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Item Association of hemoglobin levels in the first trimester and at 26 to 30 weeks with fetal and neonatal outcomes: A secondary analyses of the Global Network for Women’s and Children’s Health’s ASPIRIN Trial(Wiley, 2021) Jessani, Saleem; Saleem, Sarah; Hoffman, Matthew K.; Goudar, Shivaprasad S.; Derman, Richard J.; Moore, Janet L.; Garces, Ana; Figueroa, Lester; Krebs, Nancy F.; Okitawutshu, Jean; Tshefu, Antoinette; Bose, Carl L.; Mwenechanya, Musaku; Chomba, Elwyn; Carlo, Waldemar A.; Das, Prabir Kumar; Patel, Archana; Hibberd, Patricia L.; Esamai, Fabian; Liechty, Edward A.; Bucher, Sherri; Nolen, Tracy L.; Koso-Thomas, Marion; Miodovnik, Menachem; McClure, Elizabeth M.; Goldenberg, Robert L.; Social and Behavioral Sciences, School of Public HealthObjective: Limited data are available from low- and middle-income countries (LMICs) on the relationship of haemoglobin levels to adverse outcomes at different times during pregnancy. We evaluated the association of haemoglobin levels in nulliparous women at two times in pregnancy with pregnancy outcomes. Design: ASPIRIN Trial data were used to study the association between haemoglobin levels measured at 6+0 -13+6 weeks and 26+0 -30+0 weeks of gestation with fetal and neonatal outcomes. Setting: Obstetric care facilities in Pakistan, India, Kenya, Zambia, The Democratic Republic of the Congo and Guatemala. Population: A total of 11 976 pregnant women. Methods: Generalised linear models were used to obtain adjusted relative risks and 95% CI for adverse outcomes. Main outcome measures: Preterm birth, stillbirth, neonatal death, small for gestational age (SGA) and birthweight <2500 g. Results: The mean haemoglobin levels at 6+0 -13+6 weeks and at 26-30 weeks of gestation were 116 g/l (SD 17) and 107 g/l (SD 15), respectively. In general, pregnancy outcomes were better with increasing haemoglobin. At 6+0 -13+6 weeks of gestation, stillbirth, SGA and birthweight <2500 g, were significantly associated with haemoglobin of 70-89 g/l compared with haemoglobin of 110-129 g/l The relationships of adverse pregnancy outcomes with various haemoglobin levels were more marked at 26-30 weeks of gestation. Conclusions: Both lower and some higher haemoglobin concentrations are associated with adverse fetal and neonatal outcomes at 6+0 -13+6 weeks and at 26-30 weeks of gestation, although the relationship with low haemoglobin levels appears more consistent and generally stronger.Item Azithromycin to Prevent Sepsis or Death in Women Planning a Vaginal Birth(Massachusetts Medical Society, 2023) Tita, Alan T. N.; Carlo, Waldemar A.; McClure, Elizabeth M.; Mwenechanya, Musaku; Chomba, Elwyn; Hemingway-Foday, Jennifer J.; Kavi, Avinash; Metgud, Mrityunjay C.; Goudar, Shivaprasad S.; Derman, Richard; Lokangaka, Adrien; Tshefu, Antoinette; Bauserman, Melissa; Bose, Carl; Shivkumar, Poonam; Waikar, Manju; Patel, Archana; Hibberd, Patricia L.; Nyongesa, Paul; Esamai, Fabian; Ekhaguere, Osayame A.; Bucher, Sherri; Jessani, Saleem; Tikmani, Shiyam S.; Saleem, Sarah; Goldenberg, Robert L.; Billah, Sk M.; Lennox, Ruth; Haque, Rashidul; Petri, William; Figueroa, Lester; Mazariegos, Manolo; Krebs, Nancy F.; Moore, Janet L.; Nolen, Tracy L.; Koso-Thomas, Marion; A-PLUS Trial Group; Pediatrics, School of MedicineBackground: The use of azithromycin reduces maternal infection in women during unplanned cesarean delivery, but its effect on those with planned vaginal delivery is unknown. Data are needed on whether an intrapartum oral dose of azithromycin would reduce maternal and offspring sepsis or death. Methods: In this multicountry, placebo-controlled, randomized trial, we assigned women who were in labor at 28 weeks' gestation or more and who were planning a vaginal delivery to receive a single 2-g oral dose of azithromycin or placebo. The two primary outcomes were a composite of maternal sepsis or death and a composite of stillbirth or neonatal death or sepsis. During an interim analysis, the data and safety monitoring committee recommended stopping the trial for maternal