Evidence That STK19 Is Not an NRAS-dependent Melanoma Driver.

STK19 was proposed to be a cancer driver, and recent work by Yin et al. (2019) in Cell suggested that the frequently recurring STK19 D89N substitution represents a gain-of-function change, allowing increased phosphorylation of NRAS to enhance melanocyte transformation. Here we show that the STK19 gene has been incorrectly annotated, and that the expressed protein is 110 amino acids shorter than indicated by current databases. The "cancer driving" STK19 D89N substitution is thus outside the coding region. We also fail to detect evidence of the mutation affecting STK19 expression; instead, it is a UV signature mutation, found in the promoter of other genes as well. Furthermore, STK19 is exclusively nuclear and chromatin-associated, while no evidence for it being a kinase was found. The data in this Matters Arising article raise fundamental questions about the recently proposed role for STK19 in melanoma progression via a function as an NRAS kinase, suggested by Yin et al. (2019) in Cell. See also the response by Yin et al. (2020), published in this issue.

UV Irradiation Induces a Non-coding RNA that Functionally Opposes the Protein Encoded by the Same Gene.

The transcription-related DNA damage response was analyzed on a genome-wide scale with great spatial and temporal resolution. Upon UV irradiation, a slowdown of transcript elongation and restriction of gene activity to the promoter-proximal ∼25 kb is observed. This is associated with a shift from expression of long mRNAs to shorter isoforms, incorporating alternative last exons (ALEs) that are more proximal to the transcription start site. Notably, this includes a shift from a protein-coding ASCC3 mRNA to a shorter ALE isoform of which the RNA, rather than an encoded protein, is critical for the eventual recovery of transcription. The non-coding ASCC3 isoform counteracts the function of the protein-coding isoform, indicating crosstalk between them. Thus, the ASCC3 gene expresses both coding and non-coding transcript isoforms with opposite effects on transcription recovery after UV-induced DNA damage.

Heat shock induces premature transcript termination and reconfigures the human transcriptome.

The heat shock (HS) response involves rapid induction of HS genes, whereas transcriptional repression is established more slowly at most other genes. Previous data suggested that such repression results from inhibition of RNA polymerase II (RNAPII) pause release, but here, we show that HS strongly affects other phases of the transcription cycle. Intriguingly, while elongation rates increase upon HS, processivity markedly decreases, so that RNAPII frequently fails to reach the end of genes. Indeed, HS results in widespread premature transcript termination at cryptic, intronic polyadenylation (IPA) sites near gene 5'-ends, likely via inhibition of U1 telescripting. This results in dramatic reconfiguration of the human transcriptome with production of new, previously unannotated, short mRNAs that accumulate in the nucleus. Together, these results shed new light on the basic transcription mechanisms induced by growth at elevated temperature and show that a genome-wide shift toward usage of IPA sites can occur under physiological conditions.

Proteasome-mediated processing of Def1, a critical step in the cellular response to transcription stress.

DNA damage triggers polyubiquitylation and degradation of the largest subunit of RNA polymerase II (RNAPII), a "mechanism of last resort" employed during transcription stress. In yeast, this process is dependent on Def1 through a previously unresolved mechanism. Here, we report that Def1 becomes activated through ubiquitylation- and proteasome-dependent processing. Def1 processing results in the removal of a domain promoting cytoplasmic localization, resulting in nuclear accumulation of the clipped protein. Nuclear Def1 then binds RNAPII, utilizing a ubiquitin-binding domain to recruit the Elongin-Cullin E3 ligase complex via a ubiquitin-homology domain in the Ela1 protein. This facilitates polyubiquitylation of Rpb1, triggering its proteasome-mediated degradation. Together, these results outline the multistep mechanism of Rpb1 polyubiquitylation triggered by transcription stress and uncover the key role played by Def1 as a facilitator of Elongin-Cullin ubiquitin ligase function.

DDI2 Is a Ubiquitin-Directed Endoprotease Responsible for Cleavage of Transcription Factor NRF1.

