Religiosity is an important part of coping with grief in pregnancy after a traumatic second trimester loss.

Women (n = 15) who were pregnant after a traumatic late pregnancy loss (termination because of fetal death or serious anomalies) completed psychometric screening tests and scales, including the Perinatal Grief Scale (PGS), the Impact of Event Scale (IES), the Duke Depression Inventory (DDI), the Generalized Anxiety Disorder-7 (GAD), and the Hoge Scale for Intrinsic Religiosity (IR). Despite a mean elapsed time since the prior loss of 27 (range, 7-47) months, half (7/15, 47%) of the combined groups had high levels of grief on the PGS. Multiple positive scores on psychometric tests were frequent: Sixty percent (9/15) had high scores on the PGS Active Grief subscale or on the IES. Forty percent (6/15) had a high score on the DDI, and 17% (3/15) on the GAD. IR scores significantly and negatively correlated with scores on the Despair subscale of the PGS. The results from this pilot study suggest that high levels of grief and PTS symptoms are significant problems for pregnant women who have suffered late loss of a wanted pregnancy. Religiosity may play an important part in maternal coping during these stressful pregnancies.

Religious beliefs affect grieving after pregnancy loss.

Religious beliefs and practices may aid in coping with bereavement and grief after pregnancy loss. Data from 103 women enrolled in the original Lehigh Valley Perinatal Loss Project, and who were followed-up for at least 1 year, were evaluated for the impact of initial religious practices and beliefs on the course and severity of grief. Religious practices corresponding to standard scales of religiosity and agreement with specific beliefs were rated by the women on a Likert scale of 1-5. Neither agreement with statements corresponding to extrinsic and intrinsic religiosity or to positive religious coping, nor frequency of religious service attendance was predictive of follow-up scores on the Perinatal Grief Scale. Religious struggle, agreement with statements classified as negative religious coping, and continued attachment to the baby were all associated with more severe grief.

Childhood craniopharyngioma: survival, local control, endocrine and neurologic function following radiotherapy.

Between 1961 and 1978, 19 patients with a diagnosis of childhood or teenage craniopharyngioma received supervoltage radiotherapy. All patients had previously undergone either partial surgical resection (10 patients), total gross resection (3 patients), or aspiration and biopsy (6 patients). Fourteen patients were treated primarily and five were treated for recurrence. The five-year survival was 73% with a 10-year survival of 64%. Sixteen percent developed a recurrence following radiotherapy. Long term effects were assessed in terms of neurologic, intellectual, psychological and endocrine function. Seventy-nine percent had none or minimal neurologic disability. The mean full scale IQ for the group was 90. There were no additional endocrine deficiencies that could be directly attributed to radiation. Behavioral disorders occurred in 50%. These results are at least comparable, if not superior, to those of surgery.

Brief clinical report: not all cystic hygromas occur in the Ullrich-Turner syndrome.

We report two sib fetuses with nuchal systic hygroma and cleft palate. This condition is probably recessively inherited as the parents have normal chromosomes (G-banded) and the fetuses were of opposite sex. Nuchal cystic hygroma is a nonspecific malformation, which reflects a delay in development of the connection between the jugular lymph sacs and the internal jugular vein. This fetal malformation and its equivalent in the adult, neck webbing, has been reported to be a part of a variety of genetic malformation syndromes. Some suggestions for counseling parents of an affected fetus are made: If the chromosome karyotype of an affected fetus is unknown, ultrasound examination, rather than AFP studies, is suggested for future pregnancies.

X-linked motor-sensory neuropathy type-II with deafness and mental retardation: a new disorder.

We report on a family with an apparently X-linked neuromuscular disease. Electrophysiologic tests and electron microscopic studies are consistent with the diagnosis of hereditary motor sensory neuropathy type II (HMSN-II), one form of Charcot-Marie-Tooth disease. The manner of inheritance, the observation that males are severely affected from infancy, and the frequent association of deafness and/or mental retardation with the neuromuscular disorder are not usual for HMSN-II and suggest that this family may have a previously undescribed genetic disorder. The peripheral neuropathy did not appear to be linked to the Xg blood group. Minor abnormalities of sensory nerve conduction, electromyography, and hearing were separately identified in female relatives in this family, but were not consistent enough to be useful in the identification of carriers for this gene.

