Maternal anemia type during pregnancy is associated with anemia risk among offspring during infancy.

BACKGROUND: We evaluated the association between etiology of maternal anemia and iron status throughout infancy. METHODS: Samples from a study designed to examine Praziquantel treatment during pregnancy were used (n = 359). All women were infected with schistosomiasis and randomized to Praziquantel or placebo at 16 ± 2 weeks' gestation. Hemoglobin, serum ferritin (SF), soluble transferrin receptor (sTfR), hepcidin, C-reactive protein, and interleukin-6 were measured in maternal and infant blood. The relationship between both maternal Praziquantel treatment and etiology of anemia and infant iron status was evaluated. RESULTS: Maternal iron-deficiency anemia was associated with increased risk of infant anemia at 6 months of age. Infants of mothers with the lowest levels of circulating hepcidin during gestation, likely a marker for iron deficiency, had higher sTfR:SF levels and lower hemoglobin levels, particularly at 12 months of age. Maternal non-iron-deficiency anemia (NIDA) did not impact infant anemia risk or iron status. Maternal treatment for schistosomiasis had no effect on infant hematologic status. CONCLUSIONS: Maternal iron deficiency anemia was associated with an increased risk for anemia or iron deficiency during late infancy. We did not observe an association between maternal NIDA and increased risk for iron deficiency during infancy.

Cord blood adiponectin and leptin are associated with a lower risk of stunting during infancy.

Undernutrition is responsible for up to 45% of deaths in children under five, with low- and middle-income countries disproportionately affected. Adipokines are known modulators of metabolism and have been linked to growth rates and neurocognition during infancy. We examined the relationship(s) between cord blood adiponectin and leptin and both longitudinal growth and cognition during the first year of life using generalized estimating equations. Infants were classified as underweight (weight-for-age z-score [WAZ]), stunted (height-for-age z-score [HAZ]) or wasted (weight-for-height z-score [WHZ]) using WHOAnthro software. Cord blood adiponectin and leptin levels were highly correlated (r = 0.35, P < 0.0001) and positively associated with birth WAZ (r = 0.34 and r = 0.45, P < 0.0001, respectively). Adipokines were independently, inversely associated with weight gain. Infants in the highest quintile of adipokine production had a lower risk of being stunted, while neither was associated with lower WAZ or WHZ in final adjusted models. Cognition was not found to be independently related to cord blood leptin or adiponectin. The negative association with adipokines and rate of weight gain during infancy may reflect heightened nutritional status at birth rather than a direct hormonal influence. The relationship between leptin or adiponectin and longitudinal length gains suggests that both adipokines may promote linear growth during infancy.

Endotoxin at the Maternal-Fetal Interface in a Resource-Constrained Setting: Risk Factors and Associated Birth Outcomes.

Low- and middle-income countries (LMICs) carry a high burden of infectious diseases associated with impaired gut integrity, leading to microbial translocation. Pregnancies in this setting are at high risk of fetal growth restriction (FGR). We examined the association among specific risk factors for impaired gut integrity (schistosomiasis, hookworm infection, and alcohol consumption), blood endotoxin levels, and FGR. Endotoxins, lipopolysaccharide-binding proteins (LBPs), and cytokines were measured in blood from women at 32 weeks gestation, the maternal-fetal interface (MFI) at delivery, and cord blood at delivery. Resolution of schistosomiasis had no impact on endotoxin levels; however, maternal hookworm infection and alcohol consumption were associated with modest increases in endotoxin at the MFI. Cytokines responses within the maternal peripheral blood and blood from the MFI were positively associated with endotoxins, but many cord blood cytokines were negatively associated with endotoxins. Newborns with FGR also had higher levels of endotoxins at the MFI. Risk factors for microbial translocation may lead to increased levels of endotoxins at the MFI, which may contribute to poor growth in utero.

Mechanistic Pathways From Early Gestation Through Infancy and Neurodevelopment.

OBJECTIVE: To identify pathways through which pre- and postnatal factors directly or indirectly affect infant neurodevelopment at 12 months of age among Filipino infants. METHODS: The Bayley Scales of Infant Development, third edition was used to assess the development of 314 infants of mothers enrolled in a trial examining the safety and efficacy of praziquantel during pregnancy. Maternal covariates included socioeconomic status, iron and nutritional status, cognitive performance, and alcohol intake. Infant covariates included birth weight and feeding practices, longitudinal growth and nutritional status, hemoglobin and iron status captured at birth, and 6 and 12 months of age. Multivariable regression and structural equation modeling were used to identify significant factors associated with infant development. RESULTS: In regression models, maternal education, cognition, and iron status as well as infant weight-for-age z-score (WAZ), weight-for-length z-score, and WAZ gains were significantly associated with infant development at 12 months of age. Structural equation modeling demonstrated a direct effect of maternal cognition on most subscales of infant development and indirect effects on expressive language through effects on infant WAZ. Maternal iron status was a stronger predictor of infant cognition subscale scores than was infant iron status. Exclusive breastfeeding had a direct influence on expressive language rather than acting through improved infant iron or nutritional status. CONCLUSIONS: We identified key modifiable risk factors for impaired neurodevelopment, including prenatal risk factors such as maternal iron status. Integrated nutritional interventions that impact both maternal and infant nutritional status are likely to positively affect infant neurodevelopment through identified pathways.

Efficacy and safety of praziquantel for the treatment of human schistosomiasis during pregnancy: a phase 2, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Despite WHO recommendations to offer pregnant women treatment with praziquantel, many nations continue to withhold treatment, awaiting data from controlled trials addressing safety and efficacy. The objectives of this study were to assess whether treatment of pregnant women with schistosomiasis at 12-16 weeks gestation leads to improved maternal and newborn outcomes and to collect maternal and newborn safety data. METHODS: This phase 2, randomised, double-blind, placebo-controlled trial was done in 72 baranguays (villages) serviced by six municipal health centres in a schistosomiasis endemic region of northeastern Leyte, Philippines. Pregnant women (at 12-16 weeks gestation) who were otherwise healthy but infected with Schistosoma japonicum were enrolled and randomly assigned (1:1) to receive either over-encapsulated praziquantel (total dose 60 mg/kg given as two split doses) or placebo. Participants, investigators, midwives, and laboratory staff were all masked to treatment. The primary outcome was birthweight. Safety data were collected including immediate reactogenicity, post-dosing toxicology ascertained 24 h after study drug administration, and maternal and newborn serious adverse events. Analysis followed the intention-to-treat principle. Analyses were done using hierarchical generalised linear models to adjust for identified confounders and account for potential clustering of observations within villages and municipalities. This trial is registered with ClinicalTrials.gov, number NCT00486863. FINDINGS: Between Aug 13, 2007, and Dec 3, 2012, 370 pregnant women were enrolled and randomly assigned to each treatment group (184 to the placebo group, 186 to the praziquantel group). Most women had low-intensity infections (n=334, 90%). Treatment with praziquantel did not have a significant effect on birthweight (2·85 kg in both groups, ß=-0·002 [95% CI -0·088 to 0·083]; p=0·962). Treatment was well tolerated with reactogenicity rates similar to those seen in non-pregnant participants (severe reactions occurred in five patients in the praziquantel group and two in the placebo group, and included headache, fever, and malaise). There were no significant differences in key safety outcomes including abortion, fetal death in utero, and congenital anomalies. INTERPRETATION: Results from this study provide important data from a controlled trial in support of the expansion of treatment policies to include pregnant women as recommended by WHO. FUNDING: National Institutes of Health, National Institute of Allergy and Infectious Diseases (U01AI066050).