The Ddi1/DDI2 proteins are ubiquitin shuttling factors, implicated in a variety of cellular functions. In addition to ubiquitin-binding and ubiquitin-like domains, they contain a conserved region with similarity to retroviral proteases, but whether and how DDI2 functions as a protease has remained unknown. Here, we show that DDI2 knockout cells are sensitive to proteasome inhibition and accumulate high-molecular weight, ubiquitylated proteins that are poorly degraded by the proteasome. These proteins are targets for the protease activity of purified DDI2. No evidence for DDI2 acting as a de-ubiquitylating enzyme was uncovered, which could suggest that it cleaves the ubiquitylated protein itself. In support of this idea, cleavage of transcription factor NRF1 is known to require DDI2 activity in vivo. We show that DDI2 is indeed capable of cleaving NRF1 in vitro but only when NRF1 protein is highly poly-ubiquitylated. Together, these data suggest that DDI2 is a ubiquitin-directed endoprotease.

Reducing cardiometabolic risk with semaglutide in type 1 diabetes (RESET1): Study protocol of a phase 2 double-blinded randomised placebo-controlled trial.

BACKGROUND: Premature cardiovascular disease is the leading cause of death in people living with type 1 diabetes. Therapies are urgently needed to address cardiovascular risk in this group. Semaglutide, a long-acting glucagon-like peptide-1 receptor agonist, has been shown to reduce cardiovascular events and improve weight and glycaemia in type 2 diabetes. Semaglutide may offer cardioprotective and metabolic benefits in type 1 diabetes. METHODS: We will study 60 adults aged 25-70 years with type 1 diabetes of duration at least 2 years, body mass index ≥25 kg/m2, HbA1c ≥7% and at least one cardiovascular risk factor (microalbuminuria, hypertension or anti-hypertensive treatment, hyperlipidemia or lipid lowering therapy, current smoking). Participants will receive semaglutide up to 1.0 mg weekly or matched placebo for 26 weeks. The primary outcome is carotid femoral pulse wave velocity, a measure of arterial stiffness, as a surrogate marker of cardiovascular risk. Potential mechanisms for metabolic changes will be explored including change in insulin sensitivity determined by hyperinsulinaemic-euglycaemic clamp; and incretin and pancreatic hormone action measured during mixed meal tolerance test. CONCLUSION: The REducing cardiometabolic risk with SEmaglutide in Type 1 diabetes study will investigate whether semaglutide, a long acting glucagon-like peptide receptor agonist, can improve markers of cardiometabolic health in T1D. Underlying mechanisms predicting response, including insulin resistance and incretin hormone status, will also be explored.

A Crosswalk Analysis Between Magnet® Standards and Clinical Nurse Specialist Practice Competencies.

OBJECTIVE: The purpose of this study was to determine the alignment between the American Nurses Credentialing Center's Magnet Recognition Program® standards and clinical nurse specialist (CNS) practice competencies. BACKGROUND: Despite documentation of CNS contributions to achieving and sustaining Magnet Recognition®, there is a lack of evidence clearly aligning Magnet® standards and CNS practice competencies. METHODS: Using a crosswalk method, an expert panel of CNSs and chief nursing executives analyzed alignment of the 50 Magnet standards with the 44 National Association of Clinical Nurse Specialists core practice competencies. RESULTS: CNS practice competencies are aligned closely with Magnet standards: 86% of the 50 Magnet standards aligned with at least 1 CNS competency and 81.8% of CNS competencies aligned with at least 1 Magnet® standard. CONCLUSIONS: The alignment between Magnet standards and CNS competencies supports evidence of CNS contributions to organizational achievement of Magnet Recognition and will assist nurse executives in identifying a full scope of opportunities for CNSs to contribute to nursing excellence.

Major Depression and Survival in People With Cancer.

OBJECTIVE: The question of whether depression is associated with worse survival in people with cancer remains unanswered because of methodological criticism of the published research on the topic. We aimed to study the association in a large methodologically robust study. METHODS: We analyzed data on 20,582 patients with breast, colorectal, gynecological, lung, and prostate cancers who had attended cancer outpatient clinics in Scotland, United Kingdom. Patients had completed two-stage screening for major depression as part of their cancer care. These data on depression status were linked to demographic, cancer, and subsequent mortality data from national databases. We estimated the association of major depression with survival for each cancer using Cox regression. We adjusted for potential confounders and interactions between potentially time-varying confounders and the interval between cancer diagnosis and depression screening, and used multiple imputation for missing depression and confounder data. We pooled the cancer-specific results using fixed-effects meta-analysis. RESULTS: Major depression was associated with worse survival for all cancers, with similar adjusted hazard ratios (HRs): breast cancer (HR = 1.42, 95% confidence interval [CI] = 1.15-1.75), colorectal cancer (HR = 1.47, 95% CI = 1.11-1.94), gynecological cancer (HR = 1.36, 95% CI = 1.08-1.71), lung cancer (HR = 1.39, 95% CI = 1.24-1.56), and prostate cancer (HR = 1.76, 95% CI = 1.08-2.85). The pooled HR was 1.41 (95% CI = 1.29-1.54, p < .001, I2 = 0%). These findings were not materially different when we only considered the deaths (90%) that were attributed to cancer. CONCLUSIONS: Major depression is associated with worse survival in patients with common cancers. The mechanisms of this association and the clinical implications require further study.

