Maternal exercise increases infant resting energy expenditure: preliminary results.

Maternal obesity is associated with lower infant resting energy expenditure (REE), predisposing them to more rapid weight and adiposity gain through early infancy. Maternal exercise (ME) decreases infant adiposity and risk for childhood obesity; however, it remains unknown if this is in part mediated by changes in infant energy expenditure. Thus, we measured REE in 1-month-old infants from pregnant individuals who performed moderate-intensity exercise during pregnancy and compared it to infants from non-exercising controls. We observed higher oxygen respiratory rates (p = 0.003 for VO2 and p = 0.007 for VCO2) and REE (p = 0.002) in infants exposed to exercise in utero, independent of any differences in infant body composition. Furthermore, maternal BMI was significantly and inversely associated with infant REE in the control (r = -0.86, R2 = 0.74, p = 0.029), but not the exercise group (r = 0.33, R2 = 0.11, p = 0.473). Together, these findings associate ME with increasing infant energy expenditure which could be protective of subsequent infant adiposity gain. Clinical Trial: ClinicalTrials.gov Identifier: NCT03838146 and NCT04805502.

Pregnancy and Smoothelin-like Protein 1 (SMTNL1) Deletion Promote the Switching of Skeletal Muscle to a Glycolytic Phenotype in Human and Mice.

Pregnancy promotes physiological adaptations throughout the body, mediated by the female sex hormones progesterone and estrogen. Changes in the metabolic properties of skeletal muscle enable the female body to cope with the physiological challenges of pregnancy and may also be linked to the development of insulin resistance. We conducted global microarray, proteomic, and metabolic analyses to study the role of the progesterone receptor and its transcriptional regulator, smoothelin-like protein 1 (SMTNL1) in the adaptation of skeletal muscle to pregnancy. We demonstrate that pregnancy promotes fiber-type changes from an oxidative to glycolytic isoform in skeletal muscle. This phenomenon is regulated through an interaction between SMTNL1 and progesterone receptor, which alters the expression of contractile and metabolic proteins. smtnl1(-/-) mice are metabolically less efficient and show impaired glucose tolerance. Pregnancy antagonizes these effects by inducing metabolic activity and increasing glucose tolerance. Our results suggest that SMTNL1 has a role in mediating the actions of steroid hormones to promote fiber switching in skeletal muscle during pregnancy. Our findings also bear on the management of gestational diabetes that develops as a complication of pregnancy in ~4% of women.

The perinatal quality collaborative of North Carolina's 39 weeks project: a quality improvement program to decrease elective deliveries before 39 weeks of gestation.

BACKGROUND: Despite long-standing guidelines from the American College of Obstetricians and Gynecologists that call for avoiding elective births prior to 39 weeks of gestation, elective deliveries make up almost one-third of US births occurring in weeks 36-38. Poor outcomes are more likely for infants born electively before 39 weeks than for those born at 39 weeks. The Perinatal Quality Collaborative of North Carolina (PQCNC) undertook the 39 Weeks Project in 2009-2010 with the aim of reducing the number of early-term elective deliveries in North Carolina hospitals. METHODS: Participating hospitals (N = 33) provided retrospective data on all early-term deliveries and created new policies, or amended or enforced existing policies, to accomplish the project's goals. Project activities included in-person learning sessions, regional meetings, webinars, electronic newsletters, a secure extranet Web site where participating hospitals could share relevant materials, and individual leadership consultations with hospital teams. Hospitals submitted monthly data to PQCNC, which provided ongoing training and data analysis. RESULTS: Elective deliveries before 39 weeks of gestation decreased 45% over the project period, from 2% to 1.1% of all deliveries. The proportion of elective deliveries among all scheduled early-term deliveries also decreased, from 23.63% to 16.19%. There was an increase in the proportion of patients with documented evidence of medical indications for early delivery, from 62.4% to 88.2%. LIMITATIONS: No data were collected to determine whether outcomes changed for patients whose deliveries were deferred. The project also depended on each hospital to code its own data. CONCLUSION: The PQCNC's 39 Weeks Project successfully decreased the rate of early-term elective deliveries in participating hospitals.

