Gabriella Pridjian

Exposure to Hurricane Katrina, Post-Traumatic Stress Disorder and Birth Outcomes

Background:Little is known about the effects of natural disasters on pregnancy outcomes. We studied mental health and birth outcomes among women exposed to Hurricane Katrina. Methods:We collected data prospectively from a cohort of 301 women from New Orleans and Baton Rouge. Pregnant women were interviewed during pregnancy about their experiences during the hurricane, and whether they had experienced symptoms of post-traumatic stress disorder (PTSD) and/or depression. High hurricane exposure was defined as having 3 or more of the 8 severe hurricane experiences, such as feeling that ones life was in danger, walking through floodwaters, or having a loved one die. Results:The frequency of low birth weight was higher in women with high hurricane exposure (14.0%) than women without high hurricane exposure (4.7%), with an adjusted odds ratio (aOR): 3.3; 95% confidence interval (CI): 1.13–9.89; P < 0.01. The frequency of preterm birth was higher in women with high hurricane exposure (14.0%) than women without high hurricane exposure (6.3%), with aOR: 2.3; 95% CI: 0.82–6.38; P > 0.05. There were no significant differences in the frequency of low birth weight or preterm birth between women with PTSD or depression and women without PTSD or depression (P > 0.05). Conclusions:Women who had high hurricane exposure were at an increased risk of having low birth weight infants. Rather than a general exposure to disaster, exposure to specific severe disaster events and the intensity of the disaster experience may be better predictors of poor pregnancy outcomes. To prevent poor pregnancy outcomes during and after disasters, future disaster preparedness may need to include the planning of earlier evacuation of pregnant women to minimize their exposure to severe disaster events.

Phenylketonuria Scientific Review Conference: State of the science and future research needs

New developments in the treatment and management of phenylketonuria (PKU) as well as advances in molecular testing have emerged since the National Institutes of Health 2000 PKU Consensus Statement was released. An NIH State-of-the-Science Conference was convened in 2012 to address new findings, particularly the use of the medication sapropterin to treat some individuals with PKU, and to develop a research agenda. Prior to the 2012 conference, five working groups of experts and public members met over a 1-year period. The working groups addressed the following: long-term outcomes and management across the lifespan; PKU and pregnancy; diet control and management; pharmacologic interventions; and molecular testing, new technologies, and epidemiologic considerations. In a parallel and independent activity, an Evidence-based Practice Center supported by the Agency for Healthcare Research and Quality conducted a systematic review of adjuvant treatments for PKU; its conclusions were presented at the conference. The conference included the findings of the working groups, panel discussions from industry and international perspectives, and presentations on topics such as emerging treatments for PKU, transitioning to adult care, and the U.S. Food and Drug Administration regulatory perspective. Over 85 experts participated in the conference through information gathering and/or as presenters during the conference, and they reached several important conclusions. The most serious neurological impairments in PKU are preventable with current dietary treatment approaches. However, a variety of more subtle physical, cognitive, and behavioral consequences of even well-controlled PKU are now recognized. The best outcomes in maternal PKU occur when blood phenylalanine (Phe) concentrations are maintained between 120 and 360 μmol/L before and during pregnancy. The dietary management treatment goal for individuals with PKU is a blood Phe concentration between 120 and 360 μmol/L. The use of genotype information in the newborn period may yield valuable insights about the severity of the condition for infants diagnosed before maximal Phe levels are achieved. While emerging and established genotype-phenotype correlations may transform our understanding of PKU, establishing correlations with intellectual outcomes is more challenging. Regarding the use of sapropterin in PKU, there are significant gaps in predicting response to treatment; at least half of those with PKU will have either minimal or no response. A coordinated approach to PKU treatment improves long-term outcomes for those with PKU and facilitates the conduct of research to improve diagnosis and treatment. New drugs that are safe, efficacious, and impact a larger proportion of individuals with PKU are needed. However, it is imperative that treatment guidelines and the decision processes for determining access to treatments be tied to a solid evidence base with rigorous standards for robust and consistent data collection. The process that preceded the PKU State-of-the-Science Conference, the conference itself, and the identification of a research agenda have facilitated the development of clinical practice guidelines by professional organizations and serve as a model for other inborn errors of metabolism.

Predisposition to atypical teratoid/rhabdoid tumor due to an inherited INI1 mutation.

Germline mutations of the INI1 gene predispose children to the development of rhabdoid tumors. Reports of familial cases, however, are extremely rare.

Left ventricular mechanics in preeclampsia.

