Imperial College London

DrNatalieShenker

Faculty of MedicineDepartment of Surgery & Cancer

Research Fellow
 
 
 
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Contact

 

natalie.shenker09

 
 
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Location

 

Institute of Reproductive and Developmental BiologyHammersmith Campus

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Summary

 

Publications

Publication Type
Year
to

33 results found

Shenker N, Staff M, Vickers A, Aprigio J, Tiwari S, Nangia S, Sachdeva RC, Clifford V, Coutsoudis A, Reimers P, Israel-Ballard K, Mansen K, Mileusnic-Milenovic R, Wesolowska A, Goudoever JBV, Hosseini M, Klotz D, Grøvslien AH, Weaver G, Virtual Collaborative Network of Milk Banks and Associationset al., 2021, Maintaining human milk bank services throughout the COVID-19 pandemic: A global response, Maternal and Child Nutrition, Vol: 17, Pages: 1-13, ISSN: 1740-8695

If maternal milk is unavailable, the World Health Organization recommends that the first alternative should be pasteurised donor human milk (DHM). Human milk banks (HMBs) screen and recruit milk donors, and DHM principally feeds very low birth weight babies, reducing the risk of complications and supporting maternal breastfeeding where used alongside optimal lactation support. The COVID-19 pandemic has presented a range of challenges to HMBs worldwide. This study aimed to understand the impacts of the pandemic on HMB services and develop initial guidance regarding risk limitation. A Virtual Collaborative Network (VCN) comprising over 80 HMB leaders from 36 countries was formed in March 2020 and included academics and nongovernmental organisations. Individual milk banks, national networks and regional associations submitted data regarding the number of HMBs, volume of DHM produced and number of recipients in each global region. Estimates were calculated in the context of missing or incomplete data. Through open-ended questioning, the experiences of milk banks from each country in the first 2 months of the pandemic were collected and major themes identified. According to data collected from 446 individual HMBs, more than 800,000 infants receive DHM worldwide each year. Seven pandemic-related specific vulnerabilities to service provision were identified, including sufficient donors, prescreening disruption, DHM availability, logistics, communication, safe handling and contingency planning, which were highly context-dependent. The VCN now plans a formal consensus approach to the optimal response of HMBs to new pathogens using crowdsourced data, enabling the benchmarking of future strategies to support DHM access and neonatal health in future emergencies.

Journal article

Wedekind SIS, Shenker NS, 2021, Antiviral properties of human milk, Microorganisms, Vol: 9, ISSN: 2076-2607

Humans have always coexisted with viruses, with both positive and negative consequences. Evolutionary pressure on mammals has selected intrinsic properties of lactation and milk to support the relatively immunocompromised neonate from environmental pathogens, as well as support the normal development of diverse immune responses. Human milk supports both adaptive and innate immunity, with specific constituents that drive immune learning and maturation, and direct protection against microorganisms. Viruses constitute one of the most ancient pressures on human evolution, and yet there is a lack of awareness by both public and healthcare professionals of the complexity of human milk as an adaptive response beyond the production of maternal antibodies. This review identifies and describes the specific antiviral properties of human milk and describes how maternal support of infants through lactation is protective beyond antibodies.

Journal article

Bramer S, Boyle R, Weaver G, Shenker Net al., 2021, Use of donor human milk in nonhospitalized infants: An infant growth study, Maternal and Child Nutrition, Vol: 17, Pages: 1-9, ISSN: 1740-8695

