Changes in preterm birth and stillbirth during COVID-19 lockdowns in 26 countries.

Preterm birth (PTB) is the leading cause of infant mortality worldwide. Changes in PTB rates, ranging from -90% to +30%, were reported in many countries following early COVID-19 pandemic response measures ('lockdowns'). It is unclear whether this variation reflects real differences in lockdown impacts, or perhaps differences in stillbirth rates and/or study designs. Here we present interrupted time series and meta-analyses using harmonized data from 52 million births in 26 countries, 18 of which had representative population-based data, with overall PTB rates ranging from 6% to 12% and stillbirth ranging from 2.5 to 10.5 per 1,000 births. We show small reductions in PTB in the first (odds ratio 0.96, 95% confidence interval 0.95-0.98, P value <0.0001), second (0.96, 0.92-0.99, 0.03) and third (0.97, 0.94-1.00, 0.09) months of lockdown, but not in the fourth month of lockdown (0.99, 0.96-1.01, 0.34), although there were some between-country differences after the first month. For high-income countries in this study, we did not observe an association between lockdown and stillbirths in the second (1.00, 0.88-1.14, 0.98), third (0.99, 0.88-1.12, 0.89) and fourth (1.01, 0.87-1.18, 0.86) months of lockdown, although we have imprecise estimates due to stillbirths being a relatively rare event. We did, however, find evidence of increased risk of stillbirth in the first month of lockdown in high-income countries (1.14, 1.02-1.29, 0.02) and, in Brazil, we found evidence for an association between lockdown and stillbirth in the second (1.09, 1.03-1.15, 0.002), third (1.10, 1.03-1.17, 0.003) and fourth (1.12, 1.05-1.19, <0.001) months of lockdown. With an estimated 14.8 million PTB annually worldwide, the modest reductions observed during early pandemic lockdowns translate into large numbers of PTB averted globally and warrant further research into causal pathways.

Salivary Cystatin SN Binds to Phytic Acid In Vitro and Is a Predictor of Nonheme Iron Bioavailability with Phytic Acid Supplementation in a Proof of Concept Pilot Study.

BACKGROUND: Acute phytic acid intake has been found to decrease iron bioavailability; however, repeated phytic acid consumption leads to iron absorption adaptation. Salivary proline-rich proteins (PRPs) have been shown to inhibit iron chelation to tannins and may mediate similar iron absorption adaptation with phytic acid intake. OBJECTIVES: The objectives of this study were to determine whether salivary proteins bind to phytic acid in vitro, and to explore a proof of concept in a pilot study that examined the impact of 4-wk, daily phytic acid supplementation on individuals' iron status, bioavailability, and salivary PRP concentrations. METHODS: High-performance liquid chromatography (HPLC) and matrix-assisted laser desorption/ionization-time of flight were used to characterize in vitro salivary protein-phytic acid interactions. Nonanemic women (n = 7) consumed 350 mg phytic acid supplements 3 times daily for 4 wk, and meal challenges were employed to determine iron bioavailability, iron status, and salivary protein concentrations before and after supplementation periods. Enzyme-linked immunosorbent assay (ELISA) analysis of purified protein fractions and participant saliva identified proteins bound to phytic acid. RESULTS: In vitro salivary protein-phytic acid interaction identified cystatin SN, a non-proline rich salivary protein, as the specific bound protein to phytic acid. Iron bioavailability (P = 0.32), hemoglobin (P = 0.72), and serum ferritin (P = 0.08) concentrations were not reduced from week 0 to week 4 after phytic acid supplementation. Basic PRPs and cystatin SN concentrations were positively correlated with iron bioavailability at week 4. CONCLUSIONS: Overall, results suggest that phytic acid binds to the non-PRP cystatin SN and that salivary protein production may improve iron bioavailability with phytic acid consumption.

Novel Formulated Fortified Blended Foods Result in Improved Protein Efficiency and Hepatic Iron Concentrations Compared with Corn-Soy Blend Plus in Broiler Chickens.

