Academic Appointments

Current Research and Scholarly Interests

Rh disease, other red call isoimmunization, e.g. Kell, etc.

I.T.P. and alloimmune thrombocytopenia

Multiple pregnancy (twins, triplets, etc.) and associated problems and procedures

Ultrasound referrals -- complicated and routine

Procedures -- cordocentesis, intrauterine transfusion; selective termination or reduction in multiple pregnancy.

All Publications

  • Analysis of the Size Distributions of Fetal and Maternal Cell-Free DNA by Paired-End Sequencing CLINICAL CHEMISTRY Fan, H. C., Blumenfeld, Y. J., Chitkara, U., Hudgins, L., Quake, S. R. 2010; 56 (8): 1279-1286


    Noninvasive prenatal diagnosis with cell-free DNA in maternal plasma is challenging because only a small portion of the DNA sample is derived from the fetus. A few previous studies provided size-range estimates of maternal and fetal DNA, but direct measurement of the size distributions is difficult because of the small quantity of cell-free DNA.We used high-throughput paired-end sequencing to directly measure the size distributions of maternal and fetal DNA in cell-free maternal plasma collected from 3 typical diploid and 4 aneuploid male pregnancies. As a control, restriction fragments of lambda DNA were also sequenced.Cell-free DNA had a dominant peak at approximately 162 bp and a minor peak at approximately 340 bp. Chromosome Y sequences were rarely longer than 250 bp but were present in sizes of <150 bp at a larger proportion compared with the rest of the sequences. Selective analysis of the shortest fragments generally increased the fetal DNA fraction but did not necessarily increase the sensitivity of aneuploidy detection, owing to the reduction in the number of DNA molecules being counted. Restriction fragments of lambda DNA with sizes between 60 bp and 120 bp were preferentially sequenced, indicating that the shotgun sequencing work flow introduced a bias toward shorter fragments.Our results confirm that fetal DNA is shorter than maternal DNA. The enrichment of fetal DNA by size selection, however, may not provide a dramatic increase in sensitivity for assays that rely on length measurement in situ because of a trade-off between the fetal DNA fraction and the number of molecules being counted.

    View details for DOI 10.1373/clinchem.2010.144188

    View details for Web of Science ID 000280501400016

    View details for PubMedID 20558635

  • Noninvasive diagnosis of fetal aneuploidy by shotgun sequencing DNA from maternal blood PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Fan, H. C., Blumenfeld, Y. J., Chitkara, U., Hudgins, L., Quake, S. R. 2008; 105 (42): 16266-16271


    We directly sequenced cell-free DNA with high-throughput shotgun sequencing technology from plasma of pregnant women, obtaining, on average, 5 million sequence tags per patient sample. This enabled us to measure the over- and underrepresentation of chromosomes from an aneuploid fetus. The sequencing approach is polymorphism-independent and therefore universally applicable for the noninvasive detection of fetal aneuploidy. Using this method, we successfully identified all nine cases of trisomy 21 (Down syndrome), two cases of trisomy 18 (Edward syndrome), and one case of trisomy 13 (Patau syndrome) in a cohort of 18 normal and aneuploid pregnancies; trisomy was detected at gestational ages as early as the 14th week. Direct sequencing also allowed us to study the characteristics of cell-free plasma DNA, and we found evidence that this DNA is enriched for sequences from nucleosomes.

    View details for DOI 10.1073/pnas.0808319105

    View details for Web of Science ID 000260597400037

    View details for PubMedID 18838674

    View details for PubMedCentralID PMC2562413

  • Prenatal diagnosis of placenta accreta - Sonography or magnetic resonance imaging? JOURNAL OF ULTRASOUND IN MEDICINE Dwyer, B. K., Belogolovkin, V., Tran, L., Rao, A., Carroll, I., Barth, R., Chitkara, U. 2008; 27 (9): 1275-1281


