Vulnerable newborn types: analysis of subnational, population-based birth cohorts for 541 285 live births in 23 countries, 2000-2021.

OBJECTIVE: To examine prevalence of novel newborn types among 541 285 live births in 23 countries from 2000 to 2021. DESIGN: Descriptive multi-country secondary data analysis. SETTING: Subnational, population-based birth cohort studies (n = 45) in 23 low- and middle-income countries (LMICs) spanning 2000-2021. POPULATION: Liveborn infants. METHODS: Subnational, population-based studies with high-quality birth outcome data from LMICs were invited to join the Vulnerable Newborn Measurement Collaboration. We defined distinct newborn types using gestational age (preterm [PT], term [T]), birthweight for gestational age using INTERGROWTH-21st standards (small for gestational age [SGA], appropriate for gestational age [AGA] or large for gestational age [LGA]), and birthweight (low birthweight, LBW [<2500 g], nonLBW) as ten types (using all three outcomes), six types (by excluding the birthweight categorisation), and four types (by collapsing the AGA and LGA categories). We defined small types as those with at least one classification of LBW, PT or SGA. We presented study characteristics, participant characteristics, data missingness, and prevalence of newborn types by region and study. RESULTS: Among 541 285 live births, 476 939 (88.1%) had non-missing and plausible values for gestational age, birthweight and sex required to construct the newborn types. The median prevalences of ten types across studies were T+AGA+nonLBW (58.0%), T+LGA+nonLBW (3.3%), T+AGA+LBW (0.5%), T+SGA+nonLBW (14.2%), T+SGA+LBW (7.1%), PT+LGA+nonLBW (1.6%), PT+LGA+LBW (0.2%), PT+AGA+nonLBW (3.7%), PT+AGA+LBW (3.6%) and PT+SGA+LBW (1.0%). The median prevalence of small types (six types, 37.6%) varied across studies and within regions and was higher in Southern Asia (52.4%) than in Sub-Saharan Africa (34.9%). CONCLUSIONS: Further investigation is needed to describe the mortality risks associated with newborn types and understand the implications of this framework for local targeting of interventions to prevent adverse pregnancy outcomes in LMICs.

Taming troubled teens: the social production of mental morbidity amongst young mothers in Pelotas, Brazil.

Explanations for the association between teen-childbearing and subsequent mental morbidity vary considerably, from those based on neurological theories of development to those investigating underlying social and economic determinants. Based on longitudinal epidemiological and ethnographic sub-studies of the 1982 Pelotas birth cohort study, this paper explores the hypothesis that teen childbearing and subsequent mental morbidity have become associated through the interplay of culture, society, and biology in situations where teen pregnancy has become a stigmatised object of scientific and public health attention. Results show that the effect of teen childbearing on subsequent mental morbidity remained significant in the multivariate analysis. Ethnographic analysis, together with epidemiological effect modification analyses, suggest that this association is partially accounted for by the fact that it is more pronounced amongst a specific subgroup of women of low socio-economic status who, being more politicised about societal injustice, were also more critically engaged with - and thus troubled by - the inequitable institutionalisation of life-cycle transitions. With time, these women became highly critical of the institutionalised identification of early childbearing as a key violation of life-cycle norms and the differential class-based application of scientific knowledge on its causes and consequences. Public health campaigns should consider how the age-based institutionalisation of developmental norms has enabled the stigmatisation of those identified as transgressors.

Alternatives to randomisation in the evaluation of public-health interventions: statistical analysis and causal inference.

BACKGROUND: In non-randomised evaluations of public-health interventions, statistical methods to control confounding will usually be required. We review approaches to the control of confounding and discuss issues in drawing causal inference from these studies. METHODS: Non-systematic review of literature and mathematical data-simulation. RESULTS: Standard stratification and regression techniques will often be appropriate, but propensity scores may be useful where many confounders need to be controlled, and data are limited. All these techniques require that key putative confounders are measured accurately. Instrumental variables offer, in theory, a solution to the problem of unknown or unmeasured confounders, but identifying an instrument which meets the required conditions will often be challenging. Obtaining measurements of the outcome variable in both intervention and control groups before the intervention is introduced allows balance to be assessed, and these data may be used to help control confounding. However, imbalance in outcome measures at baseline poses challenges for the analysis and interpretation of the evaluation, highlighting the value of adopting a design strategy that maximises the likelihood of achieving balance. Finally, when it is not possible to have any concurrent control group, making multiple measures of outcome pre- and postintervention can enable the estimation of intervention effects with appropriate statistical models. CONCLUSION: For non-randomised designs, careful statistical analysis can help reduce bias by confounding in estimating intervention effects. However, investigators must report their methods thoroughly and be conscious and critical of the assumptions they must make whenever they adopt these designs.

