831: Developmental delays in children born to mothers with systemic lupus erythematosus

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including mental retardation, cardiac defects, and facial dysmor- phism. Studies have shown that these outcomes can be significantly improved if maternal Phe levels are within normal limits prior to pregnancy or early in gestation. However, achieving low levels of Phe during pregnancy can be difficult. We have developed an engineered metabolic pathway to process excess Phe. Our primary objective was to determine the safety of our approach in a mouse model of PKU. Our second objective was to obtain baseline efficacy data for future optimization. STUDY DESIGN: A stable cell line overexpressing phenylalanine hy- droxylase was encapsulated within semi-permeable alginate micro- spheres. These encapsulated cells were injected intraperitoneally into PAHenu2 mice (n5). Mice were observed for signs of illness and were bled at days 0, 1, and 28. Blood was assayed in duplicate by tandem mass spectroscopy to determine the Phe concentration. To control for the effects of the alginate microspheres, background strain, heterozygous, and homozygous mice were also injected with empty microspheres. RESULTS: All of the mice survived the encapsulated cell injection and remained alive at 28 days post-injection. Mice treated with empty microspheres did not exhibit any significant changes in Phe. In PKU model mice, Phe was significantly reduced by 15% on Day 1 and remained at this level on Day 28. CONCLUSIONS: Our approach was well-tolerated and safe in an animal model. While further optimization of our system is necessary to re- duce Phe to normal levels, we were encouraged by the ability of the encapsulated cells to significantly reduce by Phe in vivo and for this reduction to be maintained for 28 days. After further optimization, we will insert encapsulated cells or empty spheres into female PKU model mice before breeding, and at 7, and 14 days post conception and de- termine whether there are cognitive and physical differences between pups born to treated and untreated dams. 829 Pregnancy and maternal outcomes in women who have undergone repair of congenital d-transposition of the great arteries Torri Metz 1 , Marc Jackson 2 , Angela Yetman 3 1 University of Utah, Salt Lake City, UT, 2 Intermountain Healthcare, Salt Lake City, UT, 3 Primary Children’s Medical Center, Salt Lake City, UT OBJECTIVE: Women who underwent an atrial switch procedure (Sen- ning or Mustard) for repair of d-Transposition of the Great Arteries (d-TGA) are now of reproductive age. We sought to assess their car- diac and reproductive outcomes. STUDY DESIGN: Clinical and echocardiographic data were reviewed from all women with d-TGA corrected by an atrial switch procedure receiving care at 2 tertiary care centers in a single state over a 10-year period. Most had undergone annual echocardiograms, and those ex- periencing a pregnancy had at least 1 additional echocardiogram per- formed during pregnancy or postpartum. Echocardiograms were re- viewed by a single cardiologist for qualitative and quantitative (dP/dt [change in ventricular pressure over time]) measures of RV function. The degree of tricuspid insufficiency, and presence or absence of atrial baffle obstruction were recorded. RESULTS: Of 28 women identified, 3 had 1 pregnancy, and 7 had 2 or more (20 total pregnancies). The spontaneous abortion rate was 29% (N6). One medical termination was performed for cardiac indica- tions. Ten (40%) women received infertility treatment. There were 13 live births. The preterm birth rate was 64%; (mean GA 35.2 wks, range 26-40 wks). The rates of cesarean and operative vaginal delivery were both 23%. Pregnancy complications occurred in 5 women (placenta previa, severe preeclampsia, IUGR, PPROM, and preterm labor). There were no maternal or perinatal deaths. Serial echo data (N9) demonstrated a fall in measures of RV function (decreased dp/dt 31.2 /-20.1% and worsening TR) during pregnancy with improvement postpartum. Symptomatic baffle obstruction requiring postpartum stenting occurred in 38% of the pregnancies resulting in live births. CONCLUSIONS: Women who have undergone an atrial switch proce- dure for d-TGA have high rates of miscarriage, infertility, and preterm birth. RV function transiently decreases during pregnancy. Unmask- ing of occult atrial baffle obstruction is common and calls for careful pre-pregnancy imaging and treatment prior to pregnancy. 