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Summary: Inflammation has been implicated in the mechanisms responsible for preterm and term parturition, as well as fetal injury. Out of all of the suspected causes of preterm labour and delivery, infection and/or inflammation is the only pathological process for which both a firm causal link with preterm birth has been established and a molecular pathophysiology defined. Inflammation has also been implicated in the mechanism of spontaneous parturition at term. Most cases of histopathological inflammation and histological chorioamnionitis, both in preterm and term labour, are sub-clinical in nature. The isolation of bacteria in the amniotic fluid, known as microbial invasion of the amniotic cavity, is a pathological finding; the frequency of which is dependent upon the clinical presentation and gestational age. There is a window of time during which it may be possible to detect a ‘molecular signature of inflammation’ by analysis of the transcriptome before histological evidence is observed. This article reviews the role of inflammation in preterm and term parturition. It is possible that modulation of inflammation using anti-inflammatory cytokines, corticoids, antioxidants and/or other factors may complement antibiotic therapy and limit fetal injury. [Copyright &y& Elsevier]

Objective: We sought to determine whether maternal/fetal single-nucleotide polymorphisms (SNPs) in candidate genes are associated with preterm prelabor rupture of membranes (pPROM). Study Design: A case-control study was conducted in patients with pPROM (225 mothers and 155 fetuses) and 599 mothers and 628 fetuses with a normal pregnancy; 190 candidate genes and 775 SNPs were studied. Single locus/haplotype association analyses were performed; false discovery rate was used to correct for multiple testing (q* = 0.15). Results: First, a SNP in tissue inhibitor of metalloproteinase 2 in mothers was significantly associated with pPROM (odds ratio, 2.12; 95% confidence interval, 1.47–3.07; P = .000068), and this association remained significant after correction for multiple comparisons. Second, haplotypes for Alpha 3 type IV collagen isoform precursor in the mother were associated with pPROM (global P = .003). Third, multilocus analysis identified a 3-locus model, which included maternal SNPs in collagen type I alpha 2, defensin alpha 5 gene, and endothelin 1. Conclusion: DNA variants in a maternal gene involved in extracellular matrix metabolism doubled the risk of pPROM. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to determine whether maternal/fetal single nucleotide polymorphisms (SNPs) in candidate genes are associated with spontaneous preterm labor/delivery. Study Design: A genetic association study was conducted in 223 mothers and 179 fetuses (preterm labor with intact membranes who delivered <37 weeks of gestation [preterm birth (PTB)]), and 599 mothers and 628 fetuses (normal pregnancy); 190 candidate genes and 775 SNPs were studied. Single locus/haplotype association analyses were performed; the false discovery rate was used to correct for multiple testing. Results: The strongest single locus associations with PTB were interleukin-6 receptor 1 (fetus; P = .000148) and tissue inhibitor of metalloproteinase 2 (mother; P = .000197), which remained significant after correction for multiple comparisons. Global haplotype analysis indicated an association between a fetal DNA variant in insulin-like growth factor F2 and maternal alpha 3 type IV collagen isoform 1 (global, P = .004 and .007, respectively). Conclusion: An SNP involved in controlling fetal inflammation (interleukin-6 receptor 1) and DNA variants in maternal genes encoding for proteins involved in extracellular matrix metabolism approximately doubled the risk of PTB. [Copyright &y& Elsevier]

Objective: Patients with an episode of preterm labor that subsides in response to tocolysis and who, subsequently, deliver at term are considered to have false preterm labor. However, the episode of “preterm labor” may represent the uterine response (ie, uterine contractions) to an insult not severe enough to trigger preterm parturition, but which may put the fetus at risk for additional pregnancy complications, including growth restriction. The objective of this study was to compare the frequency of small-for-gestational-age (SGA) neonates among patients with an episode of increased uterine contractility who delivered at term and those who delivered preterm. Study Design: This retrospective cohort study included 849 patients. Inclusion criteria were (1) regular uterine contractions that required hospitalization, (2) intact membranes, and (3) gestational age between 20 and 36 weeks. SGA was defined as a birth weight of <10th percentile for gestational age. Placental pathologic evidence was reviewed, and the results were used to classify patients into an inflammatory cluster, vascular cluster, or both. Contingency tables, Mann-Whitney U test, and multivariate logistic regression were used for statistical analyses. A probability value of <.05 was considered significant. Results: The prevalence of SGA neonates in the study population was 16.1% (124/772). Patients who delivered at term had a significantly higher frequency of SGA neonates than those who delivered preterm (21.5% [64/298] vs 12.7% [60/474]; P = .001); the results of placental pathologic evidence were available in 63.7% (492/772) of the patients. Patients who delivered at term had a higher frequency of fetal or maternal vascular lesions without histologic evidence of inflammation than those who delivered preterm (29.1 % [43/148] vs 18.9% [65/344]; P = .01). Term delivery after an episode of regular preterm uterine contractions was associated with an odds ratio of 2.22 (95% CI, 1.28-3.85) to deliver an SGA neonate after the statistics were controlled for confounding variables. A subanalysis limited to patients who received tocolysis showed similar results. Conclusion: Patients with an episode of increased uterine contractility that subsided and who deliver at term are at risk for delivering an SGA neonate, which suggests that an episode of false preterm labor is not a benign condition. We propose that insults to the fetoplacental unit may be resolved by either irreversible preterm parturition or restriction of fetal growth. [Copyright &y& Elsevier]

Abstract: The objective of this study was to determine if very early ultrasonographic measurements obtained from human and baboon are comparable. For this purpose, the gestational, amniotic and yolk sacs, embryonic crown rump length (CRL) and heart rate were measured ultrasonographically between 35 and 47 days from the mean day of a three-day mating period in baboons (n = 18) and between 42 to 58 days from fertilization as calculated from the CRL measurements in human pregnancies (n = 82). Ultrasonographic measurements from both species were then plotted in the same graph using Carnegie stages of embryonic development as the independent variable to allow for visual comparisons. Mean gestational age at ultrasonographic studies was significantly different for humans and baboons (50.4 vs. 41 days, respectively; p > 0.01). Significant correlations (p > 0.01) were noted between ultrasonographic measurements and Carnegie stages of development in both humans and baboons. Only the gestational and the yolk sacs were significantly smaller in baboons than in humans (p > 0.05). The findings that embryonic CRL, extra-embryonic space and heart rate are very similar between the 17th and 23rd Carnegie developmental stages make the baboon a promising surrogate of human pregnancy for investigations using celocentesis. (E-mail: jsantolaya@partners.org) [Copyright &y& Elsevier]