Perspectives on Women’s, Infants’ and Children’s Health: A Research Review

Summer 2014

Perspectives on Women’s, Infants’ and Children’s Health: A Research Review

Women’s, Infants’ and Children’s Health at Christiana Care

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Table of Contents

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Welcome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

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Born Too Soon . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 Fetal Adrenal Gland Study Explores New Marker for Prematurity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 Global Focus Increasing the Survival Rate of Preterm Babies in Developing Nations . . . . . . . . . . . . . . . . . . . . . . . . . . 8 Global Focus Lowering Preterm Births in Developing Nations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10

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Improving Infants’ and Children’s Health . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 Researchers Explore Correlations Between Maternal Obesity and Child Health . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 Comprehensive Program Provides Consistency in Diagnosis and Treatment of NAS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14 New NICU Procedures Decrease Pneumothorax in VLBW Infants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 39 Weeks. Is It Really the Magic Number? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16 Genetics Studies Show the Promise of Testing Maternal Plasma DNA . . . . . . . . . . . . . . . . . . . . . . . . . . 18 New Tools Arrive in the Fight Against Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20 MRI Measures at Birth May Identify Infants at Risk for Delayed Motor Performance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21 Christiana Care Team Helps Advance Uniformity of States’ Birth Defect Reporting . . . . . . . . . . . . . . 22 Current Trials Fetal ECG Shows Promise as Early Warning Sign for Hypoxia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23

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Focusing on Women’s Health . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24 Global Focus Misoprostol Provides Better Solution in Preventing Postpartum Hemorrhage . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24 Obstetrician-Gynecologists Play Role in Cardiovascular Disease Prevention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26

Table of Contents

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Transition to Robotic Hysterectomy Can Lead to Higher Costs and Injuries, Study Suggests . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27 Christiana Care Contributes to Landmark Breast Cancer Study . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28 Loop Electrode Resection Outperforms New MyoSure® Morcellation Device for Lesion Removal . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29 Conventional Laparoscopy Produces Less Postoperative Pain than Robotically-Assisted Procedures, Study Indicates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30 Does Seprafilm® Prevent Intra-Abdominal Adhesions? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31 Peripartum Transfusion Study Identifies Anemia as Treatable Risk Factor . . . . . . . . . . . . . . . . . . . . . . 32 Bed Rest and Gestational Diabetes: More Reasons to Get Out of Bed in the Morning . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33 Foley Catheter Placement Can Affect Induction Outcomes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34 Resolved Placenta Previa Affects Pregnancy Outcomes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35

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Clinical Research Team . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36 Publications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37

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Welcome to the inaugural edition of the Christiana Care Health System Perspectives on Women’s, Infants’ and Children’s Health:

A Research Review.

For generations, Christiana Care Health System has served as an expert, compassionate partner to women, their children and their families. We provide obstetrical care to 85 percent of new mothers in the region, delivering more than 6,000 babies each year. We are the only highrisk delivering hospital in Delaware offering Level III neonatal intensive care. Our clinical services include a full range of gynecological care, including urogynecology and gynecologic oncology. We have been recognized as a Center of Excellence in Minimally Invasive Surgery.

To learn more about ongoing Women’s, Infants’ and Children’s Health research at Christiana Care Visit www.christianacare.org/ObGynResearch Women’s Research Department Christiana Hospital, Room 2905 4755 Ogletown-Stanton Road, Newark, DE 19718 302-733-3576

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Christiana Care is designated as the region’s only National Community Center of Excellence in Women’s Health by the U.S. Department of Health and Human Services.

We are committed to improving outcomes for mothers and their babies and are actively engaged in clinical and health services research, with an emphasis on maternal and child health. Our focus areas include prevention of preterm birth, medical and behavioral approaches to improving health outcomes for women and babies and understanding the causes of child development disorders. In addition, we are involved in community-engaged research, with a focus on health disparities. This and other collaborative work across Delaware and local institutions will be accelerated through the Delaware Center for Translational Research, which is supported by a $25 million grant from the National Institutes of Health (NIH).

Our patient population is a microcosm of the population of the United States. We typically provide data and track outcomes on both mother and child, which enables researchers to initiate

Welcome

David A. Paul, M.D., Chair of Pediatrics, and Richard J. Derman, M.D., MPH, FACOG, the Marie E. Pinizzotto, M.D., Endowed Chair of Obstetrics and Gynecology

their work at Christiana Care, often as a pilot, before expanding to other programs within the region and across the nation. The quality of our data has ensured that we are often called upon to contribute to studies supported by the NIH and other federal agencies.

We work closely with Nemours/Alfred I. duPont Hospital for Children, Thomas Jefferson University Hospitals and the University of Delaware on research collaborations. In addition, we support the work of the Delaware Health Sciences Alliance, which funds clinical studies and pilot studies such as Christiana Care’s work in studying determinants of childhood obesity.

Active involvement in research helps to answer compelling questions and supports evidence-based practices. Reduced rates of preterm births translate into reduced NICU admissions, healthier children and stronger families. In tandem with Christiana Care’s nationally recognized Value Institute, results from our efficacy and effectiveness trials conducted with women and children help inform our stated goal of a healthier community.

While our focus is primarily tied to the Delaware Valley, Christiana Care researchers are involved in studies around the globe. For example, our international partners recruited nearly one-third of the participants in clinical trials for the use of Misoprostol, a medicine that has proven to be lifesaving in the prevention of postpartum hemorrhage, which is the leading killer of women worldwide. These trials directly resulted in Misoprostol being listed as an essential medicine by the World Health Organization in the fight against postpartum hemorrhage. We continue to explore the appropriate use of the drug in both the United States and in developing nations.

Finally, we work with the most dedicated physicians, nurses and staff, who not only provide the best clinical care, but are also dedicated to going a step beyond, to explore and discover better methods of care and treatment that lead to better outcomes. The result of their commitment is reflected in the increased value and quality care that we provide to our neighbors.

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Overview

educing Preterm Births and Mortality R Rates of Babies Born Too Soon Being born too soon can set the stage for a lifetime of serious health consequences and developmental challenges for many children around the world.

Preterm babies are not only more likely to die in the first 30 days after being born, but are much more likely to suffer chronic medical conditions and learning difficulties when compared to infants born at full-term. Even small disparities at the time of birth can result in important differences in IQ and development.

It is for these reasons that researchers at Christiana Care have worked to understand the mechanisms of preterm birth, design strategies to prevent its

occurrence and develop better ways to care for those babies who are born prematurely. This work, which is often done with collaborators such as the World Health Organization (WHO), National Institutes of Health (NIH) and other private foundations and academic partners (Columbia University, University of Delaware), holds the potential to affect the rates and impact of preterm birth locally, nationally and internationally.

Researchers at Christiana Care, one of the largest delivering maternity hospitals in the Northeast, are uniquely positioned to contribute to the research of preterm birth and pilot efforts to improve care for some of the most vulnerable children.

Fetal Adrenal Gland Study Explores New Marker for Prematurity Preterm Birth Rates in the U.S.

Despite several promising treatment strategies to prevent preterm birth (administrating exogenous progesterone and/or providing cervical support through cerclage), the rate of preterm births in the U.S. remains at more than 11.5 percent. This is in large part due to our limited ability to accurately identify women at high risk for preterm birth. This has led researchers at Christiana Care to examine new biomarkers for preterm birth.

13.0% 12.5% 12.0% 11.5% 11.0% 10.5% 2003

2004 2005 2006 2007 2008 2009 2010 2011 2012

Source: National Vital Statistics Report, http://www.cdc.gov/nchs/data/ nvsr/nvsr62/nvsr62_09.pdf#table01

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As the primary cause of perinatal mortality, preterm birth remains the critical challenge in obstetrics, driving the rate of neonatal death and disability.

In a trial led by Matthew K. Hoffman, M.D., MPH, FACOG, Vice Chairman of Christiana Care’s

Estriol and estetrol Fetal pituitary gland

Maternal DHEAS

Estrone and estradiol

The Role of the Fetal Adrenal Gland

Placenta CRH

+

ACTH

Late gestation fetal cortisol

160H-DHEAS and 15,160H-DHEAS

DHEAS Fetal liver

Fetal adrenal glands

DHEAS

Activation of hypothalamic-pituitary-adrenal axis and endocrine signaling between the placenta and the fetal adrenal gland play an important role in initiation of labor. The biochemical activation of the fetal adrenal gland is associated with a significant enlargement of the total gland—in particular, the fetal zone.

Two published studies using different measurement techniques by Turan et al. demonstrate high sensitivity and specificity for spontaneous preterm birth among symptomatic women (N=126 & 74).

Born Too Soon

Global Focus

Do Fetuses Trigger Their Own Births?

Early studies indicate that the fetal adrenal gland plays an important role in both term and preterm spontaneous birth. Fetal adrenal glands contain a “fetal zone” that seems to grow prior to spontaneous birth. Christiana Care researchers are studying whether the growth of the fetal adrenal gland can be used as an indicator of pending preterm birth.

Department of Obstetrics and Gynecology and the Division of Education and Research, researchers at eight centers are examining whether ultrasound measurement of the fetal adrenal gland can accurately predict preterm birth.

This study, which is being conducted at sites including Columbia University, the University of Pennsylvania, Northwestern University and others, will perform a single measurement of the fetal adrenal gland at approximately 28 weeks in about 2,000 women. The study is sponsored by the NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD).

It has long been known that the fetal adrenal gland plays an important part in the birth process. Studies done in the 1950s found that the fetal adrenal gland was significantly larger in babies who went into spontaneous labor, whether preterm or term. Two recent studies have suggested that sonographic measurement of the gland early in the third trimester may very accurately predict spontaneous preterm birth.

“If confirmed, this study will help demonstrate that, in fact, the baby sends a key signal to begin its own birth process,” stated Dr. Hoffman.

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Global Focus

Increasing the Survival Rate of Preterm Babies in Developing Nations Previous research has demonstrated that administering antenatal corticosteroids (betamethasone and dexamethasone) to women at high risk of preterm birth is the single most effective intervention to reduce neonatal mortality.

