e025644.full

Transcript

1 Cohort profile Open access BMJ Open: first published as 10.1136/bmjopen-2018-025644 on 5 May 2019. Downloaded from Cohort Profile: Perinatal depression and child socioemotional development ; the Bachpan cohort study from rural Pakistan 3 6 4,5 1 1,2 Ikhlaq Ahmad, Lisa M Bates, John Gallis, Ashley Hagaman, Siham Sikander, 8 1 5 5,7 Atif Rahman, Elizabeth Louise Turner, Ahmed Zaidi, Karen O'Donnell, 6,9 Joanna Maselko To cite: Sikander S, Ahmad I, AC Abstr t s trengths and limitations of this study Bates LM, et al . Cohort Profile: Purpose y–birth cohort This is a prospective pregnanc Perinatal depression and child designed to investigate the effects of depression on The main strengths include hypothesis-led investi- ► socioemotional development socioemotional development of children. Perinatal gation, use of robust study design and a multidisci- ; the Bachpan cohort study depression is a risk factor for poor child development BMJ Open from rural Pakistan. plinary team to answer multiple research questions and for many it has a recurring chronic course. Thus, :e025644. doi:10.1136/ 9 2019; broadly related to the topic of maternal depression the exposure to depression can continue through the bmjopen-2018-025644 and child developmental trajectories. early years of the child with detrimental developmental Multiple interim assessments in between the third ► ► Prepublication history for outcomes. trimester of pregnancy and 36-month postnatal fol- this paper is available online. ebruary Participants Between October 2014 and F low-ups, using validated instruments, provide a rig- To view these files, please visit 2016, we recruited 1154 pregnant women from a rural doi. dx. the journal online (http:// orous design in analysing the relationship between subdistrict of Pakistan. Data include longitudinal and org/ 10. 1136/ bmjopen- 2018- changes in maternal depressive symptoms and child repeated measures of maternal psychosocial measures 025644). outcomes. and child growth, cognitive and socioemotional measures. Relatively low loss to follow-up rates at each as- ► Received 22 August 2018 Follow-up include mother–child dyad assessments at 3rd, sessment wave. Revised 20 December 2018 6th, 12th, 24th and 36th months of child age. All these Missing data due to attrition are usual in cohorts, ► Accepted 8 March 2019 follow-ups are community based at the household level. statistical approaches will be used to minimise bias. We have competed baseline assessment. http://bmjopen.bmj.com/ ► One of the only pregnancy–birth cohort of perinatal Findings to date yads, we followed Of the eligible d depression being followed in a low-resource setting 885 (76.6%), 929 (91%) and 940 (93.3%) at 3, 6 and or low/middle-income countries. We include a subsample 12 months post-childbirth. mother–child dyad DNA and inflammatory biomarkers, 73 and 104, respectively. role restrictions around housework and Future plans While we continue to do 24-month and infant care) and/or those with a psychiatric 36-month follow-up assessments, we plan to follow 4 history. A number of systematic reviews from these mother–child dyads up to the age of 7–8 years LMIC and high income countries (HIC) on 10 May 2019 by guest. Protected by copyright. with some children being exposed to at least 1 year of indicate that child health outcomes are nega - school environment. Investigators interested in learning 8–12 tively associated with perinatal depression. more about the study can contact ( edu) [email protected] unc. For example, recent studies highlight the and ( siham. [email protected] hdrfoundation. org). effects of perinatal depression on child socio- emotional and cognitive developmental 13–15 Introdu on C I t outcomes. Negative effects of symptoms Perinatal depression is an episode of depres - of depression for the child start as early as in © Author(s) (or their employer(s)) 2019. Re-use sion occurring either during pregnancy, pregnancy and can be observed lasting into permitted under CC BY-NC. No 1 2 14 16 The within 1 year after deliver y, or both. Reducing perinatal depres- adulthood. commercial re-use. See rights prevalence of perinatal depression is high in sion and improving outcomes in the next and permissions. Published by low/middle-income countries (LMIC), with a generation is thus a global public health BMJ. 3 17 18 prevalence of >30% reported in south Asian priority. For numbered affiliations see 3 4 end of article. While being highly countries like Pakistan. Although observational evidence shows prevalent, it also has a recurring and chronic that reductions in depressive symptomology Correspondence to 5–7 course. It is more common among poorer are associated with improvements in child Dr Siham Sikander; women exposed to gender-based risks (eg, outcomes, experimental evidence from inter - siham. hdrfoundation. [email protected] org intimate partner violence, son preference, ventions to mitigate maternal depression has 1 2019; BMJ Open . 9 sikanderfis, et al :e025644. doi:10.1136/bmjopen-2018-025644

2 Open access BMJ Open: first published as 10.1136/bmjopen-2018-025644 on 5 May 2019. Downloaded from s ummary of the cohort profile ox 1 b Profile in a nutshell Profile in a nutshell ► The perinatal depression cohort is a prospective pregnancy and birth cohort designed to investigate the effects of depression on cognitive and socioemotional development among children. Between October 2014 and February 2016, we recruited 1154 preg- ► nant women from a rural subdistrict of Pakistan. ► Longitudinal follow-up includes mother–child dyad assessments at 3rd, 6th, 12th, 24th and 36th month postnatal. All these follow-ups are community based at the household level. Of 1021 live-born chil- dren, all are eligible for follow-up and 940 have been followed up at 12 months postnatal. ► Data include longitudinal and repeated measures of maternal psy- chosocial measures and child growth, cognitive and socioemotional Figure 1 etical model of perinatal depression and Theor measures. Data also include a subsample mother–child dyad DNA child outcomes. HOME, home observation for measurement and inflammatory biomarker. of the environment; SES, socio-economic status; PD, Investigators interested in learning more about the study can email ► perinatal depression. siham. [ edu] and [ [email protected] hdrfoundation. org]. unc. [email protected] recovery at 6 and 36 months postnatal is also tested in 34 35 randomised trials figure (see —conceptual model). 1 not been as consistent. Many studies have not found a sustained impact on child outcomes when perinatal or 19–21 This inconsistency maternal depression was treated. t des Cohor on C r IP I t across studies is likely attributable to differences in design Between October 2014 and February 2016, we enrolled 22 features such as length of follow-up, - choice of compar prenatally depressed and non-depressed pregnant women 23 24 ison groups, unaddressed endogeneity and enrolment to participate in this pregnancy–birth cohort study. The 19 25–31 age differences (eg, infants aged 1–18 months). cohort is based in Kallar Syedan, which is one of the seven Apart from these limitations, the perinatal mental health rural subdistricts of Rawalpindi in Pakistan. Kallar Syedan interventions themselves are also varied in their content - has a population of 190 000–250 000; the average house and intensity. There is evidence from LMIC that effec- hold consists of 6.2 members. Most families depend on 32 ; the majority tive interventions for perinatal depression subsistence farming, supported by earnings of one or of these interventions are front with booster loaded, more adult male members serving in the armed forces, http://bmjopen.bmj.com/ sessions lasting until at most 3–6 months postnatal, which working as government employees or performing semi- may not address the recurring nature of depression or skilled or unskilled labour in the cities. The subdistrict is 32 its chronicity in the longer Finally, evaluations of term. representative of a typical low-socioeconomic rural area depression interventions also do not typically account for of Pakistan. Male and female literacy rates are 80% and important contextual factors, such as chronic exposure 50%, respectively, and infant mortality is ~84 per 1000 live 36 37 to intimate partner violence, a known risk factor for poor births. maternal mental health, which may influence their effi- We identified pregnant women through the registers 32 33 cacy. of government-employed community health workers on 10 May 2019 by guest. Protected by copyright. With this backdrop, we established a pregnancy–birth called Lady Health Workers (LHWs). One of the stat- (the word Bachpan means cohort, called Bachpan utory duties of LHWs is to register new pregnancies in cohort study, to childhood in the local Urdu language) their catchment area. All potentially eligible women were follow-up the mother–child dyads through 36 months informed about the study by the LHWs. To be eligible postnatal and beyond. We recruited both prenatally for the study women had to be married, in the third depressed and non-depressed pregnant women in our trimester of pregnancy (>28 weeks of gestation), at least cohort to be seen at 3, 6, 12 and 24 months of child age 18 years of age and intending to reside in the study area, ). The 1 before a final assessment at 36 months (see box not require immediate inpatient care for any reason multiple, frequent and long-term mother–child dyad (medical or psychiatric) and be able to speak Urdu, follow-ups will enable rigorous analyses of the relation- Punjabi or Potohari languages. All eligible women were ship between changes in women’s depressive symptoms approached by research staff for informed consent and and child outcomes like the socioemotional, cognitive screened for depression with the Patient Health Ques- and growth, in terms of multiple cofactors that mediate >10 on the PHQ-9 tionnaire-9 (PHQ-9). Those scoring the risk and underscore the potentially modifiable risk formed the prenatally depressed group with ‘moderate factors and time varying mechanisms. Alongside the to severe’ endorsement of symptoms of depression. For cohort with its child outcomes, a peer-delivered perinatal every woman who screened positive for depression, the depression intervention with outcomes of remission/ next woman in that village who scored <10 on the PHQ-9 2 2019; BMJ Open . et al 9 :e025644. doi:10.1136/bmjopen-2018-025644 sikanderfis,

