Lessons from implementation research on community management of Possible Serious Bacterial Infection (PSBI) in young infants (0-59 days), when the referral is not feasible in Palwal district of Haryana, India.

BACKGROUND: Neonatal sepsis is a major cause of death in India, which needs hospital management but many families cannot access hospitals. The World Health Organization and the Government of India developed a guideline to manage possible serious bacterial infection (PSBI) when a referral is not feasible. We implemented this guideline to achieve high coverage of treatment of PSBI with low mortality. METHODOLOGY: The implementation research study was conducted in over 50 villages of Palwal district, Haryana during August 2017-March 2019 and covered a population of 199143. Policy dialogue with central, state and district health authorities was held before initiation of the study. A baseline assessment of the barriers in the implementation of the PSBI intervention was conducted. The intervention was implemented in the program setting. The research team collected data throughout and also co-participated in the implementation of the intervention for the first six months to identify bottlenecks in the health system and at the community level. RE-AIM framework was utilized to document implementation strategies of PSBI management guideline. Implementation strategies by the district technical support unit (TSU) included: (i) empower mothers and families through social mobilization to improve care-seeking of sick young infants 0-59 days of age, (ii) build capacity through training and build confidence through technical support of health staff at primary health centers (PHC), community health centers (CHC) and sub-centers to manage young infants with PSBI signs and (iii) improve performance of accredited social health activists (ASHAs). FINDINGS: A total of 370 young infants with signs of PSBI were identified and managed in 5270 live births. Treatment coverage was 70% assuming that 10% of live births would have PSBI within the first two months of life. Mothers identified 87.6% (324/370) of PSBI cases. PHCs and CHCs became functional and managed 150 (40%) sick young infants with PSBI. Twenty four young infants (7-59days) who had only fast breathing were treated with oral amoxicillin without a referral. Referral to a hospital was refused by 126 (84%); 119 had clinical severe infection (CSI), one 0-6 days old had fast breathing and six had critical illness (CI). Of 119 CSI cases managed on outpatient injection gentamicin and oral amoxicillin, 116 (96.7%) recovered, 55 (45.8%) received all seven gentamicin injections and only one died. All 7-59 day old infants with fast breathing recovered, 23 on outpatient oral amoxicillin treatment; and 19 (79%) received all doses. Of 65 infants managed at either district or tertiary hospital, two (3.1%) died, rest recovered. Private providers managed 155 (41.9%) PSBI cases, all except one recovered, but sub-classification and treatment were unknown. Sub-centers could not be activated to manage PSBI. CONCLUSION: The study demonstrated resolution of implementation bottlenecks with existing resources, activated PHCs and CHCs to manage CSI and fast breathers (7-59 day old) on an outpatient basis with low mortality when a referral was not feasible. TSU was instrumental in these achievements. We established the effectiveness of oral amoxicillin alone in 7-59 days old fast breathers and recommend a review of the current national policy.

Special Newborn Care Plus Project in India: Preliminary Findings from Community-Based Follow-up of Newborns Discharged from Facilities.

OBJECTIVE: An innovation of structured community based followup of SNCU discharged babies by ANM and ASHA was piloted under Norway India Partnership initiative. The current study describes the survival status and other outcomes among newborns discharged from SNCUs and followed at community level in first 42 days of life. METHODS: It is a retrospective cohort study on newborns discharged from SNCUs from 13 districts across four states of India. Routine health systems data have been utilized to record key parameters like birth weight, sex, weights during follow-ups, any illnesses reported, status of feeding and survival status. These were compared between normal and low birth weight babies. Newborns discharged from special newborn care units (SNCUs) and followed up at community level at 24 hours, 7 days after first visit, and at 6 weeks of life. RESULTS: Follow up of 6319 newborns were conducted by the ANM (25.4%), ASHAs (4.7%) or both (69.8%); 97% of the babies were followed-up at all the visits. The median duration of follow- ups were 1 day post-discharge, 13th day and 45th days of life. Majority (97%) of them were breastfed, and were warm to touch at the time of the visit. More than 11% of the babies needed referral at every visit. Mortality rate in the cohort of babies discharged from SNCUs till 6 weeks of follow up was 1.5%. Among normal birth weight newborns, it was 0.4% while it was 2.02% among LBW babies. The proportion of girls among those who died increased from 20% in the first follow up to 38.1% at second follow up and 41% at 6 weeks. CONCLUSIONS: Babies with LBW were at higher risk of death as compared to babies with normal birth weight. Follow-up at critical timepoints can improve survival of small and sick newborns after discharge from SNCUs.

