Hormonal contraceptive use before and after conception in relation to preterm birth and small for gestational age: an observational cohort study.

OBJECTIVE: To evaluate whether hormonal contraceptives, used before or in early pregnancy, confer increased risk of preterm birth or reduced fetal growth. DESIGN: Population-based cohort study conducted by the Norwegian Institute of Public Health (Mother and Child Cohort Study, 1998-2008) with linkage to the Norwegian Prescription Registry and to the Medical Birth Registry of Norway. SETTING: Norway. POPULATION: Of the 48,615 pregnancies meeting study inclusion criteria, 44,734 pregnancies were included in the complete case analysis. METHODS: We characterised hormonal contraception by type (combination oral, progestin-only oral, vaginal ring, transdermal, and injectable) and specific progestin component. We used generalised estimating equations to estimate the odds of adverse outcome according to formulation used. Several sensitivity analyses were conducted. MAIN OUTCOME MEASURES: Preterm birth, small for gestational age. RESULTS: We observed a positive association between use of a combination oral contraceptive and preterm birth for all exposure periods (e.g. adjusted odds ratio 1.21, 95% confidence interval 1.04-1.41 for last use 12 to >4 months before conception); combination contraceptives containing the progestin norethisterone were consistently related to risk. Other types of hormonal contraception were generally not associated with preterm birth; none were related to small for gestational age. Observed associations were robust to sensitivity analyses. CONCLUSION: Hormonally active agents may exert dose-, agent-, and timing-specific effects on growth and development. We found that the particular progestin component is important when assessing the potential for adverse effects among former users of hormonal contraceptives.

Maternal hormonal contraceptive use and offspring overweight or obesity.

BACKGROUND/OBJECTIVES: Experiments in animal models have shown a positive association between in utero exposure to pharmacologic sex hormones and offspring obesity. The developmental effects of such hormones on human obesity are unknown. SUBJECTS/METHODS: Using data from a large, prospective pregnancy cohort study (n=19 652), with linkage to a national prescription registry, we evaluated the association between use of hormonal contraceptives before and after conception (defined from dispensed prescription data and characterized by last date of use relative to conception, 12 to >4 months before (n=3392), 4 to >1 months before (n=2541), 1 to >0 months before (n=2997) and 0-12 weeks after (n=567)) in relation to offspring overweight or obesity at age 3 years. RESULTS: We observed a weak, inverse association between early pregnancy use of a combination oral contraceptive and offspring overweight or obesity at age 3 (adjusted odds ratio (OR): 0.75, 95% confidence interval (CI): 0.53, 1.08) and a positive, but imprecise, association with use of a progestin-only oral contraceptive in early pregnancy (adjusted OR: 1.26, 95% CI: 0.79, 2.02). In general, no association was observed between the use of a hormonal contraceptive before conception and offspring overweight or obesity. A sensitivity analysis comparing combination oral contraceptive users in early pregnancy to other unplanned pregnancies without hormonal contraceptive use further strengthened the inverse association (adjusted OR: 0.70, 95% CI: 0.48, 1.02). Other sensitivity analyses were conducted to evaluate the robustness of the associations observed given varying assumptions. CONCLUSIONS: Pharmacologic sex hormones in early pregnancy may be inversely or positively associated with offspring overweight or obesity at age 3, depending on the specific formulation used. The present study provides support for the potential for environmental sources of hormonally active agents to exert developmental effects.

Birth cohort effects among US-born adults born in the 1980s: foreshadowing future trends in US obesity prevalence.

BACKGROUND: Obesity prevalence stabilized in the US in the first decade of the 2000s. However, obesity prevalence may resume increasing if younger generations are more sensitive to the obesogenic environment than older generations. METHODS: We estimated cohort effects for obesity prevalence among young adults born in the 1980s. Using data collected from the National Health and Nutrition Examination Survey between 1971 and 2008, we calculated obesity for respondents aged between 2 and 74 years. We used the median polish approach to estimate smoothed age and period trends; residual non-linear deviations from age and period trends were regressed on cohort indicator variables to estimate birth cohort effects. RESULTS: After taking into account age effects and ubiquitous secular changes, cohorts born in the 1980s had increased propensity to obesity versus those born in the late 1960s. The cohort effects were 1.18 (95% CI: 1.01, 1.07) and 1.21 (95% CI: 1.02, 1.09) for the 1979-1983 and 1984-1988 birth cohorts, respectively. The effects were especially pronounced in Black males and females but appeared absent in White males. CONCLUSIONS: Our results indicate a generational divergence of obesity prevalence. Even if age-specific obesity prevalence stabilizes in those born before the 1980s, age-specific prevalence may continue to rise in the 1980s cohorts, culminating in record-high obesity prevalence as this generation enters its ages of peak obesity prevalence.

