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Biomedical subjects

E N Allred

Publications and source records attributed to E N Allred.

At least 19 recordsLinked to original sources

Fetal vasculitis in preterm newborns: interrelationships, modifiers, and antecedents.

Histologic expressions of the fetal inflammatory response predict preterm delivery and neonatal disorders. We examined 1146 placentas in the Developmental Epidemiology Network data set for histologic evidence of membrane inflammation (subchorionitis, chorionitis, and chorioamnionitis) and fetal vasculitis (acute umbilical vasculitis or chorionic vasculitis). Our main findings are that (1) in the presence of membrane inflammation, fetal vasculitis is common, (2) duration of membrane rupture and gestational age appear to modify the risk of fetal vasculitis, (3) this risk modification differs for the different components of fetal vasculitis, i.e. umbilical and chorionic vasculitis, and (4) antecedents can be identified that appear to increase or decrease the risk of fetal vasculitis among births with membrane inflammation. We conclude that fetal vasculitis, the morphologic component of the fetal inflammatory response, might not be a homogeneous entity and deserves further study.

Adult↗

Continuous administration of endostatin by intraperitoneally implanted osmotic pump improves the efficacy and potency of therapy in a mouse xenograft tumor model.

In the first Phase I clinical trials of endostatin as an antiangiogenic therapy for cancer, the protein was administered as an i.v. bolus for approximately 20-30 min each day. This protocol was based on experimental studies in which animals were treated by s.c. bolus once a day. However, it was not clear in the previous studies whether this schedule could be maximized further. Therefore, we developed experimental models involving continuous administration of endostatin to determine the potency and efficacy of this approach. Endostatin was administered to tumor-bearing mice either s.c. or i.p. in single bolus doses. The efficacy of these regimens was compared with endostatin administered continuously via an i.p. implanted mini-osmotic pump. Our results show that endostatin remains stable and active in mini-osmotic pumps for at least 7 days. We show that endostatin injected i.p. is rapidly cleared within 2 h, whereas endostatin administered continuously via mini-osmotic pump maintains systemic concentrations of 200-300 ng/ml for the duration of administration. Furthermore, continuous i.p. administration of endostatin results in more effective tumor suppression at significantly reduced doses (5-fold), compared with bolus administration. Additional experiments using a human pancreatic cancer model in severe combined immunodeficient mice showed that there was a significant decrease in the microvessel density between the treatment groups and the control group. These data show that continuous administration of human endostatin results in sustained systemic concentrations of the protein leading to: (a) increased efficacy manifested as increased tumor regression; and (b) an 8-10-fold decrease in the dose required to achieve the same antitumor effect as the single daily bolus administration of endostatin. On the basis of this approach, an additional clinical trial has been designed and initiated and is under way in two countries.

Angiogenesis Inhibitors↗

Heterogeneity of angiogenic activity in a human liposarcoma: a proposed mechanism for "no take" of human tumors in mice.

BACKGROUND: Tumor cells are known to be heterogeneous with respect to their metastatic activity, proliferation rate, and activity of several enzymes. However, little is known about the heterogeneity of tumor angiogenic activity. We investigated whether heterogeneity of angiogenic activity could be responsible for the well-known observation of "no take" of human tumors transplanted into immunodeficient mice. METHODS: Severe combined immunodeficient (SCID) mice were xenotransplanted subcutaneously with tumor tissue (n = 55) or cell suspension of a human liposarcoma cell line (SW-872) or subclones (n = 28), with varying cell proliferation rates. Xenograft tumor growth was recorded for up to 6 months. Tumor tissues were then removed and analyzed for tumor cell apoptosis, microvessel density, and cell proliferation. All statistical tests were two-sided. RESULTS: Pieces of tumor derived from the parental cell line or its clones gave rise to three kinds of tumors: 1) highly angiogenic and fast-growing (aggressive) tumors, 2) weakly angiogenic and slow-growing tumors, and 3) nonangiogenic and stable tumors. Most tumors retained the original phenotype of their parental tumor. Tumor volume correlated positively with microvessel density (Spearman correlation coefficient [r] =.89; P< or =.0001) and inversely with tumor cell apoptosis (Spearman r = -.68; P =.002). Tumor volume was less strongly but still positively correlated with tumor cell proliferation in vivo (Spearman r =.55; P =.02). CONCLUSIONS: Human liposarcoma cells appear to be heterogeneous in their angiogenic activity. When tumor cells with little or no angiogenic activity are transplanted into SCID mice, a microscopic, dormant tumor results that may not grow further. Because such tiny tumors are neither grossly visible nor palpable, they have previously been called "no take." The finding that an angiogenic tumor can contain subpopulations of tumor cells with little or no angiogenic activity may provide a novel mechanism for dormant micrometastases, late recurrence, and changes in rate of tumor progression.