New n-nonadecanoyl-ß-sitosterol and other constituents from the stem-bark of Anacardium occidentale.

A new steroidal ester bearing n-nonadecanoyl moiety (1) and a mixture of isomeric cerebrosides (2) along with two known compounds were isolated from the methanol extract of the stem-bark of Anacardium occidentale. The structure of the new steroidal ester was determined as 3-n-nonadecanoyl-ß-sitosterol on the basis of modern spectroscopic techniques (IR, ESI-MS, HR-ESIMS, 1D and 2D NMR) and chemical degradation studies. The structures of the known compounds were identified as gallic acid and tanacetene by comparison of the spectroscopic data with those of reported data. The mixture of cerebrosides was confirmed based on the analysis of 1D and 2D NMR. These compounds were evaluated for cytotoxicity against human cancer cell lines A549, SCOV3 and rat normal cell line NRK49f.

Headache in children with Sturge-Weber syndrome - Prevalence, associations and impact.

BACKGROUND: Sturge-Weber syndrome (SWS) is a congenital neurovascular disorder characterised by capillary-venous malformations involving the skin, brain and eye. Patients experience headache, however little is known about its characteristics or associations. We aimed to estimate prevalence, associations and the impact of headache in children with SWS. MATERIALS AND METHODS: Case notes of all patients in a national tertiary paediatric SWS clinic were retrospectively reviewed. Patients were categorised into those with or without a history of headache, with an analysis performed of clinical stigmata of their disease and headache symptomology, associations and treatment. A multivariable logistic regression analysis was undertaken to elicit independent predictors of headache. RESULTS: 37% of patients with SWS (n = 84) reported headaches that were variably associated with seizures, a preceding blow to the head and a minority had migraine features. In those reporting headaches, headaches interfered with daily activities of a quarter of the children and 39% experienced headaches frequently (more than 1/month). Headache was associated with glaucoma and aspirin administration while children with monoplegia and hemiplegia were less likely to have headache. CONCLUSIONS: Headache is common in children with SWS, often without classical migraine features and affects daily activities. Awareness of headache and its associations in SWS may improve management of this complex population.

Hyperpigmentation as a cutaneous manifestation of fungal sepsis in neonates: Case series report.

With improved and prolonged survival of very and extremely low birth weight infants, invasive fungal infection has emerged as an important concern in the neonatal intensive care units. Candidiasis is the third leading cause of late onset sepsis in these neonates and is associated with 20-30% mortality. Extreme prematurity, central venous catheters, prolonged antibiotic exposure, parenteral nutrition are important risk factors. Various forms of cutaneous manifestations of candidiasis have been described ranging from local diaper dermatitis and oral thrush to widespread erosive and ulcerative lesions with extensive crusting in invasive fungal dermatitis. We report a series of four cases with cutaneous hyperpigmentation as manifestation of systemic candidiasis.

PELP1 signaling contributes to medulloblastoma progression by regulating the NF-κB pathway.

Medulloblastoma (MB) is the most common and deadliest brain tumor in children. Proline-, glutamic acid-, and leucine-rich protein 1 (PELP1) is a scaffolding protein and its oncogenic signaling is implicated in the progression of several cancers. However, the role of PELP1 in the progression of MB remains unknown. The objective of this study is to examine the role of PELP1 in the progression of MB. Immunohistochemical analysis of MB tissue microarrays revealed that PELP1 is overexpressed in the MB specimens compared to normal brain. Knockdown of PELP1 reduced cell proliferation, cell survival, and cell invasion of MB cell lines. The RNA-sequencing analysis revealed that PELP1 knockdown significantly downregulated the pathways related to inflammation and extracellular matrix. Gene set enrichment analysis confirmed that the PELP1-regulated genes were negatively correlated with nuclear factor-κB (NF-κB), extracellular matrix, and angiogenesis gene sets. Interestingly, PELP1 knockdown reduced the expression of NF-κB target genes, NF-κB reporter activity, and inhibited the nuclear translocation of p65. Importantly, the knockdown of PELP1 significantly reduced in vivo MB progression in orthotopic models and improved the overall mice survival. Collectively, these results suggest that PELP1 could be a novel target for therapeutic intervention in MB.

Correction to: Spectrum of movement disorders and neurotransmitter abnormalities in paediatric POLG disease.