Alternatives to randomisation in the evaluation of public health interventions: design challenges and solutions.

BACKGROUND: There has been a recent increase in interest in alternatives to randomisation in the evaluation of public health interventions. We aim to describe specific scenarios in which randomised trials may not be possible and describe, exemplify and assess alternative strategies. METHODS: Non-systematic exploratory review. RESULTS: In many scenarios barriers are surmountable so that randomised trials (including stepped-wedge and crossover trials) are possible. It is possible to rank alternative designs but context will also determine which choices are preferable. Evidence from non-randomised designs is more convincing when confounders are well-understood, measured and controlled; there is evidence for causal pathways linking intervention and outcomes and/or against other pathways explaining outcomes; and effect sizes are large. CONCLUSION: Non-randomised trials might provide adequate evidence to inform decisions when interventions are demonstrably feasible and acceptable, and where evidence suggests there is little potential for harm, but caution that such designs may not provide adequate evidence when intervention feasibility or acceptability is doubtful, and where existing evidence suggests benefits may be marginal and/or harms possible.

Review of the theoretical frameworks for the study of child development within public health and epidemiology.

BACKGROUND: Care for child development has gained international momentum in research and community-based programming. It encompasses various domains including cognitive, psychomotor, emotional, behavioural and social development, and a multitude of factors that have the potential to influence its trajectories. However, the multidisciplinary nature of child development initiatives is marred by a lack of unified perspectives across disciplines, especially basic conceptual understanding generated in the fields of education and psychology, which are not effectively exploited in public health programmes and epidemiological research. METHODS: The article suggests a four-point evaluation criteria to child development theories based on the ability to communicate in (1) Cross-disciplines, (2) an Overarching facility to address various developmental domains, (3) the capacity to link child development with Lifelong developmental potentials and, most importantly, (4) Epidemiological capability to provide supporting empirical evidence for community-based public health interventions (COLE criteria). RESULTS: Key child development theories have been reviewed by broadly grouping them into three categories on the basis of content and approach, such as descriptive theories, psychological construct-based theories, and context-based theories. The strengths and challenges of these theories have been evaluated on the basis of COLE criteria. CONCLUSION: Although most of these theories can contribute at different levels in child development initiatives, context-based theories have been particularly proposed to practitioners, researchers and policy makers for community-based programming, principally for its potential to address issues of social inequality, poverty and childcare practices, which are at the core of public health initiatives, and provide multiple level of opportunities to intervene.

How did formative research inform the development of a home-based neonatal care intervention in rural Ghana?

Formative research is often used to inform intervention design, but the design process is rarely reported. This study describes how an integrated home visit intervention for newborns in Ghana was designed. As a first step in the design process, the known intervention parameters were listed, information required to refine the intervention was then identified and a formative research strategy designed. The strategy included synthesizing available data, collecting data on newborn care practices in homes and facilities, on barriers and facilitators to adopting desired behaviors and on practical issues such as whom to include in the intervention. The data were used to develop an intervention plan through workshops with national and international stakeholders and experts. The intervention plan was operationalized by district level committees. This included developing work plans, a creative brief for the materials and completing a community volunteer inventory. The intervention was then piloted and the intervention materials were finalized. The design process took over a year and was iterative. Throughout the process, literature was reviewed to identify the best practice. The intervention focuses on birth preparedness, using treated bednets in pregnancy, early and exclusive breastfeeding, thermal care, special care for small babies and prompt care seeking for newborns with danger signs. The need for a problem-solving approach was identified to help ensure behavior change. A subset of behaviors were already being performed adequately, or were the focus of other interventions, but were important to reinforce in the visits. These include attending antenatal care and care seeking for danger signs in pregnancy. On the basis of the intervention content, the timing of newborn deaths and the acceptability of visits, two antenatal and three visits in the first week of life (days 1, 3 and 7) were planned. Several household members were identified to include in the visits as they were involved in newborn care or they made financial decisions. Birth attendants and health workers were often the locus of control for immediate newborn care, and sensitization activities were designed to improve their practices and to help ensure that families received consistent messages. An existing cadre of community volunteers was identified to deliver the intervention-these volunteers were already trusted and accepted by the community, already visited pregnant women at home and had the time and commitment to deliver the intervention. A supervision and remuneration system was developed through discussions with the volunteers and at the planning workshops. The need for community entry activities was identified to garner community support for the intervention, to encourage self-identification of pregnant and delivered women and to motivate the volunteer through community recognition. Formative research is an essential step in helping to ensure the development of an effective, appropriate and sustainable intervention.

