Clinical Assistant Professor, Obstetrics & Gynecology - Maternal Fetal Medicine
BA, Harvard University, Biochemical Sciences (1999)
Fetal imaging prompts maternal diagnosis: autosomal dominant polycystic kidney disease
JOURNAL OF PERINATOLOGY
2015; 35 (7): 537-538
Autosomal dominant polycystic kidney disease (ADPKD) is a common inherited disorder. Ultrasound (US) findings can include enlarged echogenic kidneys in utero and cysts in multiple organs in adults. Though a highly penetrant disease, due to varied clinical expression and the typical late onset of symptoms, reproductive-aged women may not know their carrier status. We present two cases in which fetal US findings suggested ADPKD and additional evaluation identified likely maternal ADPKD as well.
View details for DOI 10.1038/jp.2015.50
View details for Web of Science ID 000357059200015
View details for PubMedID 26111650
Correlation of continuous glucose monitoring profiles with pregnancy outcomes in nondiabetic women.
American journal of perinatology
2015; 32 (5): 461-468
Objective To determine whether hyperglycemic excursions detected by continuous glucose monitoring (CGM) correlate with birth weight percentile and other pregnancy outcomes, and whether CGM correlates better with these outcomes than a single glucose value from a 1-hour glucose challenge test (GCT). Study Design This was a prospective observational study of 55 pregnant patients without preexisting diabetes, who wore a CGM device for up to 7 days, between 24 and 28 weeks' gestation. The area under the curve (AUC) of hyperglycemic excursions above various thresholds (110, 120, 130, 140, and 180 mg/dL) was calculated. These AUC values, and results from a standard 50-g GCT, were correlated with our primary outcome of birth weight percentile, and secondary outcomes of unplanned operative delivery, pregnancy complications, delivery complications, fetal complications, and neonatal complications. Results A consistent correlation was seen between all AUC thresholds and birth weight percentile (r = 0.29, p < 0.05 for AUC-110, -120, -130, and -140; r = 0.25, p = 0.07 for AUC-180). This correlation was stronger than that of 1-hour oral GCT (r = - 0.02, p = 0.88). There was no association between AUC values and other outcomes. Conclusions Among nondiabetic pregnant patients, hyperglycemic excursions detected by CGM show a stronger correlation to birth weight percentile than blood glucose values obtained 1-hour after a 50-g oral GCT.
View details for DOI 10.1055/s-0034-1390344
View details for PubMedID 25262455
Maternal glucose response to betamethasone administration.
American journal of perinatology
2015; 30 (2): 143-148
Objective This study aims to describe the pattern of maternal glucose response to betamethasone administration using a continuous glucose monitoring system. Study Design A prospective observational trial was conducted among women receiving clinically indicated betamethasone between 24 and 34 weeks gestation. At the time of initial betamethasone administration, a continuous glucose monitoring device was inserted which measured interstitial fluid glucose levels every 5 minutes. Glucose levels were monitored for 7 days, until delivery, or until hospital discharge, whichever came first. We recorded the percentage of time women spent above three glucose thresholds: 110, 144, and 180 mg/dL, respectively. Results A total of 17 women were enrolled at the time of betamethasone administration and data were available for 15 patients. There were 11 nondiabetic and 4 diabetic women. Both diabetic and nondiabetic women had the highest recorded blood glucose readings between 24 and 48 hours after the first injection of betamethasone. In that period, nondiabetic women spent 73, 40, and 17% of the time with blood glucose levels above the 110, 144, and 180 mg/dL thresholds, respectively. Conclusion Nondiabetic women receiving betamethasone manifest significant hyperglycemia after betamethasone administration. If delivery is imminent, maternal glucose response to betamethasone may need to be monitored to prevent possible neonatal hypoglycemia.
View details for DOI 10.1055/s-0034-1376387
View details for PubMedID 24915559
- Endometrial VEGF induces placental sFLT1 and leads to pregnancy complications JOURNAL OF CLINICAL INVESTIGATION 2014; 124 (11): 4941-4952
Investigation of maternal environmental exposures in association with self-reported preterm birth.
