colon perforation. An urgent exploratory laparotomy was performed where feculent peritonitis and a stercoral perforation of the sigmoid colon was confirmed. A cesarean delivery and sigmoid colectomy with descending end colostomy was performed. While the newborn had an uncomplicated course, the mother developed an intra-abdominal abscess requiring operative management.

The objective of this study was to estimate maternal-fetal transplacental passage of granisetron in an ex vivo placental perfusion model. Term human placentas (N=8) were collected immediately after delivery. A single cotyledon from each placenta was perfused granisetron concentration to mimic systemic maternal peak plasma concentrations following either IV (50ng/mL) or transdermal administration (5ng/mL). To assess drug transfer and accumulation, samples were collected from maternal and fetal compartments. In the 50ng/mL open model, the mean transport fraction was 0.21±0.08 with clearance index of 0.53±0.66. Fetal peak concentrations achieved was 5.6±6.6ng/mL with mean accumulation of 5.35±6.4ng/mL. No drug was detected in the fetal compartment with the 5ng/mL models. Transplacental passage of granisetron was inconsistent at the 50ng/mL concentration that achieved with IV dosing. However, there consistently was no detectable passage in all the placentas evaluated of the granisetron at 5ng/mL concentration that would be achieved after transdermal patch administration.

Objective Pregnancy is associated with an increase in total cholesterol, high density lipoproteins (HDL), and low-density lipoproteins (LDL). Postpartum, HDL and LDL decrease over the first 12 weeks postpartum. Oxidized LDL (ox-LDL) is a marker of oxidative stress-related inflammation, which is associated with obesity and also with development of cardiovascular disease. Cardiovascular protection and weight loss are benefits from metformin, especially in women with diabetes. The objective of this study was to compare changes in lipid profiles and biomarkers for obesity during the initial 6 weeks postpartum between women with gestational diabetes mellitus (GDM) treated with metformin versus placebo. Methods This was a planned ancillary study of a randomized controlled trial compares metformin versus placebo in women with GDM for postpartum weight loss. Two 3 mL blood samples were collected within 24 h of delivery and 6 weeks postpartum immediately processed after collection then stored at −20°C until completion of clinical trial prior to analysis. Change in the median plasma concentrations of total cholesterol, HDL, ox-LDL, glucose, insulin, leptin, and unacylated ghrelin were compared between study groups. Results Of the 77 postpartum women were included, 35 received metformin and 42 received placebo. There was less of a reduction in HDL in the metformin group compared to placebo (−2.3 versus −7.5 mg/dL, p = 0.019). In addition, there was a greater reduction in ox-LDL in those receiving metformin (−12.2 versus −3.8 mg/dL, p = 0.038). No other differences were observed in the selected biomarkers evaluated. Conclusion Biomarker levels of HDL and ox-LDL were positively affected during the initial 6 weeks postpartum in GDM women treated with metformin. Additional studies with a longer duration of metformin treatment in the postpartum period are warranted to evaluate long-term potential benefits.

One factor women consider when deciding whether to pursue amniocentesis is the risk of miscarriage. People use mechanisms like anchoring, or the prior belief regarding the magnitude of risk, as a frame of reference for new information. This study aimed to determine a woman’s perception of miscarriage risk associated with amniocentesis before and after genetic counseling and to determine what factors anchor a woman’s perception of miscarriage risk. One hundred thirteen women being seen for prenatal genetic counseling and possible amniocentesis at six Houston clinics participated in the two-part anonymous survey. While most women (56.7 %) perceived the risk as low or average pre-counseling and indicated the numeric risk of amniocentesis as

OBJECTIVE Few studies support oral diabetic treatment in pregnant women with type 2 diabetes mellitus (T2DM). The objective of this study was to compare the effects of metformin versus insulin on achieving glycemic control and improving maternal and neonatal outcomes in pregnant women with T2DM. STUDY DESIGN A pilot randomized, controlled trial was conducted of metformin versus insulin for the treatment of T2DM during pregnancy. The primary outcome was glycemic control measured with hemoglobin A1c

