Physician Perspectives on Including Pregnant Women in Covid‐19 Clinical Trials: Time for a Paradigm Change

Upon completion of this chapter, the reader should be able to describe the appropriate management of antiretrovirals for pregnant women living with HIV. Over time, research has demonstrated that proper prevention strategies and interventions during pregnancy, labor, and delivery can significantly reduce the rate of mother-to-child transmission (MTCT) of HIV. In 1994, a pivotal study in the field of HIV medicine, the Pediatric AIDS Clinical Trials Group 076, demonstrated that the use of zidovudine (ZDV) monotherapy during pregnancy substantially reduced the risk of HIV transmission to infants by 67% (...

Download Full-text

P10 Reporting of offspring data in diabetes, HIV infection and hypertension trials during pregnancy: a systematic review

Archives of Disease in Childhood ◽

10.1136/archdischild-2019-esdppp.49 ◽

2019 ◽

Vol 104 (6) ◽

pp. e21.1-e21

Author(s):

B Aurich ◽

T Martin-Montoya ◽

D Zhang ◽

E Jacqz-Aigrain

Keyword(s):

Systematic Review ◽

Clinical Trials ◽

Hiv Infection ◽

Pregnant Women ◽

Health Care Professionals ◽

Full Text ◽

Treatment Options ◽

Safety Data ◽

Chronic Medication ◽

Neonatal Deaths

BackgroundAccording to international guidelines clinical trials are conducted during pregnancy to evaluate benefits and risks of medicines for both the mother and her offspring. Consolidated Standards of Reporting Trials (CONSORT) reporting criteria apply to these trials and should include safety data on the offspring. The safety of maternal treatments is a key issue for health care professionals and parents. Diabetes, human immunodeficiency virus (HIV) infection and hypertension are among the most frequent chronic diseases worldwide in women of child bearing potential. The objective of this systematic review was to analyse offspring data reported in clinical trials conducted in pregnant women receiving chronic drug treatment for one of these conditions.MethodsPubmed and Embase (01/01/1997–31/12/2017) were searched for drug trials in pregnant women with diabetes, HIV infection or hypertension. Titles and abstracts were screened, followed by a full text review of eligible articles. Inclusion criteria were interventional clinical trials in pregnant women treated with chronic medication and full text in English. Trial characteristics, maternal and offspring data were extracted. Data was summarised by disease and study. Twelve key items were considered for the offspring. The protocol was registered on PROSPERO (CRD42017057024).ResultsOverall, 196 articles reporting 132 clinical trials (diabetes n=55; HIV n=59; hypertension n=18) were included. The number of births were frequently not reported (diabetes 40%; HIV 24%; hypertension 56%). Congenital malformations were infrequently reported with sufficient detail (diabetes 27%; HIV 34%; hypertension 6%). Similar observations were made for other key items (e.g. foetal losses, neonatal deaths, birth weight corrected for gestational age).ConclusionsUnderreporting of key data for the offspring was frequent in publications of clinical trials in pregnant women with diabetes, HIV infection or hypertension making the assessment of the benefit-risk ratio of treatment options during pregnancy difficult.Disclosure(s)Nothing to disclose

Download Full-text

Maternal and Infant Death and the rVSV-ZEBOV Vaccine Through Three Recent Ebola Virus Epidemics-West Africa, DRC Équateur and DRC Kivu: 4 Years of Excluding Pregnant and Lactating Women and Their Infants from Immunization

Current Tropical Medicine Reports ◽

10.1007/s40475-019-00195-w ◽

2019 ◽

Vol 6 (4) ◽

pp. 213-222 ◽

Cited By ~ 9

Author(s):

David A. Schwartz

Keyword(s):

