Meredith Cruz

Update on Peripartum Cardiomyopathy

Although multiple mechanisms have been postulated, peripartum cardiomyopathy (PPCM) continues to be a cardiomyopathy of unknown cause. Multiple risk factors exist and the clinical presentation does not allow differentiation among potential causes. Although specific diagnostic criteria exist, PPCM remains a diagnosis of exclusion. Treatment modalities are dictated by the clinical state of the patient, and prognosis is dependent on recovery of function. Randomized controlled trials of novel therapies, such as bromocriptine, are needed to establish better treatment regimens to decrease morbidity and mortality. The creation of an international registry will be an important step to better define and treat PPCM. This article discusses the pathogenesis, risk factors, diagnosis, management, and prognosis of this condition.

Oscillations in Activities of Enzymes in Pancreatic Islet Subcellular Fractions Induced by Physiological Concentrations of Effectors

Glucose, the most potent insulin secretagogue, stimulates insulin secretion by aerobic glycolysis, but other secretagogues stimulate insulin release exclusively by mitochondrial metabolism. It is well known that in the intact pancreatic β-cell, either kind of secretagogue can induce oscillations in metabolism (e.g., glycolysis, ATP/ADP, NAD(P)/NAD(P)H ratios) that occur with a periodicity similar to oscillations in membrane electrical potential and insulin secretion. In this study, pancreatic islet cytosol or mitochondrial fractions were incubated in the presence of physiological concentrations of substrates. Repeated additions of physiological effectors caused oscillations in the activities of the three enzymes studied. Succinate dehydrogenase activity in islet mitochondrial extracts was made to oscillate by adding oxaloacetate (5 μmol/l) to inhibit the enzyme. The enzyme was reactivated by adding acetyl-CoA (3 μmol/l), which combines with oxaloacetate in the citrate synthase reaction and lowers the concentration of oxaloacetate, thus beginning another oscillation. Pyruvate kinase activity was made to oscillate by adding fructose bisphosphate (10 μmol/l). Fructose bisphosphate was degraded to triose phosphates fairly rapidly, and, as it was degraded, there was a parallel decrease in pyruvate kinase activity. The enzyme was reactivated and made to oscillate with subsequent additions of fructose bisphosphate. The mitochondrial glycerol phosphate dehydrogenase was made to oscillate by adding EGTA to chelate calcium, which activates the enzyme. When the concentration of free calcium was raised to >0.1 μmol/l by adding more calcium, the activity of the enzyme increased. Repeated additions of chelator and calcium caused the enzyme activity to oscillate. The results with these three enzymes and physiological concentrations of naturally occurring effectors raise the possibility that the activities of not only these enzymes but of numerous enzymes oscillate in vivo in response to levels of allosteric effectors and substrates. If this is the case, pacemaker activity may result from complex effects distributed across multiple regulatory sites in both the cytosol and mitochondria, rather than from a single enzyme acting as a primary pacemaker.

Obstetrical and perinatal outcomes among women with gestational hypertension, mild preeclampsia, and mild chronic hypertension

OBJECTIVE The purpose of this study was to compare maternal and neonatal outcomes of women with gestational hypertension (GHTN), mild chronic hypertension (CHTN), and mild preeclampsia at delivery. STUDY DESIGN A multicenter database that contained 228,668 deliveries was used to extract data on gravid women with GHTN, preeclampsia, and CHTN and on women without hypertensive disease (control group). Univariate and multivariate logistic regression analyses were performed. RESULTS There were 4918 women with GHTN, 5274 women with preeclampsia, 2531 women with CHTN, and 15,221 control subjects. Women with GHTN had the greatest risk for blood transfusion (adjusted odds ratio [aOR], 4.6; 95% confidence interval [CI], 3.4-6.3), intensive care unit admission (aOR, 25.7; 95% CI, 9.8-67.3), and lowest risk for stillbirth (aOR, 0.1; 95% CI, 0.04-0.4); women with preeclampsia had the greatest risk for postpartum hypertension (aOR, 9.6; 95% CI, 7.2-12.9). Neonates with GHTN had the greatest risk for ventilator requirements (aOR, 7.5; 95% CI, 4.6-12.4). CONCLUSION Women with gestational hypertension and their neonates had significant risks for morbidity, compared with women with mild chronic hypertension and those with mild preeclampsia.

