Michael D. Benson

Immunologic studies in presumed amniotic fluid embolism

Objective To evaluate the potential role of immunologic mechanisms that involve mast cell degranulation (anaphylaxis) or complement activation in the mechanism of amniotic fluid embolism. Methods This study was a case series of nine women with presumed amniotic fluid embolism and a control group of 22 women who had normal labor. Women were from community and tertiary referral hospitals in Japan and the United States. Main outcome measures were maternal peripartum complement levels (C3 and C4), serum levels of tryptase, urinary histamine concentrations, and serum levels of a fetal antigen (sialyl Tn). Results Serum tryptase and urinary histamine measurements were negative in women with amniotic fluid embolism; seven of nine had elevated levels of fetal antigen. All eight who had serum available for testing had abnormally low levels of complement. Mean C3 level of 44.0 mg/dL and C4 level of 10.7 mg/dL were significantly lower than corresponding postpartum control values of 117.3 mg/dL and 29.4 mg/dL (P = .018 for C3, P = .012 for C4). Postpartum C3 and C4 levels decreased by 8% and 5%, respectively, compared with intrapartum values (P = .003 for C3, P = .021 for C4) but were still within normal range. Conclusion Serologic findings suggest a role for complement activation in the mechanism of amniotic fluid embolism. Laboratory data from this series did not implicate mast cell degranulation (anaphylaxis) in the pathophysiology of the disease.

Sexual behavior in junior high school students

Objective To evaluate the association between 14 demographic variables and the loss of virginity in a specific sample of junior high school students in Chicago. Methods Nine hundred seventy-six students in nine Chicago junior high schools, sixth through eighth grades, were given an anonymous behaviour survey (the noncognitive assessment survey). Two separate logistic regression equations were used to dtermine the relative relationships of the demographic variables to self-reported virginity loss. Results Five variables were significantly associated with virginity loss in both regression equations. In rank order, they were gender, ethnic group, pubertal status, suicidal ideation, and sibling number (adjusted odds ratio 13.3, 4.57, 3.38, 1.93, and 1.24, respectively.) Nine variables did not have a consistent relation with early sexual activity: church attendance, religious affiliation, grade average, housing status, marital status of natural parents, elf-esteem, ses education knowledge, school attendance, and chronologic age. Conclusions These results call into question two widely held assumptions that form the foundation of many teen pregnancy prevention efforts. First, although many believe that sex education couses can affect behavior, we found no link, either positive or negative, between knowledge of reproductive biology and age of first intercourse. Second, self-esteem level was not associated with age of first intercourse. The variables that did seem related to early sexual activity do not lend themselves to easy manipulation. Our findings suggest that current school-based efforts to alter teen pregnancy rates and sexual behavior are unlikely to succeed.

Complement, fetal antigen, and shaking rigors in parturients

Objectives. To assess the relationship, if any, between complement, fetal antigen, and shaking rigors during labor and delivery. Methods. We recruited 13 volunteers for serial blood sampling during labor and childbirth. Results. Complement levels had a small but significant drop (11–15%) immediately following childbirth but had no association with fetal antigen levels or shaking rigors. Fetal antigen levels failed to show any consistent relationship with shaking rigors or the labor and delivery process. Conclusion. Shaking rigors do not appear to be associated with changes in either complement or fetal antigen levels. Complement levels remain stable during labor but drop immediately following birth.

Amniotic fluid embolism: the known and not known:

Amniotic fluid embolism was first recognized in 1926, in a Brazilian journal case report, on the basis of large amounts of fetal material in the maternal pulmonary vasculature at autopsy. The first English language description appeared in 1941 and consisted of eight parturients dying suddenly in which, once again, fetal material was seen in the pulmonary vasculature. A control group of 34 pregnant women dying of other recognized causes did not have fetal material in their lungs. The incidence of recognized, serious illness is on the order of two to eight per 100,000, with a mortality rate ranging from 13% to 35%. The diagnosis rests largely on one or more of four clinical signs: circulatory collapse, respiratory distress, coagulopathy, and seizures/ coma. The only confirmatory laboratory test remains autopsy findings although serum tests for fetal antigen, insulin-like growth factor binding protein-1, and complement are currently being investigated. One of the paradoxes of diagnosis is that fetal material in the pulmonary circulation at autopsy is specific for amniotic fluid embolism, while the same finding in the living is not. The mechanism of disease remains uncertain although the best available evidence suggests that complement activation might have a role. In contrast, mast cell degranulation probably is not a mechanism, so amniotic fluid embolism is not an anaphylaxis or anaphylactoid reaction as has been occasionally suggested. Perhaps the greatest unknown is not why 1 in 50,000 pregnant women develop what appears to be an immune response to their fetus, but rather why the other 49,999 do not?