Birth cohort effects on abdominal obesity in the United States: the Silent Generation, Baby Boomers and Generation X.

BACKGROUND: Abdominal obesity predicts a wide range of adverse health outcomes. Over the past several decades, prevalence of abdominal obesity has increased markedly in industrialized countries like the United States No previous analyses, however, have evaluated whether there are birth cohort effects for abdominal obesity. Estimating cohort effects is necessary to forecast future health trends and understand the past population-level trends. METHODS: This analysis evaluated whether there were birth cohort effects for abdominal obesity for the Silent Generation (born 1925-1945), children of the Great Depression; Baby Boomers (born 1946-1964); or Generation X (born 1965-1980). Cohort effects for prevalence of abdominal obesity were estimated using the median polish method with data collected from the National Health and Nutrition Examination Survey (NHANES) between 1988 and 2008. Respondents were aged 20-74 years. RESULTS: After taking into account age effects and ubiquitous secular changes, the Silent Generation and Generation X had higher cohort-specific prevalence of abdominal obesity than the Baby Boomers. Effects were more pronounced in women than men. CONCLUSIONS: This work presents a novel finding: evidence that the birth cohorts of the post-World War II Baby Boom appeared to have uniquely low cohort effects on abdominal obesity. The growing prosperity of the post-World War II US may have exposed the baby-boom generation to lower levels of psychosocial and socioeconomic stress than the previous or subsequent generations. By identifying factors associated with the Baby Boomers' low cohort-specific sensitivity to the obesogenic environment, the obesity prevention community can identify early-life factors that can protect future generations from excess weight gain.

Paclitaxel maintenance chemotherapy following intraperitoneal chemotherapy for ovarian cancer.

The aim of this study was to determine the feasibility of two treatment regimens for ovarian cancers: (1) combined intraperitoneal/intravenous (IP/IV) cisplatin/paclitaxel; or (2) IV only carboplatin/paclitaxel; both followed by 12 cycles of maintenance paclitaxel. A total of 102 subjects were identified who underwent surgery for stage III ovarian cancer. All subjects received either IV or IV/IP chemotherapy, and had a complete response. The subjects were then prescribed maintenance paclitaxel IV for an additional 12 months. Demographic and clinical data were analyzed. Forty-five subjects received combined IP/IV chemotherapy versus 57 who received IV therapy alone. IP/IV versus IV administration was not associated with differences in age, ethnicity, tumor histology, or incidence of intestinal surgery. Toxicities included fatigue, neuropathy, myelosuppression, and nausea/vomiting in both groups. In the IP/IV group, 29/47 subjects (61.7%) completed 12 cycles of maintenance paclitaxel versus 18/55 (32.7%) in the IV group (P = 0.006). The mean number completed by the IP/IV group was 8.6, while the IV group completed 5.8 cycles (P = 0.002). In subjects who received <12 cycles, the mean number of cycles completed by the IP/IV group was 3.1 versus 2.8 in the IV group. The reasons for stopping included neuropathy (33), fatigue (8), myelosuppression (7) and disease progression (6). Patients who received combined IP/IV chemotherapy were more likely to complete maintenance therapy than those who only received IV chemotherapy. Patients who stop maintenance therapy usually do so early in the course. Additional resources directed at physical and emotional support during early cycles of maintenance chemotherapy may allow more to complete the regimen.

Tirapazamine plus cisplatin in advanced or recurrent carcinoma of the uterine cervix: a Southwest Oncology Group study.