Neonatal outcomes in twin pregnancies complicated by gestational diabetes compared with non-diabetic twins.

Objective:To compare neonatal outcomes of twin pregnancies with gestational diabetes (GDM) and preexisting diabetes with non-diabetic twin pregnancies.Study Design:US birth data from 2006 to 2009 was used to compare twin pregnancies of 16 562 GDM and 2137 preexisting diabetic with 258 857 non-diabetic twin gestations. Adjusted odds ratios (aORs) were calculated to assess effects of GDM and preexisting diabetes on neonatal outcomes.Result:Twin pregnancies with GDM vs non-diabetic twin pregnancies demonstrated decreased 5-min Apgar scores <4 (aOR 0.8, 95% confidence interval (CI) 0.68–0.94), fewer births before 32 weeks gestation (aOR 0.72, 95% CI 0.68–0.76), decreased birth weight less than the tenth percentile (aOR 0.84, 95% CI 0.81–0.89) and fifth percentile (aOR 0.85, 95% CI 0.81–0.89) and a trend toward lower rates of neonatal death (aOR 0.84, 95% CI 0.68–1.02).Conclusion:Certain adverse outcomes in pregnancies with GDM may be attenuated in twin gestations; however, further investigation is warranted.

Ambulatory arrhythmia monitoring in pregnant patients with palpitations

UNLABELLED OBJECTIVE To assess the frequency of rhythm disturbances (RDs) obtained following placement of a Holter monitor or an event loop recorder (ERT) in patients referred to cardiologists. STUDY DESIGN Ninety-six gravidas were referred to the cardiology clinic for palpitations, syncope, or dizziness and had Holter monitoring or ERT after a baseline electroencephalogram. Arrhythmias were classified by severity. RESULTS Gestational age at referral was 22.6 weeks ± 8.3 days. Sixty-five patients had ERTs performed, and 19 had Holter monitors. Seventy-six percent had benign arrhythmias. In our ERT cohort, history of arrhythmias showed a fourfold increase in serious RD during gestation (odds ratio [OR] 4.7, 95% confidence interval [CI] 1.1 to 20.3, p = 0.01); obesity (body mass index > 30) had a fourfold increased risk (OR 4.0, 95% CI 1.0 to 1, p = 0.03). Serious RD did not result in greater chance of cesarean delivery or induction of labor, or a newborn with arrhythmias. CONCLUSION Most pregnant women with palpitations have benign arrhythmias. ERT appears to be a better method of diagnosis in pregnant women.

Are Adverse Neonate Outcomes in Gestational Diabetes Mellitus Twin Gestations Decreased Compared With Nondiabetic Twins