benefit. Results: A total of 29,278 women underwent randomization. The incidence of maternal sepsis or death was lower in the azithromycin group than in the placebo group (1.6% vs. 2.4%), with a relative risk of 0.67 (95% confidence interval [CI], 0.56 to 0.79; P<0.001), but the incidence of stillbirth or neonatal death or sepsis was similar (10.5% vs. 10.3%), with a relative risk of 1.02 (95% CI, 0.95 to 1.09; P = 0.56). The difference in the maternal primary outcome appeared to be driven mainly by the incidence of sepsis (1.5% in the azithromycin group and 2.3% in the placebo group), with a relative risk of 0.65 (95% CI, 0.55 to 0.77); the incidence of death from any cause was 0.1% in the two groups (relative risk, 1.23; 95% CI, 0.51 to 2.97). Neonatal sepsis occurred in 9.8% and 9.6% of the infants, respectively (relative risk, 1.03; 95% CI, 0.96 to 1.10). The incidence of stillbirth was 0.4% in the two groups (relative risk, 1.06; 95% CI, 0.74 to 1.53); neonatal death within 4 weeks after birth occurred in 1.5% in both groups (relative risk, 1.03; 95% CI, 0.86 to 1.24). Azithromycin was not associated with a higher incidence in adverse events. Conclusions: Among women planning a vaginal delivery, a single oral dose of azithromycin resulted in a significantly lower risk of maternal sepsis or death than placebo but had little effect on newborn sepsis or death.Item Corrigendum to The impact of risk factors on aspirin's efficacy for the prevention of preterm birth. American Journal of Obstetrics & Gynecology MFM. Volume 5, Issue 10, October 2023, 101095(Elsevier, 2024) Nuss, Emily E.; Hoffman, Matthew K.; Goudar, Shivaprasad S.; Kavi, Avinash; Metgud, Mrityunjay; Somannavar, Manjunath; Okitawutshu, Jean; Lokangaka, Adrien; Tshefu, Antoinette; Bauserman, Melissa; Tembo, Abigail Mwapule; Chomba, Elwyn; Carlo, Waldemar A.; Figueroa, Lester; Krebs, Nancy F.; Jessani, Saleem; Saleem, Sarah; Goldenberg, Robert L.; Kurhe, Kunal; Das, Prabir; Hibberd, Patricia L.; Achieng, Emmah; Nyongesa, Paul; Esamai, Fabian; Liechty, Edward A.; Bucher, Sherri; Goco, Norman; Hemingway-Foday, Jennifer; Moore, Janet; McClure, Elizabeth M.; Silver, Robert M.; Derman, Richard J.; Patel, Archana; Aspirin Supplementation for Pregnancy Indicated Risk Reduction In Nulliparas Study Group; Pediatrics, School of MedicineThe authors regret that the originally published manuscript erroneously excluded a contributing author Archana Patel MD, PhD. The authors would like to apologise for any inconvenience caused.Item Cost-effectiveness of low-dose aspirin for the prevention of preterm birth: a prospective study of the Global Network for Women's and Children's Health Research(Elsevier, 2023) Patterson, Jackie K.; Neuwahl, Simon; Goco, Norman; Moore, Janet; Goudar, Shivaprasad S.; Derman, Richard J.; Hoffman, Matthew; Metgud, Mrityunjay; Somannavar, Manjunath; Kavi, Avinash; Okitawutshu, Jean; Lokangaka, Adrien; Tshefu, Antoinette; Bose, Carl L.; Mwapule, Abigail; Mwenechanya, Musaku; Chomba, Elwyn; Carlo, Waldemar A.; Chicuy, Javier; Figueroa, Lester; Krebs, Nancy F.; Jessani, Saleem; Saleem, Sarah; Goldenberg, Robert L.; Kurhe, Kunal; Das, Prabir; Patel, Archana; Hibberd, Patricia L.; Achieng, Emmah; Nyongesa, Paul; Esamai, Fabian; Bucher, Sherri; Liechty, Edward A.; Bresnahan, Brian W.; Koso-Thomas, Marion; McClure, Elizabeth M.; Pediatrics, School of MedicineBackground: Premature birth is associated with an increased risk of mortality and morbidity, and strategies to prevent preterm birth are few in number and resource intensive. In 2020, the ASPIRIN trial showed the efficacy of low-dose aspirin (LDA) in nulliparous, singleton pregnancies for the prevention of preterm birth. We sought to investigate the cost-effectiveness of this therapy in low-income and middle-income countries. Methods: In this post-hoc, prospective, cost-effectiveness study, we constructed a probabilistic decision tree model to compare the benefits and costs of LDA treatment compared with standard care using primary data and published results from the ASPIRIN trial. In this analysis from a health-care sector