Due to a typesetting error the wrong Table 2 was used. The correct Table 2 is shown here.

Spectrum of movement disorders and neurotransmitter abnormalities in paediatric POLG disease.

OBJECTIVES: To describe the spectrum of movement disorders and cerebrospinal fluid (CSF) neurotransmitter profiles in paediatric patients with POLG disease. METHODS: We identified children with genetically confirmed POLG disease, in whom CSF neurotransmitter analysis had been undertaken. Clinical data were collected retrospectively. CSF neurotransmitter levels were compared to both standardised age-related reference ranges and to non-POLG patients presenting with status epilepticus. RESULTS: Forty-one patients with POLG disease were identified. Almost 50% of the patients had documented evidence of a movement disorder, including non-epileptic myoclonus, choreoathetosis and ataxia. CSF neurotransmitter analysis was undertaken in 15 cases and abnormalities were seen in the majority (87%) of cases tested. In many patients, distinctive patterns were evident, including raised neopterin, homovanillic acid and 5-hydroxyindoleacetic acid levels. CONCLUSIONS: Children with POLG mutations can manifest with a wide spectrum of abnormal movements, which are often prominent features of the clinical syndrome. Underlying pathophysiology is probably multifactorial, and aberrant monoamine metabolism is likely to play a role.

Comparative study of nano and bulk Fe3O4 induced oxidative stress in Wistar rats.

CONTEXT: Magnetic nanomaterials (Fe3O4 NMs) have become novel tools with multiple biological and medical applications because of their biocompatibility. However, adverse health effects of these NMs are of great interest to learn. OBJECTIVE: This study was designed to assess the size and dose-dependent effects of Fe3O4 NMs and its bulk on oxidative stress biomarkers after post-subacute treatment in female Wistar rats. METHODS: Rats were daily administered with 30, 300 and 1000 mg/kg b.w. doses for 28 d of Fe3O4 NMs and its bulk for biodistribution and histopathological studies. RESULTS: Fe3O4 NMs treatment caused significant increase in lipid peroxidation levels of treated rats. It was also observed that the NM treatment elicited significant changes in enzyme activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase  and glutathione-S-transferase in treated rat organs with major reduction in glutathione content. Metal content analysis revealed that tissue deposition of NM in the organs was higher when compared to bulk and caused histological changes in liver. CONCLUSION: This study demonstrated that for same dose, NM showed higher bioaccumulation, oxidative stress and tissue damage than its bulk. The difference in toxic effect of Fe3O4 nano and bulk could be related to their altered physicochemical properties.

Hybrid drug combination: Combination of ferulic acid and metformin as anti-diabetic therapy.

BACKGROUND AND PURPOSE: Ferulic acid, an anti-oxidant phytochemical present in several dietary components, is known to produce wide range of pharmacological effects. It is approved for use in food industry as a preservative and in sports food. Previous reports from our lab have shown synergistic interaction of ferulic acid with metformin in cell lines and diabetic rats. The purpose of this review is to compile information about anti-diabetic activity of ferulic acid in in vitro and in vivo models with special emphasis on activity of ferulic acid when combined with metformin. The mechanism of synergistic interaction between ferulic acid and metformin is also proposed after carefully studying effects of these compounds on molecules involved in glucose metabolism. METHODS: Scientific literature for the purpose of this review was collected using online search engines and databases such as ScienceDirect, Scopus, PubMed and Google scholar. RESULTS: Ferulic acid forms resonance stabilized phenoxyl radical which scavenges free radicals and reduce oxidative stress. It improves glucose and lipid profile in diabetic rats by enhancing activities of antioxidant enzymes, superoxide dismutase and catalase in the pancreatic tissue. Combining ferulic acid with metformin improves both, in vitro glucose uptake activity and in vivo hypoglycemic activity of the latter. It is possible to reduce the dose of metformin by four folds (from 50 to 12.5 mg/kg body weight) by combining it with 10 mg of ferulic acid/kg body weight in diabetic rats. Ferulic acid improves glucose uptake through PI3-K pathway whereas metformin activates AMPK pathway to improve glucose uptake. CONCLUSION: The synergistic interaction of ferulic acid and metformin is due their action on parallel pathways which are involved in glucose uptake. Due to synergistic nature of their interaction, it is possible to reduce the dose of metformin (by combining with ferulic acid) required to achieve normoglycemia. Since the dose of metformin is reduced, the dose associated side effects of metformin therapy can be reduced.