When mother's own milk (MOM) is unavailable or insufficient, donor human milk (DHM) is recommended as the next best alternative for low birthweight infants. DHM use for healthy, term infants is increasing, but evidence for growth and tolerability is limited. This retrospective study evaluated growth in term infants in the community who received DHM from a UK milk bank. Mothers of infants receiving DHM between 2017 and 2019 were contacted (n = 49), and 31 (63.2%) agreed to participate. Fourteen infants received DHM as a supplement to other feeds (MOM and/or infant formula) and 17 were exclusively fed DHM where breastfeeding was impossible (range: 3–6 weeks). Growth was assessed by deriving z‐scores using the WHO standard for infant growth and compared with 200 exclusively breastfed infants. Multivariate regression analysis revealed no feeding method‐specific association between z‐score and age, nor between weight and age, suggesting that z‐scores and growth velocity were not affected by feeding exclusive MOM, supplemental DHM or exclusive DHM. DHM was well‐tolerated with no adverse events that led to early cessation. After receiving supplemental DHM group, 63% of infants whose mothers had no physical barrier to breastfeeding (5/8 infants) were exclusively breastfed. This novel study reports adequate growth outcomes of healthy nonhospitalized infants receiving DHM, either as the sole milk source or supplement. Prospective studies are needed to confirm whether DHM is a suitable feeding alternative for term infants in the community, optimal durations, as well as the impact of DHM availability on breastfeeding rates and maternal mental health.

Journal article

Brown A, Shenker N, 2021, Experiences of breastfeeding during COVID-19: Lessons for future practical and emotional support, Maternal and Child Nutrition, Vol: 17, Pages: 1-15, ISSN: 1740-8695

The COVID-19 pandemic and subsequent lockdown and social distancing led to changes to breastfeeding support available to women in the United Kingdom. Face-to-face professional support was reduced, and face-to-face peer support was cancelled. Anecdotal media accounts highlighted practices separating some mothers and babies in hospitals, alongside inaccurate stories of the safety of breastfeeding circulating. Meanwhile, new families were confined to their homes, separated from families and support networks. Given that we know breastfeeding is best supported by practices that keep mother and baby together, high-quality professional and peer-to-peer support, and positive maternal well-being, it is important to understand the impact of the pandemic upon the ability to breastfeed. To explore this, we conducted an online survey with 1219 breastfeeding mothers in the United Kingdom with a baby 0-12 months old to understand the impact of the pandemic upon breastfeeding duration, experiences and support. The results highlighted two very different experiences: 41.8% of mothers felt that breastfeeding was protected due to lockdown, but 27.0% of mothers struggled to get support and had numerous barriers stemming from lockdown with some stopped breastfeeding before they were ready. Mothers with a lower education, with more challenging living circumstances and from Black and minority ethnic backgrounds were more likely to find the impact of lockdown challenging and stop breastfeeding. The findings are vital in understanding how we now support those women who may be grieving their loss of breastfeeding and are affected by their negative experiences and how we can learn from those with a positive experience to make sure all breastfeeding women are better supported if similar future events arise.

Journal article

Azad MB, Nickel NC, Bode L, Brockway M, Brown A, Chambers C, Goldhammer C, Hinde K, McGuire M, Munblit D, Patel AL, Perez-Escamilla R, Rasmussen KM, Shenker N, Young BE, Zuccolo Let al., 2020, Breastfeeding and the origins of health: Interdisciplinary perspectives and priorities, MATERNAL AND CHILD NUTRITION, Vol: 17, ISSN: 1740-8695

Journal article

Shenker NS, Perdones-Montero A, Burke A, Stickland S, McDonald JAK, Alexander-Hardiman K, Flanagan J, Takats Z, Cameron SJSet al., 2020, Metabolomic and Metataxonomic Fingerprinting of Human Milk Suggests Compositional Stability over a Natural Term of Breastfeeding to 24 Months, NUTRIENTS, Vol: 12

Journal article

Shenker NS, Wesolowska A, van Goudoever JB, Nangia S, Klotz Det al., 2020, Undermining breastfeeding will not alleviate the COVID-19 pandemic, LANCET, Vol: 396, Pages: 1064-1065, ISSN: 0140-6736

Journal article

Shenker N, Virtual Collaborative Network of Human Milk Banks and Associations, 2020, Maintaining safety and service provision in human milk banking: a call to action in response to the COVID-19 pandemic, The Lancet Child and Adolescent Health, Vol: 4, Pages: 484-485, ISSN: 2352-4642

