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635: Associations between markers of 2-3 indoleamine dioxygenase activation and inflammation in pregnant women and body mass index
Poster Session III
ajog.org 634 Physiologic blood pressure patterns in hypertensive pregnancies Lorie M. Harper, Jeffery M. Szychowski, Sarah E. Allen, Mallory Youngstrom, Alan TN Tita University of Alabama at Birmingham, Center for Women’s Reproductive Health, Department of Obstetrics and Gynecology, Birmingham, AL
OBJECTIVE: Little is understood about the pattern of blood pressure
(BP) alterations in women with chronic hypertension (HTN) during pregnancy, making distinctions between preeclampsia and normal return to elevated prepregnancy BP difficult. We aimed to assess physiologic BP changes throughout pregnancy in women with HTN who do and do not develop preeclampsia (PEC), as compared to women with no history of hypertension. STUDY DESIGN: Retrospective cohort of all singleton gestations with HTN 2000-2014 in a single tertiary care center and a randomly selected cohort of women with no history of HTN and normal pregnancy outcomes (NML) in the same time period with blood pressure measurements available <12 weeks. Subjects were excluded for major medical problems other than HTN, fetal anomalies, and initiation or increases in antihypertensives after 20 weeks. Diagnosis of PEC required both BP140/90 mm Hg and a laboratory abnormality (proteinuria, creatinine, AST, or platelets) per ACOG definitions. Comparisons were made between NML, HTN without PEC who delivered at term, and HTN with PEC. Generalized linear models were used to define and compare the nadir of systolic and diastolic BP between groups. RESULTS: Of 169 pregnancies with HTN meeting inclusion critier, 113 (67%) were included in HTN without PEC and 56 (33%) were included in HTN with PEC. 141 NML pregnancies were used as comparison group. As expected, NML subjects had lower BP throughout gestation. The nadir of systolic and diastolic BP was earliest in NML (SBP 21 (19-23 wks), DBP 23 (22-24 wks)) and HTN with PEC (SBP 21 (18-24 wks), DBP 23 (21-24 wks), Figure). In HTN without PEC, BP did not return to prepregnancy values until after 25 weeks (24-26), and remained below 140/90. CONCLUSION: Women with HTN and PEC have higher BP throughout pregnancy and earlier BP nadirs than HTN without PEC and NML. BP elevations in HTN without PEC can be expected after 25 weeks, although in this cohort blood pressures remained <140/90 mm Hg without medication adjustments.
635 Associations between markers of 2-3 indoleamine dioxygenase activation and inflammation in pregnant women and body mass index Adetola Louis-Jacques1, Dietmar Fuchs2, Allyson Duffy3, Amy D’Agata3, Teodore Postolache4, Maureen Groer3 1
University of South Florida Morsani College of Medicine, Tampa, FL, Division of Biological Chemistry, Innsbruck medical University, Innsbruck, Austria, 3University of South Florida College of Nursing, Tampa, FL, 4Mood and Anxiety Program, University of Maryland, Baltimore, MD 2
OBJECTIVE: To evaluate relationships between pregnancy body mass index (BMI), depressive mood and plasma levels of tryptophan, kynurenine, neopterin and nitrite. STUDY DESIGN: Pregnant women (N¼374) were weighed and measured once at a mean gestation of 20 weeks. Plasma was analyzed for tryptophan (trp), kynurenine (kyn), neopterin and nitrite levels. The BMI was calculated and women completed the Profile of Mood States scale. RESULTS: There was a statistically significant inverse correlation between BMI and tryptophan, and positive correlations between BMI and kyn and the kynurenine/tryptophan (kyn/trp) ratio, which correlated with neopterin concentrations BMI was also correlated with both nitrite levels and neopterin. There was no relationship between the tryptophan to kynurenine pathway and depressed mood as measured by the Profile of Mood States. There was, however a correlation between depressed mood and nitrite.