830 Trends in prevalence of peripartum cardiomyopathy and association with fetal and neonatal outcomes Valerie Whiteman 1 , Jingyi Duan 2 , Alfred Mbah 3 , Amina P. Alio 4 , Luminita Crisan 1 , Phillip J. Marty 3 , Hamisu Salihu 5 1 University of South Florida School of Medicine Dept OB/GYN, Division of Maternal Fetal Medicine, Tampa, FL, 2 University of South Florida Department of Epidemiology and Biostatistics, Tampa, FL, 3 University of South Florida Lawton Chiles Center for Healthy Mothers and Babies, Department of Community and Family Health, Tampa, FL, 4 Department of Community and Family Health, University of South Florida, Tampa, FL, 5 University of South Florida Dept OB/GYN, Division of MFM, Lawton Chiles Center for Healthy Mothers and Babies, Tampa, FL OBJECTIVE: To examine temporal trends of cardiomyopathy in preg- nancy and associated fetal and neonatal morbidities. STUDY DESIGN: A population-based retrospective cohort analysis was performed utilizing the Florida Hospital discharge data linked to de- livery information from 1998-2007 (N1,738,860 deliveries). Preva- lence rates of cardiomyopathy and trend statistics were computed. Logistic regression moders were used to generate adjusted odds ratios (AOR) and 95% confidence intervals (CI) for the risk of fetal and neonatal morbidity. RESULTS: There were 410 cardiomyopathy cases during the study pe- riod. The prevalence of cardiomyopathy increased from 9 per 100,000 births to 32 per 100,000 births (p for trend 0.0001), representingan absolute increase of 23% and a relative increase of 255% over the previous decade. Cardiomyopathy was significantly associated with obesity, smoking, African American background, 12 years educa- tion, anemia, diabetes, gestational and chronic hypertension, pre-ec- lampsia / eclampsia, placental abruption and pre-existing renal dis- ease (all P value 0.01) Infants of affected mothers were at greater risk for morbidity including low birth weight, intrauterine growth restric- tion, prematurity, neonatal seizures and NICU admission. CONCLUSIONS: The prevalence of cardiomyopathy during pregnancy has increased substantially over the previous decade. there is a dire need for more research to elucidate contributing factors to the up- surge in order to reverse the trend. Neonatal morbidity AOR (95% CI) Low brith weight 3.42 (2.72-4.31) .......................................................................................................................................................................................... Growth restriction 2.60 (1.16-5.84) .......................................................................................................................................................................................... Prematurityi 3.45 (2.78-4.28) .......................................................................................................................................................................................... Neonatal Seizures 6.24 (1.55-25.1) .......................................................................................................................................................................................... NICU admission 3.57 (2.61-4.89) .......................................................................................................................................................................................... 831 Developmental delays in children born to mothers with systemic lupus erythematosus Vivian Romero 1 , Emily Somers 2 , Marnie Hyzy 2 , Caroline Gordon 3 , William J McCune 2 , Wendy Marder 2 1 University of Michigan, Ann Arbor, MI, 2 University of Michigan Health System, Ann Arbor, MI, 3 University of Birmingham, Rheumatology Research Group OBJECTIVE: Due to the paucity of data on the long-term outcomes of children born to mothers with systemic lupus erythematosus (SLE) we conducted a study to assess the prevalence of developmental delays in the offspring and to identify associated factors. STUDY DESIGN: This cohort study included women attending the out- patient rheumatology clinics at a single institution between February and July 2010. Subjects met American College of Rheumatology (ACR) criteria for SLE prior to at least one of their pregnancies, and www.AJOG.org Academic Issues, Antepartum Fetal Assessment, Genetics, Hypertension, Medical-Surgical Complications, Ultrasound-Imaging Poster Session V Supplement to JANUARY 2011 American Journal of Obstetrics & Gynecology S323