Effects of maternal exercise on infant mesenchymal stem cell mitochondrial function, insulin action, and body composition in infancy.

Maternal exercise (ME) has been established as a useful non-pharmacological intervention to improve infant metabolic health; however, mechanistic insight behind these adaptations remains mostly confined to animal models. Infant mesenchymal stem cells (MSCs) give rise to infant tissues (e.g., skeletal muscle), and remain involved in mature tissue maintenance. Importantly, these cells maintain metabolic characteristics of an offspring donor and provide a model for the investigation of mechanisms behind infant metabolic health improvements. We used undifferentiated MSC to investigate if ME affects infant MSC mitochondrial function and insulin action, and if these adaptations are associated with lower infant adiposity. We found that infants from exercising mothers have improvements in MSC insulin signaling related to higher MSC respiration and fat oxidation, and expression and activation of energy-sensing and redox-sensitive proteins. Further, we found that infants exposed to exercise in utero were leaner at 1 month of age, with a significant inverse correlation between infant MSC respiration and infant adiposity at 6 months of age. These data suggest that infants from exercising mothers are relatively leaner, and this is associated with higher infant MSC mitochondrial respiration, fat use, and insulin action.

Exercise FITT-V during pregnancy: Association with birth outcomes.

BACKGROUND: Prenatal exercise improves birth outcomes, but research into exercise dose-response effects is limited. METHODS: This study is a retrospective, secondary analysis of pooled data from three blinded, prospective, randomized controlled trials. Prenatal exercise frequency, intensity, type, time, and volume (FITT-V) were assessed in supervised sessions throughout pregnancy. Gestational age (GA), neonatal resting heart rate (rHR), morphometrics (body circumferences, weight-to-length and ponderal index) Apgar and reflex scores, and placental measures were obtained at birth. Stepwise regressions and Pearson correlations determined associations between FITT-V and birth outcomes. RESULTS: Prenatal exercise frequency reduces ponderal index (R2 = 0.15, F = 2.76, p = .05) and increased total number of reflexes present at birth (R2 = 0.24, F = 7.89, p < .001), while exercise intensity was related to greater gestational age and birth length (R2 = 0.08, F = 3.14; R2 = 0.12, F = 3.86, respectively; both p = .04); exercise weekly volume was associated with shorter hospital stay (R2 = 0.24, F = 4.73, p = .01). Furthermore, exercise type was associated with placenta size (R2 = 0.47, F = 3.51, p = .01). CONCLUSIONS: Prenatal exercise is positively related to birth and placental outcomes in a dose-dependent manner.

Differences in substrate metabolism between African American and Caucasian infants: evidence from mesenchymal stem cells.

Type 2 diabetes is more prevalent in African American (AA) than Caucasian (C) adults. Furthermore, differential substrate utilization has been observed between AA and C adults, but data regarding metabolic differences between races at birth remains scarce. The purpose of the present study was to determine if there are racial differences in substrate metabolism evident at birth using a mesenchymal stem cells (MSCs) collected from offspring umbilical cords. Using radio-labeled tracers, MSCs from offspring of AA and C mothers were tested for glucose and fatty acid metabolism in the undifferentiated state and while undergoing myogenesis in vitro. Undifferentiated MSCs from AA exhibited greater partitioning of glucose toward nonoxidized glucose metabolites. In the myogenic state, AA displayed higher glucose oxidation, but similar fatty acid oxidation rates. In the presence of both glucose and palmitate, but not palmitate only, AA exhibit a higher rate of incomplete fatty acid oxidation evident by a greater production of acid-soluble metabolites. Myogenic differentiation of MSCs elicits an increase in glucose oxidation in AA, but not in C. Together, these data suggest that metabolic differences between AA and C races exist at birth.NEW & NOTEWORTHY African Americans, when compared with Caucasians, display greater insulin resistance in skeletal muscle. Differences in substrate utilization have been proposed as a factor for this health disparity; however, it remains unknown how early these differences manifest. Using infant umbilical cord-derived mesenchymal stem cells, we tested for in vitro glucose and fatty acid oxidation differences. Myogenically differentiated MSCs from African American offspring display higher rates of glucose oxidation and incomplete fatty acid oxidation.

