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Setting: Subnational, population-based birth cohort studies (n = 45) in 23 low-and middle-income countries (LMICs) spanning 2000–2021. Population: Liveborn infants. Methods: Subnational, population-based studies with high-quality birth outcome data from LMICs were invited to join the Vulnerable Newborn Measurement Collaboration. We defined distinct newborn types using gestational age (preterm [PT], term [T]), birthweight for gestational age using INTERGROWTH-21st standards (small for gestational age [SGA], appropriate for gestational age [AGA] or large for gestational age [LGA]), and birthweight (low birthweight, LBW [

Assessment of gestational age (GA) is key to provide optimal care during pregnancy. However, its accurate determination remains challenging in low- and middle-income countries, where access to obstetric ultrasound is limited. Hence, there is an urgent need to develop clinical approaches that allow accurate and inexpensive estimations of GA. We investigated the ability of urinary metabolites to predict GA at time of collection in a diverse multi-site cohort of healthy and pathological pregnancies (n = 99) using a broad-spectrum liquid chromatography coupled with mass spectrometry (LC–MS) platform. Our approach detected a myriad of steroid hormones and their derivatives including estrogens, progesterones, corticosteroids, and androgens which were associated with pregnancy progression. We developed a restricted model that predicted GA with high accuracy using three metabolites (rho = 0.87, RMSE = 1.58 weeks) that was validated in an independent cohort (n = 20). The predictions were more robust in pregnancies that went to term in comparison to pregnancies that ended prematurely. Overall, we demonstrated the feasibility of implementing urine metabolomics analysis in large-scale multi-site studies and report a predictive model of GA with a potential clinical value.

Maternal morbidity and mortality continue to rise, and pre-eclampsia is a major driver of this burden1. Yet the ability to assess underlying pathophysiology before clinical presentation to enable identification of pregnancies at risk remains elusive. Here we demonstrate the ability of plasma cell-free RNA (cfRNA) to reveal patterns of normal pregnancy progression and determine the risk of developing pre-eclampsia months before clinical presentation. Our results centre on comprehensive transcriptome data from eight independent prospectively collected cohorts comprising 1,840 racially diverse pregnancies and retrospective analysis of 2,539 banked plasma samples. The pre-eclampsia data include 524 samples (72 cases and 452 non-cases) from two diverse independent cohorts collected 14.5 weeks (s.d., 4.5 weeks) before delivery. We show that cfRNA signatures from a single blood draw can track pregnancy progression at the placental, maternal and fetal levels and can robustly predict pre-eclampsia, with a sensitivity of 75% and a positive predictive value of 32.3% (s.d., 3%), which is superior to the state-of-the-art method2. cfRNA signatures of normal pregnancy progression and pre-eclampsia are independent of clinical factors, such as maternal age, body mass index and race, which cumulatively account for less than 1% of model variance. Further, the cfRNA signature for pre-eclampsia contains gene features linked to biological processes implicated in the underlying pathophysiology of pre-eclampsia., Expression signatures from cell-free RNA of pregnant women can be used to reveal normal biology of pregnancy and predict development of pre-eclampsia.

Additional file 4: Table S2. Statistical difference of pairwise comparisons at phylum level. Abbreviations: MP, mother helminth-positive group; MN, mother helminth-negative group; CP, children helminth-positive group; CN, children helminth-negative group.

