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Dizziness is the third most common major medical symptom reported in general medical clinics (1) and accounts for about 3%-5% of visits across care settings. (2) In the United States, [...]

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ajog.2006.05.001 Byline: Richard L. Berkowitz (a), James B. Bussel (b), Janice G. McFarland (c) Abstract: 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/mL.sup.3 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. Author Affiliation: (a) Department of Obstetrics and Gynecology, Columbia Presbyterian Medical Center (b) Department of Pediatrics, Division of Hematology-Oncology, Weill Medical College of Cornell University, New York, NY (c) BloodCenter of Wisconsin, Milwaukee, WI Article History: Received 28 March 2006; Revised 26 April 2006; Accepted 4 May 2006

Maternal immunoglobulin G anti-platelet alloantibodies cross the placenta and cause fetal thrombocytopenia in cases of alloimmune thrombocytopenia (AIT). The diagnosis requires laboratory demonstration of incompatibility between a maternal and paternal platelet alloantigen, and detection of material antibody to the discordant paternal allonatigen.

A study was undertaken 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. Results show that low free-beta subunit human gonadotropin levels and large nuchal translucency could result in early fetal loss.

The risk of adverse outcome for pregnancies, with first-trimester threatened abortion, due to first-trimester vaginal bleeding, occurring in 16 to 25 percent of all pregnancies, is discussed. Various outcomes of the first-trimester bleeding during pregnancy include the pregnancy loss, preterm delivery, intrauterine growth restriction (IUGR), gestational hypertension, preeclampsia, preterm premature rupture of membranes (PPROM), placental abruption, placenta previa, and cesarean delivery.

A selective abortion can be done if a woman has a twin or triplet pregnancy in which one fetus has a chromosome abnormality and the others do not. In a study of 200 selective abortions, the miscarriage rate was only 4%. The risk of a miscarriage was about five times higher in women pregnant with three or more fetuses compared to those with twins.

Multifetal pregnancy reduction will cause a miscarriage in about 5% of all pregnant women who have the procedure, according to a study of 1,000 women who had the operation. This operation is done to reduce the number of fetuses in pregnancies with two or more fetuses. The rate of miscarriage is highest in women with 6 or more fetuses.

Far fewer women today die from a potentially catastrophic obstetric hemorrhage, thanks to prompt blood transfusions and surgical intervention. But what precautions can help patients like Jehovah's Witnesses, whose religious [...]

Fetuses with alloimmune thrombocytopenia are most likely to respond to treatment with intravenous gammaglobulin therapy if their initial platelet count is greater than 20,000 per microliter. Doctors can therefore minimize the use of fetal blood sampling in these fetuses.

Multifetal pregnancy reduction from quadruplets or triplets to twins can produce an outcome similar to natural twin pregnancies, according to an analysis of 3,513 cases from 11 hospitals in five countries. The more fetuses there are before the procedure, the worst the outcome will be for the remaining fetuses.

Chorionic villus sampling appears to be safe when done before a multiple pregnancy is reduced. Chorionic villus sampling is done to determine if any of the fetuses has a genetic disorder. If so, that fetus would be aborted, leaving the healthy fetuses to continue to term.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1067/mob.2000.104802 Byline: Fergal D. Malone, Richard L. Berkowitz (b), Jacob A. Canick (c), Mary E. D'Alton (a) Abstract: First-trimester screening for Down syndrome has been proposed as a significant improvement with respect to second-trimester serum screening programs, the current standard of care, because of apparently higher detection rates and an earlier gestational age at diagnosis. First-trimester nuchal translucency on ultrasonography forms the basis of this new form of screening, although studies of its efficacy have yielded widely conflicting results, with detection rates ranging from 29% to 91 %. Studies of first-trimester serum screening with measurements of pregnancy-associated plasma protein A and free [beta]-human chorionic gonadotropin serum concentrations have been much more consistent, with Down syndrome detection rates of 55% to 63% at a 5% false-positive rate. The combination of first-trimester ultrasonographic and serum screening has the potential to yield a Down syndrome detection rate of 80% at a 5% false-positive rate, although this approach has not been adequately studied. There have been no studies performed to date to directly compare the performance of first-trimester and second-trimester methods of screening. Two major trials are underway that will address this issue, one in the United Kingdom and one in the United States. Until the results of these trials are available, the current standard of care with respect to Down syndrome screening should not be changed, and first-trimester screening should remain investigational. Author Affiliation: (a) Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Columbia-Presbyterian Medical Center, New York, New York, USA (b) Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Mount Sinai Medical Center, Providence, Rhode Island, USA (c) Division of Prenatal and Special Testing, Department of Pathology and Laboratory Medicine, Women and Infants'Hospitale, New York, New York, USA