Biomarkers of oxidative stress for in vivo assessment of toxicological effects of iron oxide nanoparticles.

Iron oxide nanoparticles (Fe2O3-IONPs) have revolutionized the industry by significant economic and scientific impacts. Enormous increase in the usage of IONPs has raised concerns about their unseen adverse effects. In the current study, we investigated the effects of IONPs and its bulk on oxidative stress biomarkers, histopathology and biodistribution in rats after 28 days repeated oral treatment at 30, 300 and 1000 mg/kg body weight (b.w.). IONPs size in dry, wet forms and crystallinity was determined using TEM, DLS and XRD. The investigation of oxidative stress biomarkers demonstrated significant increase in lipid peroxidation and decrease in reduced glutathione content in the liver, kidney and the brain of the treated groups in a dose dependant manner. Further, antioxidant enzymes catalase, glutathione S transferase, glutathione peroxidase and glutathione reductase activities were significantly elevated along with significant decrease in superoxide dismutase activity in treated rat organs. ICP-OES analysis revealed dose and size dependant accumulation of IONPs in the liver followed by kidney and the brain than bulk. Moreover, accumulation of IONPs at high dose brought pathological changes only in liver. A large fraction of IONPs was eliminated in urine. Bulk material was substantially excreted in faeces than IONPs suggesting increased absorption of IONPs. In conclusion accumulated IONPs and bulk in organs trigger free radical generation, leading to the induction of oxidative stress condition in rats. The results obtained highlight the importance of toxicity assessments in evaluating the efficiency of IONPs for the safe implementation for diversified applications.

Premonitory Symptoms of Migraine in Childhood and Adolescence.

PURPOSE OF REVIEW: Premonitory symptoms in migraine; symptoms occurring before the onset of migraine pain or aura, are an increasingly recognised area of interest within headache research. It has been recently documented in the literature that these symptoms also occur in children and adolescents, with a comparable phenotype to adults. This review discusses the wide presentation of premonitory symptoms in migraine in children and adolescents, and the importance of understanding how these early symptoms are mediated in order to ensure that targeted abortive therapies are developed in the future. Recognition of these symptoms by parents, guardians, teachers and carers is of importance in ensuring early and effective attack treatment. RECENT FINDINGS: A previous clinic-based questionnaire study in 103 children found a prevalence of premonitory symptoms in paediatric migraine of 67%, with a mean number of reported symptoms of two. A recent study found that in a clinic population of 100 children or adolescents with a migraine diagnosis who were preselected as having at least one premonitory symptom associated with their attacks, two or more premonitory symptoms were reported by 85% of patients. The most common symptoms were fatigue, mood change and neck stiffness. Although the population prevalence of premonitory symptoms in migraine within the paediatric population, or their ability to predict accurately the onset of an impending headache cannot be deduced from the retrospective studies performed to date, premonitory symptoms occur in children as young as 18 months old. Understanding the biological basis of these, and their heterogeneous phenotype may help future targeted therapeutic research, helping the development of drugs that act before the onset of pain, limiting the morbidity associated with the migraine attack.

Improving Perinatal Health: Are Indian Health Policies Progressing In The Right Direction?

BACKGROUND: Strategic investments and policy directives of the Indian Government has demonstrated highest degree of political commitment for maternal and child health care. OBJECTIVES: To evaluate the impact of the rise in institutional deliveries in India on perinatal mortality. METHODS: Hospital delivery rate and perinatal mortality rate (PNMR), reported by Sample Registration System, Registrar General of India, on a representative sample was used. The correlation between relative change in hospital deliveries and PNMR was examined. RESULTS: In rural areas of India, hospital deliveries have increased during 2005-2013 from 24.4 to 69.7% and PNMR has declined from 40 to 28 per 1000 births. At the state level, there was significant correlation between the rise in hospital delivery rate and decline in PNMR (r 0.4, p 0.04). CONCLUSIONS: Decline in perinatal rates can be attributed to India's strategic initiatives in health policy and planning for increasing deliveries in hospitals.

Studies on reconstruction of large skin defects following mammary tumor excision in dogs.

