HPV prevalence and concordance in the cervix and oral cavity of pregnant women.

OBJECTIVES: This investigation examined human papillomavirus (HPV) in pregnant women in order to characterize viral prevalence, types and concordance between infection in the cervix and in the oral cavity. METHODS: A total of 577 pregnant women seeking routine obstetric care were evaluated for HPV infection in their cervix during gestation and immediately before delivery, and in the oral cavity during gestation. Male partners present during the gestational clinic visit also provided a specimen from their oral cavity. HPV assessment was performed by PCR, dot blot hybridization and DNA sequencing. A sexual and health questionnaire was completed by the pregnant women. RESULTS: HPV prevalence in women was 29% in the cervix and 2.4% in the oral cavity. Among those with both gestational and delivery specimens, 35% were infected at least once and 20% had infection at both intervals. At delivery, 68% of infected women had an oncogenic HPV type in the cervix. There was no type-specific HPV concordance between the two cervical specimens, nor cervical and oral results in women, nor with cervical and oral findings between partners. CONCLUSION: The lack of association in HPV positivity and types between the cervix and oral cavity in these women suggests that self-inoculation is uncommon. This source of infection does not appear to be from oral contact with a current male partner, since there also was no concordance between partners. These results suggest either other modes of HPV transmission or differences in susceptibility to HPV infection or its clearance in the oral cavity and genital mucosa.

X-inactivation patterns in human embryonic and extra-embryonic tissues.

Mice have skewed X chromosome inactivation (XCI) in extraembryonic tissue while examination of human placentae have yielded conflicting results. We investigated XCI patterns in human embryonic and extra-embryonic tissues. First and early second trimester placental and foetal tissues were collected. Cytotrophoblasts were isolated from the placentae. Female samples were identified and X-inactivation patterns were determined by analysis of androgen receptor (HAR) methylation patterns. Among 55 females heterozygous at the HAR, 37 had random and 18 skewed XCI. In foetal tissues a skewed XCI pattern was only observed in one liver and one intestine sample. A greater incidence of skewed XCI pattern was present in extra-embryonic compared to embryonic tissues (P=0.022). A markedly skewed XCI pattern was only found in one cytotrophoblast sample. Random and skewed XCI patterns were detected in human embryonic and extra-embryonic tissues. The extra-embryonic tissue had a higher proportion of skewed XCI, but marked skewed XCI was uncommon in both tissues. Skewed XCI may not play a role in normal human placentation.

Leukemia in pregnancy and fetal response to multiagent chemotherapy.

BACKGROUND: Leukemia is rare in pregnancy and treatment with intensive, multiagent chemotherapy produces complete remission in most adults, but might have deleterious effects on fetuses. CASE: A 24-year-old gravida 3 para 2 presented at 24 weeks with pruritus, rash, pancytopenia, and hepatitis. A bone marrow biopsy found acute lymphocytic leukemia. She completed three cycles of intensive multiagent chemotherapy with transient oligohydramnios in each cycle. Although there was decreased fetal growth rate, umbilical artery Doppler scans were normal. She delivered a normal 2150-g male infant at 36 weeks. CONCLUSION: Pregnant women with newly diagnosed leukemia should not delay treatment, but multiagent chemotherapy might have transient effects on fetuses, most notably oligohydramnios. However, if fetal testing is normal, delivery might not be indicated.

Etiology of differences in hematocrit between males and females: sequence-based polymorphisms in erythropoietin and its receptor.

