Seasonal modulation of antibody response to diphtheria-tetanus-pertussis vaccination in infants: a cohort study in rural Gambia.

BACKGROUND: In rural Gambia, rates of malnutrition and infection are higher during the annual rainy/'hungry' season (June-October) in comparison to the dry/'harvest' season (November-May). The effects of this seasonal pattern on an infant's immune development and their capacity to respond to childhood vaccinations remain unclear. The aim of the current analysis was to determine whether antibody responses to diphtheria-tetanus-pertussis (DTP) vaccinations in infants differ between seasons. METHODS: Infants received the DTP vaccine at 8, 12 and 16 weeks of age and antibody titres were measured in blood samples collected at 12 (n = 710) and 24 (n = 662) weeks of age. Mean DTP antibody titres, adjusted for maternal and infant confounders, were compared by t-tests and the effect sizes of the mean differences were calculated between seasons at mid-gestation (20 weeks gestation) and first vaccination (8 weeks of infant age). RESULTS: A smaller number of infants received their first vaccination during the rainy/hungry season months compared to the dry/harvest season (n = 224 vs. n = 486). At 12 weeks, infants vaccinated during the rainy/hungry season had lower weight-for-length Z-scores (p = 0.01) and were more likely to be anaemic (p < 0.001). Their mothers, however, were pregnant mostly during the dry/harvest season, had higher weight gain (p < 0.001) and were less likely to be anaemic during pregnancy (p < 0.001). At 12 weeks, infants vaccinated during the rainy/hungry season had significantly higher mean diphtheria, tetanus and pertussis antibody titres; by 62.3, 16.9 and 19.7%, respectively (all, p < 0.001). However, at 24 weeks, they had lower mean anti-diphtheria titres (by 20.6%, p < 0.001) compared with infants vaccinated during the dry/harvest season, and no differences were observed in mean tetanus and pertussis antibody titres by vaccination season. CONCLUSIONS: Infant antibody response to the primary dose of the DTP vaccine was influenced by both season of pregnancy and infancy, although effects were diminished following three doses. Environmental exposures, including nutrition, to both the mother and infant are hypothesised as likely drivers of these seasonal effects.

Impact of Maternal Nutritional Supplementation during Pregnancy and Lactation on the Infant Gut or Breastmilk Microbiota: A Systematic Review.

Recent evidence indicates that maternal dietary intake, including dietary supplements, during pregnancy and lactation may alter the infant gut or breastmilk microbiota, with implications for health outcomes in both the mother and infant. To review the effects of maternal nutritional supplementation during pregnancy and lactation on the infant gut or breastmilk microbiota a systematic literature search was conducted. A total of 967 studies published until February 2020 were found, 31 were eligible and 29 randomized control trials were included in the qualitative synthesis. There were 23 studies that investigated the effects of probiotic supplementation, with the remaining studies investigating vitamin D, prebiotics or lipid-based nutrient supplements (LNS). The effects of maternal nutritional supplementation on the infant gut microbiota or breastmilk microbiota were examined in 21 and 12 studies, respectively. Maternal probiotic supplementation during pregnancy and lactation generally resulted in the probiotic colonization of the infant gut microbiota, and although most studies also reported alterations in the infant gut bacterial loads, there was limited evidence of effects on bacterial diversity. The data available show that maternal probiotic supplementation during pregnancy or lactation results in probiotic colonization of the breastmilk microbiota. There were no observed effects between probiotic supplementation and breastmilk bacterial counts of healthy women, however, administration of Lactobacillus probiotic to nursing women affected by mastitis was associated with significant reductions in breastmilk Staphylococcal loads. Maternal LNS supplementation during pregnancy and lactation increased bacterial diversity in the infant gut, whilst vitamin D and prebiotic supplementation did not alter either infant gut bacterial diversity or counts. Heterogeneity in study design precludes any firm conclusions on the effects of maternal nutritional supplementation during pregnancy and lactation on the infant gut or breastmilk microbiota, warranting further research.

Maternal plasma lipid levels across pregnancy and the risks of small-for-gestational age and low birth weight: a cohort study from rural Gambia.