Corticosteroids given to mothers prior to delivery cause the fetus to speed the production of surfactant, which is often deficient in the lungs of preterm infants. Antenatal corticosteroids have been shown to reduce the incidence of Respiratory Distress Syndrome (RDS) by 34 percent, intraventricular hemorrhage (bleeding in the brain associated with preterm birth) by 46 percent and neonatal mortality by 31 percent.

In developing nations, where access to advanced health care facilities is limited, only about 10

percent of eligible women actually receive this lifesaving and inexpensive medication. Richard J. Derman, M.D., MPH, FACOG, the Marie E. Pinizzotto, M.D., Endowed Chair of Obstetrics and Gynecology, serves as a principal investigator of the National Institutes of Health-funded Global Research Network for Women’s and Children’s Health. In this capacity, he is collaborating with his partners at Jawaharlal Nehru Medical College in Belgaum, India, led by B.S. Kodkany, M.D., and Shivaprasad S. Goudar, M.D., MHPE, on a trial to determine the effectiveness of the drug in developing countries and, if the results are positive, to break down the barriers preventing the widespread use of antenatal corticosteroids in developing nations such as Guatemala, India, Kenya, Zambia and Pakistan.

Neonatal Mortality Rates in Study Countries and U.S. in 2011 (Number of Deaths/1,000 Births)

40 35 30 25 20 15 10 5 0 Argentina Guatemala 8

India

Kenya

Pakistan

Zambia United States

Source: World Health Organization www.who.int/ gho/publications/world_health_ statistics/EN_WHS2013_Full.pdf

Evidence suggests that the low use of corticosteroids in developing nations is directly linked to the availability of the drug and lack of access to the appropriate level of care. In many cases, women either deliver their babies at home or in community health facilities. In both situations, birth attendants are likely to be present, but typically lack the training to identify women at risk of preterm birth and the authority to administer corticosteroids.

To offset these factors, study investigators are trialing a strategy of training birth attendants to identify women at risk of preterm birth and empowering them to administer corticosteroids using a novel injection system. To ensure that patients are appropriate candidates, birth attendants are provided with a color-coded tape to measure uterine height to ensure the fetus is at an appropriate gestational age. In addition, the attendants receive kits with vials of corticosteroids loaded in easy-to-administer, reuse-prevention syringes.

More than 60,000 women from six developing nations are being recruited to help test the intervention. Neonatal mortality at 28 days is being measured for all low-birth-weight infants (a

Measuring the Intervention’s Effectiveness: Study Outcomes Outcome PRIMARY measures in Neonatal mortality at 28 days. infants with SECONDARY birth weight Maternal infection from birth up to 7 and 42 days below 10th postpartum. percentile and their mothers Perinatal mortality rate (stillbirths ≼ 20 weeks GA or ≼ 500 g + neonatal deaths before 7 days).

Born Too Soon

Factors and Causes of Underuse

Early neonatal mortality rate at 7 days after birth.

Mean neonatal weight at 7 and 28 days.

Neonatal and perinatal mortality rates by country.

Neonatal and perinatal mortality rates by type of setting (health facility-based deliveries vs. community-based deliveries).

Infant mortality rate at 42 days after birth.

proxy for preterm birth) and compared between clusters (areas) wherein steroids have been made available and those clusters where they have not been. This 18-month study is expected to be completed in 2014. If successful, this strategy can serve as a model to ensuring that women get this lifesaving medication in low-resource settings.

Study investigators are trialing a strategy of training birth attendants to identify women at risk of preterm birth and empowering them to administer corticosteroids using a novel injection system.

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Global Focus

Lowering Preterm Births in Developing Nations More than 15 million babies are born prematurely worldwide each year, resulting in more than 1 million deaths. The majority of the deaths occur in developing nations that lack the resources to care for these newborns.

A joint research team led by Matthew K. Hoffman, M.D., MPH, FACOG, Vice Chairman, Christiana Care Department of Obstetrics and Gynecology and Division of Education and Research, and Mrutyunjaya B. Bellad, M.D., with the Jawaharlal Nehru Medical College (JNMC) in Belgaum, India, is examining a strategy of identifying and treating a common vaginal infection that may be responsible for many cases of preterm birth and treating it early in

Estimated distribution of causes of 3.1 million neonatal deaths in 193 countries in 2010

Preterm birth is a DIRECT cause of 35 percent of all neonatal deaths

The group of women receiving clindamycin recorded a 62 percent lower incidence of spontaneous preterm labor than the placebo group.

Preterm birth is a risk factor for neonatal and postneonatal deaths. At least 50 percent of all neonatal deaths are preterm.

Preterm birth complications 1.08 million

Intrapartumrelated 0.72 million

Neonatal Infection 0.83 million Other neonatal conditions 181,000

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pregnancy with antibiotics. Working with JNMC as a research partner, Dr. Hoffman and Richard J. Derman, M.D., MPH, FACOG, the Marie E. Pinizzotto, M.D., Endowed Chair of Obstetrics and Gynecology, are testing whether an inexpensive vaginal pH screening test and five-day oral treatment regimen of clindamycin (300 mg) given early in pregnancy will reduce previously untreated maternal genital tract infections that cause preterm deliveries.

Congenital abnormalities 270,000

Source: Updated from Lawn et al., 2005, using data from 2010 published in Liu L, et al., 2012. Born Too Soon: The global epidemiology of 15 million preterm births. 2013 Blencowe et al; BioMed Central Ltd.

INDIRECT Moderate and late preterm births increase the chance of dying from infections

Born Too Soon

Matthew K. Hoffman, M.D., MPH, FACOG, Vice Chairman, Christiana Care Department of Obstetrics and Gynecology and Division of Education and Research (blue shirt in middle of front row) during a site initiation visit at a public health center in rural southwest India.

The treatment has already shown impressive results in a small, hospital-based, double-blind, placebo-controlled trial in Belgaum, India. That trial was ended early after the group of women receiving clindamycin recorded a 62 percent lower incidence of spontaneous preterm labor than the placebo group (www.clinicaltrials.gov; REF/2011/07/0025276).

Based on the success of this pilot trial conducted by the JNMC collaborators, this group of researchers has begun a three-year, double-blind, placebo-controlled study of more than 1,736 pregnant women. Researchers hope that the study, which will be completed in 2015, will demonstrate

that clindamycin given orally will prevent at least 30 percent of preterm births in women with this type of vaginal infection. The treatment has the potential to be an effective, affordable solution in community-based, developing country settings where maternal and neonatal care resources are limited.

“If this study demonstrates that this strategy works, the resulting impact could potentially echo across both the developed and developing world,” Dr. Hoffman said. “We would be able to prevent preterm birth for less than $3 per case — a fraction of what it costs to care for these children after they are born prematurely.”

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Overview

Improving Infants’ and Children’s Health

Christiana Care has developed a national reputation for the quality of its studies.

Committed to improving outcomes for mothers and their babies, we are actively engaged in clinical and health services research, with a focus on maternal and child health. This work differentiates our health system and ultimately leads to improved patient care.

Researchers Explore Correlations Between Maternal Obesity and Child Health With obesity a growing concern in the U.S. — for both adults and children — Christiana Care researchers are exploring correlations between maternal obesity (and other maternal factors) and children’s health issues, including premature birth and childhood body mass index (BMI).

A recent Christiana Care study explored the interaction of pre-pregnancy maternal obesity, race, ethnicity and preterm births.

Chair, Department of Pediatrics; and Robert Locke, D.O., MPH, Director of Neonatal Research, partnered with Beatriz de Jongh, senior fellow in Neonatal-Perinatal Medicine, on a study that included 11,711 Christiana Care births between January 2009 and December 2010. The highest rate of prematurity was found in the Black/nonHispanic births (13.5 percent), as was the highest rate of obesity (34 percent). Among Hispanics, Asians and White/non-Hispanics, obesity was associated with a higher risk of preterm birth.

However, there was no such correlation among Black/non-Hispanic births.

Matthew K. Hoffman, M.D., MPH, FACOG, Vice Chairman, Christiana Care Department of Obstetrics and Gynecology and Division of Education and Research; David A. Paul, M.D.,

A variety of programs, including antenatal and prenatal dietary and lifestyle interventions, have been created to address the presumed health risks to obese mothers and their babies. This

Racial and Ethnic Differences in the Effect of Maternal Obesity on Preterm Birth

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study shows that the goals and methods of such programs may need to be stratified by race and ethnicity. The results suggest that factors other than obesity are responsible for the high rate of premature births in Black/non-Hispanic women.

Pre-Pregnancy Maternal Factors Implicated in Childhood Obesity A second study examined the contribution of maternal prenatal risk factors — including gestational weight gain, gestational diabetes mellitus (GDM), gestational hypertension and prenatal tobacco use — to the subsequent risk of obesity in young children.

The study, published in Obstetrics & Gynecology in January 2013 (Ehrenthal et al, 2013; 121:115-121), was led by Deborah B. Ehrenthal, M.D., FACP, then a Director of Health Services Research for Women and Children and Medical Director of Women’s Health Programs in the Department of Obstetrics and Gynecology at Christiana Care.

Dr. Ehrenthal collaborated with additional Christiana Care researchers and with others from Delaware’s Nemours/Alfred I. duPont Hospital for Children, Philadelphia’s Thomas Jefferson

University, the Johns Hopkins Bloomberg School of Public Health and the University of Delaware.

The study sample of 3,302 children and their mothers was obtained through linkage of medical records from Christiana Care births to wellchild visits at private practices associated with Nemours. The availability of this data afforded the opportunity to investigate the effect of maternal health for a diverse sample of mothers and children.

Improving Infants’ and Children’s Health

Dietary and lifestyle interventions created to address health risks to obese mothers and their babies may need to be stratified by race and ethnicity.

The study results indicate that risk factors present before pregnancy make a greater contribution to the child’s risk for obesity than those limited to the prenatal period.

