Likelihood ratios for fetal trisomy 21 based on nasal bone length in the second trimester: how best to define hypoplasia?

OBJECTIVE: To determine the best measure of fetal nasal bone hypoplasia for trisomy 21 risk assessment in the second trimester. METHODS: This was a prospective, observational study performed at a single institution between February 2003 and December 2005. Fetuses with nasal bone length recorded sonographically between 16 and 20.9 weeks and known karyotype were included. Definitions of nasal bone hypoplasia assessed included: non-visualized nasal bone, nasal bone < 10th percentile, nasal bone < 2.5th percentile, biparietal diameter/nasal bone ratio >or= 10 and >or= 11 and nasal bone multiples of the median (MoM)

Relationships between maternal plasma leptin, placental leptin mRNA and protein in normal pregnancy, pre-eclampsia and intrauterine growth restriction without pre-eclampsia.

Leptin, an adipocyte hormone involved in energy homeostasis, is important in reproduction and pregnancy. Questions yet to be addressed include the source of higher leptin during pregnancy and its relationship to pregnancy outcome and fetal growth. The objective of this study was to investigate the relationship between placental leptin gene expression, placental leptin protein concentration and maternal plasma leptin concentration among control pregnant women, women with pre-eclampsia and women with growth-restricted infants. We also investigated the relationship between placental leptin expression and the placental expression of enzymes involved in cellular lipid balance: fatty acid translocase (CD36), carnitine palmitoyltransferase I (CPT-1B) and lipoprotein lipase (LPL). Placental leptin expression, placental protein and maternal plasma concentration were higher in pre-eclampsia than in controls but not in women with growth-restricted infants. Placental leptin expression and placental protein were higher in the preterm pre-eclamptic subjects, whereas maternal leptin was higher in the term pre-eclamptic subjects. The placental gene expression of CD36, CPT-1B and LPL were not different among the groups. This study suggests that despite similar failed placental bed vascular remodelling in pre-eclampsia and intrauterine growth restriction (IUGR), leptin gene expression is higher only in preterm pre-eclampsia.

Homocysteine and cellular fibronectin are increased in preeclampsia, not transient hypertension of pregnancy.

OBJECTIVE: The objective of this study was to confirm that endothelial dysfunction is present in preeclampsia and absent in transient hypertension of pregnancy, and to determine whether the cardiovascular risk factor homocysteine is associated with the degree of endothelial dysfunction. METHODS: We measured cellular fibronectin (as a marker of endothelial injury) and total plasma homocysteine in samples collected at the time of admittance to labor and delivery in 17 women with preeclampsia (increased blood pressure, proteinuria, and hyperuricemia), 16 women with transient hypertension of pregnancy (only increased blood pressure), and 34 normal pregnant women. Each subject with preeclampsia was matched by prepregnancy body mass index, race, and gestational age at delivery to one subject with transient hypertension of pregnancy and two controls. RESULTS: Cellular fibronectin was found to be significantly increased in women with preeclampsia compared to subjects with transient hypertension of pregnancy or normal pregnant women (22.9 +/- 14.1 microg/mL versus 10.9 +/- 5.4 and 10.1 +/- 6.2 microg/mL, respectively, p<0.0001). Similarly, total plasma homocysteine was also significantly increased in the women with preeclampsia compared to subjects with transient hypertension of pregnancy or normal pregnant women (8.3 +/- 2.5 microM versus <5.5 +/- 2.2 and 5.4 +/- 3.4 microM respectively, p<0.01). However, contrary to our hypothesis, there was no apparent association between cellular fibronectin and homocysteine. CONCLUSIONS: The increased concentrations of homocysteine observed in preeclampsia are not a general feature of all hypertensive complications of pregnancy. Furthermore, endothelial dysfunction is present in preeclampsia and is not evident in transient hypertension of pregnancy. However, the apparent endothelial dysfunction in preeclampsia is not explained by the increase in homocysteine concentrations observed.