INTRODUCTION: Males have a higher hematocrit (Hct) than females. The cause of this gender-based difference is unclear. We sought to determine whether polymorphisms of the erythropoietin (EPO) gene or of its receptor (EPOR) explain this situation. METHODS: We designed primers for the EPO and EPOR genes. Previously undescribed polymorphisms were found based on band migration on polyacrylamide gel, and when then sequenced. The distribution of these polymorphisms was studied in a population of 819 non-iron-deficient, healthy blood donors. To test the gender differences, analysis was done based on groups defined by Hct levels. The chi-square statistic was used to compare the frequency differences between groups, with P < .05 considered statistically significant. RESULTS: We found previously reported polymorphisms in both the EPO and EPOR genes. Sequence analysis showed that the EPO polymorphism was due to a difference in the repeat copy number of the tetranucleotide cytosine adenine cytosine thymine (CACT) at position 2153. A previously undescribed 12th allele was found for the EPOR polymorphic site. Statistical analysis showed that the EPOR alleles, EPORA1 and EPORA10, were present at a significantly higher frequency in females than in males (P = .027 and P = .041, respectively), and EPOR5 was found less frequently in females than in males (P = .048). The allelic frequency of the EPO polymorphism was not significantly different by gender or Hct groups. DISCUSSION: These results suggest that the variation of Hct level by gender may have a genetic basis. The sequence-based polymorphism for EPOR may be partly responsible for this gender-based variation in Hct level. These findings offer new clues to understanding Hct variation in the general population and to elucidating mechanisms of controlling Hct levels.

Vaginal ultrasound as an adjunct to cervical digital examination in women at risk of early delivery.

AIM: To study the utility of transvaginal ultrasound (TVU) in women at high risk of preterm delivery. METHODS: Women who were scheduled for frequent digital examinations of the cervix from 16 to 26 weeks of gestation had TVU determinations of cervical length before their clinical examinations. Clinicians were blinded to the TVU results. Therefore, clinical decision-making was independent of the unreported TVU data. The plan was to relate the ultrasound characterization of the cervix to the study's primary endpoint, the need for hospitalization prior to 26 weeks of gestation for: preterm premature rupture of membranes, preterm labor, cerclage placement, or delivery. RESULTS: Seventeen subjects completed the study. All 3 who met the primary endpoint had ultrasound cervical lengths <20 mm on earlier prenatal visits, when digital examinations of the cervix did not detect problems. A 4th woman had ultrasound lengths <20 mm (she delivered at 27(6)/(7) weeks). CONCLUSION: TVU determination of cervical length provides an earlier warning of cervical shortening than does digital examination.

Congenital fiber-type disproportion presenting antenatally with clubfoot and hydramnios.

This is a case of congenital fiber-type disproportion that presented prenatally with bilateral clubfoot, hydramnios, and reduced fetal movements. Although prognosis is generally good for this condition, the neonate presenting at birth may have a more severe form of congenital fiber-type disproportion with a high rate of mortality.

Evaluation of pregnant women exposed to respiratory viruses.

Prenatal patients are often exposed to respiratory viruses at home and at work. Understandably, these patients may be concerned and want immediate answers and advice from their physicians. While most women who are exposed to chickenpox are immune, serologic testing can be performed and susceptible patients can be treated with varicella-zoster immune globulin. If the prenatal patient is infected with the varicella-zoster virus, the risk of fetal manifestations is less than 2 percent. Women who have been exposed to fifth disease can undergo serologic testing to determine the likelihood of infection. If the prenatal patient becomes infected with fifth disease during the first 20 weeks of gestation, the risk of fetal manifestations is about 9 percent and includes nonimmune hydrops and death. Cytomegalovirus, which is the most common congenital infection, is generally asymptomatic in the mother. Infected fetuses have a 25 percent chance of developing early or late neurologic manifestations. The evidence of harm from other common respiratory viruses is inconsistent.

Oculoauriculovertebral abnormalities in children of diabetic mothers.