Journal article

Biggs KV, Fidler KJ, Shenker NS, Brown Het al., 2020, Are the doctors of the future ready to support breastfeeding? A cross-sectional study in the UK, International Breastfeeding Journal, Vol: 15, Pages: 1-8, ISSN: 1746-4358

BackgroundCurrently there is no published data on the inclusion of breastfeeding education within the UK medical school curriculum. This study aims to address this knowledge gap and explore students’ perceptions of their readiness to support breastfeeding.MethodsAn online survey was used to collect data from 32 UK undergraduate medical schools and their students. All students in their final two years of study at the 30 universities offering a 5- or 6-year medicine course, were eligible.ResultsCurriculum data was obtained from 26 (81%) institutions. Compulsory breastfeeding education was provided by 85% (N = 22) institutions with 81% (n = 21) providing lecture-based teaching and 19% (n = 5) offering formal clinical education. Overall, 411 students from 22 institutions participated. A moderate ability to identify the benefits of breastfeeding was observed; however, self-rated confidence in practical skills was poor. Assisting with latching was the least confident skill, with confidence in only 3% (14/411) students. Most students (93%) viewed doctors as playing an important role in breastfeeding, with those interested in either women’s health, paediatrics or general practice perceiving the role of doctors as more important. Overall, 93% (381/411) students requested further breastfeeding education.ConclusionsThis study suggests UK medical schools are not adequately preparing students to support breastfeeding patients. Further studies should explore the competency of doctors to meet the needs of lactating women, and design optimal training for UK medical students.

Journal article

Bramer S, Hazemi-Jebelli Y, Weaver G, Boyle R, Shenker Net al., 2019, The provision of donor human milk beyond the NICU, Academy for Breastfeeding Medicine, Publisher: Mary Ann Liebert, ISSN: 1556-8253

Background: In the UK, to date, there is little evidence to support the safe use of donor human milk (DHM) from a human milk bank beyond extremely premature babies in neonatal intensive care units. The HMB operates as part of a new charity, the Human Milk Foundation, and foremost aim to fill gaps in the provision of donor human milk (DHM) to hospital neonatal units. Secondary aims of the HMB are to facilitate research into operational aspects of human milk banking, the clinical use of DHM and the science of human milk.Objective(s): This study aimed to assess the growth and tolerance of infants provided with DHM from the Hearts Milk Bank (HMB) in the UK over the course of their first 18 months of operation, as well as the range of indications for which DHM was provided. The study also aimed to understand the impact of DHM use on infant and mother from this case series, and provide the first national and international profile of DHM usage beyond extremely premature babies cared for in NICUs.Materials/Methods: Interviews were conducted over the telephone with follow up questions answered by email when required. All interviews were conducted at the Hearts Milk Bank premises, and no identifiable data left the milk bank premises. Questionnaires were sent electronically using Qualtics to all UK‐based milk banks as well as milk banks internationally, including North America, Europe and Australia, to determine the provision of DHM beyond the NICU. Finally, infant feeding leads in hospitals offering maternity and paediatrics care across the UK was surveyed using a Qualtrics questionnaire to understand the geographical variability in DHM provision, and to understand the reasons that underpinned this. This study was assessed as a service evaluation project by the Imperial Research Ethics team, and formal ethics was not required.Conclusions: DHM that is surplus to the requirements of hospitals has been provided to more than 40 families in the community for a range of indications

Conference paper

Joffe N, Webster F, Shenker N, 2019, Support for breastfeeding is an environmental imperative, BMJ: British Medical Journal, Vol: 367, Pages: 1-2, ISSN: 0959-535X

Journal article

Reimers P, Shenker N, Weaver G, Coutsoudis Aet al., 2018, Using donor human milk to feed vulnerable term infants: a case series in KwaZulu Natal, South Africa, International Breastfeeding Journal, Vol: 13, ISSN: 1746-4358

