Browsing by Author "Nolen, Tracy L."
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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 Blood myo-inositol concentrations in preterm and term infants(Springer Nature, 2021-02) Brion, Luc P.; Phelps, Dale L.; Ward, Robert M.; Nolen, Tracy L.; Hallman, N. Mikko K.; Das, Abhik; Zaccaro, Daniel J.; Ball, M. Bethany; Watterberg, Kristi L.; Frantz, Ivan D., III.; Cotten, C. Michael; Poindexter, Brenda B.; Oh, William; Lugo, Ralph A.; Van Meurs, Krisa P.; O’Shea, T. Michael; Zaterka-Baxter, Kristin M.; Higgins, Rosemary D.; Pediatrics, School of MedicineObjective: To describe relationship between cord blood (representing fetal) myo-inositol concentrations and gestational age (GA) and to determine trends of blood concentrations in enterally and parenterally fed infants from birth to 70 days of age. Design/methods: Samples were collected in 281 fed or unfed infants born in 2005 and 2006. Myo-inositol concentrations were displayed in scatter plots and analyzed with linear regression models of natural log-transformed values. Results: In 441 samples obtained from 281 infants, myo-inositol concentrations varied from nondetectable to 1494 μmol/L. Cord myo-inositol concentrations decreased an estimated 11.9% per week increase in GA. Postnatal myo-inositol concentrations decreased an estimated 14.3% per week increase in postmenstrual age (PMA) and were higher for enterally fed infants compared to unfed infants (51% increase for fed vs. unfed infants). Conclusions: Fetal myo-inositol concentrations decreased with increasing GA. Postnatal concentrations decreased with increasing PMA and were higher among enterally fed than unfed infants.Item Evaluating the effect of care around labor and delivery practices on early neonatal mortality in the Global Network's Maternal and Newborn Health Registry(Springer Nature, 2020-11-30) Patel, Archana B.; Simmons, Elizabeth M.; Rao, Sowmya R.; Moore, Janet; Nolen, Tracy L.; Goldenberg, Robert L.; Goudar, Shivaprasad S.; Somannavar, Manjunath S.; Esamai, Fabian; Nyongesa, Paul; Garces, Ana L.; Chomba, Elwyn; Mwenechanya, Musaku; Saleem, Sarah; Naqvi, Farnaz; Bauserman, Melissa; Bucher, Sherri; Krebs, Nancy F.; Derman, Richard J.; Carlo, Waldemar A.; Koso‑ThomasMcClure, Marion Elizabeth M.; Hibberd, Patricia L.; Pediatrics, School of MedicineBackground: Neonatal deaths in first 28-days of life represent 47% of all deaths under the age of five years globally and are a focus of the United Nation's (UN's) Sustainable Development Goals. Pregnant women are delivering in facilities but that does not indicate quality of care during delivery and the postpartum period. The World Health Organization's Essential Newborn Care (ENC) package reduces neonatal mortality, but lacks a simple and valid composite index that measures its effectiveness. Methods: Data on 5 intra-partum and 3 post-partum practices (indicators) recommended as part of ENC, routinely collected in NICHD's Global Network's (GN) Maternal Newborn Health Registry (MNHR) between 2010 and 2013, were included. We evaluated if all 8 practices (Care around Delivery - CAD), combined as an index was associated with reduced early neonatal mortality rates (days 0-6 of life). Results: A total of 150,848 live births were included in the analysis. The individual indicators varied across sites. All components were present in 19.9% births (range 0.4 to 31% across sites). Present indicators (8 components) were associated with reduced early neonatal mortality [adjusted RR (95% CI):0.81 (0.77, 0.85); p < 0.0001]. Despite an overall association between CAD and early neonatal mortality (RR < 1.0 for all early mortality): delivery by skilled birth attendant; presence of fetal heart and delayed bathing were associated with increased early neonatal mortality. Conclusions: Present indicators (8 practices) of CAD were associated with a 19% reduction in the risk of neonatal death in the diverse health facilities where delivery occurred within the GN MNHR. These indicators could be monitored to identify facilities that need to improve compliance with ENC practices to reduce preventable neonatal deaths. Three of the 8 indicators were associated with increased neonatal mortality, due to baby being sick at birth. Although promising, this composite index needs refinement before use to monitor facility-based quality of care in association with early neonatal mortality.