BACKGROUND: Corn- and soybean-based fortified blended foods (FBFs) have been the primary food aid product provided by the United States. Sorghum and cowpea have been suggested as alternative FBF commodities because they are drought-tolerant, grown in food aid-receiving areas, and not genetically modified. Extrusion processing has also been suggested to improve the quality of these FBFs. OBJECTIVES: The aim of this study was to determine the protein quality and iron and vitamin A bioavailability of novel FBFs in broiler chickens. METHODS: Whey protein concentrate (WPC)-containing FBFs corn-soy blend 14, sorghum-soy, and sorghum-cowpea (SC); a soy protein isolate (SPI)-containing SC FBF (SC+SPI); 2 reformulated, overprocessed SC FBFs (O-SC+WPC, O-SC+SPI); and a nonextruded WPC-containing SC FBF were developed. Nonextruded corn-soy blend plus (CSB+), a currently used FBF, and a gamebird starter/grower diet were used as comparison diets. In the prepared FBF study, 9 groups of 8-d-old broiler chicks (n = 10) consumed prepared FBFs for 21 d. In the dry study, 8 groups of 4-d-old broiler chicks (n = 24; control: n = 23) consumed dry FBFs for 14 d. Results were analyzed by 1-factor ANOVA with least-significant-difference test. RESULTS: In the prepared study, novel formulated FBFs significantly increased caloric and protein efficiency and nonsignificantly increased body weight gain, despite similar food intake compared with CSB+. In the dry study, novel formulated FBFs, except for O-SC+SPI, significantly increased food intake, caloric efficiency, and protein efficiency and nonsignificantly increased body-weight gain compared with CSB+. Novel formulated FBFs nonsignificantly and significantly increased hepatic iron concentrations compared with all FBFs in the prepared and dry studies, respectively. CONCLUSION: Novel formulated FBFs, apart from O-SC+SPI, resulted in improved protein efficiencies and hepatic iron concentrations compared with CSB+, suggesting that they are of higher nutritional quality.

Bioavailable Iron and Vitamin A in Newly Formulated, Extruded Corn, Soybean, Sorghum, and Cowpea Fortified-Blended Foods in the In Vitro Digestion/Caco-2 Cell Model.

BACKGROUND: Fortified-blended foods (FBFs), particularly corn-soybean blend (CSB), are food aid products distributed in developing countries. The US Agency for International Development food aid quality review recommended developing extruded FBFs with the use of alternative commodities such as sorghum. OBJECTIVE: The objective of the study was to determine bioavailable iron and vitamin A content from newly developed extruded corn, soybean, sorghum, and cowpea FBFs compared with the nonextruded traditional food aid FBFs, corn-soy blend 13 (CSB13) and corn-soy blend plus (CSB+). METHODS: Eleven extruded FBFs-sorghum-cowpea (n = 7), sorghum-soy (n = 3), and corn-soy (n = 1)-along with 2 nonextruded FBFs-CSB13 and CSB+, and Cerelac (Nestlé), a commercially available fortified infant food, were prepared. Bioavailable iron and vitamin A contents were assessed by using the in vitro digestion/Caco-2 cell model. Dry FBFs, aqueous fractions, and Caco-2 cell pellet vitamin A contents were analyzed by HPLC. Dry FBF and aqueous fraction iron contents were measured by atomic absorptiometry, and bioavailable iron was assessed by measuring Caco-2 ferritin contents via ELISA. RESULTS: Iron and vitamin A concentrations in Cerelac and dry FBFs ranged from 8.0 to 31.8 mg/100 g and 0.3 to 1.67 mg/100 g, respectively. All of the extruded FBFs contained 4- to 7-fold significantly higher (P < 0.05) aqueous fraction iron concentrations compared with CSB13 and CSB+. However, there were no significant differences in Caco-2 cell ferritin and vitamin A concentrations between extruded FBFs, nonextruded FBFs, and or the basal salt solution negative control. CONCLUSION: Results support the theory that the consumption of newly developed extruded sorghum-cowpea, sorghum-soy, and corn-soy FBFs would result in iron and vitamin A concentrations comparable to traditional nonextruded CSB13 and CSB+ FBFs.

