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  1. Antinori S, Galimberti L, Milazzo L, Corbellino M
    Acta Trop, 2013 Feb;125(2):191-201.
    PMID: 23088834 DOI: 10.1016/j.actatropica.2012.10.008
    Plasmodium knowlesi was initially identified in the 30s as a natural Plasmodium of Macaca fascicularis monkey also capable of experimentally infecting humans. It gained a relative notoriety in the mid-30s as an alternative to Plasmodium vivax in the treatment of the general paralysis of the insane (neurosyphilis). In 1965 the first natural human infection was described in a US military surveyor coming back from the Pahang jungle of the Malaysian peninsula. P. knowlesi was again brought to the attention of the medical community when in 2004, Balbir Singh and his co-workers reported that about 58% of malaria cases observed in the Kapit district of the Malaysian Borneo were actually caused by P. knowlesi. In the following years several reports showed that P. knowlesi is much more widespread than initially thought with cases reported across Southeast Asia. This infection should also be considered in the differential diagnosis of any febrile travellers coming back from a recent travel to forested areas of Southeast Asia. P. knowlesi can cause severe malaria with a rate of 6-9% and with a case fatality rate of 3%. Respiratory distress, acute renal failure, shock and hyperbilirubinemia are the most frequently observed complications of severe P. knowlesi malaria. Chloroquine is considered the treatment of choice of uncomplicated malaria caused by P. knowlesi.
    Matched MeSH terms: Trophozoites/growth & development
  2. Choo KE, Davis TM, Ismail A, Tuan Ibrahim TA, Ghazali WN
    Acta Trop, 1999 Mar 15;72(2):175-83.
    PMID: 10206117
    The Typhidot test, which detects IgM and IgG antibodies to a Salmonella typhi-specific outer membrane protein, is as sensitive as, and more specific than, the Widal test in the diagnosis of enteric fever in Malaysian children. It is easier and quicker to perform. In order to increase diagnostic accuracy in an area of high endemicity, the Typhidot-M test has been developed in which IgG is first removed. This theoretically allows improved detection of IgM, and thus would differentiate new from recent infections. We evaluated both tests in 134 unselected febrile children admitted to the General Hospital Kota Bharu, Malaysia. The children were divided into two groups: (i) those who were blood and/or stool culture positive for S. typhi and/or who had clinical features strongly suggestive of enteric fever (n = 62); and (ii) those who were both culture-negative and had clinical evidence of another diagnosis (n = 72). The sensitivity and specificity of the Typhidot and Typhidot-M tests were identical at 90.3 and 93.1%, respectively. Both tests had comparable sensitivity but greater specificity than those of the Widal test (91.9 and 80.6%, respectively). When used together, a positive result for Typhidot and/or Typhidot-M was more specific than either test alone (95.2%) but specificity was lower (87.5%). We conclude that the Typhidot and Typhidot-M tests have comparatively high diagnostic accuracy, suggesting that IgM can be detected in children who may have a predominant IgG response to S. typhi. Using these tests in combination increases the negative predictive value but at the cost of a lower positive predictive value.
    Matched MeSH terms: Salmonella typhi/growth & development
  3. Mak JW, Choong MF, Lam PL, Suresh K
    Acta Trop, 1990 May;47(4):223-6.
    PMID: 1973024