3 Open access intend following this birth cohort at 7–8 years of child BMJ Open: first published as 10.1136/bmjopen-2018-025644 on 5 May 2019. Downloaded from age, by that time majority of the children would have had at least 1 year of school exposure. views are conducted face-to-face, All follow-up inter either at the woman’s home or the LHW’s house. The follow-up rates at 3, 6 and 12 months have been 76.7%, 91% and 93%, respectively. The lower attrition rates thus far are due to the process by which we engage with the community and households through the resident commu- nity health workers called LHWs. Coupled by the conve- nience of being interviewed at participants’ preferred place and time adds to minimising the overall attrition. miss any follow-ups are ensured Lastly, the women who that they are followed up in the subsequent follow-up assessment. The 24-month follow-up will be completed in August 2018 and the 36-month postnatal follow-up assess- ments are scheduled for August 2019. Baseline character - istics did not differ significantly between those missing and those present at each of the follow-up time points sure A M ents Me Child growth and development and maternal depres- sion at 36 months postnatally are the main outcomes of interest. We also incorporate a comprehensive set of measures of potential exposures, moderators, media- tors and confounders relevant to numerous etiological questions of interest that this cohort may address. What follows is the details of the constructs and measures used, broadly divided into two categories (1) maternal and (2) ofile: flowchart. Cohort pr Figure 2 child (see table 1 ). was invited to participate as part of the non-exposed http://bmjopen.bmj.com/ arm of the cohort, resulting in a 1:1 ratio of prenatally e M nd A ts C onstru C l A tern sures A A M ‘depressed’ and ‘non-depressed’ in the sample. Immedi- s ociodemographics ately after the screening, all participants were approached Information on the women’s age and level of education; for their baseline assessments. All screening, baseline and their husbands’ occupation, income, assets, economic follow-up assessments were done by trained research assis- shocks and debt; and the household structure are assessed. tants (graduates and maters in social science, psychology We also ask about the household’s overall socioeconomic and behavioural science). status through the LHW-based subjective measure previ- 38 In all, 1910 pregnant women were approached. Of on 10 May 2019 by guest. Protected by copyright. ously used in our studies. It is a 5-point likert scale- these, 154 (8%) were ineligible by the criteria above, 25 based measurement with 1 being richest and 5 being the (1.3%) refused to participate at the eligibility screening poorest. LHWs being residents of the same community stage. and the village, where the participants live, have intimate The remaining 1731 (90.6%) eligible pregnant women knowledge of the overall socioeconomic status of all the were screened for depression. In all, we enrolled 1154 households in their catchment area. pregnant women in the Bachpan cohort study; out Since socioeconomic measurements are challenging of these 570 were depressed and 584 non-depressed to record accurately, we use this measure especially in according to the PHQ-9 cut-offs mentioned above. Only combination with debt alongside other measures to help 11 (0.64%) refused enrolment into the cohort. We us create accurate categories which are also sensitive to dropped/excluded 566 (32.7%) pregnant women who change over time. were non-depressed since they were over and above the Psychosocial factors 2 figure sample we required (see ). Perinatal depression was assessed longitudinally using the After collecting prenatal baseline information, each >10 cut-off for enrolling pregnant PHQ-9; we used the mother–child dyad is followed up at child age 3, 6, 12, women into the trial portion of the cohort. The PHQ-9 24 and 36 months. The follow-ups are scheduled using inquires about frequency of depressive symptoms in the the birth dates of the index children from registers of the last 2 weeks. It has been validated and used extensively in same LHWs who registered these pregnant women. We 3 :e025644. doi:10.1136/bmjopen-2018-025644 sikanderfis, 9 2019; BMJ Open . et al

4 Open access BMJ Open: first published as 10.1136/bmjopen-2018-025644 on 5 May 2019. Downloaded from Summary of constructs and assessments points for the cohort Table 1 Antenatal Postnatal Measured/assessed months 24 months Constructs months 36 Baseline 3 months 6 months 12 Maternal constructs • Sociodemographics Age, education, household structure, • • • • • household assets household roster, occupation, economic shocks and debt Psychosocial Perinatal depression • • • • • • • • • • Perceived stress • • • • • • • Social support, instrumental and emotional Decision-making, autonomy and self-efficacy • • • • Disability/function • • • • • • Intimate partner violence • • • • • • • Height, weight, waist circumference, blood • Physical health • • pressure • • • • • • Previous pregnancies, still births and miscarriage history • • • • • Family planning/contraception use • Family history of mental illness and substance Other constructs of interest use • Religiosity Understanding and executive function • • • Life satisfaction Significant life events • • • • • • • Health services utilisation (maternal and child) • • Risk taking Adverse childhood experiences • • Parental bonding Child constructs Breastfeeding and child nutrition Child nutrition and • • • • • http://bmjopen.bmj.com/ care Beliefs, practices, investment and expectations • • • • • about children • • Immunisation • • • • Child interaction Father and household involvement in parenting • and childcare • Home environment for child rearing/parenting • • Postnatal attachment • • on 10 May 2019 by guest. Protected by copyright. • • • Mother–child interaction • • • Weight, length/height and head circumference Child health and • • development • Acute illness history • • • • • • Socioemotional development • • Cognitive development Maternal and child biomarkers (subsample) • Hair steroid hormones (mother) Hormone Hair steroid hormones (child) • • • DNA (mother) Genetic DNA (child) • 39 40 the region. validity of using the scores from the PHQ-9 to measure Given that the PHQ-9 is a screening tool, we the number of symptoms endorsed by the woman over Disor - used the Structured Clinical Interview for DSM IV ders (SCID) module for current major depressive episode time. The diagnostic and statistical manual of mental disorders (DSM) IV diagnosis of current major depressive as a diagnostic tool and to assess the criterion-related 4 et al . BMJ Open 2019; 9 sikanderfis, :e025644. doi:10.1136/bmjopen-2018-025644