    The purpose of this study was to compare the accuracy of transabdominal sonography and magnetic resonance imaging (MRI) for prenatal diagnosis of placenta accreta.A historical cohort study was undertaken at 3 institutions identifying women at risk for placenta accreta who had undergone both sonography and MRI prenatally. Sonographic and MRI findings were compared with the final diagnosis as determined at delivery and by pathologic examination.Thirty-two patients who had both sonography and MRI prenatally to evaluate for placenta accreta were identified. Of these, 15 had confirmation of placenta accreta at delivery. Sonography correctly identified the presence of placenta accreta in 14 of 15 patients (93% sensitivity; 95% confidence interval [CI], 80%-100%) and the absence of placenta accreta in 12 of 17 patients (71% specificity; 95% CI, 49%-93%). Magnetic resonance imaging correctly identified the presence of placenta accreta in 12 of 15 patients (80% sensitivity; 95% CI, 60%-100%) and the absence of placenta accreta in 11 of 17 patients (65% specificity; 95% CI, 42%-88%). In 7 of 32 cases, sonography and MRI had discordant diagnoses: sonography was correct in 5 cases, and MRI was correct in 2. There was no statistical difference in sensitivity (P = .25) or specificity (P = .5) between sonography and MRI.Both sonography and MRI have fairly good sensitivity for prenatal diagnosis of placenta accreta; however, specificity does not appear to be as good as reported in other studies. In the case of inconclusive findings with one imaging modality, the other modality may be useful for clarifying the diagnosis.

    View details for Web of Science ID 000258853200002

    View details for PubMedID 18716136

  • Subclavian vein thrombosis following IVF and ovarian hyperstimulation: a case report HUMAN REPRODUCTION Rao, A. K., Chitkara, U., Milki, A. A. 2005; 20 (12): 3307-3312


    Thromboembolic phenomena are a serious consequence of assisted reproductive technology. We present a case of upper extremity deep vein thrombosis (DVT) at 7 weeks gestation following ovarian hyperstimulation syndrome (OHSS) and IVF. Three weeks after recovering from OHSS, the patient presented with left neck pain and swelling. Ultrasound revealed a thrombus in the left jugular vein and left subclavian vein. Low molecular weight heparin (LMWH) was initiated with symptom resolution within 1 week. The patient remained on LWMH throughout her pregnancy and delivered at term. A literature review showed 97 published cases of thromboembolism following ovulation induction. A majority of these cases was associated with OHSS and pregnancy and the site of involvement was predominantly in the upper extremity and neck. Infertility physicians and obstetricians should be aware of this complication and keep in mind that it may occur weeks after resolution of OHSS symptoms.

    View details for PubMedID 16085662

  • A randomized trial of amnioreduction versus septostomy in the treatment of twin-twin transfusion syndrome AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY Moise, K. J., Dorman, K., Lamvu, G., Saade, G. R., Fisk, N. M., Dickinson, J. E., Wilson, R. D., Gagnon, A., Belfort, M. A., O'Shaughnessy, R. O., Chitkara, U., Hassan, S. S., Johnson, A., Sciscione, A., Skupski, D. E. 2005; 193 (3): 701-707


    Left untreated, severe twin-to-twin transfusion syndrome (TTTS) presenting in the early second trimester of pregnancy is often associated with significant maternal morbidity and almost universal perinatal loss. Removal of excessive amounts of amniotic fluid through serial amniocenteses (amnioreduction) has been the mainstay of therapy. We sought to compare amnioreduction to intentional perforation of the intervening twin membrane (septostomy).Pregnant women with TTTS before 24 weeks' gestation were randomly assigned to serial amnioreduction or septostomy. A single puncture technique under ultrasound guidance was used for the septostomy. The primary outcome measure was survival to neonatal discharge, and was assessed based on the number of pregnancies or the number of fetuses as appropriate.The study was terminated at the planned interim analysis stage after 73 women were enrolled. This was because the rate of survival of at least 1 infant was similar in the amnioreduction group compared to the septostomy group (78% vs 80% of pregnancies, respectively; RR=0.94, 95%CI 0.55-1.61; P=.82). Patient undergoing septostomy were more likely to require a single procedure for treatment (64% vs 46%; P=.04).Although overall perinatal survival is not enhanced, septostomy offers the advantage of often requiring a single procedure compared to serial amnioreduction in the treatment of severe twin-to-twin transfusion syndrome.