The objective of this study was to determine objective response and overall survival (OS) and progression-free survival (PFS) following cisplatin plus tirapazamine treatment in eligible consenting patients with metastatic or recurrent squamous or adenosquamous carcinoma of the cervix. Treatment consisted of intravenous tirapazamine, 260 mg/m(2), followed by cisplatin, 75 mg/m(2), every 21 days for six cycles. Of 56 registered cases, 52 were evaluable for toxicity. There were six grade 4 toxicities (anemia [three], dyspnea [one], neutropenia/granulocytopenia [one], and dehydration [one]). Fifty-three patients were evaluable for response, OS, and PFS. The 6-month OS rate was 56.6% (95% CI 43.3-69.9%). The objective response rate was 32.1% (4 complete [2 confirmed and 2 unconfirmed] and 13 partial [8 confirmed and 5 unconfirmed]). Higher response rates (16/34 [47.1%] vs 1/19 [5.3%], P= 0.0018) were observed in patients who had not previously received radiation-sensitizing chemotherapy, as were OS and PFS (13.9 vs 4.0 months, P < 0.0001; 5.3 vs 1.8 months, P= 0.01). The OS was considered too low to warrant further testing in this disease setting. Despite this, tirapazamine plus cisplatin was active in patients who had not received cisplatin previously. Prior use of radiosensitizing chemotherapy impacted response and survival significantly and should be considered in future clinical trials.

Effect of excisional therapy and highly active antiretroviral therapy on cervical intraepithelial neoplasia in women infected with human immunodeficiency virus.

OBJECTIVE: Our purpose was to determine the rates of recurrence, persistence, and progression of cervical intraepithelial neoplasia in women who were seropositive for human immunodeficiency virus after excisional therapy with and without highly active antiretroviral therapy. STUDY DESIGN: The records of 118 women with cervical intraepithelial neoplasia, 56 of whom were infected with human immunodeficiency virus and 62 of whom were not infected, were examined to compare outcomes. Demographic, behavioral, and clinical indices were analyzed. RESULTS: Of 54 women infected with human immunodeficiency virus, 31 (57.4%) had persistent or recurrent cervical intraepithelial neoplasia, in comparison with 10 (16.7%) of 60 noninfected women (P <.01). Progression occurred in 4 (16.7%) of 54 in the infected group and in 3 (5.0%) of 60 in the noninfected group (P <.05). In 21 (60.0%) of 35 infected women, in comparison with 8 (32%) of 25 noninfected women, disease persisted 6 months after diagnosis if treatment was not given (P <.05). Of 19 infected women, 10 (52.6%) had recurrent disease after treatment, compared with 2 (5.7%) of 35 noninfected women (P <.01). Risk factors for recurrence in women who were seropositive for human immunodeficiency virus included margin involvement of specimens obtained by loop electrosurgical excision (87.5% vs 20.0%l; P <.05). Exposure to highly active antiretroviral therapy, including therapy with protease inhibitors, was associated with a lower recurrence or persistence rate (17.6% vs. 70.3%; P <.05) and a lower progression rate (0% vs. 24%; P <.05). CONCLUSION: Women infected with human immunodeficiency virus had high rates of recurrent and persistent cervical intraepithelial neoplasia despite standard therapy. Low CD4(+) levels and margin involvement of specimens obtained by loop electrosurgical excision are risk factors for recurrence. The use of highly active antiretroviral therapy is associated with a lower risk of recurrence, persistence, and progression of cervical intraepithelial neoplasia.

Expression of growth hormone-releasing hormone (GHRH) messenger ribonucleic acid and the presence of biologically active GHRH in human breast, endometrial, and ovarian cancers.

GHRH is produced in a variety of extrahypothalamic tissues, including some neoplasms. We have previously reported that GHRH antagonists can inhibit the growth of various human cancers xenografted into nude mice. These observations suggest that locally produced GHRH might directly affect tumor cell proliferation. To investigate this possibility, we have examined the local production of GHRH in human endometrial, ovarian, and breast cancers obtained after surgery or grown in nude mice as xenografts. We have also examined whether the GHRH produced in these tumors is biologically active. RT-PCR and Southern blotting showed expression of messenger ribonucleic acid for GHRH in 17 of 22 endometrial and 17 of 22 ovarian cancer specimens and in all of the human endometrial, ovarian, and breast cancer xenografts studied. Acid extracts of endometrial cancer specimens and breast cancer xenografts that expressed the GHRH gene contained immunoreactive GHRH peptide, as assessed by RIA for GHRH. The level of immunoreactive GHRH detected was equivalent to 2.7-6.4 ng GHRH-(1-29)/g tissue. Purified extract from one of these tumor samples induced a powerful stimulation of GH release from rat pituitary cells. The presence of biologically and immunologically active GHRH and messenger ribonucleic acid for GHRH in human breast, endometrial, and ovarian cancers supports the hypothesis that locally produced GHRH may play a role in the proliferation of these tumors.