Transcript of 831: Developmental delays in children born to mothers with systemic lupus erythematosus

Page 1: 831: Developmental delays in children born to mothers with systemic lupus erythematosus

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www.AJOG.org Academic Issues, Antepartum Fetal Assessment, Genetics, Hypertension, Medical-Surgical Complications, Ultrasound-Imaging Poster Session V

including mental retardation, cardiac defects, and facial dysmor-phism. Studies have shown that these outcomes can be significantlyimproved if maternal Phe levels are within normal limits prior topregnancy or early in gestation. However, achieving low levels of Pheduring pregnancy can be difficult. We have developed an engineeredmetabolic pathway to process excess Phe. Our primary objective wasto determine the safety of our approach in a mouse model of PKU.Our second objective was to obtain baseline efficacy data for futureoptimization.STUDY DESIGN: A stable cell line overexpressing phenylalanine hy-

roxylase was encapsulated within semi-permeable alginate micro-pheres. These encapsulated cells were injected intraperitoneally intoAHenu2 mice (n�5). Mice were observed for signs of illness andere bled at days 0, 1, and 28. Blood was assayed in duplicate by

andem mass spectroscopy to determine the Phe concentration. Toontrol for the effects of the alginate microspheres, background strain,eterozygous, and homozygous mice were also injected with emptyicrospheres.

RESULTS: All of the mice survived the encapsulated cell injection andemained alive at 28 days post-injection. Mice treated with emptyicrospheres did not exhibit any significant changes in Phe. In PKUodel mice, Phe was significantly reduced by 15% on Day 1 and

emained at this level on Day 28.CONCLUSIONS: Our approach was well-tolerated and safe in an animal

odel. While further optimization of our system is necessary to re-uce Phe to normal levels, we were encouraged by the ability of thencapsulated cells to significantly reduce by Phe in vivo and for thiseduction to be maintained for 28 days. After further optimization, weill insert encapsulated cells or empty spheres into female PKU modelice before breeding, and at 7, and 14 days post conception and de-

ermine whether there are cognitive and physical differences betweenups born to treated and untreated dams.

829 Pregnancy and maternal outcomes in womenho have undergone repair of congenital-transposition of the great arteries

Torri Metz1, Marc Jackson2, Angela Yetman3

1University of Utah, Salt Lake City, UT, 2Intermountain Healthcare, SaltLake City, UT, 3Primary Children’s Medical Center, Salt Lake City, UTOBJECTIVE: Women who underwent an atrial switch procedure (Sen-

ing or Mustard) for repair of d-Transposition of the Great Arteriesd-TGA) are now of reproductive age. We sought to assess their car-iac and reproductive outcomes.

STUDY DESIGN: Clinical and echocardiographic data were reviewedfrom all women with d-TGA corrected by an atrial switch procedurereceiving care at 2 tertiary care centers in a single state over a 10-yearperiod. Most had undergone annual echocardiograms, and those ex-periencing a pregnancy had at least 1 additional echocardiogram per-formed during pregnancy or postpartum. Echocardiograms were re-viewed by a single cardiologist for qualitative and quantitative (dP/dt[change in ventricular pressure over time]) measures of RV function.The degree of tricuspid insufficiency, and presence or absence of atrialbaffle obstruction were recorded.RESULTS: Of 28 women identified, 3 had 1 pregnancy, and 7 had 2 or

ore (20 total pregnancies). The spontaneous abortion rate was 29%N�6). One medical termination was performed for cardiac indica-ions. Ten (40%) women received infertility treatment. There were 13ive births. The preterm birth rate was 64%; (mean GA 35.2 wks, range6-40 wks). The rates of cesarean and operative vaginal delivery wereoth 23%. Pregnancy complications occurred in 5 women (placentarevia, severe preeclampsia, IUGR, PPROM, and preterm labor).here were no maternal or perinatal deaths. Serial echo data (N�9)emonstrated a fall in measures of RV function (decreased dp/dt 31.2/-20.1% and worsening TR) during pregnancy with improvement

ostpartum. Symptomatic baffle obstruction requiring postpartum

tenting occurred in 38% of the pregnancies resulting in live births.