perspective, we considered the costs and effects of LDA treatment, pregnancy outcomes, and neonatal health-care use. We did sensitivity analyses to understand the effect of the price of the LDA regimen, and the effectiveness of LDA in reducing both preterm birth and perinatal death. Findings: In model simulations, LDA was associated with 141 averted preterm births, 74 averted perinatal deaths, and 31 averted hospitalisations per 10 000 pregnancies. The reduction in hospitalisation resulted in a cost of US$248 per averted preterm birth, $471 per averted perinatal death, and $15·95 per disability-adjusted life year. Interpretation: LDA treatment in nulliparous, singleton pregnancies is a low-cost, effective treatment to reduce preterm birth and perinatal death. The low cost per disability-adjusted life year averted strengthens the evidence in support of prioritising the implementation of LDA in publicly funded health care in low-income and middle-income countries.Item Low-Dose Aspirin for the Prevention of Preterm Delivery in Nulliparous Women with a Singleton Pregnancy: A Randomised Multi-country Placebo Controlled Trial(Elsevier, 2020) Hoffman, Matthew K.; Goudar, Shivaprasad S.; Kodkany, Bhalachandra S.; Metgud, Mrityunjay; Somannavar, Manjunath; Okitawutshu, Jean; Lokangaka, Adrien; Tshefu, Antoinette; Bose, Carl L.; Mwapule, Abigail; Mwenechanya, Musaku; Chomba, Elwyn; Carlo, Waldemar A.; Chicuy, Javier; Figueroa, Lester; Garces, Ana; Krebs, Nancy F.; Jessani, Saleem; Zehra, Farnaz; Saleem, Sarah; Goldenberg, Robert L.; Kurhe, Kunal; Das, Prabir; Patel, Archana; Hibberd, Patricia L.; Achieng, Emmah; Nyongesa, Paul; Esamai, Fabian; Liechty, Edward A.; Goco, Norman; Hemingway-Foday, Jennifer; Moore, Janet; Nolen, Tracy L.; McClure, Elizabeth M.; Koso-Thomas, Marion; Miodovnik, Menachem; Silver, Robert; Derman, Richard J.; Pediatrics, School of MedicineBackground: Preterm birth remains a common cause of neonatal mortality with a disproportionate burden occurring in low and middle-income countries. Meta-analyses of low-dose aspirin to prevent preeclampsia suggest that the incidence of preterm birth may also be decreased, particularly if initiated before 16 weeks. Methods: We completed a randomised multi-country (Democratic Republic of Congo, Guatemala, India, Kenya, Pakistan, Zambia) double masked trial of aspirin (81 mg) daily compared to placebo initiated between 6 weeks and 0 days and 13 weeks and 6 days of pregnancy in nulliparous women between14 and 40 years of age with an ultrasound confirming gestational age and singleton viable pregnancy. Randomisation (1:1) was stratified by site. The primary outcome of preterm birth, defined as delivery prior to 37 weeks gestational age, was analyzed in randomised women with pregnancy outcomes at or after 20 weeks. This study is registered with ClinicalTrials.gov, number NCT02409680, and the Clinical Trial Registry, India, number CTRI/2016/05/006970. Findings: From March 2016 through June 2018, 11,976 women were assigned to aspirin (5,990 women) or placebo (5,986 women). Amongst randomised women, an evaluable birth outcome beyond 20 weeks occurred in 5787 women who received Aspirin and 5771 women who received placebo Preterm birth occurred in 11.6% of women randomised to aspirin and 13.1% randomised to placebo (Relative Risk [RR], 0.89; 95% CI, 0.81 to 0.98; Risk Difference, −0·02; 95% CI, −0·03, −0·01). Women randomised to aspirin were less likely to experience perinatal mortality (45.7/1000 vs 53.6/1000; RR, 0.86; 95%CI, 0.73 to 1.00). Other adverse maternal/neonatal events were similar between the two groups. Interpretation: In nulliparous women with singleton pregnancies, low dose aspirin initiated between 6 weeks and 0 days and 13 weeks and 6 days results in lower rates of preterm delivery before 37 weeks and perinatal mortality.Item Predictors of Plasmodium falciparum Infection in the First Trimester Among Nulliparous Women From Kenya, Zambia, and the Democratic Republic of the Congo(Oxford University Press, 2022) Leuba, Sequoia I.; Westreich, Daniel; Bose, Carl L.; Powers, Kimberly