Can tests for IgA, IgG, or IgM antibodies to cardiolipin or phosphatidylserine substitute for lupus anticoagulant assays in screening for antiphospholipid antibodies?

Antiphospholipid antibodies (APL) are detected by both ELISA and tests for lupus anticoagulants (LA). We evaluated ELISA tests for IgG, IgM, and IgA isotopes of antibodies binding cardiolipin (CL) and phosphatidylserine (PS) in samples from LA patients presenting with recurrent miscarriages. All values were expressed in multiples of the normal median (MOM). In 32% (11/34) of cases, not only were all ELISA values at or below 2.5 MOM, but the distribution of these ELISA MOM values within the normal range was similar to distribution of values from LA negative controls with the same history. Neither the use of PS as the antigen nor the addition of IgA assays improved the correlation of ELISA results with the presence of LA. ELISAs are inadequate as the sole screening test for these separate, but often associated, families of APL.

Immunological studies in recurrent spontaneous abortion: effects of immunization of women with paternal mononuclear cells on lymphocytotoxic and mixed lymphocyte reaction blocking antibodies and correlation with sharing of HLA and pregnancy outcome.

The occurrence of maternal antipaternal lymphocytotoxic antibody (LCTA), mixed lymphocyte reaction blocking factors (MLRBF) and human leukocyte antigen (HLA) antigen sharing was studied in 115 couples with unexplained repeated spontaneous abortions (RSA). Comparisons were made to the same studies done on 41 couples with explained repeated miscarriages. We found no significant difference between the patient and control group with respect to the percent of couples sharing none, one, or two or more HLA-A,-B, or -DR antigens. Examination of the occurrence of LCTA and MLRBF likewise did not reveal differences between the groups, nor did the occurrence of these antibodies on initial testing correlate with HLA disparity between couples. Women with three or more spontaneous abortions were immunized with paternal mononuclear cells (MNC) if they met at least two of the following three criteria: they shared two or more HLA antigens; their serum was negative for paternal MNC-directed LCTA; their serum did not contain maternal versus paternal MLR blocking factors. Complete HLA, LCTA and MLRBF data pre- and post-treatment are available on 60 women. Sixty-three percent of women converted to LCTA positive 6 +/- 1 weeks after immunization, and 35% of women converted from negative to positive for MLR blocking after immunization. Fifty-eight women who had all three tests done prior to immunization became pregnant after immunization. Only 50% of this selected group have experienced successful pregnancy as judged by delivery of a live-born infant. In the patients presented, successful pregnancy outcome did not correlate with HLA antigen disparity, but successful patients were more likely than aborters to have either LCTA or MLRBF prior to pregnancy (28 vs. 7%). Post-immunization conversion to LCTA positive was more prevalent in the women who aborted after immunization (74%) compared to those who had successful pregnancy (48%) while MLR blocking antibody conversion from negative to positive was the same in both groups. The data indicate that neither HLA antigen sharing nor conversion to LCTA or MLR blocking positive after paternal WBC immunization are predictors for successful pregnancy outcome. Results so far suggest that conversion to LCTA positive after immunization may have a negative influence on pregnancy outcome.

The number of cells used for immunotherapy of repeated spontaneous abortion influences pregnancy outcome.

One hundred and sixty-eight women were immunized on a single occasion with paternal mononuclear cells (MNC) for recurrent spontaneous abortion (RSA) and pregnancy outcomes were analysed with respect to the number of MNC given. The study was done in a prospective sequential fashion using all MNC recoverable from a unit of the spouse's blood and both patients and investigators were blinded as to the number of cells injected. Women receiving low and mid-range doses of MNC (58-305 x 10(6) and 308-567 x 10(6), respectively) had a significantly higher pregnancy success rate (57%) than those receiving the high (568-2677 x 10(6)) dose of MNC (41%). In 77 consecutive patients the diameter of the largest immediate skin flare reaction at the site of subcutaneous injection was recorded. No correlation was found between the skin flare response and the number of MNC injected. Our data suggest that a blinded trial of paternal MNC immunization comparing what appears to be optimum numbers of cells (100-550 million) to a low dose inoculum (e.g., 10 million), again noting the sizes of the skin flare reactions, might answer questions about efficacy and placebo effects of immunotherapy for RSA.

