Changes in obstetrical practices and pregnancy outcomes following the ARRIVE trial.

BACKGROUND: The ARRIVE trial demonstrated the benefit of induction of labor at 39 weeks gestation. Obstetrics departments across the United States faced the challenge of adapting clinical practice in light of these data while managing logistical constraints. OBJECTIVE: To determine if there were changes in obstetrical practices and perinatal outcomes in the United States after the ARRIVE trial publication. STUDY DESIGN: This was a population-based retrospective cohort study of low-risk, nulliparous women who initiated prenatal care by 12 weeks gestation with singleton, nonanomalous pregnancies delivering at ≥39 weeks. Data were obtained from the US Natality database. The pre-ARRIVE group were women who delivered between January 1, 2015 and December 31, 2017. The post-ARRIVE group consisted of women who delivered between January 1, 2019 and December 31, 2019. Births that occurred in 2018 were excluded. Practice outcomes were rates of induction of labor, timing of delivery, and cesarean delivery rate. Adverse maternal outcomes were blood transfusion and admission to medical intensive care unit. Adverse neonatal outcomes were need for assisted ventilation (immediate and >6 hours), 5-minute APGAR score <3, neonatal intensive care unit admission, seizures, and surfactant use. Univariate and multivariate analyses were performed. Trends were tested across the time period represented by the pre-ARRIVE group using Cochran-Armitage trend test. RESULTS: There were 1,966,870 births in the pre-ARRIVE group and 609,322 in the post-ARRIVE group. The groups differed in age, race, body mass index, marital status, infertility treatment, and smoking history (P<.001). After adjusting for these differences, the post-ARRIVE group was more likely to undergo induction (36.1% vs 30.2%; adjusted odds ratio, 1.36 [1.36-1.37]) and deliver by 39+6 weeks of pregnancy (42.8% vs 39.9%; adjusted odds ratio, 1.14 [1.14-1.15]). The post-ARRIVE group had a significantly lower rate of cesarean delivery than the pre-ARRIVE group (27.3 % vs 27.9%; adjusted odds ratio, 0.94 [0.93-0.94]). Patients in the post-ARRIVE group were more likely to receive a blood transfusion (0.4% vs 0.3%; adjusted odds ratio, 1.43 [1.36-1.50]) and be admitted to medical intensive care unit (0.09% vs 0.08%; adjusted odds ratio, 1.20 [1.09-1.33]). Neonates in the post-ARRIVE group were more likely to need assisted ventilation at birth (3.5% vs 2.8%; adjusted odds ratio, 1.28 [1.26-1.30]) and >6 hours (0.6% vs 0.5%; adjusted odds ratio, 1.36 [1.31-1.41]). The neonates in the post-ARRIVE group were more likely to have low 5-minute APGAR scores (0.4% vs 0.3%; adjusted odds ratio, 0.91 [0.86-0.95]). Neonatal intensive care unit admission did not differ between the 2 groups (4.9% vs 4.9%; adjusted odds ratio, 1.01 [0.99-1.03]). There were no differences in neonatal seizures (0.04% vs 0.04%; adjusted odds ratio, 0.97 [0.84-1.13]), and surfactant use (0.08% vs 0.07%; adjusted odds ratio, 1.05 [0.94-1.17]) between the 2 groups. CONCLUSION: There were more inductions of labor, more deliveries at 39 weeks' gestation, and fewer cesarean deliveries in the year after the ARRIVE trial publication. The small but statistically significant increase in some adverse maternal and neonatal outcomes should be explored to determine if they are related with concurrent changes in obstetrical practices.

Rising above the mask wars: using nonpharmaceutical interventions to lessen the burden of influenza.

The COVID-19 pandemic imparted important lessons, both through its direct impact on society and through the manner in which society's response influenced the trajectory of other diseases. The decrements in the rates of infection and morbidity from influenza during 2020 were significant, which is particularly important for pregnant women. Despite past attempts by public health authorities to encourage nonpharmaceutical interventions for the prevention of influenza, preventive efforts have focused largely on the use of vaccines. The COVID-19 experience has demonstrated that basic nonpharmaceutical interventions can potentially make a difference in lowering the rates of influenza during future outbreaks. In this article, we discuss the prepandemic role of nonpharmaceutical interventions in disease prevention, the outcomes that were seen in the flu season of 2020, and the role obstetricians should play in using nonpharmaceutical interventions in future influenza disease prevention efforts.

Frequency of high-grade squamous cervical lesions among women over age 65 years living with HIV.

