SERUM GLP-2 is Increased in Association with Excess Gestational Weight Gain.

OBJECTIVE: Obesity in pregnancy bears unique maternal and fetal risks. Obesity has also been associated with chronic inflammation, including elevated serum levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Higher serum lipopolysaccharide (LPS) levels have been implicated in driving this inflammation, a phenomenon called metabolic endotoxemia (ME). GLP-2, a proglucagon-derived peptide, is believed to be integral in maintaining the integrity of the intestine in the face of LPS-mediated endotoxemia. We hypothesized that obesity and/or excess weight gain in pregnancy would be associated with an increase in maternal and neonatal markers of ME, as well as GLP-2. STUDY DESIGN: Paired maternal and neonatal (cord blood) serum samples (n = 159) were obtained from our pregnancy biobank repository. Serum levels of LPS, endotoxin core antibody-immunoglobulin M (EndoCAb-IgM), and GLP-2 were measured by ELISA. IL-6 and TNF-α were measured using a Milliplex assay. Results were stratified by maternal body mass index (BMI), maternal diabetes, and gestational weight gain (GWG). RESULTS: Maternal IL-6 is significantly decreased in the obese, diabetic cohort compared with the nonobese, nondiabetic cohorts (95.28 vs. 99.48 pg/mL, p = 0.047), whereas GLP-2 is significantly increased (1.92 vs. 2.89 ng/mL, p = 0.026). Neonatal TNF-α is significantly decreased in the obese cohort compared with the nonobese cohort (12.43 vs. 13.93 pg/mL, p = 0.044). Maternal GLP-2 is significantly increased in women with excess GWG compared with those with normal GWG (2.27 vs. 1.48 ng/mL, p = 0.014). We further found that neonatal IL-6 and TNF-α are negatively correlated with maternal BMI (-0.186, p = 0.036 and -0.179, p = 0.044, respectively) and that maternal and neonatal IL-6 showed a positive correlation (0.348, p < 0.001). CONCLUSION: Although we observed altered levels of markers of inflammation (IL-6 and TNF-α) with maternal obesity and diabetes, no changes in LPS or endoCAb-IgM were observed. We hypothesize that the increased GLP-2 levels in maternal serum in association with excess GWG may protect against ME in pregnancy. KEY POINTS: · Maternal serum levels of GLP-2, a proglucagon-derived peptide, are increased in obese, diabetic gravidae.. · Maternal serum GLP-2 levels are also increased in association with excess gestational weight gain compared with normal gestational weight gain.. · GLP-2 may be increased in association with obesity and weight gain to protect against metabolic endotoxemia in pregnancy..

Open Intrauterine Fetal Myelomeningocele Repair: Changes in the Surgical Procedure and Perinatal Complications during the First 8 Years of Experience at a Single Center.

INTRODUCTION: Open fetal myelomeningocele (fMMC) repair is nowadays a therapeutic option in selected cases. We aimed to evaluate changes in maternal and fetal outcome after fMMC repair during the first 8 years of experience at a tertiary referral fetal medicine center in Switzerland. -Materials and Methods: Between 2010 and 2018, fMMC repair and delivery of the neonate via planned cesarean section was performed in 67 cases. Cases were retrospectively stratified into 2 groups: a "training phase" (TP) with supervision from an external surgeon during 11 operations (2010-2014, 15 cases) followed by an "experienced phase" (EP, 2014-2018, 52 cases); each phase lasted about 4 years. Both phases were compared with regard to various maternal and fetal outcome parameters. RESULTS: Analyses did not reveal differences between TP and EP in major outcome parameters such as gestational age at delivery, chorionic membrane separation, or the incidence of placental abruption. Although more complex surgical techniques were applied in EP (e.g., dermal closure using a rotational flap), surgery time was not different from TP. At the same time, surgical complications such as oligohydramnios (27 vs. 8%, p = 0.046) with MRI-confirmed leakage (13 vs. 4%, nonsignificant) and subchorionic hematoma (20 vs. 2%, p = 0.009) were less common in EP than TP. CONCLUSIONS: This study shows that the level of competence at our center with regard to major perinatal outcome parameters was already high in the first years of fMMC repair. However, more complex surgical techniques and significantly less minor complications were observed during the most recent years.

Birth Rates Among Hispanics and Non-Hispanics and their Representation in Contemporary Obstetric Clinical Trials.

Objective Our study aims were to establish whether subjects enrolled in current obstetric clinical trials proportionately reflects the contemporary representation of Hispanic ethnicities and their birth rates in the United States. Methods Using comprehensive source data over a defined interval (January 2011-September 2015) on birth rates by ethnicity from the Centers for Disease Control and Prevention (CDC), we evaluated the proportional rate by ethnicity, then analyzed the observed to expected relative ratio of enrolled subjects. Results Hispanic women comprise a significant contribution to births in the United States (23% of all births). Systematic analysis of 90 published obstetric clinical trials showed a correlation between inclusion of Hispanic gravidae and the corresponding state's birth rates (r = 0.501, p < 0.001). While the mean was strongly correlated, individual clinical trials may have relatively over-enrolled (n = 31, or 34%) or under-enrolled (n = 33, or 37%) relative to their regional population. In 48% of obstetric clinical trials the Hispanic proportion of the study population was not reported. Conclusion Hispanic gravidae represent a significant number of contemporary U.S. births, and are generally adequately represented as obstetric subjects in clinical trials. However, this is trial-dependent, with significant trial-specific under- and over-enrollment of Hispanic subjects relative to the regional birth population.