Free leptin is increased in normal pregnancy and further increased in preeclampsia.

We measured bound and free leptin levels in preeclamptic and matched normal pregnant and never-pregnant women to determine whether the free component of leptin is increased during pregnancy and further increased in preeclampsia. Two milliliters of serum was obtained from 18 normal and 18 preeclamptic patients matched by pre-pregnancy body mass index (BMI), and from 18 never-pregnant women matched by BMI with the pregnant groups. The sample was subjected to gel filtration using Sephadex G-100. Radioimmunoassay (RIA) was performed on all fractions, and the proportions of bound and free leptin were determined by analyzing the areas under the curve of the chromatographic profile. The total maternal serum leptin concentration was significantly higher in normal pregnancy compared with the nonpregnant state and was further increased in preeclampsia (33.8 +/- 4.1 v 15.2 +/- 1.8 ng/mL, P = .002, and 48.1 +/- 5.6 ng/mL, P = .02, respectively). Free leptin was increased in normal pregnant compared with never-pregnant women (25.9 +/- 4.1 v 11.0 +/- 2.0 ng/mL, respectively, P = .01), while the increase of total leptin in preeclampsia was exclusively in the free fraction that was significantly higher versus the normal pregnant group (41.8 +/- 5.6 v25.9 +/- 4.1 ng/mL, respectively, P = .01). The bound leptin fraction, by contrast, was significantly increased in the normal pregnant group compared with the preeclamptic group and the never-pregnant group (7.9 +/- 0.56 v 6.2 +/- 0.36 and 4.1 +/- 0.36 ng/mL, respectively, P = .009 and P = <.0001). In conclusion, the free leptin concentration increases in normal pregnancy and is further increased in preeclampsia. This supports the hypothesis that biologically active leptin is elevated in normal pregnancy and is increased more in women with preeclampsia.

Urinary cotinine concentration confirms the reduced risk of preeclampsia with tobacco exposure.

OBJECTIVE: We assessed tobacco exposure in nulliparous women with preeclampsia compared with that in control subjects by measuring urinary cotinine to confirm the reduced risk of preeclampsia associated with tobacco exposure during pregnancy. STUDY DESIGN: A case-control study group of 50 women with preeclampsia after 35 weeks of gestation and a group of 50 control subjects matched for gestational age, date of delivery, and body mass index were selected from the project database. Urine obtained on admission was assayed for cotinine. Self-reported smoking information was blinded during patient selection and laboratory assay. RESULTS: Thirty-five patients had detectable urinary cotinine levels, 11 (22%) with preeclampsia and 24 (48%) control women. Mean cotinine concentrations among exposed women were 331 ng/mL for those with preeclampsia and 540 ng/mL for control subjects. The odds ratio of preeclampsia developing in an exposed woman was 0.31 (95% confidence interval, 0.12-0.79). CONCLUSION: These findings, obtained by using laboratory assay, confirm the reduced risk of developing preeclampsia with tobacco exposure.

Methylenetetrahydrofolate reductase polymorphism, folate, and susceptibility to preeclampsia.

OBJECTIVES: To test the hypothesis that the common missense mutation of 5,10-methylenetetrahydrofolate reductase (MTHFR) (677 C to T, ala to val) is more prevalent among nulliparous preeclamptic women compared with control and transient hypertension of pregnancy patients. The correlation of the MTHFR T677/T677 genotype in mothers and fetuses was also investigated to test for possible maternal-fetal interactions. Lastly, possible differences in serum folate concentrations between control and preeclampsia patients and the possibility of a correlation between serum folate and MTHFR genotype were investigated as well. METHODS: The MTHFR genotype was determined for 114 control subjects, 99 preeclamptic patients, and 24 patients with transient hypertension of pregnancy by a polymerase chain reaction/restriction fragment length polymorphism (PCR) method. To ensure homogeneity of ethnic background, only samples from white women were analyzed. Results were analyzed with a chi 2 test for homogeneity. Serum folate was determined by radioimmunoassay (RIA). RESULTS: The prevalence of the MTHFR T677/T677 genotype was not significantly different between the populations studied. There was no significant difference in the prevalence of the MTHFR T677/T677 genotype between the infants of preeclamptic and control mothers. Furthermore, there was no difference in serum folate concentrations between control and preeclampsia patients, and there was no correlation between serum folate and MTHFR genotype. CONCLUSION: These data suggest that contrary to previous published reports, the C677T missense mutation of MTHFR is not a risk factor for preeclampsia in this nulliparous patient population. Furthermore, this mutation is not related to serum folate status in late pregnancy.