    View details for DOI 10.1016/j.ajog.2005.01.067

    View details for Web of Science ID 000232013300016

    View details for PubMedID 16150263

  • Randomized comparison of intravenous nitroglycerin and subcutaneous terbutaline for external cephalic version under tocolysis AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY El-Sayed, Y. Y., Pullen, K., Riley, E. T., Lyell, D., Druzin, M. L., Cohen, S. E., Chitkara, U. 2004; 191 (6): 2051-2055


    The purpose of this study was to compare the efficacy and safety of intravenous nitroglycerin with that of subcutaneous terbutaline as a tocolytic agent for external cephalic version at term.We performed a prospective randomized trial. Patients between 37 and 42 weeks of gestation were assigned randomly to receive either 200 microg of intravenous nitroglycerin therapy or 0.25 mg of subcutaneous terbutaline therapy for tocolysis during external cephalic version. The rate of successful external cephalic version and side effects were compared between groups.Of 59 randomly assigned patients, 30 patients received intravenous nitroglycerin, and 29 patients received subcutaneous terbutaline. The overall success rate of external cephalic version in the study was 39%. The rate of successful external cephalic version was significantly higher in the terbutaline group (55% vs 23%; P = .01). The incidence of palpitations was significantly higher in patients who received terbutaline therapy (17.2% vs 0%; P = .02), as was the mean maternal heart rate at multiple time periods.Compared with intravenous nitroglycerin, subcutaneous terbutaline was associated with a significantly higher rate of successful external cephalic version at term.

    View details for DOI 10.1016/j.ajog.2004.04.040

    View details for Web of Science ID 000225925800030

    View details for PubMedID 15592291

  • Fetal renal growth as assessed through renal parenchymal area derived from prenatal and perinatal ultrasonography JOURNAL OF UROLOGY Kennedy, W. A., Chitkara, U., Abidari, J. M., Shortliffe, L. M. 2003; 169 (1): 298-302


    Few quantitative parameters allow for comparison of serial studies in children with prenatally detected genitourinary abnormalities. We establish the first ultrasonographically based fetal renal parenchymal growth curve that could serve as a standard for fetal renal growth assessment.Longitudinal ultrasounds of 246 normal fetal kidneys from 16 to 38 weeks of gestation were scanned with renal parenchymal area calculated and growth curves plotted. Our previously determined nomogram from birth to adolescence was then combined with this fetal nomogram to produce a composite renal growth curve. Data were plotted as mean parenchymal area +/- 2 SD using lines determined by polynomial regression.Renal growth curves were constructed independently for the right and left fetal kidneys as well as the total fetal renal parenchymal area. The polynomial regression equation for the right renal parenchymal area was y = -0.0076x(2) + 0.7141x - 8.5344 (r(2) = 0.91). The polynomial regression equation for the left renal parenchymal area was y = -0.0036x(2) + 0.5161x - 6.2337 (r(2) = 0.96). The polynomial regression equation for the total fetal renal parenchymal area was y = -0.0113x(2) + 1.234x - 14.814 (r(2) = 0.95).We propose a new quantitative standard to evaluate appropriate fetal kidney size the prenatal renal parenchymal area growth curve. Renal parenchymal growth curves for the normal fetal kidney may serve as a valuable tool to assess fetal renal pathology.