A.; Olshan, Andy; Taylor, Steve M.; Tshefu, Antoinette; Lokangaka, Adrien; Carlo, Waldemar A.; Chomba, Elwyn; Liechty, Edward A.; Bucher, Sherri L.; Esamai, Fabian; Jessani, Saleem; Saleem, Sarah; Goldenberg, Robert L.; Moore, Janet; Nolen, Tracy; Hemingway-Foday, Jennifer; McClure, Elizabeth M.; Koso-Thomas, Marion; Derman, Richard J.; Hoffman, Matthew; Bauserman, Melissa; Pediatrics, School of MedicineBackground: Malaria can have deleterious effects early in pregnancy, during placentation. However, malaria testing and treatment are rarely initiated until the second trimester, leaving pregnancies unprotected in the first trimester. To inform potential early intervention approaches, we sought to identify clinical and demographic predictors of first-trimester malaria. Methods: We prospectively recruited women from sites in the Democratic Republic of the Congo (DRC), Kenya, and Zambia who participated in the ASPIRIN (Aspirin Supplementation for Pregnancy Indicated risk Reduction In Nulliparas) trial. Nulliparous women were tested for first-trimester Plasmodium falciparum infection by quantitative polymerase chain reaction. We evaluated predictors using descriptive statistics. Results: First-trimester malaria prevalence among 1513 nulliparous pregnant women was 6.3% (95% confidence interval [CI], 3.7%-8.8%] in the Zambian site, 37.8% (95% CI, 34.2%-41.5%) in the Kenyan site, and 62.9% (95% CI, 58.6%-67.2%) in the DRC site. First-trimester malaria was associated with shorter height and younger age in Kenyan women in site-stratified analyses, and with lower educational attainment in analyses combining all 3 sites. No other predictors were identified. Conclusions: First-trimester malaria prevalence varied by study site in sub-Saharan Africa. The absence of consistent predictors suggests that routine parasite screening in early pregnancy may be needed to mitigate first-trimester malaria in high-prevalence settings.Item Safety of daily low-dose aspirin use during pregnancy in low-income and middle-income countries(Elsevier, 2021) Short, Vanessa L.; Hoffman, Matthew; Metgud, Mrityunjay; Kavi, Avinash; Goudar, Shivaprasad S.; Okitawutshu, Jean; Tshefu, Antoinette; Bose, Carl L.; Mwenechanya, Musaku; Chomba, Elwyn; Carlo, Waldemar A.; Figueroa, Lester; Garces, Ana; Krebs, Nancy F.; Jessani, Saleem; Saleem, Sarah; Goldenberg, Robert L.; Das, Prabir Kumar; Patel, Archana; Hibberd, Patricia L.; Achieng, Emmah; Nyongesa, Paul; Esamai, Fabian; Bucher, Sherri; Nowak, Kayla J.; Goco, Norman; Nolen, Tracy L.; McClure, Elizabeth M.; Koso-Thomas, Marion; Miodovnik, Menachem; Derman, Richard J.; Medicine, School of MedicineBACKGROUND The daily use of low-dose aspirin may be a safe, widely available, and inexpensive intervention for reducing the risk of preterm birth. Data on the potential side effects of low-dose aspirin use during pregnancy in low- and middle-income countries are needed. OBJECTIVE This study aimed to assess differences in unexpected emergency medical visits and potential maternal side effects from a randomized, double-blind, multicountry, placebo-controlled trial of low-dose aspirin use (81 mg daily, from 6 to 36 weeks’ gestation). STUDY DESIGN This study was a secondary analysis of data from the Aspirin Supplementation for Pregnancy Indicated Risk Reduction In Nulliparas trial, a trial of the Global Network for Women's and Children's Health conducted in India (2 sites), Pakistan, Guatemala, Democratic Republic of the Congo, Kenya, and Zambia. The outcomes for this analysis were unexpected emergency medical visits and the occurrence of the following potential side effects—overall and separately—nausea, vomiting, rash or hives, diarrhea, gastritis, vaginal bleeding, allergic reaction, and any other potential side effects. Analyses were performed overall and by geographic region. RESULTS Between the aspirin (n=5943) and placebo (n=5936) study groups, there was no statistically significant difference in the risk of unexpected emergency medical visits or the risk of any potential side effect (overall). Of the 8 potential side effects assessed, only 1 (rash or