5 Open access episode is generated through the SCID algorithm. SCID (2) psychological and (3) sexual, severity, timing and BMJ Open: first published as 10.1136/bmjopen-2018-025644 on 5 May 2019. Downloaded from is a semistructured interview for the diagnoses of psychi- frequency. For the cohort, we adapted the instrument for 41 It has been cross-culturally adapted for atric disorders. ease of administration, and only referenced the respon- assessing depression among women during pregnancy dent’s husband as the perpetrator. 42 and in the postpartum period. o ther maternal measures of interest Perceived stress Women’s history of mental illness, substance abuse Women’s subjective experience of their stress is assessed among family members, the mother’s engagement in 43 44 with the 10-item Cohen’s Perceived Stress Scale (PSS). traditional rituals (such as chilla which is a 40-day period It is a tool designed to measure the degree to which situa- when a woman is relieved of household responsibilities 54 tions in one’s life are apprised to be stressful. and significant negative life events in after child birth) 54 We also administer the Client Services the past 1 . year 55 Social support Receipt Inventory to record health services sought We use three instruments to capture both emotional and during the perinatal period. This will enable us to asses instrumental support. The Multidimensional Scale of cost-effectiveness of the intervention tested in the cohort 34 56 Perceived Social Support is used as a measure of subjec- (see the child constructs and measures section). We 45 It has been adapted for tively assessed social support. also assess women’s decision-making, autonomy, religi- Pakistani settings and used extensively in the study osity, risk taking, bonding with her parents (using the 38 46 57 58 It has 12 items rated on a 7-point likert scale with area. [PBI]) Parental Bonding Instrument and her adverse subdomains capturing perceived support from significant childhood experiences (including physical and psycho- other, family and friends. We use the Maternal Social logical abuse, neglect and several sorts of family dysfunc- 59 60 Support Index as a measure of instrumental support. It tion). consists of 21 questions which inquire about the avail- 47 ability of support to the woman in her daily tasks. An interview regarding who is caring for the child ts nd sures A e M A Ch C onstru C ld I during daily instrumental and social activities, a Day-in- Child nutrition and care Life (DIL) was developed for the study to assess relative e assess breastfeeding practices in accordance with W support in caregiving that the depressed and non-de- WHO guidelines, as well as complementary feeding and 61 62 pressed groups of mothers’ report. food diversity, in terms of frequency and quantity. and expectations of We also ascertain beliefs, practices Maternal self-efficacy mothers for their children with respect to vaccination We use the 10-item Maternal Self-Efficacy Scale to assess coverage. a woman’s beliefs about her ability to take care of her 48 http://bmjopen.bmj.com/ This child compared with other mothers she has seen. Child interaction tool has been used extensively in research on maternal Observation of mother–child interaction (OMCI) depression and child development, in both high/low-in- We adapted the OMCI, which is a tool to evaluate respon- 49–51 come countries. sive parenting through direct, 3–5 min OMCIs around a picture book activity. OMCI was developed and used in 63 Physical health Pakistan for 12, 24 and 48 months old children. Disability The WHO Disability Assessment Schedule (WHO-DAS) Home observation for measurement of the environment (HOME) on 10 May 2019 by guest. Protected by copyright. is used to assess women’s disability. It is a 12-item ques- inventory tionnaire that assesses levels of functionality over the last We use HOME as a measure of maternal responsiveness 30 days. Combined with two items about one’s ability to and the overall conduciveness of the home environment work in the last 30 days, the WHO-DAS generates a total for child rearing. It is an extensively used measure of the 64 disability score, quality adjusted life years and number of and it has been validated in child’s family environment 52 65–67 days the respondent is not able to work. Pakistan. Height, weight, waist circumference and the blood Attachment relationship pressure of women are measured at each encounter. We We assess the maternal attachment with the child through also assess obstetric history including number of pregnan- 68 It has the 19-item Maternal Postnatal Attachment Scale. cies, live births and contraception being used or not. been used extensively across settings. Intimate partner violence (IPV) Child caregiving practices We assess IPV using the WHO Violence Against Women 53 tool is a semistructured interview using a narra- The DiL Instrument. It minimises reporting biases by asking tive-elicitation technique, designed to elicit in detail only about specific behaviours perpetrated by a male the involvement of the mother as well as other family partner, rather than ascertaining if a woman subjectively members in daily care of the infant. The DiL tries to perceives she has experienced ‘abuse’ or ‘violence’. create a narrative about who the child spends time with by The tool addresses three types of violence (1) physical, 5 2019; 9 :e025644. doi:10.1136/bmjopen-2018-025644 sikanderfis, . et al BMJ Open

