Faculty Bibliography

BACKGROUND:Small for gestational age (SGA) can occur following a pathological process or may represent constitutionally small fetuses. However, distinguishing these processes is often difficult, especially in large studies, where the term SGA is often used as a proxy for restricted fetal growth. Since biologic variation in fetal size is largely a third trimester phenomenon, we hypothesized that the definition of SGA at term may include a sizeable proportion of constitutionally small fetuses. In contrast, since biologic variation in fetal size is not fully expressed in (early) preterm gestations, it is plausible that SGA in early preterm gestations would comprise a large proportion of growth restricted fetuses. AIM/OBJECTIVE:We compared mortality and morbidity rates between SGA and appropriate for gestational age (AGA) babies. SUBJECTS/METHODS:A population-based study of over 19million non-malformed, singleton births (1995-04) in the United States was performed. Gestational age (24-44weeks) was based on a clinical estimate. SGA and AGA were defined as sex-specific birthweight <10th and 25-74th centiles, respectively, for gestational age. All analyses were adjusted for a variety of confounding factors. OUTCOME MEASURES/METHODS:Excess mortality risk in SGA and AGA babies. RESULTS:On an additive scale, stillbirth and neonatal mortality rates were higher at every preterm gestation among SGA than AGA births, and similar at term gestations. An inverse relationship between gestational age and excess deaths between SGA and AGA babies delivered at <37weeks was evident. CONCLUSIONS:In early preterm gestations, the definition of SGA may well be justified as a proxy for IUGR. In contrast, SGA babies that are delivered at term are likely to be constitutionally small.

OBJECTIVE: The objective of this study was to determine whether an expanded amniotic fluid cytokine profile predicts spontaneous preterm birth in patients with short cervix in the midtrimester. STUDY DESIGN: Amniocentesis was performed on singleton gestations between 16-24 weeks with a cervical length <or=25 mm. Amniotic fluid from patients who received no surgical or hormonal treatment was assayed for 25 cytokines. Univariate analysis identified cytokine(s) that correlated with the interval between amniocentesis to delivery. Stepwise regression identified which cytokine(s) was most predictive of delivery, followed by the generation of receiver-operator characteristic curves. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated. RESULTS: Forty-four amniotic fluid samples were analyzed. After stepwise regression, only monocyte chemotactic protein-1 remained significant and was the most predictive of early delivery. With a cutoff of 1320 pg/mL, monocyte chemotactic protein-1 had a 69% sensitivity, 83% specificity, 36% positive predictive value, and 87% negative predictive value to predict spontaneous preterm birth within 1 week of amniocentesis (P = .015). CONCLUSION: Among 25 cytokines, monocyte chemotactic protein-1 was most predictive of spontaneous preterm birth

BACKGROUND:We explored the incidence of thromboembolic disease in relatives of women diagnosed with placental abruption, a condition that may be related to disordered coagulation. METHODS:Using data from a multicenter, case-control study of placental abruption, we assessed thromboembolic diseases in first-degree male and female relatives of women with and without abruption. The analysis was restricted to biologic parents and full siblings, below 65 years of age, and corrected for familial clustering. RESULTS:The prevalence of thromboembolic disease was 7.5% in 852 relatives of 212 placental abruption cases and 4.8% in 792 relatives of 206 controls. This increased risk was driven by an association among sisters of abruption probands (odds ratio = 6.8 [95% confidence interval = 1.8-26.0]), and to a lesser extent, among mothers (2.0 [1.0-4.2]). The risk of thromboembolic diseases was similar among the male relatives of placental abruption cases and controls. CONCLUSIONS:These data suggest that thromboembolic diseases aggregate within female relatives of women with placental abruption.

OBJECTIVE:Patterns of recurrence of restricted fetal growth provide important insights to understand the relative contributions of genetic versus environmental influences. Although there is evidence of increased tendency of small for gestational age (SGA) births to recur, whether similar patterns of recurrence in twins among women that delivered a prior singleton SGA birth remains poorly studied. METHODS:We used Missouri's maternally-linked data (1978-1997), and restricted the analysis to women that delivered their first two consecutive live births. SGA (birthweight <10th and <5th centile for gestational age) recurrence was examined in two distinct analyses: women that delivered their first two singleton live births (n = 305,654) and those that delivered their first singleton live birth followed by twin live births (n = 8594). Sib-sib pairwise odds ratio (pOR) were estimated from bivariate logistic regression with robust variance estimation after adjustments for confounders. RESULTS:Risks of SGA were 24.3% and 6.1% in the second singleton birth among women with and without a previous singleton SGA, respectively (pOR 3.9, 95% CI 3.7-4.0). The corresponding risks among twins with and without a previous singleton SGA birth were 16.9% and 6.7%, respectively (pOR 2.3, 95% CI 1.8-2.8). In the singleton-singleton cohort, the highest recurrence risk for SGA occurred around the same gestational age window as the first singleton SGA birth. These associations were stronger for more severe forms of SGA (<5th centile). CONCLUSIONS:The likelihood of SGA to recur within sibships is strong, with varying magnitude of risks between singleton-singleton and singleton-twin births.

OBJECTIVE: We sought to determine the relationship between the degree of cervical shortening and intraamniotic inflammation in patients presenting with a midtrimester short cervix. STUDY DESIGN: Amniocentesis was performed on singleton pregnancies between 16-24 weeks' gestation with a sonographic cervical length (CL) 1500 pg/mL, CL of 5 mm had an 86% sensitivity, 85% specificity, 58% positive predictive value, and 96% negative predictive value to predict elevated MCP-1 levels. After excluding patients with intraamniotic infection or labor, findings were similar. CONCLUSION: CL