Interventions are effective but must be tailored to the specific setting

Background The fetal origins hypothesis suggests that an adverse prenatal environment, indexed by low birthweight (LBW), may increase the risk of developing later disease. Recently the hypothesis has been extended to psychological outcomes, especially depression. The aim of this analysis was to test, for the first time in a developing country setting, the association between LBW and psychological symptoms, in Soweto, South Africa.

Methods A sample of 1029 children was drawn from Birth to Twenty, a longitudinal cohort followed from pregnancy to young adulthood. This sample completed the Youth Self Report at age 12 years, a validated psychological measure of behavioural and emotional adjustment. Scores were compared between LBW (<2500 g) and normal birthweight children using multivariate analysis with adjustment for potential birth and life events confounding factors.

Results No associations were found between LBW and total [adjusted odds ratio (OR) 1.09, 95% confidence interval (CI) 0.69–1.74], internalizing (adjusted OR 0.81, 95% CI 0.52–1.28) or externalizing profiles (adjusted OR 0.81, 95% CI 0.49–1.36). The only difference detected was for the internalizing sub-profile of Somatic Complaints (adjusted OR 2.02, 95% CI 1.21–3.38), which on subgroup analysis was greatest among females.

Conclusions We found no convincing evidence of an association between LBW and emotional and behavioural outcomes in 12-year olds in this sample in urban South Africa. To our knowledge, this is the first published assessment of this association in a developing world context.

Objectives

To compare the effect of donor breast milk with infant formula in preterm infants. Separate comparisons with formula were made for donor breast milk that was: (1) given as a sole diet; (2) given as a supplement to mother's own breast milk; and (3) fortified with macronutrients and micronutrients. The main outcomes were death, necrotising enterocolitis (NEC), infection, growth and development.

Data sources

Electronic databases—Cochrane, CENTRAL, MEDLINE, EMBASE, CINAHL, and HMIC: DH.

Review methods

Systematic review and meta‐analysis of trials and observational studies of preterm or low birthweight infants.

Results

Seven studies (including five randomised controlled trials), all from the 1970s and 1980s, fulfilled the inclusion criteria. All studies compared the effect of sole donor breast milk with formula (combined n = 471). One of these also compared the effect of donor breast milk with formula given as a supplement to mother's own milk (n = 343). No studies examined fortified donor breast milk. A meta‐analysis based on three studies found a lower risk of NEC in infants receiving donor breast milk compared with formula (combined RR 0.21, 95% CI 0.06 to 0.76). Donor breast milk was associated with slower growth in the early postnatal period, but its long‐term effect is unclear.

Conclusion

Donor breast milk is associated with a lower risk of NEC and slower growth in the early postnatal period, but the quality of the evidence is limited. Further research is needed to confirm these findings and measure the effect of fortified or supplemented donor breast milk.

Background

Helminths have profound effects on the immune response, allowing long-term survival of parasites with minimal damage to the host. Some of these effects "spill-over", altering responses to non-helminth antigens or allergens. It is suggested that this may lead to impaired responses to immunizations and infections, while conferring benefits against inflammatory responses in allergic and autoimmune disease. These effects might develop in utero, through exposure to maternal helminth infections, or through direct exposure in later life.

Purpose

To determine the effects of helminths and their treatment in pregnancy and in young children on immunological and disease outcomes in childhood.

Methods

The trial has three randomized, double-blind, placebo-controlled interventions at two times, in two people: a pregnant woman and her child. Pregnant women are randomized to albendazole or placebo and praziquantel or placebo. At age 15 months their children are randomized to three-monthly albendazole or placebo, to continue to age five years. The proposed designation for this sequence of interventions is a 2 X 2(x2) factorial design.

