Cesarean scar pregnancy is a precursor of morbidly adherent placenta.

OBJECTIVE: To provide further sonographic, clinical and histological evidence that Cesarean scar pregnancy (CSP) is a precursor to and an early form of second- and third-trimester morbidly adherent placenta (MAP). METHODS: This is a report of 10 cases of CSP identified early, in which the patients decided to continue the pregnancy, following counseling that emphasized the possibility of both significant pregnancy complications and a need for hysterectomy. Pregnancies were followed at 2-4-week intervals with ultrasound scans and customary monitoring. The aim was for patients to reach near term or term and then undergo elective Cesarean delivery and, if necessary, hysterectomy. Charts, ultrasound images, operative reports and histopathological examinations of the placentae were reviewed. RESULTS: The ultrasound diagnosis of CSP was made before 10 weeks. By the second trimester, all patients exhibited sonographic signs of MAP. Nine of the 10 patients delivered liveborn neonates between 32 and 37 weeks. In the tenth pregnancy, progressive shortening of the cervix and intractable vaginal bleeding prompted termination, with hysterectomy, at 20 weeks. Two other patients in the cohort had antepartum complications (bleeding at 33 weeks in one case and contractions at 32 weeks in the other). All patients underwent hysterectomy at the time of Cesarean delivery, with total blood loss ranging from 300 to 6000 mL. Placenta percreta was the histopathological diagnosis in all 10 cases. CONCLUSION: The cases in this series validate the hypothesis that CSP is a precursor of MAP, both sharing the same histopathology. Our findings provide evidence that can be used to counsel patients with CSP, to enable them to make an informed choice between first-trimester termination and continuation of the pregnancy, with its risk of premature delivery and loss of uterus and fertility.

The Ariel Project: A prospective cohort study of maternal-child transmission of human immunodeficiency virus type 1 in the era of maternal antiretroviral therapy.

In a prospective cohort study, clinical and biologic factors that contribute to maternal-child transmission of human immunodeficiency virus type 1 (HIV-1) were studied. HIV-infected pregnant women and their infants were evaluated prospectively according to a standardized protocol. Of 204 evaluable women, 81% received zidovudine during their pregnancy. The infection rate among the 209 evaluable infants was 9.1%. By univariate analysis, histologic chorioamnionitis, prolonged rupture of membranes, and a history of genital warts were significantly associated with transmission. Additional factors associated with transmission that approached significance included a higher maternal virus load at delivery and the presence of cocaine in the urine. In a logistic regression model, histologic chorioamnionitis was the only independent predictor of transmission. Despite a significantly higher transmission rate at one site, no unique viral genotype was found at any site. Thus, chorioamnionitis was found to be the major risk factor for transmission among women receiving zidovudine.

Syncytium-inhibiting and neutralizing activity in maternal sera fail to prevent vertical transmission of human immunodeficiency virus type 1.

OBJECTIVES: To measure the prevalence and titers of syncytium-inhibiting (SI) and neutralizing (Nt) antibodies to HIV-1 in mothers' blood close to the time of delivery and to correlate such findings with the infection status of their offspring. METHODS: We analyzed serum specimens from a convenience sample of 22 HIV-infected mothers. The HIV-1 infection status of their children was determined. Forty-five percent of the women transmitted and 55% did not transmit infection to their offspring. Cord blood samples from offspring of the mothers were also studied. We measured maternal SI antibody titers against cells infected with HIV-1/SB, a strain isolated from a transmitting mother in New Haven, as well as cells infected with the more prevalent MN strain of HIV-1. We compared SI antibody titers to the SB strain in 11 matched maternal and cord blood samples. Nt antibody titers to HIV-1/SB were also measured in 20 maternal sera. RESULTS: Using the SB and MN strains of HIV-1, we found no difference in the prevalence or titer of SI antibody in the sera of transmitting and nontransmitting mothers. Only 35% of samples were concordant for presence or absence of SI antibody to the two strains. Furthermore the presence or absence of SI antibody in cord blood did not correlate with virus transmission. Both the frequency and titer of Nt antibody to HIV-1/SB were higher in the sera of mothers who transmitted infection when compared to those who did not. Only one-half of maternal blood samples were concordant for either the presence or absence of SI and Nt antibodies. CONCLUSIONS: We could not demonstrate a correlation between the presence of two types of functional antibodies (i.e. SI and Nt) to HIV-1 in the sera of pregnant women and vertical transmission. Efforts to induce or to increase such antibodies in infected mothers by immunization with vaccines or hyperimmune globulins may not alter the risk of vertical transmission.