“There has been some evidence that if moms gain too much weight during pregnancy or have GDM, that something happens in the intrauterine environment that makes their kids more susceptible to obesity,” said Dr. Ehrenthal.

“But our data suggest that mom’s risk factors even before she was pregnant have a greater impact. This suggests adherence to gestational weight guidelines may not have the impact we had hoped.”

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Comprehensive Program Provides Consistency in Diagnosis and Treatment of NAS Christiana Care is at the leading edge of screening and treatment for neonatal abstinence syndrome (NAS), which can occur in newborns exposed to opioids such as methadone and oxycodone during gestation.

Led by Louis E. Bartoshesky, M.D., MPH, geneticist and former Chair of the Department of Pediatrics, the health system has developed a multidisciplinary, multi-agency approach to screening mothers and newborns, weaning infants in the hospital and after discharge and following up at regular intervals.

“A couple of years ago, we noticed that we were seeing a lot of kids — a hundred a year or more — with NAS,” Dr. Bartoshesky said.

4.0 3.5 Rate of NAS per 1000 Hospital Births

He and his colleagues informally surveyed Christiana Care’s NICU and Pediatrics Department, in partnership with other members of the Vermont Oxford Network, an international collaborative of NICUs and pediatrics departments. Discovering a lack of consistency in diagnosis and treatment of NAS, the team developed a comprehensive program of prenatal screening, diagnosis, treatment and ongoing evaluation and monitoring.

The Christiana Care NAS Program was implemented in 2014. The Vermont Oxford Network is now auditing the program every three months to monitor progress and disseminate useful findings. Special thanks to the Junior Board of Christiana Care for its exemplary support of the NAS program.

NAS Rate in the U.S. (2000-2009)

3.0 2.5 2.0 1.5 1.0 0.5

Source: Neonatal Abstinence Syndrome and Associated Health Care Expenditures: United States, 2000-2009

0.0

JAMA. 2012;307(18):1934-1940. doi:10.1001/jama.2012.3951

2000

2006

2003 Year

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Christiana Care has developed a leading-edge procedure to screen and treat for neonatal abstinence syndrome.

2009

In Christiana Care’s NICU, a multidisciplinary team was formed to evaluate and address a higher-than-average incidence of pneumothorax in ventilated very-low-birth-weight (VLBW) infants.

The results of its successful quality improvement project were published in Pediatrics in October 2012 (Pediatrics 2012; 130;e1352).

They then developed guidelines for improved monitoring and rapid feedback between nursing staff and clinicians, and they educated NICU staff on the new guidelines.

Pneumothorax is common in critically ill ventilated neonates and is associated with increased risk of intraventricular hemorrhage, chronic lung disease and death.

During the second period, 76 VLBW infants were followed for six months with the interventions in place. The rate of pneumothorax decreased from 10 percent in Period 1 to 2 percent in Period 2.

Led by neonatologist Haritha Vellanki, M.D., the team included David A. Paul, M.D., Chair of Pediatrics; Michael J. Antunes, M.D.; Robert G. Locke, D.O., MPH; Amy Mackley, MSN, RNC, CCRS; Theresa McGreevy, NNP; Jacqueline Eubanks, RN; Michael Western, RT and John Emberger, RT. Multidisciplinary participation in the project ensured representation from the many caregivers in the NICU.

“While we were conducting the intervention, we tracked the rate of pneumothorax, so we were able to show in a relatively quick period that our intervention was effective,” said Dr. Paul. “It’s really a new paradigm for improving hospital outcomes.”

The team conducted the project in two phases.

During the first period, 115 VLBW infants were followed for six months and evaluated for the presence of pneumothorax. The team met regularly to identify potential causes, based on rigorous root-cause analysis. Through this process, they noted high tidal volume (Vt) (>6mL/kg) around the time of pneumothorax occurrence.

Guidelines for mechanical ventilation in VLBW infants that were implemented within Christiana Care’s NICU. Mode of ventilation chosen by the clinician and settings ordered were based on the guidelines. Applying the guidelines decreased the incidence of pneumothorax in the NICU.

Improving Infants’ and Children’s Health

Pneumothorax can be reduced in verylow-birth-weight infants through new procedures developed in Christiana Care’s NICU.

New NICU Procedures Decrease Pneumothorax in VLBW Infants

Choose ventilation mode

Time cycled pressure limited

Ordered PIP should yield Vt of 4.0 to 6.0 mL/kg.

RT sets appropriate high tidal volume limit.

Guidelines for Initiation of Mechanical Ventilation for Infants <1500g in NICU

RT/RN notifies clinician of sustained Vt outside 4.0 to 6.0 mL/kg range. PIP adjustment may be necessary.

Volume targeted (minimum weight 500g)

RT/RN notifies clinician of sustained elevation in peak pressure.

Lower tidal volume may not be necessary.

RT/RN notifies clinician of sustained elevation in peak pressure.

Lower tidal volume may not be necessary.

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39 Weeks. Is It Really the Magic Number?

When babies are delivered later, NICU visits drop, but stillbirths and macrosomia increase, a Christiana Care study shows.

From 1990 to 2006, American women increasingly asked to deliver before reaching full term at 39 weeks of gestation, and their physicians obliged them. Rates of labor induction had increased dramatically, from 9.5 percent in 1990 to 22.5 percent by 2006, according to the National Center for Health Statistics.

The American Congress of Obstetricians and Gynecologists (ACOG) called for a stop to the practice, citing higher mortality and morbidity rates for neonates and infants delivered early during non-medically indicated elective deliveries.

In addition, The Joint Commission recently adopted the rate of elective delivery before 39 weeks as an institutional quality measure. As a result, many hospitals have instituted hard stops on elective deliveries before 39 weeks of gestation.

The study found that a policy limiting elective delivery before 39 weeks resulted in a small reduction in NICU admissions; however, macrosomia and stillbirths increased.

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Outcome for Live Births

Before (n=12,015)

After (n=12,013)

P

37 and 38

3,975 (33.1)

3,172 (26.4)

<.001

39 or more

8,040 (66.9)

8,841 (73.6)

3,393±459

3,399±463

.33

1,500–2,500

266 (2.2)

251 (2.1)

.60

2,500–4,000

10,668 (88.8)

10,626 (88.5)

4,000–4,499

928 (7.7)

975 (8.1)

4,500 or more

153 (1.3)

161 (1.3)

13 (0.11)

9 (0.07)

Gestational age (wk)

Birth weight (g)

5-min Apgar score 3 or less

Improving Infants’ and Children’s Health

Neonatal Outcomes for All Live Births Before (2005 and 2006) and After (2008 and 2009) Implementation of Guidelines

.39

Data are n (%) or mean ± standard deviation, unless otherwise specified.

Since hospitals took these measures, what has been the result? Deborah B. Ehrenthal, M.D., FACP, then a Director of Health Services Research for Women and Children and Medical Director of Women’s Health Programs in the Department of Obstetrics and Gynecology at Christiana Care, led a retrospective cohort study of more than 24,000 singleton live births at the hospital.

The study (Obstet Gynecol. 2011 Nov; 118(5):104755) found that a policy limiting elective delivery

before 39 weeks resulted in a small reduction in NICU admissions; however, macrosomia and stillbirths increased.

“This paper has stimulated a lot of research,” Dr. Ehrenthal said. “People are trying to understand stillbirth, but it’s not easy. Stillbirth is a really hard thing to measure, because it’s so uncommon in the developed world.” This was one of the early studies to examine all of the implications of what has become a national policy.

17

Example of a DNA microarray. Christiana Care researchers contributed to two recent studies showing the efficacy of using chromosomal microarray analysis or massively parallel sequencing of maternal plasma DNA for diagnosis of fetal aneuploidy.

Genetics Studies Show the Promise of Testing Maternal Plasma DNA Expectant mothers have historically been reluctant to undergo testing for chromosomal abnormalities via amniocentesis or chorionic villus sampling (CVS) because of risks to the fetus.

Christiana Care researchers contributed to two recent studies showing the efficacy of using chromosomal microarray analysis or massively parallel sequencing of maternal plasma DNA for diagnosis of fetal aneuploidy.

18

In the first instance, the ability of microarray analysis to identify aneuploidies not revealed by standard karyotyping increases the potential benefit of the test for at-risk mothers, whose tissue samples must be obtained through amniocentesis or CVS.

In the second, the efficacy of parallel sequencing of maternal plasma DNA in detecting multiple chromosomes across the genome offers the possibility of reducing invasive diagnostic procedures.

Published in the New England Journal of Medicine (Wapner et al, N Engl J Med 2012;367:217584), the first study compared the accuracy, efficacy and incremental yield of microarray analysis to karyotyping for prenatal diagnosis of chromosomal abnormalities known to cause childrenâ&#x20AC;&#x2122;s developmental delay and structural malformations. Christiana Care was one of 29 centers contributing to the study, which was funded by the NIHâ&#x20AC;&#x2122;s Eunice Kennedy Shriver

% Correctly Classified

100.00% 90.00% 80.00% 70.00% 60.00% 50.00% 40.00% Trisomy 21 Trisomy 18

Trisomy 13

Females

Males

Monosomy X

The sequencing’s high sensitivity and specificity for diagnosis of trisomies 21, 18, 13 and monosomy X suggest that testing through maternal plasma DNA may enable reduction of more invasive procedures.

Massively parallel sequencing’s high sensitivity and specificity for diagnosis of trisomies 21, 18, 13 and monosomy X suggest that testing through maternal plasma DNA may enable reduction of more invasive procedures.

National Institute of Child Health and Human Development (NICHD). Anthony C. Sciscione, D.O., who directs the Delaware Center for Maternal & Fetal Medicine and Christiana Care’s OB-GYN Residency Program, led Christiana Care’s participation.

Samples from each of the 4,000 women participating in the study were divided and analyzed through standard karyotyping and chromosomal microarray. Microarray analysis identified all of the aneuploidies and unbalanced rearrangements that karyotyping did, but did not identify balanced translocations and triploidy.