Increased systemic vascular resistance and contracted blood volume are characteristic findings in preeclampsia. These alterations in cardiovascular hemodynamics can adversely affect ejection phase indices of left ventricular performance making it difficult to separate abnormalities resulting from changes in load from those caused by depressed myocardial contractility. To address this issue the contractility-sensitive, load-independent relationship between left ventricular end-systolic wall stress and rate-corrected velocity of fiber shortening was assessed in 10 nulliparous patients with preeclampsia. Comparisons were made with data obtained from 10 age-matched normotensive women with uncomplicated pregnancies (control subjects). Studies were performed by means of two-dimensionally targeted M-mode echocardiography and calibrated carotid pulse tracings during early labor, 1 day after delivery, and 4 weeks after delivery. During early labor and 1 day after delivery, patients with preeclampsia had elevated blood pressure and increased total systemic resistance. These parameters returned to normal by 4 weeks after delivery. Before delivery and 24 hours after delivery, the patients with preeclampsia had lower overall left ventricular performance (as measured by cardiac output and rate-corrected velocity of fiber shortening) and higher left ventricular afterload (as measured by left ventricular end-systolic wall stress) when compared with control subjects. These differences were no longer present 4 weeks after delivery. Despite the time-related intergroup differences in hemodynamics, left ventricular contractility was similar between normotensive and preeclamptic subjects at all stages of the study. Thus when load is eliminated as a confounding variable, the decrements in overall left ventricular performance measured in patients with preeclampsia reflect a mechanically appropriate response to increased afterload rather than an abnormality in the ventricular contractile state.

Involvement of Marinobufagenin in a Rat Model of Human Preeclampsia

Background: Preeclampsia is a potentially devastating disorder of hypertension in pregnancy for which there is currently no definitive treatment short of delivery. The bufadienolide, marinobufagenin (MBG), an inhibitor of Na+/K+ ATPase, has been found to be elevated in extracellular fluid volume-expanded hypertensive patients, a condition similar to preeclampsia. Thus, these studies sought to examine the role of MBG in our rat model of preeclampsia. Methods and Results: Pregnant female rats were injected intraperitoneally with deoxycorticosterone acetate (DOCA) and given 0.9% saline as drinking water for the duration of their pregnancy. Urinary MBG was measured using a DELFIA immunoassay. Blood pressure was measured via the tail-cuff method. Injections of anti-MBG antibody were given intraperitoneally or intravenously to hypertensive pregnant rats. MBG was given intraperitoneally to pregnant rats. Uterine arterioles were dissected free and their diameters were measured before and after perfusion of MBG, ouabain, or digoxin. MBG was found to be elevated in the pregnant + DOCA + saline (PDS) rats compared to normal pregnant animals. In addition, when PDS rats were injected with anti-MBG antibody, there was a subsequent reduction in blood pressure. Administration of MBG in normal pregnant rats caused an elevation in blood pressure equivalent to the PDS model. Also, uterine vessel measurements showed an increased vasoconstrictive reactivity to MBG in the PDS animals vs. the normal pregnant controls; while no changes were observed with perfusion of digoxin or ouabain at the same concentration. Conclusion: These results suggest a relationship between MBG and a syndrome in rats resembling preeclampsia. Armed with these promising results, it would seem logical to further examine the role of MBG in human preeclampsia.

PERIODONTAL DISEASE IS ASSOCIATED WITH GESTATIONAL DIABETES MELLITUS: A CASE-CONTROL STUDY

BACKGROUND Few studies have specifically examined the relationship between periodontal disease and gestational diabetes mellitus (GDM). The objective of this study was to examine whether maternal periodontal disease is associated with GDM. METHODS A case-control study was conducted of 53 pregnant women with GDM and 106 pregnant women without GDM at Womans Hospital, Baton Rouge, Louisiana. The periodontal examinations were performed by a calibrated dentist who was masked to the diabetic status of the pregnant women. Periodontitis was defined as the presence of any site with a probing depth (PD) >or=4 mm or a clinical attachment loss (AL) >or=4 mm. The severity of periodontal disease was measured in quartiles of PD and clinical AL. Univariable analysis and multivariable logistic regression were used to examine the relationships between periodontal disease and GDM. RESULTS The percentage of periodontitis was 77.4% in women with GDM and 57.5% in women without GDM, with an odds ratio (OR) of 2.5 and a 95% confidence interval (CI) of 1.2 to 5.3. After adjusting for confounding variables of maternal age, parity, race, marital status, education, family income, smoking, alcohol consumption, systemic antibiotics during pregnancy, family history of diabetes, income, dental insurance coverage, and body mass index, the adjusted OR (95% CI) was 2.6 (1.1 to 6.1). The adjusted ORs (95% CIs) of GDM comparing the highest-to-lowest quartiles of PD and clinical AL were 3.8 (1.0 to 14.0) and 4.5 (1.2 to 16.9). CONCLUSION This study supports the hypothesis of an association between periodontal disease and GDM.