Histology/cytology discrepancies in HIV-infected obstetric patients with normal pap smears.

OBJECTIVE: To estimate the frequency of cervical cytologic/histologic discrepancies in a group of obstetric patients diagnosed as HIV infected by routine prenatal screening. Also, to determine if serum CD4 levels or sexually transmitted diseases (STDs) are associated with the occurrence of preinvasive cervical disease in these women. METHOD: Thirty-two women who presented for routine prenatal care to Medical Center of Louisiana were diagnosed as HIV infected by ELISA and Western blot testing and had normal Pap smears. These patients then agreed to undergo the following: colposcopy with directed biopsies; chlamydia, gonorrhea, and syphilis screening; and serum CD4 level. RESULTS: No patients had AIDS-defining diagnoses other than CD4 < 200/mm3. Ten of 32 (31%) had cervical intraepithelial neoplasia (CIN) despite normal cytology. Six of 32 (19%) had STDs. One of 10 in the group with CIN had a STD. The mean CD4 level in those patients with CIN was 249/mm2 (range 1-524) vs 501/mm2 (range 210-979) in those without CIN. (P = 0.0118) CONCLUSIONS: Newly diagnosed HIV-infected pregnant women without clinical evidence of AIDS are noted to have CIN at a rate similar to nonpregnant HIV-infected women. The Pap smear appears to have a significant false-negative rate in this group. STDs, while common, were not directly associated with false-negative Pap smears. CIN is associated with immunosuppression, as measured by low CD4 counts.

Tumor-host interaction: analysis of cytokines, growth factors, and tumor-infiltrating lymphocytes in ovarian carcinomas.

The host-tumor interaction may play an important role in determining tumor progress. Recent studies have shown that this interaction can be influenced by the release of soluble factors by tumor cells and tumor-infiltrating lymphocytes (TIL). The aim of our study is to characterize the nature of cytokines and growth factors and their relationship to the cellular infiltrates in 16 patients with ovarian cancer using reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry. Total RNA from 20 malignant and 10 benign specimens were used to assay for expression of 12 cytokines. Additionally, monoclonal antibodies (MAbs) were used to detect T cells, CD4+ helper and CD8+ cytotoxic/suppressor T-cell subtypes, B cells, and macrophages. Our results showed the expression of transforming growth factor-beta1 (TGF-beta1), interleukin-10 (IL-10), and granulocyte-macrophage colony-stimulating factor (GM-CSF) in 19, 17, and 10 malignant specimens, P < .001, .001, and .05, respectively. Other cytokines such as interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), TNF-beta/LT, IL-2, and IL-6 were expressed in a few cases, and IL-1alpha and IL-4 expression were not detected. The benign samples did not express IL-10, but GM-CSF, TGF-beta1, and IL-8 were expressed in one, one, and four specimens, respectively. Interestingly, in four cases in which samples from the primary and relapse tumors were available for analysis, the tumors in relapse showed a significant increase for TGF-beta1 (P < .05) and a decreased trend in IL-10 mRNA levels. The source of these factors was tumor cells as detected immunohistochemically. This combined alteration of TGF-beta1 and IL-10 was associated with a significant reduction in number of TIL in general, and CD8+ and macrophages in particular (P = .036 and .049, respectively). Our findings suggest the important role of certain soluble factors in the complex process of tumor progression. Furthermore, understanding the tumor-host relationship and the factors influencing the interaction may be helpful in developing effective and innovative treatment methods.

Management of cervical intraepithelial neoplasia during pregnancy with LOOP excision.