In addition, microarray analysis identified clinically significant aneuploidies not revealed by karyotyping.

Improving Infants’ and Children’s Health

Accuracy of Massively Parallel Analysis of Maternal DNA

Christiana Care also participated in a series of studies as a member of the MatErnal BLood IS Source to Accurately Diagnose Fetal Aneuploidy (MELISSA) Study Group. One of those studies, published in Obstetrics & Gynecology (Bianchi et al, Obstet Gynecol 2012 May;119(5):890901), investigated the accuracy of massively parallel sequencing of maternal plasma DNA in diagnosing fetal aneuploidy across the genome.

In the prospective, blinded study, blood samples were collected from more than 2,500 women undergoing prenatal testing at 60 U.S. sites.

All singleton pregnancies with abnormal karyotype and randomly selected pregnancies with euploid karyotypes were selected for massively parallel sequencing, producing an analysis cohort of 532 samples.

19

New Tools Arrive in the Fight Against Cerebral Palsy Anthony C. Sciscione, D.O., contributed to a trial of magnesium sulfate for the prevention of cerebral palsy, a leading cause of chronic childhood disability. As a result of this and other studies, magnesium sulfate is now used routinely for neuroprotection of at-risk fetuses. Dr. Sciscione directs the Delaware Center for Maternal & Fetal Medicine and Christiana Careâ&#x20AC;&#x2122;s OB-GYN Residency Program.

Led by Dwight J. Rouse, M.D., Brown/Women & Infants principal investigator for the Eunice Kennedy Shriver NICHD Maternal-Fetal Medicine Units (MFMU) Network, the study focused on whether intravenous administration of magnesium sulfate to women at imminent risk of preterm delivery reduced the combined risk of moderate or severe cerebral palsy or infant death. The study was published in the New England Journal of Medicine in 2008 (Rouse et al, NEJM359;9:895-905).

Preterm birth is a risk factor for cerebral palsy.

An earlier study (Nelson and Grether, Pediatrics 1995;95:263-9) showed that children with cerebral palsy were much less likely to have been exposed to magnesium sulfate before birth than were

As a result of this and other studies, magnesium sulfate is now used routinely for the neuroprotection of at-risk fetuses.

control subjects. Magnesium may reduce vascular instability, prevent hypoxic damage and lessen cytokine or excitatory amino acid damage â&#x20AC;&#x201D; factors that threaten the preterm brain.

Researchers at 20 MFMU sites enrolled 2,241 women at imminent risk for delivery between 24 and 31 weeks of gestation. The women were randomly assigned to receive an intravenous 6 g bolus of magnesium sulfate, followed by a constant infusion of 2 g per hour, or a matching placebo. The primary study outcome was the composite of stillbirth or infant death by one year of corrected age or moderate or severe cerebral palsy at or beyond one year of corrected age.

The primary, composite outcome rate did not differ significantly between the two groups.

Moderate or Severe Cerebral Palsy After Magnesium Sulfate Administration to Women at Risk of Preterm Delivery Magnesium Sulfate

Placebo

< 28 weeks of gestation at randomization

12/444 (2.7)

30/496 (6.0)

â&#x2030;Ľ 28 weeks of gestation at randomization

8/599 (1.3)

8/599 (1.3)

Moderate or severe cerebral palsy

20

Neonatal researchers at Christiana Care worked with the University of Delaware biomedical computer engineers in an NIH-funded study, which showed that volumetric MRI measures taken at birth can help identify preterm infants at risk of neurodevelopmental disability. The study was published in Pediatric Physical Therapy in 2012 (Gadin et al, Pediatr Phys Ther 2012 Spring; 24(1):38-44).

Infants born before 32 weeks gestation now represent more than 2 percent of live births. Their survival rate surpasses 85 percent, with a high risk of developmental delay. Detection at birth of cerebral injury would allow families to seek early intervention.

Erlita Gadin, M.D., then a senior fellow in Neonatal-Perinatal Medicine at Christiana Care, led the study. The final analysis included 20 infants born at less than 30 weeks and admitted to Christiana Care’s NICU between November 2007 and December 2009; four infants born at term were recruited as a comparison group. The infants underwent MRI and MRS at 36 weeks postmenstrual age or just before hospital discharge, using a 1.5-Tesla Siemens Symphony MR unit.

MRI scans were volumetrically analyzed at the University of Delaware. A pediatric physical therapist evaluated all infants at home at six months of adjusted age; the evaluations were video-recorded and scored by a second therapist.

Volumetric MRI showed that the preterm infants had smaller white matter, gray matter, subcortical gray matter, cerebellar and total brain volume than those born at term. Seven of the 20 preterm infants in the final study had low motor scores at the six-

month follow-up. These seven also had decreased subcortical gray matter volume compared with infants with normal motor scores.

The study did not find an association between MRS in the periventricular parietal white matter and low motor scores.

This study showed some potential value for clinicians and parents in imaging the brains of premature infants prior to discharge home.

However, studies with larger numbers of infants are still needed to determine whether volumetric MRI is superior to traditional Study findings suggest a relationship methods of between low brain volume and counseling in motor outcomes. Volumetric predicting motor MRIs performed prior to hospital outcomes.

Improving Infants’ and Children’s Health

MRI Measures at Birth May Identify Infants at Risk for Delayed Motor Performance

discharge may help identify neurodevelopmental disability.

Brain Volumes of Infants Born Prematurely Premature Infants With Normal Motor Scores (n = 13)

Premature Infants With Low Motor Scores (n = 7)

P

Ventricles

5.2±2.7

25.6±54.0

.18

Subcortical gray matter

19.1±3.4

15.3±3.4

.03

Cortical gray matter

113.2±19.2

117.2±28.4

.70

Cortical white matter

110.9±14.5

101.8±22.7

.28

Cerebellum

16±6.2

17.1±3

.67

Total brain

261.6±30

264.6±23.4

.82

Low motor scores defined as below 1.5SD from the mean at 6 months.

21

Christiana Care Team Helps Advance Uniformity of States’ Birth Defect Reporting A team of Christiana Care researchers is working to standardize classification of birth defects in the state of Delaware — and demonstrate the importance of doing so nationwide. The Delaware Birth Defects Registry team’s poster presentation, “A Rational Approach to Inclusion of Renal Collecting System Abnormalities,” won a firstplace award from the National Birth Defects Prevention Network.

They have also created a poster presentation on “Reporting of Ventricular Septal Defects by State Birth Defect Registries.” The poster on reporting of ventricular septal defects (VSDs), the most common congenital cardiac anomaly, addresses the current absence of standardized case ascertainment and classification strategy for state birth defect registries. This makes it difficult to compare VSD rates across states, to report a national VSD rate and to study longitudinal trends.

The absence of standardized case classification makes it difficult for Delaware to compare ventricular septal defects across states.

The Christiana Care team surveyed and categorized all Delaware residents’ live births and fetal deaths in 2007 and 2008 with a confirmed VSD. The researchers also categorized maternal and paternal characteristics, cohort characteristics and delivery outcomes.

Important findings included: ■■

Delaware’s VSD rate was 79 per 10,000, including all confirmed VSD cases.

■■

Thirty-six percent of the VSD cases reviewed were spontaneously closed isolated muscular VSDs.

Renal System Abnormalities in Delaware (2007-2009) Classified by Outcome 50% 40% 30% 20% 10% 0% Surgery 22

Resolved

Clinically Insignificant

Not Resolved

Lost to Follow-Up

Infant Death

Unknown

The poster on renal collecting system abnormalities addresses the absence of consistent criteria to define true renal obstructions, which leads to widely varying incidence rate reports by state.

Fetal ECG Shows Promise as Early Warning Sign for Hypoxia Christiana Care is contributing to an NIH-funded, multi-site ST Segment Analysis (STAN) study that aims to establish a relationship between the fetal electrocardiogram (ECG) signal and the development of hypoxia, which is a leading cause of neonatal brain injury during delivery. Eleven thousand women are participating nationwide, with nearly 480 at Christiana Care.

Matthew K. Hoffman, M.D., MPH, FACOG, Vice Chairman, Christiana Care Department of Obstetrics and Gynecology and Division of Education and Research, is Christiana Care’s principal investigator in the STAN study, which focuses on a novel approach, used in other countries but not the U.S., to determine if ECGs can be used to identify the development of metabolic acidosis, a proxy for hypoxia. A STAN monitor is used to analyze the ST segment and the T/QRS ratio of the fetal ECG. This system, an

adjunct to the traditional fetal monitoring system, will allow obstetricians either to intervene if ECG changes are of concern or to continue with current management of labor if the ST analysis is reassuring.

“STAN holds great potential for us to detect neonatal injury earlier and reduce cesarean sections and other interventions that may not be necessary,” Dr. Hoffman said.

STAN holds great potential for us to detect neonatal injury earlier and reduce cesarean sections and other interventions that may not be necessary.

The STAN study is a project of the Maternal Fetal Medicine Units (MFMU) Network, created by the NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). Dr. Hoffman is a principal investigator for MFMU.

Improving Infants’ and Children’s Health

Current Trials

8

STAN

Auscultation/CTG

40

7 35

6 5

30

4 25

3 2

20

1 15

0 2004

2005

2006 Year

2007

2008

STAN monitoring (%)

Emergency Cesarean Deliveries (%)

Proportion of emergency cesarean section deliveries by year of birth and monitoring method (STAN or auscultation/CTG; columns) and proportion of STAN monitored deliveries (line).

While the U.S. STAN study is not complete, a similar study in Norway showed that increased monitoring with ST analysis was clearly associated with a decreasing rate of operative birth interventions in low-risk labors.

