Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Spatial distribution of soil nematodes relates to soil organic matter and life strategy

Soils are among the most biodiverse and densely inhabited environments on our planet. However, there is little understanding of spatial distribution patterns of belowground biota, and this hampers progress in understanding species interactions in belowground communities. We investigated the spatial distribution of nematodes, which are highly abundant and diverse metazoans in most soil ecosystems. To gain insight into nematode patchiness, we mapped distribution patterns in twelve apparently homogeneous agricultural fields (100 m × 100 m each) with equal representation of three soil textures (marine clay, river clay and sandy soil). Quantitative PCRs were used to measure the abundances of 48 distinct nematode taxa in ≈1200 plots. Multivariate analysis showed that within this selection of sites, soil texture more strongly affected soil nematode communities than land management. Geostatistical analysis of nematode distributions revealed both taxon-specific and field-specific patchiness. The average geostatistical range (indicating patch diameter) of 48 nematode taxa in these fields was 36 m, and related to soil organic matter. Soil organic matter content affected the spatial variance (indicating within-field variation of densities) in a life-strategy dependent manner. The r-strategists (fast-growing bacterivores and fungivores) showed a positive correlation between organic matter content and spatial variance, whereas most K-strategists (slow-growing omnivores and carnivores) showed a negative correlation. Hence, the combination of two parameters, soil organic matter content and a general life-strategy characterisation, can be used to explain the spatial distribution of nematodes at field scale.</p

Spatial distribution of soil nematodes relates to soil organic matter and life strategy

Soils are among the most biodiverse and densely inhabited environments on our planet. However, there is little understanding of spatial distribution patterns of belowground biota, and this hampers progress in understanding species interactions in belowground communities. We investigated the spatial distribution of nematodes, which are highly abundant and diverse metazoans in most soil ecosystems. To gain insight into nematode patchiness, we mapped distribution patterns in twelve apparently homogeneous agricultural fields (100 m × 100 m each) with equal representation of three soil textures (marine clay, river clay and sandy soil). Quantitative PCRs were used to measure the abundances of 48 distinct nematode taxa in ≈1200 plots. Multivariate analysis showed that within this selection of sites, soil texture more strongly affected soil nematode communities than land management. Geostatistical analysis of nematode distributions revealed both taxon-specific and field-specific patchiness. The average geostatistical range (indicating patch diameter) of 48 nematode taxa in these fields was 36 m, and related to soil organic matter. Soil organic matter content affected the spatial variance (indicating within-field variation of densities) in a life-strategy dependent manner. The r-strategists (fast-growing bacterivores and fungivores) showed a positive correlation between organic matter content and spatial variance, whereas most K-strategists (slow-growing omnivores and carnivores) showed a negative correlation. Hence, the combination of two parameters, soil organic matter content and a general life-strategy characterisation, can be used to explain the spatial distribution of nematodes at field scale

Disparate gain and loss of parasitic abilities among nematode lineages - Fig 1

<p><b>Pictures of the head (A, C) and the middle regions (B, D) of two relatively basal representatives of the Tylenchida</b>. This speciose nematode order harbours most of the economically high impact plant-parasitic nematode species. Morphometrics of the stylet, an injection-needle like device used to puncture the plant cell wall (A, C), and the lateral field, indentations in the cuticle present in both sides of the nematode (B, D), are used for species identification. For these pictures, standard light microscopy was combined with differential interference contrast (DIC) optics (magnification: 1,000x).</p

A generalized overview of the phylogenetic relationships within the phylum Nematoda based on (nearly) full-length small subunit ribosomal DNA (SSU rDNA) sequences.

<p>For clade designation, we adhered to Holterman et al. [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0185445#pone.0185445.ref007" target="_blank">7</a>]. Plant parasites are found in Clades 1, 2, 10 and 12, and icons are used to distinguish four types of plant-parasitic nematodes: ectoparasites, semi-endoparasites, migratory endoparasites, and sedentary endoparasites.</p

Simplified overview of the phylogenetic relationships within the family Longidoridae (Clade 2) based on (nearly) full-length SSU rDNA sequences.

<p>For full overview see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0185445#pone.0185445.s002" target="_blank">S2 Fig</a>. Symbols behind names represent specific association with plant viruses belonging to the genus <i>Nepovirus</i>. ArMV, Arabis mosaic virus; CRLV, cherry rasp leaf virus; GFLV, grapevine fanleaf virus; PRMV, peach rosette mosaic virus; RpRSV, raspberry ringspot virus; SLRSV, strawberry latent ringspot virus; TBRV, tomato black ring virus; ToRSV, tomato ringspot virus, TRSV, tobacco ringspot virus. Only for nematode species names in bold, robust information about virus transmission could be found. An asterisk near branching pointing refers to a posterior probability > 0.95, or a bootstrap value above 65%.</p

Taxon coverage for the four plant parasite-harboring nematode lineages.

<p>Taxon coverage for the four plant parasite-harboring nematode lineages.</p

Simplified overview of the phylogenetic relationships within the family Aphelenchoididae and (Clade 10) based on (nearly) full-length SSU rDNA sequences.

<p>For full overview see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0185445#pone.0185445.s003" target="_blank">S3 Fig</a>. Plant-parasitic species are indicated in green, as well as by a plant icon in the right margin. Most non-plant-parasitic Aphelenchoididae are fungivores. A light blue background is used as an indicator for associations with insects. This may range from a simple phoretic interaction (<i>e</i>.<i>g</i>. <i>Bursaphelenchus sp</i>.) to obligate insect parasitism (<i>e</i>.<i>g</i>. <i>Entaphelenchus</i>). An asterisk near branching pointing refers to a posterior probability > 0.95, or a bootstrap value above 65%.</p