Supplement to JANUARY 2017 American Journal of Obstetrics & Gynecology
S371
Poster Session III CONCLUSION: The kyn/trp ratio and its correlation with neopterin levels indicates involvement of the 2-3 indoleamine dioxygenase (IDO-1) activity which is stimulated by inflammatory cytokines and “steals” tryptophan from serotonin production, a major neurotransmitter involved in mood. The inflammation associated with high BMI in pregnancy may be driving this reaction and depleting serotonin. Nitrite levels are a surrogate marker for nitric oxide synthase and nitrosative stress and neopterin is a marker of Th-1 immunity and both were associated with BMI. The study results suggest that pregnant obese women have an excess activation of IDO, resulting in shunting of tryptophan into the kynurenin pathway, and potentially depleting serotonin synthesis. This activation may be through obesity associated inflammation. These data provide further support for the deleterious role of obesity during pregnancy.
ajog.org considered in the model included infant characteristics, 42 log transformed metabolites and 15 metabolite ratios. Profiles generated by the tree were applied to the entire population, and relative risks (RR) adjusted for birthweight and GA were calculated with 95% confidence intervals (CIs) using Poisson logistic regression. RESULTS: Within our total population, 1,624 (0.07%) infants developed NEC, and of those, 1,267 (78.0%) were born preterm. Recursive partitioning identified eight independent risk groups (Figure). Rates of NEC within GA categories ranged from 1 in 11 to 1 in 10,000 after matched risk group criteria was applied to the entire population (Table). The individuals at highest risk were those with low levels of thyroid stimulating hormone (TSH), Black or Hispanic race/ethnicity, average to low levels of phenylalanine (PHE), and low levels of free carnitine (Figure). These factors were especially important for infants born at <34 weeks GA (RR 3.1, 95% CI 1.5-6.3) (Table). Other metabolites associated with higher risk of NEC included high levels of 17-hydroxyprogesterone (in the presence of high levels of TSH and a low PHE to tyrosine ratio) and low levels of C-8:1 (in the presence of high levels of TSH and a high PHE to tyrosine ratio) (Figure). CONCLUSION: Metabolic profiles can be used to classify infants as being at more or less risk for NEC. These profiles may be crucial for identifying groups in need of focused clinical care - particularly with respect to individualized feeding regimes.
636 Identification of independent metabolic risk groups for necrotizing enterocolitis through machine learning Scott P. Oltman1,2, Elizabeth E. Rogers3, Matthew Pantell3, Rebecca J. Baer2,4, Larry Rand2,5, Kelli K. Ryckman6, Zachary Kastenberg7, Karl Sylvester8, Laura Jeliffe-Pawlowski1,2 1 Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, 2California Preterm Birth Initiative, Benioff Children’s Hospital, University of California, San Francisco, CA, 3Department of Pediatrics, University of California San Francisco, San Francisco, CA, 4 Department of Pediatrics, University of California San Diego, La Jolla, CA, 5 Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California San Francisco, San Francisco, CA, 6Departments of Epidemiology and Pediatrics, University of Iowa, Iowa City, IA, 7Department of Surgery, Stanford University School of Medicine, Stanford, CA, 8 Department of Pediatrics, Stanford University, Stanford, CA
OBJECTIVE: To identify specific independent metabolic risk groups for necrotizing enterocolitis (NEC) at birth. STUDY DESIGN: This study included 2,276,681 singleton live births in California between 2005 and 2011 with gestational ages (GA) from 22 to 41 weeks. All infants had newborn metabolic screening data available. Data included linked birth certificate and mother and infant hospital discharge records. NEC was defined as having an ICD-9 diagnostic code. Each case of NEC was matched to four controls by GA and birthweight Z-score, which left a final sample of 1,607 cases and 6,248 controls. Recursive partitioning was used to develop a conditional inference tree from the matched sample. A Bonferonni corrected p-value of 0.10 generated from quadratic correlation hypothesis tests was used as splitting criteria. Variables