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 Neurodevelopmental outcome of preterm infants enrolled in myo-inositol randomized controlled trial(Springer Nature, 2021) Adams-Chapman, Ira; Watterberg, Kristi L.; Nolen, Tracy L.; Hirsch, Shawn; Cole, Carol A.; Cotten, C. Michael; Oh, William; Poindexter, Brenda B.; Zaterka-Baxter, Kristin M.; Das, Abhik; Backstrom Lacy, Conra; Scorsone, Ann Marie; Duncan, Andrea F.; DeMauro, Sara B.; Goldstein, Ricki F.; Colaizy, Tarah T.; Wilson-Costello, Deanne E.; Purdy, Isabell B.; Hintz, Susan R.; Heyne, Roy J.; Myers, Gary J.; Fuller, Janell; Merhar, Stephanie; Harmon, Heidi M.; Peralta-Carcelen, Myriam; Kilbride, Howard W.; Maitre, Nathalie L.; Vohr, Betty R.; Natarajan, Girija; Mintz-Hittner, Helen; Quinn, Graham E.; Wallace, David K.; Olson, Richard J.; Orge, Faruk H.; Tsui, Irena; Gaynon, Michael; Hutchinson, Amy K.; He, Yu-Guang; Winter, Timothy W.; Yang, Michael B.; Haider, Kathryn M.; Cogen, Martin S.; Hug, Denise; Bremer, Don L.; Donahue, John P.; Lucas, William R.; Phelps, Dale L.; Higgins, Rosemary D.; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network; Pediatrics, School of MedicineObjective: This study evaluates the 24-month follow-up for the NICHD Neonatal Research Network (NRN) Inositol for Retinopathy Trial. Study design: Bayley Scales of Infants Development-III and a standardized neurosensory examination were performed in infants enrolled in the main trial. Moderate/severe NDI was defined as BSID-III Cognitive or Motor composite score <85, moderate or severe cerebral palsy, blindness, or hearing loss that prevents communication despite amplification were assessed. Results: Primary outcome was determined for 605/638 (95%). The mean gestational age was 25.8 ± 1.3 weeks and mean birthweight was 805 ± 192 g. Treatment group did not affect the risk for the composite outcome of death or survival with moderate/severe NDI (60% vs 56%, p = 0.40). Conclusions: Treatment group did not affect the risk of death or survival with moderate/severe NDI. Despite early termination, this study represents the largest RCT of extremely preterm infants treated with myo-inositol with neurodevelopmental outcome data.Item Safety and pharmacokinetics of multiple dose myo-inositol in preterm infants(SpringerNature, 2016-08) Phelps, Dale L.; Ward, Robert M.; Williams, Rick L.; Nolen, Tracy L.; Watterberg, Kristi L.; Oh, William; Goedecke, Michael; Ehrenkranz, Richard A.; Fennell, Timothy; Poindexter, Brenda B.; Cotten, C. Michael; Hallman, Mikko; Frantz III, Ivan D.; Faix, Roger G.; Zaterka-Baxter, Kristin M.; Das, Abhik; Ball, M. Bethany; Lacy, Conra Backstrom; Walsh, Michele C.; Carlo, Waldemar A.; Sánchez, Pablo J.; Bell, Edward F.; Shankaran, Seetha; Carlton, David P.; Chess, Patricia R.; Higgins, Rosemary D.; Department of Pediatrics, IU School of MedicineBACKGROUND: Preterm infants with respiratory distress syndrome (RDS) given inositol had reduced bronchopulmonary dysplasia (BPD), death and severe retinopathy of prematurity (ROP). We assessed the safety and pharmacokinetics of daily inositol to select a dose providing serum levels previously associated with benefit, and to learn if accumulation occurred when administered throughout the normal period of retinal vascularization. METHODS: Infants ≤ 29 wk GA (n = 122, 14 centers) were randomized and treated with placebo or inositol at 10, 