Description of work processes used by clinical nurse specialists to improve patient outcomes.

BACKGROUND: Advanced practice registered nurses (APRN) are expected to contribute to improved patient outcomes. Traditionally, clinical nurse specialists (CNS) have been the APRN role that led system-level nursing practice initiatives to advance care for specialty populations. Little is known about the work processes used by CNSs to achieve outcomes. PURPOSE: This study identified common processes used by CNSs working in a variety of practice settings and specialties to advance nursing practice and achieve improved clinical outcomes. METHODS: Qualitative descriptive methods were used; a purposeful sample of CNSs with completed system-level projects participated in focus groups. Data were analyzed using standard content analysis process. FINDINGS: CNSs engaged in intricate interactions identified as articulation work involving the management of intersections between people, technology and organizations. This expert work is largely invisible. Self-agency, trust, and influence are a nexus upon which CNS work processes revolve. DISCUSSION: The findings provide insight into CNS work processes, lend credibility to the CNS's leadership abilities, and help explain why the CNS role and practice is often considered invisible and ambiguous.

The prevalence of depression in general hospital inpatients: a systematic review and meta-analysis of interview-based studies.

BACKGROUND: Comorbid depression in the medically ill is clinically important. Admission to a general hospital offers an opportunity to identify and initiate treatment for depression. However, we first need to know how common depression is in general hospital inpatients. We aimed to address this question by systematically reviewing the relevant literature. METHODS: We reviewed published prevalence studies in any language which had used diagnostic interviews of general hospital inpatients and met basic methodological quality criteria. We focussed on interview-based studies in order to estimate the proportion of patients with a diagnosis of depressive illness. RESULTS: Of 158 relevant articles, 65 (41%) describing 60 separate studies met our inclusion criteria. The 31 studies that focussed on general medical and surgical inpatients reported prevalence estimates ranging from 5% to 34%. There was substantial, highly statistically significant, heterogeneity between studies which was not materially explained by the covariates we were able to consider. The average of the reported prevalences was 12% (95% CI 10-15), with a 95% prediction interval of 4-32%. The remaining 29 studies, of a variety of specific clinical populations, are described. CONCLUSIONS: The available evidence suggests a likely prevalence high enough to make it worthwhile screening hospital inpatients for depression and initiating treatment where appropriate. Further, higher quality, research is needed to clarify the prevalence of depression in specific settings and to further explore the reasons for the observed heterogeneity in estimates.

A ubiquitylation site in Cockayne syndrome B required for repair of oxidative DNA damage, but not for transcription-coupled nucleotide excision repair.

Cockayne syndrome B (CSB), best known for its role in transcription-coupled nucleotide excision repair (TC-NER), contains a ubiquitin-binding domain (UBD), but the functional connection between protein ubiquitylation and this UBD remains unclear. Here, we show that CSB is regulated via site-specific ubiquitylation. Mass spectrometry analysis of CSB identified lysine (K) 991 as a ubiquitylation site. Intriguingly, mutation of this residue (K991R) does not affect CSB's catalytic activity or protein stability, but greatly affects genome stability, even in the absence of induced DNA damage. Moreover, cells expressing CSB K991R are sensitive to oxidative DNA damage, but proficient for TC-NER. K991 becomes ubiquitylated upon oxidative DNA damage, and while CSB K991R is recruited normally to such damage, it fails to dissociate in a timely manner, suggesting a requirement for K991 ubiquitylation in CSB activation. Interestingly, deletion of CSB's UBD gives rise to oxidative damage sensitivity as well, while CSB ΔUBD and CSB K991R affects expression of overlapping groups of genes, further indicating a functional connection. Together, these results shed new light on the regulation of CSB, with K991R representing an important separation-of-function-mutation in this multi-functional protein.