BACKGROUND: Current US cervical cancer screening guidelines recommend screening cessation at the age of 65 years provided women have adequate previous screening and no history of precancer. Women living with HIV are at higher risk of cervical cancer than women living without HIV. Furthermore, limited data exists to quantify the risk of cervical cancer among women who otherwise would qualify for screening cessation. OBJECTIVE: This study aimed to determine whether guidelines recommending women to discontinue cervical cancer screening at the age of 65 years are appropriate for women living with HIV. STUDY DESIGN: Semiannual Papanicolaou testing was performed as part of surveillance visits in the Women's Interagency HIV Study. Launched in October 1994, the Women's Interagency HIV Study is a federally funded US multisite cohort study that has enrolled 3678 women living with HIV and 1304 women living without HIV; we included data throughout September 2019 onward. Conventional Papanicolaou tests were collected at scheduled 6-month visits and read centrally according to the 1991 Bethesda System criteria. Results were analyzed among women at least 65 years of age. The primary endpoint was high-grade cytology, including high-grade squamous intraepithelial lesions; atypical glandular cells; atypical squamous cells, cannot exclude high-grade lesions; and malignant cytology. Wilcoxon rank-sum tests were used to compare the continuous variables, and Chi-square tests or the Fisher exact tests were used to compare the categorical variables. The Kaplan-Meier method was used to calculate the cumulative incidence. Poisson regression was used to compare 2 incidence rates. RESULTS: Of 169 eligible women (121 women living with HIV and 48 women living without HIV) who contributed 678.4 person-years of observation after reaching the age of 65 years, 2.2% had high-grade cytologic abnormalities. However, no cancer was found. Furthermore, 20 women had previous precancer results, and 74 women had abnormal Papanicolaou test results in the previous decade. Among 50 women (38 women living with HIV and 12 women living without HIV) with a previous hysterectomy and no history of cervical precancer, the cumulative incidence rates of high-grade squamous intraepithelial lesions were 0.6 (95% confidence interval, 0.0-3.2) per 100 person-years for women living with HIV and 0.0 (95% confidence interval, 0.0-8.1) per 100 person-years for women living without HIV (P=.61). Only 48 women (27 women living with HIV and 21 women living without HIV) had cervices and met the current guidelines to discontinue screening; their risk of experiencing high-grade squamous intraepithelial lesions was 2.2 (95% confidence interval, 0.6-5.5) per 100 person-years overall and did not vary by HIV status (2.3 [95% confidence interval, 0.5-6.8] per 100 person-years for women living with HIV and 1.8 [95% confidence interval, 0.0-9.8] per 100 person-years for women living without HIV; P=.81). CONCLUSION: Most women living with HIV do not meet the criteria for cervical cancer screening cessation and will need to continue screening over the age of 65 years; however, women who meet the criteria for screening cessation have risks of high-grade squamous lesions similar to women living without HIV and may choose to discontinue.

"The Pleasure Is Better as I've Gotten Older": Sexual Health, Sexuality, and Sexual Risk Behaviors Among Older Women Living With HIV.

There is limited research examining the sexual health and well-being of older women living with HIV (OWLH). Most studies focus on sexual dysfunction, leaving aside the richer context of sexuality and sexual health, including the effect of age-related psychosocial and interpersonal changes on sexual health behaviors. Guided by the integrative biopsychosocial model and the sexual health model, this study explored the importance of sex and sexuality among OWLH to identify their sexual health and HIV prevention needs for program planning. A purposive sample (n = 50) of OWLH was selected from a parent study (n = 2052). We conducted 8 focus groups and 41 in-depth interviews with 50 African American and Latina OWLH aged 50-69 years old in three U.S. cities. The triangulation approach was used to synthesize the data. Six salient themes emerged: sexual pleasure changes due to age, sexual freedom as women age, the role of relationships in sexual pleasure, changes in sexual ability and sexual health needs, sexual risk behaviors, and ageist assumptions about older women's sexuality. We found that sexual pleasure and the need for intimacy continue to be important for OWLH, but that changing sexual abilities and sexual health needs, such as the reduction of sexual desire, as well as increased painful intercourse due to menopause-associated vaginal drying, were persistent barriers to sexual fulfillment and satisfaction. Particular interpersonal dynamics, including low perceptions of the risk of HIV transmission as related to gender, viral suppression, and habitual condomless sex with long-term partners without HIV transmission have resulted in abandoning safer sex practices with serodiscordant partners. These findings suggest that HIV prevention for OWLH should focus on how sexual function and satisfaction intersect with sexual risk. HIV prevention for OWLH should promote ways to maintain satisfying and safe sex lives among aging women.