    View details for DOI 10.1097/01.ju.0000041762.66236.29

    View details for Web of Science ID 000179921200101

    View details for PubMedID 12478175

  • Central nervous system lupus and pregnancy: 11-year experience at a single center. journal of maternal-fetal & neonatal medicine El-Sayed, Y. Y., Lu, E. J., Genovese, M. C., Lambert, R. E., Chitkara, U., Druzin, M. L. 2002; 12 (2): 99-103


    To describe the pregnancy outcomes in women with central nervous system (CNS) manifestations of lupus.Between 1991 and 2002, the outcome of five pregnancies in four patients with CNS lupus were retrospectively reviewed. All patients had an established history of systemic lupus erythematosus (SLE), and either a history of CNS lupus or active CNS lupus. Pregnancy outcomes assessed included term and preterm birth, intrauterine growth restriction, abnormal antepartum testing, perinatal mortality, pre-eclampsia and other maternal morbidities.Evidence of active CNS lupus symptoms developed in three of the five pregnancies. Two pregnancies were complicated by early onset pre-eclampsia, abnormal antepartum testing and extreme prematurity, with one subsequent neonatal death. The remaining three pregnancies had good neonatal outcomes, but were complicated by severe maternal post-pregnancy exacerbations, and the eventual death of one patient.CNS lupus in pregnancy represents an especially severe manifestation of SLE, and may involve great maternal and fetal risks.

    View details for PubMedID 12420839

  • Pregnancy complicated by severe osteogenesis imperfecta: A report of two cases ANESTHESIA AND ANALGESIA Vogel, T. M., Ratner, E. F., Thomas, R. C., Chitkara, U. 2002; 94 (5): 1315-1317


    This case report discusses the anesthetic management of two parturients with severe osteogenesis imperfecta who presented for cesarean delivery. Although the anesthetic management for milder forms of the disease has been previously reported, anesthetic options for cases of this severity have not.

    View details for PubMedID 11973211

  • Fetal ear length measurement: a useful predictor of aneuploidy? ULTRASOUND IN OBSTETRICS & GYNECOLOGY Chitkara, U., Lee, L., Oehlert, J. W., Bloch, D. A., Holbrook, R. H., El-Sayed, Y. Y., Druzin, M. L. 2002; 19 (2): 131-135


    To determine the usefulness of short ear length (EL) measurement in the prenatal detection of fetuses with chromosomal abnormalities.Fetal EL measurements, routine biometry and complete anatomic survey for fetal abnormalities were prospectively performed by antenatal sonography.One thousand eight hundred and forty-eight patients with singleton pregnancies undergoing genetic amniocentesis in the second or third trimester.Complete data for EL, biometry and anatomic survey for major structural abnormalities and minor sonographic markers of chromosomal abnormality were available in 1311 fetuses. Of these, 48 (3.7%) had an abnormal karyotype and 1263 (96.3%) had a normal karyotype. Using an EL measurement of < or = 10th percentile for corresponding gestational age in normal fetuses as abnormal cut-off values, detection rates for chromosomal abnormalities by short EL were determined.Among the 48 abnormal karyotypes, 34 were considered significant, and 11 of these 34 (32.4%) fetuses had short EL. In 14 cases, the karyotypic abnormality was considered non-significant and fetal EL was normal in all cases. Of the 34 fetuses with significant chromosomal abnormalities, six (17.6%) on antenatal sonography had no detectable abnormal findings, other than short EL. An increased biparietal diameter (BPD)/EL ratio of > or = 4.0 was also noted in fetuses with an abnormal karyotype, but the sensitivity and predictive value of increased BPD/EL ratio alone or increased BPD/EL ratio in combination with short EL was no better than the sensitivity and predictive value of short EL alone. A combination of short EL and abnormal ultrasound, however, gave a much higher positive predictive value (46%) for significant chromosomal abnormalities.Our findings suggest that in women at high risk for fetal chromosomal abnormality, a short fetal EL measurement on prenatal ultrasound, either alone or in combination with other sonographically detectable structural abnormalities, may be a useful parameter in predicting fetal aneuploidy.