Diagnostic use of meternal serum alpha-fetoprotein levels.

Alpha-fetoprotein (AFP) levels in human maternal serum were elevated in 14 patients when measured by a radioimmunoassay. In 8 patients the elveated serum levels of AFP correlated with increased concentration of AFP in amiotic fluid and were diagnostic of fetal defects. The elevated AFP levels in the remaining 6 patients were shown to be the result of fetomaternal transfusion from either amniocentesis or natural causes. Serum samples drawn after amniocentesis through an anterior placenta may show false-positive elevations. The use of both maternal serum and amniotic fluid samples in pregnancies at high risk for neural tube defects can decrease the risk of diagnostic errors due to mistakes in gestational datind and may increase the diagnostic sensitivity of amniocentesis.

PIP: 14/150 patients studied over a 2-year span had elevated serum alpha fetoprotein (AFP) in the course of pregnancy; fetal abnormality or a source of fetomaternal transfusion was present in each case. The fetomaternal transfusions generally resulted from amniocentesis through an anterior placenta. In 4 cases, fetal demise with fetal maceration occurred. In 3 of these, amniotic fluid AFP concentrations were 10 times the normal for that gestational week. Sequential serum AFP rose to nearly twice the initial value in 1-3 weeks. In 3 cases, the fetuses had neural tube defects, and in each case both amniotic fluid and maternal serum AFP were elevated. In 5 cases with initially false positive serum elevations not accompanied by elevated amniotic fluid AFP, fetomaternal transfusion resulting from amniocentesis was the cause; in all, 7 cases of maternal serum elevation secondary to fetomaternal transfusion were recorded. Analyzing both maternal serum and amniotic fluid samples in pregnancies at high risk for neural tube defects can decrease diagnostic errors caused by mistakes in gestational dating and may increase the diagnostic sensitivity of amniocentesis.

Daily blood hormone levels related to the luteinizing hormone surge in anovulatory cycles.

We have evaluated daily blood levels of gonadal steroids and trophic hormones in the cycles of four ovulatory and six anovulatory patients with a luteinizing hormone (LH) surge. The cycles of anovulatory nonhirsute patients were characterized by a premature and blunted LH surge and by low levels of follicle-stimulating hormone (FSH) throughout the study period in the face of normal tonic and peak levels of estrone and estradiol (E2). These observations, together with decreased levels of prolactin, suggest a hypothalamic pituitary abnormality as the cause of anovulation in these patients. The cycles of anovulatory hirsute patients were marked by a decrease in E2 production and a blunted and delayed E2 peak. Androgen levels were elevated throughout the cycle and may have a direct inhibitory effect on ovarian folliculogenesis. The LH/FSH ratio in the follicular phase was high in both groups of anovulatory patients when compared with ovulatory controls; however, the shifts in gonadotropin levels producing the increase in this ratio were different for these two groups.

Chromosome errors as a cause of spontaneous abortion: the relative importance of maternal age and obstetric history.

OBJECTIVE: To evaluate the likelihood of obtaining a chromosome diagnosis in cases of spontaneous abortion (SAB) and of the relative importance of maternal age versus obstetric history in predicting the fetal karyotype. DESIGN: Obstetric history was obtained from all 100 cases of miscarriage in 1 year when products of conception were sent for chromosome studies. Multiple logistic regression analysis was used to calculate odds ratio and statistical significance for correlations between historical factors and the probability of any chromosomal abnormality or trisomy. RESULTS: A chromosome diagnosis was made in 84% of cases. Maternal age was a more important predictor of chromosome abnormality, specifically trisomy, than history of previous livebirths or miscarriages. CONCLUSION: Results from chromosome studies using chorionic villi from SABs are diagnostically useful, even when the patient has a history of repeated miscarriages.

Management of immune thrombocytopenic purpura associated with the antiphospholipid antibody syndrome.