Children are immunized with BCG and against polio, Diphtheria, tetanus, Pertussis, Haemophilus, hepatitis B and measles. Primary immunological outcomes are responses to BCG antigens and tetanus toxoid in whole blood cytokine assays and antibody assays at one, three and five years of age. Primary disease outcomes are incidence of malaria, pneumonia, diarrhoea, tuberculosis, measles, vertical HIV transmission, and atopic disease episodes, measured at clinic visits and twice-monthly home visits. Effects on anaemia, growth and intellectual development are also assessed.

Conclusion

This trial, with a novel design comprising related interventions in pregnant women and their offspring, is the first to examine effects of helminths and their treatment in pregnancy and early childhood on immunological, infectious disease and allergic disease outcomes. The results will enhance understanding of both detrimental and beneficial effects of helminth infection and inform policy. Clinical Trials 2007; 4: 42–57. http://ctj.sagepub.com

Background

Maternal schistosomiasis and filariasis have been shown to influence infant responses to neonatal bacille Calmette-Guérin (BCG) immunisation but the effects of maternal hookworm, and of de-worming in pregnancy, are unknown.

Methods

In Entebbe, Uganda, we conducted a randomised, double-blind, placebo-controlled trial of a single dose of 400 mg of albendazole in the second trimester of pregnancy. Neonates received BCG. Interferon-gamma (IFN-γ) and interleukin (IL)-5 responses to a mycobacterial antigen (crude culture filtrate proteins (CFP) of Mycobacterium tuberculosis) were measured in a whole blood assay. We analysed results for binary variables using χ2 tests and logistic regression. We analysed continuous variables using Wilcoxon's tests.

Results

Maternal hookworm was associated with reduced maternal IFN-γ responses to CFP (adjusted odds ratio for IFN-γ > median response: 0.14 (95% confidence interval 0.02–0.83, p = 0.021). Conversely, maternal hookworm was associated with subsequent increased IFN-γ responses in their one-year-old infants (adjusted OR 17.65 (1.20–258.66; p = 0.013)). Maternal albendazole tended to reduce these effects.

Conclusion

Untreated hookworm infection in pregnancy was associated with reduced maternal IFN-γ responses to mycobacterial antigens, but increased responses in their infants one year after BCG immunisation. The mechanisms of these effects, and their implications for protective immunity remain, to be determined.

Objective To investigate the burden of later disease associated with moderate/late preterm (32-36 weeks) and early term (37-38 weeks) birth.

Design Secondary analysis of data from the Millennium Cohort Study (MCS).

Setting Longitudinal study of infants born in the United Kingdom between 2000 and 2002.

Participants 18 818 infants participated in the MCS. Effects of gestational age at birth on health outcomes at 3 (n=14 273) and 5 years (n=14 056) of age were analysed.

Main outcome measures Growth, hospital admissions, longstanding illness/disability, wheezing/asthma, use of prescribed drugs, and parental rating of their children’s health.

Results Measures of general health, hospital admissions, and longstanding illness showed a gradient of increasing risk of poorer outcome with decreasing gestation, suggesting a “dose-response” effect of prematurity. The greatest contribution to disease burden at 3 and 5 years was in children born late/moderate preterm or early term. Population attributable fractions for having at least three hospital admissions between 9 months and 5 years were 5.7% (95% confidence interval 2.0% to 10.0%) for birth at 32-36 weeks and 7.2% (1.4% to 13.6%) for birth at 37-38 weeks, compared with 3.8% (1.3% to 6.5%) for children born very preterm (<32 weeks). Similarly, 2.7% (1.1% to 4.3%), 5.4% (2.4% to 8.6%), and 5.4% (0.7% to 10.5%) of limiting longstanding illness at 5 years were attributed to very preterm birth, moderate/late preterm birth, and early term birth.

Conclusions These results suggest that health outcomes of moderate/late preterm and early term babies are worse than those of full term babies. Additional research should quantify how much of the effect is due to maternal/fetal complications rather than prematurity itself. Irrespective of the reason for preterm birth, large numbers of these babies present a greater burden on public health services than very preterm babies.