2014; 45: 1-7
Identification of maternal environmental factors influencing preterm birth risks is important to understand the reasons for the increase in prematurity since 1990. Here, we utilized a health survey, the US National Health and Nutrition Examination Survey (NHANES) to search for personal environmental factors associated with preterm birth. 201 urine and blood markers of environmental factors, such as allergens, pollutants, and nutrients were assayed in mothers (range of N: 49-724) who answered questions about any children born preterm (delivery <37 weeks). We screened each of the 201 factors for association with any child born preterm adjusting by age, race/ethnicity, education, and household income. We attempted to verify the top finding, urinary bisphenol A, in an independent study of pregnant women attending Lucile Packard Children's Hospital. We conclude that the association between maternal urinary levels of bisphenol A and preterm birth should be evaluated in a larger epidemiological investigation.
View details for DOI 10.1016/j.reprotox.2013.12.005
View details for PubMedID 24373932
Cloacal dysgenesis diagnosis by prenatal ultrasound and MRI
2014; 44 (2): 230-233
Cloacal malformations are a spectrum of congenital pelvic malformations that result from abnormal cloacal division during early embryogenesis. Depending on the timing of the developmental arrest, a spectrum of abnormalities can result, ranging from urogenital sinus malformations to cloacal dysgenesis. This case highlights the unique imaging features of cloacal dysgenesis, which is an extremely rare variant of this malformation spectrum. This variant is also the most severe manifestation of the cloacal malformation spectrum.
View details for DOI 10.1007/s00247-013-2792-0
View details for Web of Science ID 000330987900015
View details for PubMedID 24042433
Utilization of available prenatal screening and diagnosis: effects of the California screen program
JOURNAL OF PERINATOLOGY
2012; 32 (12): 907-912
In 2009, the California Genetic Disease Branch introduced an aneuploidy screening program allowing Medi-Cal (state insured) patients access to state-sponsored first-trimester screening. The objective of this study was to assess the effect of greater access to prenatal screening on available resources at a single center.Data of prenatal screening and diagnostic procedures performed 4 months before the introduction of the program were compared with those of 12 months following the introduction.Between December 2008 and March 2010, 7689 women underwent first trimester screening, 1286 underwent amniocentesis and 398 underwent chorionic villus sampling. When a comparison was made between the 4 months before and the 12 months after the program's introduction, a greater number of nuchal translucency (NT) examinations was seen to have been performed (384 per month vs 513 per month, P=0.001). Prenatal diagnostic procedures did not increase, but a greater proportion was performed for positive screen results.Introduction of the California screening program was associated with increased NT procedures and fewer invasive procedures for advanced maternal age.
View details for DOI 10.1038/jp.2012.8
View details for Web of Science ID 000311831700002
View details for PubMedID 22402484
- Continuous Glucose Monitoring During Pregnancy in Women With Polycystic Ovary Syndrome OBSTETRICS AND GYNECOLOGY 2012; 119 (2): 383-384
Continuous glucose monitoring in pregnancy: new frontiers in clinical applications and research.
Journal of diabetes science and technology
2012; 6 (6): 1478-1485
Current treatment of diabetes in pregnancy relies on intermittent self-monitoring of blood glucoses using finger sticks to monitor capillary blood glucoses. Continuous glucose monitoring (CGM) systems are an emerging technology that allow frequent glucose measurements (every 5 min) and the ability to monitor glucose trends in real time. Although these devices are currently expensive and mildly invasive to use, there is huge potential for their use in both the research and clinical realms. From a research perspective, there is the potential to better understand glucose metabolism in pregnancy, both in patients with and without diabetes. For the treating clinician, CGM has the potential to improve detection of hyperglycemic excursions as well as asymptomatic hypoglycemia and the data to improve management of glucose levels in diabetes patients. In this article, we review current literature examining use of CGM in both research and clinical applications.
View details for PubMedID 23294795
- O1. Dramatic upregulation of HIF-1a in the endovascular and extravillous trophoblasts at the maternal-fetal interface in preeclamptic pregnancies. Pregnancy hypertension 2011; 1 (3-4): 257-?