Plasma homocysteine concentration is increased in preeclampsia and is associated with evidence of endothelial activation.

OBJECTIVE: We tested the hypothesis that the independent risk factor for atherosclerosis of increased plasma homocysteine concentration is associated with the pregnancy syndrome of preeclampsia. We further hypothesized that increased plasma homocysteine concentration during pregnancy may advance endothelial dysfunction in preeclampsia by promoting oxidative stress. STUDY DESIGN: Antepartum blood samples were collected >/=6 hours after the last meal from 33 women with normal, uncomplicated pregnancies and from 21 women with preeclampsia. These plasma samples were analyzed for concentrations of total homocysteine; folate; triglycerides; creatinine; a marker of endothelial activation, cellular fibronectin; and a marker of oxidative stress, malondialdehyde. RESULTS: The mean value of total plasma homocysteine in preeclampsia was significantly higher than that observed in normal pregnancy (P <. 04). Similarly, plasma malondialdehyde (P <.001), triglyceride (P <. 001), and cellular fibronectin (P <.006) concentrations were also greater in women with preeclampsia than in control subjects. However, no differences were observed between women with preeclampsia and control subjects in folate (P =.97) or creatinine (P =.28) concentrations. Homocysteine concentration did not correlate with plasma creatinine (P =.61), malondialdehyde (P =.32), or triglyceride (P =.89) concentrations. However, cellular fibronectin concentration correlated positively with homocysteine concentration in both women with preeclampsia and control subjects (r = 0.87, P <. 0001, and r = 0.50, P <.004, respectively), and folate concentrations were weakly but negatively correlated with homocysteine values (P =.03, r = 0.32). CONCLUSIONS: Total plasma homocysteine concentration is increased in preeclampsia and is significantly correlated with cellular fibronectin concentration, suggesting that homocysteine plays a role in promoting endothelial dysfunction in preeclampsia. Furthermore, despite the use of pregnancy multivitamins and no indications of overt folate deficiency in this subject population, homocysteine concentration weakly and negatively correlates with plasma folate concentration.

Reproductive Genetic Counseling to Asian-Pacific and Latin American Immigrants.

Latin and Asian-Pacific immigrants are the fastest growing new-comer groups in the U.S. contributing to 85% of immigration totals. New immigrants experience multiple barriers to accessing genetic counseling resulting from cultural, linguistic, financial, and educational factors as well as having unique perceptions on health, illness, reproduction, and life as a whole. In addition, new immigrants lack familiarity with Western medical practices as well as genetic risk and available interventions. We provided perinatal genetic services to 2430 clients, mostly new immigrants of Latin and Asian-Pacific descent over a period of 6 years. Counseling aides sharing the clients' cultural backgrounds were employed. A study assessing the efficacy of cross-cultural education regarding advanced maternal age risk and amniocentesis was implemented and linked to a database containing demographic and clinical information. Practical observations relating to cultural beliefs in the two groups relevant to perinatal genetic counseling were made.

Parturients infected with human immunodeficiency virus and regional anesthesia. Clinical and immunologic response.