Further research is needed before doctors begin testing pregnant women for Down's syndrome in their baby in the first trimester. Many doctors believe it is best to detect Down syndrome as early as possible, they must first identify the most accurate test.

It appears possible to abort one fetus in a twin pregnancy without harming the remaining fetus, according to an international study of 402 such cases. Most often this is done because one of the fetuses has a severe birth defect and is not expected to live.

Women who have more than 10 children may have a greater risk of childbirth complications. However, the infant death rate is low, so having more than 10 children is not necessarily dangerous provided the mother receives adequate prenatal care.

Byline: Agota Babinszki, Thomas Kerenyi, Olga Torok, Victor Grazi, Robert H. Lapinski, Richard L. Berkowitz Keywords: Grand multipara; great-grand multipara; risk factors Abstract: Objective: We sought to compare obstetric and neonatal complications among great-grand multiparous, grand multiparous, and multiparous women. Study Design: One hundred thirty-three great-grand multiparas, 314 grand multiparas, and 2195 multiparas who were delivered of their infants between 1988 and 1998 were selected for the study. To facilitate comparison, the patients were all >35 years old and had similar socioeconomic characteristics. Results: The incidence of malpresentation at the time of delivery, maternal obesity, anemia, preterm delivery, and meconium-stained amniotic fluid increased with higher parity, whereas the rate of excessive weight gain and cesarean delivery decreased. Compared with grand multiparas, great-grand multiparas had significantly elevated risks for abnormal amounts of amniotic fluid, abruptio placentae, neonatal tachypnea, and malformations but lower rates of placenta previa (P < .05). The incidence of postpartum hemorrhage, preeclampsia, placenta previa, macrosomia, postdate pregnancy, and low Apgar scores was significantly higher in grand multiparas than in multiparas, whereas the proportion of induction, forceps delivery, and total labor complications was significantly lower than in the multiparous group (P < .05). Similar frequency of maternal diabetes, infection, uterine wall scar rupture, variations in fetal heart rate, fetal death, and neonatal mortality was found in the 3 groups. Conclusion: Both high-parity groups have their own risk factors, but the rate of some complications decreases with higher parity. In addition, perinatal mortality remains low in these patients, and therefore, under satisfactory socioeconomic and health care conditions, high parity should not be considered dangerous. (Am J Obstet Gynecol 1999;181:669-74.) Article History: Received 2 November 1998; Revised 8 February 1999; Accepted 8 May 1999 Article Note: (footnote) [star] From the Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology and Reproductive Sciences, Mount Sinai School of Medicine., [star][star] Reprint requests: Thomas Kerenyi, MD, 1126 Park Ave, New York, NY 10128., a 0002-9378/99 $8.00 + 0 6/1/99918

Amniocentesis does not appear to increase the risk of miscarriage in women who have had multifetal pregnancy reduction. Many women who take fertility pills become pregnant with more than one fetus. If there are four or more embryos, some doctors will remove two or three embryos so the remaining embryos will have a better outcome. Researchers analyzed fetal outcomes in 294 pregnant women who had multifetal pregnancy reduction, 127 of whom also had amniocentesis. Both procedures together did not increase the risk of miscarriage above the small risk attributed to multifetal pregnancy reduction alone.