Systemic Cytokine Levels Do Not Predict CD4(+) T-Cell Recovery After Suppressive Combination Antiretroviral Therapy in Chronic Human Immunodeficiency Virus Infection.

Background. Subjects on suppressive combination antiretroviral therapy (cART) who do not achieve robust reconstitution of CD4(+) T cells face higher risk of complications and death. We studied participants in the Women's Interagency HIV Study with good (immunological responder [IR]) or poor (immunological nonresponder [INR]) CD4(+) T-cell recovery after suppressive cART (n = 50 per group) to determine whether cytokine levels or low-level viral load correlated with INR status. Methods. A baseline sample prior to viral control and 2 subsequent samples 1 and 2 years after viral control were tested. Serum levels of 30 cytokines were measured at each time point, and low-level human immunodeficiency virus (HIV) viral load and anti-HIV antibody levels were measured 2 years after viral suppression. Results. There were minimal differences in cytokine levels between IR and INR subjects. At baseline, macrophage inflammatory protein-3ß levels were higher in IR subjects; after 1 year of suppressive cART, soluble vascular endothelial growth factor-R3 levels were higher in IR subjects; and after 2 years of suppressive cART, interferon gamma-induced protein 10 levels were higher in INR subjects. Very low-level HIV viral load and anti-HIV antibody levels did not differ between IR and INR subjects. Conclusions. These results imply that targeting residual viral replication might not be the optimum therapeutic approach for INR subjects.

Longitudinal Trends in Sexual Behaviors with Advancing Age and Menopause Among Women With and Without HIV-1 Infection.

We assessed changes in self-reported sexual activity (SA) over 13 years among HIV-infected and uninfected women. The impact of aging and menopause on SA and unprotected anal or vaginal intercourse (UAVI) was examined among women in the Women's Interagency HIV Study (WIHS), stratifying by HIV status and detectable viral load among HIV-infected women. Generalized mixed linear models were fitted for each outcome, adjusted for relevant covariates. HIV-uninfected women evidenced higher levels of SA and UAVI than HIV-infected. The odds of SA declined by 62-64 % per decade of age. The odds of SA in a 6-month interval for women aged 40-57 declined by 18-22 % post-menopause (controlling for age). Among HIV+/detectable women only, the odds of any UAVI decreased by 17 % per decade of age; the odds of UAVI were unchanged pre-menopause, and then decreased by 28 % post-menopause. Elucidating the factors accounting for ongoing unprotected sex among older women should inform interventions.

NIH consensus development conference: diagnosing gestational diabetes mellitus.

OBJECTIVE: To provide healthcare providers, patients, and the general public with a responsible assessment of currently available data on diagnosing gestational diabetes mellitus (GDM). PARTICIPANTS: A non-U.S. Department of Health and Human Services, nonadvocate 15-member panel representing the fields of obstetrics and gynecology, maternal-fetal medicine, pediatrics, diabetic research, biostatistics, women's health issues, health services research, decision analysis, health management and policy, health economics, epidemiology, and community engagement. In addition, 16 experts from pertinent fields presented data to the panel and conference audience. EVIDENCE: Presentations by experts and a systematic review of the literature prepared by the University of Alberta Evidence-based Practice Centre, through the Agency for Healthcare Research and Quality (AHRQ). Scientific evidence was given precedence over anecdotal experience. CONFERENCE PROCESS: The panel drafted its statement based on scientific evidence presented in open forum and on published scientific literature. The draft statement was posted at http://prevention.nih.gov/ for public comment and the panel released a final statement approximately 10 weeks later. The final statement is an independent report of the panel and is not a policy statement of the NIH or the Federal Government. CONCLUSIONS: At present, GDM is commonly diagnosed in the United States using a 1-hour screening test with a 50-gram glucose load followed by a 3-hour 100-gram glucose tolerance test (a two-step approach) for those found to be abnormal on the screen. This approach identifies approximately 5% to 6% of the population as having GDM. In contrast, newly proposed diagnostic strategies rely on the administration of a 2-hour glucose tolerance test (a one-step approach) with a fasting component and a 75-gram glucose load. These strategies differ on whether a 1-hour sample is included, whether two abnormal values are required, and the diagnostic cutoffs that are used. The International Association of Diabetes and Pregnancy Study Groups (IADPSG) has proposed diagnostic thresholds based on demonstrated associations between glycemic levels and an increased risk of obstetric and perinatal morbidities. The panel considered whether a one-step approach to the diagnosis of GDM should be adopted in place of the two-step approach. The one-step approach offers certain operational advantages. The current two-step approach is used only during pregnancy and is largely restricted to the United States. There would be value in a consistent, international diagnostic standard across one's lifespan. This unification would allow better standardization of best practices in patient care and comparability of research outcomes. The one-step approach also holds potential advantages for women and their health care providers, as it would allow a diagnosis to be achieved within the context of one visit as opposed to two. However, the one-step approach, as proposed by the IADPSG, is anticipated to increase the frequency of the diagnosis of GDM by twofold to threefold, to a prevalence of approximately 15% to 20%. There are several concerns regarding the diagnosis of GDM in these additional women. It is not well understood whether the additional women identified by this approach will benefit from treatment, and if so, to what extent. Moreover, the care of these women will generate additional direct and indirect health care costs. There is also evidence that the labeling of these women may have unintended consequences, such as an increase in cesarean delivery and more intensive newborn assessments. In addition, increased patient costs, life disruptions, and psychosocial burdens have been identified. Available studies do not provide clear evidence that a one-step approach is cost-effective in comparison with the current two-step approach. After much deliberation, the panel believes that there are clear benefits to international standardization with regard to the one-step approach. Nevertheless, at present, the panel believes that there is not sufficient evidence to adopt a one-step approach. The panel is particularly concerned about the adoption of new criteria that would increase the prevalence of GDM, and the corresponding costs and interventions, without clear demonstration of improvements in the most clinically important health and patient-centered outcomes. Thus, the panel recommends that the two-step approach be continued. However, given the potential benefits of a one-step approach, resolution of the uncertainties associated with its use would warrant revision of this conclusion.