hives) presented a different risk by treatment group (4.2% in the aspirin group vs 3.5% in the placebo group; relative risk, 1.20; 95% confidence interval, 1.01–1.43; P=.042). CONCLUSION The daily use of low-dose aspirin seems to be a safe intervention for reducing the risk of preterm birth and well tolerated by nulliparous pregnant women between 6 and 36 weeks’ gestation in low- and middle-income countries.Item The efficacy of low-dose aspirin in pregnancy among women in malaria-endemic countries(Springer, 2022-04-10) Bauserman, Melissa; Leuba, Sequoia I.; Hemingway-Foday, Jennifer; Nolen, Tracy L.; Moore, Janet; McClure, Elizabeth M.; Lokangaka, Adrien; Tsehfu, Antoinette; Patterson, Jackie; Liechty, Edward A.; Esamai, Fabian; Carlo, Waldemar A.; Chomba, Elwyn; Goldenberg, Robert L.; Saleem, Sarah; Jessani, Saleem; Koso-Thomas, Marion; Hoffman, Matthew; Derman, Richard J.; Meshnick, Steven R.; Bose, Carl L.; Pediatrics, School of MedicineBackground Low dose aspirin (LDA) is an effective strategy to reduce preterm birth. However, LDA might have differential effects globally, based on the etiology of preterm birth. In some regions, malaria in pregnancy could be an important modifier of LDA on birth outcomes and anemia. Methods This is a sub-study of the ASPIRIN trial, a multi-national, randomized, placebo controlled trial evaluating LDA effect on preterm birth. We enrolled a convenience sample of women in the ASPIRIN trial from the Democratic Republic of Congo (DRC), Kenya and Zambia. We used quantitative polymerase chain reaction to detect malaria. We calculated crude prevalence proportion ratios (PRs) for LDA by malaria for outcomes, and regression modelling to evaluate effect measure modification. We evaluated hemoglobin in late pregnancy based on malaria infection in early pregnancy. Results One thousand four hundred forty-six women were analyzed, with a malaria prevalence of 63% in the DRC site, 38% in the Kenya site, and 6% in the Zambia site. Preterm birth occurred in 83 (LDA) and 90 (placebo) women, (PR 0.92, 95% CI 0.70, 1.22), without interaction between LDA and malaria (p = 0.75). Perinatal mortality occurred in 41 (LDA) and 43 (placebo) pregnancies, (PR 0.95, 95% CI 0.63, 1.44), with an interaction between malaria and LDA (p = 0.014). Hemoglobin was similar by malaria and LDA status. Conclusions Malaria in early pregnancy did not modify the effects of LDA on preterm birth, but modified the effect of LDA on perinatal mortality. This effect measure modification deserves continued study as LDA is used in malaria endemic regions.Item The impact of risk factors on aspirin's efficacy for the prevention of preterm birth(Elsevier, 2023) Nuss, Emily E.; Hoffman, Matthew K.; Goudar, Shivaprasad S.; Kavi, Avinash; Metgud, Mrityunjay; Somannavar, Manjunath; Okitawutshu, Jean; Lokangaka, Adrien; Tshefu, Antoinette; Bauserman, Melissa; Mwapule Tembo, Abigail; Chomba, Elwyn; Carlo, Waldemar A.; Figueroa, Lester; Krebs, Nancy F.; Jessani, Saleem; Saleem, Sarah; Goldenberg, Robert L.; Kurhe, Kunal; Das, Prabir; Hibberd, Patricia L.; Achieng, Emmah; Nyongesa, Paul; Esamai, Fabian; Liechty, Edward A.; Bucher, Sherri; Goco, Norman; Hemingway-Foday, Jennifer; Moore, Janet; McClure, Elizabeth M.; Silver, Robert M.; Derman, Richard J.; Aspirin Supplementation for Pregnancy Indicated Risk Reduction In Nulliparas Study Group; Pediatrics, School of MedicineBackground: The Aspirin Supplementation for Pregnancy Indicated Risk Reduction In Nulliparas trial was a landmark study that demonstrated a reduction in preterm birth and hypertensive disorders of pregnancy in nulliparous women who received low-dose aspirin. All women in the study had at least 1 moderate-risk factor for preeclampsia (nulliparity). Unlike current US Preventative Service Task Force guidelines, which recommend low-dose aspirin for ≥2 moderate-risk factors, women in this study were randomized to receive low-dose aspirin regardless of the presence or absence of an additional risk factor. Objective: This study aimed to compare how low-dose aspirin differentially benefits nulliparous women