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.

Gestational age-specific birthweight of twins in vital records.

Analysis of singleton preterm birth from vital statistics data is hampered by inaccurate gestational age dating. This is most notably evidence by the large fraction of implausibly high birthweights for gestational age given in birth records. Using natality statistics for New England, 1977-88, birthweight distributions were plotted for representative preterm gestations. Confounding by improbable birthweights was observed to be considerably less among preterm twin births than among preterm singleton births.

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.

Excess males in preterm birth: interactions with gestational age, race, and multiple birth.

OBJECTIVE: To confirm an excess of males among preterm births and study its interaction with other risk factors to better understand its potential etiologic significance. METHODS: Fetal gender was analyzed in 1,781,960 white and 103,329 black singleton births, and in 37,429 white twin births using vital statistics data from the six New England states for 1977-1988. RESULTS: A 7.2% excess of males was found among white singleton preterm births. There was only a 2.8% excess among comparable blacks, a highly significant difference between the races (P < .001). The effect was roughly constant for 20-37 weeks' gestation. Being married increased the effect for white, but not black, women, and was also found among white fetal deaths. Among white twins, male excess in preterm births occurred only in 20-33 week's gestations. CONCLUSIONS: Male fetal gender is associated with singleton preterm birth, an effect most evident in white women, particularly if married. Among preterm white twins, there is also a male excess, limited to gestations under 34 weeks. The excess of males in selected groups suggests the existence of a mechanism of preterm birth influenced by fetal gender. Preterm births in blacks and in twin gestations greater than 33 weeks may be more often due to alternative mechanisms that are independent of fetal gender.

Evaluation of new anti-infective drugs for the treatment of acute infectious diarrhea. Infectious Diseases Society of America and the Food and Drug Administration.

This guideline includes diarrhea causing infantile mortality in which a bacterial pathogen is recovered and for which oral rehydration therapy is an important component of care as well as traveler's diarrhea (with or without recovery of a pathogen). Diarrhea is defined as the passage of three or more unformed stools per day plus--in all patients except infants--one or more signs or symptoms of enteric infection. The preferred study design is prospective and randomized, with an active concurrent control and (when possible) blinding. Placebo-controlled trials may be performed if the severity of disease is judged by the investigator to be mild or moderate. It is desirable that both clinical and microbiological outcome be determined. Microbiological eradication is paramount.

Evaluation of new anti-infective drugs for the treatment of typhoid fever. Infectious Diseases Society of America and the Food and Drug Administration.

Typhoid fever is an acute febrile illness caused by Salmonella typhi. The evidence of blood-borne infection required for study entry includes clinical signs and symptoms plus confirmation of the presence of S. typhi in blood or other tissues or body fluids. The preferred study design is prospective and randomized with an active concurrent control. It is preferred that the investigator or an evaluator be blinded to therapy. In general, treatment should be administered for 2 weeks until it is demonstrated that a shorter course is as efficacious and as safe. Follow-up cultures of specimens from sites originally shown to be infected with S. typhi should be performed unless the diagnostic procedure places the patient at unnecessary risk.

Evaluation of new anti-infective drugs for the treatment of cholera. Infectious Diseases Society of America and the Food and Drug Administration.

Cholera is an acute gastrointestinal infection caused by Vibrio cholerae. It is characterized by watery diarrhea that may lead to massive fluid loss, which in turn may result in hypotension, shock, and death within hours. Key to the treatment of cholera is fluid replacement. Anti-infective therapy decreases the severity and duration of diarrhea and the duration of shedding of V. cholerae. Enrolled patients should have diarrhea that is moderate to severe and a culture that ultimately yields V. cholerae. A prospective, randomized, active-controlled clinical trial is preferred. Studies should be double-blinded or evaluator-blinded. The rapidity with which the organism is eliminated from stool may be assessed. Both clinical and microbiological outcome should be determined. Assessment of microbiological eradication is paramount, since fluid replacement may suffice for treatment of signs and symptoms.

Evaluation of new anti-infective drugs for the treatment of diarrhea caused by Giardia lamblia. Infectious Diseases Society of America and the Food and Drug Administration.

Giardia lamblia is a flagellate protozoan that produces symptoms by infecting the small bowel and biliary tract in the trophozoite form. Diagnosis is currently established by microscopic visualization of the organism in appropriate intestinal contents (stool, small-bowel contents, or biopsy specimen). Adult patients with diarrhea and one or more enteric symptoms may be enrolled in clinical trials of new drugs for the treatment of giardial disease. A randomized, double-blind, active-concurrent-control design is recommended. Post hoc stratification by age, immune status, chronicity of disease, and ease of establishing diagnosis (organism load) may be performed. Microbiological assessment 48 hours to 7 days after the completion of therapy is paramount for determining final outcome.