Interarm blood pressure differences in the women's interagency HIV study.

Hypertension has been reported in 8-32% of HIV-infected individuals. Large interarm blood pressure differences (IABPD) may cause misclassification of blood pressure (BP) status. The objectives of this study were to determine the magnitude and factors associated with IABPD in HIV-infected women and uninfected controls. Using automated devices, two BP recordings were measured and averaged from each arm in Brooklyn enrollees of the Women's Interagency HIV Study. Absolute IABPD was calculated for each patient. Among 335 subjects, 238 were HIV infected and 97 were uninfected. Mean systolic and diastolic IABPD were 6 +/- 5 mm Hg and 4 +/- 3 mm Hg, respectively. Twenty-six percent of subjects had systolic IABPD >10 mm Hg and 6% had systolic IABPD >20 mm Hg. Fifteen percent of subjects had diastolic IABPD >10 mm Hg. Interarm BP differences were not associated with HIV serostatus, CD4(+) cell count, and use of highly active antiretroviral therapy. Systolic IABPD >20 mm Hg was associated with obesity (ORadj 5.37, 95% CI 1.47, 19.65), and LDL cholesterol above 160 (ORadj 9.12, 95% CI 2.53, 32.88). Right arm BP measurement resulted in 10% of subjects with high/uncontrolled BP. Bilateral arm BP measurement increased the yield to 15% (p < 0.001). In conclusion, systolic and diastolic IABPD are common and appear to be of clinically important magnitude. Systolic IABPD are related to cardiovascular risk factors but not to HIV-related factors. Bilateral BP determination is important to detect and manage hypertension as well as for accurate cardiovascular risk assessment.

Six-month natural history of oral versus cervical human papillomavirus infection.

Human papillomavirus (HPV) infection is etiologically associated with a subset of oral cancers, and yet, the natural history of oral HPV infection remains unexplored. The feasibility of studying oral HPV natural history was evaluated by collecting oral rinse samples on 2 occasions at a 6-month interval from 136 HIV-positive and 63 HIV-negative participants. Cervical vaginal lavage samples were concurrently collected for comparison. HPV genomic DNA was detected in oral and cervical samples by consensus primer PCR and type-specified for 37 HPV types. The six-month cumulative prevalence of oral HPV infection was significantly less than for cervical infection (p < 0.0001). HIV-positive women were more likely than HIV-negative women to have an oral (33 vs. 15%, p = 0.016) or cervical (78 vs. 51%, p < 0.001) infection detected. Oral HPV infections detected at baseline were as likely as cervical infections to persist to 6 months among HIV-negative (60% vs. 51%, p = 0.70) and HIV-positive (55% vs. 63%, p = 0.27) women. Factors that independently elevated odds for oral HPV persistence differed from cervical infection and included current smoking (OR = 8, 95% CI = 1.3-53), age above 44 years (OR = 20, 95% CI = 4.1-83), CD4 < 500 (OR = 6, 95% CI = 1.1-26), use of HAART therapy (OR = 12, 95% CI = 1.0-156), and time on HAART therapy (trend p = 0.04). The rate of oral HPV infections newly detected at follow-up was significantly lower than cervical infection among HIV-positive (p < 0.001) and HIV-negative women (p < 0.001). Our study not only demonstrates that it is feasible to study the natural history of oral HPV infection with oral rinse sampling, but also indicates that oral and cervical HPV natural history may differ.