Our two patients had "primary" antiphospholipid antibody syndrome without underlying systemic lupus erythematosus or other systemic autoimmune process, as well as symptomatic immune thrombocytopenic purpura (ITP). The thrombocytopenia did not respond to prolonged courses of corticosteroids and/or immune globulin infusions, but was controlled following splenectomy. The presence of serum antibodies to platelet surface glycoproteins, typical of ITP, could be helpful in the confirmation of both of these disorders in the same patient, rather than secondary thrombocytopenia. Management of such cases is confounded by an increased risk for both bleeding and thrombosis, including fetal death. To reduce the risk of fetal loss and thrombosis, both patients were advised to take aspirin 80 mg daily. The frequency and clinical significance of this association would suggest that patients with ITP should be tested for antiphospholipid antibodies, particularly before pregnancy or surgical procedures. Patients with coexistent antiphospholipid antibody syndrome would be at increased risk for thrombosis in the post-operative period following splenectomy and should be given prophylactic anticoagulation.

Evaluation of the prethrombotic state in pregnancy and in women using oral contraceptives.

The purpose of this study was to determine the effects of pregnancy and oral contraceptive use on in vivo coagulation by measurement of plasma levels of prothrombin fragment 1 + 2 and thrombin antithrombin III complex. Fifty-four women with uncomplicated singleton gestations, 34 women using oral contraceptives and 45 non-pregnant controls were the subjects of this study. Levels of prothrombin fragment 1 + 2 and thrombin-antithrombin III complex were measured using enzyme linked immunoassays. In uncomplicated pregnancies, levels of prothrombin fragment 1 + 2 and thrombin antithrombin III complex increased significantly with advancing gestational age. Women using oral contraceptives had significantly higher levels of prothrombin fragment 1 + 2 and thrombin antithrombin III complex compared to non-pregnant controls. The significant increase in levels of prothrombin fragment 1 + 2 and thrombin-antithrombin III complex throughout gestation and in women using oral contraceptives provided evidence of thrombin activation during these clinical conditions.

Predictors for live birth after unexplained spontaneous abortions: correlations between immunologic test results, obstetric histories, and outcome of next pregnancy without treatment.

Our objective was to determine whether results from tests for maternal serum antinuclear antibodies, cytotoxic antibodies to paternal lymphocytes, parental histocompatibility types, and blocking factors for maternal-paternal mixed lymphocyte reactions were predictive of pregnancy outcome without immunologic treatment. Pregnancy outcome data from 95 women with a history of unexplained recurrent spontaneous abortions who underwent immunologic tests at Jefferson Medical College were evaluated with multiple logistic regression analyses. The number of prior spontaneous abortions, history of another relevant diagnosis, parental sharing of one histocompatibility antigen, and maternal age were related to the outcome of the next pregnancy in women given no immunologic treatment (p = 0.05). No significant correlation was found between results from the immunologic tests or other history characteristics evaluated and outcome of the next pregnancy. The immunologic tests evaluated were not clinically useful predictors of pregnancy outcome.

Fertility among women with recurrent spontaneous abortions--the effect of paternal cell immunization treatment.

PROBLEM: The risk of women whose chief complaint is recurrent spontaneous abortions (RSA) for secondary infertility (infecundability) has not been evaluated prospectively. The effect of paternal mononuclear cell immunization on conception rates is unknown. METHOD: Two hundred women whose chief complaint was RSA were randomly assigned to be immunized with paternal mononuclear cells either before or after (up to 6 postmenstrual weeks) conception. Fertility rates (both conception and live birth) were evaluated for the group immunized before conception and compared to those for the control group, who were not immunized until after conception, using life table and multiple logistic regression analyses. RESULTS: Prospectively ascertained, age-related conception rates for nonimmunized RSA controls appeared to be similar to those for general populations. Immunization before pregnancy had no significant effect (power +/- 14%) on rates of conception (66% before, 77% after) or time to conceive (median weeks before 19.5, after 27.0). Live birth rates (before 59%, after 63%) were also similar for both groups (P = 0.7). CONCLUSION: Women whose only prior complaint was RSA were not at high risk for secondary infecundability, and immunization did not alter either conception rates or time to conceive. Postponement of immunization until after conception did not affect live birth rates for women selected for study because they did not have a history of prior infecundability or early repeated miscarriages.