Background Inositols (INOs) supplementation during pregnancy, specifically the combination of myo-inositol (MI) and D-chiro-inositol (DCI), has been reported to improve vascular parameters in women with gestational diabetes mellitus. We demonstrated previously that offspring born to pregnant mice lacking the endothelial nitric oxide synthase (eNOS+/–) gene have hypertension (HTN) as adults and, when fed a high-fat diet (HFD), develop a metabolic syndrome (MS) phenotype. Objective Our aim was to evaluate whether INOs treatment in pregnancy complicated by MS improves the vascular and metabolic profile in mice offspring programmed in utero to develop HTN and MS. Materials and Methods Heterozygous eNOS+/– mice fed an HFD manifest a MS phenotype. Female eNOS+/– mice with MS were bred with a wild-type (WT) male. On gestational day 1, pregnant females were randomly allocated to receive either a mixture of INOs (MI/DCI: 7.2/0.18 mg/mL) or water as placebo until delivery. The female offspring obtained were genotyped and categorized as: WT (genetically normal, with eNOS gene) and eNOS+/– offspring (genetically modified, heterozygous for eNOS gene). Both offspring developed in an abnormal uterine environment due to maternal MS. At 9–10 weeks of age, the offspring underwent a glucose tolerance test (GTT) and systolic blood pressure (SBP) measurement. The mice were then sacrificed, and the carotid arteries were isolated for evaluation of vascular responses. Responses to phenylephrine (PE), in the presence and absence of a nonspecific nitric oxide inhibitor (N-nitro-L-arginine methyl ester [L-NAME]), the vasodilator acetylcholine (ACh), and sodium nitroprusside (SNP) were assessed. Results The GTT showed lower glucose levels in both eNOS+/–INOs (P = .03) and WT-INOs (P = .05) offspring born to MS dams on INOs supplementation compared to offspring born to untreated dams. SBP was higher in eNOS+/– offspring compared to WT (169 ± 7 vs 142 ± 9 mm Hg, respectively, P = .04) and INOs treatment decreased SBP in WT-INOs (110 ± 10 mm Hg, P = .01) but not in eNOS+/–INOs offspring. Maximal (%Max) contractile response to PE was higher in eNOS+/– offspring born to MS dams and was decreased in those born to MS dams treated with INOs (%Max, eNOS+/–, 123 ± 7 vs eNOS+/–INOs, 82 ± 11 mm Hg, P = .007). No differences were seen in PE contractile responses in WT offspring born to MS dams treated or not treated with INOs (WT, 92 ± 4 vs WT-INOs, 75 ± 7). The L-NAME response was decreased in eNOS+/–INOs and WT-INOs offspring compared to untreated ones. The ACh vasorelaxation was impaired in eNOS+/– and WT offspring born to MS dams, and maternal INOs treatment improved offspring vascular relaxation in both offspring (P = .01 and P = .03, respectively). No differences were seen in response to SNP. Conclusion Inositols supplementation improved glucose tolerance, SBP, and vascular responses in adult eNOS+/– and WT offspring born to dams with MS. Interestingly, WT born to MS dams show an altered vascular profile similar to eNOS+/– offspring and exhibit an improved response to INOs treatment. Our findings suggest that the benefits of INOs treatment are more pronounced in offspring exposed to environmental factors in utero, and less likely in those due to genetic factors.

Preterm labor caused by uterine contractions is a major contributor to neonatal morbidity and mortality. Treatment intended to reduce uterine contractions include tocolytic agents, such as indomethacin. Unfortunately, clinically used tocolytics are frequently inefficient and cross the placenta causing fetal side effects. Here we show for the first time in obstetrics the use of a targeted nanoparticle directed to the pregnant uterus and loaded with a tocolytic for reducing its placental passage and sustaining its efficacy. Nanoliposomes encapsulating indomethacin and decorated with clinically used oxytocin receptor antagonist were designed and evaluated in-vitro, ex-vivo and in-vivo. The proposed approach resulted in targeting uterine cells in-vitro, inhibiting uterine contractions ex-vivo, while doubling uterine drug concentration, decreasing fetal levels, and maintaining the preterm birth rate in vivo in a pregnant mouse model. This promising approach opens new horizons for drug development in obstetrics that could greatly impact preterm birth, which currently has no successful treatments.