    View details for Web of Science ID 000174123500004

    View details for PubMedID 11876803

  • Concurrent IVF and spontaneous conception resulting in a quadruplet pregnancy HUMAN REPRODUCTION Milki, A. A., Hinckley, M. D., GRUMET, F. C., Chitkara, U. 2001; 16 (11): 2324-2326


    Blastocyst transfer of just one or two embryos has been used to help limit the number of high-order gestations. In this case report we describe the occurrence of a quadruplet pregnancy after the transfer of only two blastocysts during IVF. Sonographic examination showed four fetuses and what appeared to be quadriamniotic/quadrichorionic sacs, suggesting that a concomitant spontaneous conception had occurred. Definite confirmation of zygosity was obtained by genetic testing using DNA microsatellite polymorphism determinations after the birth of one boy and three girls at 32 weeks gestation. Although this event has not been reported previously, the possibility of its occurrence should be kept in mind. IVF patients with patent Fallopian tubes should be cautioned against intercourse late in their controlled ovarian stimulation, especially if they would decline multifetal reduction.

    View details for Web of Science ID 000172097200017

    View details for PubMedID 11679513

  • Decreased amniotic fluid index in low-risk pregnancy JOURNAL OF REPRODUCTIVE MEDICINE Kreiser, D., El-Sayed, Y. Y., Sorem, K. A., Chitkara, U., Holbrook, R. H., Druzin, M. L. 2001; 46 (8): 743-746


    To evaluate the perinatal outcomes of pregnancies complicated by isolated decreased amniotic fluid volume (AFI) after 30 weeks' gestation (AFI < or = 5 or > 5 cm but < 2.5th percentile).We retrospectively studied 150 low-risk singleton pregnancies > 30 weeks' gestation with decreased AFI. We also compared the outcomes of 57 pregnancies with AFI < or = 5 cm to those of 93 pregnancies with AFI > 5 cm but < 2.5th percentile (borderline AFI). Pregnancy outcome was assessed with respect to antepartum, intrapartum and neonatal measures. Statistical significance (P < .05) between groups was determined by means of the Student t test and chi 2 analysis.There were no statistically significant differences between pregnancies with AFI < or = 5 cm and those with AFI > 5 cm but < 2.5th percentile with respect to labor induction for an abnormal nonstress test (7.0% vs. 7.5%, overall 7.3%), cesarean sections for fetal heart rate abnormalities (7.0% vs. 7.5%, overall 7.3%), presence of meconium (16.1% vs. 15.7%, overall 16%) and Apgar score < 7 at five minutes (0 vs. 1.1%, overall 0.66%). There were no perinatal deaths in either group. Antepartum variable decelerations were more common in pregnancies with AFI < or = 5 cm as compared to those with AFI > 5 cm but < 2.5th percentile (63.1% vs. 45.1%, P = .007; overall 53.3%).With antepartum monitoring, perinatal outcome in low-risk pregnancies with an isolated decreased AFI after 30 weeks' gestation (< or = 5 or > 5 cm but < 2.5th percentile) appears to be good.

    View details for Web of Science ID 000170694100009

    View details for PubMedID 11547649

  • Ultrasonographic ear length measurement in normal second-and third-trimester fetuses AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY Chitkara, U., Lee, L., El-Sayed, Y. Y., Holbrook, R. H., Bloch, D. K., Oehlert, J. W., Druzin, M. L. 2000; 183 (1): 230-234


    We sought to develop a nomogram for fetal ear length measurements from a large population of healthy second- and third-trimester fetuses and to investigate the correlation of fetal ear length with other standard fetal biometry measurements, as follows: biparietal diameter, head circumference, abdominal circumference, femur length, and humerus length.Ear length measurement was obtained prospectively in 4240 singleton fetuses between 15 and 40 weeks' gestational age. Either complete data for normal karyotype on amniocentesis or normal infant examination at birth or both were available in 2583 cases. These constituted the final study population.A nomogram was developed by linearly regressing ear length on gestational age (Ear length [in millimeters] = 1.076 x Gestational age [in weeks] - 7. 308). There was a high correlation between ear length and gestational age (r = 0.96; P =.0001).The results of this study provide normative data on growth of fetal ear length from 15 to 40 weeks' gestation. Good correlation was also observed between ear length and other fetal biometric measurements (biparietal diameter, head circumference, abdominal circumference, femur length, and humerus length).

