Effects of an Eating Pattern Including Colorful Fruits and Vegetables on Management of Gestational Diabetes: A Randomized Controlled Trial.

Gestational diabetes mellitus (GDM), defined as abnormal glucose tolerance that presents during the second and third trimesters of pregnancy, is a growing issue in the United States and worldwide. If left untreated or poorly controlled, GDM can result in numerous consequences for both the mother and the fetus; thus, it is imperative that different avenues of management for GDM be explored. There is a paucity of studies that examine how lifestyle changes, including dietary and physical activity, affect management of GDM. We examined how counseling on lifestyle changes can affect cardiometabolic risks in women with GDM. We conducted a 12-week randomized controlled trial based on behavioral counseling in which women with GDM (N = 38) were randomized into either a nutrition education (control) (N = 18) group or nutrition intervention (N = 20) group. The nutrition education group were given dietary counseling regarding healthy dietary choices based on USDA guidelines, while the nutrition intervention group were instructed to consume a total of one cup of whole berries and one cup of leafy vegetables daily along with performing postprandial exercise (walking). Blood samples, anthropometric measures, and dietary and physical activity data, recorded in daily food and activity logs, were collected at baseline and at the end of the study and compared between the two groups. Dietary counseling on supplementation with whole berries and leafy vegetables resulted in increased fiber intake, increased antioxidant intake and total serum antioxidant capacity, improved random blood glucose, decreased serum IL-6, and improved HDL cholesterol versus the control group (all p < 0.05). These results highlight that whole berry and leafy vegetable supplementation-based dietary counseling can improve the metabolic pathways involved in gestational diabetes pathogenesis and prognosis. These functional foods must be recommended in the management of pregnancies affected by GDM.

Socioeconomic impacts on the intergenerational associations of preterm birth.

BACKGROUND: The impact of socioeconomic status on intergenerational associations of preterm birth (PTB) is poorly understood. OBJECTIVE: To estimate the socioeconomic status of intergenerational impact of PTB transmission. STUDY DESIGN: This retrospective cohort study included all eligible singleton female infants born in Nebraska from 1995 to 2005 (n = 6631) and followed up from 2009 to 2019. Mothers' first singleton infants born 2009-2019 were linked to the mothers and included in the description and generalized estimating equations. RESULTS: Mothers born PTB were 37% more likely to have a PTB infant after controlling for maternal and grandmother's prenatal care adequacy, maternal residential poverty, pre-pregnancy diabetes, hypertension, C-section, and infants' gender. In poor neighborhoods, the adjusted preterm odds ratio of former born preterm mothers (compared with mother not born PTB) was 1.56 (95% confidence interval (CI): 1.02, 2.38). Moreover, moving from a poor neighborhood to a relatively well-off neighborhood was a protective factor for PTB with an adjusted odds ratio of 0.47 (95% CI: 0.23, 0.95). CONCLUSIONS: Mothers born preterm were at increased risk of having PTB infants, especially in poor areas. Maternal upward social mobility was a protective factor for PTB recurrence.

Utility of the cerebroplacental ratio (CPR) in marijuana exposed growth restricted fetuses.

OBJECTIVE: Fetal growth restriction (FGR) is associated with an increased risk of adverse perinatal outcomes. The cerebroplacental ratio (CPR) represents the interaction of alterations in blood flow to the fetal brain and placenta. CPR has been utilized as a superior reflection of fetal hypoxia/acidemia and therefore a better predictor of fetal morbidity. We sought to determine the role of the CPR as an adjunctive tool to identify fetuses at increased risk of adverse perinatal outcomes in a study population of marijuana (MJ) exposed FGR fetuses. METHODS: This was a retrospective cohort study of high-risk singleton pregnancies over a 4-year period. Self-identified daily MJ users with FGR fetuses in the 3rd trimester were isolated. Fetal biometry, amniotic fluid indices, and CPRs were calculated. A CPR <1 was considered abnormal. FGR fetuses with normal and abnormal CPRs were then compared. RESULTS: 26/192 (13.5%) of MJ exposed fetuses were diagnosed with FGR in the 3rd trimester. 12/26 (46%) had an abnormal CPR and 14 had a normal CPR (mean CPR 0.60 vs 1.57, p = .0001). The mean EFW percentile was lower in the abnormal CPR group in comparison to the group with normal CPR (3.33 vs 7.64, p = .0001). Both groups showed evidence of brain sparing with an overall mean head circumference of 17.55 in comparison to a mean abdominal circumference of 5.63. A CPR <1 was associated with more severe FGR, oligohydramnios, and abnormal UA Doppler studies. CONCLUSIONS: Approximately half of the MJ exposed FGR fetuses had an abnormal CPR. In this subset of patients, >90% had severe FGR, a higher proportion had absence/reversal of end diastolic flow in the UA, and a higher proportion had oligohydramnios. This demonstrates that an abnormal CPR identifies a group of FGR fetuses at a greater risk of adverse perinatal outcomes.

