Type 2 diabetes and neonatal hypoglycemia: role of route of delivery and insulin infusion.

OBJECTIVE: To compare the rate of neonatal hypoglycemia among newborns delivered by individuals with Type 2 diabetes mellitus (T2DM) in two clinical scenarios: who attempted vaginal delivery vs. had a planned cesarean delivery (CD); who had intrapartum insulin infusion vs. who did not. METHODS: This was a retrospective cohort study of individuals with insulin-treated T2DM who had non-anomalous singleton pregnancy and delivered at a single tertiary center (March 2012 and May 2018). Individuals with chronic renal failure, proliferative retinopathy, or major congenital anomalies were excluded. The primary outcome was neonatal hypoglycemia (blood glucose < 40 mg/dl <24 h of age or < 50 mg/dl >24 h of age). Secondary outcomes included neonatal outcomes. Multivariable Poisson regression models with robust error variance were used to examine the association between groups and the primary outcome. Adjusted relative risk (aRR) and 95% confidence intervals (CI) were calculated. RESULTS: Of 233 individuals with T2DM, 215 (92.2%) met the inclusion criteria, of whom 95 (44%) attempted vaginal delivery and 120 (56%) had a planned CD. Individuals who labored had a higher gestational age at delivery (36.6 vs. 35.8 weeks, p = .005), and higher blood glucose levels upon admission (125 vs 103, p < .001) compared to those with a planned CD. After adjustment for potential confounders, there was no difference in risk of neonatal hypoglycemia between the groups (41.2 vs 44.1%, aRR 1.05, 95% CI = 0.75-1.45). Among those who attempted vaginal delivery, 34 (35.8%) required insulin infusion. There was no difference in the risk of neonatal hypoglycemia (aRR = 0.79, 95% CI = 0.45-1.37) between newborns delivered by individuals who required insulin infusion and those who did not. CONCLUSION: Over 40% of newborns delivered by individuals with insulin-dependent T2DM had hypoglycemia; however, there was no significant difference in the risk of hypoglycemia, irrespective of the route of delivery and the use of insulin infusion.

A Case Report of Fetal Thrombotic Vasculopathy in a COVID Placenta.

COVID-19 has affected patients of all ages and demographics, not excluding pregnant women. The effects of COVID-19 on pregnant women are still largely unknown. Several adverse perinatal outcomes have been reported in COVID-19-positive pregnant women, including pre-eclampsia, miscarriage, pre-term labor, and stillbirth. Histopathological examination of COVID-19 placentas can contribute significant data regarding maternal and fetal health and can elucidate more findings in this novel disease. A 23-year-old female with morbid obesity and scant antenatal care presented to the emergency department complaining of shortness of breath and fever; she was found to be positive for COVID-19. Grossly, her placenta showed no abnormalities. Histological examination of her placenta showed chronic lymphoplasmacytic deciduitis, villous fibrosis, loss of capillarization, extravasation of erythrocytes, chorangiosis, and thrombosis of upstream stem vessels, including large fetal vessels on the chorionic plate. These changes were deemed to be consistent with fetal thrombotic vasculopathy (FTV). In conclusion, this case of FTV in the placenta of a patient with COVID-19 is a significant finding, as it can be critical to clinicians in the management of prenatal care for expecting mothers during this pandemic.This case was presented at the annual meeting of the Association of Clinical Scientists (ACS) on May 13, 2021.

Transcervical Foley Balloon Plus Vaginal Misoprostol versus Vaginal Misoprostol Alone for Cervical Ripening in Nulliparous Obese Women: A Multicenter, Randomized, Comparative-Effectiveness Trial.