Placental pathology and antiphospholipid antibodies: a descriptive study.

We described placental pathology in antiphospholipid antibody (APL) syndrome, APL and no history of recurrent pregnancy loss, and in treated and untreated pregnancies of APL syndrome. Thirty-nine pregnancies of 28 patients were studied: 23 placentas delivered from 23 women with APL (13 with APL syndrome and 10 with serological APL); 8 untreated miscarriages before APL diagnosis from 6 of the 13 patients with APL syndrome and 1 of 10 with serological APL; and 8 miscarriages by 5 additional women before APL syndrome diagnosis. Histopathology was reviewed by a pathologist blinded except to gestational age. Contingency tables and analysis of variance (ANOVA) considered p < 0.05 significant. Comparing the placentas delivered at > 18 weeks' gestation, excessive perivillous coagulation, avascular terminal villi, and chronic villitis/uteroplacental vasculitis tended to be more common in treated APL syndrome than serological APL cases (p = 0.07). Of the 16 miscarriages before diagnosis of APL, 11 were lost at < 18 weeks' gestation. None had pathology typical of APL, but 4 of 11 (36%) had chronic intervillositis. Five of 16 miscarriages before the diagnosis of APL were miscarried between 18-22 weeks. Three of 5 (60%) miscarried after 18 weeks had multifocal uteroplacental thromboses, compared to 6 of 13 (46%) treated pregnancies with APL syndrome and 0 of 10 cases with serological APL.

Pregnancy after corticosteroid administration in premature ovarian failure (polyglandular endocrinopathy syndrome).

A patient with polyglandular failure syndrome first had documented ovarian failure at age 28 years. Fifteen years later after treatment for Addisonian crisis, she resumed menses, conceived, and was delivered of a normal infant. Patients with this syndrome should be identified because they are at risk for other endocrinopathies and because they may have a treatable form of ovarian failure.

Successful treatment in two women with antiphospholipid antibodies and refractory pregnancy losses with intravenous immunoglobulin infusions.

In two women with antiphospholipid antibodies and recurrent fetal losses refractory to usual treatments, therapy consisting of aspirin, heparin, and intravenous gamma-globulin infusions was successful. Production of antiphospholipid antibodies was not suppressed. The transient decrease in anticoagulant activity noted in one case was not reproduced in vitro and was probably not physiologically important.

First-trimester maternal serum alpha-fetoprotein and chorionic gonadotropin in aneuploid pregnancies.

First-trimester maternal serum alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) levels were measured in samples from 29 women with cytogenetically abnormal pregnancies and 145 women with cytogenetically normal pregnancies matched for gestational age, race, and sample storage time. All patients had a risk of fetal aneuploidy greater than or equal to that of a mother 35 years of age. AFP was significantly lower in samples from pregnancies affected with trisomy 21 (0.67 MoM; p less than 0.05), while HCG values were no different from those of matched controls. Trisomies 13 and 18 could not be distinguished from matched controls by AFP. However, levels of HCG were significantly lower in such pregnancy samples, with median values of 0.65 MoM in trisomy 13 and 0.32 MoM in trisomy 18 (p less than 0.05). Variations in AFP and HCG levels suggest that expressed differences between autosomal aneuploidies include differences in fetal and placental protein production in the first trimester.

Anticardiolipin antibodies in patients with rheumatic diseases.

Recent attention has focused on the presence of anticardiolipin (ACL) antibodies and their possible role in recurrent thrombosis and abortions in patients with systemic lupus erythematosus. We analyzed ACL antibodies in 243 consecutive patients to determine their frequency in patients with different rheumatic disorders. A significantly elevated frequency was found in patients with systemic lupus erythematosus (38%), rheumatoid arthritis (33%), and psoriatic arthritis (28%). No correlation could be found between ACL antibody levels and recurrent thrombosis. In patients with rheumatoid arthritis there was a significant correlation between ACL antibodies and a history of repeated abortions. No significant association was found between ACL antibodies and other autoantibodies except in patients with rheumatoid arthritis; ACL antibody-positive rheumatoid arthritis patients were much more likely to be antinuclear antibody-positive (P less than 0.0002).