Source: Intrapartum monitoring of high-risk deliveries with ST analysis of the fetal electrocardiogram: an observational study of 6,010 deliveries. Kessler J, Moster D, Albrechtsen S. http://www.neoventa.com/2012/09/ new-publication-five-years-of-st-analysis-usage-inbergen-a-quality-improvement-study/

23

Overview

Focusing on Women’s Health

Christiana Care’s OB-GYN researchers have a global impact on women’s health, from studies on medications and treatments that could reduce the leading cause of maternal death worldwide to important contributions into breast cancer research. Based in part on the large database of information from women who deliver at the hospital, much of Christiana Care’s research into women’s health issues focuses on the influence of maternal health and health care on perinatal outcomes.

Global Focus

Misoprostol Provides Better Solution in Preventing Postpartum Hemorrhage With long-term funding from the NIH and other agencies and foundations, Christiana Care researchers have contributed to multiple global studies on prevention of postpartum hemorrhage, the leading cause of maternal death worldwide.

The latest study builds upon the work published in The Lancet by the NIHfunded Global Network for Women’s and Children’s Health Research. It shows that sublingual Misoprostol is more effective than intravenous oxytocin in preventing postpartum blood loss, as published in BJOG: An International Journal of Obstetrics 24

and Gynaecology in 2012 (M. B. Bellad et al, BJOG 2012;119:975-986). Christiana Care’s Richard J. Derman, M.D., MPH, FACOG, the Marie E. Pinizzotto, M.D., Endowed Chair of Obstetrics and Gynecology, with Nancy L. Sloan, DrPH, is a principal investigator for the Global Network and contributed to the BJOG study.

Intramuscular oxytocin has been considered the “gold standard,” with multiple studies showing higher efficacy and lower incidence of side effects than Misoprostol. The BJOG study tested sublingual rather than oral Misoprostol; its greater bioavailability permitted a lower dose than that tested previously. The double-blind randomized

The women were assigned by computer-generated randomization to receive the study medications — 400 micrograms of powdered sublingual Misoprostol and 10 IU intramuscular (IM) oxytocin — and placebos within one minute of cutting and clamping the umbilical cord. Blood loss was precisely measured and analyzed.

The study found 400 micrograms of sublingual Misoprostol to be significantly more effective than 10 IU intramuscular oxytocin in reducing postpartum blood loss and hemorrhage. Mean blood loss was 192 +/- 124 ml in women receiving Misoprostol, compared with 366 +/- 136 ml in women receiving oxytocin.

“We recruited nearly one-third of the participants of trials conducted worldwide for a drug that is now listed as an essential medicine in the fight against maternal deaths from postpartum hemorrhage. We continue our work in that area, as well as explore the use of the drug in community health conditions in less developed nations around the world.”

Focusing on Women’s Health

controlled trial was conducted with a cohort of 652 consenting pregnant women in the KLES teaching hospital attached to Jawaharlal Nehru Medical College in Belgaum, Karnataka, India.

– Richard J. Derman, M.D., MPH, FACOG, the Marie E. Pinizzotto, M.D., Endowed Chair of Obstetrics and Gynecology

“Among the reasons that use of Misoprostol is a giant step forward are that it is heat stable and it is not injectable — it’s not like oxytocin that we use in our delivery rooms. It’s foil-packed, and there are studies showing that you can give this to women who are delivering at home and they won’t misuse it,” Dr. Derman said.

Effects of Misoprostol Compared to Oxytocin Mean (bootstrapped) blood loss (ml) Postpartum hemorrhage Hemoglobin decline >10%

Misoprostol

Oxytocin

192 ± 124

366 ± 136

3.1%

9.1%

10.1 ± 1.3

9.6 ± 1.1

The trial found sublingual Misoprostol is more effective in preventing postpartum hemorrhage compared with oxytocin.

25

Obstetrician-Gynecologists Play Role in Cardiovascular Disease Prevention Cardiovascular disease (CVD) remains the leading cause of death in the U.S. and worldwide for both women and men. Christiana Care’s Deborah Ehrenthal, M.D., MPH, along with Janet M. Catov, Ph.D., of the University of Pittsburgh, performed a review of recent medical research to provide new insights into the importance of addressing modifiable risk factors for CVD during women’s childbearing years.

Traditional and sex-specific factors among women during their reproductive years were identified, along with their importance in lifetime risk for CVD. These risk factors include: 1. Traditional risks: Smoking, diabetes, blood pressure/hypertension and dyslipidemia.

2. Reproductive risks: Polycystic ovary syndrome, infertility and adverse pregnancy outcomes.

3. Other behavioral risks: Physical activity, diet, obesity and lactation.

Risk factors for CVD are often identified by an OB-GYN during a woman’s course of reproductive care. Though OB-GYNs may consider CVD prevention outside their scope of practice, they are in a key position to recognize women who are at high risk for future CVD. Gaps in the current hybrid U.S. health care system lead to undiagnosed risk factors that have an impact on the lifetime risk of CVD in women. Thus, engaging OB-GYN providers in CVD prevention may help pave a new path for at-risk women to get the primary and secondary prevention they need.

“This research provides a new rationale and vision for an innovative strategy toward primary and secondary prevention of CVD in women,” Dr. Ehrenthal said. “It is now clear that pregnancy provides an opportunity to identify women who have a high lifetime risk for CVD and implement preventive measures moving forward.”

It is now clear that pregnancy provides an opportunity to identify women who have a high lifetime risk for CVD. Though OB-GYNs may consider CVD prevention outside their scope of practice, they are in a key position to recognize women who are at high risk for future CVD. Engaging OB-GYNs in CVD prevention will enable earlier intervention and provide a new avenue to engaging women in prevention.

26

Studies of gynecologic oncology patients have shown robotic hysterectomies result in shorter patient hospital stays and less blood loss. As a result, robotic hysterectomies are rapidly replacing abdominal hysterectomies as the procedure of choice at Christiana Care and hospitals around the world. However, most of the studies that resulted in the transition to robotic hysterectomies involved expert surgeons who performed a high volume of the procedures.

Our study suggests that even in the initiation phase, robotic hysterectomy for benign indications is relatively safe, although further evaluation of the learning curve and risks for GU injury is needed. cost is associated with a 65 percent increase in procedure times for robotic hysterectomies, which was high enough to offset cost savings from the 51 percent reduction in hospital stays experienced by patients of the procedure.

Focusing on Women’s Health

Transition to Robotic Hysterectomy Can Lead to Higher Costs and Injuries, Study Suggests

To determine whether the same positive outcomes would be found in a large community hospital with physicians in the learning phase of “Our study suggests that even in the initiation experience with robotic hysterectomy, Gretchen phase, robotic hysterectomy for benign indications E. Makai, M.D., Director of Minimally Invasive is relatively safe, although further evaluation Gynecologic Surgery, worked with a team of the learning curve and risks for GU injury is of physicians and researchers from the needed,” Makai said.

Department of Obstetrics and Gynecology on a retrospective study of nearly 400 women who had hysterectomies performed at Hysterectomy Trends at Christiana Care (2004-2011) Christiana Care.

80.0% Outcomes for a retrospective cohort of women who underwent robotic hysterectomy for benign indications at Christiana Care between 2007 and 2010 were compared to outcomes of abdominal hysterectomy by the same surgeons in prior years.

The study found that robotic hysterectomy in the learning phase is associated with a higher incidence of bladder injury and higher cost than abdominal hysterectomy. The higher

70.0% 60.0% 50.0% 40.0% 30.0% 20.0% 10.0% 0.0% 2004

2005

2006

2007

2008

2009

2010

2011

Year LAPAROSCOPIC

ROBOTIC

TOTAL ABDOMINAL

VAGINAL

27

Christiana Care Contributes to Landmark Breast Cancer Study A study published in the Journal of the American Medical Association (Giuliano et al, JAMA 2011;305(6):569-575) investigated the effects of complete axillary lymph node dissection (ALND) on the survival of breast cancer patients with sentinel lymph node (SLN) metastasis.

92.5 percent with SLND alone, while diseasefree survival rates were 82.2 and 83.9 percent, respectively. Fewer than one percent of patients in either arm of the study experienced an axillary recurrence of tumor. The women who had only sentinel lymph nodes removed also experienced lower rates of swelling of the arm and other complications.

Christiana Care was among the top 20 sites for the number of patients participating. Patients were women with clinical T1-T2 invasive breast cancer, no palpable adenopathy and one to two SLNs containing metastases. All patients underwent a lumpectomy and received whole-breast irradiation; all had sentinel lymph node biopsy that revealed metastasis in one or two nodes. They were randomized to undergo removal of 10 or more nodes or no further lymph node surgery.

Diana Dickson-Witmer, M.D., FACS, Medical Director, Christiana Care Breast Center, Helen F. Graham Cancer Center & Research Institute, was principal investigator for the study at Christiana Care. “The results of this study are truly practice changing,” Dr. Dickson-Witmer said. “The standard of care has been to perform a complete axillary node dissection on every patient with a positive sentinel node. Most surgeons are now omitting complete dissection in appropriately selected sentinel node positive patients. Thousands of women may now safely be spared the swollen arms and other complications of full lymph node removal.”

The results showed that sentinal lymph node dissection (SNLD) alone did not result in lower survival rates than ALND. The five-year overall survival rate was 91.8 percent with ALND and

Survival of the ALND Group Compared With SLND-Alone Group Many women with early breast cancer do not appear to benefit from complete removal of the lymph nodes under their arm (in the axilla), even when cancer is found in one or two representative (sentinel) nodes.

ALIVE

100 90

90

80

80

70

70

60

60

50

50

40

40

30

30

20

20

10

10

0

0

1

2

3

4

5

Year

28

ALIVE AND DISEASE-FREE

100

ALND

6

7

8

1

2

3

SLND alone

4

5

Year

Log-rank P = .25 ALND

6

7

8

Log-rank P = .14

SLND alone

In 2009, the FDA approved the MyoSure® hysteroscopic morcellation device for the removal of lesions in the endometrial cavity, or lesions within the walls of the uterus, as an alternative to loop electrode resections. Christiana Care implemented the use of the MyoSure device for its hospital facilities in 2010.

A sample group of 186 subjects was identified— 89 subjects had the procedure with the morcellation device and 97 had the procedure with the loop electrode resection device. For each sample, researchers looked at four criteria for analysis: operation time, pathologic type and volume, complications and cost.