BACKGROUND: It is estimated that 1.5 million Americans are infected with the human immunodeficiency virus (HIV-1), and the consequences of HIV infection are a leading cause of death in women aged 15-44 yr. Thus, HIV-1 disease, or acquired immunodeficiency syndrome, occurs with increasing frequency in the parturient, and there is little information concerning the risks of regional anesthesia. Fear of spreading infection to the central nervous system or adverse neurologic sequelae have led some clinicians to advise against regional anesthesia. Thus, this study was undertaken to evaluate the possible problems or risks associated with regional anesthesia in parturients infected with HIV-1 and to determine whether anesthesia affected the clinical course of the disease. METHODS: The clinical course and immunologic function of 30 parturients infected with HIV-1 were evaluated prospectively. Extensive medical and laboratory evaluation before delivery and 4-6 months postpartum was undertaken. Medical problems related to HIV-1 disease and use of antiviral drugs also were monitored. The anesthetic management was dictated by the clinical situation and the patient's wishes were careful postpartum follow-up to evaluate possible neurologic changes or infection. RESULTS: Regional anesthesia was administered in 18 parturients, and 12 received small doses of opioids or no analgesia. There were no changes in the immunologic parameters studied (CD4+, p24, beta 2 microglobulins), and HIV-1 disease remained stable in the peripartum period. There were no infections, complications, or neurologic changes in the peripartum period. Sixty-eight percent of the infants were HIV-1-negative and, in 21% of infants, the HIV-1 status was indeterminate (probably negative). CONCLUSIONS: This prospective study of parturients infected with HIV-1 demonstrated that regional anesthesia can be performed without adverse sequelae. There were no neurologic or infectious complications related to the obstetric or anesthetic course. The immune function of the parturient was stable in the peripartum period. Although the number of patients studied was small, with careful medical evaluation, regional anesthesia is an acceptable choice in the parturient infected with HIV-1.

Randomized comparison of ampicillin-sulbactam to cefoxitin and doxycycline or clindamycin and gentamicin in the treatment of pelvic inflammatory disease or endometritis.

OBJECTIVE: To evaluate the efficacy and safety of ampicillin-sulbactam (3 g every 6 hours) in patients with pelvic inflammatory disease or postpartum endometritis using a randomized, comparative, multicenter study of parallel design. METHODS: Eligible patients with pelvic inflammatory disease were randomized to receive either ampicillin-sulbactam or cefoxitin (2 g every 6 hours) plus doxycycline (100 mg every 12 hours). Those with endometritis were randomized to ampicillin-sulbactam or clindamycin (900 mg every 8 hours) plus gentamicin (1.5 mg/kg every 8 hours). In the ampicillin-sulbactam group, chlamydia-positive patients also received oral doxycycline. RESULTS: For pelvic inflammatory disease, the clinical response rates (cure or improvement) were 85.5% (47 of 55) and 89.6% (43 of 48) in the ampicillin-sulbactam and cefoxitin and doxycycline groups, respectively (chi 2 = 0.10, P = .76). For endometritis, the clinical response rates were 88.7% (141 of 159) and 90.8% (139 of 153) in the ampicillin-sulbactam and clindamycin and gentamicin groups, respectively (chi 2 = 0.15, P = .70). The percentages of patients with pelvic inflammatory disease who had adverse experiences were not significantly different in the cefoxitin and doxycycline group (47% [29 of 62]) than in those receiving ampicillin-sulbactam (33% [22 of 66]) (P = .12). These adverse effects were mostly mild or moderate. In the endometritis subjects, the incidence of adverse experiences in the ampicillin-sulbactam group (11% [20 of 179]) was comparable to that during treatment with clindamycin and gentamicin (12% [22 of 180]). These adverse experiences were also mostly mild to moderate. CONCLUSION: Ampicillin-sulbactam is as effective and well tolerated as combination regimens using cefoxitin plus doxycycline and clindamycin plus-gentamicin for the treatment of pelvic inflammatory disease or endometritis, respectively.

Cord-containing amniotic fluid pocket: a useful measurement in the management of oligohydramnios.