Self-Reported Intake and Circulating EPA and DHA Concentrations in US Pregnant Women.

In the United States, pregnant women have low concentrations of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), which are essential for fetal development. Although maternal blood provides accurate polyunsaturated fatty acid (PUFA) concentrations, venipuncture is expensive and not always accessible. PUFA-containing foods consumption, both omega-3 ad omega-6 is supposed to reflect in the status (plasma, RBC, adipose tissue) of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). De novo synthesis of DHA and EPA during pregnancy is supposed to be higher compared to pre and/or post-pregnancy periods. Thus, this study aimed to determine the association between maternal self-reported dietary intake of foods high in DHA and EPA, along with vegetable oils as a source of omega-6 fatty acids, with maternal blood DHA and EPA concentrations. Pregnant women (13-16 weeks gestation) were recruited and asked to complete a food-frequency questionnaire (FFQ) and blood draw at enrollment and 36 weeks. Circulating concentrations of DHA and EPA were quantified and change scores were calculated. Correlations were done to determine associations between FFQ results and EPA/DHA maternal blood concentrations. Regression analyses were run to examine significant predictors of the main outcomes. Overall, PUFA-food consumption and RBC's DHA levels decreased from early to late pregnancy; self-reported PUFA-rich food consumption positively correlated with DHA and EPA levels. DHA concentration was predicted by self-reported PUFA-rich oils (sunflower/soy/corn/olive) consumption, but EPA concentration was predicted by maternal BMI. These findings suggest that EPA and DHA consumption decreased across pregnancy and the FFQ can be utilized as an effective method for estimating PUFA blood concentration during pregnancy.

Influence of prenatal exercise on the relationship between maternal overweight and obesity and select delivery outcomes.

Women with overweight or obesity (OWOB) have an increased risk of cesarean birth, preterm birth (PTB), and high birth weight infants. Although regular exercise decreases this risk in healthy weight women, these associations have not been explored in OWOB. Women were randomized at 13-16 weeks' gestation to 150-min of moderate-intensity exercise (n = 131) or non-exercising control (n = 61). Delivery mode, gestational age (GA), and birth weight (BW) were obtained via electronic health records. Pregnant exercisers had no differences in risk of cesarean birth, PTB, or BW compared to control participants. OWOB exercisers had higher rates of cesarean birth (27.1% vs. 11.1%), trends of higher PTB (15.3% vs. 5.6%), but normal weight babies relative to normal weight exercisers. Controlling for race and body mass index (BMI), maternal exercise reduced the relative risk (RR) for cesarean birth from 1.63 to 1.43. Cesarean births predicted by pre-pregnancy BMI and fitness level, whereas BW was predicted by race, gestational weight gain (GWG), pre-pregnancy fitness level, and exercise level. Cesarean birth was predicted by pre-pregnancy BMI and fitness level, while maternal exercise reduced the magnitudes of the relative risks of cesarean birth. Maternal exercise, pre-pregnancy fitness level, and GWG predict neonatal BW.Trial Registration: Influence of Maternal Exercise on Infant Skeletal Muscle and Metabolomics-#NCT03838146, 12/02/2019, https://register.clinicaltrials.gov/prs/app/template/EditRecord.vm?epmode=Edit&listmode=Edit&uid=U0003Z0X&ts=8&sid=S0008FWJ&cx=77ud1i .

Maternal Aerobic Exercise, but Not Blood Docosahexaenoic Acid and Eicosapentaenoic Acid Concentrations, during Pregnancy Influence Infant Body Composition.