Byline: Belgin Selam, Olga Torok, Arda Lembet, Joanne Stone, Robert Lapinski, Richard L. Berkowitz Keywords: Genetic amniocentesis; multifetal pregnancy reduction; pregnancy loss Abstract: Objective: Our purpose was to evaluate the pregnancy loss rate resulting from genetic amniocentesis after multifetal pregnancy reduction. Study Design: A cohort study was performed in pregnancies with maternal age >30 years. Pregnancy loss in a study population of 127 patients who underwent genetic amniocentesis after multifetal pregnancy reduction were compared with a control group of 167 patients who did not have genetic amniocentesis after multifetal pregnancy reduction. Results: The pregnancy loss rate in patients who underwent genetic amniocentesis after multifetal pregnancy reduction was 3.1% (4/127 cases) compared with 7.2% (12/167 cases) in the controls (P > .05). In the study group evidence of infection was found in only 1 case, in which the pregnancy loss occurred 1 day after the amniocentesis. In the other cases the pregnancy losses occurred 5 weeks after genetic amniocentesis, and these losses could not be directly attributed to either genetic amniocentesis or the multifetal reduction procedure. Conclusion: Our data suggest that the performance of genetic amniocentesis after multifetal pregnancy reduction does not increase the risk of pregnancy loss over that observed in association with the reduction itself. (Am J Obstet Gynecol 1999;180:226-30.) Author Affiliation: Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology, and Reproductive Science, Mount Sinai School of Medicine. New York, New York Article History: Received 7 April 1998; Revised 2 June 1998; Accepted 16 July 1998 Article Note: (footnote) [star] Reprint requests: Richard L. Berkowitz, MD, Department of Obstetrics, Gynecology, and Reproductive Sciences, Mount Sinai School of Medicine, 5 E 98th St, Box 1171, New York, NY 10029., [star][star] 0002-9378/99 $8.00 + 0 6/1/93245

In vitro fertilization that results in five or more embryos appears to increase the risk of intrauterine growth restriction (IUGR) even if the pregnancy is reduced to two fetuses. Researchers analyzed the rates of IUGR in 441 women with twin pregnancies after undergoing multifetal pregnancy reduction and 136 women with natural twin pregnancies. No differences were found in the rate of IUGR except in the women who had five or more fetuses before the reduction procedure. These women had twice the risk of IUGR.

Byline: Olga Torok, Robert Lapinski, Carolyn M. Salafia, James Bernasko, Richard L. Berkowitz Keywords: Multifetal pregnancy reduction; intrauterine growth restriction; twins Abstract: OBJECTIVE: Our purpose was to investigate whether multifetal pregnancies reduced to twins have an increased risk of intrauterine growth restriction and discordant birth weight. STUDY DESIGN: This retrospective cohort study investigated the rates of birth weight discordance >20% and intrauterine growth restriction using both twin and singleton birth weight curves in 441 twin deliveries after multifetal pregnancy reduction (233 reduced from triplets, 156 from quadruplets, and 52 from quintup-lets or greater) compared with 136 nonreduced dichorionic twins. RESULTS: No significant difference was found in the frequency of birth weight discordance and in the overall incidence of intrauterine growth restriction by both twin and singleton birth weight curves when pregnancies that underwent multifetal pregnancy reduction were compared with the control group. There was, however, an almost twofold increase in the rate of intrauterine growth restriction in pregnancies with a starting fetal number of 5 or more (23.1%) compared with that in those reduced from triplets or quadruplets (12.1%) when the twin curve standard was used (P = .03). This difference disappeared when these groups were compared with a singleton nomogram. CONCLUSION: This study suggests that multifetal pregnancy reduction is not associated with an increased risk of intrauterine growth restriction unless the starting fetal number is [greater than or equal to]5. This finding provides a further rationale to avoid transferring excessive numbers of preembryos after in vitro fertilization. (Am J Obstet Gynecol 1998;179:221-5.) Author Affiliation: New York, New York Article History: Received 3 September 1997; Revised 14 November 1997; Accepted 13 December 1997 Article Note: (footnote) [star] From the Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences, Mount Sinai School of Medicine., [star][star] Reprint requests: Richard L. Berkowitz, MD, Department of Obstetrics, Gynecology, and Reproductive Sciences, Mount Sinai School of Medicine, 1 Gustave E. Levy Place, New York, NY 10029., a 0002-9378/98 $5.00 + 0 6/1/88527