Looking back at the results of procedures conducted since the new device was approved for use at the hospital, Christiana Care researchers evaluated the comparative effectiveness of hysteroscopic morcellation (MyoSure) versus the traditional loop electrode resection for intrauterine lesions.

The research study showed that the morcellation device does not appear to be more effective than the traditional loop electrode resection device for removal of intrauterine lesions. On average, each morcellation procedure took two minutes longer than the average loop electrode procedure and cost a mean difference of $844 more per case. Both procedures showed equivalent pathologic type and volume and insufficient complications, which included perforations, conversions and fluid complications.

The study was led by Gretchen E. Makai, M.D., Director of Minimally-Invasive Gynecologic Surgery, Christiana Care Department of Obstetrics and Gynecology, and Matthew K. Hoffman, M.D., MPH, FACOG, Vice Chairman, Christiana Care Department of Obstetrics and Gynecology and Division of Education and Research. Dr. Makai and Dr. Hoffman studied in-house electronic hospital and billing records at Christiana Care to identify patients who underwent intrauterine lesion removal procedures utilizing either device between July 2010 and March 2012.

The research study showed that the morcellation device does not appear to be more effective than the traditional loop electrode resection device for removal of intrauterine lesions.

Focusing on Women’s Health

Loop Electrode Resection Outperforms New MyoSure® Morcellation Device for Lesion Removal

Further studies are needed to determine the patient and clinical scenarios in which the potential benefits of morcellation may be realized.

In recognition of the team’s work, Dr. Makai was presented the AAGL 2013 Golden Hysteroscope Award for the best paper on hysteroscopy.

Loop Electrode Resection Vs. New Morcellation Device

Operative Time (Mean) Pathologic Type and Volume (Mean) Complications Cost

Hysteroscopic Morcellation

Loop Electrode Resection

34 minutes

32 minutes

1.9 +/- 1.7 cm

3.1 +/- 2.8 cm

4 (4.5%) Insufficient

3 (3.1%) Insufficient

$1,972+/- $77

$1,128+/- $56 29

Conventional Laparoscopy Produces Less Postoperative Pain than Robotically-Assisted Procedures, Study Indicates Minimally invasive laparoscopic surgery is recommended by the American Congress of Obstetricians and Gynecologists as an alternative when vaginal hysterectomy is not possible.

Surgeons can either perform conventional laparoscopy or robotically-assisted hysterectomy.

To learn more about the short-term effects of these procedures on patients, Christiana Care resident Megan N. Wasson, D.O., set out to determine if there was a difference in postoperative pain following laparoscopic hysterectomy performed via a conventional versus robotically-assisted approach.

All women who underwent laparoscopic hysterectomy at Christiana Care between January 2009 and September 2012 were considered for the study. A total of 353 women met study inclusion criteria. Total postoperative oxycodone equivalent (OOE) measured in the first 24 hours following

Conventional laparoscopy produces less postoperative pain than robotically-assisted procedures.

surgery was used as a surrogate for postoperative pain. The total OOE administered to women who underwent conventional laparoscopic hysterectomy (27.83 mg) was significantly lower than the amount administered to patients who underwent a robotically-assisted procedure (37.92 mg).

Wassonâ&#x20AC;&#x2122;s study was awarded the Jerome Hoffman Award for the best paper among residents and fellows at the national conference for the American Association of Gynecologic Laparoscopists.

Postoperative Analgesia Stratified According to Laparoscopic (LH) vs. Robotically-Assisted (RAH) Hysterectomy

30

LH n=116

RAH n=237

p-value

Oral narcotic oxycodone equivalent (mg)

19.09

17.04

Parinatal narcotic oxycodone equivalent (mg)

14.17

25.68

Total narcotic oxycodone equivalent (mg)

27.83 (21.59-34.08)

37.92 (32.99-42.854)

0.0167

Total ketorolac administered (mg)

64.01 (56.28-71.74)

69.53 (63.40-75.67)

.2903

Focusing on Women’s Health

Does Seprafilm® Prevent Intra-Abdominal Adhesions?

Seprafilm® is a clear, thin film that is applied to the anterior uterus of patients at the time of cesarean delivery to separate organs and body tissues and prevent scar tissue (adhesion) formation as they heal. How effective is this treatment?

Courtney Levenson, M.D., Christiana Care resident, studied the effect of previous Seprafilm use by determining the amount of scar tissue at the time of the second cesarean delivery.

One hundred ninety four patients at Christiana Care were enrolled in the study. The 35 enrolled

patients who had Seprafilm used during previous cesarean deliveries were compared to the 122 patients without Seprafilm.

Levenson found that there was no significant difference in adhesions, blood loss, complications or infant Apgars between the two groups. Based on the data, the study indicated that there is a lack of evidence to recommend the routine use of Seprafilm at cesarean section to reduce the presence of adhesions and complications due to adhesions.

There is a lack of evidence to recommend the routine use of Seprafilm at cesarean section.

31

Peripartum Transfusion Study Identifies Anemia as Treatable Risk Factor More than one out of every 60 women receives a blood transfusion during the peripartum period, increasing morbidity, length of stay and health care costs. In a study published in the Journal of Women’s Health (Ehrenthal et al, JWH 2012; 21:792-797), Christiana Care researchers explored the association of maternal and obstetric factors and peripartum transfusion, and they identified anemia as a treatable risk factor.

The study was led by Melanie L. Chichester, BSN, RNCOB, CPLC, Christiana Care Labor and Delivery, and Deborah B. Ehrenthal, M.D., MPH, then a Director of Health Services Research for Women and Children and Medical Director of Women’s Health Programs in Christiana Care’s Department of Obstetrics and Gynecology, and completed by Oluwaseun Suzanne Cole, M.D., Christiana Care Obstetrics and Gynecology Residency Program.

The team analyzed a retrospective cohort of 59,282 women delivering at Christiana Hospital between January 2000 and July 2008. Maternal and obstetric factors were examined. Increased odds of perinatal

Greater attention to anemia may reduce the number of peripartum blood transfusions, limiting exposure to transfusion-associated risks.

transfusion were seen for women with anemia and those undergoing a cesarean delivery.

This research, addressing risk factors associated with transfusion, builds upon an associated base of departmental published research. This research includes Dr. Nancy Sloan et al, What measured blood loss tells us about postpartum bleeding: a systematic review, April 20, 2010, British Journal of Obstetrics and Gynaecology, and R.J. Derman and B.S. Kodkany, Pitfalls in assessing quantity of blood loss and decision to transfer secondary to postpartum hemorrhage, in A Textbook of Postpartum Hemorrhage, London: Sapiens Publishing, p. 35-44. 2006.

Joint Effects of Anemia and Cesarean Delivery on Odds of Transfusion, Adjusting for all Other Factors Anemia (Hgb < 10.5)

Cesarean delivery

n (%)

aORa

No

No

37,128 (62.6)

Referent

Yes

15,732 (26.5)

2.74

2.21 – 3.40

No

4,450 (7.5)

3.08

2.28 - 4.16

Yes

1,972 (3.3)

15.08

11.84-19.21

Yes

Adjusted for maternal and obstetric factors

32

95% CL

Focusing on Womenâ&#x20AC;&#x2122;s Health

Bed Rest and Gestational Diabetes: More Reasons to Get Out of Bed in the Morning One of the most commonly prescribed obstetric interventions is bed rest. But even though it has been recommended for generations, there is little data actually demonstrating it works. In fact, bed rest prevents women with gestational diabetes (GDM) from exercising, which has been shown to promote glycemic control.

A Christiana Care team of researchers, including Audrey A. Merriam, M.D.; Melanie Chichester, BSN, RNC-OB, CPLC, Christiana Care Labor and Delivery; Nima Patel, M.D.; and Matthew K. Hoffman, M.D., MPH, FACOG, Vice Chairman of the Department of Obstetrics and Gynecology and the Division of Education and Research, set out to quantify the impact that bed rest has on GDM.

The retrospective cohort study tracked 509 women who were prescribed bed rest after diagnosis of preterm labor, cervical shortening and other related risk factors. Fifty-four of these women were diagnosed with GDM during a prolonged hospital stay. For every day a patient was admitted to the hospital on bed rest, her risk of GDM increased 1.04 times.

This finding supports the mounting evidence that bed rest during pregnancy does more harm than good.

Mounting evidence indicates that bed rest during pregnancy does more harm than good.

33

Foley Catheter Placement Can Affect Induction Outcomes More than one in five pregnant women will be induced into labor for various medical and obstetrical reasons. But these women often require preinduction cervical ripening. A common procedure is the use of the Foley catheter, which not only mechanically dilates the cervix but also triggers the release of endogenous prostaglandins.

Studies have recommended that the Foley catheter be placed transcervically through the internal cervical os into the lower uterine segment. But in practice, the catheters are often placed blindly, manually and with or without a stylet for stability.

Christiana Care researcher Siobhan McCartySingleton, M.D., set out to determine how often Foley catheters were placed transcervically in practice and whether placement could affect labor induction outcomes.

Foley catheters are often placed intracervically, rather than transcervically, but it has no effect on labor outcomes.

As she expected, Dr. McCarty-Singleton found that Foley catheters were more often placed intracervically: in her observational study, only 35 of the 65 women had them placed transcervically.

However, the study also showed that the placement made no difference to labor outcomes in times of completion for the first stage of labor and total time until deliveryâ&#x20AC;&#x201D;more importantly, the mode of delivery was not significantly different.

Induction of labor and cesarean delivery rates among late preterm births: United States, 1990-2006 40.0% 30.0%

Notes: Singleton births only. Induction of labor rates are for vaginal births only.

20.0% 10.0% 0.0% 1990

1992

1994

1996

1998

2000

2002

Year INDUCED

34

CECAREAN

2004

2006

Source: CDC/NCHS, National Vital Statistics System.