BackgroundDonor human milk is the World Health Organization’s recommendation for infant feeding when the mother’s own breast milk is unavailable. Breast milk has been shown to reduce morbidity and mortality and in low birthweight infants, donor milk reduces the incidence of necrotising enterocolitis, late onset sepsis and improves outcomes. There is a paucity of literature documenting outcomes of using donor human milk in older children who need additional support for a variety of health issues.Case presentationA series of seven case studies is presented of orphaned and abandoned children, many of whom were either HIV exposed or positive. All children were fed with pasteurised donor human milk at a transition home and their progress reported.ConclusionsAlthough detailed medical records were not always available, the case studies provide anecdotal evidence of the protective effects of donor human milk against failure to thrive, diarrhoea, atopic dermatitis, and opportunistic infections.

Journal article

Shenker NS, 2018, Corrections: The resurgent influence of big formula, BMJ: British Medical Journal, Vol: 362, ISSN: 0959-535X

Journal article

Shenker NS, 2018, The resurgent influence of big formula Education on infant feeding must not be left to industry, BMJ: British Medical Journal, Vol: 362, ISSN: 0959-535X

Journal article

Flower KJ, Shenker NS, el-Bahrawy M, Goldgar DE, Parsons MT, KConFab, AFFECT, Spurdle AB, Morris JR, Brown R, Flanagan JMet al., 2016, DNA methylation profiling to assess pathogenicity of BRCA1 unclassified variants in breast cancer., Epigenetics, Vol: 10, Pages: 1121-1132, ISSN: 1559-2308

Germline pathogenic mutations in BRCA1 increase risk of developing breast cancer. Screening for mutations in BRCA1 frequently identifies sequence variants of unknown pathogenicity and recent work has aimed to develop methods for determining pathogenicity. We previously observed that tumor DNA methylation can differentiate BRCA1-mutated from BRCA1-wild type tumors. We hypothesized that we could predict pathogenicity of variants based on DNA methylation profiles of tumors that had arisen in carriers of unclassified variants. We selected 150 FFPE breast tumor DNA samples [47 BRCA1 pathogenic mutation carriers, 65 BRCAx (BRCA1-wild type), 38 BRCA1 test variants] and analyzed a subset (n=54) using the Illumina 450K methylation platform, using the remaining samples for bisulphite pyrosequencing validation. Three validated markers (BACH2, C8orf31, and LOC654342) were combined with sequence bioinformatics in a model to predict pathogenicity of 27 variants (independent test set). Predictions were compared with standard multifactorial likelihood analysis. Prediction was consistent for c.5194-12G>A (IVS 19-12 G>A) (P>0.99); 13 variants were considered not pathogenic or likely not pathogenic using both approaches. We conclude that tumor DNA methylation data alone has potential to be used in prediction of BRCA1 variant pathogenicity but is not independent of estrogen receptor status and grade, which are used in current multifactorial models to predict pathogenicity.

Journal article

Shenker NS, Flower KJ, Wilhelm-Benartzi C, Dai W, Bell E, El Bahrawy M, Weaver G, Flanagan JM, Brown Ret al., 2015, Transcriptional implications of intragenic DNA methylation in the estrogen receptor alpha gene in breast cancer cells and tissues, 106th Annual Meeting of the American-Association-for-Cancer-Research (AACR), Publisher: American Association for Cancer Research, ISSN: 1538-7445

Conference paper

Shenker NS, Flower KJ, Wilhelm-Benartzi CS, Dai W, Bell E, Gore E, El Bahrawy M, Weaver G, Brown R, Flanagan JMet al., 2015, Transcriptional implications of intragenic DNA methylation in the oestrogen receptor alpha gene in breast cancer cells and tissues., BMC Cancer, Vol: 15, Pages: 337-337, ISSN: 1471-2407

