Moy Fong Chen

Stress Pathways to Spontaneous Preterm Birth: The Role of Stressors, Psychological Distress, and Stress Hormones

The authors investigated a large number of stressors and measures of psychological distress in a multicenter, prospective cohort study of spontaneous preterm birth among 5,337 Montreal (Canada)-area women who delivered from October 1999 to April 2004. In addition, a nested case-control analysis (207 cases, 444 controls) was used to explore potential biologic pathways by analyzing maternal plasma corticotrophin-releasing hormone (CRH), placental histopathology, and (in a subset) maternal hair cortisol. Among the large number of stress and distress measures studied, only pregnancy-related anxiety was consistently and independently associated with spontaneous preterm birth (for values above the median, adjusted odds ratio = 1.8 (95% confidence interval: 1.3, 2.4)), with a dose-response relation across quartiles. The maternal plasma CRH concentration was significantly higher in cases than in controls in crude analyses but not after adjustment (for concentrations above the median, adjusted odds ratio = 1.1 (95% confidence interval: 0.8, 1.6)). In the subgroup (n = 117) of participants with a sufficient maternal hair sample, hair cortisol was positively associated with gestational age. Neither maternal plasma CRH, hair cortisol, nor placental histopathologic features of infection/inflammation, infarction, or maternal vasculopathy were significantly associated with pregnancy-related anxiety or any other stress or distress measure. The biologic pathways underlying stress-induced preterm birth remain poorly understood.

A study of nerve fibers and histopathology of postsurgical, postinfectious, and endometriosis-related adhesions

Objective To evaluate the presence of nerve fibers and histopathology of endometriosis-related adhesions, postsurgical adhesions, and postinfectious adhesions in women with and without pelvic pain. Methods We evaluated the presence of nerve fibers and histopathology of endometriosis-related adhesions, postsurgical adhesions, and postinfectious adhesions in 50 women. The nerve fibers were identified by immunocytochemistry staining with an antibody to neurofilament. Results Nerve fibers were found in the intraabdominal adhesions in 39 of the total 50 patients with such adhesions (78%). There was no significant difference in the proportion and the mean nerve score in adhesions due to previous intra-abdominal infection, endometriosis, and previous uninfected intra-abdominal surgery. The degree of lymphocytes and edema in endometriosis-related adhesions was significantly higher than in postsurgical adhesions and postinfectious adhesions (P < .05). No difference was found in the amount of nerve fibers and the mean nerve score in adhesions from women with pelvic pain and from those without pelvic pain. Conclusion Nerve fibers are found commonly in intraabdominal adhesions, and their presence are not related to the underlying pathology or pelvic pain. Endometriosisrelated adhesions contain more inflammatory cells and tissue edema than postsurgical or postinfectious adhesions.

Inherited thrombophilia and preeclampsia within a multicenter cohort: the Montreal Preeclampsia Study.

OBJECTIVE We sought to evaluate the association between inherited thrombophilia and preeclampsia. STUDY DESIGN From a multicenter cohort of 5337 pregnant women, we prospectively identified 113 women who developed preeclampsia and selected 443 control subjects who did not have preeclampsia or nonproteinuric gestational hypertension. Blood samples were tested for DNA polymorphisms affecting thrombophilia (factor V Leiden mutation, prothrombin G20210A mutation, methylenetetrahydrofolate reductase C677T polymorphism), homocysteine, and folate levels, and placentae underwent pathological evaluation. RESULTS Thrombophilia was present in 14% of patients and 21% of control subjects (adjusted logistic regression odds ratio, 0.6; 95% confidence interval, 0.3-1.3). Placental underperfusion was present in 63% of patients vs 46% of control subjects (P < .001) and was more frequent in women with folate levels in the lowest quartile (P = .04), but was not associated with thrombophilia. CONCLUSION We did not find evidence to support an association between inherited thrombophilia and increased risk of preeclampsia. Placental underperfusion is associated with preeclampsia, but this does not appear to be consequent to thrombophilia.