Supplem

CONCLUSIONS: Women who have undergone an atrial switch proce-ure for d-TGA have high rates of miscarriage, infertility, and pretermirth. RV function transiently decreases during pregnancy. Unmask-

ng of occult atrial baffle obstruction is common and calls for carefulre-pregnancy imaging and treatment prior to pregnancy.

830 Trends in prevalence of peripartum cardiomyopathynd association with fetal and neonatal outcomes

Valerie Whiteman1, Jingyi Duan2, Alfred Mbah3, Amina P.lio4, Luminita Crisan1, Phillip J. Marty3, Hamisu Salihu5

1University of South Florida School of Medicine Dept OB/GYN, Divisionf Maternal Fetal Medicine, Tampa, FL, 2University of South Floridaepartment of Epidemiology and Biostatistics, Tampa, FL, 3University

of South Florida Lawton Chiles Center for Healthy Mothers and Babies,Department of Community and Family Health, Tampa, FL, 4Department

f Community and Family Health, University of South Florida, Tampa, FL,5University of South Florida Dept OB/GYN, Division of MFM, Lawton

hiles Center for Healthy Mothers and Babies, Tampa, FLOBJECTIVE: To examine temporal trends of cardiomyopathy in preg-

ancy and associated fetal and neonatal morbidities.STUDY DESIGN: A population-based retrospective cohort analysis was

erformed utilizing the Florida Hospital discharge data linked to de-ivery information from 1998-2007 (N�1,738,860 deliveries). Preva-ence rates of cardiomyopathy and trend statistics were computed.ogistic regression moders were used to generate adjusted odds ratiosAOR) and 95% confidence intervals (CI) for the risk of fetal andeonatal morbidity.

RESULTS: There were 410 cardiomyopathy cases during the study pe-iod. The prevalence of cardiomyopathy increased from 9 per 100,000irths to 32 per 100,000 births (p for trend 0.0001), representinganbsolute increase of 23% and a relative increase of 255% over therevious decade. Cardiomyopathy was significantly associated withbesity, smoking, African American background, � 12 years educa-ion, anemia, diabetes, gestational and chronic hypertension, pre-ec-ampsia / eclampsia, placental abruption and pre-existing renal dis-ase (all P value �0.01) Infants of affected mothers were at greater riskor morbidity including low birth weight, intrauterine growth restric-ion, prematurity, neonatal seizures and NICU admission.

CONCLUSIONS: The prevalence of cardiomyopathy during pregnancyas increased substantially over the previous decade. there is a direeed for more research to elucidate contributing factors to the up-urge in order to reverse the trend.

Neonatalmorbidity AOR (95% CI)

Low brith weight 3.42 (2.72-4.31)..........................................................................................................................................................................................

Growth restriction 2.60 (1.16-5.84)..........................................................................................................................................................................................

Prematurityi 3.45 (2.78-4.28)..........................................................................................................................................................................................

Neonatal Seizures 6.24 (1.55-25.1)..........................................................................................................................................................................................

NICU admission 3.57 (2.61-4.89)..........................................................................................................................................................................................

831 Developmental delays in children born toothers with systemic lupus erythematosus

Vivian Romero1, Emily Somers2, Marnie Hyzy2, Carolineordon3, William J McCune2, Wendy Marder2

1University of Michigan, Ann Arbor, MI, 2University ofichigan Health System, Ann Arbor, MI, 3University

f Birmingham, Rheumatology Research GroupOBJECTIVE: Due to the paucity of data on the long-term outcomes ofhildren born to mothers with systemic lupus erythematosus (SLE)e conducted a study to assess the prevalence of developmental delays

n the offspring and to identify associated factors.STUDY DESIGN: This cohort study included women attending the out-patient rheumatology clinics at a single institution between Februaryand July 2010. Subjects met American College of Rheumatology

(ACR) criteria for SLE prior to at least one of their pregnancies, and

ent to JANUARY 2011 American Journal of Obstetrics & Gynecology S323

Page 2: 831: Developmental delays in children born to mothers with systemic lupus erythematosus