BACKGROUND: DNA methylation variability regions (MVRs) across the oestrogen receptor alpha (ESR1) gene have been identified in peripheral blood cells from breast cancer patients and healthy individuals. In contrast to promoter methylation, gene body methylation may be important in maintaining active transcription. This study aimed to assess MVRs in ESR1 in breast cancer cell lines, tumour biopsies and exfoliated epithelial cells from expressed breast milk (EBM), to determine their significance for ESR1 transcription. METHODS: DNA methylation levels in eight MVRs across ESR1 were assessed by pyrosequencing bisulphite-converted DNA from three oestrogen receptor (ER)-positive and three ER-negative breast cancer cell lines. DNA methylation and expression were assessed following treatment with DAC (1 μM), or DMSO (controls). ESR1 methylation levels were also assayed in DNA from 155 invasive ductal carcinoma biopsies provided by the Breast Cancer Campaign Tissue Bank, and validated with DNA methylation profiles from the TCGA breast tumours (n = 356 ER-pos, n = 109 ER-neg). DNA methylation was profiled in exfoliated breast epithelial cells from EBM using the Illumina 450 K (n = 36) and pyrosequencing in a further 53 donor samples. ESR1 mRNA levels were measured by qRT-PCR. RESULTS: We show that ER-positive cell lines had unmethylated ESR1 promoter regions and highly methylated intragenic regions (median, 80.45%) while ER-negative cells had methylated promoters and lower intragenic methylation levels (median, 38.62%). DAC treatment increased ESR1 expression in ER-negative cells, but significantly reduced methylation and expression of ESR1 in ER-positive cells. The ESR1 promoter was unmethylated in breast tumour biopsies with high levels of intragenic methylation, independent of ER status. However, ESR1 methylation in the strongly ER-positive EBM DNA samples were very similar to ER-positive tumour cell lines. CONCLUSION:

Journal article

Kidher E, Harling L, Nihoyannopoulos P, Shenker N, Ashrafian H, Francis DP, Mayet J, Athanasiou Tet al., 2014, High aortic pulse wave velocity is associated with poor quality of life in surgical aortic valve stenosis patients, INTERACTIVE CARDIOVASCULAR AND THORACIC SURGERY, Vol: 19, Pages: 189-197, ISSN: 1569-9293

Journal article

Shenker NS, Ueland PM, Polidoro S, van Veldhoven K, Ricceri F, Brown R, Flanagan JM, Vineis Pet al., 2013, DNA Methylation as a Long-term Biomarker of Exposure to Tobacco Smoke, EPIDEMIOLOGY, Vol: 24, Pages: 712-716, ISSN: 1044-3983

Journal article

Burge DM, Shah K, Spark P, Shenker N, Pierce M, Kurinczuk JJ, Draper ES, Johnson PRV, Knight Met al., 2013, Contemporary management and outcomes for infants born with oesophageal atresia, BRITISH JOURNAL OF SURGERY, Vol: 100, Pages: 515-521, ISSN: 0007-1323

Journal article

Shenker NS, Polidoro S, van Veldhoven K, Sacerdote C, Ricceri F, Birrell MA, Belvisi MG, Brown R, Vineis P, Flanagan JMet al., 2013, Epigenome-wide association study in the European Prospective Investigation into Cancer and Nutrition (EPIC-Turin) identifies novel genetic loci associated with smoking, HUMAN MOLECULAR GENETICS, Vol: 22, Pages: 843-851, ISSN: 0964-6906

Journal article

Shenker NS, Weaver G, Flanagan JM, 2013, Molecular epidemiology, the Milky Way: use of a hospital milk bank as a source of exfoliated breast epithelial cells for breast cancer research., European Milk Bank Association

Conference paper

Polidoro S, Shenker N, van Veldhoven K, Sacerdote C, Ricceri F, Critelli R, Brown R, Vineis P, Flanagan JMet al., 2012, Epigenome-wide Association Study in the European Prospective Investigation Into Cancer and Nutrition (EPIC-Turin) Identifies Novel Genes Associated With Smoking, 22nd Biennial Congress of the European-Association-for-Cancer-Research, Publisher: ELSEVIER SCI LTD, Pages: S124-S125, ISSN: 0959-8049

Conference paper

Shah K, Spark P, Shenker N, Kurinczuk J, Draper ES, Johnson PRV, Knight M, Burge Det al., 2012, A prospective survey of current practice with oesophageal atresia in the United Kigndom., B J Surg