Early initiation of breast-feeding in Ghana: barriers and facilitators.

To explore why women in Ghana initiate breast-feeding early or late, who gives advice about initiation and what foods or fluids are given to babies when breast-feeding initiation is late. Qualitative data were collected through 52 semistructured interviews with recent mothers, 8 focus group discussions with women of child-bearing age and 13 semistructured interviews with health workers, policy makers and implementers. The major reasons for delaying initiation of breast-feeding were the perception of a lack of breast milk, performing postbirth activities such as bathing, perception that the mother and the baby need rest after birth and the baby not crying for milk. Facilitating factors for early initiation included delivery in a health facility, where the staff encouraged early breast-feeding, and the belief in some ethnic groups that putting the baby to the breast encourages the milk. Policy makers tended to focus on exclusive breast-feeding rather than early initiation. Most activities for the promotion of early initiation of breast-feeding were focused on health facilities with very few community activities. It is important to raise awareness about early initiation of breast-feeding in communities and in the policy arena. Interventions should focus on addressing barriers to early initiation and should include a community component.

Impact of early infant feeding practices on mortality in low birth weight infants from rural Ghana.

OBJECTIVE: To assess the impact of early infant feeding practices on low birth weight- (LBW) specific neonatal mortality in rural Ghana. STUDY DESIGN: A total of 11 787-breastfed babies were born between July 2003 and June 2004 and survived to day 2. Overall, 3411 (30.3%) infants had weight recorded within 48 h. Two hundred and ninety-six (8.7%) infants were <2.5 kg and 15 died in the neonatal period. Associations were examined using multivariate logistic regression. RESULT: Initiation of breastfeeding after day 1 was associated with a threefold increase in mortality risk (adjusted odds ratio (adjOR) 3.23, 95% confidence interval (95% CI) (1.07-9.82)) in infants aged 2 to 28 days. Prelacteal feeding was associated with a threefold significantly increased mortality risk (adjOR 3.12, 95% CI (1.19-8.22)) in infants aged 2 to 28 days but there was no statistically significant increase in risk associated with predominant breastfeeding (adjOR 1.91, 95% CI (0.60-6.09)). There were no modifications of these effects by birth weight. The sample size was insufficient to allow assessment of the impact of partial breastfeeding. CONCLUSION: Improving early infant feeding practices is an effective, feasible, low-cost intervention that could reduce early infant mortality in LBW infants in developing countries. These findings are especially relevant for sub-Saharan Africa where many LBW infants are born at home, never taken to a health facility and mortality rates are unacceptably high.

Spousal sexual violence and poverty are risk factors for sexually transmitted infections in women: a longitudinal study of women in Goa, India.

OBJECTIVES: To describe factors associated with incident sexually transmitted infections (STI) in a population-based sample of women in Goa, India. METHODS: A random sample of women aged 18-45 years was enrolled in Goa from November 2001 to May 2003. All subjects who consented to participate and completed the recruitment procedure were interviewed six and 12 months after recruitment. Incident chlamydia, gonorrhoea or trichomoniasis from vaginal and/or urine specimens were detected using a commercial polymerase chain reaction and the InPouch TV Culture Kit. RESULTS: Of the 2180 women followed up, 64 had an incident STI (incidence of 1.8% in the first six months, and 1.4% in the second six months). Incident STI was associated with low socioeconomic status, marital status, and with concurrent bacterial vaginosis. Incidence was highest among women who were married and exposed to sexual violence (10.9%), were concerned about their husbands' affairs (10.5%), or were separated, divorced or widowed women (11.0%). CONCLUSIONS: Socially disadvantaged women are at increased risk of STI in this population. Sexual intercourse outside marriage was rarely reported in this population, and women are at risk of becoming infected within marriage, especially those with sexual violence. This highlights the vulnerabilities of socially disadvantaged married women in India, and the need for healthcare professionals to screen STI patients for violence, and provide the necessary support. The results also stress the importance of effectively diagnosing and treating married men with STI and promoting safer sex within marriage.