Dietary Blueberry and Soluble Fiber Improve Serum Antioxidant and Adipokine Biomarkers and Lipid Peroxidation in Pregnant Women with Obesity and at Risk for Gestational Diabetes.

Pregnancies affected by obesity are at high risk for developing metabolic complications with oxidative stress and adipocyte dysfunction contributing to the underlying pathologies. Few studies have examined the role of dietary interventions, especially those involving antioxidants including polyphenolic flavonoids found in fruits and vegetables on these pathologies in high-risk pregnant women. We conducted an 18 gestation-week randomized controlled trial to examine the effects of a dietary intervention comprising of whole blueberries and soluble fiber vs. control (standard prenatal care) on biomarkers of oxidative stress/antioxidant status and adipocyte and hormonal functions in pregnant women with obesity (n = 34). Serum samples were collected at baseline (<20 gestation weeks) and at the end of the study period (32-26 gestation weeks). Study findings showed maternal serum glutathione and antioxidant capacity to be significantly increased, and malondialdehyde to be decreased in the dietary intervention vs. control group (all p < 0.05). Among the adipokine biomarkers, serum plasminogen activator inhibitor-1 and visfatin, as biomarkers of adipocyte dysfunction and insulin resistance, were also decreased following dietary intervention (all p < 0.05). These findings support the need for supplementing maternal diets with berries and fiber to improve oxidative stress and risks of metabolic complications during pregnancy.

Dietary Blueberry and Soluble Fiber Supplementation Reduces Risk of Gestational Diabetes in Women with Obesity in a Randomized Controlled Trial.

BACKGROUND: Gestational diabetes mellitus (GDM) is a growing public health concern and maternal obesity and poor dietary intakes could be implicated. Dietary polyphenols and fiber mitigate the risk of diabetes and its complications, but little is known about their efficacy in preventing GDM. OBJECTIVES: We examined the effects of whole blueberry and soluble fiber supplementation on primary outcomes of cardiometabolic profiles in women at high risk of developing GDM. METHODS: Women (n = 34; mean ± SD age: 27 ± 5 y; BMI: 35.5 ± 4.0 kg/m2; previous history of GDM ∼56%; Hispanic ∼79%) were recruited in early pregnancy (<20 weeks of gestation) and randomly assigned to 1 of the following 2 groups for 18 wk: intervention (280 g whole blueberries and 12 g soluble fiber per day) and standard prenatal care (control). Both groups received nutrition education and maintained 24-h food recalls throughout the study. Data on anthropometrics, blood pressure, and blood samples for biochemical analyses were collected at baseline (<20 weeks), midpoint (24-28 weeks), and end (32-36 weeks) of gestation. Diagnosis of GDM was based on a 2-step glucose challenge test (GCT). Data were analyzed using a mixed-model ANOVA. RESULTS: Maternal weight gain was significantly lower in the dietary intervention than in the control group at the end of the trial (mean ± SD: 6.8 ± 3.2 kg compared with 12.0 ± 4.1 kg, P = 0.001). C-reactive protein was also lower in the intervention than in the control group (baseline: 6.1 ± 4.0 compared with 6.8 ± 7.2 mg/L; midpoint: 6.1 ± 3.7 compared with 7.5 ± 7.3 mg/L; end: 5.5 ± 2.2 compared with 9.5 ± 6.6 mg/L, respectively, P = 0.002). Blood glucose based on GCT was lower in the intervention than in the control (100 ± 33 mg/dL compared with 131 ± 40 mg/dL, P < 0.05). Conventional lipids (total, LDL, and HDL cholesterol and triglycerides) did not differ between groups over time. No differences were noted in infant birth weight. CONCLUSIONS: Whole blueberry and soluble fiber supplementation may prevent excess gestational weight gain and improve glycemic control and inflammation in women with obesity.This trial was registered at clinicaltrials.gov as NCT03467503.

