Peter G. Napolitano

Persistent Pulmonary Hypertension of the Newborn Is Associated with Mode of Delivery and Not with Maternal Use of Selective Serotonin Reuptake Inhibitors

We sought to determine if maternal use of selective serotonin reuptake inhibitors (SSRIs) in the second half of pregnancy is associated with persistent pulmonary hypertension of the newborn (PPHN). We performed a case-controlled study (1:6 ratio) of infants delivered at Madigan Army Medical Center with primary PPHN from 2003 through 2009. Study and control patients were compared for the following clinical factors: SSRI use after 20 weeks gestation, mode of delivery, maternal disease, body mass index, tobacco use, fetal gender, maternal age, and parity. We identified 20 cases of primary PPHN out of 11,923 births for an incidence of 0.17%. Mode of delivery was the only factor we found to be associated with PPHN. Specifically, cesarean delivery (CD) prior to the onset of labor increased the risk for PPHN: odds ratio (OR) = 4.9, confidence interval (CI) 1.7 to 14.0. Importantly, use of SSRIs in the second half of pregnancy was identified in 5% of the controls but none of the cases (OR = 0, CI 0 to 3). PPHN is associated with CD prior to the onset of labor but not with SSRI use in the second half of pregnancy. Previous studies linking PPHN to SSRI use relied on after-the-fact patient interviews and incomplete records. Additional studies are needed to verify these results.

On the Front Lines of Patient Safety: Implementation and Evaluation of Team Training in Iraq

BACKGROUND Team training has been identified as a key strategy for reducing medical errors and building a culture of safety in health care. Communication and coordination skills can serve as barriers to potential errors, as in the modern deployed U.S. Military Healthcare System (MHS), which emphasizes rapid movement of critically injured patients to facilities capable of providing definitive care. A team training intervention--TeamSTEPPS--was implemented on a large scale during one of the most intense phases of the conflict in Iraq. This evaluation of the program constituted the first undertaken in a combat theater of operations. IMPLEMENTING TEAMSTEPPS IN IRAQ: The Baghdad combat support hospital (CSH) conducted continuous operations from a fixed facility for a 13-month deployment--between November 2007 and December 2008. The TeamSTEPPS implementation in Iraq began at this facility and spread throughout the combat theater of operations. Teamwork training was implemented in two primary training sessions, followed up with reinforcement of team behaviors on the unit by hospital leadership. RESULTS A total of 153 patient safety reports were submitted during the 13 months reviewed, 94 before TeamSTEPPS implementation and 59 afterwards. After training, there were significant decreases in the rates of communication-related errors, medication and transfusion errors, and needlestick incidents. There was a significant decrease in the rate of incidents coded communication as the primary teamwork skill that could have potentially prevented the event. CONCLUSIONS Process improvement programs such as TeamSTEPPS implementation can be conducted under the extremely austere conditions of a CSH in a combat zone. Teamwork training decreased medical errors in the CSH while deployed in the combat theater in Iraq.

Vitamin D Deficiency in Early Pregnancy

Objective Vitamin D deficiency is a common problem in reproductive-aged women in the United States. The effect of vitamin D deficiency in pregnancy is unknown, but has been associated with adverse pregnancy outcomes. The objective of this study was to analyze the relationship between vitamin D deficiency in the first trimester and subsequent clinical outcomes. Study Design This is a retrospective cohort study. Plasma was collected in the first trimester from 310 nulliparous women with singleton gestations without significant medical problems. Competitive enzymatic vitamin D assays were performed on banked plasma specimens and pregnancy outcomes were collected after delivery. Logistic regression was performed on patients stratified by plasma vitamin D concentration and the following combined clinical outcomes: preeclampsia, preterm delivery, intrauterine growth restriction, gestational diabetes, and spontaneous abortion. Results Vitamin D concentrations were obtained from 235 patients (mean age 24.3 years, range 18-40 years). Seventy percent of our study population was vitamin D insufficient with a serum concentration less than 30 ng/mL (mean serum concentration 27.6 ng/mL, range 13-71.6 ng/mL). Logistic regression was performed adjusting for age, race, body mass index, tobacco use, and time of year. Adverse pregnancy outcomes included preeclampsia, growth restriction, preterm delivery, gestational diabetes, and spontaneous abortion. There was no association between vitamin D deficiency and composite adverse pregnancy outcomes with an adjusted odds ratio of 1.01 (p value 0.738, 95% confidence intervals 0.961-1.057). Conclusion Vitamin D deficiency did not associate with adverse pregnancy outcomes in this study population. However, the high percentage of affected individuals highlights the prevalence of vitamin D deficiency in young, reproductive-aged women.

Insulinoma in pregnancy: a case report and review of the literature.