Blood platelets may effectively seal punctures in fetal membranes. Premature rupture of fetal membranes rapidly leads to delivery and, therefore, a premature infant. A technique to patch ruptured fetal membranes may permit a pregnancy to continue, improving the outcome for the baby. Researchers experimented with fresh fetal membranes, amniotic fluid, and platelets obtained from a blood bank. Fetal membrane connective tissue, as would be exposed in a rupture, caused platelet activation and the formation of a platelet plug. This may form the basis of a membrane repair.

Byline: Christine Louis-Sylvestre (a), Jacob H. Rand (b), Ronald E. Gordon (c), Carolyn M. Salafia (c), Richard L. Berkowitz (a) Abstract: Objective: Thus far there is no satisfactory treatment for preterm premature rupture of the amniotic membranes. To evaluate the use of platelets to seal the membranes, we investigated in vitro interactions between platelets and the membranes. Study design: Platelet aggregation in the presence of amnion, chorion, and amniotic fluid was quantified. Platelet adhesion to the fetal membranes was investigated by electron microscopy. In addition, a model system was designed to evaluate the capacity of platelets to seal a standardized puncture in the membranes. Results: Platelets aggregated in response to amnion but not to chorion or amniotic fluid. Adhesion and activation occurred on connective tissues underlying amnion and chorion but not on the amniotic epithelium. Platelets sealed a puncture in fetal membranes, and the platelet plug was visualized by electron microscopy. Conclusions: Exposed connective tissue of amniotic membranes was demonstrated to trigger platelet adhesion, aggregation, and activation, and platelets were shown to seal a standardized puncture in fetal membranes. Our results indicate that platelets might be useful for treatment of ruptured membranes after needle puncture Author Affiliation: (a) Department of Obstetrics, Gynecology, and Reproductive Science, Mount Sinai School of Medicine, New York, New York USA (b) Department of Medicine, Mount Sinai School of Medicine New York, New York USA (c) Department of Pathology, Mount Sinai School of Medicine, Supported by a grant from the College National des Gynecologues et Obstetriciens Francais New York, New York USA Article History: Received 22 April 1997; Revised 17 June 1997; Accepted 13 August 1997

Fetuses with very low platelet counts may benefit from intravenous gamma-globulin treatment. Researchers compared the effects of intravenous gamma-globulin treatment with or without dexamethasone or prednisone administered to 54 pregnant women whose fetuses had low platelet counts. Weekly treatments of intravenous gamma-globulin significantly increased platelet counts from time of diagnosis until birth. None of the treated fetuses experienced brain hemorrhage, which can occur in up to 50% of fetuses with low platelet counts. The addition of dexamethasone to treatment did not enhance the platelet count. The addition of prednisone raised platelet counts in half of the fetuses who did not respond to initial treatments. A noninvasive method of determining platelet counts would be useful.

Selective reduction of triplet pregnancies to twins may be fairly safe in light of the increased risks of preterm birth of triplets. Prevention of multifetal pregnancies in the first place is much more preferable to selective reduction after assisted reproduction treatments. Selective reduction of multifetal pregnancies to twins can reduce the risk of preterm birth and of losing the entire pregnancy, but may still result in loss of the entire pregnancy. Selective reduction may be warranted in triplet pregnancies as well as in pregnancies with four or more fetuses. The transvaginal approach where potassium chloride is injected into the fetus's chest appears to be the most effective method of selective reduction with a pregnancy loss rate of 9%. Selective reduction should not become a backup for infertility providers.