Placenta previa can increase the risk of bleeding in pregnant women, lower the likelihood of successful vaginal delivery and cause a number of other concerning obstetrical and perinatal outcomes. However, in most cases, placenta previa resolves during the course of the pregnancy. There is little evidence on whether pregnancy outcomes are affected in cases of resolved placenta previa.

A Christiana Care research effort, led by Neha M. Vora, M.D., Philip Shlossman, M.D. and Melanie Chichester, BSN, RNC-OB, CPLC, evaluated outcomes for 882 pregnant women who, during their first trimester ultrasounds, were diagnosed with placenta previa. Only 12 of those cases did not resolve before delivery.

Regarding the 870 women whose placenta previa did resolve, the Christiana researchers found that they were not only more likely to deliver at term than the women with ongoing previa, but also than that of the general population. Their babiesâ&#x20AC;&#x2122; birth weights and 5-minute Apgar test scores were

Focusing on Womenâ&#x20AC;&#x2122;s Health

Resolved Placenta Previa Affects Pregnancy Outcomes Patients with resolved placenta previa were found to have a slightly lower chance of a number of adverse pregnancy outcomes compared to the general population.

also higher than those of the babies delivered by women in the two other groups. Patients with resolved previa were also significantly older and included a greater proportion of the Asian race relative to the general population.

A secondary result of the study findings could affect the frequency and timing of follow-up ultrasounds for pregnant women diagnosed with previa. The study showed that 98.6 percent of cases resolved before delivery; this data could result in less frequently recommended follow-up ultrasounds, yielding significant cost savings.

Joint Effects of Anemia and Cesarean Delivery on Odds of Transfusion, Adjusting for all Other Factors Gestational Age

22

24

26

28

30

32

34

36

Chance of Resolution (%)

94.66

90.85

86.54

76.27

68.18

50.0

36.36

0.0

Chance of Persistence (%)

5.34

9.15

13.46

23.73

31.82

50.0

63.64

100.0

Total Previae (n)

262

153

104

59

44

28

22

14

35

Clinical Research Team ■■ Amy Acheson, MS, Program Assistant ■■ Caitlin Almeida, BS, Administrative Assistant II, Regulatory ■■ Michael Antunes, M.D., Associate Director of Neonatology ■■ Louis Bartoshesky, M.D., MPH, Geneticist and former Chair of the

Department of Pediatrics

■■ Jenny Benson, BSN, RN, CCRC, Research Nurse Coordinator ■■ Debra Booth, Research Administrator ■■ Samantha Brown, Breastfeeding Peer Counselor ■■ Richard Butler, MS, Senior Systems Analyst ■■ Deanna Caudell, RDMS, Sonographer ■■ Colleen DeBosier, MSN, RN, Research Nurse Coordinator ■■ Richard Derman, M.D., MPH, FACOG, the Marie E. Pinizzotto, M.D.,

Endowed Chair of Obstetrics and Gynecology

■■ Diana Dickson-Witmer, M.D., FACS, Medical Director of the

Christiana Care Breast Center, Helen F. Graham Cancer Center & Research Institute

■■ LaWana Dill-Grant, Clinical Studies Associate ■■ Deborah Ehrenthal, M.D., MPH, FACP, then a Director of Health

Services Research of Women and Children and Medical Director of Women’s Health Programs in the Department of Obstetrics and Gynecology

■■ John Emberger, RT, Respiratory Therapist ■■ Neal Goldstein, MBI, Research Associate ■■ Mark Gooss, Research Assistant ■■ Kelly Gray, BSN, RN, Neonatal Research Coordinator ■■ Ursula Guillen, M.D., Associate Director of Neonatal Research ■■ Matthew Hoffman, M.D., MPH, FACOG, Vice Chair of the

Department of Obstetrics and Gynecology and the Division of Education and Research for Christiana Care

■■ Fran Jaeger, MA, DrPH, Senior Clinical Researcher and Manager,

Special Projects

■■ Vanita Jain, M.D., Delaware Center for Maternal & Fetal Medicine of

Christiana Care

■■ Emily Katzen, MSN, Senior Social Worker ■■ Carrie Kitto, Clinical Studies Coordinator ■■ Elisha Lockhart, Research Assistant ■■ Robert Locke, D.O., MPH, Director of Neonatal Research ■■ Stephanie Lynch, BSN, RN, CCRC, Manager of OB-GYN Research ■■ Gloria Mack, BSN, RN, Case Manager

36

■■ Amy Mackley, MSN, RNC, CCRC, Neonatal Research Nurse

Supervisor

■■ Gretchen Makai, M.D., Director of Minimally Invasive Gynecologic

Surgery

■■ James Manley, M.D., Delaware Center for Maternal & Fetal Medicine

of Christiana Care

■■ Jennifer Mann, BSN, RN, CCRC, Research Nurse Coordinator ■■ Cindy Maser, Administrative Assistant II ■■ Michele McBride, Clinical Studies Coordinator ■■ Jennifer Merriman, M.D., Delaware Center for Maternal & Fetal

Medicine of Christiana Care

■■ Sherry Monson, MSN, MBA, RN, Vice President of Women’s, Infants’

and Children’s Health, Research Administration

■■ Jennifer Nava, Research Assistant ■■ Maureen O’Brien, MS, RD, CDN, Registered Dietician ■■ David Paul, M.D., Chair of the Department of Pediatrics ■■ Lindsay Parson, Breastfeeding Peer Counselor ■■ Stephen Pearlman, M.D., Neonatologist ■■ Stephanie Rogers, BSN, RN, Manager of Women’s Health Programs

and Research

■■ Alice Ruff, BS, Breastfeeding Peer Counselor ■■ Kathy Russell, BSN, RN, Case Manager ■■ Anthony Sciscione, D.O., Director of the Delaware Center for

Maternal & Fetal Medicine and Christiana Care’s OB-GYN Residency Program

■■ Philip Shlossman, M.D., Delaware Center for Maternal & Fetal

Medicine of Christiana Care

■■ Nancy Sloan, DrPH, Chief Epidemiologist ■■ Karen Spring, MSW, LCSW, Senior Social Worker ■■ John Stefano, M.D., Director of Neonatology ■■ Joann Stevens, Research Assistant ■■ Kate Stomieroski, BS, Program Assistant ■■ Adrienne Talabisco, RDMS, Sonographer ■■ Dana Thompson, MPH, Research Associate ■■ Karin VanLandeghem, RDMS, Sonographer ■■ Ashley Vanneman, Clinical Studies Coordinator ■■ Haritha Vellanki, M.D., Neonatologist ■■ Elizabeth Zadzielski, M.D., Medical Director, Women’s Ambulatory

Services

Bodnar, L., Rouse, D., Momirova, V., Peaceman, A., Sciscione, A., Spong, C., Varner, M., Malone, F., Iams, J., Mercer, B., Thorp, J. Jr., Sorokin, Y., Carpenter, M., Lo, J., Ramin, S., Harper, M.; for the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Maternal 25-Hydroxyvitamin D and Preterm Birth in Twin Gestations. Obstetrics & Gynecology. July 2013; 122(1):91-98. PMID: 23743453.

Figueroa, D., Landon, M., Mele, L., Spong, C., Ramin, S., Casey, B., Wapner, R., Varner, M., Thorp, J. Jr., Sciscione, A., Catalano, P., Harper, M., Saade, G., Caritis, S., Sorokin, Y., Peaceman, A., Tolosa, J.; for the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Relationship between 1-Hour Glucose Challenge Test Results and Perinatal Outcomes. Obstetrics & Gynecology. June 2013; 121(6):1241-1247. PMID: 23812458.

Thorp, J. Jr., Rice, M., Harper, M., Klebanoff, M., Sorokin, Y., Varner, M., Wapner, R., Caritis, S., Iams, J., Peaceman, A., Mercer, B., Sciscione, A., Rouse, D., Ramin, S., Anderson, G.; for the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Advanced lipoprotein measures and recurrent preterm birth. American Journal of Obstetrics and Gynecology.

June 13, 2013; doi:pii: S0002-9378(13)00613- 3. 10.1016/j. ajog.2013.06.005. PMID: 23770464.

Johnson, J., Clifton, R., Roberts, J., Myatt, L., Hauth, J., Spong, C., Varner, M., Wapner, R., Thorp, J. Jr., Mercer, B., Peaceman, A., Ramin, S., Samuels, P., Sciscione, A., Harper, M., Tolosa, J., Saade, G., Sorokin, Y.; for the Eunice Kennedy Shriver National Institute of Child Health and Human Development MaternalFetal Medicine Units Network. Pregnancy Outcomes With Weight Gain Above or Below the 2009 Institute of Medicine Guidelines. Obstetrics & Gynecology. May 2013; 121(5):969975.

Bianchi, D., Prosen, T., Platt, L., Goldberg, J., Abuhamad, A., Rava, R., Sehnert, A.; MatErnal BLood IS Source to Accurately diagnose fetal aneuploidy (MELISSA) Study Group. Collaborator: A. Sciscione. Massively parallel sequencing of maternal plasma DNA in 113 cases of fetal nuchal cystic hygroma. Obstetrics & Gynecology. May 2013; 121(5):1057-62. doi: 0.1097/ AOG.0b013e31828ba3d8. PMID: 23635743.

Irene Marete, MBChB, MMed; Constance Tenge, M.D.ChB, MMed; Omrana Pasha, M.D., MPH; Shivaprasad Goudar, M.D., MHPE; Elwyn Chomba, MHVhB, DCH, MRCP; Archana Patel, M.D., Ph.D.; Fernando Althabe, M.D.; Ana Garces, M.D., MPH; Elizabeth M. McClure, Med; Sarah Saleem, MBBS, DCH, MSc; Fabian Esamai, MBChB, MMed, Ph.D.; Bhala S. Kodkany, M.D., MPH; Jose M. Belizan, M.D.; Richard J. Derman, M.D., MPH, FACOG, Marie E. Pinizzotto, M.D., Endowed Chair of Obstetrics and Gynecology; Patricia L. Hibberd, M.D., Ph.D.; Nancy

Krebs, M.D.; Pierre Buekens, M.D.; Robert L. Goldenberg, M.D.; Waldemar A. Carlo, M.D.; Dennis Wallace, Ph.D.; Janet Moore, MS; Marion Koso-Thomas, M.D., MPH; Linda L. Wright, M.D.; Edward A. Liechty, M.D. Perinatal outcomes of multiple-gestation pregnancies in Kenya, Zambia, Pakistan, India, Guatemala, and Argentina: A global network study. Am J Perinatol. 2014 Feb;31(2):125-32. Doi: 10.1055/s-00331338173. Epub 2013 March 19.