Vitamin A supplementation increases ratios of proinflammatory to anti-inflammatory cytokine responses in pregnancy and lactation.

Vitamin A supplementation reduces child mortality in populations at risk of vitamin A deficiency and may also reduce maternal mortality. One possible explanation for this is that vitamin A deficiency is associated with altered immune function and cytokine dysregulation. Vitamin A deficiency in pregnancy may thus compound the pregnancy-associated bias of cellular immune responses towards Th-2-like responses and exacerbate susceptibility to intracellular pathogens. We assessed mitogen and antigen-induced cytokine responses during pregnancy and lactation in Ghanaian primigravidae receiving either vitamin A supplementation or placebo. This was a double-blind, randomized, placebo-controlled trial of weekly vitamin A supplementation in pregnant and lactating women. Pregnancy compared to postpartum was associated with a suppression of cytokine responses, in particular of the proinflammatory cytokines interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha. Mitogen-induced TNF-alpha responses were associated with a decreased risk of peripheral parasitaemia during pregnancy. Furthermore, vitamin A supplementation was significantly associated with an increased ratio of mitogen-induced proinflammatory cytokine (IFN-gamma) to anti-inflammatory cytokine (IL-10) during pregnancy and in the postpartum period. The results of this study indicate that suppression of proinflammatory type 1 immune responses and hence immunity to intracellular infections, resulting from the combined effects of pregnancy and vitamin A deficiency, might be ameliorated by vitamin A supplementation.

The burden and determinants of reproductive tract infections in India: a population based study of women in Goa, India.

BACKGROUND/OBJECTIVE: Reproductive tract infections (RTI) present major health, social, and economic problems in developing countries. Our objective was to describe the prevalence and risk factors of RTIs in a population based sample of women aged 18-45 years. METHOD: 2494 women of 3000 randomly selected from the population defined by a primary health centre catchment area consented to participate. Participants were interviewed regarding complaints and risk factors. Laboratory specimens were collected for the diagnosis of RTIs. Analyses of risk factors were carried out separately for the outcomes of sexually transmitted infections: chlamydia, gonorrhoea, trichomoniasis; and endogenous infections: bacterial vaginosis (BV) and candida. RESULTS: Endogenous infections were relatively common (BV 17.8%; candida 8.5%), and sexually transmitted infections (STI) were infrequent (4.2%). Factors indicative of poverty and marginalisation were associated with STIs and BV. Gender disadvantage, particularly spousal violence, was associated with BV, while concern about a husband's extramarital relationships, an indicator of sexual risk, was associated with STI. Husband's discharge was strongly associated with STI, and a non-white vaginal discharge was associated with both STI and BV. Condom use and oral contraceptive use were associated with a reduced risk of BV. CONCLUSIONS: Most of the population burden of RTIs is attributed to endogenous infections. Socioeconomic deprivation and gender disadvantage are associated with raised risk for BV, while the risk factors for STIs indicated that disadvantaged women were likely to be infected by their husbands.

Potential interventions for the prevention of childhood pneumonia in developing countries: improving nutrition.

Acute respiratory infections are the leading cause of childhood death in developing countries. Current efforts at mortality control focus on case management and immunization, but other preventive strategies may have a broader and more sustainable effect. This review, commissioned by the World Health Organization, examines the relations between pneumonia and nutritional factors and estimates the potential effect of nutritional interventions. Low birth weight, malnutrition (as assessed through anthropometry), and lack of breast-feeding appear to be important risk factors for childhood pneumonia, and nutritional interventions may have a sizeable effect in reducing deaths from pneumonia. For all regions except Latin America, interventions to prevent malnutrition and low birth weight look more promising than does breast-feeding promotion. In Latin America, breast-feeding promotion would have an effect similar to that of improving birth weights, whereas interventions to prevent malnutrition are likely to have less of an effect. These findings emphasize the need for tailoring interventions to specific national and even local conditions.