The number of disorders for which genetic testing is available has increased nearly 500% in the past 15 years. Access to genetic tests and services often hinges on physicians’ ability to identify patients at risk for genetic disease and provide appropriate testing and counseling or refer to genetic specialists. Recent research demonstrates the need for referrals to genetic specialists by showing that many physicians lack skills required to perform appropriate genetic services, such as making proper risk assessments, providing genetic counseling, ordering genetic testing and interpreting results. However, little research exists on physicians’ awareness and utilization of genetic services. In this study, an electronic survey evaluating practicing physicians’ awareness of, utilization of and perceived barriers to genetic services in Texas, and interest in learning more about genetics and genetic services was distributed via state physician organizations. Of the 157 participants, approximately half reported they were moderately or very aware of genetic testing and services in their area. Very few reported awareness of telemedicine services. Over two-thirds reported never or rarely referring to genetic counselors or other genetic specialists, despite 75% reporting they had noticed an increased impact of genetics on their field and 61% reporting they had discussed genetics more in their day-to-day practice in the last 5–10 years. Only 20% reported genetics was very integral to their specialty. Over three-fourths of all participants indicated interest in learning more about genetics, genetic testing, and genetic services. Among the most frequently chosen barriers to genetic counselors were awareness-related barriers such as not knowing how to refer to a genetic counselor. Responses to many items varied significantly by medical specialty. The results identify a need to increase awareness of genetic services and referral logistics. Specific findings can help direct outreach efforts to educate clinicians, such as developing clinically meaningful, specialty-specific educational objectives.

Objective To compare the effectiveness of intravenous acetaminophen with that of morphine in reducing pain in the first stage of labor. Methods An open-label, randomized controlled trial of women ≥ 34 weeks gestation in the first stage of labor, assigned to either intravenous acetaminophen or morphine. The primary outcome was improved analgesia measured by difference of visual analog scale (VAS) score at 120 minutes from baseline. Secondary outcomes were request for rescue analgesia, maternal side effects, and fetal heart rate changes. Statistical analyses performed were chi-square, Student's t-test, and Kaplan-Meier survival analysis. Results Of 40 women randomized, 18 received acetaminophen (2 did not receive study drug), and 20 received morphine. Because of difficulties in recruitment, the sample size of 88 was not achieved. The primary outcome was similar between groups (p = 0.53). Within 120 minutes of initial treatment, more women receiving intravenous acetaminophen required rescue analgesia (acetaminophen: 52.9% vs. morphine: 17.6%, p Conclusion There was no difference in VAS scores between groups. However, as half of women receiving intravenous acetaminophen required rescue analgesia within 120 minutes of treatment, intravenous acetaminophen may be less effective for analgesia in early labor compared with intravenous morphine.

BACKGROUND We previously reported that offspring heterozygous mice partially lacking endothelial nitric oxide synthase (eNOS) gene, and born to hypertensive eNOS-/- Knockout mother, are hypertensive. We hypothesized that those offspring when placed on high-fat diet (HFD) will undergo altered metabolic programming increasing their risk for developing metabolic syndrome. METHODS eNOS-/-KO and wild-type mice (eNOS+/+WT) were cross-bred to produce heterozygous offspring: maternal heterozygous (Mat, eNOS-/+), born from hypertensive eNOS-/-KO mothers; and paternal heterozygous (Pat, eNOS-/+), born from normotensive WT mothers. Mat, eNOS-/+ and Pat, eNOS-/+ female were allocated to HFD or control diet (CD) until 8 weeks of age. Then a metabolic profile was obtained: weight, glucose/insulin tolerance test (GTT, ITT), systolic blood pressure (SBP), serum fasting levels of insulin, adiponectin, leptin, and a lipid panel. RESULTS Weight was not different between all offspring within each diet. GTT curve was higher in Mat, eNOS-/+ vs. Pat, eNOS-/+ offspring on both diet (P < 0.001). In ITT, glucose level at 15 minutes was higher in Mat, eNOS-/+ on HFD. Insulin level was increased in Mat, eNOS-/+ vs. Pat, eNOS-/+ on either diet. SBP was elevated in Mat, eNOS-/+ vs. Pat, eNOS-/+ on CD and was further raised in Mat, eNOS-/+ offspring on HFD (P < 0.001). No other differences were seen except for lower high-density lipoprotein levels in Mat, eNOS-/+ fed HFD (P < 0.003). CONCLUSIONS Mat, eNOS-/+ offspring exposed in utero to maternal hypertension and fed HFD postnatally have increased susceptibility for metabolic abnormalities. Thus, maternal HTN is a risk factor for altered fetal metabolic programming.