637 Microcephaly in the era of the Zika virus: diagnostic criteria needed Tracy Grossman, Shari Gelber Weill Cornell Medical College, New York, NY
OBJECTIVE: CDC guidelines endorse evaluation of an infant for possible congenital Zika virus infection in the setting of
S372 American Journal of Obstetrics & Gynecology Supplement to JANUARY 2017
ajog.org 634 Physiologic blood pressure patterns in hypertensive pregnancies Lorie M. Harper, Jeffery M. Szychowski, Sarah E. Allen, Mallory Youngstrom, Alan TN Tita University of Alabama at Birmingham, Center for Women’s Reproductive Health, Department of Obstetrics and Gynecology, Birmingham, AL
OBJECTIVE: Little is understood about the pattern of blood pressure
(BP) alterations in women with chronic hypertension (HTN) during pregnancy, making distinctions between preeclampsia and normal return to elevated prepregnancy BP difficult. We aimed to assess physiologic BP changes throughout pregnancy in women with HTN who do and do not develop preeclampsia (PEC), as compared to women with no history of hypertension. STUDY DESIGN: Retrospective cohort of all singleton gestations with HTN 2000-2014 in a single tertiary care center and a randomly selected cohort of women with no history of HTN and normal pregnancy outcomes (NML) in the same time period with blood pressure measurements available <12 weeks. Subjects were excluded for major medical problems other than HTN, fetal anomalies, and initiation or increases in antihypertensives after 20 weeks. Diagnosis of PEC required both BP140/90 mm Hg and a laboratory abnormality (proteinuria, creatinine, AST, or platelets) per ACOG definitions. Comparisons were made between NML, HTN without PEC who delivered at term, and HTN with PEC. Generalized linear models were used to define and compare the nadir of systolic and diastolic BP between groups. RESULTS: Of 169 pregnancies with HTN meeting inclusion critier, 113 (67%) were included in HTN without PEC and 56 (33%) were included in HTN with PEC. 141 NML pregnancies were used as comparison group. As expected, NML subjects had lower BP throughout gestation. The nadir of systolic and diastolic BP was earliest in NML (SBP 21 (19-23 wks), DBP 23 (22-24 wks)) and HTN with PEC (SBP 21 (18-24 wks), DBP 23 (21-24 wks), Figure). In HTN without PEC, BP did not return to prepregnancy values until after 25 weeks (24-26), and remained below 140/90. CONCLUSION: Women with HTN and PEC have higher BP throughout pregnancy and earlier BP nadirs than HTN without PEC and NML. BP elevations in HTN without PEC can be expected after 25 weeks, although in this cohort blood pressures remained <140/90 mm Hg without medication adjustments.
635 Associations between markers of 2-3 indoleamine dioxygenase activation and inflammation in pregnant women and body mass index Adetola Louis-Jacques1, Dietmar Fuchs2, Allyson Duffy3, Amy D’Agata3, Teodore Postolache4, Maureen Groer3 1
University of South Florida Morsani College of Medicine, Tampa, FL, Division of Biological Chemistry, Innsbruck medical University, Innsbruck, Austria, 3University of South Florida College of Nursing, Tampa, FL, 4Mood and Anxiety Program, University of Maryland, Baltimore, MD 2
OBJECTIVE: To evaluate relationships between pregnancy body mass index (BMI), depressive mood and plasma levels of tryptophan, kynurenine, neopterin and nitrite. STUDY DESIGN: Pregnant women (N¼374) were weighed and measured once at a mean gestation of 20 weeks. Plasma was analyzed for tryptophan (trp), kynurenine (kyn), neopterin and nitrite levels. The BMI was calculated and women completed the Profile of Mood States scale. RESULTS: There was a statistically significant inverse correlation between BMI and tryptophan, and positive correlations between BMI and kyn and the kynurenine/tryptophan (kyn/trp) ratio, which correlated with neopterin concentrations BMI was also correlated with both nitrite levels and neopterin. There was no relationship between the tryptophan to kynurenine pathway and depressed mood as measured by the Profile of Mood States. There was, however a correlation between depressed mood and nitrite.