A mild case of amniotic fluid embolism

In work previously published, we demonstrated complement activation in eight consecutive patients with amniotic fluid embolism (AFE) [1]. During this study, a patient was enrolled in our amniotic fluid embolism protocol because she had transient symptoms that suggested to her healthcare providers that she was about to become seriously ill. She subsequently had an uneventful labor and delivered a healthy child. She clearly did not have AFE as it is commonly understood, and was not included in our published series. However, her laboratory data showed some remarkable similarities to our mortally sick patients prompting us to consider that a subclinical diagnostic category of AFE may exist. A 35-year-old G4P3003 woman with three prior vaginal deliveries was admitted to the hospital at 39 weeks in early labor. Within a few hours her contractions subsided and she fell asleep. At approximately 1:30 a.m. she awoke and voided. As she walked back to her bed, she became dizzy and faint and developed chest pain radiating to the back at the level of the diaphragm. Though the nurse was unable to detect a change in vital signs, she became concerned that the patient might be having an embolic event. The attending physician was summoned to the hospital on an emergency basis. Within ten minutes the chest pressure largely disappeared and the patient’s dizzy episode had passed. Within a half-hour of the initial sensation of illness, the patient developed shaking rigors that lasted about 90 minutes. Her contraction intensity greatly increased and she was dilated to 3 cm; she received an epidural anesthetic. She subsequently delivered a healthy female infant after a 3-hour active phase of labor and a 10-minute second stage. During the episode, pulse oximetry revealed an oxygen saturation of over 95%. Subsequently, a cardiogram, gall-bladder ultrasound, and duplex imagining of the lower extremities were all normal. With the onset of her symptoms suggesting for a moment that she might become seriously ill, the patient provided written, informed consent to be treated according to our amniotic fluid embolism protocol that had been previously approved by the institution’s Institutional Review Board. This protocol permitted blood sampling for complement and tryptase during labor and post-partum as well as the use of any blood obtained on admission that was to be discarded. The patient’s serum, which had been obtained prior to the onset of symptoms, was refrigerated and after five days, frozen. On the patient’s three subsequent blood draws, the blood was placed on ice, spun down in a refrigerated centrifuge and promptly frozen. Additional serum was collected nine days after the event to be sure that her laboratory abnormalities had returned to normal. The results of the protocol laboratory analysis are provided in Table I. Her platelet count, which was initially normal, dropped to 114 000/mL one hour after the onset of symptoms. This corresponded with the development of a positive D-dimer that became more abnormal at 11 hours after the initial event. Her fetal antigen (STN) levels, as we have previously described for the diagnosis of AFE, were remarkably stable at 7 mIU/mL, doubled in the hour after symptoms began, and then returned to baseline [2]. From a normal starting point, the patient’s C3 dropped to the lower limit of normal and her C4 dropped below normal in the first hour. By 11 hours, complement levels began to rise toward baseline levels. If taken out of a research context, neither this patient’s symptomatology nor her clinical outcome would be noteworthy. That said, her symptoms and The Journal of Maternal-Fetal and Neonatal Medicine, March 2007; 20(3): 261–262

Intrapartum Intrauterine Fetal Demise with Normal Umbilical Cord Blood Gas Values at Birth

A case is presented in which a fetus was delivered by cesarean section for failure to progress and a “nonreassuring heart rate tracing” in which the Apgar scores were unexpectedly 0 at 1, 5, and 10 minutes. Resuscitation was unsuccessful after 30 minutes. The venous cord gas was normal and the arterial blood gas was not consistent with intrapartum asphyxia. At the time of surgery, the placenta appeared grossly normal. The autopsy was entirely normal. This case raises questions about our understanding of intrauterine fetal demise and suggests an approach to future research.

Amniotic fluid embolism mortality rate

The objective of this study was to determine the mortality rate of amniotic fluid embolism (AFE) using population‐based studies and case series.