Background Myoinositol and D-chiroinositol improve insulin resistance in women with obesity and gestational diabetes and in postmenopausal women with metabolic syndrome. We previously reported that offspring born to hypertensive dams lacking endothelial nitric oxide synthase and fed a high-fat diet develop metabolic-like syndrome phenotype. Objective The objective of the study was to investigate the effect of a mixture of myoinositol/D-chiroinositol supplementation during pregnancy on the maternal metabolic profile in pregnancies complicated by the metabolic-like syndrome and obesity using a pregnant mouse model. Study Design Female heterozygous endothelial nitric oxide synthase –/+ mice with moderate hypertension were placed on a high-fat diet for 4 weeks to induce a metabolic-like syndrome phenotype. Similarly, wild-type C57BL/6 mice were placed on a high-fat diet for 4 weeks to induce a murine obesity model. Mice were then bred with wild-type males. On gestational day 1, dams were randomly allocated to receive either a mixture of myoinositol/D-chiroinositol in water (7.2/0.18 mg/mL, respectively) or water as control (placebo). At term (gestational day 18), maternal weights, systolic blood pressure, and a glucose tolerance test were obtained. Dams were then killed; pups and placentas were weighed and maternal blood collected. Serum levels of metabolic biomarkers relevant to diabetes and obesity (ghrelin, gastric inhibitory peptide, glucagon-like peptide 1, glucagon, insulin, leptin, resistin) were measured by a multiplex enzyme-linked immunosorbent assay. Analysis was done comparing metabolic-like syndrome-myoinositol/D-chiroinositol–treated vs metabolic-like syndrome–nontreated mice and obese-myoinositol/D-chiroinositol–treated vs obese nontreated mice. Results Mean systolic blood pressure was lower in metabolic-like syndrome pregnant mice treated with myoinositol/D-chiroinositol compared with placebo ( P = .04), whereas there was no difference in systolic blood pressure between treated and placebo-treated obese pregnant mice. Pregnant metabolic-like syndrome mice treated with myoinositol/D-chiroinositol showed lower glucose values during the glucose tolerance test and in the area under the curve (myoinositol/D-chiroinositol: 17512.5 ± 3984.4 vs placebo: 29687.14 ± 8258.7; P = .003), but no differences were seen in the obese pregnant mice. Leptin serum levels were lower in the metabolic-like syndrome-myoinositol/D-chiroinositol–treated mice compared with the placebo group (myoinositol/D-chiroinositol: 16985 ± 976.4 pg/dL vs placebo: 24181.9 ± 3128.2 pg/dL, P = .045). No other differences were seen in any of the remaining serum metabolic biomarkers studied in metabolic-like syndrome and in obese pregnant mice. Maternal weight gain was not different in the pregnant metabolic-like syndrome dams, whereas it was lower in the obese myoinositol/D-chiroinositol–treated dams compared with the placebo group (myoinositol/D-chiroinositol: 10.9 ± 0.5 g vs 12.6 ± 0.6 g, P = .04). Fetal and placental weights did not differ between myoinositol/D-chiroinositol–treated and nontreated pregnant dams with metabolic-like syndrome and obesity. Conclusion Combined inositol treatment during pregnancy improves blood pressure, glucose levels at the glucose tolerance test, and leptin levels in pregnant dams with metabolic-like syndrome phenotype but not in obese pregnant dams. In addition, inositol treatment was associated with lower gestational weight gain in the obese but not in the metabolic-like syndrome pregnant dams.

Treatment of nonsevere hypertension during pregnancy is controversial. Sildenafil is a phosphodiesterase inhibitor that potentiates nitric oxide by promoting vasodilation. Nitric oxide plays a vital role in mediating the vascular adaptations during pregnancy.The objective of the study was to determine whether treatment with sildenafil during pregnancy would lower maternal systolic blood pressure without adversely affecting fetal growth.Females with nonsevere hypertension (endothelial nitric oxide synthase(+/-)) were cross-bred with normotensive wild-type males. At gestational day 1, pregnant dams were randomized to either sildenafil (0.4 mg/mL per day, comparable dose used in human pregnancy) or water for 3 weeks. Four groups were then generated: wild type (n = 7), wild type-sildenafil (n = 11), endothelial nitric oxide synthase(+/-) (n = 8), and endothelial nitric oxide synthase(+/-)sildenafil (n = 7). On gestational day 18, systolic blood pressure was measured. Dams were killed, fetal and placental weights were obtained, and carotid arteries were dissected to measure in vitro vascular reactivity with a wire-myography system. Responses to phenylephrine, L-NG-nitroarginine methyl ester, acetylcholine, and sodium nitroprusside were studied.Mean systolic blood pressure was elevated in the endothelial nitric oxide synthase(+/-) dams compared with wild-type controls (P = .03). Treatment with sildenafil decreased systolic blood pressure in the endothelial nitric oxide synthase(+/-)-treated dams compared with nontreated endothelial nitric oxide synthase(+/-) dams (P = .03). No differences were seen in the wild-type dams with or without sildenafil (P = .47). Fetuses from endothelial nitric oxide synthase(+/-) dams were smaller compared with wild-type controls (P.001); however, when these endothelial nitric oxide synthase(+/-) dams were treated with sildenafil, fetal weight increased compared with the nontreated endothelial nitric oxide synthase(+/-) group (P.001). No difference were seen in wild-type groups treated or not treated with sildenafil (P = .41). Placental weights were not significantly different among groups (endothelial nitric oxide synthase(+/-)sildenafil vs endothelial nitric oxide synthase(+/-) [P = .48]; wild-type-sildenafil vs wild type [P = .52]). Maximal vascular contraction induced by phenylephrine was blunted in endothelial nitric oxide synthase(+/-) dams treated with sildenafil compared with nontreated endothelial nitric oxide synthase(+/-) dams (P.01). No change in contractile response was seen in wild-type groups treated or not treated (P = .53). When vessels were preincubated with L-NG-nitroarginine methyl ester, the contractile responses were similar among all groups (P = .54). In addition, maximal vascular relaxation induced by acetylcholine was improved in the endothelial nitric oxide synthase(+/-) dams treated with sildenafil compared with endothelial nitric oxide synthase(+/-) nontreated dams (P.01). No change in relaxation response was seen in wild-type groups treated or not treated (P = .62). Sodium nitroprusside did not change the contractile response in any of the groups (P = .31).Pregnant dams deficient in endothelial nitric oxide synthase, a nonsevere hypertensive murine model, treated with sildenafil had lower maternal systolic blood pressure, increased fetal growth, and improvement in vascular reactivity. Treatment with sildenafil may be beneficial in pregnancies complicated by nonsevere hypertension.