OBJECTIVE: Management of severe cervical dysplasia/possible microinvasive carcinoma during pregnancy is frequently associated with significant morbidity. The purpose of this study is to determine the efficacy of LOOP excision performed during pregnancy, and also to record the nature and frequency of complications of the procedure. METHODS: Twenty women underwent LOOP excision during pregnancy. The gestational age range was 8-34 weeks. Data concerning indications, complications, and histopathologic results were recorded. RESULTS: Fourteen of 20 (70%) had dysplastic changes in the LOOP specimen. Eight of 14 (57%) had involved margins. Nine of 19 (47%) had residual dysplasia 3 months postpartum, including 3 patients whose initial LOOP specimens were negative for dysplasia. Significant morbidity included 3 preterm births, 2 patients who required blood transfusion following LOOP, and 1 unexplained intrauterine fetal demise documented 4 weeks post-LOOP. The gestational age range of those patients who had significant morbidity was 27-34 weeks. CONCLUSIONS: LOOP excision of the cervix during pregnancy does not consistently produce diagnostic specimens and is associated with a significant rate of residual disease. Morbidity appears similar to that of cone biopsy during pregnancy and occurs primarily when the procedure is performed in the third trimester. Until refinements in technique occur, LOOP excision during pregnancy should be reserved for limited indications.

Femoral artery occlusion following pelvic cancer surgery.

Acute arterial occlusion in the lower extremities of patients with gynecologic cancers may not be immediately recognized in the postoperative period, despite the known risk of hypercoagulability associated with malignancy. Such delays in recognition and treatment can result in irreversible but potentially preventable tissue injury. This report describes three cases of acute arterial occlusion of the femoral and/or external iliac arteries in the immediate postoperative period following radical pelvic surgery. Two patients lost the involved limb due to irreversible changes resulting from prolonged ischemia. One patient was diagnosed while the involved limb was still viable and surgical revascularization was successfully performed. These cases illustrate the potential morbidity in unrecognized acute limb ischemia and the case with which it may be overlooked. Systematic documentation of arterial patency is recommended in the postoperative period, noting peripheral pulses and patient complaints related to the lower extremities. Rapid diagnosis and surgical intervention significantly increase the chance of maintaining viability of the involved limb.

Cervical neoplasia. Pathogenesis, diagnosis, and management.

Cervical neoplasia is a common problem among HIV-infected women. HIV appears to accelerate human papillomavirus-related oncogenic events via in completely understood mechanisms. Cytologic screening for cervical neoplasia appears to be unreliable in HIV-infected women. Treatment is also not very effective. Invasive cervical cancer in particular has a very poor prognosis. Innovative therapeutic modalities are currently being investigated.

An 81-year-old woman with an abdominal mass.

An 81-year-old woman was admitted with a large abdominal mass that had grown rapidly over the previous few months. The differential diagnosis, pathology, and treatment of such masses are discussed.

Gynecological surgical outcomes among asymptomatic human immunodeficiency virus-infected women and uninfected control subjects.

To determine the effect of asymptomatic human immunodeficiency virus (HIV) infection on the risk of complications and outcomes in women undergoing gynecological surgical procedures, retrospective analysis was performed of 62 asymptomatic HIV-infected women who underwent gynecological procedures. One hundred forty seronegative women who had similar procedures during the same time period served as controls. Procedures included tubal sterilization, hysterectomy, and diagnostic laparotomy. The following variables were compared: length of hospital stay, age, blood loss, white blood cell count, hemoglobin, and hematocrit. Laboratory parameters were compared pre-and postoperatively, as well as between the study and control groups. Race and parity were similar in both groups. HIV-infected women were younger (mean: 25 years versus 31 years) than controls. Length of hospital stay was similar. Blood loss was higher in the HIV-infected group than controls. (318 cc versus 122 cc) Differences in white blood cell counts, hematocrits, and febrile morbidity were insignificant. Asymptomatic HIV infection has minimal effect on the outcome of elective gynecologic surgery. The younger age of the HIV-infected women reflects the demographics of HIV infection and sterilization reflects the desire to prevent perinatal transmission.

Effect of successive single-gestation pregnancies on the course of maternal human immunodeficiency virus disease and perinatal transmission.