OBJECTIVE: To test the hypothesis that among patients with a low amniotic fluid (AF) index, those who have a large cord-containing AF pocket will have a lower risk for adverse perinatal outcome than women with a small cord-containing pocket. METHODS: Gravidas with an antepartum AF index no greater than 5 cm were studied prospectively. The vertical diameter of the single largest cord-containing pocket, which was excluded from the calculation of the AF index, was measured. Women with rupture of the membranes, multiple gestation, or fetal anomalies were excluded. RESULTS: Fifty-one women with gestational ages of 35-43 weeks were analyzed. Among 35 who had a cord-containing pocket of no more than 5 cm, eight (23%) had fetal distress necessitating operative delivery and eight neonates had cord arterial pH below 7.20. None of these complications occurred in the 16 women who had a cord-containing pocket above 5 cm (P < .05). The mean AF index (2.9 versus 2.8 cm) was not significantly different between the groups. CONCLUSION: Among women with a low AF index, a cord-containing pocket above 5 cm identifies a subgroup of women at lower perinatal risk compared with those with a smaller cord-containing pocket. The need for intervention may be reduced in women with a cord-containing pocket greater than 5 cm.

AIDS (HIV) risk assessment in an inner-city women's clinic.

Risk assessment and antibody testing are potential modalities through which interventions to reduce heterosexual and perinatal transmission of human immunodeficiency virus (HIV) can occur. More than 98% of women attending inner-city adult gynecology, adult contraception and teen family planning clinics successfully completed self-administered HIV (AIDS) risk assessment questionnaires and received individual counseling, risk-reduction education and referral for antibody testing. Fourteen percent of the women (671/4,802) reported at least one HIV risk factor. Multiple sexual partners and intravenous drug use were the most commonly reported HIV risk factors in this population.

Comparison of rapid tests for detection of group B streptococcal colonization.

Accurate rapid detection of maternal lower genital tract colonization with group B streptococci (GBS) in high-risk patients is essential for selective institution of intrapartum antibiotic treatment to reduce neonatal GBS infection. In this study, pure GBS isolates were used to evaluate five commercially available rapid tests in terms of speed, ease of use, and sensitivity. The products tested were Directigen, Equate, Bactigen, PathoDx, and Phadebact. Although each test could be performed relatively quickly, the ease of performance and level of sensitivity (10(5) to 10(8) CFU/ml) varied markedly. Quantitative cultures obtained from 17 known GBS carriers showed concentrations ranging from less than 10(2) to greater than 10(8) CFU/gm of vaginal material. Since only 40% of the women had greater than or equal to 10(5) CFU/gm of vaginal material, it appears that many colonized women would not be identified by these rapid tests.

High plasma cellular fibronectin levels correlate with biochemical and clinical features of preeclampsia but cannot be attributed to hypertension alone.

Current concepts of the pathogenesis of preeclampsia involve the generalized dysfunction of maternal vascular endothelial cells. We measured the endothelial isoform of fibronectin as a marker of endothelial cell injury throughout pregnancy in a prospective, case-control study. Nineteen women met strict criteria for the diagnosis of preeclampsia. Nineteen normal pregnant women, and 19 women with gestational hypertension but without other stigmata of preeclampsia (transient hypertension) were selected from the same cohort and matched according to race, age, nulliparity, and gestational age at delivery. Plasma levels of cellular fibronectin were significantly elevated in women meeting strict clinical and biochemical criteria for preeclampsia but not in women with normal pregnancies or transient hypertension. Moderate but significant elevations in mean levels were found in the second trimester in women destined to have preeclampsia, as compared with matched normal and transient hypertension groups (p less than 0.05). The results indicate that elevated plasma levels of cellular fibronectin are not simply the result of increased blood pressure but reflect a maternal insult specific to the syndrome of preeclampsia. Elevation of the mean concentration during the midtrimester is consistent with the hypothesis that endothelial cell injury is a specific lesion that occurs early in the course of preeclampsia, before clinical signs and symptoms.