Preterm birth and its associations with residence and ambient vehicular traffic exposure.

BACKGROUND: Preterm birth (PTB) is a multifactorial disorder, and air pollution has been suggested to increase the risk of occurrence. However, large population studies controlling for multiple exposure measures in high-density settings with established commuter patterns are lacking. OBJECTIVE: We performed a geospatial analysis with the use of a publicly available database to identify whether residence during pregnancy, specifically with regard to exposure to traffic density and mobility in urban and suburban neighborhoods, may be a contributing risk factor for premature delivery. STUDY DESIGN: In our cohort study, we analyzed 9004 pregnancies with as many as 4900 distinct clinical and demographic variables from Harris County, Texas. On the basis of primary residency and occupational zip code information, geospatial analysis was conducted. Data on vehicle miles traveled (VMT) and percentages of inhabitants traveling to work were collected at the zip code level and additionally grouped by the three recognized regional commuter loop high-density thoroughfares resulting from two interstate/highway belts (inner, middle, and outer loops). PTB was categorized as late (34 1/7 to 36 6/7 weeks) and early PTB (22 1/7 to 33 6/7 weeks), and unadjusted odds ratios (OR) and adjusted ORs were ascribed. RESULTS: PTB prevalence in our study population was 10.1% (6.8% late and 3.3% early preterm), which is in accordance with our study and other previous studies. Prevalence of early PTB varied significantly between the regional commuter loop thoroughfares [OR for inner vs outer loop: 0.58 (95% confidence interval, 0.39-0.87), OR for middle vs outer loop, 0.74 (0.57-0.96)]. The ORs for PTB and early PTB were shown to be lower in gravidae from neighborhoods with the highest VMT/acre [OR for PTB, 0.82 (0.68-0.98), OR for early PTB, 0.78 (0.62-0.98)]. Conversely, risk of PTB and early PTB among subjects living in neighborhoods with a high percentage of inhabitants traveling to work over a greater distance demonstrated a contrary tendency [OR for PTB, 1.18 (1.03-1.35), OR for early PTB, 1.48 (1.17-1.86)]. In logistic regression models, the described association between PTB and residence withstood and could not be explained by differences in maternal age, gravidity or ethnicity, tobacco use, or history of PTB. CONCLUSION: While PTB is of multifactorial origin, the present study shows that community-based risk factors (namely urban/suburban location, differences in traffic density exposure, and need for traveling to work along high-vehicle density thoroughfares) may influence risk for PTB. Further research focusing on previously unrecognized community-based risk factors may lead to innovative future prevention measures.

Increasing maternal obesity is associated with alterations in both maternal and neonatal thyroid hormone levels.

OBJECTIVE: Obesity is associated with alterations in thyroid hormone (TH) levels in obese, pregnant individuals. The maintenance of TH levels throughout gestation is important for proper foetal development. The aim of this study was to measure levels of fT3, fT4 and TSH in maternal and matched cord blood serum from normal weight, overweight and obese gravidae to determine alterations in maternal and neonatal TH levels by virtue of maternal obesity. DESIGN, SETTING, SUBJECTS, OUTCOME MEASURES: ELISA was utilized to measure fT3, fT4 and TSH levels from banked, matched maternal and neonatal (cord blood) serum (N = 205 matched pairs). Data were stratified according to prepregnancy or first trimester BMI. RESULTS: Both maternal and neonatal fT3 levels consistently increased with increasing maternal obesity, and maternal and neonatal fT3 were significantly correlated (r = 0·422, P < 0·001). Maternal and neonatal fT3 were also significantly associated with birthweight (ß = 0·155, P = 0·027 and ß = 0·171, P = 0·018, respectively). Both the maternal and neonatal fT3 to fT4 ratio significantly increased with increasing maternal obesity. We further found that excess gestational weight gain was associated with a decrease in maternal fT4 compared with gravidae who had insufficient gestational weight gain (0·86 ± 0·17 vs 0·95 ± 0·22, P < 0·01). CONCLUSION: Maternal obesity is not only associated with maternal alterations in TH, but with accompanying neonatal changes. Because both maternal obesity and alterations in TH levels are associated with childhood obesity, based on these findings and our prior analyses in a nonhuman primate model, we propose that changes in fT3 levels in the offspring of obese mothers may be a potential molecular mediator of foetal overgrowth and childhood obesity.

Changes in Myocardial Contractility and Electromechanical Interval During the First Month of Life in Healthy Neonates.