Supplement to JANUARY 2017 American Journal of Obstetrics & Gynecology
S371
Poster Session III CONCLUSION: The kyn/trp ratio and its correlation with neopterin levels indicates involvement of the 2-3 indoleamine dioxygenase (IDO-1) activity which is stimulated by inflammatory cytokines and “steals” tryptophan from serotonin production, a major neurotransmitter involved in mood. The inflammation associated with high BMI in pregnancy may be driving this reaction and depleting serotonin. Nitrite levels are a surrogate marker for nitric oxide synthase and nitrosative stress and neopterin is a marker of Th-1 immunity and both were associated with BMI. The study results suggest that pregnant obese women have an excess activation of IDO, resulting in shunting of tryptophan into the kynurenin pathway, and potentially depleting serotonin synthesis. This activation may be through obesity associated inflammation. These data provide further support for the deleterious role of obesity during pregnancy.
ajog.org considered in the model included infant characteristics, 42 log transformed metabolites and 15 metabolite ratios. Profiles generated by the tree were applied to the entire population, and relative risks (RR) adjusted for birthweight and GA were calculated with 95% confidence intervals (CIs) using Poisson logistic regression. RESULTS: Within our total population, 1,624 (0.07%) infants developed NEC, and of those, 1,267 (78.0%) were born preterm. Recursive partitioning identified eight independent risk groups (Figure). Rates of NEC within GA categories ranged from 1 in 11 to 1 in 10,000 after matched risk group criteria was applied to the entire population (Table). The individuals at highest risk were those with low levels of thyroid stimulating hormone (TSH), Black or Hispanic race/ethnicity, average to low levels of phenylalanine (PHE), and low levels of free carnitine (Figure). These factors were especially important for infants born at <34 weeks GA (RR 3.1, 95% CI 1.5-6.3) (Table). Other metabolites associated with higher risk of NEC included high levels of 17-hydroxyprogesterone (in the presence of high levels of TSH and a low PHE to tyrosine ratio) and low levels of C-8:1 (in the presence of high levels of TSH and a high PHE to tyrosine ratio) (Figure). CONCLUSION: Metabolic profiles can be used to classify infants as being at more or less risk for NEC. These profiles may be crucial for identifying groups in need of focused clinical care - particularly with respect to individualized feeding regimes.
636 Identification of independent metabolic risk groups for necrotizing enterocolitis through machine learning Scott P. Oltman1,2, Elizabeth E. Rogers3, Matthew Pantell3, Rebecca J. Baer2,4, Larry Rand2,5, Kelli K. Ryckman6, Zachary Kastenberg7, Karl Sylvester8, Laura Jeliffe-Pawlowski1,2 1 Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, 2California Preterm Birth Initiative, Benioff Children’s Hospital, University of California, San Francisco, CA, 3Department of Pediatrics, University of California San Francisco, San Francisco, CA, 4 Department of Pediatrics, University of California San Diego, La Jolla, CA, 5 Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California San Francisco, San Francisco, CA, 6Departments of Epidemiology and Pediatrics, University of Iowa, Iowa City, IA, 7Department of Surgery, Stanford University School of Medicine, Stanford, CA, 8 Department of Pediatrics, Stanford University, Stanford, CA
OBJECTIVE: To identify specific independent metabolic risk groups for necrotizing enterocolitis (NEC) at birth. STUDY DESIGN: This study included 2,276,681 singleton live births in California between 2005 and 2011 with gestational ages (GA) from 22 to 41 weeks. All infants had newborn metabolic screening data available. Data included linked birth certificate and mother and infant hospital discharge records. NEC was defined as having an ICD-9 diagnostic code. Each case of NEC was matched to four controls by GA and birthweight Z-score, which left a final sample of 1,607 cases and 6,248 controls. Recursive partitioning was used to develop a conditional inference tree from the matched sample. A Bonferonni corrected p-value of 0.10 generated from quadratic correlation hypothesis tests was used as splitting criteria. Variables
637 Microcephaly in the era of the Zika virus: diagnostic criteria needed Tracy Grossman, Shari Gelber Weill Cornell Medical College, New York, NY
OBJECTIVE: CDC guidelines endorse evaluation of an infant for possible congenital Zika virus infection in the setting of
S372 American Journal of Obstetrics & Gynecology Supplement to JANUARY 2017