Effect of intrauterine marijuana exposure on fetal growth patterns and placental vascular resistance.

OBJECTIVE: The recent legalization of marijuana has increased overall use, including in pregnancy. Studies have previously associated marijuana use with adverse fetal neurodevelopmental outcomes. We sought to compare fetal sonographic growth parameters and placental perfusion, as measured by umbilical artery Dopplers, in women using daily marijuana versus nonusers. METHODS: A retrospective cohort study capturing self - identified pregnant daily marijuana users with gestational aged matched controls was performed. We compared maternal demographics, fetal biometry, nuchal translucency, and umbilical artery Dopplers in marijuana users versus controls. Intrauterine growth restriction was defined as an estimated fetal weight <10th %. RESULTS: In 55 first trimester ultrasounds, there were no differences in crown rump lengths or nuchal translucencies between the groups. Likewise, in 195-second trimester ultrasounds, no differences were noted in biometry. Second trimester umbilical artery systolic to diastolic ratios were higher in marijuana users compared to nonusers (4.02 versus 3.92, p = .024). In the third trimester, 26 of 192 marijuana exposed fetuses were growth restricted compared to 6 of 192 controls (p = .002), and umbilical artery systolic to diastolic ratios were higher (3.52 versus 3.12, p = .0001). Four cases of absent and reversed end diastolic flow were observed in marijuana users, while no cases were observed in controls. CONCLUSIONS: Our data shows that daily marijuana use is associated with impaired fetal growth and increased placental vascular resistance. Marijuana consumption in pregnancy should be avoided until further studies delineate its exact potential for fetotoxicity.

Associations of Dietary Bioactive Compounds with Maternal Adiposity and Inflammation in Gestational Diabetes: An Update on Observational and Clinical Studies.

Gestational diabetes mellitus (GDM) is a common complication of pregnancy that adversely affects maternal and offspring health. Maternal obesity, oxidative stress, and inflammation have been implicated in GDM. In non-pregnant adults, intakes of dietary bioactive compounds inversely associate with insulin resistance and inflammation. However, associations of dietary bioactive compounds with biomarkers of adiposity, antioxidant vitamin and mineral status, oxidative stress, and inflammation in GDM have not been fully elucidated. We addressed this gap by conducting a semi-quantitative review of observational studies and randomized controlled trials published between 2010 and 2020 and retrieved from Google Scholar, Medline, and PubMed. Our analysis revealed that women with GDM are more likely to consume a pro-inflammatory diet before pregnancy and tend to consume fewer antioxidant vitamins and minerals during pregnancy than healthy pregnant women. Women with GDM also have lower blood levels of vitamins A, C, and D and certain adipokines. Several dietary bioactive compounds were noted to improve antioxidant status and biomarkers of inflammation. The Dietary Approaches to Stop Hypertension (DASH) diet and soybean oligosaccharides increased antioxidant enzyme levels. Supplementing n-3 fatty acids, probiotics, synbiotics, and trace elements increased antioxidant enzymes and reduced hs-CRP and MDA. Improvements in inflammation by vitamin D may be contingent upon co-supplementation with other dietary bioactive compounds.

"New or not-so-new" labor management practices and cesarean delivery for arrest of progress.