6 Open access the infant; similarly, the narrative building continues into BMJ Open: first published as 10.1136/bmjopen-2018-025644 on 5 May 2019. Downloaded from Table 2 Summary of baseline findings the afternoon and night until the time the child sleeps Total unweighted again. The household members like the mother, father, (n=1154), % Weighted, Baseline maternal and mother-in-law, aunt and so on are recorded against each % and means (SD) and means (SD) household measures activity and overall impression of time spent without the Age 26.6 (5.5) 26.7 (4.5) mother is made; the data thus provide a detailed picture Education (grades passed) of both whom the infant spends the day with and what 7.7 (4.5) Women 8.1 (5.5) kind of support the mother receives and from whom. 8.8 (4.1) 8.6 (3.4) Husbands Child growth and development Women’s occupation We collect anthropometric measurements for physical Housewives 93.70% 93.80% and head circum- development (including weight, height Manual or skilled work 6.30% 6.20% ference) based on WHO standards and norms. We also Husband’ s occupation assess diarrheal and acute respiratory illness episodes Unemployed 9% 8% using WHO definitions. 91.20% 90.90% Manual work Strengths and Difficulties Questionnaire (SDQ) Skilled work 8.70% 9.10% The SDQ is a screening tool for child’s socioemotional/ Asset-based SES variable cut into quintiles behavioural development using parental report of 25 19.90% Lowest quintile 17.10% child attributes divided into five subscales: emotional 18.60% 20.00% Lower middle quintile symptoms, conduct problems, hyperactivity, peer prob- 69 70 20.20% 20.00% Middle quintile The SDQ has been lems and prosocial behaviour. 20.00% 21.80% Upper middle quintile extensively translated into 50 other languages (including 71–73 Urdu) and used in LMIC including the study area. 20.00% Upper quintile 22.30% Household structure Ages and Stages Questionnaire (ASQ) Nuclear 21.90% 22.50% We also use the socioemotional component of the ASQ 65.80% 67.20% Joint/extended (ASQ-SE) during the follow-up assessments as well as at 74 75 10.90% Multiple households 11.70% the final outcome assessment at 36 months postnatal. The ASQ-SE includes a simple set of 25 questions asking Number of living children the caregiver to report age-appropriate psychosocial mile- First pregnancy 30.20% 32.20% 76 77 stones. It has been widely used. 1–3 children 60.10% 59.80% 7.90% 9.20% >4 children http://bmjopen.bmj.com/ Bayley Scales of Infant and Toddler Development Third Edition Gender of the children (BSID-III) 1.4 (2.0) years of age 1.4 (1.6) Girls <18 We use the BSID-III, which is an individually administered assessment of the child’s achievement of developmental 1.3 (1.9) Boys <18 years of age 1.3 (1.6) milestones across five areas: cognitive, language, motor, PHQ-9 scor es 8.7 (6.7) 6.7 (7.7) 78 Raw scores in each socioemotional and adaptive skills. SCID current MDE 26.60% 38.30% domain are summarised by chronological age-related PSS scores 17.7 (9.0) 15.8 (10.6) scaled scores and composite scores for each domain. The 4.5 (1.3) 4.6 (1.5) MSPSS scores on 10 May 2019 by guest. Protected by copyright. child is assessed with the full test at the 12-month contact 9.1 (10.9) WHO-DAS scores 10.9 (9.4) and with only the receptive language and fine motor IPV in last 12 months domains at 36 moths, due to time demands and also the difficulties involved in administering the language laden 12.80% Physical violence 15.90% instructions in other domains. Psychological violence 32.80% 38% 29.20% 31.20% Sexual violence pigenetics and biomarkers (subsamples) e Life events (last 12 months) 3.6 (2.4) 3.4 (2.9) We conducted a small nested feasibility study of buccal DNA samples from 73 mothers in the third trimester currency. PKR, local , Intimate Partner Violence; MPSS, Multidimensional Scale of IPV of pregnancy and the same 73 mother–child dyads at 3 Perceived Social Support; MDE,Major Depressive Episode; PHQ- months postchild birth (approximately half from prena- 9, Patient Health Questionnaire-9; PSS, Perceived Stress Scale; tally depressed and half from prenatally non-depressed). SCID, Structured Clinical Interview for DSM IV Disorders; WHO- We also collected, apart from the above, hair samples DAS, WHO Disability Assessment Schedule. from 104 mother–child dyads at 12 months postnatal. These components will enable us to examine epigenetic and hair cortisol (and other biomarkers of stress) among taking an account of all the activities done with the child. depressed versus non-depressed mothers and their This begins with the account starting from early morning children. instrumental tasks such as who wakes, washes and feeds 6 . 2019; 9 :e025644. doi:10.1136/bmjopen-2018-025644 et al sikanderfis, BMJ Open

7 Open access BMJ Open: first published as 10.1136/bmjopen-2018-025644 on 5 May 2019. Downloaded from Summary of postnatal follow-ups Table 3 3rd month 12th month 6th month n=885, % or mean (SD) Maternal measures n=940, % or mean (SD) n=929, % or mean (SD) Response rate 76.60% 91% 93.30% PHQ-9 scores 5.2 (5.8) 4.8 (5.6) NA SCID current MDE 12.90% 18.70% 15.30% PSS scores 19.9 (3.8) 19.8 (3.7) 20.0 (3.4) MSPSS scores 4.7 (1.1) 4.8 (1.3) NA MSES scores 37.0 (3.9) 37.4 (3.3) NA MSSI scores 2.8 (1.8) NA 2.7 (1.6) asks done alone T 2.8 (1.1) T asks done by someone else 2.9 (0.9) Tasks shared 2.4 (1.5) 2.4 (1.7) 4.9 (7.3) WHO-DAS 5.0 (7.2) 5.0 (7.6) Life events checklist 1.1 (1.4) NA 3.6 (2.4) Life satisfaction NA Very satisfied NA 26.40% Satisfied 40.90% Moderately satisfied 24.30% 3.00% Dissatisfied Very dissatisfied 2.70% Intimate partner violence last 12 months Physical violence NA NA 10.90% Psychological violence 33.10% Sexual violence 28.50% Child measures 8.70% Exclusive breastfeeding 48% NA http://bmjopen.bmj.com/ 92.90% 85.60% 72.90% Breastfeeding HOME-IT scores Total score 22.8 (5.0) NA 31.7 (5.3) Responsivity (subscale) 8.2 (2.1) 9.8 (1.3) 86.8 (5.4) NA MPAS scores 87.6 (5.7) DiL NA Daily waking, bathing, feeding of the child on 10 May 2019 by guest. Protected by copyright. Done by mom alone 87.10% 79.90% Shar ed by grandmother, father or others 9.80% 18% Daily interacting, holding, soothing of the child Done by mom alone 57% 44.60% ed by 30.50% 51.60% Done by mom alone shar grandmother, father or others ASQ-SE scores NA 9.5 (12.2) NA Height for age z-scores 0.1 (1.8) 0.1 (1.7) −0.7 (1.3) −0.9 (1.2) Weight for age z-scores −1.1 (1.3) −0.8 (1.1) – Immunisation completion (measles vaccination 97.10% – at 9 months of infant’s age) BSID scaled scores Continued 7 9 sikanderfis, et al . BMJ Open 2019; :e025644. doi:10.1136/bmjopen-2018-025644