OBJECTIVE: This study was undertaken to examine the effect of successive pregnancies over a 3-year period on the course of maternal human immunodeficiency virus (HIV) infection and the rate of perinatal transmission of HIV. METHODS: A retrospective analysis of 32 pregnancies in 14 known HIV-infected women vs. a matched control group of HIV-infected women who had been pregnant only once was done. RESULTS: The multiple-pregnancy group was similar to the single-pregnancy group for age, race, duration of known HIV infection, initial CD(4) count, and date of first pregnancy. The delivery data were similar as well. The CD(4) counts in the multiple-pregnancy group fell from 595 to 460, while counts in the single-pregnancy group fell comparably from 669 to 638, both over 37 months (P = 0.1476). Five of 5 second-born infants of known serostatus vs. 8 of 21 first-born infants were HIV-infected (P < 0.05). CONCLUSIONS: Successive pregnancies do not alter the course of HIV infection in asymptomatic women followed up to 3 years. The infants of second pregnancies of known HIV-infected women may be at higher risk for perinatal transmission.

Prenatal human immunodeficiency virus testing and patient management by obstetricians in a high seroprevalence community.

OBJECTIVE: In order to determine the practice habits of obstetricians concerning frequency of prenatal human immunodeficiency virus (HIV) testing and management strategies for HIV-seropositive obstetric patients, we conducted a telephone survey of practicing obstetricians over a 3-month period. METHODS: In the New Orleans metropolitan area, 71/104 (68%) obstetricians participated and completed the survey. RESULTS: Of these obstetricians, 43/71 (60.6%) test all new obstetric patients for HIV; 64/71 (84.5%) routinely ask the patients about risk factors for infection; and 28/71 (39.4%) have actually cared for an HIV-positive patient in their practice. Those obstetricians who routinely tested for HIV were more likely to have personally managed an infected patient and more likely to ask about risk factors. The number of obstetricians who would manage infected patients without consultative assistance was 8/71 (11%). CONCLUSIONS: We concluded that obstetricians in this community have largely accepted routinely offered prenatal testing and risk assessment, but they have assumed a relatively small role in risk reduction counseling and treatment.

Spinal cord compression in metastatic cervical cancer.

Spinal cord compression secondary to metastatic cervical cancer may not be considered as a possible cause of neurologic symptoms by primary care physicians who do not often treat these patients. Delays in diagnosis and treatment may result in irreversible but potentially preventable neurologic changes. This report describes 5 cases of spinal cord compression in patients with metastatic cervical carcinoma, 2 of whom were previously undiagnosed with cervical cancer. These 2 patients represent 1.6% (2 of 121) of all new cervical cancer cases diagnosed during this time period. Two of 5 patients (40%) with spinal cord compression showed improvement following therapy by regaining the ability to walk, while none of the remaining patients had further acute deterioration of neurologic function. The mean survival of patients presenting with spinal cord compression from cervical cancer in this series was 4 months (maximum 6 months). This series illustrates the relative frequency with which spinal cord compression is seen in patients with a new diagnosis of invasive cancer. This diagnosis should be considered when evaluating neurologic complaints in known cervical cancer patients or any woman with apparent pelvic pathology. Rapid diagnosis and treatment of these lesions, while not likely to improve overall survival significantly, can improve function and alleviate symptoms.

Operative staging and conservative surgery in the management of low malignant potential ovarian tumors.

The medical records of 45- patients with intraoperative diagnosis of borderline or low malignant potential (LMP) ovarian tumor were reviewed to identify factors affecting intraoperative management. The correlation between gross and histologic staging was examined, as was the complication rate following surgery. Patient age and presence of qualifying pathologic terms on frozen section diagnosis were the only important factors relating to performance of surgical procedure. Surgical complications were closely associated with non-conservative surgery. Thirteen of 14 (92.8%) patients with significant complications had a hysterectomy. These 14 patients had staging procedures at essentially the same rate as the entire population. Thirteen of 45 patients (28.8%) thought to have LMP by frozen section had a different diagnosis on permanent review; 5 were benign and 8 were frankly malignant, confirming the limitations of frozen section in the diagnosis of LMP ovarian tumor. Of 40 with LMP or frankly malignant tumors 5(12.5%) were upstaged based on unsuspected histopathologic findings. These results indicate the need for a standard approach to staging in patients who are suspected to have an LMP ovarian tumor and should encourage the performance of conservative surgery when appropriate.