Newly formulated, protein quality-enhanced, extruded sorghum-, cowpea-, corn-, soya-, sugar- and oil-containing fortified-blended foods lead to adequate vitamin A and iron outcomes and improved growth compared with non-extruded CSB+ in rats.

Corn and soyabean micronutrient-fortified-blended foods (FBF) are commonly used for food aid. Sorghum and cowpeas have been suggested as alternative commodities because they are drought tolerant, can be grown in many localities, and are not genetically modified. Change in formulation of blends may improve protein quality, vitamin A and Fe availability of FBF. The primary objective of this study was to compare protein efficiency, Fe and vitamin A availability of newly formulated extruded sorghum-, cowpea-, soya- and corn-based FBF, along with a current, non-extruded United States Agency for International Development (USAID) corn and soya blend FBF (CSB+). A second objective was to compare protein efficiency of whey protein concentrate (WPC) and soya protein isolate (SPI) containing FBF to determine whether WPC inclusion improved outcomes. Eight groups of growing rats (n 10) consumed two white and one red sorghum-cowpea (WSC1 + WPC, WSC2 + WPC, RSC + WPC), white sorghum-soya (WSS + WPC) and corn-soya (CSB14 + WPC) extruded WPC-containing FBF, an extruded white sorghum-cowpea with SPI (WSC1 + SPI), non-extruded CSB+, and American Institute of Nutrition (AIN)-93G, a weanling rat diet, for 4 weeks. There were no significant differences in protein efficiency, Fe or vitamin A outcomes between WPC FBF groups. The CSB+ group consumed significantly less food, gained significantly less weight, and had significantly lower energy efficiency, protein efficiency and length, compared with all other groups. Compared with WSC1 + WPC, the WSC1 + SPI FBF group had significantly lower energy efficiency, protein efficiency and weight gain. These results suggest that a variety of commodities can be used in the formulation of FBF, and that newly formulated extruded FBF are of better nutritional quality than non-extruded CSB+.

Long-Term Dose-Response Condensed Tannin Supplementation Does Not Affect Iron Status or Bioavailability.

Background: Repeated phytic acid consumption leads to iron absorption adaptation but, to the best of our knowledge, the impact of repeated tannin consumption has not yet been established. Salivary proline-rich proteins (PRPs) may improve iron absorption by precipitating tannins. Objectives: This study aimed to determine the effect of long-term, dose-response condensed tannin supplementation on iron bioavailability and status and to assess the effect of salivary proteins on iron bioavailability during prolonged condensed tannin consumption. A secondary objective was to assess astringency as a potential marker for adaptation to tannins and iron bioavailability. Methods: Eleven nonanemic women were enrolled in a double-blind 3-dose crossover trial. Three (1.5, 0.25, or 0.03 g) condensed tannin supplements were consumed 3 times/d for 4 wk in random order, with 2-wk washouts in between. Meal challenges were employed before and after supplementation to assess iron bioavailability, iron status, salivary PRP changes, and astringency. Results: Tannin supplementation in any dose did not change iron bioavailability at any dose (P > 0.82) from weeks 0 to 4. Hemoglobin (P = 0.126) and serum ferritin (P = 0.83) were unchanged by tannin dose from weeks 0 to 4. There were significant correlations among tannin supplementation and iron bioavailability, basic proline-rich proteins (bPRPs) (r = 0.366, P = 0.003), and cystatin production (r = 0.27, P = 0.03). Astringency ratings did not change significantly within or between tannin doses (P > 0.126), but there were negative relations among bPRP (r < -0.32, P < 0.21), cystatin production (r < -0.2, P < 0.28), and astringency ratings. Conclusions: Condensed tannin consumption did not affect iron bioavailability or status regardless of the supplementation period in premenopausal nonanemic women. Correlation analyses suggest that bPRPs and cystatins are associated with improved iron bioavailability and that lower ratings of astringency may predict improved iron absorption with repeated tannin consumption.