AIM: The main objective of the study was to describe the use of skin fold advancement flaps (SFAFs) and other reconstructive techniques for closure of large skin defects following mammary tumor excision in dogs. MATERIALS AND METHODS: Twelve dogs underwent reconstruction of large ventral skin defects following mammary tumor excision with wide margins. Skin fold flaps (flank fold flap and elbow fold flap) were elevated from the flank and elbow region, respectively, and transposed and sutured onto the large ventral skin defect following mastectomy in all the dogs. In addition to the skin fold flaps, other reconstructive techniques such as undermining, walking sutures, and tension-relieving suture techniques were followed during surgery in the closure of large skin defects without skin tension and compromising limb mobility. The skin flap viability was assessed subjectively by gross observation of the flap such as color, temperature, capillary perfusion, and cosmetic appearance, and scoring (1-4) was done. Tissue samples were collected from a surgical site on days 3, 6, and 12 post-operatively for histopathological evaluation and healing status of the skin flap. RESULTS: All the surgical wounds healed primarily, without any major complications and the skin flap remained healthy throughout the healing process post-operatively. Distal flap necrosis was noticed in one case and necrosis of skin flap between two suture lines was noticed in another case in which the necrotized distal portion healed by secondary intention after 7 days. The mean survival of subdermal plexus flap in the above cases was 98% which was a subjective evaluation based on surface area of the skin defect measured by Image' J software and the flap dimensions. The average healing of skin flap in days was 14.91±0.86. CONCLUSION: The SFAFs along with other reconstructive techniques help in the reconstruction of large ventral skin defects following mastectomy in dogs without much compromising limb mobility.

State of newborn health in India.

About 0.75 million neonates die every year in India, the highest for any country in the world. The neonatal mortality rate (NMR) declined from 52 per 1000 live births in 1990 to 28 per 1000 live births in 2013, but the rate of decline has been slow and lags behind that of infant and under-five child mortality rates. The slower decline has led to increasing contribution of neonatal mortality to infant and under-five mortality. Among neonatal deaths, the rate of decline in early neonatal mortality rate (ENMR) is much lower than that of late NMR. The high level and slow decline in early NMR are also reflected in a high and stagnant perinatal mortality rate. The rate of decline in NMR, and to an extent ENMR, has accelerated with the introduction of National Rural Health Mission in mid-2005. Almost all states have witnessed this phenomenon, but there is still a huge disparity in NMR between and even within the states. The disparity is further compounded by rural-urban, poor-rich and gender differentials. There is an interplay of different demographic, educational, socioeconomic, biological and care-seeking factors, which are responsible for the differentials and the high burden of neonatal mortality. Addressing inequity in India is an important cross-cutting action that will reduce newborn mortality.

Inpatient care of small and sick newborns in healthcare facilities.

Neonatal units in teaching and non-teaching hospitals both in public and private hospitals have been increasing in number in the country since the sixties. In 1994, a District Newborn Care Programme was introduced as a part of the Child Survival and Safe Motherhood Programme (CSSM) in 26 districts. Inpatient care of small and sick newborns in the public health system got a boost under National Rural Health Mission with the launch of the national programme on facility-based newborn care (FBNC). This has led to a nationwide creation of Newborn Care Corners (NBCC) at every point of child birth, newborn stabilization units (NBSUs) at First Referral Units (FRUs) and special newborn care units (SNCUs) at district hospitals. Guidelines and toolkits for standardized infrastructure, human resources and services at each level have been developed and a system of reporting data on FBNC created. Till March 2015, there were 565 SNCUs, 1904 NBSUs and 14 163 NBCCs operating in the country. There has been considerable progress in operationalizing SNCUs at the district hospitals; however establishing a network of SNCUs, NBSUs and NBCCs as a composite functional unit of newborn care continuum at the district level has lagged behind. NBSUs, the first point of referral for the sick newborn, have not received the desired attention and have remained a weak link in most districts. Other challenges include shortage of physicians, and hospital beds and absence of mechanisms for timely repair of equipment. With admission protocols not being adequately followed and a weak NBSU system, SNCUs are faced with the problem of admission overload and poor quality of care. Applying best practices of care at SNCUs, creating more NBSU linkages and strengthening NBCCs are important steps toward improving quality of FBNC. This can be further improved with regular monitoring and mentoring from experienced pediatricians, and nurses drawn from medical colleges and the private sector. In addition there is a need to further increase such units to address the unmet need of facility-based care.

Care of newborn in the community and at home.