Effect of combination chemotherapy with cisplatin and cyclophosphamide on human immunodeficiency virus type-1 surrogate markers in a patient with advanced epithelial ovarian cancer.

This is the first report to evaluate the effects of combination chemotherapy on HIV-1 surrogate markers in an HIV-1-infected patient with an advanced epithelial ovarian cancer. Cisplatin combined with cyclophosphamide was well-tolerated, without significant changes in the HIV-1 p24 antigen, neopterin, beta 2-microglobulin, and CD4 values. The patient demonstrated a chemical and clinical response to therapy, without evidence of opportunistic infection or severe neutropenia. During the 6-month period of observation, treatment with cisplatin and cyclophosphamide did not significantly increase the risk of HIV-1 disease progression.

Association between anti-human immunodeficiency virus type 1 (HIV-1) antibody-dependent cellular cytotoxicity antibody titers at birth and vertical transmission of HIV-1.

Because vertical transmission of human immunodeficiency virus type 1 (HIV-1) from mother to infant occurs in only 15%-35% of possible opportunities, natural immune defenses of the mother, fetus, or neonate may be protective against infection. The relation between antibody-dependent cellular cytotoxicity (ADCC) antibodies and HIV-1 infection was explored in 78 neonates born to HIV-infected women. More than 90% of sera had measurable ADCC titers against HIV-1IIIB. Infant titers were closely correlated with maternal titers but were independent of total IgG and total antibody reactive to the same strain in whole virus ELISA. At birth, mean ADCC antibody levels of infants or their mothers were the same for infants who were infected and those who ultimately seroreverted and remained healthy. ADCC antibody titers against HIV-1SF2 were weakly correlated with anti-HIV-1IIIB titers and did not predict protection from HIV-1 infection. High levels of anti-HIV-1 ADCC antibody at birth are not protective against vertical transmission of HIV-1.

Is the risk of perinatal transmission of human immunodeficiency virus increased by the intrapartum use of spiral electrodes or fetal scalp pH sampling?

OBJECTIVE: Our aim was to determine whether the intrapartum use of fetal scalp electrodes or fetal scalp pH sampling increases the rate of perinatal transmission of human immunodeficiency virus. STUDY DESIGN: The rate of perinatal transmission of human immunodeficiency virus in 31 monitored pregnancies was determined, and those pregnancies were compared with a control group of 117 pregnancies. RESULTS: The monitored group was comparable to the control group with respect to maternal age, race, human immunodeficiency virus risk behavior, CD4+ cell count, p24 antigen status, and stage of human immunodeficiency virus disease. The mean gestational age at delivery and the mean birth weight were similar in the monitored group and the control group. The perinatal transmission rate for the monitored group (29.0%) was not statistically different from that of the control group (25.6%). CONCLUSIONS: If confirmed by larger studies, our findings suggest that the intrapartum use of fetal scalp electrodes or fetal scalp pH sampling does not appear to increase the perinatal transmission of human immunodeficiency virus.

Fetal blood sampling in human immunodeficiency virus--seropositive women before elective midtrimester termination of pregnancy.

OBJECTIVES: To explore the diagnostic potential of fetal blood sampling in the prenatal diagnosis of intrauterine human immunodeficiency virus infection and to investigate the transplacental transfer of human immunodeficiency virus antibody and p24 antigen in the second trimester of pregnancy, we studied serum and amniotic fluid obtained from 13 seropositive women and their fetuses before elective termination of pregnancy. STUDY DESIGN: Enzyme-linked immunosorbent assay, Western blot antibody analyses, and p24 antigen assays were performed on all samples. RESULTS: Human immunodeficiency virus antibody was detected by enzyme-linked immunosorbent assay and Western blot analysis in aliquots of maternal serum, amniotic fluid, and fetal serum from all 13 pregnancies. Each mother-fetus pair had identical antibody banding patterns. In contrast, p24 antigen was found in the maternal serum and amniotic fluid samples from five of 13 women (38%) and in serum from only three of 13 fetuses (23%). CONCLUSIONS: We conclude that fetal blood sampling, if combined with sophisticated serologic analysis, may have the potential to provide the diagnosis of congenital infection with human immunodeficiency virus. The correlation of immunologic, virologic, and molecular biologic methods with subsequent infant outcome and risk of iatrogenic infection of the fetus remains to be determined.