OBJECTIVE: Nulliparous obese women are at increased risk of labor induction and cesarean delivery (CD). We sought to determine whether the combination of a transvaginal Foley balloon plus misoprostol prostaglandin E1 (PGE1) is superior to misoprostol alone in reducing the risk for CD. STUDY DESIGN: We undertook a multicenter, open-label, comparative-effectiveness randomized clinical trial of nulliparous obese women with unfavorable cervix (Bishop's score ≤ 6) undergoing labor induction from January 2016 to June 2018 at three tertiary centers. Those at <32 weeks' gestation, premature rupture of membranes, stillbirth, and major fetal anomalies were excluded. Women were randomized 1:1 to either a combination of Foley balloon and misoprostol or misoprostol alone. Once Bishop's score was >6, further management was deferred to treating physicians. Primary outcome was the rate of CD. Secondary maternal outcomes included duration of induction-to-delivery interval, occurrence of tachysystole, clinical chorioamnionitis, need for operative vaginal delivery, as well as a composite of maternal morbidity (postpartum endometritis, surgical-site infection, venous thromboembolism, need for transfusion, intensive care unit admission, and maternal death). Secondary neonatal outcomes included need for neonatal intensive care unit admission, transient tachypnea of the newborn, respiratory distress syndrome, meconium aspiration syndrome, culture-proven sepsis, neonatal seizures, and a composite of neonatal morbidity (Apgar's score ≤7 at 5 minutes, umbilical artery cord pH ≤7.10, birth injury, perinatal death). With the rate of CD rate being 53% at Children's Memorial Herman Hospital among nulliparous obese women who underwent induction of labor at ≥32 weeks and met our inclusion criteria; 250 women (125 women per group) were required to answer the study question. All analyses were by intention to treat. RESULTS: Of the 236 women randomized, 113 (48%) were allocated to group 1 (combined Foley and PGE1) and 123 (52%) to group 2 (PGE1 alone). The rate of CD was similar between the groups (45 vs. 43%, p = 0.84, relative risk [RR]: 1.03, 95% CI: 0.75-1.42). There was no difference in the occurrence of tachysystole that resulted in fetal heart rate abnormalities between the groups (8.8 vs. 16.2%, p = 0.09, RR: 0.54, 95% CI: 0.27-1.11). The total duration of the induction-to-delivery interval was also similar between the groups (24.8 ± 13.8 vs. 24.5 ± 14.0 hours, p = 0.87) regardless of the mode of delivery. No differences were seen in the indications for CD and secondary maternal or neonatal outcomes. CONCLUSION: In this trial of nulliparous obese women undergoing labor induction, cervical ripening with combined Foley balloon and PGE1 resulted in similar CD rates than ripening with vaginal PGE1 alone. KEY POINTS: · Nulliparous obese women are at increased risk for cesarean delivery.. · Combined intravaginal misoprostol-Foley balloon versus misoprostol alone resulted in similar rates of cesarean delivery.. · Further research is warranted to determine the optimal cervical ripening strategy in this population..

Maternal Supplementation of Inositols, Fucoxanthin, and Hydroxytyrosol in Pregnant Murine Models of Hypertension.

BACKGROUND: Myoinositol (M) and D-chiro-inositol (D) are insulin sensitizer compounds, while fucoxanthin (F) and hydroxytyrosol (H) are antioxidant substances. We aim to investigate if the combination of these compounds, will improve the vascular responses in pregnant mouse models of hypertension: a genetic model, transgenic heterozygous mice lacking endothelial nitric oxide synthase gene (eNOS-/+); and environmental, wild-type (WT) mice. Those mouse models will allow a better understanding of the genetic/environmental contribution to hypertension in pregnancy. METHODS: eNOS-/+ and WT female were fed high fat diet for 4 weeks, then at 7-8 weeks of age were mated with WT male. On gestational day (GD) 1, they were randomly allocated to receive MDFH treatment or water as control: eNOS-/+ MDFH (n = 13), eNOS-/+ (n = 13), WT-MDFH (n = 14), and WT (n = 20). Systolic blood pressure (SBP) was obtained at GD 18, then dams were sacrificed; fetuses and placentas collected, and 2 mm segments of carotid arteries isolated for vascular responses using the wire-myograph system. Responses to phenylephrine (PE), with/without the NOS inhibitor (N-nitro-l-arginine methyl ester (l-NAME)), and to acetylcholine (Ach) and sodium nitroprussiate (SNP) were performed. RESULTS: SBP decreased in eNOS-/+ and WT dams after MDFH supplementation. In eNOS-/+, MDFH lower the contractile response to PE and l-NAME and improved Ach vasorelaxation. In WT dams, MDFH treatment did not affect PE response; MDFH treatment lowered the vascular PE response after incubation with l-NAME. No differences were seen in SNP relaxation in both models. CONCLUSIONS: MDFH decreased SBP in both genetically and environmentally hypertensive dams and improved vascular responses mostly in the eNOS-/+ dams.

Prevalence and Risk Factors for New-Onset Hypertension in Labor.