Effects of Plasmodium falciparum infection on umbilical artery resistance and intrafetal blood flow distribution: a Doppler ultrasound study from Papua New Guinea.

BACKGROUND: Doppler velocimetry studies of umbilical artery (UA) and middle cerebral artery (MCA) flow help to determine the presence and severity of fetal growth restriction. Increased UA resistance and reduced MCA pulsatility may indicate increased placental resistance and intrafetal blood flow redistribution. Malaria causes low birth weight and fetal growth restriction, but few studies have assessed its effects on uteroplacental and fetoplacental blood flow. METHODS: Colour-pulsed Doppler ultrasound was used to assess UA and MCA flow in 396 Papua New Guinean singleton fetuses. Abnormal flow was defined as an UA resistance index above the 90th centile, and/or a MCA pulsatility index and cerebroplacental ratio (ratio of MCA and UA pulsatility index) below the 10th centile of population-specific models fitted to the data. Associations between malaria (peripheral infection prior to and at ultrasound examination, and any gestational infection, i.e., 'exposure') and abnormal flow, and between abnormal flow and birth outcomes, were estimated. RESULTS: Of 78 malaria infection episodes detected before or at the ultrasound visit, 62 (79.5%) were Plasmodium falciparum (34 sub-microscopic infections), and 16 were Plasmodium vivax. Plasmodium falciparum infection before or at Doppler measurement was associated with increased UA resistance (adjusted odds ratio (aOR) 2.3 95% CI 1.0-5.2, P = 0.047). When assessed by 'exposure', P. falciparum infection was significantly associated with increased UA resistance (all infections: 2.4, 1.1-4.9, P = 0.024; sub-microscopic infections 2.6, 1.0-6.6, P = 0.051) and a reduced MCA pulsatility index (all infections: 2.6, 1.2-5.3, P = 0.012; sub-microscopic infections: 2.8, 1.1-7.5, P = 0.035). Sub-microscopic P. falciparum infections were additionally associated with a reduced cerebroplacental ratio (3.64, 1.22-10.88, P = 0.021). There were too few P. vivax infections to draw robust conclusions. An increased UA resistance index was associated with histological evidence of placental malaria (5.1, 2.3-10.9, P < 0.001; sensitivity 0.26, specificity 0.93). A low cerebroplacental Doppler ratio was associated with concurrently measuring small-for-gestational-age, and with low birth weight. DISCUSSION/CONCLUSION: Both microscopic and sub-microscopic P. falciparum infections impair fetoplacental and intrafetal flow, at least temporarily. Increased UA resistance has high specificity but low sensitivity for the detection of placental infection. These findings suggest that interventions to protect the fetus should clear and prevent both microscopic and sub-microscopic malarial infections. Trial Registration ClinicalTrials.gov NCT01136850. Registered 06 April 2010.

Screening Medical Patients for Depression: Lessons From a National Program in Cancer Clinics.

BACKGROUND: Screening has been recommended to improve the identification of depression in medical patients. There is, therefore, a need for useful practical information on how to successfully implement large-scale depression screening in medical clinics. OBJECTIVE: To describe the practical lessons learned from our experience of implementing a large-scale depression screening program in cancer clinics throughout Scotland, UK. METHOD: Reflective review based on the experience of the screening team and records of the iterative development of the program. FINDINGS: Systematic screening for depression in patients with medical illnesses can be delivered in clinics as long as the program is well designed. Design issues include ensuring the engagement of staff and patients, implementing efficient 2-stage screening processes and effectively managing workflow and quality assurance. DISCUSSION: Screening has the potential to offer a solution to the well-documented problem of missed depression and other psychiatric diagnoses, thereby improving patient care if closely linked to treatment provision.

Preparing linked population data for research: cohort study of prisoner perinatal health outcomes.