Publications

Selected Publications

Deborah B. Ehrenthal, M.D., MPH; Suzanne G. Haynes, Ph.D.; Kristen E. Martin, BA; Jeanne A. Hitch, MEd, MA, LPC; Sonya Feinberg Addo, MPH; Elizabeth O’Neill, BA; Ileana L. Piña, M.D., MPH, FAHA, FACC; Ann Taubenheim, Ph.D.; Nancy L. Sloan, DrPH. Evaluation of the Heart Truth professional education campaign on provider knowledge of women and heart disease. Women’s Health Issues. 2013 MarApr;23(2):e87-93. Doi: 10.1016/j.whi.2013.01.001 de Jongh, B., Locke, R., Paul, D., Hoffman, M. The differential effect of maternal age, race/ethnicity and insurance on neonatal intensive care unit admission rates. BMC Pregnancy and Childbirth. September 17, 2012; 12:97.

Ehrenthal, D., Maiden, K., Rao, A., West, D., Gidding, S., Bartoshesky, L., et al. Independent relation of maternal prenatal factors to early childhood obesity in the offspring. Obstetrics & Gynecology. Jan. 2013; 121(1):115-121. PMID: 23262935.

Lobo, M., Paul, D., Mackley, A., Maher, J., Galloway, J.C. Instability of delay classification and determination of early intervention eligibility in the first two years of life.

Research in Developmental Disabilities. 2013; doi 10.1016/j. ridd.2013.10.017.

Spear, M., Guillen, U., Elliott, D., Roettger, L., Zukowsky, K. The use of role play for interdisciplinary teaching of palliative care communication skills. Journal of Palliative Medicine. 2013; 16(8); 1-2.

Freidland, A., Queller, H., Paul, D. Field trips as a novel means of experiential learning in ambulatory pediatrics. Graduate Medical Education. 2012; 4, 246-249.

Gadin, E., Lobo, M., Paul, D., Sem, K., Steiner, K., Mackley, A., Anzilotti, K., Galloway, C. Volumetric MRI and MRS and early motor development in premature infants. Pediatric Physical Therapy. 2012; 24, 38-44.

Guillen, U., DeMauro, S., Ma, L., Zupanic, J., Roberts, R., Schmidt, B., Kirpalani, H. Relationship between attrition and neurodevelopmental impairment rates in extremely preterm infants at 18-24 months. Archives of Pediatrics & Adolescent Medicine. 2012; 166, 178-184.

Guillen, U., Suh, S., Munson, D., Posencheg, M., Truitt, E., Zupanic, J., Gafni, A., Kirpalani, H. Development and pretesting of decision-aid to use when counseling parents facing imminent extreme premature delivery. Journal of Pediatrics. 2012; 160, 382-387.

37

Kukreja, R., Locke, R., Hack, D., Paul, D. Knowledge of preconception health care among primary care physicians in Delaware. Delaware Medical Journal. 2012; 84 349-352.

de Jongh, B., Paul, D., Ziegler, K., Hoffman, M., Locke, R. Racial differences in the effects of maternal age on NICU admission rates.

Epub 2914.183. Abstracts2view.com/pas. 2011.

Guillen, U., Cummings, J., Bell, E., et al. International survey of transfusion practices for extremely low birth weight infants.

Seminars in Perinatology. 2012; 36, 244-247.

de Jongh, B., Mackley, A., Locke, R., Jain, N., Paul, D. Advanced maternal age and race adversely influence placental weight in very-low-birth-weight infants. Epub 2917.233. Abstracts2view.com/ pas. 2011.

Vellanki, H., Antunes, M., Locke, R., McGreevy, T., Eubanks, J., Western, M., Emberger, J., Mackley, A., Paul, D. Decreased incidence of pneumothorax in very-low-birth-weight infants following increased monitoring. Pediatrics. 2012; 130, e13521358.

Patel, S., Landers, T., Larson, E., Zaoutis, T., Delamora, P., Paul, D., Wong-McLoughlin, J., Ferng, Y., Saiman, L. Clinical vignettes provide an understanding of antibiotic prescribing practices in neonatal intensive care units. Infect Control and Hospital Epidemiology. 2011; 32, 597- 602.

Behme, R., Mackley, A., Bartoshesky, L., Paul, D. Thyroid function in late preterm infants in relation to mode of delivery and respiratory support. Journal of Pediatric Endocrinology and Metabolism. [In Press]. de Jongh, B., Lock, R., Paul, D., Hoffman, M. Effects of prepregnancy obesity, race, ethnicity and prematurity. Maternal Child Health Journal. [In Press].

Zisk, J., Mackley, A., Christensen, R., Paul, D. Transfusing neonates based on platelet count vs. platelet mass: a randomized feasibilitypilot study. Platelets. [In Press].

Abstracts Behme, R., Mackley, A., Bartoshesky, L., Paul, D. Thyroid function in late preterm infants in relation to respiratory morbidity and mode of delivery. Epub 454. Abstracts2view.com/pas. 2011. de Jongh, B., Locke, R., Hoffman, M., Paul, D. Maternal predictors of large for gestational age infants. Epub 3850.583. Abstracts2view. com/pas. 2012. de Jongh, B., Ryan, J., Locke, R., Hoffman, M., Paul, D. Prepregnancy BMI, race/ethnicity and prematurity. Epub 3850.584.

Abstracts2view.com/pas. 2012.

Paul, D., Patel, S., Gray, K., Zaoutis, T., DeLaMora, P., Ferng, Y., Saiman, L. Antibiotic prescribing for hospital-acquired pneumonia in four tertiary NICUs. Epub 1519.338. Abstracts2view.com/ pas.2012 (iNAP study / grant) Paul, D., Mackley, A., Lobo, M., Anzilotti, K., Steiner, K., Galloway, C. Motor delay in preterm infants is not associated with changes in cerebellar volume measured prior to hospital discharge. Epub 1531.529. Abstracts2view.com/pas. 2012.

Ryan, J., Paul, D., Locke, R., Mackley, A., Hoffman, M. Maternal pre-pregnancy body mass index increases admission to neonatal intensive care unit. Epub 2935.542. Abstracts2view.com/pas. 2012.

38

Duchon, J., Wong-McLoughlin, J., DelaMora, P., Alba, L., Zaoutis, T., Paul, D., Saiman, J. Antibiotic prescribing practices for necrotizing enterocolitis: data from a multi-center study. Epub 3821.176. Abstracts2view.com/pas. 2011.

Guillen, U., Suh, S., Munson, D., Posencheg, M., Truitt, E., Zupanix, J., Gafni, A., Kirplani, H. The development of a decisionaid to guide counseling of parents facing imminent extreme premature delivery. Epub 4521.296. Abstracts2view.com/pas.2011.

Guillen, U., Cummings, J., Bell, E., Widness, J., Kirpalani, H. International survey of transfusion practices for extremely premature infants. Epub 502. Abstracts2view.com/pas.2011.

Novitsky, A., Tuttle, D., Locke, R., Saiman, L., Mackley, A., Paul, D. Prolonged antibiotics in the first week of life increase the odds of chronic lung disease in very-low-birth-weight infants. Epub.

3814.120. Abstracts2view.com/pas. 2011.

Paul, D., Vishnubhakta, V. State, regional and racial comparisons of 5-minute Apgar scores: 2002-2006. Epub 4516.247.

Abstracts2view.com/pas. 2011.

Sekhon, R., Mackley, A., Paul, D. Increased odds of mechanical ventilation at 36 weeks gestation: gestational age paradox. Epub 631. Abstracts2view.com/pas.2011.

Sindall, C., Hoffman, M., Lock, R., Paul, D. Late maternal presentation negatively influences antenatal steroid administration.

Epub 2914.202. Abstracts2view.com/pas. 2011.

Suh, S., Guillen, U., Kirpalani, H. Which visual formats of complex data best help patients make informed health decisions? Epub 4505.152. Abstracts2view.com/pas.2011.

Tuttle, D., Pearlman, S., Mackley, A., Stefano, J. Performance improvement reduces peripheral long-line CLABSIs in preterm infants. Epub1165.8. Abstracts2view.com/pas.2011.

Vellanki, H., Antunes, M., Locke, R., McGreevy, T., Mackley, A., Eubanks, J., Emberger, J., Western, M., Paul D. Decreased incidence of pneumothorax in very-low-birth-weight infants following increased monitoring of tidal volumes. Epub 4160.4.

Abstracts2view.com/pas. 2011.

Ziegler, K., Paul, D., Hoffman, M., Cohn, J., Locke, R. Variation in NICU late preterm admission rates without identifiable cause. Epub 4516.253. Abstracts2view.com/pas. 2011.

Zisk, J., Mackley, A., Cleary, G., Chang, E., Christensen, R., Paul, D. Randomized multi-center pilot study of platelet transfusion using platelet count vs platelet mass. Epub 689. Abstracts2view.com/ pas.2011.

Publications

As a private, not-for-profit regional health care system, we rely in part on the generosity of

individuals, foundations and corporations to fulfill our mission.

To learn more about how you can help support

Women’s, Infants’ and Children’s Health priorities, please contact Karen Gadson in the Development

Office at 302-327-3337 or kgadson@christianacare.org, or visit www.christianacare.org/donors.

39

4755 Ogletown-Stanton Road Newark, DE 19718 302-733-3576 www.christianacare.org 15WHS14