OBJECTIVE: Little is known about prevalence, risk factors, rate of treatment, or adverse outcomes associated with intrapartum hypertension. Thus, our objective was to describe these findings. STUDY DESIGN: This was a retrospective study of laboring term gestations with no history of hypertensive disorders. Intrapartum blood pressures were reviewed, and women were subdivided based on blood pressures: normal (<140 mm Hg systolic and <90 mm Hg diastolic), mild hypertension (140-159 or 90-109), and severe hypertension (≥ 160 or ≥ 110). Groups were compared using chi-square test and analysis of variance. RESULTS: A total of 724 women were studied during 4 months: 248 (34%) had mild and 69 (10%) had severe hypertension. Severe hypertensives were more likely to be nulliparous, obese, or have received an epidural or oxytocin. There were no cases of eclampsia, stroke, or pulmonary edema in severe hypertensives (95% confidence interval, 0-5). Despite severely elevated pressures, only 4/69 (6%) patients received intravenous antihypertensive therapy, and 3 (4%) required medications at discharge. CONCLUSION: One in 3 women exhibits mild hypertension and 1 in 10 develop severe hypertension in labor. Only 6% of patients received treatment for severe blood pressures. This study highlights lack of treatment of hypertension in labor and further investigation into causes and outcomes of intrapartum elevations of blood pressures.

Adherence to Consensus Guidelines for the Management of Labor Arrest Disorders in a Single Academic Tertiary Care Medical Center.

OBJECTIVE: To evaluate the degree of adherence to the new the American College of Obstetricians and Gynecologists/Society for Maternal-Fetal Medicine guidelines in labor arrest management. STUDY DESIGN: A retrospective study of term, live, singleton deliveries with intrapartum primary cesarean delivery solely for failed induction of labor or labor arrest. Adherence was defined according to the Safe Prevention of the Primary Cesarean Delivery 2014 criteria. We evaluated adherence and compared maternal and perinatal outcomes, delivery time frame, and billing provider. Multivariable Poisson regression models with robust error variance were used to calculate adjusted relative risk (aRR) and 95% confidence interval (CI). RESULTS: Two-hundred six deliveries met the inclusion criteria; 73% were deemed not adherent to the guidelines. The majority of cases were under the care of nonacademic private practice OB/GYN physicians. The adherence rate was higher in the active phase of labor (45%) than in second stage (17%) and latent phase (14%). There were no differences in perinatal outcomes between the two groups. The adherence to guidelines was higher among academic OB/GYN physicians (aRR, 2.24, 95% CI, 1.49-3.36) and during the weekday-night shift (aRR, 1.81, 95% CI, 1.10-2.98). CONCLUSION: Despite recent guidelines aimed to reduce the primary cesarean delivery rate, most cesarean deliveries performed for labor arrest disorders were not adherent to the guidelines.

Vascular and metabolic profiles in offspring born to pregnant mice with metabolic syndrome treated with inositols.

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.

Torsemide for Prevention of Persistent Postpartum Hypertension in Women With Preeclampsia: A Randomized Controlled Trial.

OBJECTIVE: To evaluate whether torsemide reduces the rate of persistent postpartum hypertension in women with preeclampsia. METHODS: We conducted a randomized, double-blind, placebo-controlled trial of women with preeclampsia at a tertiary center from August 2016 to September 2017. Those with gestational hypertension or renal or cardiopulmonary failure were excluded. Within 24 hours of delivery, women were randomized one to one to oral torsemide, 20 mg/d, or placebo, for 5 days. Our primary outcome was blood pressure greater than or equal to 150 mm Hg systolic or 100 mm Hg diastolic (or both) on two occasions at least 4 hours apart by postpartum day 5 or by the time of hospital discharge. Assuming a 50% rate of persistent hypertension in women with preeclampsia, 118 participants were required to detect a 50% rate reduction. Analyses were by intention to treat. RESULTS: From August 2016 to September 2017, 118 women were randomized: 59 were allocated to torsemide and 59 to placebo. Overall, 43 (73%) women in the torsemide and 45 (76%) in the placebo group had either preeclampsia with severe features or preeclampsia superimposed on chronic hypertension. The rate of persistent postpartum hypertension was 44% in the torsemide and 58% in the placebo group (relative risk 0.76, 95% CI 0.5-1.1). No differences were seen in rate of hypertension 7-10 days or 6 weeks postpartum, severe hypertension, length of postpartum hospital stay, readmission for hypertension, or adverse events. There were no cases of severe composite morbidity or deaths. CONCLUSION: In this trial of women with preeclampsia, a 5-day course of postpartum torsemide did not have a significant effect on the rate of postpartum hypertension. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02813551.