Animals↗

Mediators of fetal inflammation in extremely low gestational age newborns.

To establish levels of mediators of inflammation in cord blood and postnatal serum from extremely low gestational age newborns (ELGANs, < or =28 weeks), we measured sixteen markers of inflammation by recycling immunoaffinity chromatography in 15 ELGANs who had serum sampled at days 2-5. Median levels of IL-1, IL-6, IL-8, IL-11, IL-13, TNF-alpha, G-CSF, M-CSF, GM-CSF, MIP-1alpha, and RANTES were considerably higher than published values of these inflammatory mediators from term newborns. In three of eight ELGANS who had serial measurements taken, levels of IL-1, IL-6, IL-8, IL-11, TNF-alpha, G-CSF, and MIP-1alpha declined from initially very high levels to reach an apparent baseline towards the end of the first postnatal week. In these same three infants, GM-CSF and TGF-beta1 levels increased continuously during the first week. In the other five ELGANs, no consistent changes were observed. We speculate, that in some ELGANs, a fetal systemic inflammatory response is characterized by an antenatal wave of pro-inflammatory cytokines, followed by a second, postnatal wave of anti-inflammatory cytokines. Large epidemiologic studies are needed to clarify relationships among inflammation markers and their expression in the fetal and neonatal circulation over time. Such studies would also add to our understanding of the possible role of inflammatory mediators in the pathophysiology of the major complications of extreme prematurity.

Adult↗

Growth-restricted premature infants are at increased risk for low thyroxine.

OBJECTIVE: To evaluate, in extremely premature infants, the relationship between growth restriction and early total thyroxine levels, and to determine how maternal, prenatal, perinatal and neonatal variables influence the relationship. STUDY DESIGN: 719 infants born at four medical centers in Massachusetts, New York and New Jersey between 1991 and 1993 were studied. Entry criteria included: gestational age 23--30 weeks, birth weight 500--1500 g, and a serum thyroxine level obtained in the first week of life. Infants born to mothers with a history of thyroid disease were excluded. Birth weight and total thyroxine level are expressed as z-scores (standard deviation units) to adjust for their relationship to gestational age. RESULTS: In linear regression analysis, there was a 0.18 decrease in the total thyroxine z-score for each 1.0 (1 standard deviation unit) decrease in birth weight z-score (p=0.0001). Adjustment for multiple potential maternal, prenatal, perinatal and neonatal confounders failed to identify a factor or factors that could account for the observed association. CONCLUSIONS: The early total thyroxine level in extremely preterm infants was significantly associated with birth weight z-score. This relationship persisted even after adjustment for maternal, prenatal, perinatal and neonatal confounders suggesting antenatal influences. Of clinical importance, growth-restricted infants are at increased risk for early hypothyroxinemia and, possibly, to its related morbidities.

Adult↗

Fetal growth restriction is not associated with a reduced risk for bilateral spastic cerebral palsy in very-low-birthweight infants.

OBJECTIVE: To evaluate the influence of confounding and sampling bias on the relationship between fetal growth restriction in a very-low-birthweight-defined cohort (VLBW, < or =1500 g) and bilateral spastic cerebral palsy (BSCP) at early school-age. METHODS: Three hundred twenty-four of 407 long-term survivors of a regional cohort of VLBW newborns were followed until age 6 years. We categorized as small for gestational age (SGA) all infants whose birthweight Z-score was below -2 relative to published reference values. Uni- and multivariable logistic regression models were fit to estimate the risk of BSCP associated with SGA in the total sample, in subsamples defined by gestational age, and in a gestational age-matched case-control sample. RESULTS: In the total sample, no child below 28 weeks was SGA, and no child above 32 weeks had an appropriate birthweight for gestational age (AGA). The prevalence of BSCP was 14% in AGA and 2% in SGA infants. In both uni- and multivariable logistic regression analyses of the total sample, SGA was associated with a prominently reduced risk of BSCP (odds ratios range from 0.1 to 0.2, all 95% confidence limits exclude 1.0). However, analyses performed in samples defined by different gestational age cutoffs (24--31 weeks, 28--31 weeks) and in a sample using three gestational age-matched controls per BSCP-case did not show a protection by growth restriction (odds ratios range from 0.8 to 2.2, all 95% confidence limits include 1.0). CONCLUSIONS: In VLBW-defined samples, the apparent protective effect of SGA for BSCP can be explained, at least in part, by the highly skewed distribution of SGA over the available gestational age range. From this follows that study cohorts should be defined by gestational age and not by birthweight. In distorted samples like this one, even controlling for gestational age does not reduce the illusion of a reduced cerebral palsy risk for growth restricted infants. Only restriction of the sample by gestational age and/or matching for gestational age reveals the absence of this apparent protective effect.