Evaluation of new anti-infective drugs for the treatment of diarrhea caused by Cryptosporidium. Infectious Diseases Society of America and the Food and Drug Administration.

Cryptosporidium is a coccidian protozoan that produces symptoms by infesting the small bowel. The illness is characterized by watery stools, anorexia, weight loss, and abdominal pain. Diagnosis is made by visualization of the organisms on microscopic examination of stool. There currently is no approved therapy for this infection. A randomized, double-blind, placebo-controlled study design is recommended. Stratification of patients by age and immune status should be considered. Two stool samples obtained 48 hours to 7 days after completion of therapy should be negative for Cryptosporidium oocysts. Assessment of microbiological outcome is paramount.

Evaluation of new anti-infective drugs for the treatment of diarrhea caused by Entamoeba histolytica. Infectious Diseases Society of America and the Food and Drug Administration.

Entamoeba histolytica causes colonic infection that ranges from asymptomatic carriage to invasive disease with infection of extraintestinal organs, particularly the liver. The disease occurs in both sporadic and epidemic forms. Diagnosis requires visualization of trophozoites or cysts by microscopic examination of stool, colonic scrapings, or biopsy specimens. Patients with either asymptomatic or symptomatic disease may be eligible for clinical trials. A prospective, randomized, double-blind, placebo-controlled study design is recommended for asymptomatic carriers and an active-concurrent-control study design for symptomatic patients. Final outcome should be assessed 48 hours to 7 days after completion of therapy. Assessment of microbiological outcome is paramount.

Evaluation of new anti-infective drugs for the treatment of chronic carriage of Salmonella. Infectious Diseases Society of America and the Food and Drug Administration.

The chronic carriage of salmonellae is defined as the shedding of a Salmonella species for > or = 1 year, as documented by an initial positive culture of a stool sample obtained at least 1 month after resolution of the acute illness and repeated positive cultures for at least 1 year. Clinical trials of investigational anti-infective drugs for the treatment of the salmonella carrier state may be conducted with a placebo control or an active concurrent control. A crossover design also may be employed for establishing efficacy. Patients should generally receive therapy for at least 6 weeks. Outcome will be assessed only by microbiological criteria. Determination of the interval required for the suppression of salmonellae and follow-up for 6 months after completion of therapy are recommended.

Evaluation of new anti-infective drugs for the treatment of antibiotic-associated colitis. Infectious Diseases Society of America and the Food and Drug Administration.

Colitis due to Clostridium difficile is diagnosed in 10%-15% of hospitalized patients who develop diarrhea after treatment with antimicrobial drugs. Diagnosis is based on the concurrence of diarrhea, one or more signs or symptoms of enteric intoxication, and stool from which toxigenic C. difficile is isolated or from which its toxins are identified. Clinical trials evaluating therapy may be placebo controlled (for mild disease) or concurrently controlled with an active drug. A randomized, double-blind study design is preferred. Outcome should be assessed by monitoring of the degree of inflammation of the bowel mucosa, the intensity and severity of diarrhea, the duration of illness, changes in stool form, and the eradication of C. difficile or its toxins from stool. Because C. difficile can be a component of the normal gastrointestinal flora, assessment of clinical outcome is paramount.

Evaluation of new anti-infective drugs for the treatment of gastritis and peptic ulcer disease associated with infection by Helicobacter pylori. Infectious Diseases Society of America and the Food and Drug Administration.

Helicobacter pylori is a gram-negative, microaerophilic, spiral bacillus. Infection by this organism is currently believed to be the major cause of type B gastritis. Inflammation and infection may persist for years in the absence of therapeutic intervention. There is currently no approved antimicrobial therapy for gastritis. Clinical investigations have shown that combination regimens including bismuth salts and antimicrobial drugs result in the relief of symptoms, the resolution of histologic evidence of gastritis, the eradication of H. pylori, high rates of ulcer healing, and lower rates of ulcer relapse than have been found with other therapies (antacids and H2 antagonists). A randomized, double-blind, placebo-controlled study design is recommended for evaluation of new therapies. Study participants should have their progress monitored by endoscopy performed at enrollment, at completion of therapy, and 3 months thereafter. Assessment of microbiological outcome is paramount for final evaluation of the patient.