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Biomedical subjects

Richard L Berkowitz

Publications and source records attributed to Richard L Berkowitz.

At least 19 recordsLinked to original sources
PubMed2006

Alloimmune thrombocytopenia: state of the art 2006.

In alloimmune thrombocytopenia maternal immunoglobulin G anti-platelet alloantibodies cross the placenta and cause fetal thrombocytopenia. The diagnosis requires laboratory demonstration of incompatibility between a maternal and paternal platelet alloantigen, and detection of maternal antibody to the discordant paternal alloantigen. This disorder should be treated in utero because of its propensity to cause fetal intracranial bleeding. Administration of intravenous immunoglobulin 1 gm/kg/wk to the mother is successful in substantially raising the platelet count in many fetuses, but this is most successful if the count is >20,000/mL3 at the time that the therapy is initiated. The addition of prednisone administered daily to the mother and/or increasing the dose of intravenous immunoglobulin has a therapeutic benefit in cases that have failed to respond to initial therapy with intravenous immunoglobulin alone. The only reliable noninvasive indicator of the potential for severe fetal thrombocytopenia is a history of an antenatal intracranial hemorrhage in a prior affected sibling. Because fetal blood sampling to determine the fetal platelet count may be associated with significant fetal morbidity, attempts are being made to derive a rational, non-invasive, stratified approach to patient-specific therapy of this disorder in affected pregnancies.

Antigens, Human Platelet↗
PubMed2006

Is there a nuchal translucency millimeter measurement above which there is no added benefit from first trimester serum screening?

OBJECTIVE: The purpose of this study was to evaluate whether there is a nuchal translucency (NT) measurement, independent of gestational age, above which immediate diagnostic testing should be offered without waiting for first trimester serum markers. STUDY DESIGN: Thirty-six thousand one hundred twenty patients had successful measurement of simple NT at 10 3/7 to 13 6/7 weeks and had first trimester serum screening. No risks were reported until second trimester serum screening was completed. RESULTS: Thirty-two patients (0.09%) had NT > or = 4.0 mm; the lowest combined first trimester trisomy 21 risk assessment in euploid cases was 1 in 8 and among aneuploidy cases was 7 in 8. One hundred twenty-eight patients (0.3%) had simple NT > or = 3.0 mm: the lowest combined first trimester trisomy 21 risk assessment of any patient in this group was 1 in 1479 and the lowest risk assessment among aneuploid cases was 1 in 2. Ten patients (8%) had first trimester trisomy 21 risk assessments lowered to less that 1:200 and none of these 10 cases had an abnormal outcome. CONCLUSION: During first trimester Down syndrome screening, whenever an NT measurement of 3.0 mm or greater is obtained there is minimal benefit in waiting for serum screening results, and no benefit for NT of 4.0 mm or greater. Differentiation between cystic hygroma and enlarged simple NT (> or = 3.0 mm) is now a moot point as both are sufficiently high risk situations to warrant immediate CVS.

Chorionic Gonadotropin, beta Subunit, Human↗
PubMed2006

Parallel randomized trials of risk-based therapy for fetal alloimmune thrombocytopenia.

OBJECTIVE: Antenatal therapy with intravenous immunoglobulin (IVIG) and prednisone has been shown to improve fetal thrombocytopenia and reduce the incidence of intracranial hemorrhage in neonatal alloimmune thrombocytopenia. Optimization of this therapy for individual patients, however, has yet to be achieved. METHODS: In these parallel, randomized, multicenter studies, 78 patients in 79 pregnancies were stratified to 2 different treatment arms based on the presence of a peripartum intracranial hemorrhage in a previously affected sibling and/or the initial fetal platelet count. Patients with a history of an antenatal intracranial hemorrhage in a prior pregnancy were excluded. RESULTS: Forty women whose children from a previous birth had a peripartum intracranial hemorrhage or whose current fetus had an initial platelet count less than 20,000/mL3 were randomly assigned to receive IVIG plus prednisone or IVIG alone. The mean increase in fetal platelet counts in the following 3 to 8 weeks was 67,100/mL3 and 17,300/mL3, respectively (P < .001). Thirty-nine patients whose prior affected child did not have an intracranial hemorrhage and whose initial platelet count was more than 20,000/mL3 were randomly assigned to receive IVIG alone or prednisone alone. There were no significant differences, and 33 (85%) had birth platelet counts more than 50,000/mL3. There were 11 (6%) significant complications after a total of 175 fetal blood sampling procedures, 2 of which led to fetal or neonatal deaths. CONCLUSION: The spectrum of disease severity of alloimmune thrombocytopenia is reflected in the initial fetal platelet count and response to therapy. Fetal blood sampling may be associated with significant fetal/neonatal morbidity and mortality. Empiric therapy sufficient to treat the most severely affected fetuses will overtreat others and is likely to be associated with additional maternal morbidity.