Although discrete maternal exercise and polyunsaturated fatty acid (PUFA) supplementation individually are beneficial for infant body composition, the effects of exercise and PUFA during pregnancy on infant body composition have not been studied. This study evaluated the body composition of infants born to women participating in a randomized control exercise intervention study. Participants were randomized to aerobic exercise (n = 25) or control (stretching and breathing) groups (n = 10). From 16 weeks of gestation until delivery, the groups met 3×/week. At 16 and 36 weeks of gestation, maternal blood was collected and analyzed for Docosahexaenoic Acid (DHA) and Eicosapentaenoic Acid (EPA). At 1 month postnatal, infant body composition was assessed via skinfolds (SFs) and circumferences. Data from 35 pregnant women and infants were analyzed via t-tests, correlations, and regression. In a per protocol analysis, infants born to aerobic exercisers exhibited lower SF thicknesses of triceps (p = 0.008), subscapular (p = 0.04), SF sum (p = 0.01), and body fat (BF) percentage (%) (p = 0.006) compared with controls. After controlling for 36-week DHA and EPA levels, exercise dose was determined to be a negative predictor for infant skinfolds of triceps (p = 0.001, r2 = 0.27), subscapular (p = 0.008, r2 = 0.19), SF sum (p = 0.001, r2 = 0.28), mid-upper arm circumference (p = 0.049, r2 = 0.11), and BF% (p = 0.001, r2 = 0.32). There were no significant findings for PUFAs and infant measures: during pregnancy, exercise dose, but not blood DHA or EPA levels, reduces infant adiposity.

The Influence of Maternal Aerobic Exercise, Blood DHA and EPA Concentrations on Maternal Lipid Profiles.

Exercise and polyunsaturated fatty acid (PUFA) supplementation independently improve lipid profiles. The influence of both exercise and PUFAs on lipids during pregnancy remains unknown. This study evaluated exercise, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) concentrations on lipids during pregnancy. Participants were randomized to aerobic exercise or control groups. From 16 weeks gestation until delivery, groups met 3x/week; exercisers performed moderate-intensity aerobic activity, controls performed low-intensity stretching and breathing. At 16 and 36 weeks' gestation, maternal blood was analyzed for lipids (total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides (TG)), DHA and EPA. In intent-to-treat analysis, the aerobic group (n = 20), relative to controls (n = 10), exhibited a higher HDL change across gestation (p = 0.03). In a per protocol analysis, the aerobic group, relative to controls, exhibited 21.2% lower TG at 36 weeks (p = 0.04). After controlling for 36-week DHA and EPA, exercise dose predicts 36 weeks' TG (F (1,36) = 6.977, p = 0.012, r2 = 0.16). Aerobic exercise normalizes late pregnancy TG. During pregnancy, exercise dose controls the rise in TG, therefore maintaining normal levels. DHA and EPA do not have measurable effects on lipids. Regardless of PUFA levels, exercise at recommended levels maintains appropriate TG levels in pregnant women. Normal TG levels are critical for pregnancy outcomes, and further studies are warranted to investigate this association in broader populations.

Smoothelin-like 1 protein regulates myosin phosphatase-targeting subunit 1 expression during sexual development and pregnancy.

Pregnancy coordinately alters the contractile properties of both vascular and uterine smooth muscles reducing systemic blood pressure and maintaining uterine relaxation. The precise molecular mechanisms underlying these pregnancy-induced adaptations have yet to be fully defined but are likely to involve changes in the expression of proteins regulating myosin phosphorylation. Here we show that smoothelin like protein 1 (SMTNL1) is a key factor governing sexual development and pregnancy induced adaptations in smooth and striated muscle. A primary target gene of SMTNL1 in these muscles is myosin phosphatase-targeting subunit 1 (MYPT1). Deletion of SMTNL1 increases expression of MYPT1 30-40-fold in neonates and during development expression of both SMTNL1 and MYPT1 increases over 20-fold. Pregnancy also regulates SMTNL1 and MYPT1 expression, and deletion SMTNL1 greatly exaggerates expression of MYPT1 in vascular smooth muscle, producing a profound reduction in force development in response to phenylephrine as well as sensitizing the muscle to acetylcholine. We also show that MYPT1 is expressed in Type2a muscle fibers in mice and humans and its expression is regulated during pregnancy, suggesting unrecognized roles in mediating skeletal muscle plasticity in both species. Our findings define a new conserved pathway in which sexual development and pregnancy mediate smooth and striated muscle adaptations through SMTNL1 and MYPT1.

The effects of aerobic exercise on markers of maternal metabolism during pregnancy.