Byline: Richard L. Berkowitz, Lauren Lynch, Joanne Stone, Manuel Alvarez Keywords: Multifetal pregnancy reduction; multiple gestation; infertility therapy; assisted reproductive technology Abstract: The number of women conceiving three or more fetuses has increased dramatically as a result of successful infertility therapy with ovulation-inducing agents and assisted reproductive technology. Higher-order multiple gestations have an increased risk of premature delivery and its attendant sequelae of increased neonatal mortality or irreversible morbidity. Multifetal pregnancy reduction is a procedure designed to decrease the increased propensity to deliver very prematurely in these patients by reducing the number of live fetuses they are carrying. The procedure has proved to be both safe and effective, and pregnancies reduced to twins proceed as if that were the number of fetuses originally conceived. Nevertheless, this invasive procedure does have the potential to result in loss of the entire pregnancy and causes considerable emotional distress for some couples who view it as their 'least bad' alternative. The medical benefits of performing multifetal pregnancy reduction in women with four or more fetuses seem fairly well established, but this is less true for triplets. Serious attention should be paid to reducing the number of higher-order multiple pregnancies resulting from infertility therapy. In the meantime, when three or more fetuses have been conceived, multifetal pregnancy reduction offers a reasonable option to patients whose only choices in the past were either to accept the risk of delivering extremely prematurely or to terminate the entire pregnancy. (AM J OBSTET GYNECOL 1996;174:1265-72.) Author Affiliation: New York, New York Article Note: (footnote) [star] From the Department of Obstetrics, Gynecology and Reproductive Science, Mount Sinai Medical Center., [star][star] Reprint requests: Richard L. Berkowitz, MD, Department of Obstetrics, Gynecology and Reproductive Science, One Gustave L. Levy Place, New York, NY 10029., a 0002-9378/96 $5.00 + 0 6/1/69361

Women who had first-trimester multifetal pregnancy reduction generally found it psychologically stressful but recovered. A smaller subgroup tended to experience long-lasting feelings of sadness and guilt. Ninety-one women who underwent multifetal reduction after conceiving triplets to nonituplets via in vitro fertilization agreed to a telephone interview one to three years after the procedure. More than 65% found the procedure emotionally painful, stressful, and frightening. Seventy percent of the women mourned the lost fetuses, but few mourned longer than one month. Moderately severe feelings of sadness or guilt persisted for 20% of the group, especially among younger, more religious women, who had viewed the embryos more frequently on ultrasound. However, 93% would make the same decision again. It is thought that relief and bonding to the remaining fetuses served to buffer negative feelings. Additional psychological support may be of benefit, especially among women fitting the profile of the subgroup that was more likely to experience prolonged or severe reaction.

Fetuses with blood clotting disorders are at increased risk from bleeding to death from cordocentesis. Cordocentesis is a procedure where a blood sample is taken from the fetal umbilical cord by passing a needle through the mother's abdomen. Five fetuses with alloimmune thrombocytopenia, a disease in which the mother's immune system attacks fetal platelets, a blood component responsible for clotting, bled to death after cordocentesis. They were compared with 44 fetuses with the same disease who survived the procedure. The mean platelet count among fetuses who died was 6 versus 33 X 10 to the ninth power per liter among surviving fetuses. Fetuses who died were also more likely to have a sibling with the disease from a prior pregnancy who had a brain hemorrhage before birth. It is strongly recommended that fetuses with platelet counts of 50 or less at the time of cordocentesis receive a blood transfusion before withdrawing the sampling needle.