Nerve Fibers and Histopathology of Endometriosis-Harboring Peritoneum

STUDY OBJECTIVE To evaluate the presence of nerve fibers and histopathology of normal peritoneum and endometriosis-harboring peritoneum. DESIGN Prospective, nonrandomized study (Canadian Task Force classification II-1). SETTING University hospital. MATERIALS Peritoneal specimen from 40 women with laparoscopic findings of endometriosis (24 confirmed histopathologically, group H, 16 diagnosed by laparoscopy, group L) and from 9 women with no endometriosis (controls). INTERVENTION Histopathologic examination of peritoneal specimens with nerve fibers identified by immunocytochemistry staining with an antibody to neurofilament. MEASUREMENTS AND MAIN RESULTS No differences in mean nerve score were seen among the three groups. Degrees of lymphocytic infiltration and mesothelial hyperplasia were higher in group H than in the other two groups (p <0.01 and <0.05, respectively). The degree of lymphocytic infiltration was significantly higher in group L than in the control group (p <0.05). There were no differences in all measurements between women in group H who experienced chronic pelvic pain and those who did not. CONCLUSION The presence of nerve fibers in peritoneum is not related to endometriosis. Endometriosis-harboring peritoneum contains more lymphocytic infiltration than normal peritoneum. (J Am Assoc Gynecol Laparosc 8(1):95-98, 2001)

Vasculopathic and thrombophilic risk factors for spontaneous preterm birth

BACKGROUND Mothers who give birth to preterm infants are at increased risk of mortality from coronary heart disease and stroke, but the biological pathways underlying these associations have not been explored. METHODS We carried out a case-control study nested in a large (n = 5337) prospective, multicentre cohort. All cohort women had an interview, examination and venipuncture at 24-26 weeks. Frozen plasma samples in spontaneous preterm births (n = 207) and 444 term controls were analysed for plasma homocysteine, folate, cholesterol (total, low-density lipoprotein and high-density lipoprotein) and thrombin-antithrombin (TAT) complexes. DNA was extracted and analysed for seven gene polymorphisms involved in thrombophilia or folate or homocysteine metabolism. Fresh placentas were fixed, stained and blindly assessed for histologic evidence of infarction and decidual vasculopathy. RESULTS High (above the median) plasma homocysteine and HDL cholesterol were significantly and independently associated with the risk of spontaneous preterm birth [adjusted odds ratios (OR)s = 1.9 (95% 1.1-3.3) and 0.5 (0.3-0.9), respectively]. A higher proportion of women with high homocysteine concentrations had decidual vasculopathy [(13.0 vs 6.8%; OR = 1.9 (1.1-3.5)], although the positive association between decidual vasculopathy and preterm birth did not achieve statistical significance [OR = 1.5 (0.9-2.7)]. No significant associations were observed with the DNA polymorphisms or with plasma TAT or folate levels. CONCLUSIONS Similar vasculopathic risk factors may underlie preterm birth and adult coronary heart disease and stroke.

Mid-trimester maternal plasma cytokines and CRP as predictors of spontaneous preterm birth.

Most previous studies of maternal cytokines and preterm birth have analyzed immunologic biomarkers after the onset of labor or membrane rupture; fewer have examined the systemic (blood) immune response prior to labor onset. We carried out a case-control study nested in a large (n=5337) prospective, multi-center cohort. Cohort women had an interview, examination, and venipuncture at 24-26 weeks. Frozen plasma samples in women with spontaneous preterm birth (n=207) and approximately 2 term controls per case (n=444) were analyzed using Luminex multianalyte profiling technology. Fresh placentas were fixed, stained, and blindly assessed for histologic evidence of infection/inflammation, decidual vasculopathy, and infarction, and vaginal swabs were analyzed for bacterial vaginosis and fetal fibronectin concentration. High maternal matrix metalloproteinase-9 (MMP-9) concentration, but none of the other cytokines or C-reactive protein (CRP), was significantly associated with spontaneous preterm birth [adjusted OR=1.7 (1.1-2.4)] and showed a dose-response relation across quartiles. No association was observed, however, between maternal MMP-9 and placental infection/inflammation, bacterial vaginosis, or vaginal fetal fibronectin concentration. Our results require confirmation in future studies but suggest that a systemic immune response implicating MMP-9 may have an etiologic role in spontaneous preterm birth.