    View details for Web of Science ID 000088565500039

    View details for PubMedID 10920337

  • Randomized comparison of intravenous nitroglycerin and magnesium sulfate for treatment of preterm labor OBSTETRICS AND GYNECOLOGY El-Sayed, Y. Y., Riley, E. T., Holbrook, R. H., Cohen, S. E., Chitkara, U., Druzin, M. L. 1999; 93 (1): 79-83


    To compare the safety and efficacy of high-dose intravenous (IV) nitroglycerin with those of IV magnesium sulfate for acute tocolysis of preterm labor.Thirty-one women with preterm labor before 35 weeks' gestation were assigned randomly to IV magnesium sulfate or IV nitroglycerin for tocolysis. Preterm labor was defined as the occurrence of at least two contractions in 10 minutes, with cervical change or ruptured membranes. Acute tocolysis was defined as tocolysis for up to 48 hours. Magnesium sulfate was administered as a 4-g bolus, then at a rate of 2-4 g/h. Nitroglycerin was administered as a 100-microg bolus, then at a rate of 1- to 10-microg/kg/min. The primary outcome measure was achievement of at least 12 hours of successful tocolysis.Thirty patients were available for analysis. There were no significant differences in gestational age, cervical dilation, or incidence of ruptured membranes between groups at the initiation of tocolysis. Successful tocolysis was achieved in six of 16 patients receiving nitroglycerin, compared with 11 of 14 receiving magnesium sulfate (37.5 versus 78.6%, P = .033). Tocolytic failures (nitroglycerin versus magnesium sulfate) were due to persistent contractions with cervical change or rupture of previously intact membranes (five of 16 versus two of 14), persistent hypotension (four of 16 versus none of 14), and other severe side effects (one of 16 versus one of 14). Maternal hemodynamic alterations were more pronounced in patients who received nitroglycerin, and 25% of patients assigned to nitroglycerin treatment had hypotension requiring discontinuation of therapy.Tocolytic failures were more common with nitroglycerin than with magnesium sulfate. The hemodynamic alterations noted in patients receiving nitroglycerin, including a 25% incidence of persistent hypotension, might limit the usefulness of IV nitroglycerin for the acute tocolysis of preterm labor.

    View details for Web of Science ID 000077885200017

    View details for PubMedID 9916961

  • Diltiazem for maintenance tocolysis of preterm labor: comparison to nifedipine in a randomized trial. The Journal of maternal-fetal medicine El-Sayed, Y. Y., Holbrook, R. H., Gibson, R., Chitkara, U., Druzin, M. L., Baba, D. 1998; 7 (5): 217-221


    The objective of this study was to compare the safety and efficacy of maintenance tocolysis with oral diltiazem to oral nifedipine in achieving 37 weeks gestation. After successful intravenous tocolysis with magnesium sulfate, 69 women with preterm labor at <35 weeks gestation were randomly assigned to nifedipine (20 mg orally every 4-6 hr), or diltiazem (30-60 mg orally every 4-6 hr). The primary outcome was the percentage of patients achieving 37 weeks gestation. Maternal cardiovascular alterations and neonatal outcomes were also assessed. Sixty-nine patients were available for final analysis. Less patients on diltiazem as compared to nifedipine achieved 37 weeks (15.1% vs. 41.7%, P = 0.019). Gestational age at delivery was also less for patients receiving diltiazem (35.5 +/- 3.5 weeks vs. 33.4 +/- 3.9 weeks, P = 0.022). There were fewer days gained in utero from randomization to delivery with diltiazem as compared to nifedipine; however, this difference was not statistically significant (22.4 +/- 16.3 days vs. 31.2 +/- 24.4 days, P = 0.084). Maternal blood pressure and pulse during tocolysis did not differ significantly between groups. Despite the theoretical advantages of diltiazem tocolysis, maintenance tocolysis with diltiazem offered no benefit over nifedipine in achieving 37 weeks gestation. The cardiovascular alterations with either drug in normotensive, pregnant patients appear minimal.