    The leaf-monkeys, Presbytis cristata and Presbytis melalophos, experimentally infected with subperiodic Brugia malayi, have been used for studies on the pathoimmunology of the infection and the screening of potential filaricides during the last 6-8 years, and considerable information on the pattern of microfilaraemia and adult worm recoveries have been obtained. The prepatent periods in 97 P. cristata and 45 P. melalophos, each infected with about 200 infective larvae, were similar, these being approximately 70 and 68 days respectively. Although all infected animals became microfilaraemic, the peak geometric mean count was much higher in P. cristata than in P. melalophos, this being 182.0 and 65.8 per ml blood respectively. Mean adult worm recovery expressed as the percentage of the infective dose was 4.7% and 2.5%, respectively. Most worms were recovered from the sacral nodes/thoracic duct or inguinal lymph nodes in these animals. In view of the higher worm recovery and the higher peak microfilaraemia attained, it is concluded that P. cristata is a better model for the infection than P. melalophos.
    Matched MeSH terms: Brugia/growth & development*
  4. Lee HY, Loong SK, Ya'cob Z, Low VL, Teoh BT, Ahmad-Nasrah SN, et al.
    Acta Trop, 2021 Jul;219:105923.
    PMID: 33878305 DOI: 10.1016/j.actatropica.2021.105923
    Although the microbiome of blood-feeding insects serves an integral role in host physiology, both beneficial and pathogenic, little is known of the microbial community of black flies. An investigation, therefore, was undertaken to identify culturable bacteria from one of Malaysia's most common black flies, Simulium tani Takaoka and Davies, using 16S rDNA sequencing, and then evaluate the isolates for antibiotic resistance and virulence genes. A total of 20 isolates representing 11 bacterial species in four genera were found. Five isolates showed β-hemolysis on Columbia agar, and virulence genes were found in three of these isolates. Some degree of resistance to six of the 12 tested antibiotics was found among the isolates. The baseline data from this study suggest rich opportunities for comparative studies exploring the diversity and roles of the microbiome of S. tani and other Southeast Asian black flies.
    Matched MeSH terms: Bacteria/growth & development*
  5. Bänziger H
    Acta Trop, 1979 Mar;36(1):23-37.
    PMID: 35931
    1. Of the scarce Calyptra minuticornis, C. orthograpta and C. labilis, 51, 24, and 7 adults, respectively, were observed during some 600 night inspections at over 100 sites in 1965--1967 and 1971--1977. 2. Hitherto biologically completely unknown, and not recorded before in S.E. Asia, the latter two species flew in or near tropical monsoon forests in hilly regions (300--600 m) of N. Thailand (C. orthograpta also N. Laos). C. minuticornis was found in these and in tropical evergreen and semi-evergreen rain forests of S. Thailand and N.W. Malaysia. 3. In N. Thailand the three species were more common at the end of the cool season/start of the hot season and at the start of the rainy season. They were active mainly during the first half of the night 4. Flight and piercing behaviour, alighting, resting, enemies, and the lack of females, were similar to virtually identical with the "classical" skin-piercing blood-sucking C. eustrigata. 5. C. labilis was seen attacking elephant, C. orthograpta also water buffalo and sambar, C. minuticornis also zebu and tapir but not sambar. C. minuticornis settled on man also but did not pierce. 6. Through no piercing of hosts' skin has actually been seen in nature, indirect evidence suggests that the 3 moths are likely to be occasional blood-suckers. They pierced and sucked blood from the author's skin in experiments. 7. Reasons for lack of direct evidence may be: less developed hematophagy, less favoured hosts, lack of easy-to-pierce injured skin (which also trigger the piercing response), different climatic and phytoecological environment, fewer specimens than in the case of C. eustrigata. 8. Field observations and experiments indicate that the closely related, fruit-piercing Oraesia emarginata is not skin-piercing blood-sucking--a habit likely to be exhibited mainly in humid equatorial regions by a few Calyptra only.
    Matched MeSH terms: Moths/growth & development
  6. Loh HS, Mohd-Azmi ML, Sheikh-Omar AR, Zamri-Saad M, Tam YJ
    Acta Virol., 2007;51(1):27-33.
    PMID: 17432941