Insulinomas are rare tumors with an incidence of approximately four cases per million person-years. Nineteen cases of insulinoma during pregnancy have been reported. Hypoglycemic symptoms usually appear during the first trimester. A 28-year-old primigravida was admitted at 6 weeks of gestation after referral for uncontrolled seizures. Her previous seizure work-up included a normal EEG and a normal magnetic resonance imaging of the brain. Elevated fasting insulin and C-peptide levels accompanied severe hypoglycemia. The patient was managed with glucose monitoring, frequent small meals, and rare doses of glucagon. Postpartum testing was consistent with insulinoma, and magnetic resonance imaging indicated a mass in the tail of the pancreas. During surgical exploration with intraoperative ultrasound, two insulinomas were removed from the tail of the pancreas. The hypoglycemic episodes resolved and the fasting glucose levels normalized. Insulinomas are rare in pregnancy and can be difficult to diagnose. Symptoms may resolve during the second and third trimesters, possibly due to changes in glucose metabolism associated with pregnancy. Misdiagnosis has been fatal. Careful management during pregnancy and aggressive treatment after delivery are essential. Target Audience: Obstetricians and Gynecologists, Family Physicians Learning Objectives: After completion of this article, the reader will be able to describe the pathophysiology of an insulinoma, to list the potential tests used to make the diagnosis of insulinoma, and to outline potential treatment options for a patient with an insulinoma.

Nausea, vomiting, and heartburn in pregnancy: a prospective look at risk, treatment, and outcome

Objective: To examine risk factors, treatment, and outcomes for nausea/vomiting (N/V) and heartburn during pregnancy. Methods: We included 2731 women from a prospective cohort study of gallbladder disease in pregnancy. Subjects completed questionnaires at enrollment, early third trimester, and 4–6 weeks postpartum. We used logistic regression to examine independent predictors of upper gastrointestinal symptoms. Results: Ninety-five percent of pregnant women experienced either heartburn and/or N/V. Independent predictors for heartburn included prepregnancy heartburn (OR 5.28, 95% CI 3.78–7.37), multigravidity, prepregnancy body mass index, and pregnancy weight gain. Independent predictors for N/V included prepregnancy N/V (OR 2.25, 95% CI 1.52–3.31), other digestive problems prepregnancy, younger age, single gestation, and carrying a female fetus. 11% of women with N/V and 47% of women with heartburn used pharmacologic therapy. Infants born to women with heartburn had significantly higher birth weights (p = 0.03), but gestational age at delivery was not significantly different. N/V was not associated with birth weight or gestational age at delivery. 19.7% of women with heartburn during pregnancy reported postpartum heartburn. Conclusions: Heartburn and N/V are common pregnancy symptoms, particularly among women with a history of such symptoms. Neither condition appears to adversely affect the outcome of pregnancy. Pregnancy-related heartburn predisposes to early postpartum heartburn.

Fetoplacental vascular tone during fetal circuit acidosis and acidosis with hypoxia in the ex vivo perfused human placental cotyledon

OBJECTIVES Our purpose was to determine the effects of acidosis and acidosis-hypoxia on fetoplacental perfusion pressure and its response to angiotensin II. STUDY DESIGN Perfused cotyledons from 14 placentas were studied with either an acidotic fetal circuit perfusate (n = 7) or an acidotic-hypoxic fetal circuit perfusate (n = 7). Each cotyledons fetal vasculature was initially perfused under standard conditions and bolus injected with 1 x 10(-10) moles of angiotensin II. Fetoplacental perfusate was then replaced with either an acidotic medium (pH 6.90 to 7.00 and Po2 516 to 613 mm Hg) or an acidotic-hypoxic medium (pH 6.90 to 7.00 and Po2 20 to 25 mm Hg) followed by an angiotensin II injection. The vasculature was subsequently recovered with standard perfusate and again injected with angiotensin II. Perfusion pressures within each group were compared by one-way analysis of variance, and results were expressed as mean pressure +/- SEM. RESULTS Resting fetoplacental perfusion pressure did not change when the fetal circuit perfusate was made acidotic (28 +/- 1 mm Hg vs 25 +/- 2 mm Hg) or acidotic-hypoxic (26 +/- 2 mm Hg vs 25 +/- 2 mm Hg). The maximal fetoplacental perfusion pressure achieved in response to angiotensin II did not differ with an acidotic perfusate (41 +/- 2 mm Hg vs 38 +/- 1 mm Hg) or with an acidotic-hypoxic perfusate (39 +/- 2 mm Hg vs 36 +/- 2 mm Hg). CONCLUSIONS In the perfused placental cotyledon fetoplacental perfusion pressure and pressor response to angiotensin II are not affected by fetal circuit acidosis or acidosis-hypoxia. This suggests that neither fetal acidosis nor fetal acidosis combined with hypoxia has a direct effect on fetoplacental vascular tone.