BACKGROUND: A study of pregnancy outcomes related to pregnancy in prison in New South Wales, Australia, designed a two stage linkage to add maternal history of incarceration and serious mental health morbidity, neonatal hospital admission and infant congenital anomaly diagnosis to birth data. Linkage was performed by a dedicated state-wide data linkage authority. This paper describes use of the linked data to determine pregnancy prison exposure pregnancy for a representative population of mothers. METHODS: Researchers assessed the quality of linked records; resolved multiple-matched identities; transformed event-based incarceration records into person-based prisoner records and birth records into maternity records. Inconsistent or incomplete records were censored. Interrogation of the temporal relationships of all incarceration periods from the prisoner record with pregnancies from birth records identified prisoner maternities. Interrogation of maternities for each mother distinguished prisoner mothers who were incarcerated during pregnancy, from prisoner control mothers with pregnancies wholly in the community and a subset of prisoner mothers with maternities both types of maternity. Standard descriptive statistics are used to provide population prevalence of exposures and compare data quality across study populations stratified by mental health morbidity. RESULTS: Women incarcerated between 1998 and 2006 accounted for less than 1 % of the 404,000 women who gave birth in NSW between 2000 and 2006, while women with serious mental health morbidity accounted for 7 % overall and 68 % of prisoners. Rates of false positive linkage were within the predicted limits set by the linkage authority for non-prisoners, but were tenfold higher among prisoners (RR 9.9; 95%CI 8.2, 11.9) and twice as high for women with serious mental health morbidity (RR 2.2; 95%CI 1.9, 2.6). This case series of 597 maternities for 558 prisoners pregnant while in prison (of whom 128 gave birth in prison); and 2,031 contemporaneous prisoner control mothers is one of the largest available. CONCLUSIONS: Record linkage, properly applied, offers the opportunity to extend knowledge about vulnerable populations not amenable to standard ascertainment. Dedicated linkage authorities now provide linked data for research. The data are not research ready. Perinatal exposures are time-critical and require expert processing to prepare the data for research.

Integrated collaborative care for comorbid major depression in patients with cancer (SMaRT Oncology-2): a multicentre randomised controlled effectiveness trial.

BACKGROUND: Medical conditions are often complicated by major depression, with consequent additional impairment of quality of life. We aimed to compare the effectiveness of an integrated treatment programme for major depression in patients with cancer (depression care for people with cancer) with usual care. METHODS: SMaRT Oncology-2 is a parallel-group, multicentre, randomised controlled effectiveness trial. We enrolled outpatients with major depression from three cancer centres and their associated clinics in Scotland, UK. Participants were randomly assigned in a 1:1 ratio to the depression care for people with cancer intervention or usual care, with stratification (by trial centre) and minimisation (by age, primary cancer, and sex) with allocation concealment. Depression care for people with cancer is a manualised, multicomponent collaborative care treatment that is delivered systematically by a team of cancer nurses and psychiatrists in collaboration with primary care physicians. Usual care is provided by primary care physicians. Outcome data were collected up until 48 weeks. The primary outcome was treatment response (≥50% reduction in Symptom Checklist Depression Scale [SCL-20] score, range 0-4) at 24 weeks. Trial statisticians and data collection staff were masked to treatment allocation, but participants could not be masked to the allocations. Analyses were by intention to treat. This trial is registered with Current Controlled Trials, number ISRCTN40568538. FINDINGS: 500 participants were enrolled between May 12, 2008, and May 13, 2011; 253 were randomly allocated to depression care for people with cancer and 247 to usual care. 143 (62%) of 231 participants in the depression care for people with cancer group and 40 (17%) of 231 in the usual care group responded to treatment: absolute difference 45% (95% CI 37-53), adjusted odds ratio 8·5 (95% CI 5·5-13·4), p<0·0001. Compared with patients in the usual care group, participants allocated to the depression care for people with cancer programme also had less depression, anxiety, pain, and fatigue; and better functioning, health, quality of life, and perceived quality of depression care at all timepoints (all p<0·05). During the study, 34 cancer-related deaths occurred (19 in the depression care for people with cancer group, 15 in the usual care group), one patient in the depression care for people with cancer group was admitted to a psychiatric ward, and one patient in this group attempted suicide. None of these events were judged to be related to the trial treatments or procedures. INTERPRETATION: Our findings suggest that depression care for people with cancer is an effective treatment for major depression in patients with cancer. It offers a model for the treatment of depression comorbid with other medical conditions. FUNDING: Cancer Research UK and Chief Scientist Office of the Scottish Government.

(1)H MRS: a potential biomarker of in utero placental function.