Effects of human immunodeficiency virus on protracted amenorrhea and ovarian dysfunction.

OBJECTIVE: To characterize ovarian failure and prolonged amenorrhea from other causes in women who are both human immunodeficiency virus (HIV) seropositive and seronegative. METHODS: This was a cohort study nested in the Women's Interagency HIV Study, a multicenter U.S. study of HIV infection in women. Prolonged amenorrhea was defined as no vaginal bleeding for at least 1 year. A serum follicle stimulating hormone more than 25 milli-International Units/mL and prolonged amenorrhea were used to define ovarian failure. Logistic regressions, chi2, and t tests were performed to estimate relationships between HIV-infection and cofactors with both ovarian failure and amenorrhea from other causes. RESULTS: Results were available for 1,431 women (1,139 HIV seropositive and 292 seronegative). More than one half of the HIV positive women with prolonged amenorrhea of at least 1 year did not have ovarian failure. When adjusted for age, HIV seropositive women were about three times more likely than seronegative women to have prolonged amenorrhea without ovarian failure. Body mass index, serum albumin, and parity were all negatively associated with ovarian failure in HIV seropositive women. CONCLUSION: HIV serostatus is associated with prolonged amenorrhea. It is difficult to ascertain whether the cause of prolonged amenorrhea is ovarian in HIV-infected women without additional testing. LEVEL OF EVIDENCE: II-2.

The myth of the precious baby.

Each year tens of thousands of pregnancies are conceived through assisted reproductive technologies, and increasing numbers of pregnant women are aged older than 40 years. The obstetric management of these pregnancies, including more liberal recourse to cesarean delivery, has at times reflected the belief of providers that they are dealing with "precious babies". A leitmotif in discussions of the "precious child" is the concept that precious equates to irreplaceable (ie, mother who has tried harder to conceive may well have less chance to succeed again in the future). We believe that the obstetrician who decides to modify obstetric care because of these factors is, in fact, substituting physician assumption for patient autonomy. Although it is not counterintuitive to believe that a woman who has gone through assisted reproductive technologies would willingly (perhaps even eagerly) undergo cesarean delivery to avoid even remote risks, it is not safe to assume that women who conceived naturally would not. It is our contention that ultimately all women are best served if every pregnancy were treated as although it had preeminent value.

Effect of hormonal contraceptive use on plasma HIV-1-RNA levels among HIV-infected women.

We compared the HIV-1-RNA and CD4 lymphocyte counts from users and non-users of hormonal contraception cross-sectionally upon entry into the Women's Interagency HIV Study, and again longitudinally. There did not appear to be an association between hormonal contraception use and HIV-1-RNA levels in our study. There was a small increase in CD4 cell counts among hormonal users of doubtful clinical significance.

Prenatal and postpartum zidovudine adherence among pregnant women with HIV: results of a MEMS substudy from the Perinatal Guidelines Evaluation Project.

Adherence to HIV treatment regimens during pregnancy may affect efforts to eliminate vertical transmission and influence the emergence of drug-resistant HIV strains that can affect maternal health and the risk of vertically-transmitted resistant strains. Study objectives were to document patterns of adherence to zidovudine (ZDV) during the perinatal period. Pregnant women with HIV who were seen at public clinics, taking ZDV, and willing to use Medication Event Monitoring Systems (MEMS) caps participated in this adherence substudy. Fifty-three women were included in prenatal analyses; however, 19 women were excluded from postnatal analyses because medical records failed to confirm a postpartum maternal prescription for ZDV. Adherence to ZDV, defined as doses per day taken/prescribed during the last 3 weeks of pregnancy, was extremely low (mean = 50.0%), and declined significantly 3 weeks postpartum (mean = 34.1%) (p =.004). Clinical emphasis must be placed on enhancing adherence during and particularly after pregnancy when ZDV is continued for a mother's own care.