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Poster Session V Academic Issues, Antepartum Fetal Assessment, Genetics, Hypertension, Medical-Surgical Complications, Ultrasound-Imaging www.AJOG.org

had at least one live birth following SLE diagnosis. Data on mother’smedical and obstetric histories, as well as children’s perinatal, medicaland developmental outcomes were collected through a structuredclinical interview and hospital record review. Autoantibody profileswere obtained. Developmental outcomes were stratified by 0-2 yearsor � 2 years of life.RESULTS: Data on 30 mothers and 43 eligible offspring were analyzed.

5 (60%) of the offspring were male. During the first 2 years of life, 614%) of the children were reported to have developmental delays,ncluding motor skills (fine and gross) and speech delays. After age 2ears, 10 (23.3%) of the children had special educational needs, in-luding 8 (18.6%) who required speech therapy. No difference in thencidence of prematurity among the 2 groups with or without speechelay was found. No associations were detected between requirement

or speech therapy and sex of offspring, or medication exposures dur-ng first trimester of pregnancy. However, maternal history of anti-hospholipid antibody syndrome (APS) was significantly associatedith speech therapy requirement of offspring after 2 years of age: 4/9

44.4%) with maternal APS history vs. 4/34 (11.8%) without maternalPS history (p�0.046 by Fisher’s exact test).

CONCLUSIONS: Maternal SLE, and in particular APS history, may bessociated with speech or other developmental delays among off-pring. Prospective, controlled studies should investigate these asso-iations in more depth, and to explore the role of specific types ofntiphospholipid antibodies.

832 At midgestation fetal cardiac exam is possible in mostf the morbidly obese and super obese pregnant women

Asha Rijhsinghani1, Diedre Fleener1

1University of Iowa Hospitals and Clinics, Iowa City, IAOBJECTIVE: Previous studies have reported a 2 to 6.5 fold increase inate of fetal cardiac defects in obese pregnant patients. Fetal echocar-iography is often suboptimal and visualization of the outflow tracts iseported to be possible in �30% of obese patients. Our aim was to seef current technology and experience contributes to an improvementn fetal cardiac examination in the severely obese pregnant patient.

STUDY DESIGN: We conducted a retrospective cohort study of severelybese women (BMI�40) undergoing routine fetal cardiac ultrasoundxams at mid gestation. The study included patients seen from 2007 to010. Women with BMI of � 40 and those that had a mid gestationltrasound performed between 18 and 22 weeks, were included in thenalysis. Fetal heart exam included a 4 chamber view of the heart,VOT and RVOT. Maternal abdominal (MA) wall thickness was mea-ured in cm in all patients.

RESULTS: 139 severely obese pregnant women (BMI�40) were seen inhe Fetal Diagnosis unit from 2007 to 2010. Fetal cardiac examinationas attempted on all patients. 83 / 138 were examined between gesta-

ion ages of 18 - 22 weeks and included in the analysis, rest were seent �22 weeks and therefore excluded. Average BMI at registration was7.2 in this subgroup. 49 were super obese (BMI�45) and 35 wereorbidly obese (BMI 40-44.9). Average gestational age at ultrasoundas similar in super obese and morbidly obese patients (20.19 vs.0.35 wks). Average MA thickness was 10.25 � 2.27 cm vs.7.98 �1.77m in super vs. morbidly obese women (p�0.001). In the morbidlybese women, the fetal cardiac exam was adequate in over 85% ofatients. The success in adequately visualizing the fetal heart was

ower in the super obese, but still much higher than previously re-orted.

CONCLUSIONS: In super obese and morbidly obese patients, it is possi-le to adequately examine the fetal heart in majority of the patients,etween 18-22 weeks with the current technology and experience.

m

S324 American Journal of Obstetrics & Gynecology Supplement to JANUARY 2

BMI nGA atSono wks

Mat Abd incms

4CHSeen %

LVOTSeen %

RVOTSeen %

0-44.9 35 20.35 7.98 � 1.77 85.7 91.4 88.6..........................................................................................................................................................................................