Cerebral Palsy↗

Antenatal glucocorticoid treatment does not reduce chronic lung disease among surviving preterm infants.

BACKGROUND: Antenatal glucocorticoid treatment (AGT) is associated with a number of postnatal benefits to the preterm infant, including reduced risk of respiratory distress syndrome, patent ductus arteriosus, intraventricular hemorrhage, and necrotizing enterocolitis. OBJECTIVE: To evaluate the hypothesis that maternal AGT not only reduces the risk of surfactant deficiency but also reduces the occurrence of chronic lung disease (CLD) among surviving preterm infants. STUDY DESIGN: Case-referent study of 1454 very low birth weight infants born between January 1991 and December 1993 at 4 university medical centers. RESULTS: Rates of AGT varied among the 4 centers (11%-69%), as did rates of CLD (4%-21%), defined as a requirement for supplemental oxygen at 36 weeks' postmenstrual age. CLD rates at each center, however, did not vary with the rate of AGT exposure. In multivariate logistic regression analyses, AGT did not contribute significantly to CLD risk. CONCLUSION: AGT may play a less prominent role in modifying CLD risk than other factors such as biologic immaturity, infection, or neonatal intensive care unit practices, such as mechanical ventilation, continuous positive airway pressure, and surfactant replacement therapy.

Chronic Disease↗

Congenital microcephaly: phenotypic features in a consecutive sample of newborn infants.

OBJECTIVE: We compared the prevalence of major and minor anomalies in a consecutive sample of newborn infants with congenital microcephaly with that among normocephalic infants. STUDY DESIGN: Head measurements from >19,000 liveborn infants at 1 hospital during the years 1991 and 1992 were reviewed. Infants whose head circumference was in the lowest quartile (n = 850) were remeasured by research assistants to identify all whose head circumference was 2 SD below the mean for gestational age; 106 infants with congenital microcephaly were identified. Infants with microcephaly (n = 65) and 294 infants in a control group were examined systematically for major malformations and minor physical features. RESULTS: Four (6.2%) of the 65 infants examined either had a major malformation or were considered dysmorphic. One of the 4 had a specific multiple malformation syndrome, and 1 dysmorphic infant had a rare metabolic defect. Overall, the infants with microcephaly did not have a higher frequency of minor anomalies. However, there was a higher frequency of frontal bossing, small chin, and short nose with anteverted nares, which was associated with small body size rather than microcephaly. CONCLUSIONS: Congenital microcephaly is infrequently accompanied by major malformations and occurs rarely as part of a recognizable syndrome.

Abnormalities, Multiple↗

Sequential thoracic metastasectomy prolongs survival by re-establishing local control within the chest.

OBJECTIVE: The value of sequential thoracic metastasectomies is unknown. We evaluate repeat metastasectomy for limited recurrences within the thorax. METHODS: From July 1988 to September 1998, 54 patients underwent 2 to 6 separate sequential procedures to excise metastases after recurrence isolated to the thorax. Kaplan-Meier survival and Cox modeling determined prognostic variables. RESULTS: Thirty-three men and 21 women, 22 to 76 years underwent 2 (100%, n = 54), 3 (50%), 4 (22%), or 5 to 6 (11%) metastasectomies. Fifty-four percent of patients had carcinoma, 35% sarcoma, 9% germ cell, and 2% melanoma. There were no operative deaths; all late deaths occurred from cancer. Median follow-up was 48 months. Cumulative 5-year survival from the second procedure was 57%. After the second, third, fourth, and fifth procedures, respectively, permanent control was achieved in 15 (27%) of 54 patients, 5 (19%) of 27, 1 (8%) of 12, and 0 of 7. Recurrence amenable to additional surgery occurred in 27 (50%) of 54, 12 (44%) of 27, 6 (50%) of 12, and 1 (17%) of 6. Mean hazard for the development of unresectable recurrence increased from 0.21 after the second procedure to 0.91 after the fifth procedure. The 5-year survival for the 27 patients undergoing only 2 metastasectomies was 60% (median not yet reached), 33% for the 15 patients undergoing only 3 metastasectomies (median 34.7 months), and 38% for the 12 patients undergoing 4 or more (median 45.6 months). From the time a recurrence was declared unresectable, patients had a 19% 2-year survival (median 8 months). CONCLUSIONS: Multiple attempts to re-establish intrathoracic control of metastatic disease is justified in carefully selected patients, but the magnitude of benefit decays with each subsequent attempt.