The placenta is a temporary organ that is essential for a healthy pregnancy. It performs several important functions, including the transport of nutrients, the removal of waste products and the metabolism of certain substances. Placental disorders have been found to account for over 50% of stillbirths. Despite this, there are currently no methods available to directly and non-invasively assess placental function in utero. The primary aim of this pilot study was to investigate the use of (1)H MRS for this purpose. (1)H MRS offers the possibility to detect several placental metabolites, including choline, lipids and the amino acids glutamine and glutamate (Glx), which are vital to fetal development and placental function. Here, in utero placental spectra were acquired from nine small for gestational age (SGA) pregnancies, a cohort who are at increased risk of perinatal morbidity and mortality, and from nine healthy gestation-matched pregnancies. All subjects were between 26 and 39 weeks of gestation. Placenta Glx, choline and lipids at 1.3 and 0.9 ppm were quantified as amplitude ratios to that of intrinsic H2O. Wilcoxon signed rank tests indicated a significant difference in Glx/H2O (p = 0.024) between the two groups, but not in choline/H2O (p = 0.722) or in either lipid/H2O ratio (1.3 ppm, p = 0.813; 0.9 ppm, p = 0.058). This study has demonstrated that (1)H MRS has potential for the detection of placental metabolites in utero. This warrants further investigation as a tool for the monitoring of placental function.

Updates in Psychosomatic Medicine: 2014.

BACKGROUND: The amount of literature published annually related to psychosomatic medicine is vast; this poses a challenge for practitioners to keep up-to-date in all but a small area of expertise. OBJECTIVES: To introduce how a group process using volunteer experts can be harnessed to provide clinicians with a manageable selection of important publications in psychosomatic medicine, organized by specialty area, for 2014. METHODS: We used quarterly annotated abstracts selected by experts from the Academy of Psychosomatic Medicine and the European Association of Psychosomatic Medicine in 15 subspecialties to create a list of important articles. RESULTS: In 2014, subspecialty experts selected 88 articles of interest for practitioners of psychosomatic medicine. For this review, 14 articles were chosen. CONCLUSIONS: A group process can be used to whittle down the vast literature in psychosomatic medicine and compile a list of important articles for individual practitioners. Such an approach is consistent with the idea of physicians as lifelong learners and educators.

Factors associated with ultrasound-aided detection of suboptimal fetal growth in a malaria-endemic area in Papua New Guinea.

BACKGROUND: Fetal growth restriction (FGR) is associated with increased infant mortality rates and ill-health in adulthood. Evaluation of fetal growth requires ultrasound. As a result, ultrasound-assisted evaluations of causes of FGR in malaria-endemic developing countries are rare. We aimed to determine factors associated with indicators of abnormal fetal growth in rural lowland Papua New Guinea (PNG). METHODS: Weights and growth of 671 ultrasound-dated singleton pregnancies (<25 gestational weeks) were prospectively monitored using estimated fetal weights and birthweights. Maternal nutritional status and haemoglobin levels were assessed at enrolment, and participants were screened for malaria on several occasions. FGR was suspected upon detection of an estimated fetal weight or birthweight <10(th) centile (small-for-gestational age) and/or low fetal weight gain, defined as a change in weight z-score in the first quartile. Factors associated with fetal weight and fetal weight gain were additionally assessed by evaluating differences in weight z-scores and change in weight z-scores. Log-binomial and linear mixed effect models were used to determine factors associated with indicators of FGR. RESULTS: SGA and low weight gain were detected in 48.3% and 37.0% of pregnancies, respectively. Of participants, 13.8%, 21.2%, and 22.8% had a low mid-upper arm circumference (MUAC, <22 cms), short stature (<150 cms) and anaemia (haemoglobin <90 g/L) at first antenatal visit. 24.0% (161/671) of women had at least one malaria infection detected in peripheral blood. A low MUAC (adjusted risk ratio [aRR] 1.51, 95% CI 1.29, 1.76, P < 0.001), short stature (aRR 1.27, 95% CI 1.04, 1.55, P = 0.009), and anaemia (aRR 1.27, 95% CI 1.06, 1.51, P = 0.009) were associated with SGA, and a low body mass index was associated with low fetal weight gain (aRR 2.10, 95% CI 1.62, 2.71, P < 0.001). Additionally, recent receipt of intermittent preventive treatment in pregnancy was associated with increased weight z-scores, and anaemia with reduced change in weight z-scores. Malaria infection was associated with SGA on crude but not adjusted analyses (aRR 1.13, 95% CI 0.95, 1.34, P = 0.172). CONCLUSION: Macronutrient undernutrition and anaemia increased the risk of FGR. Antenatal nutritional interventions and malaria prevention could improve fetal growth in PNG.