Postpartum mental health after Hurricane Katrina: A cohort study

BackgroundNatural disaster is often a cause of psychopathology, and women are vulnerable to post-traumatic stress disorder (PTSD) and depression. Depression is also common after a woman gives birth. However, no research has addressed postpartum womens mental health after natural disaster.MethodsInterviews were conducted in 2006–2007 with women who had been pregnant during or shortly after Hurricane Katrina. 292 New Orleans and Baton Rouge women were interviewed at delivery and 2 months postpartum. Depression was assessed using the Edinburgh Depression Scale and PTSD using the Post-Traumatic Stress Checklist. Women were asked about their experience of the hurricane with questions addressing threat, illness, loss, and damage. Chi-square tests and log-binomial/Poisson models were used to calculate associations and relative risks (RR).ResultsBlack women and women with less education were more likely to have had a serious experience of the hurricane. 18% of the sample met the criteria for depression and 13% for PTSD at two months postpartum. Feeling that ones life was in danger was associated with depression and PTSD, as were injury to a family member and severe impact on property. Overall, two or more severe experiences of the storm was associated with an increased risk for both depression (relative risk (RR) 1.77, 95% confidence interval (CI) 1.08–2.89) and PTSD (RR 3.68, 95% CI 1.80–7.52).ConclusionPostpartum women who experience natural disaster severely are at increased risk for mental health problems, but overall rates of depression and PTSD do not seem to be higher than in studies of the general population.

A rat model of preeclampsia.

Preeclampsia/eclampsia is a disorder of human pregnancy that continues to exact significant maternal morbidity and mortality and fetal wastage. Therapy of these disorders has not changed in over 50 years and there are no proven preventive measures. We describe a model of the development of a syndrome in the pregnant rat that resembles preeclampsia, which results from the imposition of excessive volume expansion early in gestation. We administered desoxycorticosterone acetate (DOCA) to pregnant animals whose drinking water had been replaced with saline. We compared the results obtained in these animals with those resulting from the study of control, virgin animals, virgin animals receiving DOCA and saline, and normal pregnant (NP) animals. The virgin animals given DOCA and saline did not become hypertensive. The experimental paradigm in the DOCA plus saline pregnant (PDS) animals provides many of the phenotypic characteristics of the human disorder including the development of hypertension, proteinuria, and intrauterine growth restriction. In addition, the mean blood nitrite/nitrate concentration was reduced in the PDS rats compared with their NP counterparts. We propose that this model may prove to be useful in the study of the human condition.

Labor After Prior Cesarean Section

1. All women with PCS should be considered candidates for vaginal delivery. Certain high-risk factors then should be used to recommend elective repeat cesarean section. Currently, a scar in the active segment of the uterus is considered an absolute contraindication to labor. 2. Women should be informed of the chances of success (which in most instances are excellent), course of action in labor, and the rare risk of uterine rupture. 3. Women in a very low risk category (one low-transverse PCS) should be managed like any laboring patient but including fetal monitoring. 4. The remaining laboring patients may benefit from more intensive intrapartum surveillance, including continuous electronic fetal monitoring, early rupture of the fetal membranes, and placement of an intrauterine pressure catheter. 5. The labor course in women with PCS will depend on the number of vaginal deliveries achieved previously and the stage of labor reached before the cesarean section was done. 6. Labor disorders in patients with PCS, as in all patients, should be diagnosed and managed promptly. 7. Neither oxytocin nor epidural use is contraindicated in these patients. As in any patient, care should be taken to avoid iatrogenic uterine hyperstimulation. 8. Uterine rupture may have many different presentations. However, the most common is abnormal fetal heart rate patterns that are especially variable or prolonged decelerations. 9. Most uterine ruptures can be repaired and do not require hysterectomy. Hysterectomy may be the appropriate choice in some situations. 10. A history of a prior uterine rupture is not a contraindication to future childbearing, but it may place the woman at greater risk for a repeat event.

Racial differences in cesareans: an analysis of U.S. 2001 National Inpatient Sample Data.

OBJECTIVE: To evaluate racial differences in potentially unnecessary cesareans in the United States. METHODS: The 2001 Healthcare Cost and Utilization Project Nationwide Inpatient Sample database was used to analyze various maternal demographic and clinical parameters among women having cesarean deliveries. For the purpose of our study, if there were no diagnoses related to cesarean delivery on the discharge certificate, the cesarean was classified as potentially unnecessary RESULTS: Using our methodology, 11% of 540,174 primary and 65% of 371,863 repeat cesareans for the year 2001 in the United States were classified as potentially unnecessary. After controlling for age, payment source, ZIP income, admission day, region of the country, and hospital size, location, and teaching status, black women had a higher likelihood of having potentially unnecessary primary cesareans when compared with white (P < .001) or Hispanic women (P < .001). White women had a higher likelihood of having potentially unnecessary repeat cesareans than black women (P < .001), although the magnitude of the odds ratio for race was not as striking as in primary cesarean. Potentially unnecessary primary cesareans were also more likely to occur in women aged 35 years or older, Medicare patients, weekend admissions, or those residing in the South or Northeast. Potentially unnecessary repeat cesareans were more likely to occur in women younger than 35 years, in rural hospitals, and in weekday admissions. CONCLUSION: In the United States, racial differences exist in the proportion of cesarean deliveries that are potentially unnecessary. Further exploration of these differences is warranted. LEVEL OF EVIDENCE: III