Adult↗
PubMed2006

Aneuploidy screening: what test should I use?

Screening for the risk of fetal aneuploidy can be effectively performed in either the first or second trimester. When obtained independently, the interpretation of those data is straightforward. However, the effectiveness of screening can be enhanced by combining studies performed in each trimester in a variety of ways. In this commentary we will define and discuss both the advantages and disadvantages of using integrated, stepwise, sequential or contingency screening for risk assessment of fetal aneuploidy.

Adult↗
PubMed2006

Pregnancy loss rates after midtrimester amniocentesis.

OBJECTIVE: The purpose of this study was to quantify the contemporary procedure-related loss rate after midtrimester amniocentesis using a database generated from patients who were recruited to the First And Second Trimester Evaluation of Risk for Aneuploidy trial. METHODS: A total of 35,003 unselected patients from the general population with viable singleton pregnancies were enrolled in the First And Second Trimester Evaluation of Risk for Aneuploidy trial between 10 3/7 and 13 6/7 weeks gestation and followed up prospectively for complete pregnancy outcome information. Patients who either did (study group, n=3,096) or did not (control group, n=31,907) undergo midtrimester amniocentesis were identified from the database. The rate of fetal loss less than 24 weeks of gestation was compared between the two groups, and multiple logistic regression analysis was used to adjust for potential confounders. RESULTS: The spontaneous fetal loss rate less than 24 weeks of gestation in the study group was 1.0% and was not statistically different from the background 0.94% rate seen in the control group (P=.74, 95% confidence interval -0.26%, 0.49%). The procedure-related loss rate after amniocentesis was 0.06% (1.0% minus the background rate of 0.94%). Women undergoing amniocentesis were 1.1 times more likely to have a spontaneous loss (95% confidence interval 0.7-1.5). CONCLUSION: The procedure-related fetal loss rate after midtrimester amniocentesis performed on patients in a contemporary prospective clinical trial was 0.06%. There was no significant difference in loss rates between those undergoing amniocentesis and those not undergoing amniocentesis. LEVEL OF EVIDENCE: II-2.

Abortion, Spontaneous↗
PubMed2006

Comparison of serum markers in first-trimester down syndrome screening.

OBJECTIVE: To estimate patterns of total hCG and inhibin A levels in the late first trimester of Down syndrome pregnancies, compare them with that of free beta-hCG, and assess screening performance of these markers individually and in combination with pregnancy-associated plasma protein-A (PAPP-A) and nuchal translucency. METHODS: Seventy-nine matched case-control sets of maternal serum samples (each Down syndrome case matched to 5 controls) from 11 through 13 completed weeks of gestation were taken from the sample bank of the First and Second Trimester Evaluation of Risk Consortium, a population-based study, and assayed for levels of free beta-hCG, total hCG, and inhibin A. Distribution characteristics and correlations of the multiples of the median values were estimated in cases and controls. Screening performance for each marker, alone and in combination with PAPP-A, nuchal translucency, and maternal age, was calculated. RESULTS: Median multiples of the median levels of free beta-hCG, total hCG, and inhibin A in cases were more elevated as gestation increased from 11 to 13 weeks, with univariate detection rates of 31%, 23%, and 29%, respectively, at a 5% false-positive rate. At 12 weeks, the multivariate detection rates at a 5% false-positive rate for nuchal translucency and PAPP-A (with maternal age) with either free beta-hCG, total hCG, or inhibin A were 84%, 83%, and 85%, respectively. The improvement in performance from nuchal translucency and PAPP-A to any of the three-marker tests was significant, while performance of any of the three-marker combinations was not significantly different from each other. CONCLUSION: Although levels of free beta-hCG in affected pregnancies were higher earlier than the levels of either total hCG or inhibin A, there was no significant difference in screening performance when either of the three markers was used with nuchal translucency and PAPP-A at 11-13 weeks of pregnancy. LEVEL OF EVIDENCE: II-2.

Adult↗
PubMed2005

First-trimester or second-trimester screening, or both, for Down's syndrome.