Adult↗

The relationship between dental overbite and eustachian tube dysfunction.

OBJECTIVE: The purpose of this study was to investigate the association between deep dental overbite and eustachian tube dysfunction (ETD). DESIGN: Case-control study. SETTING: Tertiary care pediatric otolaryngology outpatient clinic at the Children's Hospital, Boston, Massachusetts. PATIENTS: 105 patients between the ages of 2 and 6 years. STUDY MEASUREMENTS: Dental overbite, overjet, and occlusal relationships were measured by an observer who was unaware of ETD status. ETD was defined as having ventilation tubes in place or having the recommendation for ventilation tube placement by an attending pediatric otolaryngologist. In addition, demographic information and medical and social histories were prospectively recorded. RESULTS: In a multivariate logistic regression model, children with deep bites were 2.8 times more likely to have ETD than those without deep bites (P = .03). Other independent risk factors for ETD identified in this model were family history of otitis media (OM) and age less than 3 years. CONCLUSIONS: Children with deep dental overbites are at a significantly increased risk for developing ETD.

Child↗

Topography of cerebral white-matter disease of prematurity studied prospectively in 1607 very-low-birthweight infants.

The objective of this study was to evaluate to what extent (1) the characteristics of localization, distribution, and size of echodense and echolucent abnormalities enable individuals to be designated as having either periventricular hemorrhagic infarction or periventricular leukomalacia and (2) the characteristics of periventricular hemorrhagic infarction and periventricular leukomalacia are independent occurrences. The population for this study consisted of 1607 infants with birthweights of 500 to 1500 g, born between January 1991 and December 1993, who had at least one cranial ultrasound scan read independently by at least two ultrasonographers. The ultrasound data collection form diagrammed six standard coronal views. The cerebrum was divided into 17 zones in each hemisphere. All abnormalities were described as being echodense or echolucent and were classified on the basis of their size, laterality, location, and evolution. Eight percent (134/1607) of infants had at least one white-matter abnormality. The prevalence of white-matter disease decreased with increasing gestational age. Most abnormalities were small or medium sized and unilateral; only large echodensities tended to be bilateral and asymmetric. Large abnormalities, whether echodense or echolucent, were more likely than smaller abnormalities to be widespread, and the extent of cerebral involvement was independent of whether abnormalities were unilateral or bilateral. Large abnormalities were relatively more likely than small abnormalities to involve anterior planes. Small abnormalities, whether echodense or echolucent, or whether unilateral or bilateral, preferentially occurred near the trigone. Using the characteristics of location, size, and laterality/symmetry, we were able to allocate only 53% of infants with white-matter abnormalities to periventricular hemorrhagic infarction or periventricular leukomalacia. Assuming that periventricular leukomalacia and periventricular hemorrhagic infarction are independent and do not share risk factors, and that each occurs in approximately 5% of infants, we would have expected 0.25%, or about 4 individuals, to have abnormalities with characteristics of both periventricular leukomalacia and periventricular hemorrhagic infarction, whereas we found 63 such infants. Most infants with white-matter disease could not be clearly designated as having periventricular hemorrhagic infarction or periventricular leukomalacia only. Periventricular hemorrhagic infarction contributes to the risk of periventricular leukomalacia occurrence, or the two sorts of abnormalities share common risk antecedent factors. The descriptive term echodense or echolucent and the generic term white-matter disease of prematurity should be used instead of periventricular leukomalacia or periventricular hemorrhagic infarction when referring to sonographically defined white-matter abnormalities.

Brain Mapping↗

Hypocarbia during the first 24 postnatal hours and white matter echolucencies in newborns < or = 28 weeks gestation.