The impact of vitamin A supplementation given during a pneumonia episode on the subsequent morbidity of children.

OBJECTIVE: To evaluate the impact of large-dose vitamin A supplementation given to infants > 6 months old (200000 IU) and to preschool children aged 1-4 years (400000 IU) during a pneumonia episode, on their subsequent morbidity and severe morbidity. METHOD: In a randomized, double-blind, placebo controlled trial, the children were followed-up with 2-weekly visits at home for 16 weeks, with the first visit 2 weeks after treatment for pneumonia was initiated. The field workers asked about the presence of morbidity on the day of the visit and in the previous two weeks and about the occurrence and number of clinic attendances and hospital admissions since the last visit. They also measured the patients respiratory rate and temperature and assessed the children for the presence of cyanosis, chest indrawing and wheezing. RESULTS: Except for the prevalence of diet refusal which was higher in the vitamin A group, no differences between the study groups were observed, either in the prevalence of morbidity or in the incidence of clinic attendances and hospital admissions. CONCLUSION: No evidence was found for a beneficial effect of vitamin A given during acute pneumonia on the subsequent morbidity and severe morbidity of children in a population with marginal vitamin A deficiency.

Issues in the design and interpretation of studies to evaluate the impact of community-based interventions.

Increasingly, epidemiologists are faced with the need to evaluate the impact of an intervention that is delivered at the level of a community or cluster of individuals, rather than at the individual level. This has profound implications for the design and interpretation of a study to evaluate its impact. We start by discussing the issues arising in the extension of the randomized double-blind controlled trial methodology to the evaluation of interventions delivered to clusters of individuals, or to whole communities, where the unit of randomization is a cluster of individuals rather than an individual. We then consider alternative approaches to design, discuss their relative strengths and weaknesses and present a framework of design options. Finally we propose a pragmatic approach to evaluation design in this setting. We believe that the answer lies in the judicious selection of different design elements, combined in such a way that when the evidence from each is presented together, a clear picture of the impact of the intervention emerges. We illustrate this using an example from the recent literature.

Randomised, double blind, placebo controlled clinical trial of efficacy of vitamin A treatment in non-measles childhood pneumonia.

OBJECTIVE: To evaluate the impact on clinical recovery and severity of the addition of large doses of vitamin A to the standard treatment for childhood pneumonia. DESIGN: A randomised, double blind, placebo controlled trial. SETTING: Study children were recruited at a public hospital in Recife, north east Brazil, an area of marginal vitamin A deficiency. SUBJECTS: 472 children aged 6 to 59 months with clinical diagnosis of pneumonia. INTERVENTIONS: 200,000 IU (infants) or 400,000 IU (1-4 year olds) of vitamin A in oil or similar capsules of placebo divided into two daily oral doses, in addition to the standard treatment. MAIN OUTCOME MEASURES: Duration of the episode and incidence of adverse outcomes. RESULTS: The groups were similar with respect to overall duration of pneumonia and incidence of adverse outcomes. Children who received vitamin A, however, were less likely to have fever by day 3 (P = 0.008) and were 29% less likely to fail to respond to the first line antibiotic (P = 0.054). CONCLUSION: There was little evidence for an effect of vitamin A treatment on the immediate outcome of the pneumonia episode.

Low body weight: a simple indicator of the risk of dehydration among children with diarrhoea.

The early identification of children at high risk of dehydration as a consequence of diarrhoea would be of great value for health care workers in developing countries. By comparing children aged less than two years with diarrhoea and moderate to severe dehydration with matched controls who had uncomplicated diarrhoea, a number of prognostic factors were assessed. Low body weight, regardless of age, was strongly associated with the risk of dehydration; using 7.0 kg as a cut-off, it had a sensitivity of 75% and a specificity of 68%. Low body weight was superior to more complex anthropometric indices, including weight for age, weight for length or length for age, and also to early signs and symptoms during the episode. By reflecting the effects of both young age and those of malnutrition, low body weight may prove to be a simple indicator for predicting dehydration among children with diarrhoea presenting at a health service.