    The present study described the kinetics of Rat cytomegalovirus (RCMV) infection in newborn rats by monitoring infectious virus and viral antigens in various organs, viral DNA in the blood (DNAemia) and antibody response. These parameters were evaluated quantitatively using double-antibody sandwich ELISA (DAS-ELISA), real-time PCR, indirect ELISA and virus infectivity assay. For the first time DAS-ELISA was used for detection of RCMV antigen directly from organ samples. The relationships between the presence of viral antigens in the infected organs and antibody levels were established by the Spearman's rank test. It was found that the virus was present in the blood, spleen, liver, lungs, and kidneys earlier than in the salivary glands. Furthermore, the early immunity of the newborn rats led to a delayed seroconversion. We suggested that the prolonged presence of the virus in salivary glands could augment the antibody response that conversely might be responsible for a reduction of viremia. This study expanded our understanding of RCMV pathogenesis leading to improved therapeutic and preventive treatment regimens particularly for the neonatal Human cytomegalovirus (HCMV) infections. Additionally, the detection procedures developed in this study such as DAS-ELISA and real-time PCR could serve as alternative techniques for rapid screening of large number of samples.
    Matched MeSH terms: Muromegalovirus/growth & development*
  7. Hasmah MS, Omar AR, Wan KF, Hair-Bejo M, Aini I
    Acta Virol., 2004;48(2):85-9.
    PMID: 15462283
    It has been shown that a chicken anemia virus (CAV) isolates which had undergone 60 passages in MSB-1 cells (SMSC-1/P60, 3-1/P60) acquired 33-66 nucleotide substitutions at the coding region resulting in 13-16 amino acid changes as compared to the CAV isolates passaged only 5 times in MSB-1 cells (SMSC-1 and 3-1) (Chowdhury et al., Arch. Virol. 148, 2437-2448, 2003). In this study we found that a low CAV (BL-5) and a high CAV passage (BL-5/P90) differed by only 15 nucleotide substitutions resulting in 11 amino acid changes. Phylogenetic analysis based on VP1 also revealed that both isolates were close to each other but not to other CAV isolates from Malaysia, namely SMSC-1 and 3-1.
    Matched MeSH terms: Chicken anemia virus/growth & development*
  8. El Enshasy H, Malik K, Malek RA, Othman NZ, Elsayed EA, Wadaan M
    PMID: 26907552
    Human gastrointestinal microbiota (HGIM) incorporate a large number of microbes from different species. Anaerobic bacteria are the dominant organisms in this microbial consortium and play a crucial role in human health. In addition to their functional role as the main source of many essential metabolites for human health, they are considered as biotherapeutic agents in the regulation of different human metabolites. They are also important in the prevention and in the treatment of different physical and mental diseases. Bifidobacteria are the dominant anaerobic bacteria in HGIM and are widely used in the development of probiotic products for infants, children and adults. To develop bifidobacteria-based bioproducts, therefore, it is necessary to develop a large-scale biomass production platform based on a good understanding of the ideal medium and bioprocessing parameters for their growth and viability. In addition, high cell viability should be maintained during downstream processing and storage of probiotic cell powder or the final formulated product. In this work we review the latest information about the biology, therapeutic activities, cultivation and industrial production of bifidobacteria.
    Matched MeSH terms: Bacteria, Anaerobic/growth & development*; Bifidobacterium/growth & development*
  9. Perkin GW
    Adv Fertil Control, 1969 Sep;4(3):37-42.
    PMID: 12146214
    Matched MeSH terms: Population Growth
  10. Ng WJ, Ken KW, Kumar RV, Gunasagaran H, Chandramogan V, Lee YY
    PMID: 25435614
    BACKGROUND: Different researches on therapeutic effects of honey have been conducted in different regions; however the study on the potential antibacterial activity of Malaysian honey is still limited. In this study, antibacterial activities of different monofloral honey samples were tested against several common human pathogenic bacteria.