BACKGROUND: It is uncertain how best to screen pregnant women for the presence of fetal Down's syndrome: to perform first-trimester screening, to perform second-trimester screening, or to use strategies incorporating measurements in both trimesters. METHODS: Women with singleton pregnancies underwent first-trimester combined screening (measurement of nuchal translucency, pregnancy-associated plasma protein A [PAPP-A], and the free beta subunit of human chorionic gonadotropin at 10 weeks 3 days through 13 weeks 6 days of gestation) and second-trimester quadruple screening (measurement of alpha-fetoprotein, total human chorionic gonadotropin, unconjugated estriol, and inhibin A at 15 through 18 weeks of gestation). We compared the results of stepwise sequential screening (risk results provided after each test), fully integrated screening (single risk result provided), and serum integrated screening (identical to fully integrated screening, but without nuchal translucency). RESULTS: First-trimester screening was performed in 38,167 patients; 117 had a fetus with Down's syndrome. At a 5 percent false positive rate, the rates of detection of Down's syndrome were as follows: with first-trimester combined screening, 87 percent, 85 percent, and 82 percent for measurements performed at 11, 12, and 13 weeks, respectively; with second-trimester quadruple screening, 81 percent; with stepwise sequential screening, 95 percent; with serum integrated screening, 88 percent; and with fully integrated screening with first-trimester measurements performed at 11 weeks, 96 percent. Paired comparisons found significant differences between the tests, except for the comparison between serum integrated screening and combined screening. CONCLUSIONS: First-trimester combined screening at 11 weeks of gestation is better than second-trimester quadruple screening but at 13 weeks has results similar to second-trimester quadruple screening. Both stepwise sequential screening and fully integrated screening have high rates of detection of Down's syndrome, with low false positive rates.

Adult↗
PubMed2005

Prenatal diagnosis and multiple pregnancy.

The incidence of twins, triplets, and high-order multiples has increased dramatically in the last two decades secondary to greater reliance on fertility treatments and to delayed childbearing. Offspring of a multiple gestation are at increased risk for both chromosomal and structural abnormalities. Prenatal diagnosis in these patients is challenging. Options for screening tests are limited. Invasive diagnostic procedures are complex. Likewise, physicians and patients may be faced with the dilemma of deciding how to manage discordant results. The following paper will review the unique concerns associated with prenatal diagnosis in a multiple pregnancy and the current methods of prenatal screening in these patients. Invasive prenatal diagnosis will also be explored.

Adult↗
PubMed2005

First trimester screening for Down syndrome in multiple pregnancy.

The incidence of twins, triplets, and high-order multiples has increased substantially in the last two decades secondary to fertility treatments and to delayed childbearing. Prenatal diagnosis in these patients is challenging. Options for screening tests are limited. First trimester screening for Down syndrome in patients with multiples appears promising. This paper will review the advantages of first trimester screening in this high-risk patient population.

Aneuploidy↗
PubMed2005

First-trimester septated cystic hygroma: prevalence, natural history, and pediatric outcome.

OBJECTIVE: To estimate prevalence, natural history, and outcome of septated cystic hygroma in the first trimester in the general obstetric population, and to differentiate this finding from simple increased nuchal translucency. METHODS: Patients at 10.3-13.6 weeks of gestation underwent nuchal translucency sonography as part of a multicenter clinical trial. Septated cystic hygroma cases were offered chorionic villi sampling for karyotype, and targeted fetal anatomical and cardiac evaluations. Survivors were followed up for fetal and long-term pediatric outcome (median 25 months, range 12-50 months). Cases of septated cystic hygroma were also compared with cases of simple increased nuchal translucency. RESULTS: There were 134 cases of cystic hygroma (2 lost to follow-up) among 38,167 screened patients (1 in 285). Chromosomal abnormalities were diagnosed in 67 (51%), including 25 trisomy-21, 19 Turner syndrome, 13 trisomy-18, and 10 others. Major structural fetal malformations (primarily cardiac and skeletal) were diagnosed in 22 of the remaining 65 cases (34%). There were 5 cases (8%) of fetal death and 15 cases of elective pregnancy termination without evidence of abnormality. One of 23 (4%) normal survivors was diagnosed with cerebral palsy and developmental delay. Overall, survival with normal pediatric outcome was confirmed in 17% of cases (22 of 132). Compared with simple increased nuchal translucency, cystic hygroma has 5-fold, 12-fold, and 6-fold increased risk of aneuploidy, cardiac malformation, and perinatal death, respectively. CONCLUSION: First-trimester cystic hygroma was a frequent finding in a general obstetric screening program. It has the strongest prenatal association with aneuploidy described to date, with significantly worse outcome compared with simple increased nuchal translucency. Most pregnancies with normal evaluation at the completion of the second trimester resulted in a healthy infant with a normal pediatric outcome.