Prevalence and prognostic significance of anticardiolipin antibodies in pregnancies complicated by human immunodeficiency virus-1 infection.

OBJECTIVES: Anticardiolipin antibodies are estimated to occur in 2.2% of all pregnancies and are associated with adverse outcomes including thrombotic events, fetal wastage, intrauterine growth retardation, and preterm delivery. We studied 32 human immunodeficiency virus-seropositive gravidas (1) to determine the prevalence of anticardiolipin antibodies in pregnant women infected with human immunodeficiency virus-1 and (2) to investigate the association between the presence of anticardiolipin antibodies and pregnancy outcome, disease status, and perinatal transmission of human immunodeficiency virus-1. STUDY DESIGN: Serum samples obtained at the first prenatal visit were analyzed for anticardiolipin immunoglobulin M and immunoglobulin G by enzyme-linked immunosorbent assay. Relevant antepartum, intrapartum, and postpartum data, including maternal CD4+ lymphocyte subsets, human immunodeficiency virus p24 antigen determinations, Venereal Disease Research Laboratory test, hematocrit, platelet counts, and placental pathologic tissue of the anticardiolipin antibody-positive and anticardiolipin antibody-negative groups were compared. RESULTS: Test results for 17 (53%) of patients were positive for anticardiolipin antibody: 4 had only immunoglobulin M, 1 had only immunoglobulin G, and the remaining 12 had both antibodies. The patients in the anticardiolipin antibody-positive group were delivered of infants with a mean gestational age of 39 weeks and mean birth weight of 2983 gm. In the anticardiolipin antibody-negative group 15 deliveries had a mean gestational age of 36.3 weeks and a mean birth weight of 2330 gm. CONCLUSIONS: We conclude that there is a high prevalence of anticardiolipin antibodies in patients who have human immunodeficiency virus, which is not associated with adverse maternal or neonatal outcome, maternal human immunodeficiency virus status, or perinatal transmission of human immunodeficiency virus-1.

Limb-body wall complex associated with cocaine abuse: further evidence of cocaine's teratogenicity.

Limb-body wall complex is a complicated fetal malformation with the essential features of body wall disruption and limb abnormalities. Data from studies in the rat model suggest that vascular disruption is an etiology for limb-body wall complex. Because of its vasospastic properties, cocaine can act as a teratogen by impairing uteroplacental fetal blood flow during critical periods of development. We describe the prenatal detection of two fetuses with limb-body wall complex, whose mothers smoked large amounts of cocaine during the first trimester of pregnancy. Ultrasonographic evaluation of the fetus should be offered routinely in pregnancies complicated by maternal cocaine abuse.

Approximate entropy: a regularity measure for fetal heart rate analysis.

Approximate entropy (ApEn), a recently developed mathematical formula quantifying regularity, was applied to fetal heart rate (FHR) data. Three groups were analyzed: 1) 19 women had normal labors (uncomplicated course of labor, vaginal delivery, no unusual FHR tracings, and 1- and 5-minute Apgar scores of at least 7 and 9, respectively; 2) 15 women had presumed fetal distress (severe cord or late decelerations, bradycardia, or tachycardia; delivery by cesarean with both arterial and venous cord pH above 7.20); and 3) 20 women had acidotic fetuses (both venous and arterial cord pH less than 7.20). Hourly mean (+/- SD) ApEn values for the three groups were: acidotic fetuses, 0.924 +/- 0.235, 102 hours; normal fetuses, 1.051 +/- 0.145, 97 hours; and nonacidotic "distressed" fetuses, 1.043 +/- 0.147, 74 hours. The ApEn values for nonacidotic, presumed distressed fetuses were not significantly different from those of normal fetuses (P greater than .75). Acidotic fetuses had many more instances of ApEn hourly values less than 0.8 (28%, 29 of 102) than did the normal and the nonacidotic, presumed distressed fetuses combined (5%, nine of 171). The probability that ApEn was less than 0.8 was larger for acidotic fetuses than for the other groups (P less than .00003), supporting the hypothesis that extremely regular FHR patterns imply a greater likelihood of acidosis. Significant hourly deviations in ApEn generally corresponded to drug administration or to physiologic changes such as cord compression and its relief. Thus ApEn, a major departure from variability statistics, appears to be able to detect subtle and possibly important differences in heart rate that are not visually apparent.