At Risk ◽

Clinical Trials ◽

West Africa ◽

Pregnant Women ◽

Ebola Virus ◽

Disease Outbreaks ◽

Case Fatality ◽

Viral Disease ◽

Lactating Women ◽

Health Communities

Abstract Purpose of Review Ebola virus infection has one of the highest overall case fatality rates of any viral disease. It has historically had an especially high case mortality rate among pregnant women and infants—greater than 90% for pregnant women in some outbreaks and close to 100 % in fetuses and newborns. The Merck recombinant vaccine against Ebola virus, termed rVSV-ZEBOV, underwent clinical trials during the 2013–2015 West Africa Ebola epidemic where it was found to be 100% efficacious. It was subsequently used during the 2018 DRC Équateur outbreak and in the 2018 DRC Kivu Ebola which is still ongoing, where its efficacy is 97.5 %. Pregnant and lactating women and their infants have previously been excluded from the design, clinical trials, and administration of many vaccines and drugs. This article critically examines the development of the rVSV-ZEBOV vaccine and its accessibility to pregnant and lactating women and infants as a life-saving form of prevention through three recent African Ebola epidemics—West Africa, DRC Équateur, and DRC Kivu. Recent Findings Pregnant and lactating women and their infants were excluded from participation in the clinical trials of rVSV-ZEBOV conducted during the West Africa epidemic. This policy of exclusion was continued with the occurrence of the DRC Équateur outbreak in 2018, in spite of calls from the public health and global maternal health communities to vaccinate this population. Following the onset of the DRC Kivu epidemic, the exclusion persisted. Eventually, the policy was reversed to include vaccination of pregnant and lactating women. However, it was not implemented until June 2019, 10 months after the start of the epidemic, placing hundreds of women and infants at risk for this highly fatal infection. Summary The historical policy of excluding pregnant and lactating women and infants from vaccine design, clinical trials, and implementation places them at risk, especially in situations of infectious disease outbreaks. In the future, all pregnant women, regardless of trimester, breastfeeding mothers, and infants, should have access to the Ebola vaccine.

Download Full-text

Randomized clinical trials of oral vitamin D supplementation in need of a paradigm change: The vitamin D autacoid paradigm

Medical Hypotheses ◽

10.1016/j.mehy.2019.109417 ◽

2020 ◽

Vol 134 ◽

pp. 109417

Author(s):

Tanguy Chabrol ◽

Didier Wion

Keyword(s):

Vitamin D ◽

Clinical Trials ◽

Randomized Clinical Trials ◽

Vitamin D Supplementation ◽

Paradigm Change ◽

Oral Vitamin

Download Full-text

Immunogenicity of influenza vaccines administered to pregnant women in randomized clinical trials in Mali and South Africa

Vaccine ◽

10.1016/j.vaccine.2020.07.020 ◽

2020 ◽

Vol 38 (41) ◽

pp. 6478-6483

Author(s):

Avnika B. Amin ◽

Marta C. Nunes ◽

Milagritos D. Tapia ◽

Shabir A. Madhi ◽

Clare L. Cutland ◽

...

Keyword(s):

South Africa ◽

Clinical Trials ◽

Pregnant Women ◽

Randomized Clinical Trials ◽

Influenza Vaccines

Download Full-text

Sepsis in pregnancy and early goal-directed therapy

Obstetric Medicine ◽

10.1258/om.2009.090024 ◽

2009 ◽

Vol 2 (3) ◽

pp. 93-99 ◽

Cited By ~ 6

Author(s):

Julie Joseph ◽

Aneeta Sinha ◽

Michael Paech ◽

Barry N J Walters

Keyword(s):

Clinical Trials ◽

Pregnant Women ◽

Randomized Clinical Trials ◽

Surviving Sepsis Campaign ◽

Goal Directed Therapy ◽

Early Goal Directed Therapy ◽

Conventional Management ◽

Serious Infection ◽

Underlying Pathophysiology ◽

In Pregnancy

Sepsis is a major cause of serious morbidity and mortality in pregnant women and their babies. Conventional management has evolved over many years. Improved understanding of the underlying pathophysiology and randomized clinical trials have led to recommendations for the formalization and standardization of the management of severe sepsis in non-pregnant patients. Most of these recommendations are applicable to pregnancy. The Surviving Sepsis Campaign and Early Goal Directed Therapy have relevance to the care of pregnant women with serious infection and are reviewed here.

