Twin birth weight discordance and risk of preterm birth.

OBJECTIVES: Our purpose was to determine whether birth weight discordance is a risk factor for preterm birth of twins, and to further characterize the relationships involved. STUDY DESIGN: Maternally linked 1978-1990 Missouri birth certificates were used to analyze gestations resulting in live twins. We used contingency tables and multiple logistic regression. RESULTS: The degree of discordance correlated strongly with risk for live preterm birth but only for discordances >30% and preterm birth at <32 weeks' gestation. Among 9479 pregnancies with discordance <30%, 9.5% ended in birth at <32 weeks' gestation, versus 13.7% of 326 with discordance of 30% to 40% (P =.03) and versus 34.1% of 126 with discordance > or =40% (P <. 001). There were 42 preterm twin births at <32 weeks' gestation with discordances > or =40%. Of these, 51% were attributable to fetal growth restriction and 16% to large size for gestational age in one infant; in 72% the smaller twin was the second born, and in 86% the twins were like sex. The relative association between > or =40% discordance and preterm birth at <32 weeks' gestation was strengthened (final odds ratio, 9.54; P <.0001) in a multivariate model containing other risk factors for delivery at <32 weeks' gestation: black race, either twin small for gestational age, unmarried, teenage mother, number of male fetuses, like fetal sex, education <12 years, nulliparity, and cigarette smoking. CONCLUSIONS: Twin birth weight discordance has now clearly been demonstrated to be a risk factor for preterm birth. The effect was found particularly with discordances > or =40% before 32 weeks' gestation. Discordance was usually attributable to fetal growth restriction, most often in the second-born twin.

Cat-scratch disease causing status epilepticus in children.

Status epilepticus from cat-scratch encephalopathy is often recalcitrant to usual therapies, causing treatment to focus on critical care management of the patient that may require aggressive interventions, such as continuous pentobarbital administration. We describe two children whose initial clinical presentation of cat-scratch disease was status epilepticus with normal cerebrospinal fluid studies. A history of cat exposure (specifically, kitten and/or fleas), regional lymphadenopathy, and a papule or inoculation site should be sought, but are not essential for diagnosis. The presumptive diagnosis of cat-scratch disease can be made by serology alone even in the absence of classic diagnostic criteria. Our two cases and other reports in the literature show a favorable prognosis in most cases, despite the occurrence of status epilepticus. The diagnosis of cat-scratch disease should be strongly considered in all children with unexplained status epilepticus or encephalopathy and serologic testing for Bartonella henselae should be done.

Effects of fetal sex and race on risk of very preterm birth in twins.

OBJECTIVE: Our purpose was to determine whether the risk of twin preterm birth correlates with the number of male fetuses. STUDY DESIGN: Among 8109 white and 1884 black twin pregnancies in the Missouri Successive Pregnancy Birth/Death Data Set, 1978 through 1990, risk for preterm birth at various gestational ages was determined with 0, 1, or 2 male infants. RESULTS: Studied as individuals, white preterm twins <35 weeks' gestation demonstrated a 9.2% excess of male fetuses (P < .001). Adjusted for monozygosity, risk for preterm birth <35 weeks' gestation was 15.7% in white female-female pairs, 17.9% in unlike-sex white fetuses, and 20.2% in white male-male pairs (r = .999, P = .01). The effect was absent in black pregnancies and was unrelated to birth order, cesarean delivery, parity, twins' weight differential, year, or season. CONCLUSIONS: In white twin gestations the observed linear relationship between the number of male fetuses and the likelihood of preterm birth <35 weeks' gestation suggests a fetal mechanism for preterm birth <35 weeks' gestation linked to fetal sex. Studies of mechanisms for preterm birth must stratify by fetal sex and race.

Association of sociodemographic variables with risk for very preterm birth in twins.

OBJECTIVE: To assess the influence of maternal race, age, marital status, and education on risk for earlier and later preterm births in twin pregnancies. METHODS: We analyzed 8109 white and 1906 black liveborn twin pregnancies in the Missouri Linked Sibship files for the years 1978-1990, using contingency tables and multiple logistic regression. RESULTS: Black twin gestations had 1.61-fold (95% confidence interval [CI] 1.46, 1.76) greater risk than whites for preterm birth before 34 weeks' gestation. However, there was no race difference after 33 weeks. Among whites, teen age, unmarried status, and education fewer than 12 years were independently associated with risk for delivery before 34 weeks in multivariate analysis (odds ratios [OR] 1.28-1.51, each P < or=.001). These associations were diminished or absent for preterm births after 33 weeks' gestation. White unmarried teen mothers with fewer than 12 years of education had 1.83-fold (95% CI 1.39, 2.40) greater risk for preterm birth before 34 weeks' gestation compared with white married women more than 19 years of age with at least 12 years of education. In blacks, this difference was 1.47-fold (95% CI 1.13, 1.92). In both races, these differences were absent after 33 weeks' gestation. CONCLUSION: Traditional sociodemographic risk factors were present for twin preterm birth, but mainly before 34 weeks' gestation. This, together with previous data from Missouri Linked Sibship files, indicates that dominant pathogenic mechanisms of early preterm birth in twin gestations are likely to be different from those causing later preterm twin birth. Therefore, gestational age should be accounted for in future studies seeking to identify predictive factors or biomechanisms for twin preterm birth.

Fetal intestinal transplant model for mucosal immune responses.