Is prevalence of diarrhea a better predictor of subsequent mortality and weight gain than diarrhea incidence?

A number of different outcome measures have been proposed for use in prospective studies of morbidity associated with childhood diarrhea. These include the number of episodes experienced by each child over a defined period (a measure of incidence) and the number of days of diarrhea divided by the total number of days of observation for each child (a measure denoted "longitudinal prevalence"). The authors examined data from Ghana to determine which of these measures is more strongly associated with weight gain over a 4-month period and subsequent mortality. Both diarrhea incidence and longitudinal prevalence were associated with weight gain in children aged 6-23 months, but a statistically stronger association was observed with longitudinal prevalence (likelihood ratio statistic 28.95 on 1 degree of freedom against 19.70 for incidence). Neither measure was associated with weight gain in younger or older children. Longitudinal prevalence, but not incidence, was strongly associated with subsequent mortality (p = 0.002 for longitudinal prevalence; p = 0.557 for incidence). Although many epidemiologic studies of diarrhea focus on incidence, these data suggest that longitudinal prevalence is more strongly predictive of long-term health outcome. The authors conclude that longitudinal prevalence merits greater attention as a measure of outcome in diarrhea studies.

PIP: During June 1990 to June 1991, weekly home visits and periodic clinical examinations were conducted among 1872 children 0-5 years old living in northern Ghana. The data obtained from the home visits and the clinical examinations were analyzed to determine whether diarrhea incidence (number of episodes experienced by each child over a defined period) or longitudinal prevalence (number of days of diarrhea divided by the total number of days of observation for each child) had the strongest association between weight gain over a 4-month period and subsequent mortality. Diarrhea burden, be it diarrhea incidence or prevalence, was strongly associated with weight gain in children 6-23 months old only. Yet, longitudinal prevalence of diarrhea had more explanatory power with regards to weight gain than did incidence (likelihood ratio statistic: 28.95 on 1 degree of freedom vs. 19.70). When the researchers adjusted for longitudinal prevalence, the strength of the association between the number of incident episodes and weight gain declined. On the other hand, when they adjusted for incidence, the strength of the association between longitudinal prevalence and weight gain remained very strong. Longitudinal prevalence was also a strong predictor of subsequent mortality (5% absolute increase in longitudinal prevalence associated with a 17% relative increase in the risk of mortality; p = 0.002 vs. p = 0.557 for incidence). These findings suggest that longitudinal prevalence of diarrhea is a stronger predictor of long-term health outcome than incidence. Longitudinal prevalence may be best suited for studies of interventions expected to improve host response to diarrhea (e.g., vitamin A supplementation or treatment of acute diarrhea with zinc) or those seeking to quantify the burden on children of morbidity from diarrhea. In conclusion, longitudinal prevalence should receive greater attention as a measure of outcome in studies of childhood diarrhea.

Effect of vitamin A supplementation on the growth of young children in northern Ghana.

The effect of prophylactic vitamin A supplementation on child growth was studies in two randomized, placebo-controlled trials carried out in adjacent areas of northern Ghana between 1989 and 1991. In the Health Study, the midupper arm circumference (MUAC) and weight of the approximately 1500 children (aged 6-59 mo) in the trial were measured every 4 wk for up to 52 wk. In addition, MUAC, weight, and height were measured at each of the four potential vitamin A or placebo dosing times, which were at 4-mo intervals. In the Survival Study, MUAC and weight were measured at 4-mo intervals at each of seven dosing rounds in the approximately 15 000 children currently in the trial. Overall, there were > 90 000 observations of weight and MUAC in > 25 000 children, and 3347 observations of length/height in 1546 children. Within each study, the mean monthly weight, MUAC, and gains in length/height in each treatment group were compared by using multilevel modeling. There were no significant differences in either MUAC or gains in length/height. The only significant difference in weight gain was in the Survival Study: children in the vitamin A-supplemented group who were > or = 36 mo of age had a mean weight gain that was 3 g lower per month (95% CI: 0.4, 5.0, P = 0.02) than that in the placebo group; a difference that was unlikely to be functionally important in this age group. Vitamin A supplementation did not lead to any increased growth in this population of young children, in whom supplementation reduced mortality and severe morbidity substantially.