    View details for PubMedID 9775988

  • Medical management of interstitial ectopic pregnancy: a case report and literature review HUMAN REPRODUCTION Fisch, J. D., Ortiz, B. H., Tazuke, S. I., Chitkara, U., Giudice, L. C. 1998; 13 (7): 1981-1986


    Recent reports describe successful treatment of interstitial ectopic pregnancies using methotrexate. While the number of reported cases is increasing, no consensus exists regarding the management of this complication of pregnancy. We present the successful use of combined systemic and direct intrasac injection of methotrexate for an interstitial pregnancy with the highest yet reported initial beta-human chorionic gonadotrophin concentration (102,000 mIU/ml). We also describe the use of Doppler ultrasound for monitoring treatment progression. Through a review of the current literature, we propose to facilitate management decisions and increase outcome success by summarizing previously reported treatment regimens and by describing enhanced parameters for patient selection and monitoring.

    View details for Web of Science ID 000075324200051

    View details for PubMedID 9740461

  • Gestational age-dependent expression of insulin-like growth factor-binding protein-1 (IGFBP-1) phosphoisoforms in human extraembryonic cavities, maternal serum, and decidua suggests decidua as the primary source of IGFBP-1 in these fluids during early pregnancy JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM Martina, N. A., Kim, E., Chitkara, U., Wathen, N. C., Chard, T., Giudice, L. C. 1997; 82 (6): 1894-1898


    The insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) are important regulators of fetal and maternal tissue development during pregnancy. Posttranslational modification of IGFBP-1 yields up to six IGFBP-1 phosphovariants and a nonphosphorylated form, which in vitro, have some different properties. Nonphospho IGFBP-1 has less affinity for IGFs than the phospho isoforms and also may have IGF-independent actions. Herein, we have investigated the complement of IGFBP-1 phosphoisoforms present in extraembryonic coelomic (EEC) fluid, amniotic fluid (AF), and maternal serum (MS) throughout human gestation. Also, to determine potential tissue source(s) of IGFBP-1 in these fluids, we have quantified IGFBP-1 and examined IGFBP-1 phosphoisoforms in conditioned media (CM) from maternal decidua, fetal liver, and fetal kidney explants throughout gestation. Western immunodetection revealed that IGFBP-1, present in EEC and AF in early pregnancy and in CM from early pregnancy decidua, is primarily in the nonphosphorylated form. MS in this period contains primarily the nonphospho form and, as in nonpregnant adults, the highly phosphorylated form of IGFBP-1. The phosphorylation profile of IGFBP-1 in AF, MS, and decidua CM changes as pregnancy progresses. All the IGFBP-1 phosphoisoforms ultimately are produced by decidua and are present in midgestation MS, and all but the most highly phosphorylated form are present in AF. In late gestation, MS contains primarily the highly phosphorylated form. In contrast, profiles in CM from explants of fetal liver and kidney at different gestational ages remain unchanged. Nonphosphorylated IGFBP-1 is the primary form in fetal kidney CM, whereas fetal liver CM contains all IGFBP-1 phosphoisoforms. Concentrations of IGFBP-1 in fetal liver and kidney CM are significantly lower (482 +/- 146 and 120 +/- 32 ng/mL x 100 mg wet wt tissue, respectively) than in decidua CM (11,417 +/- 2,358 ng/mL x 100 mg wet wt tissue). The data cumulatively suggest that maternal decidua is the primary source of IGFBP-1 in EEC, AF, and MS in early pregnancy and that fetal liver and kidney are not likely significant contributors. The presence of nonphospho IGFBP-1 in AF, EEC, and MS suggests an important role for this isoform during early gestation.