BACKGROUND: Because nearly one-third of births in the United States are now achieved by cesarean delivery, comprising more than 1.27 million women each year, national organizations have recently published revised guidelines for the management of labor. These new guidelines stipulate that labor arrest should not be diagnosed unless ≥6 cm cervical dilatation has been reached or labor has been stimulated for at ≥6 hours. OBJECTIVE: To determine the cervical dilatation and hours of labor stimulation prior to cesarean delivery for arrest of dilatation. MATERIALS AND METHODS: Between January 1, 1999, andDecember 31, 2000, a prospective observational study of all primary cesarean deliveries was conducted at 13 university centers comprising the Eunice Kennedy Shriver National Institute for Child Health and Human Development, Maternal-Fetal Medicine Units Network. This secondary analysis includes all live-born, singleton, nonanomalous, cephalic gestations delivered by primary cesarean delivery at ≥37 weeks. A cesarean delivery was considered to have been performed for arrest of dilatation if the indication for the procedure was failure to progress, cephalopelvic disproportion, or failed induction. Augmentation was defined as stimulation after spontaneous labor had been previously diagnosed. Analysis included both the latent and active phases of labor. The active phase of labor was diagnosed when cervical dilatation was ≥4 cm in the presence of uterine contractions. RESULTS: A total of 13,269 primary cesarean deliveries were available for analysis, 8,546 (65%) of which were performed for inadequate progress of labor with cervical dilatation recorded at the time of cesarean delivery. Of these cesarean deliveries for labor arrest, a total of 719 (8%) were performed in the latent phase of labor and 7827 (92%) were performed when cervical dilatation was ≥4 cm (active phase). Approximately two-thirds (n = =5876; 69%) received intrauterine pressure monitoring. A total of 5636 women (66% of those reaching the active phase of labor) had reached ≥6 cm cervical dilatation before cesarean delivery was performed. Moreover, 7440 (95%) of the 7827 women in active labor had ≥6 cm dilatation or had received labor stimulation ≥6 hours prior to cesarean delivery for arrest of dilatation. CONCLUSION: Women undergoing primary cesarean delivery for arrest of dilatation 15 years before the recommendations of the Obstetrics Care Consensus had received bona fide efforts to achieve adequate labor consistent with the recommendations of the Consensus. Because 95% of these women had ≥6 cm dilatation or had received labor stimulation ≥6 hours prior to cesarean delivery for arrest of dilatation, these new recommendations are unlikely to change the cesarean delivery rates.

Estrogen-related receptor γ serves a role in blood pressure homeostasis during pregnancy.

Persistent hypoxia caused by shallow trophoblast invasion and poor placental perfusion may underlie the pathophysiology of preeclampsia, a leading cause of maternal and neonatal morbidity and mortality. Previously, we found that estrogen-related receptor γ (ERRγ) serves a critical and O2-dependent role in differentiation of human trophoblasts in culture and expression of tissue kallikrein and voltage-gated K(+) channels. In this study, we surprisingly observed that ERRγ expression was significantly increased in placentas from preeclamptic women compared with that in gestation-matched normotensive women. To further investigate a functional role for ERRγ during pregnancy, we analyzed ERRγ-deficient mice. Maternal systolic blood pressure was significantly reduced in pregnant ERRγ(+/-) females bred to ERRγ(+/-) males compared with that in wild-type (WT) mice and was markedly up-regulated by treatment of WT pregnant mice with the ERRγ agonist DY131. Placentas of ERRγ(+/-) mice manifested increased vascular endothelial growth factor A expression compared with that in WT mice. Notably, circulating levels of the antiangiogenic factor, soluble fms-like tyrosine kinase-1, were significantly reduced in ERRγ(+/-) pregnant mice as was serum aldosterone. These effects were associated with a decrease in maternal adrenal Cyp11b1 (steroid 11ß-hydroxylase) and Cyp11b2 (aldosterone synthase) expression. In contrast, adrenal Cyp11b1 and Cyp11b2 mRNA were increased in pregnant WT mice treated with DY131. Moreover, chromatin immunoprecipitation and luciferase reporter assays identified Cyp11b2 as a transcriptional target of ERRγ. Collectively, these findings reveal a potential role of ERRγ in maternal blood pressure homeostasis during pregnancy and suggest that aberrant ERRγ expression may contribute to the pathogenesis of preeclampsia.