Cryptophthalmos Syndrome with Bilateral Renal Agenesis

We conducted a postmortem study of an infant with the abortive form of the cryptophthalmos syndrome. He had syndactyly and anal atresia and also showed features of Potters (renal nonfunction) syndrome, including bilateral renal agenesis, pulmonary hypoplasia, and the typical facies. Histopathologic examination of both globes disclosed that the superior eyelid folds were partially replaced by skin that fused with the superior third of each cornea; there were also anomalies of the superior canaliculi and scarring of the corneas. We found no specific abnormality of the intraocular contents.

Antioxidant vitamins, long-chain fatty acids, and spontaneous preterm birth.

Background: Neither macro- nor micronutrient supplements have been clearly demonstrated to reduce the risk of preterm birth. However, there has been little attention to carotenoids, tocopherols, and long-chain fatty acids other than n-3 polyunsaturates. Methods: We conducted a case–control study nested in a large (n = 5337) prospective, multicenter cohort. All cohort women had an interview, examination, and venipuncture at 24–26 weeks’ gestation. Frozen plasma samples in spontaneous preterm births (n = 207) and approximately 2-term controls per case (n = 443) were analyzed for carotenoids, retinol, tocopherols, and long-chain fatty acids. Fresh placentas were fixed, stained, and assessed (without knowledge of pregnancy outcome) for histologic evidence of infection or inflammation, decidual vasculopathy, and infarction. Results: High (above the median) plasma concentrations of &agr;- and &bgr;-carotene, &agr;- and &bgr;-cryptoxanthin, and lycopene were all associated with reductions in risk of spontaneous preterm birth, with evidence of dose-response effects across quartiles. Modest increases in risk were observed with elevated total monounsaturated, total polyunsaturated, and total n-6 polyunsaturated long-chain fatty acids concentrations. Paradoxically, a high &ggr;-tocopherol concentration was associated with increased preterm birth risk (adjusted odds ratio = 1.8 [95% confidence interval = 1.2–2.6]). Only one of the studied micronutrients (lutein) was independently associated with a reduced risk of decidual vasculopathy (0.5 [0.3–0.9]). Conclusions: Carotenoids and long-chain fatty acids warrant further investigation in in vitro, animal, and human studies of preterm birth.

Placental mesenchymal dysplasia and an estimation of the population incidence

Placental mesenchymal dysplasia (PMD) is a rare placental malformation of as yet undetermined etiology. We report a single centers experience of this diagnosis and present an estimation of the population incidence. Within our institution, all placentae are examined within a pathology department that provides a dedicated perinatal service. In this study, we evaluated the incidence of PMD over a period of 18 years following the description and recognition of PMD as a pathological diagnosis. During the period 1991–2009, only two cases were identified amongst over 95 000 deliveries at our institution. This series of placental examinations is by far the largest in a normal population within which the occurrence of PMD is reported, and the resulting incidence of only 0.02 per 1000 deliveries is some 10 times less than that which has previously been estimated.

Hyperreactio luteinalis in association with multiple foetal malformations – a consequence of supra-physiological HCG?

Abstract Aim: Hyperreactio luteinalis (HL) is characterised by ovarian cystic enlargement that is associated with high levels of human chorionic gonadotropin (hCG). Here the possible effects of abnormally high hCG levels on foetal development are demonstrated. Method: We report a 28-year-old patient who was referred for evaluation of bilateral maternal ovarian enlargement in the second trimester. Abnormally elevated hCG (887,514 IU/L) was found with ultrasound examination identifying various foetal malformations. The karyotype was normal. Spontaneous abortion occurred at 20 weeks. Autopsy showed testicular hypertrophy with marked Leydig cell hyperplasia. The HL resolved with normalisation of the hCG levels following delivery. Conclusion: HL is a rare finding in normal pregnancies; the potential effects of abnormally elevated hCG on the foetus are discussed.