India has contributed immensely toward generating evidence on two key domains of newborn care: Home Based Newborn Care (HBNC) and community mobilization. In a model developed in Gadchiroli (Maharashtra) in the 1990s, a package of Interventions delivered by community health workers during home visits led to a marked decline in neonatal deaths. On the basis of this experience, the national HBNC program centered around Accredited Social Health Activists (ASHAs) was introduced in 2011, and is now the main community-level program in newborn health. Earlier in 2004, the Integrated Management of Neonatal and Childhood Illnesses (IMNCI) program was rolled out with inclusion of home visits by Anganwadi Worker as an integral component. IMNCI has been implemented in 505 districts in 27 states and 4 union territories. A mix of Anganwadi Workers, ASHAs, auxiliary nursing midwives (ANMs) was trained. The rapid roll out of IMNCI program resulted in improving quality of newborn care at the ground field. However, since 2012 the Ministry of Health and Family Welfare decided to limit the IMNCI program to ANMs only and leaving the Anganwadi component to the stewardship of the Integrated Child Development Services. ASHAs, the frontline workers for HBNC, receive four rounds of training using two modules. There are a total of over 900 000 ASHAs per link workers in the country, out of which, only 14% have completed the fourth round of training. The pace of uptake of the HBNC program has been slow. Of the annual rural birth cohort of over 17 million, about 4 million newborns have been visited by ASHA during the financial year 2013-2014 and out of this 120 000 neonates have been identified as sick and referred to health facilities for higher level of neonatal care. Supportive supervision remains a challenge, the role of ANMs in supervision needs more clarity and there are issues surrounding quality of training and the supply of HBNC kits. The program has low visibility in many states. Now is the time to tap the missed opportunity of miniscule coverage of HBNC; that at least half of the country's birth cohort should be covered by this program by 2016, coupled with rapid scale up of the community-based treatment of neonates with pneumonia or sepsis, where referral is not possible.

Surgical management of extensive oral tumors by bilateral rostral mandibulectomy in two dogs.

Two dogs of different age groups were presented with the history of oral growth, bleeding, excessive salivation, bad breath, inappetance and dysphagia. Physical examination revealed cauliflower like reddish growth in the gingiva enclosing the mandibular incisiors and canine tooth. Haematology and serum biochemical profiles were within the normal range. Plain radiography revealed extensive growth involving the lower mandible and gingiva. Hence rostral mandibulectomy was performed to excise the tumor mass. The dogs recovered uneventfully after surgery with no difficulty in feeding liquid and semisolid diet. The post operative prognosis for dogs with oral neoplasia depends on type of tumor and extent of disease at the time of surgery. In the above two cases the tumors were benign and rostral mandibulectomy provided excellent prognosis and recovery with no recurrence of tumor.

Characterising the premonitory stage of migraine in children: a clinic-based study of 100 patients in a specialist headache service.

BACKGROUND: The premonitory stage of migraine attacks, when symptomatology outside of pain can manifest hours to days before the onset of the headache, is well recognised. Such symptoms have been reported in adults in a number of studies, and have value in predicting an impending headache. These symptoms have not been extensively studied in children. We aimed to characterise which, if any, of these symptoms are reported in children seen within a Specialist Headache Service. METHODS: We reviewed clinic letters from the initial consultation of children and adolescents seen within the Specialist Headache Service at Great Ormond Street Hospital between 1999 and 2015 with migraine in whom we had prospectively assessed clinical phenotype data. We randomly selected 100 cases with at least one premonitory symptom recorded in the letter. For these patients, the age at headache onset, presence of family history of headache, headache diagnosis, presence of episodic syndromes which may be associated with headache, developmental milestones, gestation at birth, mode of delivery and presence of premonitory symptoms occurring before or during headache were recorded. RESULTS: Of the 100 patients selected, 65 % were female. The age range of the patients was 18 months to 15 years at the time of headache onset. The most common diagnosis was chronic migraine in 58 %, followed by episodic migraine (29 %), New Daily Persistent Headache with migrainous features (8 %) and hemiplegic migraine (5 %). A history of infantile colic was noted in 31 % and was the most common childhood episodic syndrome associated with migraine. The most common premonitory symptoms recorded were fatigue, mood change and neck stiffness. The commonest number of reported premonitory symptoms was two. CONCLUSION: Premonitory symptoms associated with migraine are reported in children as young as 18 months, with an overall clinical phenotype comparable to adults. Better documentation of this stage will aid parents and clinicians to better understand the phenotype of attacks, better recognise migraine and thus initiate appropriate management. Larger studies with a broader base are warranted to understand the extent and implications of these symptoms for childhood and adolescent migraine.