The purpose of the present study was to test the hypothesis that newborns < or = 28 wk gestation who have a PCO(2) measurement in the lowest gestational age-specific quartile (hypocarbia) on the first day of life are not at increased risk for ultrasonographic white matter echolucency (EL) after adjustment for confounders. The sample consisted of 799 infants < or = 28 wk gestation born during 1991-1993. Forty-eight infants with EL were classified as cases and compared with 751 controls, i.e. those without EL. We performed univariable comparisons, stratified analyses, and multivariable logistic regression. In the univariable analyses, hypocarbia on the first day of life was associated with an increased EL risk. The odds ratios for the hypocarbia-EL relationship were prominently elevated in the strata of infants who did not have other major risk factors for EL (e.g. gestational age 26-28 wk, normothyroxinemia, no characteristics of antenatal infection). In the multivariable analyses, the association diminished after adjustment with a hypocarbia propensity score (odds ratio = 1.7; 95 % confidence interval, 0.8-3.2) or with potential confounders.

Brain↗

Congenital heart disease in maternal phenylketonuria: report from the Maternal PKU Collaborative Study.

The frequency and types of congenital heart disease in offspring from pregnancies in women with hyperphenylalaninemia were examined in the international prospective Maternal Phenylketonuria Collaborative Study. Relationships of congenital heart disease in offspring to the basal blood phenylalanine level in the mother, metabolic control through diet during pregnancy, and phenylalanine hydroxylase mutations in mother and offspring were determined. The 416 offspring from 412 maternal phenylketonuria pregnancies that produced live births and 100 offspring from the 99 control pregnancies were included in this examination. Thirty-four of the 235 offspring (14%; 95% CI, 10.2 to 19.6%) from pregnancies in phenylketonuric women with a basal phenylalanine level > or = 900 microM (15 mg/dL) [normal blood phenylalanine < 120 microM (2 mg/dL)] and not in metabolic control [phenylalanine level < or = 600 microM (10 mg/dL)] by the eighth gestational week had congenital heart disease compared with one control offspring (1%) with congenital heart disease. One offspring among the 50 (2%) from mothers with non-phenylketonuria mild hyperphenylalaninemia also had congenital heart disease. Coarctation of the aorta and hypoplastic left heart syndrome were overrepresented compared with expected percentages among those with congenital heart disease in the general population. A basal maternal phenylalanine level > 1800 microM (30 mg/dL) significantly increased the risk for bearing a child with congenital heart disease (p = 0.003). Phenylalanine hydroxylase mutations in the mothers and offspring did not have an independent relationship to congenital heart disease but were related through the basal maternal phenylalanine levels. The data in this study indicate that a basal maternal phenylalanine level of 900 microM may be a threshold for congenital heart disease, that women with the most severe degree of phenylketonuria are at highest risk for bearing such a child, and that prevention of the congenital heart disease requires initiation of the low phenylalanine diet before conception or early in pregnancy with metabolic control no later than the eighth gestational week.

Female↗

Quality assurance in gynecologic cytology. The value of cytotechnologist-cytopathologist discrepancy logs.

We describe a simple method for displaying and evaluating the concordance or discordance between cytotechnologists (CTs) and cytopathologists (CPs) on gynecologic cases. The provisional diagnoses made by the CTs and the final diagnoses of the CPs are captured by the laboratory information system; data generated for specified periods are displayed as a 10 x 10 matrix that classifies each possible diagnosis made by the CT and CP into 1 of 10 major categories. Matrices are generated for the entire laboratory and for individual CTs; individual CTs are evaluated based on their deviation from the laboratory average. Three statistical measures are generated: percentage of discordant diagnoses, a kappa statistic, and a weighted measure. During a 2.5-year period, approximately 4,200 cases were referred to a CP for review every 6 months. The median discordance in diagnoses increased during 2 years from 21% to 34%, and the kappa value fell from 0.69 to 0.38. This was attributed primarily to 1 CT, whose performance, as well as that of the entire laboratory, improved after remedial action. Measures of CT-CP diagnostic concordance are a useful and efficient measure of CT performance and can be incorporated into mandatory semiannual performance evaluations.

Boston↗

Child health status, neurodevelopmental outcome, and parental satisfaction in a randomized, controlled trial of nitric oxide for persistent pulmonary hypertension of the newborn.