    MATERIALS AND METHODS: The well-diffusion method, minimum inhibitory concentrations (MIC) and minimum bactericidal concentration (MBC) techniques were employed to investigate the putative antibacterial activity of Malaysian monofloral honey from Koompassia excelsa (Becc.) Taub (Tualang), Melaleuca cajuputi Powell (Gelam) and Durio zibethinus Murr. (Durian). Honey samples were tested against Staphylococcus aureus ATCC6518 and ATCC25923, Staphylococcus epidermidis ATCC12228, Enterococcus faecium LMG16192, Enterococcus faecalis LMG16216 and ATCC29212, Escherichia coli ATCC25922, Salmonella enterica serovar Typhimurium ATCC14028 and Klebsiella pneumoniae ATCC13883.

    RESULTS: Marked variations were observed in the antibacterial activity of these honey samples. Durian honey failed to produce substantial antibacterial activity, whereas Tualang and Gelam honey showed a spectrum of antibacterial activity with their growth inhibitory effects against all of the tested bacterial species including vancomycin-resistant enterococci (VRE).

    CONCLUSION: Present findings suggested Gelam honey possesses highest antibacterial effect among the tested Malaysian honey samples.

    Matched MeSH terms: Bacteria/growth & development
  11. Kord-Varkaneh H, Rinaldi G, Hekmatdoost A, Fatahi S, Tan SC, Shadnoush M, et al.
    Ageing Res Rev, 2020 01;57:100996.
    PMID: 31816443 DOI: 10.1016/j.arr.2019.100996
    BACKGROUND: Inconsistencies exist with regard to influence of vitamin D supplementation on IGF-1 levels. The inconsistencies could be attributed to several factors, such as dosage and duration of intervention, among others. To address these inconsistencies, this study was conducted to determine the impact of vitamin D supplementation on IGF-1 levels through a systematic review and meta-analysis of randomized controlled trials (RCTs).

    METHODS: A comprehensive systematic search was carried out in PubMed/MEDLINE, Web of Science, SCOPUS and Embase for RCTs that investigated the impact of vitamin D intake on circulating IGF-1 levels from inception until June 2019. Weighted mean difference (WMD) with the 95 % CI were applied for estimating combined effect size. Subgroup analysis was performed to specify the source of heterogeneity among studies.

    RESULTS: Pooled results from eight studies demonstrated an overall non-significant increase in IGF-1 following vitamin D supplementation (WMD: 4 ng/ml, 95 % CI: -4 to 11). However, a significant degree of heterogeneity among studies was observed (I2 = 66 %). The subgroup analyses showed that vitamin D dosage of ≤1000 IU/day (WMD: 10 ng/ml) significantly increased IGF-1 compared to the vitamin D dosage of <1000 IU/day (WMD: -1 ng/ml). Moreover, intervention duration ≤12 weeks (WMD: 11 ng/ml) significantly increased IGF-1 compared to intervention duration <12 weeks (WMD: -3 ng/ml). In the epidemiological cohort study, participants under 60 years of age with a higher dietary vitamin D intake had significantly higher IGF-1 levels when compared to those with lower dietary vitamin D intake in second categories.

    CONCLUSION: The main results indicate a non-significant increase in IGF-1 following vitamin D supplementation. Additionally, vitamin D dosages of <1000 IU/day and intervention durations of <12 weeks significantly raised IGF-1 levels.

    Matched MeSH terms: Insulin-Like Growth Factor I/analysis*
  12. Mellone M, Hanley CJ, Thirdborough S, Mellows T, Garcia E, Woo J, et al.
    Aging (Albany NY), 2016 12 15;9(1):114-132.
    PMID: 27992856 DOI: 10.18632/aging.101127
    Cancer-associated fibroblasts (CAF) remain a poorly characterized, heterogeneous cell population. Here we characterized two previously described tumor-promoting CAF sub-types, smooth muscle actin (SMA)-positive myofibroblasts and senescent fibroblasts, identifying a novel link between the two. Analysis of CAF cultured ex vivo, showed that senescent CAF are predominantly SMA-positive; this was confirmed by immunochemistry in head & neck (HNSCC) and esophageal (EAC) cancers. In vitro, we found that fibroblasts induced to senesce develop molecular, ultrastructural and contractile features typical of myofibroblasts and this is dependent on canonical TGF-β signaling. Similar to TGF-β1-generated myofibroblasts, these cells secrete soluble factors that promote tumor cell motility. However, RNA-sequencing revealed significant transcriptomic differences between the two SMA-positive CAF groups, particularly in genes associated with extracellular matrix (ECM) deposition and organization, which differentially promote tumor cell invasion. Notably, second harmonic generation imaging and bioinformatic analysis of SMA-positive human HNSCC and EAC showed that collagen fiber organization correlates with poor prognosis, indicating that heterogeneity within the SMA-positive CAF population differentially impacts on survival. These results show that non-fibrogenic, SMA-positive myofibroblasts can be directly generated through induction of fibroblast senescence and suggest that senescence and myofibroblast differentiation are closely linked processes.
    Matched MeSH terms: Transforming Growth Factor beta1/metabolism
  13. Taylor ML, Cooper RL, Schneider EL, Osborn JM
    Am J Bot, 2015 Oct;102(10):1685-702.
    PMID: 26419810 DOI: 10.3732/ajb.1500249
    A knowledge of pollen characters in early-diverging angiosperm lineages is essential for understanding pollen evolution and the role of pollen in angiosperm diversification. In this paper, we report and synthesize data on mature pollen and pollen ontogeny from all genera of Nymphaeales within a comparative, phylogenetic context and consider pollen evolution in this early-diverging angiosperm lineage. We describe mature pollen characters for Euryale, Barclaya, and Nymphaea ondinea, taxa for which little to no structural data exist.
    Matched MeSH terms: Pollen/growth & development*; Nymphaeaceae/growth & development*; Nymphaea/growth & development
  14. Dean SJ, Perks CM, Holly JM, Bhoo-Pathy N, Looi LM, Mohammed NA, et al.
    Am J Clin Pathol, 2014 Mar;141(3):323-33.
    PMID: 24515759 DOI: 10.1309/AJCPR11DEAYPTUSL
    OBJECTIVES: To investigate the association between PTEN loss and IGFBP2 expression in a series of triple-negative breast cancers and to relate this expression to basal cytokeratin expression and clinicopathologic features.

