Adherence to criteria for transvaginal ultrasound imaging and measurement of cervical length.

OBJECTIVE: Adherence to published criteria for transvaginal imaging and measurement of cervical length is uncertain. We sought to assess adherence by evaluating images submitted to certify research sonographers for participation in a clinical trial. STUDY DESIGN: We reviewed qualifying test results of sonographers seeking certification to image and measure cervical length in a clinical trial. Participating sonographers were required to access training materials and submit 15 images, 3 each from 5 pregnant women not enrolled in the trial. One of 2 sonologists reviewed all qualifying images. We recorded the proportion of images that did not meet standard criteria (excess compression, landmarks not seen, improper image size, or full maternal bladder) and the proportion in which the cervical length was measured incorrectly. Failure for a given patient was defined as >1 unacceptable image, or >2 acceptable images with incorrect caliper placement or erroneous choice of the "shortest best" cervical length. Certification required satisfactory images and cervical length measurement from ≥4 patients. RESULTS: A total of 327 sonographers submitted 4905 images. A total of 271 sonographers (83%) were certified on the first, 41 (13%) on the second, and 2 (0.6%) on the third submission. Thirteen never achieved certification. Of 314 who passed, 196 submitted 15 acceptable images that were appropriately measured for all 5 women. There were 1277 deficient images: 493 were acceptable but incorrectly measured images from sonographers who passed certification because mismeasurement occurred no more than twice. Of 784 deficient images submitted by sonographers who failed the certification, 471 were rejected because of improper measurement (caliper placement and/or failure to identify the shortest best image), and 313 because of failure to obtain a satisfactory image (excessive compression, required landmarks not visible, incorrect image size, brief examination, and/or full maternal bladder). CONCLUSION: Although 83% of sonographers were certified on their first submission, >1 in 4 ultrasound images submitted did not meet published quality criteria. Increased attention to standardized education and credentials is warranted for persons who perform ultrasound examinations of the cervix in pregnancy.

Proteomic identification of serum peptides predicting subsequent spontaneous preterm birth.

OBJECTIVE: We sought to identify serum markers of subsequent spontaneous preterm birth (SPTB) in asymptomatic women prior to labor. STUDY DESIGN: Serum proteomics was applied to sera from 80 pregnant women sampled at 24 weeks and an additional 80 pregnant women sampled at 28 weeks. Half had uncomplicated pregnancies and half had SPTB. RESULTS: Three specific peptides arising from inter-alpha-trypsin inhibitor heavy chain 4 protein were significantly reduced in women at 24 and 28 weeks having subsequent SPTB. The most discriminating peptide had a sensitivity of 65.0% and specificity of 82.5%; odds ratio, 8.8; and 95% confidence interval, 3.1-24.8. A combination of the 3 new biomarkers and 6 previously studied biomarkers increased sensitivity to 86.5%, with a specificity of 80.6% at 28 weeks. CONCLUSION: Three novel serum markers of SPTB have been identified using serum proteomics. Using a combination of these new markers with additional markers, women at risk of SPTB can be identified weeks prior to SPTB.

The relationship between resolution of asymptomatic bacterial vaginosis and spontaneous preterm birth in fetal fibronectin-positive women.

OBJECTIVE: The purpose of this study was to determine the impact of persistent bacterial vaginosis (BV) on the occurrence of spontaneous preterm birth (SPB) in women who test positive for fetal fibronectin. STUDY DESIGN: This is a secondary analysis of a subset of pregnant women who tested positive for BV and fetal fibronectin between 16(0/7) and 25(6/7) weeks of gestation and who participated in randomized placebo controlled trials of antibiotic therapy. Nugent's criteria were used for the diagnosis of BV. Patients were reassessed for the presence of BV after treatment. The rate of SPB at <34 weeks of gestation was analyzed on the basis of treatment mode and BV status at the follow-up visit. RESULTS: The primary studies included a total of 3285 women. A subset of 215 women met the criteria for this analysis. Seventy-seven of 100 patients (77%) in the antibiotics group vs 33 of the 115 patients (28.7%) in the placebo group became BV negative (P < .0001). The rate of SPB at <34 weeks of gestation was lower for BV resolution compared with persistent BV (0 vs 5.7%, respectively; P = .01). CONCLUSION: In women who tested positive for fetal fibronectin and BV, resolution of BV is associated with less SPB before 34 weeks of gestation.

