Monica Longo

Serum nitrites predict the response to prostaglandin-induced delivery at term

OBJECTIVE To evaluate whether the clinical response to prostaglandin-induced labor is modulated by nitric oxide (NO) activity. METHODS Fifty-two cases of nulliparous women at term who delivered vaginally after prostaglandin E (PGE) induction of labor were enrolled. The induction was required mainly for amniotic fluid reduction or late-onset gestational hypertension. Either intracervical (0.5 mg) or vaginal (2.0 mg) PGE was administered every 12 hours, according to the Bishop score. After the third PGE application, in absence of labor onset, intravenous oxytocin was used. Nitrites/nitrates (NOx) serum levels were used as a marker of NO activity. They were measured just before the start of induction by using an enzymatic reduction and then a colorimetric evaluation. Time to delivery from the first PGE application was the main outcome variable. RESULTS Time to delivery ranged from 4 to 62 hours (median: 15.5). Nitrites/nitrates levels were unaffected by both gestational age, Bishop score at entry, indication allowing labor-induction, fetal position, and birth weight. In a multiple regression analysis including the previous factors, NOx levels significantly explained 33.9% of the variance of the time to delivery. Indeed, patients delivering within 15 hours (26.4 +/- 6.9) showed NOx levels significantly lower than in patients delivering after more than 15 hours (39.5 +/- 16.4) from the first PGE application. CONCLUSIONS A reduced level of NOx is associated with a prompt clinical response to PGE-induced labor. Provided we do not know the origin of NOx in the general circulation, these data indicate NOx levels as predictors of the response to PGE-induced delivery at term and support the hypothesis that labor onset is modulated by the endogenous NO activity.

Rate of Gestational Diabetes Mellitus and Pregnancy Outcomes in Patients with Chronic Hypertension

Objective This study aims to determine the rate of gestational diabetes mellitus (GDM) in pregnancies complicated by chronic hypertension and to compare the adverse outcomes in chronic hypertensive pregnancies with and without GDM. Study Design A secondary analysis from a multicenter trial of low-dose aspirin for preeclampsia prevention in women with chronic hypertension. The rate of GDM was evaluated among singleton pregnancies complicated with chronic hypertension and grouped according to their GDM status. Pregnancy outcomes and rates of preterm delivery < 35 weeks and < 32 weeks, preeclampsia, indicated preterm birth, small for gestational age, abruptio placentae, and perinatal death were compared between those with and without GDM. A subgroup analysis comparing women who developed superimposed preeclampsia with and without GDM was studied. Multivariate logistic-regression analysis was used to adjust for potentially confounding factors. Results A total of 763 women met the inclusion criteria: 129 (17%) developed GDM. Parity, race, maternal baseline blood pressure, antihypertensive drug use, and assignment to low-dose aspirin were not significantly different between the groups with and without GDM. Using univariate analysis, maternal age (33 vs. 24%, p = 0.03) and body mass index (88 vs. 57%, p < 0.001) were higher in those who had GDM, whereas the rate of preterm delivery < 32 weeks (12 vs. 5%, p = 0.02) was higher among those without GDM. Using logistic-regression analysis, the rate of composite adverse outcomes (adjusted odds ratio [aOR], 0.77; 95% confidence interval [CI], 0.41-1.47) that included indicated preterm birth, small for gestational age, abruptio placentae, and perinatal death showed no significant differences.Superimposed preeclampsia developed in 34 (26%) women with GDM and in 182 (29%) without GDM. When superimposed preeclampsia was present, it developed at an earlier gestational age among the group without GDM (35 ± 5 vs. 37 ± 3 weeks, p = 0.003), and had higher rates of small for gestational age infants (18 vs. 3%, p = 0.03). After adjustment for confounders, only length of stay in neonatal intensive care unit was longer for those without GDM who developed superimposed preeclampsia (aOR, 0.42; 95% CI, 0.2-0.93). Conclusion Women with chronic hypertension are at a high risk for developing GDM. Outcomes in patients with chronic hypertension and GDM are not significantly different from those with chronic hypertension only.