40, or 80 mg/kg/d. Intravenous administration converted to enteral when feedings were established, and continued to the first of 10 wk, 34 wk postmenstrual age (PMA) or discharge. Serum collection employed a sparse sampling population pharmacokinetics design. Inositol urine losses and feeding intakes were measured. Safety was prospectively monitored. RESULTS: At 80 mg/kg/d mean serum levels reached 140 mg/l, similar to Hallman's findings. Levels declined after 2 wk, converging in all groups by 6 wk. Analyses showed a mean volume of distribution 0.657 l/kg, clearance 0.058 l/kg/h, and half-life 7.90 h. Adverse events and comorbidities were fewer in the inositol groups, but not significantly so. CONCLUSION: Multiple dose inositol at 80 mg/kg/d was not associated with increased adverse events, achieves previously effective serum levels, and is appropriate for investigation in a phase III trial.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 Stillbirth 2010-2018: a prospective, population-based, multi-country study from the Global Network(Springer Nature, 2020-11-30) McClure, Elizabeth M.; Saleem, Sarah; Goudar, Shivaprasad S.; Garces, Ana; Whitworth, Ryan; Esamai, Fabian; Patel, Archana B.; Sunder Tikmani, Shiyam; Mwenechanya, Musaku; Chomba, Elwyn; Lokangaka, Adrien; Bose, Carl L.; Bucher, Sherri; Liechty, Edward A.; Krebs, Nancy F.; Kumar, S. Yogesh; Derman, Richard J.; Hibberd, Patricia L.; Carlo, Waldemar A.; Moore, Janet L.; Nolen, Tracy L.; Koso-Thomas, Marion; Goldenberg, Robert L.; Pediatrics, School of MedicineBackground: Stillbirth rates are high and represent a substantial proportion of the under-5 mortality in low and middle-income countries (LMIC). In LMIC, where nearly 98% of stillbirths worldwide occur, few population-based studies have documented cause of stillbirths or the trends in rate of stillbirth over time. Methods: We undertook a prospective, population-based multi-country research study of all pregnant women in defined geographic areas across 7 sites in low-resource settings (Kenya, Zambia, Democratic Republic of Congo, India, Pakistan, and Guatemala). Staff collected demographic and health care characteristics with outcomes obtained at delivery. Cause of stillbirth was assigned by algorithm. Results: From 2010 through 2018, 573,148 women were enrolled with delivery data obtained. Of the 552,547 births that reached 500 g or 20 weeks gestation, 15,604 were stillbirths; a rate of 28.2 stillbirths per 1000 births. The stillbirth rates were 19.3 in the Guatemala site, 23.8 in the African sites, and 33.3 in the Asian sites. Specifically, stillbirth rates were highest in the Pakistan site, which also documented a substantial decrease in stillbirth rates over the study period, from 56.0 per 1000 (95% CI 51.0, 61.0) in 2010 to 44.4 per 1000 (95% CI 39.1, 49.7) in 2018. The Nagpur, India site also documented a substantial decrease in stillbirths from 32.5 (95% CI 29.0, 36.1) to 16.9 (95% CI 13.9, 19.9) per 1000 in 2018; however, other sites had only small declines in stillbirth over the same period. Women who were less educated and older as well as those with less access to antenatal care and with vaginal assisted delivery were at increased risk of stillbirth. The major fetal causes of stillbirth were birth asphyxia (44.0% of stillbirths) and infectious causes (22.2%). The maternal conditions that were observed among those with stillbirth were obstructed or prolonged labor, antepartum hemorrhage and maternal infections. Conclusions: Over the study period, stillbirth rates have remained relatively high across all sites. With the exceptions of the Pakistan and Nagpur sites, Global Network sites did not observe substantial changes in their stillbirth rates. Women who were less educated and had less access to antenatal and obstetric care remained at the highest burden of stillbirth.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.