Is there a seasonal variation in the diagnosis of oligohydramnios?

OBJECTIVE: We hypothesized that oligohydramnios would be diagnosed more frequently in the warm summer months when dehydration might be more common. METHODS: The clinical diagnosis of oligohydramnios was extracted from the databases of four completed National Institute of Child Health and Human Development Maternal Fetal Medicine Units Network protocols. These data were stratified by quarter of delivery and compared using Fisher's Exact Test. RESULTS: The clinical diagnosis of oligohydramnios was made more frequently in deliveries occurring in the summer months of June, July and August as compared with the remainder of the calendar year (7.2% vs 5.9%, p=0.0178). CONCLUSIONS: In these studies the diagnosis of oligohydramnios is made more frequently in those pregnancies delivered during the summer months. Although not proven by this association, maternal dehydration may contribute to this finding.

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.

Effect of smoking on circulating angiogenic factors in high risk pregnancies.

OBJECTIVE: Changes in maternal concentrations of the anti-angiogenic factors, soluble fms-like tyrosine kinase 1 (sFlt1) and soluble endoglin (sEng), and the pro-angiogenic placental growth factor (PlGF) precede the development of preeclampsia in healthy women. The risk of preeclampsia is reduced in women who smoke during pregnancy. The objective of this study was to investigate whether smoking affects concentrations of angiogenic factors (sFlt1, PlGF, and sEng) in women at high risk for developing preeclampsia. STUDY DESIGN: We performed a secondary analysis of serum samples from 993 high-risk women (chronic hypertension, diabetes, multifetal gestation, and previous preeclampsia) in a preeclampsia prevention trial. sFlt1, sEng and PlGF were measured in serum samples obtained at study entry, which was prior to initiation of aspirin (median 19.0 weeks' [interquartile range of 16.0-22.6 weeks']). Smoking status was determined by self-report. RESULTS: sFlt1 was not significantly different in smokers from any high-risk groups compared to their nonsmoking counterparts. PlGF was higher among smokers compared to nonsmokers among diabetic women (142.7 [77.4-337.3] vs 95.9 [48.5-180.7] pg/ml, p = 0.005) and women with a history of preeclampsia (252.2 [137.1-486.0] vs 152.2 [73.6-253.7] pg/ml, p = 0.001). sEng was lower in smokers with multifetal gestations (5.8 [4.6-6.5] vs 6.8 [5.5-8.7] ng/ml, p = 0.002) and trended lower among smokers with diabetes (4.9 [3.8-5.6] vs 5.3 [4.3-6.3] ng/ml, p = 0.05). Smoking was not associated with a lower incidence of preeclampsia in any of these groups. CONCLUSIONS: In certain high-risk groups, smoking is associated with changes in the concentrations of these factors towards a pro-angiogenic direction during early pregnancy; however, there was no apparent association between smoking and the development of preeclampsia in our cohort.

Soluble fms-Like tyrosine kinase 1 (sFlt1), endoglin and placental growth factor (PlGF) in preeclampsia among high risk pregnancies.