This study aims at documenting the changes in ventricular tissue velocities, longitudinal strain and electromechanical coupling during the first month of life. During the neonatal period, when the ventricular myocardium is not yet fully maturated, the heart is subjected to significant hemodynamic changes. We studied the ventricular performance of 16 healthy neonates at three time points over the first month of life: on days 2 (IQR [2;2]), 13 [12;14] and 27 [25;29]. We found that systolic and diastolic tissue velocities increased significantly in both left and right ventricle (by 1.2-1.7 times, p < 0.001). Congruently, we found that peak systolic longitudinal strain of the right and left ventricles increased significantly. However, no significant changes in longitudinal strain rate were observed. Finally, QS-intervals shortened during the neonatal period: being measured at 12 points throughout the left ventricle, time to peak systolic velocity decreased on average to 89 % in the second and to 80 % in the fourth week of life (22.3 ± 0.2 vs. 19.8 ± 0.3 vs. 17.8 ± 0.5 ms, r = -0.564, p < 0.001). When comparing opposing walls of the left ventricle, no dyssynchrony in left ventricular contraction was found. In addition to increasing systolic and diastolic tissue velocities during the first month of life, the time to peak systolic contraction shortens in the neonatal heart, which may reflect an increasing efficiency of the excitation-contraction coupling in the maturing myocardium. While there appears to be no dyssynchrony in ventricular contraction, these findings may extend our appreciation of the immature neonatal heart and certain disease states.

Geospatial analysis of food environment demonstrates associations with gestational diabetes.

BACKGROUND: Gestational diabetes mellitus (GDM) is one of most common complications of pregnancy, with incidence rates varying by maternal age, race/ethnicity, obesity, parity, and family history. Given its increasing prevalence in recent decades, covariant environmental and sociodemographic factors may be additional determinants of GDM occurrence. OBJECTIVE: We hypothesized that environmental risk factors, in particular measures of the food environment, may be a diabetes contributor. We employed geospatial modeling in a populous US county to characterize the association of the relative availability of fast food restaurants and supermarkets to GDM. STUDY DESIGN: Utilizing a perinatal database with >4900 encoded antenatal and outcome variables inclusive of ZIP code data, 8912 consecutive pregnancies were analyzed for correlations between GDM and food environment based on countywide food permit registration data. Linkage between pregnancies and food environment was achieved on the basis of validated 5-digit ZIP code data. The prevalence of supermarkets and fast food restaurants per 100,000 inhabitants for each ZIP code were gathered from publicly available food permit sources. To independently authenticate our findings with objective data, we measured hemoglobin A1c levels as a function of geospatial distribution of food environment in a matched subset (n = 80). RESULTS: Residence in neighborhoods with a high prevalence of fast food restaurants (fourth quartile) was significantly associated with an increased risk of developing GDM (relative to first quartile: adjusted odds ratio, 1.63; 95% confidence interval, 1.21-2.19). In multivariate analysis, this association held true after controlling for potential confounders (P = .002). Measurement of hemoglobin A1c levels in a matched subset were significantly increased in association with residence in a ZIP code with a higher fast food/supermarket ratio (n = 80, r = 0.251 P < .05). CONCLUSION: As demonstrated by geospatial analysis, a relationship of food environment and risk for gestational diabetes was identified.

A qualitative assessment of the perceived risks of electronic cigarette and hookah use in pregnancy.

BACKGROUND: Studies reveal that electronic cigarette (e-cigarette) and hookah use are increasing among adolescents and young adults. However, the long-term health effects are unknown, especially with regards to pregnancy. Because of the increased use in women of reproductive age, and the unknown long-term health risks, our primary objectives were to determine the perceived risks of e-cigarette and hookah use in pregnancy, and learn common colloquial terms associated with e-cigarettes. Furthermore, we sought to determine if there is a stigma associated with e-cigarette use in pregnancy. METHODS: Eleven focus groups including 87 participants were conducted immediately following regularly scheduled CenteringPregnancy® prenatal care with women at three different clinics in the greater Houston area. A minimum of two facilitators led the groups, using ten lead-in prompts, with Spanish translation as necessary. Facilitators took notes which were compared immediately following each group discussion and each group was audio recorded and transcribed. Three facilitators utilized NVivo 9.0 software to organize the transcribed data into nodes to identify major themes. To increase rigor, transcripts were further analyzed by two obstetricians who were instructed to find the major themes. RESULTS: Analyses revealed contradicting themes concerning e-cigarette use. In general, e-cigarettes were perceived as safer alternatives to regular tobacco cigarettes, especially if used as smoking cessation devices. A major theme is that use in pregnancy is harmful to the fetus. However, it was perceived that use for smoking cessation in pregnancy may have fewer side effects. We found that a common term for e-cigarettes is "Blu." In our discussion of hookah use, participants perceived use as popular among teenagers and that use in pregnancy is dangerous for the fetus. CONCLUSIONS: Although a strong theme emerged against hookah use, we found contradicting themes in our discussions on e-cigarette use in pregnancy. It is possible that e-cigarette use will not carry the same stigma as regular cigarette smoking in pregnancy. In addition, the impression of e-cigarettes as a healthier alternative to smoking may influence use in pregnancy. Clinicians need to be prepared for questions of e-cigarette safety and efficacy as smoking cessation devices from their pregnant patients who smoke, and women who smoke and are planning to become pregnant.