Elizabeth Thom

The relationship of the factor V Leiden mutation and pregnancy outcomes for mother and fetus.

Objective: We sought to estimate the frequency of pregnancy-related thromboembolic events among carriers of the factor V Leiden (FVL) mutation without a personal history of thromboembolism, and to evaluate the impact of maternal and fetal FVL mutation carriage or other thrombophilias on the risk of adverse outcomes. Methods: Women with a singleton pregnancy and no history of thromboembolism were recruited at 13 clinical centers before 14 weeks of gestation from April 2000 to August 2001. Each was tested for the FVL mutation, as was the resultant conceptus after delivery or after miscarriage, when available. The incidence of thromboembolism (primary outcome), and of other adverse outcomes, was compared between FVL mutation carriers and noncarriers. We also compared adverse outcomes in a secondary nested carrier-control analysis of FVL mutation and other coagulation abnormalities. In this secondary analysis, we defined carriers as women having one or more of the following traits: carrier for FVL mutation, protein C deficiency, protein S deficiency, antithrombin III deficiency, activated protein C resistance, or lupus anticoagulant-positive, heterozygous for prothrombin G20210A or homozygous for the 5,10 methylenetetrahydrofolate reductase mutations. Carriers of the FVL mutation alone (with or without activated protein C resistance) were compared with those having one or more other coagulation abnormalities and with controls with no coagulation abnormality. Results: One hundred thirty-four FVL mutation carriers were identified among 4,885 gravidas (2.7%), with both FVL mutation status and pregnancy outcomes available. No thromboembolic events occurred among the FVL mutation carriers (0%, 95% confidence interval 0–2.7%). Three pulmonary emboli and one deep venous thrombosis occurred (0.08%, 95% confidence interval 0.02–0.21%), all occurring in FVL mutation noncarriers. In the nested carrier-control analysis (n = 339), no differences in adverse pregnancy outcomes were observed between FVL mutation carriers, carriers of other coagulation disorders, and controls. Maternal FVL mutation carriage was not associated with increased pregnancy loss, preeclampsia, placental abruption, or small for gestational age births. However, fetal FVL mutation carriage was associated with more frequent preeclampsia among African-American (15.0%) and Hispanic (12.5%) women than white women (2.6%, P = .04), adjusted odds ratio 2.4 (95% confidence interval 1.0–5.2, P = .05). Conclusion: Among women with no history of thromboembolism, maternal heterozygous carriage of the FVL mutation is associated with a low risk of venous thromboembolism in pregnancy. Neither universal screening for the FVL mutation, nor treatment of low-risk carriers during pregnancy is indicated. Level of Evidence: II-2

Frequency of congenital varicella syndrome in a prospective cohort of 347 pregnant women

OBJECTIVE To estimate the rate of congenital varicella zoster virus syndrome in neonates born to women developing varicella zoster virus infections during pregnancy. METHODS Pregnant women with clinical varicella zoster virus infection were enrolled at ten perinatal centers. Maternal and fetal immunoglobulin (Ig) G and IgM by fluorescent antibody confirmed 74.3% of cases. Specialists examined neonates at 0–6 months, 7–18 months, and 19–30 months after delivery to detect abnormalities of their eyes, hearing, and physical and developmental features. A hierarchical set of criteria was used to define congenital varicella syndrome. A jury of four investigators assigned the classification of all findings. RESULTS In 362 women enrolled from 1993 to 1996, 15 had herpes zoster, and 347 had primary varicella zoster virus infection. Varicella zoster virus affected 140 women (38.7%) in the first trimester, 122 (33.7%) in the second trimester, and 100 (27.6%) in the third trimester. Five twin pairs were included. Only one case (0.4%) of definite congenital varicella syndrome was found, a 3360‐g female infant having a left retinal macular lesion with typical skin scars after maternal varicella at 24 weeks. The maternal blood sample at birth was negative for IgG antibodies to toxoplasmosis and cytomegalovirus. Two cases involved fetal death at 20 weeks and fetal hydrops at 17 weeks after maternal varicella at 11 and 5 weeks, respectively. We found no cases of limb hypoplasia, microcephalus, or cataract. CONCLUSION The frequency of congenital varicella syndrome is very low (0.4%) in a prospectively studied cohort. Eye examinations of exposed infants had a low yield.