45-49.9 25 20.01 9.60 � 2.2 80.8 76.9 80.8..........................................................................................................................................................................................

50-54.9 12 20.43 10.33 � 1.97 58.3 50.0 58.3..........................................................................................................................................................................................

� 55 10 20.37 11.80 � 2.0 80 60 70..........................................................................................................................................................................................

833 The impact of a customized growth chart on thessociation between small for gestational ageSGA) and neonatal morbidity and mortality

Cindy Zhang1, Alison Cahill2, George Macones2, Anthony Odibo2

1Duke University Hospital, Durham, NC, 2Washingtonniversity in St. Louis, St. Louis, MO

OBJECTIVE: To estimate the association between SGA and adverse neo-atal outcomes in infants identified by the population-based growthhart (SGApop) and the customized growth chart (SGAcust) for a

idwestern USA population.STUDY DESIGN: This is a nested case-control study from a perinataldatabase of 72,422 births between 1990 and 2008. Cases identified asSGA using either growth chart (n�6,668) were compared to a controlgroup without SGA (n�1,864). Preterm births, congenital anomalies,and multifetal pregnancies were excluded. Primary outcomes exam-ined were periventricular leukomalacia (PVL), necrotizing enteroco-litis (NEC), intraventricular hemorrhage categories 3 or 4 (IVH 3/4),hypoglycemia, respiratory distress syndrome (RDS), neonatal death,and a composite adverse neonatal outcomes (including any one ofthese outcomes). Adjusted odds ratios for each of these events, bygrowth chart, were estimated with multivariable logistic regression.RESULTS: Outcomes of 6,668 fetuses identified as SGA were examined;

,757 (32.31%) defined as SGApop and 3,911 (45.84%) as SGAcust.eonates with hypoglycemia were significantly more likely to be iden-

ified as SGApop (OR 4.78, 95%CI 1.08-21.02) than as SGAcust (OR.15, 95%CI 0.46-9.95). Neonatal death and composite adverse out-omes, however, were more likely identified as SGAcust (OR 4.33 and.94) than as SGApop (OR 1.02 and 0.73). PVL and NEC were ex-luded from analysis due to rare occurrence. The incidences ofVH3/4 and RDS were not significantly different in either of the tworoups.

CONCLUSIONS: While small for gestational age pregnancies identifiedsing either method are associated with adverse neonatal outcomes,

he customized growth chart appears to be better at identifying thoset risk for the more severe outcome of neonatal death.

AdverseNeonatalOutcome

Neonatalcomplications(%)

SGApop (OR,95% CI)

SGAcust (OR,95% CI)

PVL 4 (0.05) – –..........................................................................................................................................................................................

NEC 7 (0.08) – –..........................................................................................................................................................................................

IVH 3/4 11 (0.13) 1.70 (0.33-8.77) 0.95 (0.17-5.21)..........................................................................................................................................................................................

Hypoglycemia 25 (0.29) 4.78 (1.08-21.02) 2.15 (0.46-9.95)..........................................................................................................................................................................................

RDS 231 (2.71) 3.67 (2.24-6.02) 2.81 (1.72-4.59)..........................................................................................................................................................................................

Neonatal Death 222 (2.60) 1.02 (0.32-3.23) 4.33 (1.72-10.93)..........................................................................................................................................................................................

CompositeAdverseOutcomes

367 (4.30) 0.73 (0.42-1.27) 2.94 (1.91-4.50)

..........................................................................................................................................................................................

834 Evaluating the efficacy of a detailed fetal anatomicurvey to detect congenital heart disease

Joseph Chappelle1, Jolene Muscat1, Lillian Meek1,aul L. Ogburn1, Reinaldo Figueroa1

1Stony Brook-Winthrop University Hospitals, Long Island, NYOBJECTIVE: Congenital heart disease (CHD) is one of the most com-

on congenital malformations and prenatal diagnosis allows for fur-

011