Liberal versus Indicated Maternal Oxygen Supplementation in Labor: A Before-and-After Trial.

BACKGROUND: Although supplemental oxygen (SO2) is routinely administered to laboring gravidas, benefits and harms are not well studied. OBJECTIVE: This article compares strategies of liberal versus indicated SO2 therapy during labor on cesarean delivery (CD) rate and neonatal outcomes. STUDY DESIGN: A controlled, before-and-after trial of laboring women with term, singleton pregnancies. During an initial 8-week period, maternal SO2 was administered at the discretion of the provider followed by an 8-week period where SO2 was to be given only for protocol indications. RESULTS: Our study included 844 women. There was no difference in number of women receiving SO2 (53% liberal vs. 50% indicated; p = 0.33). For those receiving SO2, there was no difference in SO2 duration (median, 89 minutes [interquartile range, 42-172] vs. 87 minutes [36-152]; p = 0.42). There were no differences in overall CD rate (20% vs. 17%; p = 0.70), CD for nonreassuring fetal status, or use of intrauterine resuscitative measures. There were more 5-minute APGAR < 7 in the indicated group, but no difference in umbilical artery pH < 7.1 or neonatal intensive care unit (NICU) admission. CONCLUSION: Approximately half of women receive SO2 intrapartum regardless of a strategy of liberal or indicated oxygen use. There were no clinically significant differences in outcomes between strategies.

Association of Nonsteroidal Antiinflammatory Drugs and Postpartum Hypertension in Women With Preeclampsia With Severe Features.

OBJECTIVE: To estimate whether nonsteroidal antiinflammatory drugs (NSAIDs) are associated with persistent postpartum hypertension in a cohort of women with preeclampsia and severe features. METHODS: We conducted a retrospective cohort study at a single, tertiary center from January 2013 to December 2015. All women diagnosed with severe preeclampsia who remained hypertensive for greater than 24 hours after delivery were included. The primary outcome was the rate of persistent postpartum hypertension, defined as systolic blood pressure 150 mm Hg or greater or diastolic 100 mm Hg or greater (or both), on two occasions, at least 4 hours apart. Secondary outcomes included severe maternal morbidity: pulmonary edema, renal dysfunction, stroke, eclampsia, and intensive care unit admission. Additional outcomes included length of postpartum hospital stay, receipt of narcotics, and hospital readmission. Multivariable logistic regression was performed to adjust for confounders. Adjusted odds ratios (ORs) are reported for applicable study outcomes. RESULTS: Of the 399 women with severe preeclampsia, 324 (81%) remained hypertensive 24 hours after delivery. Two hundred forty-three (75%) received NSAIDs (either ibuprofen or ketorolac) and 81 (25%) did not. After multivariable logistic regression, the likelihood of reaching a blood pressure of 150 mm Hg systolic or 100 mm Hg diastolic (or both), on two occasions, at least 4 hours apart, was similar between those who received NSAIDs compared with those who did not (70% compared with 73%; adjusted OR 1.1, 95% CI 0.6-2.0). Similarly, puerperal occurrence of pulmonary edema (3% compared with 10%; OR 4.4, 95% CI 1.5-13.1), renal dysfunction (5% compared with 8%; OR 1.7, 95% CI 0.6-4.8), eclampsia (1% compared with 0%; P=.34), or intensive care unit admission (3% compared with 8%; OR 2.4, 95% CI 0.8-7.1) was similar between the groups. There were no differences in the rate of narcotic use (89% compared with 75%; adjusted OR 0.6 95% CI 0.18-1.70). CONCLUSION: In this cohort of women with preeclampsia and severe features before delivery, NSAIDs were not associated with increased rates of persistent postpartum hypertension.

Obesity epidemic: impact from preconception to postpartum.

The obesity epidemic is on the rise throughout the USA and the world. Not only does it affect the general population but it also specifically poses unique threats to a woman's life in the antepartum, peripartum and postpartum periods. An increased BMI is associated with worse perinatal outcomes, including higher rates of preeclampsia (and other hypertensive disorders), macrosomia, other neonatal morbidities and gestational diabetes. Isolated maternal obesity and additional maternal diabetes predispose the infant to potential adult disease through fetal programming. This review of the literature examines the effects of obesity on a woman's life, outlining complications beginning with preconception through the postpartum period.