Abortion, Therapeutic↗
PubMed2004

Threatened abortion: A risk factor for poor pregnancy outcome, a population-based screening study.

OBJECTIVE: The purpose of this study was to determine whether patients with first-trimester threatened abortion are at increased risk for poor pregnancy outcome. STUDY DESIGN: A large prospective multicenter database was studied. Subjects were divided into three groups: (1) no bleeding, (2) light bleeding, and (3) heavy bleeding. Univariate and multivariable logistic regression analyses were used. RESULTS: The study comprised 16,506 patients: 14,160 patients without bleeding, 2094 patients with light bleeding, and 252 patients with heavy bleeding. Patients with vaginal bleeding, light or heavy, were more likely to experience a spontaneous loss before 24 weeks of gestation (odds ratio, 2.5 and 4.2, respectively) and cesarean delivery (odds ratio, 1.1 and 1.4, respectively). Light bleeding subjects were more likely to have preeclampsia (odds ratio, 1.5), preterm delivery (odds ratio, 1.3), and placental abruption (odds ratio, 1.6). Heavy vaginal bleeding subjects were more likely to have intrauterine growth restriction (odds ratio, 2.6), preterm delivery (odds ratio, 3.0), preterm premature rupture of membranes (odds ratio, 3.2), and placental abruption (odds ratio, 3.6). CONCLUSION: First-trimester vaginal bleeding is an independent risk factor for adverse obstetric outcome that is directly proportional to the amount of bleeding.

Abortion, Spontaneous↗
PubMed2004

First-trimester maternal serum PAPP-A and free-beta subunit human chorionic gonadotropin concentrations and nuchal translucency are associated with obstetric complications: a population-based screening study (the FASTER Trial).

OBJECTIVE: The purpose of this study was to determine whether maternal serum levels of pregnancy-associated plasma protein A, free-beta subunit human chorionic gonadotropin, or nuchal translucency size are associated with obstetric complications. STUDY DESIGN: Data were obtained from the First and Second Trimester Evaluation of Risk trial. Pregnancy-associated plasma protein A and free-beta subunit human chorionic gonadotropin levels were analyzed, and nuchal translucency was measured between 10 weeks 3 days and 13 weeks 6 days of gestation in 34,271 pregnancies. RESULTS: Women with pregnancy-associated plasma protein A of < or =5th percentile were significantly more likely to experience spontaneous fetal loss at < or =24 weeks of gestation, low birth weight, preeclampsia, gestational hypertension, preterm birth ( P < .001) and stillbirth, preterm premature rupture of membranes, and placental abruption ( P < .02). Nuchal translucency at > or =99th percentile and free-beta subunit human chorionic gonadotropin at < or =1st percentile were associated with an increased risk of spontaneous loss at < or =24 weeks of gestation (adjusted odds ratios, 3.90, 3.62, respectively; P < .001). CONCLUSION: Low pregnancy-associated plasma protein A levels in the first trimester were associated strongly with a number of adverse pregnancy outcomes. Low free-beta subunit human chorionic gonadotropin levels and large nuchal translucency were both associated with early fetal loss.

Abortion, Spontaneous↗
PubMed2004

Is discordant growth in twins an independent risk factor for adverse neonatal outcome?

OBJECTIVE: To estimate whether discordant growth is associated with adverse perinatal outcomes in twins after adjusting for growth restriction. METHODS: This was a retrospective, hospital-based cohort study of twin gestations with 2 live births delivered at 24 weeks or later from 1992 to 2001. Twin gestations were classified as small for gestational age (SGA) if one or both infants was less than the 10th percentile at birth by singleton Brenner norms and discordant if there was a 20% or more weight discordance. RESULTS: Of 1318 twin pairs, 856 were appropriate for gestational age (AGA) and concordant, 70 pairs were AGA and discordant, 254 pairs were SGA and concordant, and 138 pairs were SGA and discordant. The 4 groups had similar maternal demographics and medical comorbidity. When adjusting for chorionicity, antenatal steroid use, oligohydramnios, preeclampsia, and gestational age at delivery, discordant twins were more likely to have a cesarean delivery (odds ratio 1.87; 95% confidence interval 1.22, 2.87) and to be associated with some adverse neonatal outcomes (low and very low birthweight, neonatal intensive care unit admission, neonatal oxygen requirement and hyperbilirubinemia) independent of SGA status. A statistically nonsignificant trend (odds ratio 2.4; 95% confidence interval 0.99, 6.01) toward higher rates of intraventricular hemorrhage was noted in discordant twins, and no difference was seen for ventilator requirement, respiratory distress syndrome, or necrotizing enterocolitis. CONCLUSION: Discordance places twins at increased risk for some adverse perinatal outcomes, whether they are AGA or SGA. Discordance was not an independent risk factor for serious neonatal morbidity or mortality; however, this study was underpowered to detect those differences.