8 Open access BMJ Open: first published as 10.1136/bmjopen-2018-025644 on 5 May 2019. Downloaded from Table 3 Continued 3rd month 6th month 12th month n=929, % or mean (SD) n=940, % or mean (SD) Maternal measures n=885, % or mean (SD) NA NA 9.4 (2.2) Cognitive Receptive language 8.0 (1.4) Expressive language 9.1 (1.5) 9.0 (1.8) Fine motor 8.1 (2.3) Gross motor ASQ-SE, socioemotional component of the ASQ; BSID, Bayley Scales of Infant and Toddler Development; DiL, Day-in-Life; HOME-IT, home observation measurement of enviornment infant toddler; MSES, Maternal Self-Efficacy Scale; MPAS, maternal postnatal attachment scale; MSPSS, Multidimensional Scale of Perceived Social Support; MSSI, Maternal Social Support Index; NA, Not Assessed; PHQ-9, Patient Health Questionnaire-9 ; PSS, Perceived Stress Scale; SCID, Structured Clinical Interview for DSM IV Disorders; WHO-DAS, WHO Disability Assessment Schedule. Maternal psychosocial factors Patient and public involvement At baseline, the mean PHQ-9 and PSS scores were 6.7 No patients were involved in development of the research and 15.8 showing mild levels of depressive symptoms as questions, design of the study or the recruitment. well as mild levels of perceived stress. While 26.6% were found to have major depressive episode on SCID. Rates of d ata management major depressive episode are comparable to our previous All data are collected electronically via tablets and is 38 54 studies in the same area. The stress levels rise margin- uploaded daily onto the main server. Quality checks for ally while the severity of depressive symptoms go down - consistency, accuracy, missing data and other irregular over time. Overall at baseline (prenatal), 32.8% and ities are conducted weekly. Any issues are shared with 29.2% of women experienced psychological and sexual the research team and discussed during a weekly field abuse in the last 12 months, respectively, while 15.9% staff meeting. Data are backed up daily to a secondary reported physical violence in the last 12 months. Simi- server. All data are deidentified/anonymised before larly, a high proportion report experiencing abuse at 12 being shared with coinvestigators. At all stages/levels, months postnatal, which other studies also report and is protected with multiple layers of data are password 79 80 The correlated with maternal mental health issues. authorisation. support women have (both physical and instrumental) http://bmjopen.bmj.com/ Prior to analysis, we upweighted the mothers whose months postnatal is relatively low. from prenatal to 12 depression levels were <10 on the PHQ-9 in order to make the baseline sample representative of the local population, since only one in three of these women was e M sures ld I Ch A invited to participate in the study. We generated clus- The rates of exclusive breastfeeding at 3 and 6 months ter-specific weights and assigned them to these non-de- postnatal were 48% and 8.7%, respectively. These figures women. Since all of the women who scored a 10 pressed are comparable to what are reported in national surveys or above on the PHQ-9 were invited to participate, their 11 79 as well as from the study area. The mean z-scores for on 10 May 2019 by guest. Protected by copyright. default weight was 1. both height-for-age and weight–for-age were poor but 79 Simi- slightly better than the overall national trends. Findings to date larly, our cohort at 12 months had a very high vaccination 2 and 3 , we summarise our key findings to date. In tables coverage of 97%. To make the 1154 women representative of the local In terms of the responsivity, attachment seems to population, we report the weighted values along with the improve over time as shown by the HOME and MPAS raw (unweighted) numbers at baseline. mean scores. Interesting to note is that time spent during the day interacting with the child drops as the s ociodemographics child grows older (DiL—57% of the time mother inter - The mean age of pregnant women in our cohort is 26.6 acting, soothing and holding at 3 months vs 44.6% at 12 years, with an average of 8.1 years of education. Almost months), meaning other family members like the grand- all of them being housewives (94%), with a third of these mother and the father get more involved. women being pregnant for the first time (the rest have up We do not have normative data on cognitive and socio- to four children); 67.2% live in a joint family structure. emotional development of children in Pakistan, especially All of these findings are comparable to what we have seen of this age group. Thus, our values will be most useful for in our previous studies from the same area and what is making internal group comparisons as well as observing 54 79 reported in the national demographic survey. changes over time. 8 sikanderfis, :e025644. doi:10.1136/bmjopen-2018-025644 9 2019; BMJ Open . et al

9 Open access the follow-up of mother–child dyads up to 36 months postnatal under award R01 I t A M ons n strengths A nd l IMI t AI BMJ Open: first published as 10.1136/bmjopen-2018-025644 on 5 May 2019. Downloaded from HD075875. The main strengths include hypothesis-led investiga- lared. None dec Competing interests tion, use of robust study design and a multidisciplinary Obtained. Patient consent for publication team. Multiple interim assessments in between the third trimester of pregnancy and 36-month postnatal follow-ups venance and peer review Not commissioned; externally peer reviewed. Pro provide a rigorous design in analysing the relationship d Currently the da ta are not available since the cohort is ata sharing statement between changes in maternal depressive symptoms and ongoing. child outcomes. We have taken great care to utilise stan- o pen access This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which dardised and validated instruments. permits others to distribute, remix, adapt, build upon this work non-commercially, The loss to follow-up rates is relatively low at each and license their derivative works on different terms, provided the original work is assessment wave. However, missing data are common in properly cited, appropriate credit is given, any changes made indicated, and the use longitudinal studies, due to attrition or non-response 4. nc/ by- 0/. licenses/ org/ creativecommons. is non-commercial. See: http:// to questionnaire items, and inappropriate handling of missing data can lead to biased statistical interpretation. In addition to likelihood-based statistical methods, which eren F e r es C are valid under the missing at random assumption, we Br 1. . Risks, and the nutrition et al enda MY, Leung ND, Bonnie JK, J Am Diet Assoc 2009;109:1566–75. link—a review of the literature. will employ multiple imputation to address the issue of 2. Gavin NI, Gaynes BN, Lohr KN, . Perinatal depression: a et al missing data, which will help minimise bias and make use systematic review of prevalence and incidence. Obstet Gynecol 2005;106:1071–83. of all available data. One of the limitations is not having . Postnatal depression and oung KS, Rochat TJ, et al Parsons CE, Y 3. administered PHQ-9 at 12 months postnatal. Thus, the its effects on child development: a review of evidence from low- and severity of depressive symptoms across the cohort will not middle-income countries. 2012;101:57–79. Br Med Bull Fisher J, Cabral de Mello M, Patel V et al . Prevalence and 4. , be known—only if they are depressed or not though the determinants of common perinatal mental disorders in women in diagnostic interview (SCID). low- and lower-middle-income countries: a systematic review. Bull World Health Organ 2012;90:139–49. In summary, this pregnancy–birth cohort with a 5. Maselko J, Sikander S, Bangash O, et al . Child mental health and follow-up period of at least 3 years postnatal is well suited maternal depression history in Pakistan. Soc Psychiatry Psychiatr to answer multiple research questions broadly related to Epidemiol 2016;51:49–62. et al . Effect of an early perinatal 6. Maselko J, Sikander S, Bhalotra S, the topic of maternal depression and child developmental depression intervention on long-term child development outcomes: trajectories. We are not aware of any other pregnancy– follow-up of the Thinking Healthy Programme randomised controlled Lancet Psychiatry 2015;2:609–17. trial. birth cohort of perinatal depression being followed in eed F. Outcome of prenatal depression and risk factors 7. Rahman A, Cr other low-resource settings or LMIC. The findings are associated with persistence in the first postnatal year: prospective J Affect Disord 2007;100:115–21. study from Rawalpindi, Pakistan. especially relevant for rural based women and children , Huttly S, De Silva MJ, et al . Maternal mental health and Harpham T 8. living in LMIC and low-resource settings. child nutritional status in four developing countries. J Epidemiol http://bmjopen.bmj.com/ Community Health 2005;59:1060–4. 9. . Mothers' mental health and infant et al Rahman A, Lovel H, Bunn J, Author affiliations 1 Child Care growth: a case-control study from Rawalpindi, Pakistan. Human Development Research Foundation, Islamabad, Pakistan 2 Health Dev 2004;30:21–7. Public Health, Health Services Academy, Islamabad, Pakistan 10. . Impact of maternal depression et al Rahman A, Iqbal Z, Bunn J, 3 Epidemiology, Columbia University Mailman School of Public Health, New York, Arch Gen on infant nutritional status and illness: a cohort study. New York, USA Psychiatry 2004;61:946–52. 4 Biostatistics, Duke University, Durham, North Carolina, USA . The impact of perinatal et al 11. Rahman A, Hafeez A, Bilal R, 5 depression on exclusive breastfeeding: a cohort study. Matern Child Duke Global Health Institute, Duke University, Durham, North Carolina, USA 6 2016;12. Nutr Carolina Population Center, University of North Carolina at Chapel Hill, Chapel Hill, , DeSouza N, Rodrigues M. Postnatal depression and infant 12. Patel V North Carolina, USA growth and development in low income countries: a cohort study on 10 May 2019 by guest. Protected by copyright. 7 Biostatistics and Bioinformatics, Duke University, Durham, North Carolina, USA 2003;88:34–7. Arch Dis Child from Goa, India. 8 Child Mental Health Unit, University of Liverpool, Liverpool, UK . Maternal depression et al , Ramchandani PG, 13. Herba CM, Glover V 9 and mental health in early childhood: an examination of underlying Department of Epidemiology, Gillings School of Global Public Health, University of Lancet mechanisms in low-income and middle-income countries. North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA 2016;3:983–92. Psychiatry 14. . Maternal mental health, et al , Krutikova S, Bennett IM, Schott W e would like to thank the team at the Human Development Acknowledgements W and child growth and development, in four low-income and middle- Research Foundation (HDRF) including Rakshanda Liaqat, Tayyiba Abbasi, Maria J Epidemiol Community Health 2016;70:168–73. income countries. A, Lukose A, Srinivasan K. Maternal mental health in 15. Satyanarayana V Sharif, Samina Bilal, Quratul-Ain, Anum Nisar, Amina Bibi, Shaffaq Zufiqar, Sonia pregnancy and child behavior. Indian J Psychiatry 2011;53:351–61. Khan, Ahmed Zaidi, Ikhlaq Ahmad and Najia Atif. Finally, we are very grateful to the et al . Lifecourse health development: past, 16. Halfon N, Larson K, Lu M, women and their children who are part of this cohort. 2014;18:344–65. Matern Child Health J present and future. F or any further information or potential collaboration Drs Joanna Collaborators . Postnatal depression: a global public health perspective. Almond P 17. Perspect Public Health 2009;129:221–7. unc. siham. edu) and Siham Sikander ( [email protected] [email protected] hdrfoundation. Maselko ( , Maselko J, . The neglected 'm' in MCH et al Rahman A, Patel V 18. org) can be contacted. programmes--why mental health of mothers is important for child per and all authors reviewed and approved it. SS, Contributors SS drafted the pa nutrition. 2008;13:579–83. Trop Med Int Health IA, AR and JM were responsible for the design of the study. SS, IA, LMB, KO, AH and , Egger M. Effect of preventive interventions 19. Siegenthaler E, Munder T in mentally ill parents on the mental health of the offspring: JM were responsible for data gathering instruments. SS and IA were responsible for J Am Acad Child Adolesc systematic review and meta-analysis. the conduct of the cohort. JG, AZ and ELT were responsible for database design and 2012;51:8–17. Psychiatry management. . Effective treatment for et al , Stuart S, 20. Forman DR, O'Hara MW Funding tional Institute of Child Health & This work was supported by the Na postpartum depression is not sufficient to improve the developing 2007;19:585–602. mother-child relationship. Dev Psychopathol Human Development (NICHD), US to establish the pregnancy–birth cohort and 9 sikanderfis, et al . BMJ Open 2019; :e025644. doi:10.1136/bmjopen-2018-025644 9