Fetal endothelin levels exceed those of the mother, but there is no correlation with gestational age. Endothelin is produced by the cells lining blood vessels, and its secretion primarily causes blood vessel constriction. Sixty-four women had blood samples drawn from the umbilical cord by passing a needle through the maternal abdomen. This was done for diagnostic purposes, but all fetuses selected for the study were normal. Prior to the procedure blood was also drawn from the mother. In addition, blood was drawn from the umbilical cord of eight healthy newborns. No correlation was found between either fetal and maternal endothelin levels and gestational age or between endothelin levels between the mother and the fetus. Fetal endothelin levels averaged 2.5 picograms per milliliter versus maternal levels of 1.3 picograms per milliliter versus newborn levels of 15.77 picograms per milliliter. The increase in endothelin level after birth seems reasonable considering the changes in vascular resistance that follow birth.

Increased levels of interleukin-6 (IL-6) in cervical secretions may be associated with preterm birth. IL-6 is produced during inflammatory processes. Vaginal and cervical secretion samples were collected from 161 pregnant women at 3- to 4-week intervals starting at 24 weeks and analyzed for IL-6 by immnunoassay. A single IL-6 value greater than 250 pg/ml of sample buffer accurately identified 50% of the women who gave birth before 37 weeks gestation, and the absence of elevated IL-6 levels identified 85% of the women who gave birth at term. Vaginal IL-6 levels had less predictive accuracy. A woman with cervical secretion IL-6 levels above 250 pg/ml had 4.8 times the odds of preterm birth. Despite the known involvement of IL-6 in infective processes, elevated IL-6 levels were not associated with mean white blood cell count, the prevalence of vaginal pathogens, alkaline vaginal pH, chorioamnionitis, or endometritis.

Insulin-like growth factor-binding protein-1 (IGFBP-1) found in the vaginal fluid of pregnant women may be used as a diagnostic indicator of fetal membrane rupture. Almost 75% of 100 women complaining of possible premature rupture of the membranes were found to have vaginal IGFBP-1 values greater than three micrograms per liter. Some false-negative but few false-positive results were observed. Testing for the presence of IGFBP-1 in vaginal fluid could be used to confirm whether membrane rupture has occurred. This measure should be used with clinical observation. The optimal cutoff value for IGFBP-1 remains to be determined.

Selective termination of an abnormal twin fetus or multiple fetuses in a dizygotic (fraternal) pregnancy may be safely performed by an experienced physician with injections of potassium chloride. A multicenter study of 180 fetuses that were selectively aborted correlated early gestational age at the time of the procedure with a low loss rate and with an older gestational age at birth. The study also found that the air embolization method of abortion was riskier for the surviving fetus(es) than was potassium chloride injection. Losses occurred every time for both twins when selective termination was performed to a twin of a monochorial pregnancy, in which the twins shared the same placenta. Genetic prenatal diagnosis should be performed as early as possible, using chorionic villus sampling rather than waiting to do amniocentesis. Thus, if selective termination is chosen, it can be performed early in the pregnancy. Exact identification of the fetus(es) to be aborted is also necessary, to avoid accidentally aborting the healthy fetus.

A multifetal pregnancy may be managed safely and effectively by either transabdominal or transvaginal methods of pregnancy reduction. Fertility drugs or assisted reproductive techniques sometimes result in multifetal pregnancies. In order to improve the chances of a successful pregnancy and healthy infants, one or more fetuses may be eliminated by pregnancy reduction. The transabdominal technique involves inserting an ultrasound-guided needle through the abdomen into the fetal heart and injecting a fatal substance. Transvaginal techniques involve either the same sort of injection through the vagina or disruption and aspiration of the embryo. Of 1074 pregnancy reductions studied, 846 used the transabdominal technique and 238 used transvaginal techniques. The miscarriage rate for transvaginal procedures was 13%. For the transabdominal procedure, the miscarriage rate improved over time from 16% to just under 9%. More than 84% of pregnancies reduced by either technique were carried to 33 weeks' gestation or longer.