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The ATM gene variants segregating in ataxia-telangiectasia families are associated with increased breast cancer risk, but the contribution of specific variants has been difficult to estimate. Previous small studies suggested two functional variants, c.7271T>G and c.1066-6T>G (IVS10-6T>G), are associated with increased risk. Using population-based blood samples we found that 7 out of 3,743 breast cancer cases (0.2%) and 0 out of 1,268 controls were heterozygous for the c.7271T>G allele (P=0.1). In cases, this allele was more prevalent in women with an affected mother (odds ratio [OR]=5.5, 95% confidence interval [CI]=1.2-25.5; P=0.04) and delayed child-bearing (OR=5.1; 95% CI=1.0-25.6; P=0.05). The estimated cumulative breast cancer risk to age 70 years (penetrance) was 52% (95% CI=28-80%; hazard ratio [HR]=8.6; 95% CI=3.9-18.9; P<0.0001). In contrast, 13 of 3,757 breast cancer cases (0.3%) and 10 of 1,268 controls (0.8%) were heterozygous for the c.1066-6T>G allele (OR=0.4; 95% CI=0.2-1.0; P=0.05), and the penetrance was not increased (P=0.5). These findings suggest that although the more common c.1066-6T>G variant is not associated with breast cancer, the rare ATM c.7271T>G variant is associated with a substantially elevated risk. Since c.7271T>G is only one of many rare ATM variants predicted to have deleterious consequences on protein function, an effective means of identifying and grouping these variants is essential to assess the contribution of ATM variants to individual risk and to the incidence of breast cancer in the population. Hum Mutat 27(11), 1122-1128, 2006. Published 2006 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Objective: Fetal alloimmune thrombocytopenia is the result of maternal fetal platelet antigen incompatibility; intracranial hemorrhage is its most serious complication. Our previous studies have demonstrated an inability to accurately predict fetal platelet counts in this disorder. The goal of the present investigation was to identify factors that would predict the response of the fetal platelet count to therapy so that use of fetal blood sampling could be minimized.Study Design: Patients who were eligible for the study were all those who (1) had alloimmune thrombocytopenia secondary to Pl(A1) (HPA-1a, Zw(A)) platelet antigen incompatibility, (2) were treated with maternally administered intravenous immunoglobulin at 1 g/kg of body weight per week, with or without low dose steroids, and (3) had percutaneous fetal blood sampling before the initiation of therapy (first fetal blood sampling) and again 3 to 7 weeks afterwards (second fetal blood sampling).Results: In this retrospective review, 74 patients who were affected by alloimmune thrombocytopenia had a median platelet count of 21,000 per microliter at the first fetal blood sampling and 47,000 per microliter at the second fetal blood sampling, with a median increase in platelet count of 24,000 per microliter. Response to treatment was defined as either (1) an improvement in platelet count (the second fetal blood sampling greater than the first fetal blood sampling, and second fetal blood sampling > 20,000 per microliter) or (2) a minimal decline in platelet count (the first fetal blood sampling > or = 40,000 per microliter and the difference between the first and second fetal blood sampling < or = 10,000 per microliter). The first fetal blood sampling had prognostic value for the second fetal blood sampling (P = .0001), although the previous sibling birth platelet count and history of sibling intracranial hemorrhage did not predict the platelet count at the first or second fetal blood sampling or the change in platelet count between the samplings. When the patients were segregated to first fetal blood sampling of > 20,000 per microliter versus < or = 20,000 per microliter, the response rates for the 2 groups were 89% (33/37 patients) versus 51% (19/37 patients; P = .001).Conclusion: In fetal alloimmune thrombocytopenia secondary to Pl(A1) platelet antigen incompatibility, fetuses with platelet counts > 20,000 per microliter at the initiation of therapy were predicted to maintain their platelet count at the second fetal blood sampling at > 20,000 per microliter. The characteristics of the previous sibling, as previously reported, did not predict the initial fetal blood sampling, the second fetal blood sampling, or the response to treatment. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Context: Pregnancies complicated by abruption result in increased frequency of perinatal death and decreased fetal size and gestational duration, yet the extent of placental separation and its effect on these adverse outcomes is unknown.Objective: To assess the contribution of placental abruption and extent of placental separation to stillbirth, preterm delivery, and fetal growth restriction.Design: Hospital-based, retrospective cohort study.Setting: Mount Sinai Hospital, New York City, NY.Participants: A total of 53,371 pregnancies occurring in 40,789 women who were delivered of singleton births between 1986 and 1996.Main Outcome Measures: Risks and relative risks for stillbirth (>20 weeks), preterm delivery (<37 weeks), and fetal growth restriction (birth weight below 10th percentile for gestational age) in relation to abruption.Results: The incidence of abruption was 1 % (n = 530). Abruption was associated with an 8.9-fold (95% confidence interval [CI], 6.0-13.0) adjusted relative risk (aRR) of stillbirth. Preterm birth proportions among women with and without abruption were 39.6% and 9.1 %, respectively, yielding an aRR of 3.9 (95% CI, 3.5-4.4). In the abruption group, 14.3% of neonates were growth restricted, compared with 8.1 % among all other births (aRR, 2.0; 95% CI, 1.5-2.4). Extent of placental separation had a profound effect on stillbirth (aRR for 75% separation, 31.5; 95% CI, 17.0-58.4), although evident only among those with at least 50% separation. However, the risk of preterm delivery was substantially increased even for mild abruptions (aRR for 25% separation, 5.5; 95% CI, 4.2-7.3).Conclusions: In this cohort, placental abruption had a profound impact on stillbirth, preterm delivery, and fetal growth restriction. The risk of stillbirth was dramatically increased for severe placental separation, but preterm delivery was common even among women with lesser degrees of placental separation. [ABSTRACT FROM AUTHOR]

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 quintuplets 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 > or = 5. This finding provides a further rationale to avoid transferring excessive numbers of preembryos after in vitro fertilization. [ABSTRACT FROM AUTHOR]

Intravenous heparin is frequently used to treat thromboembolic disease, but the consequences of stopping heparin have not been studied systematically. To determine whether discontinuing heparin poses a clinical risk, we examined the charts of 378 patients treated with heparin for transient ischaemic attack (TIA), reversible ischaemic neurological deficit, or ischaemic stroke from October 1979 to June 1985. Clinical deterioration, or a new TIA or stroke was more likely (p = 0.01) during the 24 hours after heparin was stopped in patients not already on aspirin or warfarin (10/143, 7%) than in patients receiving aspirin or warfarin before heparin withdrawal (3/215, 1%). Stopping heparin in patients not receiving aspirin or warfarin appears to expose them to an increased risk for TIA, stroke, or clinical deterioration. [ABSTRACT FROM AUTHOR]

We conducted serial neurologic examinations on 500 patients in nontraumatic coma to identify factors predicting recovery. Overall, 81 patients (16%) led an independent life at some point within the first year; the remainder either died without recovery from coma (61%), never improved beyond the vegetative state (12%), or regained consciousness but remained dependent on others for daily activities (11%). Functional recovery did not depend on age but was to some degree related to the cause of coma (subarachnoid hemorrhage and other cerebrovascular disease having the worst recovery; hypoxia-ischemia, intermediate; and hepatic and miscellaneous causes, best) and especially to early clinical signs of brain dysfunction. Even within hours of the onset of coma, only one of 120 patients lacking two of corneal, pupillary, and oculovestibular responses ever regained independent function. The study identifies clinical features of comatose patients that appear within the first week and that are important for predicting recovery and designing future therapeutic trials. [ABSTRACT FROM AUTHOR]