Adult↗
PubMed2004

Responses by pregnant Jehovah's Witnesses on health care proxies.

OBJECTIVE: To review the treatment options presented on the New York State Health Care Proxy for Jehovah's Witnesses, which is signed by pregnant women when they present for care. METHODS: Chart reviews were performed for all women who presented to labor and delivery at our institution from 1997 to 2002 and identified themselves as Jehovah's Witnesses. A patient was included in the study if a completed health care proxy was available in her chart. Data were derived from the health care proxy and from the Mount Sinai School of Medicine's Blood Product Checklist for Jehovah's Witness Patients. Variables of interest included age, race, parity, and antenatal and perinatal complications. RESULTS: A total of 61 patients were identified. Of these, 39.3% agreed to accept a variety of donated blood products, 9.8% would accept donated packed red blood cells, and 50.1% would accept neither from a homologous donor. With respect to nonstored autologous blood, 55% of respondents would accept either intraoperative normovolemic hemodilution or transfusion of their own blood obtained by a cell salvage system. No significant differences in responses were noted for any of the above-mentioned variables. CONCLUSION: This review refutes the commonly held belief that all Jehovah's Witnesses refuse to accept blood or any of its products. In this population of pregnant women, the majority were willing to accept some form of blood or blood products. This information can be used to help health care providers counsel a patient when she is initially faced with considering these issues and may help to remove the stigma of accepting one of the options.

Adult↗
PubMed2004

First-trimester nasal bone evaluation for aneuploidy in the general population.

OBJECTIVE: To evaluate the role of fetal nasal bone imaging at 10 3/7 to 13 6/7 weeks as a screening tool for aneuploidy, in a prospective multicenter trial. METHODS: Unselected patients from the general population with viable singleton pregnancies at 10 3/7 to 13 6/7 weeks were recruited at 15 U.S. centers. All had screening with nuchal translucency (NT) ultrasound by specially trained sonographers. In the last 8 months of this trial, first trimester nasal bone evaluation was added to the screening protocol. Nasal bones were described as present, absent, or unable to determine. RESULTS: A total of 38,189 patients completed first trimester NT screening, of whom 6,324 also underwent nasal bone sonography. An acceptable nasal image was obtained in 4,801 cases (76%), with nasal bones described as present in 4,779 (99.5%), and absent in 22 (0.5%). There were 11 identified cases of trisomy-21 in the population of 6,324 patients. In 9 of the 11 cases (82%) the nasal bones were described as present, and 2 cases were described as unable to determine. The only other aneuploidies were 2 cases of trisomy-18, in 1 of which the nasal bones were described as absent, and in 1 present. Absence of nasal bones had sensitivity for aneuploidy of 7.7%, false-positive rate 0.3%, and positive predictive value 4.5%. CONCLUSION: First-trimester nasal bone evaluation was not a useful test for population screening for trisomy-21 and added little to first-trimester NT screening. The difficulty in performing first-trimester nasal bone sonography consistently, in the general population setting, will significantly limit the usefulness of this aneuploidy screening technique.

Aneuploidy↗
PubMed2003

Ethical and medicolegal considerations in the obstetric care of a Jehovah's Witness.

Jehovah's Witnesses comprise a unique obstetric population. Their refusal of blood stems from an interpretation of a literal translation of the Bible, and it is this belief that puts them at an increased risk of morbidity and mortality if hemorrhage occurs. Many Jehovah's Witnesses feel that accepting a blood transfusion will lead them to eternal damnation. A patient's self-determination, or autonomy, allows her to make decisions regarding her care. The decision to refuse blood or blood products has been upheld in court. This brings a new twist to the physician's obligation to "do no harm." When one undertakes the care of one of these patients, it is important to understand the ethical and medicolegal ramifications. The decision to be the primary caregivers can only be made once the physicians have decided they can let the patient die when all other options have been exhausted. This commentary discusses the ethical concerns and reviews the alternatives available to a Jehovah's Witness.

Ethics, Medical↗