A rat fetal intestinal transplant model was developed for long-term study of intestinal immune responses. For the model, fetal small intestine is transplanted into the dorsal subcutaneous tissue of syngeneic adults and allowed to mature, providing an accessible site, isolated from the intestinal stream. We previously demonstrated normal histologic maturation of the transplant. Specific antibody-producing cells appeared in the lamina propria of both transplant and native in situ intestine following intraluminal immunization of the transplant with cholera toxin, and conversely, in transplants after immunization of in situ intestine. An enterointestinal lymphocyte migratory pathway (originating in intestine and migrating to another region of the intestine) was thus demonstrated unequivocally. We found a bacterial flora in the transplant, and showed normal villus morphology in scanning electron microscopy. Less than 200 pg, i.e., a 10(-7) fraction, of 2 mg macromolecular lipopolysaccharide placed in the transplant lumen was absorbed per plasma lipopolysaccharide half-life. Immunization of the transplant with cholera toxin resulted in specific IgA and IgG antibody in the transplant lumen and in bile, and specific IgG, but not IgA, antibody in serum. A second dose of antigen gave an anamnestic rise in intra-transplant antibody. Intestinal immune tolerance was also demonstrated: sheep red blood cells (SRBC) administered into the transplant for 7 days suppressed splenic IgM plaque forming responses to subsequent intraperitoneal challenge with SRBC. These studies further demonstrate that the fetal intestinal transplant behaves immunologically like native intestine, and therefore provides a useful model for investigation of the intestinal immune system.

Nosocomial Clostridium difficile reservoir in a neonatal intensive care unit.

A new bacteriophage/bacteriocin typing system was used to study Clostridium difficile colonization in a neonatal intensive care unit. C. difficile was isolated from 21 of 62 (34%) stools from 15 of 37 (41%) infants. Colonization was reduced during antimicrobial therapy and for about 1 week thereafter. One of five nurses and one of two parents studied were carriers. Eight isolates were cultured from environmental surfaces. Thirty of 31 C. difficile isolates were found to be a single type, Cld 6,9,10,13; bacteriocin 1320,1537,2304. No C. difficile was found in 29 specimens obtained in the delivery room from mothers and infants, and there was no association of early colonization with vaginal delivery. The data provide strong evidence for nosocomial acquisition of C. difficile by infants in the neonatal intensive care unit. No obvious pathologic role for C. difficile could be identified among colonized infants. Among 22 C. difficile isolates from 7 adult inpatients with diarrhea and 13 healthy infants attending the center's well baby clinic, 4 were the same type as the strain found in the intensive care nursery. Only one of these patients had had direct contact with the neonatal intensive care unit, indicating that the nursery strain may also be found elsewhere in the community.

Clostridium difficile in normal infants and sudden infant death syndrome: an association with infant formula feeding.

Large numbers Clostridium difficile were found in the stools of two victims of sudden infant death syndrome (SIDS). This prompted a study of normal infants in the SIDS age group. Thirty-two infants were studied, using two selective culture techniques and two assays for bacterial products. Thirteen of the normal infants (39%) were found to carry C difficile, and fecal toxins were detected in eight of these, four with cytotoxin detectable at 10(-4) or higher dilution. Colonization was observed in one of 13 (7%) breast-fed babies and 12 of 17 (71%) of those whose primary milk source was infant formula (P less than .01). Fecal C difficile toxin was detected only in the latter group. The isolation of C difficile or its toxins in the stools of infants with SIDS, diarrhea, or even if large quantities of fecal cytotoxin are present.

Possible pathogenic role of endotoxin in Reye's syndrome.

Evidence of circulating endotoxin was sought in children with Reye's syndrome, on the thesis that severe hepatic failure is likely to result in loss of capacity to detoxify intestinal endotoxins entering the circulation. A modification of the Limulus assay was used to demonstrate high levels of endotoxin-like activity (E.L.A.) in nine comatose patients with Reye's syndrome and in one of the two non-comatose patients. The symptom-free sibling of one patient had raised liver enzymes and a negative Limulus test. Plasma E.L.A. correlated significantly with degree of electroencephalographic disturbance early in the course of the illness. E.L.A. was also found in both of two cerebrospinal fluids evaluated. Preliminary in-vitro characterisation of this substance indicated that it resembled endotoxin derived from anaerobic intestinal bacteria. Intestinally derived endotoxin could be one factor in the pathogenesis of encephalopathy and other features of Reye's syndrome.

Lymphangiographic findings in histoplasmosis.

The lymphangiographic findings of histoplasmosis in an 11-year-old girl are presented and correlated with the histopathology of a mediastinal lymph node. Nonconfluent lymphadenographic defects with discrete margins measuring 2-4 mm in diameter were seen, corresponding to the microscopic demonstration of nodal granulomas of the same size. This is quite different from the lymphadenographic pattern usually present in lymphoma but might be seen in certain stages of other granulomatosis diseases.

Inactivation of endotoxin by polymyxin B.

The limulus gelation assay was utilized to investigate endotoxin inactivation by a number of antibiotics in vitro. Endotoxin activity was sharply reduced by polymyxin B and sodium colistimethate. The effect of the polymyxin was not significantly inhibited by 0.001 M calcium or 90% serum. Crude endotoxins from a variety of aerobic gram-negative bacteria, including several not previously studied, could be inactivated 1 or more logs by as little as 1 mug of polymyxin B per ml, whereas Bacteroides fragilis endotoxin was poorly detoxified. A 10,000-fold range in the relative susceptibility of different endotoxins to inactivation by polymyxin B was found. The endotoxin most susceptible to polymyxin B was derived from an organism resistant to polymyxin B by disk sensitivity testing, suggesting that the bacteriocidal and endotoxin detoxifying properties of polymyxin need not be directly related.