Alternate methods of first-trimester diagnosis.

Fetal medicine is a new discipline that emerged out of the expansion of modern technology. Evaluation of the fetus heretofore was not possible except by indirect methods. Pregnancy management focused primarily on the care of the mother with the expectation that the fetus would be an indirect beneficiary. Our present-day approach to pregnancy and prenatal evaluation has been altered by the introduction of new techniques such as ultrasound, amniocentesis, and CVS, which have made the fetus and its intrauterine environment accessible. Improvements in ultrasonographic equipment have allowed for better visualization of the fetus, earlier detection of structural anomalies, and facilitation of the performance of invasive procedures. The recent introduction of CVS represents a major step toward achieving the goal of early diagnosis. Prevailing experience has demonstrated that it is a relatively safe and reliable procedure with a low complication rate. Early amniocentesis may be considered as an alternative to CVS when the latter is not advisable, although future studies are needed to accurately estimate the procedure-related risks (Table 5). Transcervical endoscopy allows a more detailed appreciation of fetal anatomy, although its role in clinical practice remains to be defined. Biochemical markers such as alpha fetoprotein, unconjugated estriol, and hCG, alone and in combination, have been studied regarding their potential to predict chromosomal abnormalities. Today there is a changing trend in prenatal diagnosis with women requesting more information about their unborn child and expecting such information earlier in gestation. The goal of prenatal diagnosis has been directed toward earlier detection to reduce the anxiety of waiting and permit the safer option of first-trimester termination of pregnancy.

Transcervical endoscopic verification of congenital anomalies in the second trimester of pregnancy.

Transcervical endoscopy was used to confirm prenatally diagnosed anomalies before elective termination of pregnancy. A complete anatomic survey was accomplished in 10 (70%) of 14 cases studied. Information was added to the ultrasonographic diagnosis in two cases, which changed the diagnosis in one fetus.

AIDS. Natural history and prognosis.

Infection with HIV results in a chronic, persistent infection that usually progresses slowly from an asymptomatic state to full-blown AIDS. AIDS remains a lethal disease with no effective cure. A great deal of information has been learned in the past decade, yet many questions remain unresolved. Much more research is needed into the conditions surrounding the perinatal transmission of HIV. Many women who give birth to a child with AIDS are themselves asymptomatic for HIV infection during pregnancy and at delivery; thus, routine voluntary prenatal HIV screening programs must be instituted in areas of high seroprevalence. Such screening programs must provide pretest and post-test counseling with consent and confidentiality. Seroprevalence studies conducted during the perinatal period or at birth using newborn blood samples will provide important epidemiologic data for further research investigations as well as continued estimates of the prevalence of HIV infection. Currently, there is no formal reporting system for HIV infection, only for the clinical expression of AIDS. There may be a need to develop a centralized reporting unit for HIV infection. As the epidemic continues and the true prevalence rates are determined, additional resources for public health care, housing, insurance, and foster care for children will be needed. The number of women who are infected is increasing at an alarming rate. Every opportunity to increase public awareness about the AIDS epidemic and modes of transmission must be exploited if we are to impact on the spread of HIV infection. Prospective studies of pregnant HIV-positive women and pediatric follow-up can provide a wealth of data about AIDS and disease progression in both the mother and the infant. Even if some children do not develop AIDS, the possibility of permanent effects of in utero exposure to the virus still exists. At what exact point in gestation does infection occur? Can infection be prevented or delayed with current chemotherapeutic protocols? Even if a cure or vaccine is developed in the near future, the impact of this deadly virus will have repercussions for many years to come.

Pelvic masses in pregnancy: MR imaging.

The value of magnetic resonance (MR) imaging was assessed for 17 pregnant patients with sonograms suggestive of a pelvic mass. The MR imaging signal features improved lesion characterization in 47% (eight of 17) of cases, including two of four mature cystic teratomas of the ovary, three uterine fibroids, one solid ovarian tumor, one endometrioma, and a distended urinary bladder that had been mistaken for an ovarian cystic mass. Both MR imaging and sonography were accurate for the characterization of three ovarian cystadenomas and two simple ovarian cysts. On both MR images and sonograms, two simple ovarian cysts were incorrectly diagnosed as complex cystic masses and one teratoma was incorrectly diagnosed as a simple cyst. The origin of the pelvic mass (13 in the ovary, three in the uterus, and one distended urinary bladder) was accurately determined on 100% (17 of 17) of the MR images versus 71% (12 of 17) of the sonograms. In three cases, the results of MR imaging led to cancellation of surgery, which would have proceeded on the basis of the sonographic results alone. MR imaging is a valuable complement to sonography for preoperative evaluation of pelvic masses in pregnant patients.