    View details for Web of Science ID A1997XC08000046

    View details for PubMedID 9177402



    Hypertensive disorders in pregnancy contribute to substantial maternal and perinatal morbidity and mortality. Clinically, these disorders are characterized by hypertension and proteinuria. However, these signs appear some time after the physiologic derangements have been initiated. The primary objectives of this study were as follows: 1) to establish baseline values for the maternal renal artery systolic-diastolic ratio (S/D) as a function of gestational age in normal pregnancies, and 2) to determine whether renal artery blood flow indices can accurately identify those pregnancies complicated by, or destined to develop, hypertensive disorders. Using a pulsed Doppler scanner, maternal renal artery duplex evaluation was performed in four groups of women: normotensive nonpregnant, normotensive pregnant, chronic hypertensive pregnant, and preeclamptic. In 30 normotensive pregnant women followed longitudinally, no change was noted in the renal artery S/D as gestational age advanced, with mean (+/- SD) values of 2.5 +/- 0.20 and 2.6 +/- 0.21 for the left and right sides, respectively. No clinically meaningful discriminations were detected when the four groups were compared. We conclude that maternal renal artery Doppler waveforms are not significantly altered by either pregnancy or hypertensive complications in pregnancy.

    View details for Web of Science ID A1992HB18900021

    View details for PubMedID 1731297

  • Antenatal treatment of alloimmune thrombocytopenia Obstet Gynecol Chitkara U, Lynch L, Bussel JB, McFarland JG, Berkowitz RL 1992


    Ultrasound fetal biometry is widely used for detection of intrauterine growth retardation (IUGR). Since fetal growth is a dynamic process, studies estimating validity of ultrasound near term may not be applicable earlier in pregnancy. This study applied receiver operating characteristic (ROC) curve analysis to ultrasound biometric data obtained at 26-34 weeks gestation to predict fetuses destined to be IUGR at birth. In this method, the area under the curve (theta) is the index of performance. Sixty-nine (9%) of the 768 singleton infants studied were IUGR at birth. Ultrasound estimated fetal weight (theta = .793) and abdominal circumference (theta = .785) had equivalent performance, significantly better than head circumference (theta = .724) or femur length/abdominal circumference ratio (theta = .619). Performance was not as good as suggested by studies conducted within 2 weeks of delivery.

    View details for Web of Science ID A1991FC26800007

    View details for PubMedID 2027188



    Intrauterine intravascular transfusion is now believed to be a more precise method for treating fetal anemia in erythroblastosis fetalis than is intraperitoneal transfusion. Previously established guidelines for the volume of blood to be given in intraperitoneal transfusion at a specific gestational age are not applicable for intravascular transfusion. In 28 patients, intravascular transfusion was performed on 81 occasions between 19-34 weeks' gestation. The total number of transfusions ranged from one to six per patient. The aim at each procedure was to achieve a final hematocrit of 35-50%. Factors examined as likely to determine the volume of blood required included pre-transfusion hematocrit, post-minus pre-transfusion hematocrit (hematocrit increase), the hematocrit of the transfused blood, gestational age, estimated fetal weight, and interval from last transfusion. The factors found to be most predictive of total volume of blood required for transfusion were the hematocrit increase and either estimated fetal weight or gestational age.

    View details for Web of Science ID A1990DE77800015

    View details for PubMedID 2342745



    Eighty-five cases of multifetal pregnancy reduction were performed transabdominally at 9.5-13 weeks' gestation. All pregnancies consisted of three or more fetuses (28 triplets, 47 quadruplets, four quintuplets, four sextuplets, one septuplet, and one nontuplet), and all except five were reduced to twins. Forty-five women have delivered viable infants and eight lost all of the fetuses; 32 pregnancies are ongoing. No temporal relationship was noted between the pregnancy losses and the procedures. The mean gestational age at delivery was 35.7 weeks; 16 women (35.5%) delivered at or after 37 weeks, 16 (35.5%) between 34.5-37 weeks, nine (20%) between 32-34.5 weeks, and four (9%) before 32 weeks. There were no perinatal deaths, and all infants are healthy except for one who developed sequelae of severe hyaline membrane disease.

    View details for Web of Science ID A1990DA50400001

    View details for PubMedID 2183104

  • High dose intravenous gamma globulin: Does it have a role in the treatment of severe erythroblastosis fetails? Obstet Gynecol Chitkara U, Bussel J, Alvarez M, Lynch L, Meisel RL, Berkowitz RL 1990