Download Full-text

Challenges in Assessing Outcomes among Infants of Pregnant HIV-Positive Women Receiving ART in Uganda

AIDS Research and Treatment ◽

10.1155/2017/3202737 ◽

2017 ◽

Vol 2017 ◽

pp. 1-4

Author(s):

Barbara Castelnuovo ◽

Frank Mubiru ◽

Ivan Kalule ◽

Shadia Nakalema ◽

Agnes Kiragga

Keyword(s):

Clinical Trials ◽

Pregnant Women ◽

Median Time ◽

Hiv Transmission ◽

Cd4 Count ◽

Hiv Positive ◽

Hiv Positive Women

Since 2012, the WHO recommends lifelong ART with TDF+FTC/3TC+EFV for all HIV-positive pregnant and breastfeeding women (Option B-plus). In this analysis we describe the proportion of early and late transmission in mothers with high retention in Kampala, Uganda. We included 700 pregnant women from January 2012 to August 2014 with a follow-up extended to August 2016; the median age was 31 years (IQR: 26–35), 36.3% in WHO stage 3/4; median CD4 count was 447 cells/μL (IQR: 301–651) and 73.3% were already on ART for a median time of 28 (IQR: 10–57) months; 52% infants were male and median weight was 3.2 Kg (IQR: 2.5–3.5). Five hundred and sixty-five (80.7%) infants had at least one test for HIV; 22 (3.1%) infants died, all with unknown serostatus; 3 tested positive at week 6 and one additional at months 12 and 18. Two of the mothers of the 4 HIV-positive infants were ART-naïve at the time of pregnancy. We report very low documented HIV transmission comparable with those reported in clinical trials settings; however, demonstrating the efficacy of Option B-plus in terms of averted transmission in routine settings is challenging since high proportion of infants do not have documented HIV tests.

Download Full-text

Opening windows of opportunities: Evidence for interventions to prevent or treat depression in pregnant women being associated with changes in offspring's developmental trajectories of psychopathology risk

Development and Psychopathology ◽

10.1017/s0954579418000536 ◽

2018 ◽

Vol 30 (3) ◽

pp. 1179-1196 ◽

Cited By ~ 11

Author(s):

Sherryl H. Goodman ◽

Katherine A. Cullum ◽

Sona Dimidjian ◽

Laura M. River ◽

Christine Youngwon Kim

Keyword(s):

Clinical Trials ◽

Pregnant Women ◽

Fetal Programming ◽

Randomized Clinical Trials ◽

Programming Model ◽

Developmental Trajectories ◽

Meta Analysis ◽

Experimental Studies ◽

Behavioral Changes ◽

Small Effect Size

AbstractAlthough animal models and correlational studies support a model of fetal programming as a mechanism in the transmission of risk for psychopathology from parents to children, the experimental studies that are required to empirically test the model with the human prenatal dyad are scarce. With a systematic review and meta-analysis of the literature, we critically examined the evidence regarding the neurobiological and behavioral changes in infants as a function of randomized clinical trials to prevent or reduce maternal depression during pregnancy, treating randomized clinical trials as experiments testing the fetal programming model. Based on 25 articles that met inclusion criteria, we found support for interventions designed to change maternal prenatal mood being associated with changes in offspring functioning, but with a very small effect size. Effect sizes ranged broadly, and were higher for younger children. The findings enhance understanding of putative mechanisms in the transmission of risk from women's prenatal depression to infants’ vulnerabilities to, and early signs of, the development of psychopathology. We note limitations of the literature and suggest solutions to advance understanding of how preventing or treating depression in pregnant women might disrupt the transmission of risk to the infants.

Download Full-text