Immunoproteins in the endometrium: clinical correlates of the presence of complement fractions C3 and C4.

The presence of complement fractions C3 and C4 in endometrial tissue was studied in a consecutive series of patients undergoing diagnostic laparoscopy, to determine their specific association with endometriosis. The incidence of complement in eutopic endometrium of patients grouped according to four diagnoses was: endometriosis, 66% positive (23 of 35); active pelvic inflammatory disease, 85% positive (11 of 13); combined endometriosis with pelvic inflammatory disease, 25% positive (one of four); laparoscopically normal pelvis, 67% positive (10 of 15). These differences were not statistically significant. Complement was equally likely to be found in proliferative, secretory, menstrual, or inflammatory endometrium. Endometrial complement was found less frequently in patients with severe endometriosis as compared with those with the mild form. Among patients with endometriosis and infertility, complement was much more likely to be found in patients with primary infertility than in those with secondary infertility (p less than 0.007). In short-term follow-up of these patients, the absence of complement in the eutopic endometrium appeared to be a good predictor of subsequent pregnancies.

CT of the normal pituitary gland.

Retrospective evaluation of the pituitary gland on coronal post-contrast CT scan in 251 patients demonstrated that the pituitary gland is somewhat larger in females than in males. In males, glands measuring greater than 7.7 mm should be considered abnormal; in females, a statistically significant decline of gland height occurs with increasing age, the upper limit of normal for female gland height decreasing from 9.2 cm for a 20-year-old to 6.0 cm for a 90-year-old. Focal low densities greater than 3 mm are rare in males and probably should be considered abnormal.

CT appearance of the adolescent and preadolescent pituitary gland.

Coronal computed tomographic scans of the pituitary gland in 27 normal children, adolescents, and young adults (ages, 8-21 years) and in a comparison group of adults (ages, 24-91 years) were evaluated retrospectively to test the applicability of published criteria for size and configuration of normal adult pituitary glands to younger patients. Statistically significant differences were found between the two groups, indicating that the pituitary gland in adolescents, particularly girls, is larger than in younger or older patients. The authors suggest that pubertal pituitary hyperplasia accounts for these findings. They conclude that standards for normal pituitary glands are probably inappropriate for adolescents.

Rapid, sequential changes in surface morphology of PC12 pheochromocytoma cells in response to nerve growth factor.

The effect of nerve growth factor (NGF), a substance that promotes the differentiation and maintenance of certain neurons, was studied via scanning electron microscopy utilizing the PC12 clonal NGF-responsive pheochromocytoma cell line. After 2-4 d of exposure to NGF, these cells acquire many of the properties of normal sympathic neurons. However, by phase microscopy, no changes are discernible within the first 12-18 h. Since the primary NGF receptor appears to be a membrane receptor, it seemed likely that some of the initial responses to the factor may be surface related. PC12 cells maintained without NGF are round to ovoid and have numerous microvilli and small blebs. After the addition of NGF, there is a rapidly initiated sequential change in the cell surface. Ruffles appear over the dorsal surface of the cells with 1 min, become prominent by 3 min, and almost disappear by 7 min. Microvilli, conversely, disappear as the dorsal ruffles become prominent. Ruffles are seen at the the periphery of cell at 3 min, are prominent on most of the cells by 7 min and are gone by 15 min. The surface remains smooth from 15 min until 45 min when large blebs appear. The large blebs are present on most cells at 2 h and are gone by 4 h. The surface remains relatively smooth until 6-7 h of NGF treatment, when microvilli reappear as small knobs. These microvilli increase in both number and length to cover the cell surface by 10 h. These changes were not observed with other basic proteins, with alpha-bungarotoxin (which binds specifically to PC12 membranes), and were not affected by an RNA synthesis inhibitor that blocks initiation of neurite outgrowth. Changes in the cell surface architecture appear to be among the earlist NGF responses yet detected and may represent or reflect primary events in the mechanism of the factor's action.