Maternal diabetes is known to have teratogenic effects. Malformations including neural tube defects, caudal dysgenesis, vertebral defects, congenital heart defects, femoral hypoplasia, and renal anomalies are described in infants of diabetic mothers. However, craniofacial anomalies have rarely been reported in such infants. Here we document craniofacial anomalies of patients born to diabetic mothers. We describe two patient populations: individuals evaluated through our genetics services for multiple malformations and individuals identified through a database search in our craniofacial clinic. The first group consists of 14 individuals evaluated in our genetics clinics who were born to diabetic mothers and had craniofacial anomalies. The second group consists of seven individuals who were identified from a craniofacial database search of patients with hemifacial microsomia and who were born to diabetic mothers. Thus, both groups were born to diabetic mothers and had hemifacial microsomia (67%), microtia (52%), hearing loss (43%), epibulbar dermoids (24%), and fused cervical vertebrae (24%). Therefore, the teratogenic effects of maternal diabetes probably include such craniofacial malformations as the oculoauriculovertebral/Goldenhar complex. Infants of diabetic mothers should be evaluated for craniofacial anomalies. Conversely, mothers of infants with craniofacial anomalies should be evaluated for diabetes to aid in counseling concerning cause and recurrence risks.

Videotaping obstetric procedures. Assessment of obstetricians and family physicians.

OBJECTIVE: To compare the attitudes and practice of Iowa obstetricians (OBs) and family physicians (FPs) regarding patients' desires to videotape obstetric procedures. DESIGN: All Iowa OBs (172) and FPs (438) who practice obstetrics received a questionnaire exploring their attitudes and practice patterns regarding videotaping obstetric procedures. Data were analyzed using chi 2, odds ratios with 95% confidence intervals, and multiple logistic regression. SETTING: The state of Iowa. MAIN OUTCOME MEASURES: Degree to which physicians allow videotaping and characteristics that contribute to any differences between OBs and FPs. RESULTS: The response rate was 87.8% (536 of 610 participants). Obstetricians were more likely than FPs to prevent patients from filming medical procedures (40.8% vs 19.1%, respectively, P < .001), modify their actions and conversation when video cameras were present (34.5% vs 25.5%, respectively, P = .046), and be tempted to turn off the camera when complications arose (35.1% vs 14.0%, respectively, P < .001). Younger OBs (aged, 25-40 years) were more likely than older OBs (aged, 41-80 years) to disallow videocameras (52.7% vs 33.3%, respectively, P = .02). Legal concerns were cited by more than 80% of OBs and FPs who disallowed videotaping. CONCLUSIONS: A significant difference was noted between OBs and FPs in their willingness to allow video recording of obstetric procedures. Legal concerns were cited by most OBs and FPs who had disallowed videotaping.

Discordance between fetal RhD typing using molecular methods and neonatal typing with serology.

Polymerase chain reaction (PCR)-based genotyping on amniotic fluid in an RhD-negative alloimmunized woman predicted an RhD-negative fetal blood type. The neonate was RhD-positive and developed hemolytic disease. Discrepant results were also observed on paternal testing. PCR analysis with a different set of primers correctly predicted the RhD-positive fetal and paternal blood type. Use of more than one set of primers and parental testing can avoid some of the problems associated with use of PCR genotyping.

A case illustrating the continued dilemmas in treating abdominal pregnancy and a potential explanation for the high rate of postsurgical febrile morbidity.

BACKGROUND: Abdominal pregnancy is potentially highly morbid and often complicated by postoperative fever. CASE: A 29-year-old gravida 2 para 0 presented with a 17-week size-demised abdominal pregnancy. We describe the continued difficulty in determining the timing and type of intervention. In addition, we found that the gestational sac was colonized by group B streptococcus at the time of surgery. CONCLUSION: This case illustrates that preoperative colonization of the intra-abdominal gestational sac may contribute to postoperative febrile morbidity. We suggest treating patients with prophylactic antibiotics and avoiding spill of gestational sac contents into the peritoneal cavity. Placement of a sterile Foley bulb into the uterine cavity can confirm the extrauterine position of the pregnancy prior to undertaking surgery.

Antenatal sonographic diagnosis of club foot with particular attention to the implications and outcomes of isolated club foot.