with and without additional preeclampsia risk factors for the prevention of preterm birth and hypertensive disorders of pregnancy. Study design: This was a non-prespecified secondary analysis of the Aspirin Supplementation for Pregnancy Indicated Risk Reduction In Nulliparas trial that randomized nulliparous women with singleton pregnancies from 6 low-middle-income countries to receive low-dose aspirin or placebo. Our primary exposure was having an additional preeclampsia risk factor beyond nulliparity. Our primary outcome was preterm birth before 37 weeks of gestation, and our secondary outcomes included preterm birth before 34 weeks of gestation, preterm birth before 28 weeks of gestation, hypertensive disorders of pregnancy, and perinatal mortality. Results: Among 11,558 nulliparous women who met the inclusion criteria, 66.8% had no additional risk factors. Low-dose aspirin similarly reduced the risk of preterm birth at <37 weeks of gestation in women with and without additional risk factors (relative risk: 0.75 vs 0.85; P=.35). Additionally for our secondary outcomes, low-dose aspirin similarly reduced the risk of preterm birth at <28 weeks of gestation, hypertensive disorders of pregnancy, and perinatal mortality in women with and without additional risk factors. The reduction of preterm birth at <34 weeks of gestation with low-dose aspirin was significantly greater in women without additional risk factors than those with an additional risk factor (relative risk: 0.69 vs 1.04; P=.04). Conclusion: Low-dose aspirin's ability to prevent preterm birth, hypertensive disorders of pregnancy, and perinatal mortality was similar in nulliparous women with and without additional risk factors. Professional societies should consider recommending low-dose aspirin to all nulliparous women.Item Trends over time in the knowledge, attitude and practices of pregnant women related to COVID-19: A cross-sectional survey from seven low- and middle-income countries(Wiley, 2023) Jessani, Saleem; Saleem, Sarah; Fogleman, Elizabeth; Billah, Sk Masum; Haque, Rashidul; Figueroa, Lester; Lokangaka, Adrien; Tshefu, Antoinette; Goudar, Shivaprasad S.; Kavi, Avinash; Esamai, Fabian; Mwenchanya, Musaku; Chomba, Elwyn; Patel, Archana; Das, Prabir; Mazariegos, Manolo; Bauserman, Melissa; Petri, William A., Jr.; Krebs, Nancy F.; Derman, Richard J.; Carlo, Waldemar A.; Bucher, Sherri; Hibberd, Patricia L.; Koso-Thomas, Marion; Bann, Carla M.; McClure, Elizabeth M.; Goldenberg, Robert L.; Pediatrics, School of MedicineObjective: To understand trends in the knowledge, attitudes and practices (KAP) of pregnant women related to COVID-19 in seven low- and middle-income countries. Design: Multi-country population-based prospective observational study. Setting: Study sites in Bangladesh, the Demographic Republic of Congo (DRC), Guatemala, India (two sites), Kenya, Pakistan and Zambia. Population: Pregnant women in the Global Network's Maternal and Neonatal Health Registry (MNHR). Methods: Pregnant women enrolled in the MNHR were interviewed to assess their KAP related to COVID-19 from September 2020 through July 2022 across all study sites. Main outcome measures: Trends of COVID-19 KAP were assessed using the Cochran-Armitage test for trend. Results: A total of 52 297 women participated in this study. There were wide inter-country differences in COVID-19-related knowledge. The level of knowledge of women in the DRC was much lower than that of women in the other sites. The ability to name COVID-19 symptoms increased over time in the African sites, whereas no such change was observed in Bangladesh, Belagavi and Guatemala. All sites observed decreasing trends over time in women avoiding antenatal care visits. Conclusions: The knowledge and attitudes of pregnant women related to COVID-19 varied substantially among the Global Network sites over a period of 2 years; however, there was very little change in knowledge related to COVID-19 over time across these sites. The major change observed was that fewer women reported avoiding medical care because of COVID-19 across all sites over time.