Longitudinal Analysis of Maternal Plasma Apolipoproteins in Pregnancy: A Targeted Proteomics Approach

Minimally invasive diagnostic tests are needed in obstetrics to identify women at risk for complications during delivery. The apolipoproteins fluctuate in complexity and abundance in maternal plasma during pregnancy and could be incorporated into a blood test to evaluate this risk. The objective of this study was to examine the relative plasma concentrations of apolipoproteins and their biochemically modified subtypes (i.e. proteolytically processed, sialylated, cysteinylated, dimerized) over gestational time using a targeted mass spectrometry approach. Relative abundance of modified and unmodified apolipoproteins A-I, A-II, C-I, C-II, and C-III was determined by surface-enhanced laser desorption/ionization-time of flight-mass spectrometry in plasma prospectively collected from 11 gravidas with uncomplicated pregnancies at 4–5 gestational time points per patient. Apolipoproteins were readily identifiable by spectral pattern. Apo C-III2 and Apo C-III1 (doubly and singly sialylated Apo C-III subtypes) increased with gestational age (r2>0.8). Unmodified Apo A-II, Apo C-I, and Apo C-III0 showed no correlation (r2 = 0.01–0.1). Pro-Apo C-II did not increase significantly until third trimester (140 ± 13% of first trimester), but proteolytically cleaved, mature Apo C-II increased in late pregnancy (702 ± 130% of first trimester). Mature Apo C-II represented 6.7 ± 0.9% of total Apo C-II in early gestation and increased to 33 ± 4.5% in third trimester. A label-free, semiquantitative targeted proteomics approach was developed using LTQ-Orbitrap mass spectrometry to confirm the relative quantitative differences observed by surface-enhanced laser desorption/ionization-time of flight-mass spectrometry in Apo C-III and Apo C-II isoforms between first and third trimesters. Targeted apolipoprotein screening was applied to a cohort of term and preterm patients. Modified Apo A-II isoforms were significantly elevated in plasma from mothers who delivered prematurely relative to term controls (p = 0.02). These results support a role for targeted proteomics profiling approaches in monitoring healthy pregnancies and assessing risk of adverse obstetric outcomes.

Fetoplacental vascular tone is modified by magnesium sulfate in the preeclamptic ex vivo human placental cotyledon.

OBJECTIVE The purpose of this study was to evaluate fetoplacental vascular tone and response to a vasoconstrictor in placentas of preeclamptic and normotensive pregnancies with and without the presence of magnesium sulfate. STUDY DESIGN Two cotyledons from each placenta were selected from preeclamptic (n=8) and normotensive (n=7) pregnancies. In one cotyledon from each pair, the maternal circuit was perfused with magnesium sulfate. The fetal arteries were injected sequentially with angiotensin II (10(-10)mol and 10(-11.5) mol). Perfusion pressures and response to angiotensin II were compared, with regard to preeclampsia and exposure to magnesium sulfate. RESULTS Perfusion pressure was higher in preeclamptic placentas, compared with normotensive placentas (30.4 mm Hg vs 24.4 mm Hg, P=.02). There was a decrease in perfusion pressure with exposure to magnesium sulfate in preeclamptic placentas (22.5 mm Hg, P<.01), but not in normotensive placentas. Fetoplacental vascular response to angiotensin II was not affected by preeclampsia or magnesium sulfate. CONCLUSION In placentas from preeclamptic pregnancies there is increased fetoplacental perfusion pressure, which decreases with exposure to sulfate.

Clinical guidelines for occupational lifting in pregnancy: evidence summary and provisional recommendations

Empirically based lifting criteria established by the National Institute for Occupational Safety and Health (NIOSH) to reduce the risk of overexertion injuries in the general US working population were evaluated for application to pregnant workers. This report proposes criteria to guide decisions by medical providers about permissible weights for lifting tasks performed at work over the course of an uncomplicated pregnancy. Our evaluation included an extensive review of the literature linking occupational lifting to maternal and fetal health. Although it has been 29 years since the American Medical Associations Council on Scientific Affairs published its report on the Effects of Pregnancy on Work Performance, these guidelines continue to influence clinical decisions and workplace policies. Provisional clinical guidelines derived from the NIOSH lifting criteria that account for recent evidence for maternal and fetal health are presented and aim to improve the standard of care for pregnant workers.

Effect of Dexamethasone Administered With Magnesium Sulfate on Inflammation-Mediated Degradation of the Blood–Brain Barrier Using an In Vitro Model

Patients at risk for preterm delivery are frequently administered both antenatal steroids for fetal maturation and magnesium sulfate for neuroprotection. In this study, we investigate whether steroids coadministered with magnesium sulfate preserve blood–brain barrier integrity in neuroinflammation. Human umbilical vein endothelial cells were grown in astroglial conditioned media in a 2-chamber cell culture apparatus. Treatment with tumor necrosis factor-α (TNF-α) or catalytically active recombinant matrix metalloproteinase 9 (MMP-9) simulated neuroinflammation. Membrane integrity was assessed by zona occludens 1 (ZO-1) immunoreactivity, permeability to fluorescently conjugated dextran, and transendothelial electrical resistance (TEER). The TNF-α and MMP-9 treatment increased the rate of dextran transit, decreased TEER, and decreased ZO-1 immunoreactivity at junctional interfaces. Dexamethasone pretreatment alone or in combination with 0.5 mmol/L magnesium sulfate preserved monolayer integrity after inflammatory insult. Magnesium sulfate alone was not protective. This study supports a possible interaction between steroids and magnesium in neuroprotection.