Decreased Circulating Soluble Tie2 Levels in Preeclampsia May Result from Inhibition of Vascular Endothelial Growth Factor (VEGF) Signaling
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
2011; 96 (7): E1148-E1152
Recent studies have found dysregulation in circulating levels of a number of angiogenic factors and their soluble receptors in preeclampsia. In this study, we examined the mechanism of production of soluble Tie2 (sTie2) and its potential connection to the failure of vascular remodeling in preeclamptic pregnancies.Serum samples were collected prospectively from 41 pregnant subjects at five different time points throughout pregnancy. Five of these subjects developed preeclampsia. For a second study, serum and placental samples were collected at delivery from preeclamptic and gestational age-matched controls. We examined serum sTie2 levels, and angiopoietin 1, angiopoietin 2, and Tie2 mRNA expression and localization in placental samples from the central basal plate area. We also examined the effects of vascular endothelial growth factor (VEGF) and a matrix metalloproteinase (MMP) inhibitor on proteolytic shedding of Tie2 in uterine microvascular endothelial cells.Serum sTie2 levels were significantly lower in preeclamptic subjects starting at 24-28 wk of gestation and continued to be lower through the time of delivery. In culture experiments, VEGF treatment significantly increased sTie2 levels in conditioned media, whereas the MMP inhibitor completely blocked this increase, suggesting that VEGF-induced Tie2 release is MMP dependent.Our data suggest, for the first time, an interaction between VEGF and Tie2 in uterine endothelial cells and a potential mechanism for the decrease in circulating sTie2 levels in preeclampsia, likely through inhibition of VEGF signaling. Further studies on VEGF-Tie2 interactions during pregnancy should provide new insights into the mechanisms underlying the failure of vascular remodeling in preeclampsia and other pregnancy complications.
View details for DOI 10.1210/jc.2011-0063
View details for Web of Science ID 000292454500015
View details for PubMedID 21525162
Second-Trimester Serum Cytokines in Women Who Develop Spontaneous Preterm Labor at Less than 28 Weeks' Gestation versus Term Labor
AMERICAN JOURNAL OF PERINATOLOGY
2010; 27 (1): 31-36
We sought to determine if there is a relationship between serum concentrations of cytokines and the development of preterm labor. A panel of 28 cytokines was measured using the multiplex assay in serum samples collected between 15 and 18 weeks' gestation from women who developed spontaneous preterm labor and delivered between 24 and 28 weeks' gestation (N = 25) and from women who delivered at term (>or=37 weeks; N = 25). Sixteen of the 28 cytokines measured were detected. Except for vascular endothelial growth factor, which showed a trend toward a significant increase in patients who developed preterm labor, there was no difference in cytokine levels between groups in preterm labor and in term labor. Serum cytokine changes in women who develop spontaneous preterm labor possibly occur in the period between 18 weeks' gestation and the onset of labor.
View details for DOI 10.1055/s-0029-1234037
View details for Web of Science ID 000273825200006
View details for PubMedID 19644787
Stercoral Perforation of the Colon With Favorable Pregnancy Outcome
OBSTETRICS AND GYNECOLOGY
2009; 113 (2): 491-492
Stercoral perforation of the colon is a rarely reported disease with high mortality rate. Our literature review identified one prior case reported during pregnancy, with mortality in both mother and infant.A nulliparous female presented at 36 weeks of gestation with fever, tachycardia, and severe abdominal pain. She delivered by cesarean when purulent ascites and stercoral perforation of the sigmoid colon were discovered. After a sigmoid resection with end colostomy, she and her infant recovered uneventfully.Stercoral perforation of the colon is rare in pregnancy. Prompt surgical treatment is necessary. Surgical exploration may be warranted in the pregnant patient with unexplained abdominal pain.