BACKGROUND: Optimal maternal metabolism during pregnancy is essential for healthy fetal growth and development. Chronic exercise is shown to positively affect metabolism, predominantly demonstrated in nonpregnant populations. OBJECTIVE: To determine the effects of aerobic exercise on maternal metabolic biomarkers during pregnancy, with expected lower levels of glucose, insulin, and lipids among exercise-trained pregnant women. METHODS: Secondary data analyses were performed using data from two, longitudinal prenatal exercise intervention studies (ENHANCED by MOM and GESTAFIT). Exercisers completed 150 min of weekly moderate-intensity exercise during pregnancy (24+ weeks) while nonexercisers attended stretching sessions. Pregnant women were 31-33 years of age, predominantly non-Hispanic white, and "normal weight" body mass index. At 16 and 36 weeks of gestation, fasting blood samples were collected via fingerstick and venipuncture. Maternal glucose, insulin, insulin resistance (HOMA-IR), total cholesterol (TC), low-density lipoproteins (LDL), high-density lipoproteins (HDL), and triglycerides (TG) were analyzed. ANCOVA analyses were performed to evaluate the effects of aerobic exercise on markers of maternal metabolism in late pregnancy, controlling for baseline levels. RESULTS: Our sample included 12 aerobic exercisers and 54 nonexercising control groups. Significant between-groups differences at 16 weeks of gestation were found for TG (92.3 vs. 121.2 mg/dl, p = .04), TC (186.8 vs. 219.6 mg/dl, p = .002), and LDL (104.1 vs. 128.8 mg/dl, p = .002). Aerobic-trained pregnant women exhibited lower insulin levels in late pregnancy (ß = -2.6 µIU/ml, 95% CI:-4.2, -0.95, p = .002) and a reduced increase in insulin levels from 16 to 36 week of gestation (ß = -2.3 µIU/ml, 95% CI: -4.4, -0.2, p = .034) compared with nonexercising pregnant women. No statistically significant effects were observed for maternal HOMA-IR, TC, LDL, HDL, TC:HDL, and TG in late pregnancy. CONCLUSIONS: The observations of this study demonstrate that prenatal exercise may positively affect maternal insulin, with aerobic-trained pregnant women exhibiting lower insulin levels in late pregnancy. Additionally, we found no appreciable effects of prenatal exercise on maternal lipids in late pregnancy.

Gestational diabetes is associated with depressed adiponectin levels.

OBJECTIVE: Adiponectin is a 29-kd adipocyte-secreted protein that has been linked to insulin resistance in obesity and diabetes. The aim of the present study was to evaluate adiponectin levels in the insulin-resistant state of diabetes in gestation. METHODS: Term, gravid subjects with diabetes (n = 31; age, 30.0 +/- 0.9 years; weight, 98.8 +/- 4.6 kg) and healthy, term, gravid subjects (n = 27; age, 26.1 +/- 1.1 years; weight, 91.2 +/- 3.78 kg) were examined. The diabetes group consisted of 11 class A1, 11 class A2, and nine class B subjects. Plasma insulin, glucose, adiponectin, and leptin were measured on samples obtained immediately before Cesarean or vaginal delivery. Data were presented as means +/- SE, and significance is set at P < or = .05. RESULTS: We observed decreased adiponectin levels in class A2 (4.93 +/- 0.58 microg/mL; P = .013) and class B diabetics (3.33 +/- 0.56 microg/mL; P = .001) as compared to controls (8.17 +/- 0.82 microg/mL), while a nonsignificant decrease was also observed in class A1 (6.58 +/- 1.13 microg/mL; P = .213). When grouping all gravid subjects, we observed that non-Caucasian subjects (n = 42) (5.51 +/- 0.51 microg/mL; P = .003) had lower adiponectin levels than Caucasian subjects (n = 16) (8.88 +/- 1.11 microg/mL). Within the non-Caucasian group, we found significantly lower adiponectin levels in diabetic gravid subjects (class A2: 4.24 +/- 0.75 microg/mL; P = .044; and class B: 3.33 +/- 0.56 microg/mL; P = .005) compared with nondiabetic gravid subjects (7.05 +/- 0.80 microg/mL). CONCLUSION: Class A2 and B gestational diabetes are associated with suppressed levels of adiponectin, similar to that found in other insulin-resistant states (type II diabetes and obesity).