Background Soil-transmitted helminths infect about one fifth of the world’s population and have a negative impact on health. The Kato-Katz technique is the recommended method to detect soil-transmitted helminth eggs in stool samples, particularly in programmatic settings. However, some questions in its procedure remain. Our study aimed to investigate the effect of storage time, storage temperature and stirring of stool samples on fecal egg counts (FECs). Methodology/Principal findings In the framework of a clinical trial on Pemba Island, United Republic of Tanzania, 488 stool samples were collected from schoolchildren. These samples were evaluated in three experiments. In the first experiment (n = 92), two Kato-Katz slides were prepared from the same stool sample, one was stored at room temperature, the other in a refrigerator for 50 hours, and each slide was analyzed at nine time points (20, 50, 80, 110, 140 minutes, 18, 26, 42 and 50 hours). In the second experiment (n = 340), whole stool samples were split into two, one part was stored at room temperature, and the other part was put in a refrigerator for 48 hours. From each part one Kato-Katz slide was prepared and analyzed at three time points over two days (0, 24 and 48 hours). In the third experiment (n = 56), whole stool samples where stirred for 15 seconds six times and at each time point a Kato-Katz slide was prepared and analyzed. Mean hookworm FECs of Kato-Katz slides stored at room temperature steadily decreased following slide preparation. After two hours, mean hookworm FECs decreased from 22 to 16, whereas no reduction was observed if Kato-Katz slides were stored in the refrigerator (19 vs 21). The time x storage interaction effect was statistically significant (coefficient 0.26, 95% CI: 0.17 to 0.35, p < 0.0001). After 24 hours mean hookworm FECs dropped close to zero, irrespective of the storage condition. Whole stool samples stored at room temperature for one day resulted in a mean hookworm FEC decrease of 23% (p < 0.0001), compared to a 13% reduction (p < 0.0001) if samples were stored in the refrigerator. Fecal egg counts of A. lumbricoides and T. trichiura remained stable over time regardless of storage temperature of whole stool samples. Finally, we found a significant reduction of the variation of hookworm and T. trichiura eggs with increasing rounds of stirring the sample, but not for A. lumbricoides. For hookworm we observed a simultaneous decrease in mean FECs, making it difficult to draw recommendations on stirring samples. Conclusions/Significance Our findings suggest that stool samples (i) should be analyzed on the day of collection and (ii) should be analyzed between 20–30 minutes after slide preparation; if that is not possible, Kato-Katz slides can be stored in a refrigerator for a maximum of 110 minutes., Author summary Intestinal worms, such as hookworm, Ascaris lumbricoides, and Trichuris trichiura, infect one in five people worldwide. In children, they can cause cognitive and physical impairment. Accurate detection of these infections is important to treat patients and control the spread of intestinal worms. Currently, the Kato-Katz technique is the most commonly used diagnostic method, particularly, in programmatic settings. However, there are still several open questions to be resolved. In this study, we aimed at exploring the effect of storage time, storage temperature, and stirring of stool samples on the number of worm eggs detectable by the Kato-Katz technique. We included 488 stool samples collected from schoolchildren on Pemba Island, United Republic of Tanzania. We found that, at room temperature, hookworm eggs rapidly disappear from Kato-Katz slides, but storing them in a refrigerator preserves eggs for up to 110 minutes. For A. lumbricoides and T. trichiura no relevant trend in fecal egg counts in Kato-Katz slides over time and or influence of storing temperature was detected. However, storing whole stool samples in a refrigerator overnight did not prevent hookworm eggs from disappearing, thus, we recommend analyzing all samples on the day of collection. For A. lumbricoides and T. trichiura fecal egg counts remained stable in whole stool samples over time, regardless of storage temperature. Finally, we found that stirring samples reduced the variation of fecal egg counts for hookworm and T. trichiura, but not for A. lumbricoides. Hookworm fecal egg counts decreased with increasing rounds of sample stirring.

Additional file 2: Table S1. Sample codes of all the 32 pairs of mothers and children and infection burdens of helminth-infected participants.

Additional file 5: Table S3. Statistical difference of pairwise comparisons at genus level. Abbreviations: MP, mother helminth-positive group; MN, mother helminth-negative group; CP, children helminth-positive group; CN, children helminth-negative group.

Additional file 1: Material S1. The questionnaire used in this study for each volunteer.