A randomized trial of the effects of antibiotic prophylaxis on epidural-related fever in labor.

BACKGROUND: It has been suggested that the development of maternal fever during epidural analgesia could be due to intrapartum infection. We investigated whether antibiotic prophylaxis before epidural placement decreases the rate of epidural-related fever. METHODS: In this double-blind, placebo-controlled trial, 400 healthy nulliparous women requesting epidural analgesia were randomly assigned to receive either cefoxitin 2 g or placebo immediately preceding initiation of epidural labor analgesia. Maternal tympanic temperature was measured hourly, and intrapartum fever was defined as a maternal temperature of ≥38°C. Neonates born to women with fever were evaluated for possible sepsis, and available placentas were evaluated for the presence of neutrophilic inflammation. The primary outcome was maternal fever during epidural analgesia. RESULTS: Thirty-eight percent of women in the cefoxitin group and 40% of women in the placebo group developed fever (P = 0.68). The risk difference (95% confidence interval) for fever ≥38°C during labor (antibiotic versus placebo) was -2.0% (-11.5 to 7.5), and for fever >39°C during labor was -1.5% (-4.7 to 1.7). Approximately half of each study group had placental neutrophilic inflammation, but administration of cefoxitin had no significant effect on any grade of neutrophilic inflammation. Fever developed significantly more often in the women with placental neutrophilic inflammation compared with those without such inflammation (73/158 vs 33/144, P < 0.001; risk difference 23% [95% confidence interval, 13.0-34.0]). There were no significant differences in any neonatal outcomes between the antibiotic and placebo study groups. Sepsis was not diagnosed in any of the infants. There were no neonatal deaths. CONCLUSION: Fever during labor epidural analgesia is associated with placental inflammation, but fever and placental inflammation were not reduced with antibiotic prophylaxis. This finding suggests that infection is unlikely to be the cause in its development.

Intrapartum hemorrhage.

Intrapartum hemorrhage is a serious and sometimes life-threatening event. Several etiologies are known and include placental abruption, uterine atony, placenta accreta, and genital tract lacerations. Prompt recognition of blood loss, identification of the source of the hemorrhage, volume resuscitation, including red blood cells and blood products when required, will result in excellent maternal outcomes.

Hypertensive emergencies of pregnancy.

Hypertension is commonly encountered in pregnancy and has both maternal and fetal effects. Acute hypertensive crisis most commonly occurs in severe preeclampsia and is associated with maternal stroke, cardiopulmonary decompensation, fetal decompensation due to decreased uterine perfusion, abruption, and stillbirth. Immediate stabilization of the mother including the use of intervenous antihypertensives is required and often delivery is indicated. With appropriate management, maternal and fetal outcomes can be excellent.

Seizures and intracranial hemorrhage.

Seizures and intracranial hemorrhage are possible medical diseases that any obstetrician may encounter. This article reviews the cause, treatment, and medical management in pregnancy for seizures and intracranial hemorrhage, and how the two can overlap into preeclampsia or eclampsia. This article also highlights some challenging management issues from the obstetrician's perspective.

Placenta accreta, increta, and percreta.

Placenta accreta is an abnormal adherence of the placenta to the uterine wall that can lead to significant maternal morbidity and mortality. The incidence of placenta accreta has increased 13-fold since the early 1900s and directly correlates with the increasing cesarean delivery rate. The prenatal diagnosis of placenta accreta by ultrasound along with risk factors including placenta previa and prior cesarean delivery can aid in delivery planning and improved outcomes. Referral to a tertiary care center and the use of a multidisciplinary care team is recommended.

The c-Myc-regulated microRNA-17~92 (miR-17~92) and miR-106a~363 clusters target hCYP19A1 and hGCM1 to inhibit human trophoblast differentiation.