BACKGROUND: Differences in circulating concentrations of antiangiogenic factors sFlt1 and soluble endoglin (sEng) and the pro-angiogenic growth factor PlGF are reported to precede the onset of preeclampsia weeks to months in low-risk pregnant women. The objective of this study was to investigate whether similar changes can be detected in pregnant women at high-risk to develop the syndrome. METHODS: This study is a secondary analysis of the NICHD MFMU trial of aspirin to prevent preeclampsia in high-risk pregnancies. Serum samples were available from 194 women with pre-existing diabetes, 313 with chronic hypertension, 234 with multifetal gestation, and 252 with a history of preeclampsia in a previous pregnancy. Samples collected across pregnancy were analyzed in a blinded fashion for sFlt1, sEng and PlGF. RESULTS: The odds of developing preeclampsia were significantly increased among women with multiple fetuses for each 2-fold elevation in sFlt1, sEng and the ratio of angiogenic factors (e.g. OR 2.18, 95% CI 1.46-3.32), and significantly decreased for each 2-fold elevation in circulating PlGF (OR 0.50, 95% CI 0.30-0.82) between 7 and 26 weeks' gestation. Cross-sectional analysis of the angiogenic factors across gestation showed significant differences during the third trimester in women who develop preeclampsia compared with appropriate controls in all high-risk groups. However, when data were examined in relation to the gestational week when preeclampsia was diagnosed only sFlt1 was significantly higher 2 to 5 weeks before the clinical onset of preeclampsia and only in women with previous preeclampsia. CONCLUSIONS: The pattern of elevated concentrations of sFlt1 and sEng, and low PlGF in high-risk pregnant subjects who develop preeclampsia is similar to that reported in low-risk pregnant women. However, differences in these factors among high-risk women who do and do not develop preeclampsia are modest, and do not appear to be clinically useful predictors in these high-risk pregnant women.

Is early-pregnancy proteinuria associated with an increased rate of preeclampsia in women with pregestational diabetes mellitus?

OBJECTIVE: The purpose of this study was to determine whether the rate of preeclampsia in pregnant diabetic women is increased in those women with early-pregnancy proteinuria of 190 to 499 mg/24 hours compared with women with proteinuria of <190 mg/24 hours. STUDY DESIGN: Secondary analysis was performed with relevant data from 194 pregnant women with type 1 and type 2 diabetes mellitus whose condition required insulin and who were enrolled previously in a multicenter trial of low-dose aspirin for the prevention of preeclampsia. The women were assigned to 1 of 3 groups, based on the level of proteinuria at enrollment (13-26 weeks of gestation). Group 1 comprised women with <190 mg protein/24 hours (n=94); group 2 comprised women with 190 to 499 mg protein/24 hours (n=35); and group 3 comprised women with >/=500 mg protein/24 hours (n=65). The rate of preeclampsia, according to strict predefined criteria, was then determined. RESULTS: The rate of preeclampsia was not increased statistically significantly in patients with early-pregnancy proteinuria of 190 to 499 mg/24 hours (7/35 women; 20%) when compared with women with proteinuria of <190 mg/24 hours (16/94 women; 17%). CONCLUSION: We did not find an increased rate of preeclampsia in women with pregestational diabetes mellitus with early-pregnancy proteinuria of 190 to 499 mg/24 hours when compared with women with pregestational diabetes mellitus with proteinuria of <190 mg/24 hours.

Risk factors and outcome of varicella-zoster virus pneumonia in pregnant women.

To determine the factors associated with an increased risk of developing varicella-zoster virus (VZV) pneumonia during pregnancy, a case-control analysis was done in which 18 pregnant women with VZV pneumonia were compared with 72 matched control subjects. VZV infection was identified clinically, and VZV pneumonia was diagnosed by dyspnea and findings on chest radiographs. Of 347 pregnant women with VZV infection, 18 (5.2%) had pneumonia treated with acyclovir, and none died. Mean gestational age at rash onset was 25.8 plus minus 8.8 weeks for patients with pneumonia and 17.7 +/- 10.3 weeks for control subjects, which was not significant in the multivariable model. Women with VZV pneumonia were significantly more likely to be current smokers (odds ratio [OR], 5.1; 95% confidence interval [CI], 1.6-16.7) and to have > or = 100 skin lesions (OR, 15.9; 95% CI, 1.9-130.2). Pregnant women with VZV infection may be more likely to develop varicella pneumonia if they are smokers or manifest > or = 100 skin lesions.