    METHODS: One hundred and one formalin-fixed and paraffin-processed triple-negative breast cancer cases from the University of Malaya Medical Centre were tested immunohistochemically for cytokeratins 5/6 and 14, PTEN, and IGFBP2. The resulting slides were scored for proportion and intensity of staining.

    RESULTS: Loss of tumor nuclear and cytoplasmic staining for PTEN occurred in 48.3% of cases and was significantly associated with younger age at diagnosis (47 years compared with 57 years in those without PTEN loss; P = .005). Independent predictors of PTEN loss were late stage at presentation (P = .026), cytokeratin 5/6 positivity (P = .028), and IGFBP2 expression (P = .042). High levels of IGFBP2 expression were seen in 32% of cases; an independent predictor of high levels was cytokeratin 14 negativity (P = .005). PTEN loss and high levels of IGFBP2 expression were associated with poorer survival, but neither of these trends was significant.

    CONCLUSIONS: PTEN loss is a frequent event in triple-negative breast cancers and is significantly associated with younger age at onset of breast cancer, late stage, and IGFBP2 expression.

    Matched MeSH terms: Insulin-Like Growth Factor Binding Protein 2/metabolism*
  15. Fix AG
    Am J Hum Biol, 1989;1(4):463-469.
    PMID: 28514113 DOI: 10.1002/ajhb.1310010409
    The fertility and parameters of population growth of the Semai Senoi of Malaysia are studied by using a two-census method based on nonstable population theory. Semai fertility is shown to be moderately high; female completed fertility is 7.42 children and the crude birth rate is greater than 0.050. Previous estimates of Semai mortality rates are also moderately high but are insufficient to balance birth; thus, the overall rate of growth is presently nearly 2%. Compared with an earlier description of the pre-1969 Semai population, fertility has increased markedly leading to a nearly threefold increase in the annual growth rate.
    Matched MeSH terms: Population Growth
  16. Reijnders MRF, Ansor NM, Kousi M, Yue WW, Tan PL, Clarkson K, et al.
    Am J Hum Genet, 2017 Sep 07;101(3):466-477.
    PMID: 28886345 DOI: 10.1016/j.ajhg.2017.08.007
    RAC1 is a widely studied Rho GTPase, a class of molecules that modulate numerous cellular functions essential for normal development. RAC1 is highly conserved across species and is under strict mutational constraint. We report seven individuals with distinct de novo missense RAC1 mutations and varying degrees of developmental delay, brain malformations, and additional phenotypes. Four individuals, each harboring one of c.53G>A (p.Cys18Tyr), c.116A>G (p.Asn39Ser), c.218C>T (p.Pro73Leu), and c.470G>A (p.Cys157Tyr) variants, were microcephalic, with head circumferences between -2.5 to -5 SD. In contrast, two individuals with c.151G>A (p.Val51Met) and c.151G>C (p.Val51Leu) alleles were macrocephalic with head circumferences of +4.16 and +4.5 SD. One individual harboring a c.190T>G (p.Tyr64Asp) allele had head circumference in the normal range. Collectively, we observed an extraordinary spread of ∼10 SD of head circumferences orchestrated by distinct mutations in the same gene. In silico modeling, mouse fibroblasts spreading assays, and in vivo overexpression assays using zebrafish as a surrogate model demonstrated that the p.Cys18Tyr and p.Asn39Ser RAC1 variants function as dominant-negative alleles and result in microcephaly, reduced neuronal proliferation, and cerebellar abnormalities in vivo. Conversely, the p.Tyr64Asp substitution is constitutively active. The remaining mutations are probably weakly dominant negative or their effects are context dependent. These findings highlight the importance of RAC1 in neuronal development. Along with TRIO and HACE1, a sub-category of rare developmental disorders is emerging with RAC1 as the central player. We show that ultra-rare disorders caused by private, non-recurrent missense mutations that result in varying phenotypes are challenging to dissect, but can be delineated through focused international collaboration.
    Matched MeSH terms: Zebrafish/growth & development