Magnetically Bioprinted Human Myometrial 3D Cell Rings as A Model for Uterine Contractility

Deregulation in uterine contractility can cause common pathological disorders of the female reproductive system, including preterm labor, infertility, inappropriate implantation, and irregular menstrual cycle. A better understanding of human myometrium contractility is essential to designing and testing interventions for these important clinical problems. Robust studies on the physiology of human uterine contractions require in vitro models, utilizing a human source. Importantly, uterine contractility is a three-dimensionally (3D)-coordinated phenomenon and should be studied in a 3D environment. Here, we propose and assess for the first time a 3D in vitro model for the evaluation of human uterine contractility. Magnetic 3D bioprinting is applied to pattern human myometrium cells into rings, which are then monitored for contractility over time and as a function of various clinically relevant agents. Commercially available and patient-derived myometrium cells were magnetically bioprinted into rings in 384-well formats for throughput uterine contractility analysis. The bioprinted uterine rings from various cell origins and patients show different patterns of contractility and respond differently to clinically relevant uterine contractility inhibitors, indomethacin and nifedipine. We believe that the novel system will serve as a useful tool to evaluate the physiology of human parturition while enabling high-throughput testing of multiple agents and conditions.

Uterus-targeted liposomes for preterm labor management: Studies in pregnant mice

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.

A Rapidly Growing Abdominal Mass: Desmoid Tumor in Pregnancy

Background Desmoid tumors are benign soft tissue tumors that locally invade adjacent tissue. There is a paucity of reports describing the rapid growth of these tumors during pregnancy. Case A giant desmoid tumor arising from the left abdominal wall of a young female patient with rapid growth during pregnancy is described. Preoperative evaluation included ultrasonography and magnetic resonance imaging. Decision made by a multidisciplinary team was not to intervene before birth, and abdominal delivery at term was accomplished. Conclusion Desmoid tumors should be part of the differential diagnosis in an abdominal wall tumor of rapid growth during pregnancy. Future studies are needed for better understanding of the pathogenesis, diagnosis, and treatment of desmoid tumors in pregnant women.

Adverse Effect of High-Fat Diet on Metabolic Programming in Offspring Born to a Murine Model of Maternal Hypertension

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.

Maternal interventions to improve offspring outcomes in rodent models of diet-induced obesity: a review

Abstract Maternal obesity is an adverse factor that affects the intrauterine environment during critical periods of fetal developmental causing adverse lifelong effects on offspring health. Several different interventions have been performed in animal models of obesity to ameliorate maternal conditions and consequently reduce the adverse effects on offspring. Our aim was to critically review studies involving murine models of obesity induced by high fat diet (HFD), assessing maternal outcomes during pregnancy and the related offspring conditions. We carried out a computerized literature search of PubMed and Medline. We identified eight studies that fulfilled the inclusion criteria and have performed interventions in pregnancy with natural, synthetized compounds, and lifestyle modifications. Metabolic profile and lipid metabolism were improved by inositols, resveratrol, germinated brown rice (GBR), and exercise in the mother. The offspring whose mother received resveratrol, adiponectin, GBR, and exercise, showed an improvement in leptin, triglycerides, adiponectin levels, and a decrease in insulin resistance. These experimental studies demonstrate that several interventions in pregnant rodents improve the metabolic profile of both the mother and the offspring. Clinical research could now explore the efficacy and safety of such interventions, interrupting the vicious circle that an obese mother generates a child prone to develop metabolic (and cardiovascular) disease in adult life.

Twin gestation in a Swyer syndrome patient with superimposed pre-eclampsia

Jaimin S. Shah , Oscar A. Viteri, Monica Longo, Mazen Abdallah and Baha Sibai Department of Obstetrics, Gynecology and Reproductive Sciences, The University of Texas at Houston McGovern Medical School, Houston, TX, USA; Department of Maternal-Fetal Medicine, The University of Texas at Houston McGovern Medical School, Houston, TX, USA; Department of Reproductive, Endocrinology and Infertility, The University of Texas at Houston McGovern Medical School, Houston, TX, USA