Preterm Prediction Study: Comparison of the Cervical Score and Bishop Score for Prediction of Spontaneous Preterm Delivery

OBJECTIVE: To prospectively compare digital cervical score with Bishop score as a predictor of spontaneous preterm delivery before 35 weeks of gestation. METHODS: Data from a cohort of 2,916 singleton pregnancies enrolled in a multicenter preterm prediction study were available. Patients underwent digital cervical examinations at 22–24 and 26–29 weeks of gestation for calculation of Bishop score and cervical score. Relationships between Bishop score, cervical score, and spontaneous preterm delivery were assessed with multivariable logistic regression analysis, McNemar test, and receiver operating characteristic (ROC) curves to identify appropriate diagnostic thresholds and predictive capability. RESULTS: One hundred twenty-seven of 2,916 patients (4.4%) undergoing cervical examination at 22–24 weeks had a spontaneous preterm delivery before 35 weeks. Eighty-four of the 2,538 (3.3%) reexamined at 26–29 weeks also had spontaneous preterm delivery. Receiver operating characteristic curves indicated that optimal diagnostic thresholds for Bishop score were at least 4 at 22–24 weeks, at least 5 at 26–29 weeks, and less than 1.5 at both examinations for cervical score. At 22–24 weeks, areas under the ROC curve favored Bishop score. At 26–29 weeks, there was no significant difference in areas under the ROC curve; however, a cervical score less than 1.5 (sensitivity 35.7%, false positive rate 4.8%) was superior to a Bishop score of 5 or more (P<.001). CONCLUSION: Both cervical evaluations are associated with spontaneous preterm delivery in a singleton population; however, predictive capabilities for spontaneous preterm delivery were modest among women with low event prevalence. Although Bishop score performed better in the mid trimester, by 26–29 weeks a cervical score less than 1.5 was a better predictor of spontaneous preterm delivery before 35 weeks than a Bishop score of at least 5. LEVEL OF EVIDENCE: II

Absence of Mitochondrial Progesterone Receptor Polymorphisms in Women With Spontaneous Preterm Birth

Objective: The truncated mitochondrial progesterone receptor (PR-M) is homologous to nuclear PRs with the exception of an amino terminus hydrophobic membrane localization sequence, which localizes PR-M to mitochondria. Given the matrilineal inheritance of both spontaneous preterm birth (SPTB) and the mitochondrial genome, we hypothesized that (a) PR-M is polymorphic and (b) PR-M localization sequence polymorphisms could result in variable progesterone-mitochondrial effects and variable responsiveness to progesterone prophylaxis. Methods: Secondary analysis of DNA from women enrolled in a multicenter, prospective, study of 17 alpha-hydroxyprogesterone caproate (17OHPC) versus placebo for the prevention of recurrent SPTB. DNA was extracted from stored saliva. Results: The PR-M localization sequence was sequenced on 344 patients. Sequences were compared with the previously published 48 base-pair sequence, and all were identical. Conclusions: We did not detect genetic variation in the mitochondrial localization sequence of the truncated PR-M in a group of women at high risk for SPTB.

Steering Committee of the Eunice Kennedy Shriver National Institute of Child Health and Human Development's (NICHD) Maternal-Fetal Medicine Units Network

found only in women with endometriosis. A double-blind trial to assess in more detail the place of endometrial biopsy for the diagnosis of endometriosis in women with pelvic pain or infertility is currently underway. f Moamar Al-Jefout, MD Ian Fraser, MD Department of Obstetrics and Gynaecology Queen Elizabeth II Research Institute for Mothers and Infants University of Sydney Sydney, NSW, 2006, Australia aljefoutmr@yahoo.co.uk