INTRODUCTION: To compare neonate outcomes of twin pregnancies complicated by gestational diabetes mellitus (GDM) or pregestational diabetes with those of nondiabetic twin pregnancies. METHODS: U.S. birth cohort period linked birth and infant death data 2006–2009 were used to conduct a retrospective cohort study on 5,454 GDM twins diagnosed by standard definitions. They were compared with 60,018 nondiabetic twin gestations. Seven hundred forty-eight pregestational diabetic twins were also compared with nondiabetic twin pregnancies. Exclusions include: eclampsia, lack of prenatal care, suspected aneuploidy, birth weights less than 500 g, and births over 45 weeks of gestation. Neonatal outcomes included: extremes of birth weight, neonatal death, low 5-minute Apgar scores (less than 4), neonatal intensive care unit admission and fetal congenital anomalies. Adjusted odds ratios (ORs) were calculated to assess the effect of GDM on adverse neonatal outcomes when compared with nondiabetic twins while controlling for maternal factors. Data analyses were performed using logistic regression in SAS 9.2. RESULTS: Gestational diabetes mellitus twins compared with nondiabetic twins demonstrated a 50% decrease in neonatal death (adjusted OR 0.54, 95% confidence interval [CI] 0.44–0.69), decreased low 5-minute Apgar scores (adjusted OR 0.63, 95% CI 0.44–0.68), and small-for-gestational age (adjusted OR 0.90, 95% CI 0.85–0.96). Decreases in adverse neonatal outcomes were not demonstrated in pregestational diabetic twins compared with nondiabetic twins. CONCLUSION: Gestational diabetes mellitus in twins may exert a protective effect on important neonatal outcomes suggesting that GDM in twins may be more a compensatory physiologic state; differential management may be indicated for these pregnancies such as mild hyperglycemia or modifying criteria for the diagnosis of GDM in twins.

Elucidating discrepant results in a prenatal diagnosis of 48,XXY,+18 (Edwards and Klinefelter syndromes)

Keywords: Edwards syndrome; Klinefelter syndrome; 48,XXY,+18; 47,XY,+18; mosaicism; non-invasive prenatal testing (NIPT); chorionic villus sampling (CVS)

New Insights in Peripartum Cardiomyopathy

Significant progress in understanding the pathophysiology of peripartum cardiomyopathy, especially hormonal and genetic mechanisms, has been made. Specific criteria should be used for diagnosis, but the disease remains a diagnosis of exclusion. Both long-term and recurrent pregnancy prognoses depend on recovery of cardiac function. Data from large registries and randomized controlled trials of evidence-based therapeutics hold promise for future improved clinical outcomes.

362: The impact of fetal anomalies on contemporary labor patterns

• The most significant trends were observed in the preterm nulliparous and multiparous groups • Labor curves for these groups indicate labor progressed more slowly for patients with pregnancies affected by fetal anomalies (Figures 1,2) • The median traverse times from 4cm to complete dilation • Preterm nulliparous patients • 5.2 hours in the control and 6.6 hours in the anomaly group (p<0.05). • Preterm multiparous • 5.2 hours in the control and 6.2 hours for the anomaly group (p<0.05) • Labor proceeds at a slower rate for patients with pregnancies affected by fetal anomalies in preterm nulliparous and multiparous groups. • This slower rate should be considered while caring for these patients in labor. RESULTS BACKGROUND

Does Induction with Misoprostol Impact the Small for Gestational Age Neonate

OBJECTIVE To compare outcomes in small for gestational age neonates induced with misoprostol to other cervical ripening agents. We hypothesized that misoprostol use will demonstrate no significant difference in outcomes compared with alternative agents. STUDY DESIGN Small for gestational age neonates (<10th percentile for gestational age) from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) sponsored Consortium on Safe Labor database were analyzed. Neonates induced with misoprostol ± oxytocin (n = 451) were compared with neonates induced with prostaglandin E2 ± oxytocin and/or mechanical dilation ± oxytocin (n = 663). Primary outcomes included intrapartum fetal distress, cesarean section for fetal distress, cesarean section for any reason, neonatal intensive care unit admission, low 5-minute Apgar, and composite neonatal morbidity. Multiple logistic regression was used to calculate adjusted odds ratios (aORs). Data were analyzed using SAS. RESULTS Small for gestational age neonates induced with misoprostol ± oxytocin compared with alternative agents had decreased low 5-minute Apgar scores (aOR 0.27 [0.10-0.71]). No significant differences were demonstrated among very small for gestational age neonates (<5th percentile for gestational age). CONCLUSION Our results suggest that misoprostol does not increase risk of adverse outcomes in small for gestational age neonates; however, prospective studies are warranted to further assess optimal cervical ripening agents in this population.