Fibroepithelial polyps of the vagina in pregnancy.

A 38-year old pregnant woman presented with a polypoid tumor of the vagina. A biopsy revealed benign fibroepithelial polyps. Her pregnancy progressed normally, and she underwent an uncomplicated vaginal delivery. Once the benign nature of the lesion has been established, a spontaneous vaginal delivery is not contraindicated. However, operative vaginal delivery should be avoided to reduce the risk of trauma and hemorrhage. Local excision is curative and may be performed as an interval procedure when the vaginal vascularity has returned to normal.

Peripartum cocaine use: estimating risk of adverse pregnancy outcome.

Pregnancy outcome of 83 patients with a positive urine toxicology screen for cocaine in the third trimester were reviewed. The outcomes of pregnancies complicated by cocaine abuse were compared to those of matched controls selected from our general obstetric population. We observed a statistically significant increase in the incidence of premature separation of the placenta, low birthweight infants, preterm deliveries, and the incidence of fetal distress requiring cesarean section. On admission, 55% of patients denied recent cocaine use. These observations have implications for planning perinatal services.

HIV infection. Managing exposure risks for the obstetrician/gynecologist.

Human immunodeficiency virus infection in women is geographically widespread throughout the US. Infected blood is the single most important source for HIV transmission in the health care setting. Occupationally acquired HIV infection appears to be an uncommon event, with prospective studies thus far reporting an incidence of 0.6 per cent or less. Strategies for preventing transmission of HIV infection in an obstetric/gynecologic setting are a matter of appropriate barrier protection, good infection control technique, and a large measure of common sense.

Fetal trauma: relation to maternal injury.

Conventional surgical wisdom is that fetal death is a predictable consequence of severe maternal injury. In order to define the natural history of maternal-fetal trauma and better formulate management strategies, we reviewed our recent experience with 32 cases of maternal trauma at a major trauma center. There were three cases of fetal death; two were associated with severe maternal injury, but one had no significant injury to the mother. All cases had placental injury. Conversely, there were five cases of severe maternal trauma but only two unsuccessful pregnancy outcomes. We conclude that the extent of maternal injury does not necessarily correlate with the degree of fetal injury. Lethal placental or direct fetal injury can occur even in the absence of significant maternal injury. In selected cases, fetal salvage after maternal-fetal trauma may be achieved by early delivery and prompt pediatric surgical intervention.

Amoxicillin therapy for Chlamydia trachomatis in pregnancy.

For treating Chlamydia trachomatis cervical infection in pregnancy, the Centers for Disease Control guidelines recommend either erythromycin base or erythromycin ethylsuccinate. There is no alternate therapy. Because of compliance problems with erythromycin regimens due to gastrointestinal side effects, such an alternative is needed. For this reason, we compared, in an open trial, the efficacy and patient compliance of amoxicillin (500 mg three times a day for 7 days) with those of erythromycin base (500 mg four times a day for 7 days) in treating C trachomatis cervical infections during pregnancy. In the amoxicillin group, 63 of 64 women (98.4%) had negative cervical cultures after treatment, compared with 55 of 58 women (94.8%) treated with erythromycin base. Vertical transmission to the infants was assessed by culture and/or persistent or rising immunoglobulin G antichlamydial antibody. In the amoxicillin group, 37 of 39 infants (94.9%) had no evidence of chlamydial infection, compared with 32 of 36 infants (88.8%) in the erythromycin group. These differences were not significant. The frequency of side effects was higher with erythromycin base than with amoxicillin (15 versus 8%), although not significantly so. However, the frequency of stopping medication because of side effects was significantly higher with erythromycin base than with amoxicillin (13 versus 2%; P less than .006). These results suggest that amoxicillin may be an acceptable alternative treatment for chlamydial infections in pregnancy.