To compare the timing, duration, and severity of corticosteroid-associated hyperglycemia in pregnant women with and without diabetes mellitus (DM). An observational study was conducted of pregnant women with DM and controls who received corticosteroids. Median glucose levels were calculated over 4-hour intervals after the first dose of corticosteroid with a continuous glucose monitor. A glucose level increase of at least 15% above baseline was considered significant. Nine pregnant women participated in this study (six with DM and three without DM). Elevations of glucose levels occurred at hour 20, 44, and 68 in both groups and lasted for up to 4 hours. In those with DM, glucose levels increased 33 to 48%, whereas in those without DM, glucose levels rose 16 to 33%. Several, relatively short episodes of glucose elevation occur in response to corticosteroids, and are more pronounced in diabetic women.

We sought to quantify how often women with late preterm birth (LPTB) receive antenatal corticosteroid (ACS) therapy prior to 34 weeks and to determine its effects on neonatal respiratory morbidity. LPTBs (34 (0)/ (7) to 36 (6)/ (7) weeks) over a 1-year period at a single tertiary care hospital were studied. A composite neonatal respiratory outcome was defined as mechanical ventilation, continuous positive airway pressure with fraction of inspired oxygen (F IO(2))40% for2 hours or F IO(2)40% for4 hours within the first 72 hours of life. Multivariate logistic regression analysis was used to evaluate the association between ACS therapy and neonatal respiratory morbidity. Over the study period, 503 LPTBs met the study criteria and 6.8% ( N = 34) had ACS therapy34 weeks. Most had exposure7 days prior to delivery (64.7%). Almost one-half of those receiving prior ACS therapy delivered between 34 and 35 weeks. There was no difference in the rate of prior ACS therapy based on LPTB indication for delivery. After adjusting for confounding factors, prior ACS therapy was not associated with lower respiratory morbidity (odds ratio [OR] 2.0, 95% confidence interval [CI] 0.2 to 16.3, P = 0.53). Advancing gestational age was the only variable associated with respiratory morbidity (OR 0.50, 95% CI 0.26 to .94, P = 0.03). In our population, prior ACS therapy was infrequent and was not associated with improvements in neonatal respiratory morbidity following LPTB.

Multiple studies have been published illustrating the use of oral hypoglycemic agents in pregnancy. Glyburide and metformin have been shown to be as effective as insulin for the treatment of gestational diabetes. Both are safe with breastfeeding. Although both glyburide and metformin appear safe for the treatment of type 2 diabetes mellitus, more studies are needed to support this practice.

White's classification system (WCS) was created 60 years ago to identify diabetic (DM) pregnancies at increased risk for perinatal morbidity and mortality. Our objective was to assess the association between WCS and adverse pregnancy outcome (APO) in contemporary DM pregnancies. We studied diabetic women with singleton pregnancies who delivered at >20 weeks at a single institution over a 1-year period (2007 to 2008). Perinatal outcomes were compared between WCS groups. APO was defined as any of the following: preterm birth