OBJECTIVE: There are no studies to date on the implications and outcomes of antenatally detected isolated club foot. The purpose of this study was to perform a contemporary evaluation of club foot diagnosed in the antenatal period. DESIGN: We performed a retrospective analysis of all ultrasound examinations performed in 1989-96 in the Fetal Diagnosis and Treatment Unit of the University of Iowa Hospitals and Clinics (n = 23,863). SUBJECTS AND METHODS: All cases of club foot (n = 35) were evaluated for the presence of other detectable abnormalities and karyotype results if available. Postnatal follow-up was performed until over 1 year of age. RESULTS: We diagnosed unilateral (n = 18) and bilateral (n = 17) club foot from 17.4 to 37.0 weeks. Defects involving other systems were found in 28 of 35 cases. Of the seven cases considered to be isolated antenatally, three were diagnosed with additional malformations in the neonatal period. CONCLUSION: Most cases of antenatally diagnosed club foot were not isolated. Even when they were thought to be isolated on antenatal ultrasound, over half of them were later found to be associated with additional severe abnormalities that were detectable only in the neonatal period.

Update on vertical HIV transmission.

OBJECTIVE: To describe the factors that contribute to vertical transmission of human immunodeficiency virus (HIV) and review means of decreasing the risk of transmission. STUDY DESIGN: Medline search of the international English-language literature pertaining to HIV in pregnancy from 1989 to the present. Special emphasis was placed on articles published in the last three years related to vertical transmission as well as to antepartum, intrapartum and postpartum management to reduce transmission. RESULTS: High levels of maternal viral load and more advanced maternal disease are associated with a greater risk of vertical transmission of HIV. Antepartum and intrapartum maternal treatment with zidovudine and postpartum neonatal zidovudine treatment decreases the risk of transmission by two-thirds, at least in patients with earlier stages of the disease. Breast-feeding is a source of postpartum HIV transmission and may double the total transmission rate. CONCLUSION: Zidovudine should be used in pregnancy to decrease the viral load and reduce transmission of HIV to the fetus. Other antiviral agents should be used during pregnancy if indicated, although current information is lacking about their effects on the fetus and any potential benefits in decreasing vertical transmission of HIV. Breast-feeding should be avoided.

PIP: A search of MEDLINE for English-language literature published from 1989 to the present was conducted to identify the factors that affect vertical transmission of HIV infection as well as ways to reduce risk. As of August 1998, there were an estimated million people infected with HIV in the US, and, in 1994, AIDS was the third-leading cause of death among women aged 25-44 years. The prevalence of maternal-fetal transmission is approximately 1.6/1000 births. Neonatal transmission rates in the US are 15-25% as compared to 25-35% in Africa. It is believed that 50% of vertical transmission occurs during labor and delivery through exposure to secretions and blood. HIV is also transmitted through breast milk. The literature review revealed several postulated determinants of vertical transmission, such as maternal, obstetric, infant, and viral factors. The literature indicates that high levels of maternal viral load and advanced maternal disease increase risk of vertical transmission, that treatment of pregnant women and newborns with zidovudine decreases transmission risk, and that breast feeding should be avoided unless there is no safe alternative to breast milk. In addition, it is recommended that HIV-positive pregnant women undergo assessment of viral load and degree of immunosuppression, that infected women be treated with oral zidovudine during pregnancy and intravenous zidovudine during labor, that combination therapy be considered when appropriate, and that patients be counseled about the risk of transmission during invasive prenatal testing.

Choroid plexus cysts and aneuploidy.

The association of choroid plexus cysts with fetal aneuploidy, particularly trisomy 18, was first noted in 1986. Through the years there have been numerous reports on this subject, but no consensus has been reached with regard to chromosomal risk. In this review, we attempt to summarise published reports on second trimester choroid plexus cysts, with an emphasis on the strengths and weaknesses of each report. Based on these reports, additional malformations are a significant risk factor for aneuploidy and an indication for determination of fetal karyotype. The management of isolated choroid plexus cysts remains controversial.

Detection of intrauterine viral infection using the polymerase chain reaction.