BACKGROUND: Sub-optimal maternal lipid levels during pregnancy may be implicated in the pathophysiological mechanisms leading to low birth weight (LBW) and small-for-gestational-age (SGA). We aimed to determine whether maternal lipid levels across pregnancy were associated with birth weight and the risks of LBW and SGA in rural Gambia. METHODS: This secondary analysis of the ENID trial involved 573 pregnant women with term deliveries. Plasma levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), and triglycerides (TG) were analyzed at enrolment (mean (SD) = 13.9 (3.3) weeks gestation), 20 and 30 weeks gestation as continuous variables and percentile groups. Regression models with adjustment for confounders were used to examine associations between gestational lipid levels and birth weight and the risks of LBW (birth weight < 2500 g) and SGA (<10th percentile INTERGROWTH-21ST for birth weight). RESULTS: There were 7.9% LBW and 32.5% SGA infants. At enrolment, every unit increase in HDL-c was associated with a 2.7% (P = 0.011) reduction in relative risk of LBW. At 20 weeks gestation, every unit increase in TC levels was associated with a 1.3% reduction in relative risk of LBW (P = 0.002). Low (<10th percentile) HDL-c at enrolment or at 20 weeks gestation was associated with a 2.6 (P = 0.007) and 3.0 (P = 0.003) times greater risk of LBW, respectively, compared with referent (10th─90th) HDL-c. High (>90th percentile) LDL-c at 30 weeks gestation was associated with a 55% lower risk of SGA compared with referent LDL-c (P = 0.017). Increased levels of TC (ß = 1.3, P = 0.027) at 20 weeks gestation and of TC (ß = 1.2, P = 0.006) and LDL-c (ß = 1.5, P = 0.002) at 30 weeks gestation were all associated with higher birth weight. CONCLUSIONS: In rural Gambia, lipid levels during pregnancy were associated with infant birth weight and the risks of LBW and SGA. Associations varied by lipid class and changed across pregnancy, indicating an adaptive process by which maternal lipids may influence fetal growth and birth outcomes. TRIAL REGISTRATION: This trial was registered as ISRCTN49285450 on: 12/11/2009.

Impact of nutritional supplementation during pregnancy on antibody responses to diphtheria-tetanus-pertussis vaccination in infants: A randomised trial in The Gambia.

BACKGROUND: Exposure to a nutritionally deficient environment during fetal life and early infancy may adversely alter the ontogeny of the immune system and affect an infant's ability to mount an optimal immune response to vaccination. We examined the effects of maternal nutritional supplementation during pregnancy on infants' antibody responses to the diphtheria-tetanus-pertussis (DTP) vaccine included in the Expanded Programme on Immunisation (EPI). METHODS AND FINDINGS: The Early Nutrition and Immune Development (ENID) trial was a randomised, partially blinded trial conducted between April 2010 and February 2015 in the rural West Kiang region of The Gambia, a resource-poor region affected by chronic undernutrition. Pregnant women (<20 weeks' gestation) with a singleton pregnancy (n = 875) were randomised to receive one of four supplements: iron-folic acid (FeFol; standard of care), multiple micronutrient (MMN), protein-energy (PE), or PE + MMN daily from enrolment (mean [SD] 13.7 [3.3] weeks' gestation) until delivery. Infants were administered the DTP vaccine at 8, 12, and 16 weeks of age according to the Gambian Government protocol. Results for the primary outcome of the trial (infant thymic size) were described previously; here, we report on a secondary outcome, infant antibody response to vaccination. The effects of supplementation on mean DTP antibody titres measured in blood samples collected from infants at 12 weeks (n = 710) and 24 weeks (n = 662) were analysed with adjustment for confounders including maternal age, compliance to supplement, and infant sex and season. At 12 weeks, following a single dose of the vaccine, compared with FeFol (mean 95% confidence interval [CI]; 0.11 IU/mL, 0.09-0.12), antenatal supplementation with MMN or MMN + PE resulted in 42.4% (95% CI 20.1-64.6; p < 0.001) and 29.4% (6.4-52.5; p = 0.012) higher mean anti-diphtheria titres, respectively. Mean anti-tetanus titres were higher by 9.0% (5.5-12.5), 7.8% (4.3-11.4), and 7.3% (4.0-10.7) in MMN, PE, and PE + MMN groups (all, p < 0.001), respectively, than in the FeFol group (0.55 IU/mL, 0.52-0.58). Mean anti-pertussis titres were not significantly different in the FeFol, MMN, and PE + MNN groups but were all higher than in the PE group (all, p < 0.001). At 24 weeks, following all three doses, no significant differences in mean anti-diphtheria titres were detected across the supplement groups. Mean anti-tetanus titres were 3.4% (0.19-6.5; p = 0.038) higher in the PE + MMN group than in the FeFol group (3.47 IU/mL, 3.29-3.66). Mean anti-pertussis titres were higher by 9.4% (3.3-15.5; p = 0.004) and 15.4% (9.6-21.2; p < 0.001) in PE and PE + MMN groups, compared with the FeFol group (74.9 IU/mL, 67.8-82.8). Limitations of the study included the lack of maternal antibody status (breast milk or plasma) or prevaccination antibody measurements in the infants. CONCLUSION: According to our results from rural Gambia, maternal supplementation with MMN combined with PE during pregnancy enhanced antibody responses to the DTP vaccine in early infancy. Provision of nutritional supplements to pregnant women in food insecure settings may improve infant immune development and responses to EPI vaccines. TRIAL REGISTRATION: ISRCTN49285450.