Graphical abstract Madrassa teachers are influential in the society and hence important change agents within our community-level behavioral intervention for the elimination of urogenital schistosomiasis transmission in Zanzibar., Highlights • Madrassa teachers participate in behavior intervention to eliminate schistosomiasis. • Teachers valued the opportunity to educate students about schistosomiasis. • Teachers can be influential and effective change agents in the intervention. • Teachers can help to expand and increase acceptance of elimination activities. • Teachers can help to increase participation in elimination activities., In Zanzibar, United Republic of Tanzania, Madrassa schools are influential institutions, where children and adults can learn about the interpretation of the Koran. We aimed to explore the involvement of Madrassa teachers for behavior change interventions in a randomized operational research trial designed to investigate the impact of multiple approaches to eliminate urogenital schistosomiasis transmission from Zanzibar. Madrassa teachers performing in the 30 communities of the behavior change study arm were trained in new interactive and participatory teaching methods by the local behavioral team and provided with schistosomiasis-teaching tools for teaching about transmission and prevention in their Madrassa. In July 2014, in a qualitative research study, we conducted 25 semi-structured interviews with Madrassa teachers to find out how they perceived their involvement in interventions against schistosomiasis. In 2014, 5926 among the 8497 registered Madrassa students in 30 communities on Unguja and Pemba islands received health education and participated in interactive behavior change exercises about schistosomiasis. Madrassa teachers reported that they valued their inclusion in the study and the opportunity to educate their students about schistosomiasis transmission, prevention, and treatment. They also perceived personal and community benefits as a result of their training and strongly supported the inclusion of additional Madrassa teachers in future intervention activities. Madrassa teachers are influential in the Zanzibari society, and hence are important change agents within our community-level behavioral intervention. They might constitute an untapped resource that can help to expand and increase acceptance of and participation in schistosomiasis and other neglected tropical disease control activities in African Muslim communities.

We evaluated the Newton Nm1, a commercially available handheld light microscope and compared it with conventional light microscopy for the diagnosis of soil-transmitted helminth infections. A total of 91 Kato-Katz thick smears were examined by experienced microscopists and helminth eggs were counted and expressed as eggs per gram of stool (EPG). Mean egg counts were significantly higher with the conventional light microscope (5,190 EPG versus 2,386 EPG for Ascaris lumbricoides; 826 versus 456 for Trichuris trichiura; both P < 0.05). Using regression coefficients and accounting for intensity of infection, we found that the agreement between the two devices was excellent for both species (κ = 0.90, 95% confidence interval = 0.82–0.99 for A. lumbricoides and κ = 0.96, 95% CI = 0.91–1.00 for T. trichiura). The Newton Nm1 microscope may be a useful tool for the detection and quantification of soil-transmitted helminth infection in clinical, epidemiologic, and public health settings.

Geophagia may be harmful as a method for the transmission of geohelminths. In this study, we pose two questions in a representative sample of 970 pregnant women from Pemba Island, Zanzibar, Tanzania. Can consumed earth be a vector for geohelminth infection? And do geophagists have differential parasitic infection? The parasitological content of 59 non-food substance samples was analysed. Cross-sectional data regarding pica behaviour were collected through interviews conducted by local researchers. Ascaris, Trichuris and hookworm status was ascertained through Kato-Katz smears. The prevalence of geophagia at baseline was 5.6% and the overall prevalence of Ascaris, Trichuris and hookworm infection was 5.6%, 33.2% and 32.9%, respectively. No consumed soil samples contained infectious parasitic stages, and only one of the consumed pica substances (charcoal) contained parasites of potential risk to human health. In bivariate analyses, neither the prevalence nor the intensity of infection with Ascaris, Trichuris or hookworm differed significantly by geophagia status. Furthermore, in multivariate models, geophagia was not a significant predictor of helminth infection status. We conclude that geophagia is not a source of Trichuris or hookworm infection among pregnant women in Pemba (insufficient power to evaluate the effect of Ascaris), which is in contrast to existing findings of helminth infection and geophagia.