Mononuclear cytotrophoblasts of the human placenta proliferate rapidly, subsequently fuse, and differentiate to form multinucleated syncytiotrophoblast with induction of aromatase (hCYP19A1) and chorionic gonadotropin (hCGß) expression. Using microarray analysis, we identified members of the miR-17~92 cluster and its paralogs, miR-106a~363 and miR-106b~25, that are significantly downregulated upon syncytiotrophoblast differentiation. Interestingly, miR-19b and miR-106a directly targeted hCYP19A1 expression, while miR-19b also targeted human GCM1 (hGCM1), a transcription factor critical for mouse labyrinthine trophoblast development. Overexpression of these microRNAs (miRNAs) impaired syncytiotrophoblast differentiation. hGCM1 knockdown decreased hCYP19A1 and hCGß expression, substantiating its important role in human trophoblast differentiation. Expression of the c-Myc proto-oncogene was increased in proliferating cytotrophoblasts compared to that in differentiated syncytiotrophoblast. Moreover, c-Myc overexpression upregulated miR-17~92 and inhibited hCYP19A1 and hCGß expression. Binding of endogenous c-Myc to genomic regions upstream of the miR-17~92 and miR-106a~363 clusters in cytotrophoblasts dramatically decreased upon syncytiotrophoblast differentiation. Intriguingly, we observed higher levels of miR-106a and -19b and lower aromatase and hGCM1 expression in placentas from preeclamptic women than in placentas from gestation-matched normotensive women. Our findings reveal that c-Myc-regulated members of the miR-17~92 and miR-106a~363 clusters inhibit trophoblast differentiation by repressing hGCM1 and hCYP19A1 and suggest that aberrant regulation of these miRNAs may contribute to the pathogenesis of preeclampsia.

Effect of maternal body mass index on serum magnesium levels given for seizure prophylaxis.

OBJECTIVE: To estimate the effect of body mass index (BMI) on magnesium levels for eclampsia prophylaxis. METHODS: This is a retrospective study from 2004 to 2011, examining magnesium levels in women receiving seizure prophylaxis. Women received 6 g and then 2 g/h. Women had 4-hour and 12-hour levels drawn. Levels were considered subtherapeutic at less than 4.9 mg/dL, therapeutic from 4.9 to 8.4 mg/dL, and supratherapeutic at 8.5 mg/dL or more. If the 4-hour value was not therapeutic, the dose was adjusted and a 12-hour level was drawn. Levels at 4 and 12 hours were compared among the women with different BMI classifications and clinical characteristics. RESULTS: During the study period,106,265 women delivered, and 7,799 (7.4%) had preeclampsia diagnosed and received magnesium sulfate for seizure prophylaxis. A total of 5,304 (68%) of these women had a recorded BMI. At 4 hours, 2,698 (51%) were subtherapeutic. These women were more likely to be older, parous, undergo cesarean delivery, have a higher systolic blood pressure, and have central nervous system manifestations. At 12 hours, 2,342 (90%) of therapeutic women remained therapeutic, and 5% became subtherapeutic (n=118) or supratherapeutic (n=140). Using logistic regression, we were able to predict being subtherapeutic in women with greater BMI and to predict being supratherapeutic if women had labor longer than 12 hours and worsening severity of preeclampsia. CONCLUSION: Women receiving seizure prophylaxis with a BMI of more than 30 may benefit from routine serum magnesium evaluation 4 hours after the loading dose. LEVEL OF EVIDENCE: III.

Defining uterine tachysystole: how much is too much?

OBJECTIVE: We sought to determine if uterine tachysystole, ≥ 6 contractions per 10 minutes, within the first 4 hours of labor induction, is associated with adverse infant outcomes. STUDY DESIGN: This was a prospective cohort study of 584 women ≥ 37 weeks' gestation undergoing induction of labor with 100 µg of oral misoprostol. Fetal heart rate tracings were analyzed for contractions per 10 minutes during the initial 4 hours after misoprostol administration. Patients were analyzed based on the maximum number of contractions per 10 minutes. Infant condition at birth was assessed using the fetal vulnerability composite. RESULTS: Adverse infant outcomes showed no association with increasing number of contractions per 10 minutes. Six or more contractions in 10 minutes were significantly associated with fetal heart rate decelerations (P ≤ .001). Analysis was performed using the maximum number of contractions per 30 minutes with similar results. CONCLUSION: Uterine tachysystole, as currently defined, when occurring remote from delivery is not associated with adverse infant outcomes.