10 Open access . Multidimensional scale of Akhtar A, Rahman A, Husain M, 46. et al Gunlicks ML, W 21. eissman MM. Change in child psychopathology with BMJ Open: first published as 10.1136/bmjopen-2018-025644 on 5 May 2019. Downloaded from perceived social support: psychometric properties in a South Asian improvement in parental depression: a systematic review. J Am Acad 2010;36:845–51. J Obstet Gynaecol Res population. Child Adolesc Psychiatry 2008;47:379–89. 47. . The reliability and validity of et al n WF, Pascoe JM, Ialongo NS, Hor . The efficacy of toddler-parent et al oth SL, Rogosch FA, Manly JT, T 22. 1988;20:271–6. Fam Med the maternal social support index. psychotherapy to reorganize attachment in the young offspring of 48. T eti DM, Gelfand DM. Behavioral competence among mothers of mothers with major depressive disorder: a randomized preventive infants in the first year: the mediational role of maternal self-efficacy. 2006;74:1006–16. trial. J Consult Clin Psychol 1991;62:918–29. Child Dev . Children of et al , Gameroff MJ, Pilowsky DJ, Wickramaratne P 23. 49. Hn L, Cultur e LSF. Context, and Maternal Self-Efficacy in Latina depressed mothers 1 year after remission of maternal depression: 2008;12:198–201. Appl Dev Sci Mothers. findings from the STAR*D-Child study. Am J Psychiatry . parenting self-efficacy, and et al Surkan PJ, Kawachi I, Ryan LM, 50. 2011;168:593–602. 2008;98:125–32. child growth. Am J Public Health , Maughan B, . Relative impact of Barker ED, Copeland W 24. et al nal self-efficacy beliefs, Coleman PK, Karraker KH. Mater 51. maternal depression and associated risk factors on offspring competence in parenting, and toddlers' behavior and developmental 2012;200:124–9. psychopathology. Br J Psychiatry status. Infant Ment Health J 2003;24:126–48. . Controlled trial of the short- et al Murray L, Cooper PJ, Wilson A, 25. et al . Developing the World 52. Ustün TB, Chatterji S, Kostanjsek N, and long-term effect of psychological treatment of post-partum Health Organization Disability Assessment Schedule 2.0. Bull World depression: 2. Impact on the mother-child relationship and child 2010;88:815–23. Health Organ outcome. Br J Psychiatry 2003;182:420–7. 53. WHO. Multi-Countr y Study on Women's Health and Domestic . A et al , Riksen-Walraven JM, Hosman CM, 26. van Doesum KT Violence Study Protocol . Geneva: WHO, 2001. randomized controlled trial of a home-visiting intervention aimed at 54. Rahman A, Iqbal Z, Harrington R. Life events, social support and preventing relationship problems in depressed mothers and their depr ession in childbirth: perspectives from a rural community in the infants. Child Dev 2008;79:547–61. developing world. Psychol Med 2003;33:1161–7. 27. Fryer RG, Levitt SD. T esting for Racial Differences in the Mental Beecham J, Knapp M. , 2001. 55. Costing Psychiatric Interventions Ability of Young Children. . American Economic Review forthcoming Rahman A, Malik A, Sikander S, et al . Cognitive behaviour therapy- 56. A, Toth SL. The efficacy of toddler-parent 28. Cicchetti D, Rogosch F based intervention by community health workers for mothers with psychotherapy for fostering cognitive development in offspring of depression and their infants in rural Pakistan: a cluster-randomised J Abnorm Child Psychol 2000;28:135–48. depressed mothers. 2008;372:372:902–9. Lancet controlled trial. Hart S, Field T , Nearing G. Depressed mothers' neonates improve 29. et al , Stewart R, Khan M, Qadir F . The validity of the Parental Bonding 57. following the MABI and a Brazelton demonstration. J Pediatr Psychol Instrument as a measure of maternal bonding among young Pakistani 1998;23:351–6. women. Soc Psychiatry Psychiatr Epidemiol 2005;40:276–82. et al , Pawlby S, . The impact of postnatal depression Sharp D, Hay DF 30. ental Bonding Instrument: psychometric properties Parker G. The Par 58. on boys' intellectual development. J Child Psychol Psychiatry 1989;7:317–35. Psychiatr Dev reviewed. 1995;36:1315–36. ol and Prevention (CDC). Adverse Centers for Disease Contr 59. et al . and Child 31. Goodman SH, Rouse MH, Connell AM, MMWR childhood experiences reported by adults - five states, 2009. Clin Child Fam Psychol Psychopathology: A Meta-Analytic Review. 2010;59:1609–13. Morb Mortal Wkly Rep 2011;14:1–27. Rev 60. WHO. Adverse Childhood Experiences Inter national Questionnaire . Interventions for common , et al 32. Rahman A, Fisher J, Bower P prevention/ who. int/ violence_ injury_ (ACE-IQ). 2015 http://www. perinatal mental disorders in women in low- and middle-income adverse_ activities/ violence/ experiences/ childhood_ en/. Bull World Health countries: a systematic review and meta-analysis. 61. UNICEF. WHO, , Global Strategy for Infant and Young Child Feeding 2013;91:593–601. Organ 2003. Ali TS, Mogr en I, Krantz G. Intimate partner violence and mental 33. 62. oung Child Feeding Indicators for Assessing Infant and Y WHO. health effects: a population-based study among married women in Practices: Part 1 Definitions . Geneva: World Health Organization, 2013;20:131–9. Karachi, Pakistan. Int J Behav Med 2008. et al . The effectiveness and cost- 34. Sikander S, Lazarus A, Bangash O, ousafzai AK. The development and reliability of 63. Rasheed MA, Y effectiveness of the peer-delivered Thinking Healthy Programme for an observational tool for assessing mother-child interactions in perinatal depression in Pakistan and India: the SHARE study protocol http://bmjopen.bmj.com/ field studies- experience from Pakistan. Child Care Health Dev for randomised controlled trials. Trials 2015;16:015–1063. 2015;41:1161–71. et al urner EL, Sikander S, Bangash O, . The effectiveness of 35. T 64. Caldwell B, Bradley R. Home observation for measurement of the the peer delivered Thinking Healthy Plus (THPP+) Programme . Tempe, AZ: Family & Human environment: Administration manual for maternal depression and child socio-emotional development Dynamics Research Institute, Arizone State University, 2003. in Pakistan: study protocol for a three-year cluster randomized Y ousafzai AK, Rasheed MA, Rizvi A, et al . and Emotional Availability: 65. controlled trial. Trials 2016;17:016–1530. An RCT. 2015;135:e1247–e57. Pediatrics orld Development Indicators 2013 36. . Washington, DC: World Bank, W Sarwat K A, Pervez A S. Adaptation of Home Inventory (Infant 66. 2013. ersion) For Pakistani Children. Pakistan Jouranl of Psychological V vey - Preliminary 37. Pakistan Demographic and Health Sur PDHS. 1991;6:103–15. Research . Islamabad, Pakistan: National Institute of Population Studies, Report et al . Assessing Home Nadeem S, Rafique G, Khowaja L, 67. 2012-13. on 10 May 2019 by guest. Protected by copyright. Child Care in Environment for Early Child Development in Pakistan. Rahman A, Malik A, Sikander S, et al 38. . Cognitive behaviour therapy- Practice 2014;20:194–206. based intervention by community health workers for mothers with , Corkindale CJ. The assessment of parent-to-infant 68. Condon JT depression and their infants in rural Pakistan: a cluster-randomised J attachment: Development of a self-report questionnaire instrument. controlled trial. 2008;372:902–9. The Lancet 1998;16:57–76. Reprod Infant Psychol et al . Detecting common mental , Araya R, Chowdhary N, 39. Patel V 69. Goodman R. The Str engths and Difficulties Questionnaire: a research disorders in primary care in India: a comparison of five screening 1997;38:581–6. J Child Psychol Psychiatry note. Psychol Med 2008;38:221–8. questionnaires. oader 70. Goodman A, Lamping DL, Ploubidis GB. When to use br Fraz K, Khan S A, Sikander S. Scr 40. eening for depression in coronary internalising and externalising subscales instead of the hypothesised artery disease patients using PHQ-9. theHealth 2013;4:3–6. five subscales on the Strengths and Difficulties Questionnaire (SDQ): SCID-I/NP (for DSM-IV) Non- First MB, Spitzer RL, Gibbon M. 41. J Abnorm Child data from British parents, teachers and children. patient Edition. Structured Clinical Interview for DSM-IV-TR Axis I Psychol 2010;38:1179–91. . (SCID-I/NP) New Disorders, Research Version, Non-patient Edition et al . The Strengths and oerner W, Fleitlich-Bilyk B, Martinussen R, 71. W York: Biometrics Research, New York State Psychiatric Institute, Difficulties Questionnaire overseas: evaluations and applications 2002. of the SDQ beyond Europe. 2004;13 Eur Child Adolesc Psychiatry . Adaptation of the , Figueiredo B, et al 42. Gorman LL, O'Hara MW Suppl 2:II47–54. structured clinical interview for DSM-IV disorders for assessing eening for emotional and 72. Syed EU, Hussein SA, Mahmud S. Scr depression in women during pregnancy and post-partum across behavioural problems amongst 5-11-year-old school children countries and cultures. Br J Psychiatry Suppl 2004;46:s17–s23. Soc Psychiatry Psychiatr Epidemiol in Karachi, Pakistan. ck T, Mermelstein R. A global measure of perceived 43. Cohen S, Kamar 2007;42:421–7. stress. J Health Soc Behav 1983;24:385–96. Samad L, Hollis C, Prince M, et al . Child and adolescent 73. html. 2012. scales. scohen/ cmu. psy. Cohen S. http://www. edu/~ . 44. psychopathology in a developing country: testing the validity of the , Zimet GD, Walker RR. The Multidimensional Scale 45. Dahlem NW strengths and difficulties questionnaire (Urdu version). Int J Methods of Perceived Social Support: a confirmation study. J Clin Psychol 2005;14:158–66. Psychiatr Res 1991;47:756–61. 10 sikanderfis, et al . BMJ Open 2019; 9 :e025644. doi:10.1136/bmjopen-2018-025644