View details for Web of Science ID 000262835400008
View details for PubMedID 19155931
Cesarean delivery outcomes after a prolonged second stage of labor
27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine
We hypothesized that prolonged second stage of labor increases the incidence of unintentional hysterotomy extensions at cesarean delivery.A retrospective cohort of term pregnant women who underwent primary cesarean delivery after failed second stage of labor at Stanford University was assessed for hysterotomy extensions and other maternal and neonatal morbidities. Groups included second stage length of 1-3 hours and >4 hours. Data were analyzed with the use of chi-square and Fisher's exact tests.Of the 239 women who were studied, the second stage of labor lasted 1-3 hours in 82 patients and >4 hours in 157 patients. Prolonged second stage of labor was associated with unintentional hysterotomy extensions (40% vs 26%; P = .03), particularly to the cervix (29% vs 5%; P = .005), and with surgery that lasted >90 minutes (9% vs 1%; P = .01). The incidence of hysterotomy extensions was associated positively with the length of the second stage. Other maternal and neonatal morbidities were similar between groups.Prolonged second stage of labor is associated with an increase in unintentional hysterotomy extensions at cesarean delivery and prolonged operative time. The future risk of hysterotomy extensions merits further investigation.
View details for DOI 10.1016/j.ajog.2007.07.005
View details for Web of Science ID 000249531300033
View details for PubMedID 17826431
Rupture of ectopic pregnancy with minimally detectable beta-human chorionic gonadotropin levels: A report of 2 cases
JOURNAL OF REPRODUCTIVE MEDICINE
2007; 52 (6): 541-542
Several studies have demonstrated that 25-77% of ectopic pregnancies spontaneously resolve with expectant management. However, expectant management is controversial and should be considered only for patients with small, unruptured gestational sacs, low beta-human chorionic gonadotropin (beta-hCG) levels and absence of symptoms. There is no consensus on how long to follow such patients.Two patients with beta-hCG levels < 10 mIU/mL presented with ruptured ectopic pregnancy and hemoperitoneum.While expectant management of a suspected ectopic pregnancy may allow spontaneous resolution of such an ectopic pregnancy, rupture may occur at any time and even with extremely low beta-hCG levels. Patients need to be counseled about the risks of rupture and symptoms, immediate action should be taken if symptoms develop, and serum beta-hCG levels should be followed to zero.
View details for Web of Science ID 000247354600017
View details for PubMedID 17694977
Ribosomal S6 kinase 1 (RSK1) activation requires signals dependent on and independent of the MAP kinase ERK
1999; 9 (15): 810-820
The rsk1 gene encodes the 90 kDa ribosomal S6 kinase 1 (RSK1) protein, which contains two kinase domains. RSK1, which is involved in regulating cell survival and proliferation, lies at the end of the signaling cascade mediated by the extracellular signal-regulated kinase (ERK) subfamily of mitogen-activated protein (MAP) kinases. ERK activation and subsequent phosphorylation of the RSK1 carboxy-terminal catalytic loop stimulates phosphotransferase activity in the RSK1 amino-terminal kinase domain. When activated, RSK1 phosphorylates both nuclear and cytoplasmic substrates through this amino-terminal catalytic domain. It is thought that stimulation of the ERK/MAP kinase pathway is sufficient for RSK1 activation, but how ERK phosphorylation activates the RSK1 amino-terminal kinase domain is not known.The individual isolated RSK1 kinase domains were found to be under regulatory control. In vitro kinase assays established that ERK phosphorylates RSK1 within the carboxy-terminal kinase domain, and the phosphoinositide-dependent kinase 1 (PDK1) phosphorylates RSK1 within the amino-terminal kinase domain. In transiently transfected HEK 293E cells, PDK1 alone stimulated phosphotransferase activity of an isolated RSK1 amino-terminal kinase domain. Nevertheless, activation of full-length RSK1 in the absence of serum required activation by both PDK1 and ERK.RSK1 is phosphorylated by PDK1 in the amino-terminal kinase-activation loop, and by ERK in the carboxy-terminal kinase-activation loop. Activation of phosphotransferase activity of full-length RSK1 in vivo requires both PDK1 and ERK. RSK1 activation is therefore regulated by both the mitogen-stimulated ERK/MAP kinase pathway and a PDK1-dependent pathway.
View details for Web of Science ID 000081850800021
View details for PubMedID 10469565