  17. Baxter JS, Johnson N, Tomczyk K, Gillespie A, Maguire S, Brough R, et al.
    Am J Hum Genet, 2021 Jul 01;108(7):1190-1203.
    PMID: 34146516 DOI: 10.1016/j.ajhg.2021.05.013
    A combination of genetic and functional approaches has identified three independent breast cancer risk loci at 2q35. A recent fine-scale mapping analysis to refine these associations resulted in 1 (signal 1), 5 (signal 2), and 42 (signal 3) credible causal variants at these loci. We used publicly available in silico DNase I and ChIP-seq data with in vitro reporter gene and CRISPR assays to annotate signals 2 and 3. We identified putative regulatory elements that enhanced cell-type-specific transcription from the IGFBP5 promoter at both signals (30- to 40-fold increased expression by the putative regulatory element at signal 2, 2- to 3-fold by the putative regulatory element at signal 3). We further identified one of the five credible causal variants at signal 2, a 1.4 kb deletion (esv3594306), as the likely causal variant; the deletion allele of this variant was associated with an average additional increase in IGFBP5 expression of 1.3-fold (MCF-7) and 2.2-fold (T-47D). We propose a model in which the deletion allele of esv3594306 juxtaposes two transcription factor binding regions (annotated by estrogen receptor alpha ChIP-seq peaks) to generate a single extended regulatory element. This regulatory element increases cell-type-specific expression of the tumor suppressor gene IGFBP5 and, thereby, reduces risk of estrogen receptor-positive breast cancer (odds ratio = 0.77, 95% CI 0.74-0.81, p = 3.1 × 10-31).
    Matched MeSH terms: Insulin-Like Growth Factor Binding Protein 5/genetics*
  18. Ghoussaini M, French JD, Michailidou K, Nord S, Beesley J, Canisus S, et al.
    Am J Hum Genet, 2016 Oct 06;99(4):903-911.
    PMID: 27640304 DOI: 10.1016/j.ajhg.2016.07.017
    Genome-wide association studies (GWASs) have revealed increased breast cancer risk associated with multiple genetic variants at 5p12. Here, we report the fine mapping of this locus using data from 104,660 subjects from 50 case-control studies in the Breast Cancer Association Consortium (BCAC). With data for 3,365 genotyped and imputed SNPs across a 1 Mb region (positions 44,394,495-45,364,167; NCBI build 37), we found evidence for at least three independent signals: the strongest signal, consisting of a single SNP rs10941679, was associated with risk of estrogen-receptor-positive (ER+) breast cancer (per-g allele OR ER+ = 1.15; 95% CI 1.13-1.18; p = 8.35 × 10-30). After adjustment for rs10941679, we detected signal 2, consisting of 38 SNPs more strongly associated with ER-negative (ER-) breast cancer (lead SNP rs6864776: per-a allele OR ER- = 1.10; 95% CI 1.05-1.14; p conditional = 1.44 × 10-12), and a single signal 3 SNP (rs200229088: per-t allele OR ER+ = 1.12; 95% CI 1.09-1.15; p conditional = 1.12 × 10-05). Expression quantitative trait locus analysis in normal breast tissues and breast tumors showed that the g (risk) allele of rs10941679 was associated with increased expression of FGF10 and MRPS30. Functional assays demonstrated that SNP rs10941679 maps to an enhancer element that physically interacts with the FGF10 and MRPS30 promoter regions in breast cancer cell lines. FGF10 is an oncogene that binds to FGFR2 and is overexpressed in ∼10% of human breast cancers, whereas MRPS30 plays a key role in apoptosis. These data suggest that the strongest signal of association at 5p12 is mediated through coordinated activation of FGF10 and MRPS30, two candidate genes for breast cancer pathogenesis.
    Matched MeSH terms: Receptor, Fibroblast Growth Factor, Type 2/metabolism; Fibroblast Growth Factor 10/genetics*; Fibroblast Growth Factor 10/metabolism
  19. Crawford K, Hong J, Kumar S
    Am J Obstet Gynecol MFM, 2023 Dec;5(12):101187.
    PMID: 37832646 DOI: 10.1016/j.ajogmf.2023.101187
    BACKGROUND: Many risk factors for stillbirth are linked to placental dysfunction, which leads to suboptimal intrauterine growth and small for gestational age infants. Such infants also have an increased risk for stillbirth.