11 Open access et al elikonja T, Edbrooke-Childs J, Calderon A, . The psychometric 77. V 74. Squir es J, Bricker D, Potter L. Revision of a parent-completed BMJ Open: first published as 10.1136/bmjopen-2018-025644 on 5 May 2019. Downloaded from properties of the Ages & Stages Questionnaires for ages 2-2.5: a development screening tool: Ages and Stages Questionnaires. J Child Care Health Dev systematic review. 2017;43:1–17. Pediatr Psychol 1997;22:313–28. Bayley scales of infant and toddler development: Bayley N, Reuner G. 78. eh CJ, Boone Blanchard S, Ages BBS. Ages and Stages Singh A, Y 75. Bayley-III.: Harcourt Assessment: Psych. Corporation , 2006. Bol Med Hosp Infant Mex Questionnaire: a global screening scale. 79. NIPS. Pakistan Demographic and Health Sur vey . Islamabad, 2017;74:5–12. Pakistan: National Institute of Population Studies, 2012-13. 76. Squir es JK, Bricker DD, Twombly E. Ages and Stages Questionnaire: 80. . Intimate partner violence in urban et al en I, Ali TS, Asad N, Mogr Social-Emotional (ASQ:SE): a parent-completed, child-monitoring Pakistan: prevalence, frequency, and risk factors. Int J Womens . Baltimore, MD: Paul H system for social-emotional behaviors Health 2011;3:105–15. Brookes Publishing, 2002. http://bmjopen.bmj.com/ on 10 May 2019 by guest. Protected by copyright. 11 . :e025644. doi:10.1136/bmjopen-2018-025644 sikanderfis, 9 2019; BMJ Open et al