OBJECTIVE: To describe health and neurodevelopmental outcomes and parental satisfaction with hospital care among surviving intervention and control enrollees in a randomized, controlled trial of nitric oxide for persistent pulmonary hypertension of the newborn (PPHN). METHODS: All surviving enrollees 1 to 4 years of age were eligible for follow-up. Outcomes were assessed by telephone using a trained interviewer and standardized instruments. Domains assessed included parental report of specific conditions and hospital use, rating of general health, cognitive and motor development, behavior problems, temperament, and satisfaction with the hospital stay. Fisher's exact test and the Wilcoxon rank sum test assessed differences between intervention and control infants. RESULTS: Interviews were completed on 60 of 83 survivors (72%). Eighteen families (22%) could not be located, 2 (2%) were non-English-speaking, and 3 (4%) declined participation. No postdischarge deaths were ascertained. Among those interviewed, race, income, and education of parents of intervention and controls were comparable, as were entry oxygenation index, extracorporeal oxygenation utilization, and days of hospitalization. No differences were found in pulmonary, neurologic, cognitive, behavioral, or neurosensory outcomes; hospital readmission rates; or parental ratings of child's health. The overall neurologic handicap rate was 15%. The rate of hearing deficit was 7%. The rate of significant behavioral problems was 26%. Levels of satisfaction expressed were high for each group. No differences in parental ratings were found between the 2 groups. CONCLUSIONS: No adverse health or neurodevelopmental outcomes have been observed among infants treated with nitric oxide for PPHN. The parents of the critically ill infants enrolled in our clinical trial welcomed their child's inclusion and all expressed satisfaction with the care that their child received while at a tertiary care hospital. Enrollment in either arm of this randomized, controlled trial did not seem to affect parental satisfaction with the hospital care that their child received.

Adult↗

Reduced visual resolution acuity and cerebral white matter damage in very-low-birthweight infants.

Neonatal cerebral white matter echolucencies predict visual resolution acuity deficits in very-low-birthweight (VLBW) infants. We examined maternal sociodemographic, lifestyle, intrapartum, infant birth/perinatal, and ocular motor/refractive characteristics to determine whether they accounted for this association in infants who were tested once between postnatal age 25 and 56 weeks (corrected for gestational age at birth). Cranial ultrasound scans were read by consensus to identify echolucency in a population of VLBW infants with no known ocular abnormalities. Visual resolution acuity was measured with the Acuity Card Procedure (ACP) in 14 infants with echolucency and compared with that of 81 VLBW infants born in the same hospitals with normal ultrasound scans. In time-oriented logistic regression models, echolucency remained a consistent predictor of abnormal visual resolution acuity after adjustment for covariates in three developmental periods (pre-, peri-, and postnatal). Odds ratios ranged from 19.3 (95% confidence interval, 4.5 to 82.2; p=0.001) to 10.4 (95% confidence interval, 1.3 to 81.9; p=0.03). Reduced visual resolution acuity in VLBW infants appears to be due to cerebral white matter damage.

Cerebral Cortex↗

What explains away the increased risk of histological chorioamnionitis in African-American mothers of very-low-birthweight infants? Developmental Epidemiology Network Investigators.

We sought explanations for African-American mothers' increased risk of chorioamnionitis by sequentially adjusting for confounder variables both individually and in groups. We searched for a subset of covariates that had the most influence on the chorioamnionitis odds ratio (OR) of these women. The sample consisted of 305 African-American and 520 White mothers who gave birth to a very-low-birthweight (< or = 1500 g) infant between 1991 and 1993, whose placenta was examined according to protocol and whose hospital chart was reviewed. Histologically proven chorioamnionitis was present in 43% of the placentas from African-American women and in 27% of those from Whites (crude OR 2.1, 95% confidence interval 1.5, 2.8). Singleton status appeared to be the most important effect modifier, with significant crude ORs of 1.5 among singletons and 3.4 among non-singletons. Using logistic regression models in the whole sample and in subgroups, we sought to 'explain away' this increased risk. Indeed, addition of information about confounder variables resulted in considerable reduction in the ORs to 1.1 among singletons and 1.9 among non-singletons. Particularly important among the confounders were singleton birth, Medicaid insurance, duration of ruptured membranes and gestational age. We discuss the possibility that this set of confounding variables conveys, in part, the same information as the variable African-American, and also perhaps information about the availability and/or utilisation of prenatal health care.

Black or African American↗