Pending

Journal article

Shenker N, Flanagan JM, 2011, Intragenic DNA methylation: implications of this epigenetic mechanism for cancer research, British Journal of Cancer, Vol: 106, Pages: 248-253, ISSN: 1532-1827

Epigenetics is the study of all mechanisms that regulate gene transcription and genome stability that are maintained throughout the cell division, but do not include the DNA sequence itself. The best-studied epigenetic mechanism to date is DNA methylation, where methyl groups are added to the cytosine base within cytosine–guanine dinucleotides (CpG sites). CpGs are frequently clustered in high density (CpG islands (CGIs)) at the promoter of over half of all genes. Current knowledge of transcriptional regulation by DNA methylation centres on its role at the promoter where unmethylated CGIs are present at most actively transcribed genes, whereas hypermethylation of the promoter results in gene repression. Over the last 5 years, research has gradually incorporated a broader understanding that methylation patterns across the gene (so-called intragenic or gene body methylation) may have a role in transcriptional regulation and efficiency. Numerous genome-wide DNA methylation profiling studies now support this notion, although whether DNA methylation patterns are a cause or consequence of other regulatory mechanisms is not yet clear. This review will examine the evidence for the function of intragenic methylation in gene transcription, and discuss the significance of this in carcinogenesis and for the future use of therapies targeted against DNA methylation.

Journal article

Shenker NS, Brown B, Flanagan JM, 2011, INTRAGENIC ESR1 DNA METHYLATION LEVELS DIFFER BETWEEN ER-POSITIVE AND ER-NEGATIVE BREAST TUMOURS IN VITRO AND IN VIVO

Conference paper

Patel G, Sadiq J, Shenker N, Impey L, Lakhoo Ket al., 2009, Neonatal survival of prenatally diagnosed exomphalos, PEDIATRIC SURGERY INTERNATIONAL, Vol: 25, Pages: 413-416, ISSN: 0179-0358

Journal article

Shenker NS, 2007, Review of internet information for Crohn’s disease., Annals of the Royal College of Surgeons of England

Journal article

Huynh J, Shenker NS, Nightingale S, Hutson JMet al., 2007, Signalling molecules: clues from development of the limb bud for cryptorchidism?, Pediatr Surg Int, Vol: 23, Pages: 617-624

Recent studies of testicular descent suggest not only that the gubernaculum does not initially attach to the scrotum, but also that it must migrate from the groin. Two findings suggest that the gubernaculum may behave like an embryonic limb bud during this phase. First, the active growth centre is at the distal tip of the gubernaculum. Secondly, the gubernaculum is loose in the subcutaneous tissues beneath Scarpa's fascia. The free protrusion of the gubernaculum from the abdominal wall was so reminiscent of a developing embryonic limb bud, we thought that the biological controls of both processus may be similar. This review examines what is known about vertebrate limb bud development, and compares the mechanisms to what has recently been discovered in the gubernaculum. The hypothesis that both processes may be similar is initially consistent with the current facts, encouraging us to investigate this further experimentally.

Journal article

Shenker NS, Ellis H, 2007, John Hilton (1805-78): anatomist and surgeon., Vol: 15, Pages: 219-226

John Hilton was the foremost anatomist of his day. From only humble beginnings he became an anatomy demonstrator at Guy's Hospital. When appointed Surgeon to Guy's Hospital, his meticulous clinical skills, arising from his depth of anatomical knowledge, led him to develop many anatomical principles culminating in a series of lectures on 'Rest and Pain'. For the first time the clinical importance of each was highlighted in surgical practice. By public demand the lectures were published as a book, still in print today, which brought a new emphasis to clinical anatomy that would permeate surgery thereafter. He became President of the Royal College of Surgeons and was Surgeon Extraordinary to Queen Victoria. A substantial review of his life has not been published; with the present decline in anatomical teaching, we can learn much from understanding a surgeon who dedicated his life to anatomy.

Journal article

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