Related documents

CityNT2019TentRoll 1

CityNT2019TentRoll 1

STATE OF NEW YORK 2 0 1 9 T E N T A T I V E A S S E S S M E N T R O L L PAGE 1 VALUATION DATE-JUL 01, 2018 COUNTY - Niagara T A X A B L E SECTION OF THE ROLL - 1 CITY - North Tonawanda TAX MAP NUMBER ...

More info »
Out of Reach 2018

Out of Reach 2018

2018 of OUT REACH THE HIGH COST OF HOUSING MADE POSSIBLE BY THE GENEROSITY OF:

More info »
Out of Reach 2016

Out of Reach 2016

No Refuge for Low Income Renters MADE POSSIBLE BY THE GENEROSITY OF:

More info »
DER Directory

DER Directory

FAA CONSULTANT DER DIRECTORY May 9, 2019 AIR-6F0, Delegation & Organizational Procedures Branch This directory is generated from information in the FAA Designee Information Network (DIN). If you are a...

More info »
time is the enemy

time is the enemy

is TIME the ENEMY The surprising truth about why today’s college students graduating ... and wha T needs To change aren’t n 1 Time Is the Enemy

More info »
50 Year Trends expanded version

50 Year Trends expanded version

Expanded Edition THE AMERICAN HERI A R CIRP T B I E N L G E C 50 F S I F R T A Y E Y FRESHMAN FIFTY-YEAR TRENDS | 1966-2015 KEVIN EAGAN | ELLEN BARA STOLZENBERG | JOSEPH J. RAMIREZ | MELISSA C. ARAGON...

More info »
Implementation Handbook For The Convention On The Rights Of The Child

Implementation Handbook For The Convention On The Rights Of The Child

IMPLEMENTATION HANDBOOK FOR THE CONVENTION ON THE RIGHTS OF THE CHILD FULLY REVISED THIRD EDITION IMPLEMENTATION HANDBOOK IMPLEMENTATION HANDBOOK FOR THE CONVENTION ON THE FOR THE CONVENTION ON THE RI...

More info »
Abstract and Concrete Categories   The Joy of Cats

Abstract and Concrete Categories The Joy of Cats

Jiˇr ́ı Ad ́amek Horst Herrlich George E. Strecker Abstract and Concrete Categories The Joy of Cats Dedicated to Bernhard Banaschewski

More info »
IWMF Global Report

IWMF Global Report

Global Report on the Status of Women in the News Media INTERNATIONAL WOMEN’S MEDIA FOUNDATION

More info »
What's It Worth? The Economic Value of College Majors

What's It Worth? The Economic Value of College Majors

Anthony P. Carnevale Jeff Strohl Michelle Melton

More info »
S:\FULLCO~1\HEARIN~1\Committee print 2018\Henry\Jan. 9 report

S:\FULLCO~1\HEARIN~1\Committee print 2018\Henry\Jan. 9 report

1 C . RT S. P 115 TH ONGRESS " ! COMMITTEE PRINT 2d Session 115–21 PUTIN’S ASYMMETRIC ASSAULT ON DEMOCRACY IN RUSSIA AND EUROPE: IMPLICATIONS FOR U.S. NATIONAL SECURITY A MINORITY STAFF REPORT PREPARE...

More info »
AndersBehringBreivikManifesto

AndersBehringBreivikManifesto

2011 , London – By Andrew Berwick

More info »
DoD7045.7H

DoD7045.7H

DoD 7045.7-H EPARTMENT OF D EFENSE D F UTURE Y EARS D EFENSE P ROGRAM (FYDP) S TRUCTURE Codes and Definitions for All DoD Components Office of the Director, Program Analysis and Evaluation A pril 2004

More info »
Web Tables—Profile of Undergraduate Students: 2011–12

Web Tables—Profile of Undergraduate Students: 2011–12

Profile of WEB Undergraduate 12 Students: 2011– TABLES EDUCATION OF DEPARTMENT U.S. NCES 2015-1 OCTOBER 2014 67 These Web Tables provide comprehen- distance from home; and participation carried a bala...

More info »
Microsoft Word   cust subm Book 251 Cover.doc

Microsoft Word cust subm Book 251 Cover.doc

Summary of Reciprocity Agreements Between Texas and Other Jurisdictions Vehicle Titles and Registration Division Austin, Texas Issued November 2002

More info »
summer schedule full

summer schedule full

Summer Semester 2019 Class Schedule May 9, 2019 as of Subj Crse CRN Course Type Title Days Time Bldg/Rm Cred Instructor Course Fee Start Date - End Date Campus Part Term BB 321 Financial Accounting I ...

More info »
An Introduction to Computer Networks

An Introduction to Computer Networks

An Introduction to Computer Networks Release 1.9.18 Peter L Dordal Mar 31, 2019

More info »
G:\COMP\PHSA\PHSA.bel

G:\COMP\PHSA\PHSA.bel

G:\COMP\PHSA\PHSA-MERGED.XML PUBLIC HEALTH SERVICE ACT [As Amended Through P.L. 115–408, Enacted December 31, 2018] References in brackets ¿ ø¿ ø are to title 42, United States Code TITLE I—SHORT TITL...

More info »
U.S. Mexico Canada Trade Agreement: Likely Impact on the U.S. Economy and on Specific Industry Sectors

U.S. Mexico Canada Trade Agreement: Likely Impact on the U.S. Economy and on Specific Industry Sectors

United States International Trade Commission U.S. -Mexico -Canada Trade Agreement: Likely Impact on the U.S. Economy and on Specific Industry Sectors April 2019 Publication Number: 4889 Investigation ...

More info »