Intrauterine viral infection commonly presents as nonimmune hydrops fetalis or intrauterine growth restriction. Cytomegalovirus (CMV) and parvovirus are commonly recognized causes of fetal infection using serology and cultures. We used the polymerase chain reaction (PCR) to evaluate the frequency of fetal viral infection and the associated clinical course and outcome. Specimens (amniotic fluid, fetal blood, pleural fluid, tissue) from 303 abnormal pregnancies at risk for viral infection and 154 controls were analyzed using primers for CMV, herpes simplex virus, parvovirus B19, adenovirus, enterovirus, Epstein-Barr virus, and respiratory syncytial virus. Viral genome was detected in 144/371 samples (39%) or 124/303 patients (41%), with adenovirus (n = 74 patients; 24%), CMV (n = 30 patients; 10%), and enterovirus (n = 22 patients; 7%) most common. Only 4/154 (2.6%), unaffected control patients' samples were PCR positive. We conclude that diagnosis of fetal viral infection by PCR is common in abnormal pregnancies. Adenovirus and enterovirus may cause fetal infection that have been previously unrecognized.

Prospective evaluation of prenatal maternal serum screening for trisomy 18.

OBJECTIVE: Our goal was to evaluate the performance of prenatal serum screening for trisomy 18. STUDY DESIGN: All 40,762 samples for maternal serum testing (August 1991 to June 1994) with a trisomy 18-positive screen (n = 175, alpha-fetoprotein < or =0.75 multiples of the median, unconjugated estriol < or =0.60 multiples of the median, human chorionic gonadotropin < or =0.55 multiples of the median) were analyzed. Results of all amniocenteses, ultrasonographic studies, and birth or death certificate information were obtained from the Iowa Expanded Serum Screening Program, the Iowa Department of Public Health, and the Iowa Birth Defects Registry. RESULTS: We obtained the expected screen-positive rate for trisomy 18 (0.43%, 175/40,762). Fourteen samples from outside the state were excluded, which left 161 cases with outcome data obtained through amniocentesis (n = 121), birth certificates (n = 34), telephone contact (n = 2), or a sonogram indicating a nonviable gestation (n = 4). Of 121 screen-positive women undergoing amniocentesis, 119 had a normal karyotype and 2 had an abnormal karyotype: 69,XXY and 47,XY,+18. Of 36 who declined amniocentesis, none had findings consistent with aneuploidy on clinical neonatal examination. Of the 103 patients who had a detailed ultrasonographic study at the University of Iowa, 27 had a subtle fetal abnormality or growth alteration. Both cases with aneuploidy were in this group. An additional 7 cases of trisomy 18 without the typical trisomy 18 maternal serum screening pattern were diagnosed during this period either at amniocentesis performed because of increased Down syndrome risk indicated by serum screening (n = 1), by elevated alpha-fetoprotein level (n = 1), or by advanced maternal age (n = 2) with serum for screening drawn coincidentally, or they were diagnosed postnatally (n = 3). Three of the 7 cases had early second-trimester ultrasonographic examinations, and all showed abnormalities. CONCLUSIONS: The detection rate of trisomy 18 among patients offered amniocentesis was significantly lower (p < 0.05) than the expected rate (10/161 on the basis of published data). Combining serum screening with detailed ultrasonographic evaluations may improve predictive value by more precisely targeting amniocentesis toward those at highest risk.

Legal implications of birth videos.

There is little information available in the peer-reviewed literature on the medical and legal aspects of videotaping obstetric procedures. To manage legal risks, some large medical centers do not allow families to videotape the birth. One liability insurer is now attempting to limit video cameras in labor and delivery suites throughout its state. These policies can have significant implications for physicians and their patients. In an effort to examine approaches to the problem, we gathered the experiences of physician and attorney members of the American College of Legal Medicine through letters and telephone conversations, and we performed a review of the available medical and legal literature. Based on this research and review, we present the benefits and risks of permitting families to videotape the birth process, and we make recommendations for reducing potential liability.