Surgical management of massive labial edema in a gravid preeclamptic diabetic.

Background. Massive labial edema is a rare complication during pregnancy that can jeopardize vaginal delivery, as well as leading to maternal and fetal morbidity. It can be related to systemic pathologies, but has been commonly associated with preeclampsia and diabetes. This increased and sometimes longstanding pressure may result in a "labial compartment syndrome" leading to microvascular damage and tissue necrosis if not resolved in a timely fashion. Case. Massive labial edema was treated first conservatively and then surgically in a gravid diabetic patient with severe preeclampsia. Immediately after Cesarean section, the labial compartment syndrome was relieved surgically and resolved rapidly. Conclusion. When conservative attempts at management of labial edema fail, or rapid resolution is critical to maternal and fetal outcome, surgical alternatives should be considered.

Postpartum prolapsed leiomyoma with uterine inversion managed by vaginal hysterectomy.

Background. Uterine inversion is a rare, but life threatening, obstetrical emergency which occurs when the uterine fundus collapses into the endometrial cavity. Various conservative and surgical therapies have been outlined in the literature for the management of uterine inversions. Case. We present a case of a chronic, recurrent uterine inversion, which was diagnosed following spontaneous vaginal delivery and recurred seven weeks later. The uterine inversion was likely due to a leiomyoma. This late-presenting, chronic, recurring uterine inversion was treated with a vaginal hysterectomy. Conclusion. Uterine inversions can occur in both acute and chronic phases. Persistent vaginal bleeding with the appearance of a prolapsing fibroid should prompt further investigation for uterine inversion and may require surgical therapy. A vaginal hysterectomy may be an appropriate management option in select populations and may be considered in women who do not desire to maintain reproductive function.

Gestational diabetes is characterized by reduced mitochondrial protein expression and altered calcium signaling proteins in skeletal muscle.

The rising prevalence of gestational diabetes mellitus (GDM) affects up to 18% of pregnant women with immediate and long-term metabolic consequences for both mother and infant. Abnormal glucose uptake and lipid oxidation are hallmark features of GDM prompting us to use an exploratory proteomics approach to investigate the cellular mechanisms underlying differences in skeletal muscle metabolism between obese pregnant women with GDM (OGDM) and obese pregnant women with normal glucose tolerance (ONGT). Functional validation was performed in a second cohort of obese OGDM and ONGT pregnant women. Quantitative proteomic analysis in rectus abdominus skeletal muscle tissue collected at delivery revealed reduced protein content of mitochondrial complex I (C-I) subunits (NDUFS3, NDUFV2) and altered content of proteins involved in calcium homeostasis/signaling (calcineurin A, α1-syntrophin, annexin A4) in OGDM (n = 6) vs. ONGT (n = 6). Follow-up analyses showed reduced enzymatic activity of mitochondrial complexes C-I, C-III, and C-IV (-60-75%) in the OGDM (n = 8) compared with ONGT (n = 10) subjects, though no differences were observed for mitochondrial complex protein content. Upstream regulators of mitochondrial biogenesis and oxidative phosphorylation were not different between groups. However, AMPK phosphorylation was dramatically reduced by 75% in the OGDM women. These data suggest that GDM is associated with reduced skeletal muscle oxidative phosphorylation and disordered calcium homeostasis. These relationships deserve further attention as they may represent novel risk factors for development of GDM and may have implications on the effectiveness of physical activity interventions on both treatment strategies for GDM and for prevention of type 2 diabetes postpartum.

Uterine hyperstimulation by intravenous access in a mammary vein: a case report and literature review.

Breast stimulation can produce contractions in a contraction stress test and has been considered for the augmentation of labor and prevention of postpartum hemorrhage. We present a case of intravenous access of a mammary vein in an obstetric patient that led to uterine hyperstimulation. Potential dangers of mammary vein intravenous access are discussed.