    OBJECTIVE: This study aimed to investigate the effect of known causal risk factors for stillbirth, and to identify those that have a large proportion of their risk mediated through small for gestational age birth.

    STUDY DESIGN: This retrospective cohort study used data from all births in the state of Queensland, Australia between 2000 and 2018. The total effects of exposures on the odds of stillbirth were determined using multivariable, clustered logistic regression models. Mediation analysis was performed using a counterfactual approach to determine the indirect effect and percentage of effect mediated through small for gestational age. For risk factors significantly mediated through small for gestational age, the relative risks of stillbirth were compared between small for gestational age and appropriate for gestational age infants. We also investigated the proportion of risk mediated via small for gestational age for late stillbirths (≥28 weeks).

    RESULTS: The initial data set consisted of 1,105,612 births. After exclusions, the final study cohort constituted 925,053 births. Small for gestational age births occurred in 9.9% (91,859/925,053) of the study cohort. Stillbirths occurred in 0.5% of all births (4234/925,053) and 1.5% of small for gestational age births (1414/91,859). Births at ≥28 weeks occurred in 99.4% (919,650/925,053) of the study cohort and in 98.9% (90,804/91,859) of all small for gestational age births. Of the ≥28-week births, stillbirths occurred in 0.2% (2156/919,650) of all births and 0.8% (677/90,804) of the small for gestational age births. Overall, increased odds of stillbirth were significantly mediated through small for gestational age for age <20 years, low socioeconomic status, Indigenous ethnicity, birth in sub-Saharan and North Africa or the Middle East, smoking, nulliparity, multiple pregnancy, assisted conception, previous stillbirth, preeclampsia, and renal disease. Preeclampsia had the largest proportion mediated through small for gestational age (66.7%), followed by nulliparity (61.6%), smoking (29.4%), North-African or Middle Eastern ethnicity (27.6%), multiple pregnancy (26.3%), low socioeconomic status (25.8%), and Indigenous status (18.7%). Sensitivity analysis showed that for late stillbirths, the portions mediated through small for gestational age remained very similar for many of the risk factors.

    CONCLUSION: Although small for gestational age is an important mediator between many pregnancy risk factors and stillbirth, mitigating the risk of small for gestational age is likely to be of value only when it is a major contributor in the pathway to fetal demise.

    Matched MeSH terms: Fetal Growth Retardation/epidemiology
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