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.

Periapical infection may affect birth outcomes via systemic inflammation.

OBJECTIVES: Maternal dental periapical infections are associated with preterm birth and intrauterine growth restriction. This study investigates whether the association is mediated through bacterial spread from periapical lesions to placenta (direct pathway) or systemic inflammatory reaction (indirect pathway). MATERIALS AND METHODS: We compared birth outcomes in Malawian mothers with and without periapical infection. As markers of a direct pathway, we identified placental bacteria using a 16S rDNA approach and assessed histological evidence of inflammation in the placenta and amniotic membranes. We measured C-reactive protein, alpha-1-acid glycoprotein, and salivary cortisol as markers of an indirect pathway. We used regression models to associate the predictor variables with duration of pregnancy and newborn size. RESULTS: Of 1,024 women, 23.5% had periapical infection. There was no association of periapical infection with either bacterial DNA or histological inflammation in placenta or membranes. Periapical infection was associated with C-reactive protein, alpha-1-acid glycoprotein, and cortisol concentrations in a dose-dependent manner at 36 weeks. Addition of alpha-1-acid glycoprotein or cortisol concentration into regression models attenuated the association between periapical infection and pregnancy outcomes. CONCLUSION: There was no evidence of direct spread of periapical bacteria to the placenta. Periapical infections and adverse pregnancy outcomes are in part mediated through systemic inflammation.

Effect of 12-month intervention with lipid-based nutrient supplement on the physical activity of Malawian toddlers: a randomised, controlled trial.

Physical activity is beneficial for children's well-being. The effect of dietary supplementation on children's physical activity in food-insecure areas remains little studied. We examined the effects of a lipid-based nutrient supplement (LNS) on children's objectively measured physical activity in a randomised, controlled, outcome-assessor-blinded trial. Mothers of the children received one capsule daily of Fe-folic acid (IFA), one capsule containing eighteen micronutrients (MMN) or one 20 g sachet of LNS (containing twenty-two MMN, protein, carbohydrates, essential fatty acids and 494 kJ (118 kcal)) during pregnancy and for 6 months thereafter. Children in the IFA and MMN groups received no supplementation, and these groups were collapsed into a single control group; children in the LNS group received 20 g LNS from 6 to 18 months. We measured physical activity with accelerometers over 1 week at 18 months. The main outcome was mean vector magnitude counts/15 s. Of the 728 children at the beginning of child intervention at 6 months, 570 (78 %) provided sufficient data for analysis. The mean accelerometer counts for the 190 children in the LNS group and for the 380 children in the control group were 303 (sd 59) and 301 (sd 56), respectively (P for difference=0·65). LNS, given to mothers during pregnancy and 6 months postpartum and to their infants from 6 to 18 months of age, did not increase physical activity among 18-month-old children.

Breast milk from women living near Lake Malawi is high in docosahexaenoic acid and arachidonic acid.

Adequate long-chain polyunsaturated fatty acid (LCPUFA) intake is critical during the fetal and infant periods. We quantified fatty acid content of breast milk (n=718) and plasma from six month old infants (n=412) in southern Malawi, and in usipa (n=3), a small dried fish from Lake Malawi. Compared to global norms, Malawian breast milk fatty acid content (% of total fatty acids) was well above average levels of arachidonic acid [ARA] (0.69% vs. 0.47%) and docosahexaenoic acid [DHA] (0.73% vs. 0.32%). Average Malawian infant plasma ARA (7.5%) and DHA (3.8%) levels were comparable to those reported in infants consuming breast milk with similar fatty acid content. The amounts (mg) of DHA, EPA and ARA provided by a 3 oz (85 g) portion of dried usipa (1439, 659 and 360, respectively) are considerably higher than those for dried salmon. Usipa may be an important source of LCPUFA for populations in this region.

Effect of 12-month intervention with lipid-based nutrient supplements on physical activity of 18-month-old Malawian children: a randomised, controlled trial.

BACKGROUND/OBJECTIVES: This study measured the effects of dietary supplementation with lipid-based nutrient supplements (LNSs) on 18-month-old children's physical activity. SUBJECTS/METHODS: In a randomised, controlled, outcome-assessor blinded trial 1932 six-month-old children from Malawi received one of five interventions daily from 6-18 months of age: 10-g milk-LNS, 20-g milk-LNS, 20-g non-milk-LNS, 40-g milk-LNS or 40-g non-milk-LNS, or received no intervention in the same period (control). The control group received delayed intervention with corn-soy blend from 18-30 months. Physical activity was measured over 1 week by ActiGraph GT3X+ accelerometer at 18 months. Main outcome was mean vector magnitude accelerometer counts/15 s. Analyses were restricted to children with valid accelerometer data on at least 4 days with minimum 6 h of wearing time per day. RESULTS: Of the 1435 children recruited to this substudy, 1053 provided sufficient data for analysis. The mean (s.d.) vector magnitude accelerometer counts in the total sample were 307 (64). The difference (95% CI) in mean accelerometer counts, compared with the control group, was 8 (-6 to 21, P=0.258) in 10-g milk-LNS, 3 (-11 to 17, P=0.715) in 20-g milk-LNS, 5 (-8 to 19, P=0.445) in 20-g non-milk-LNS, 10 (-3 to 23, P=0.148) in 40-g milk-LNS and 2 (-12 to 16, P=0.760) in 40-g non-milk-LNS groups. CONCLUSIONS: Provision of 10-40 g doses of LNS daily for 12 months did not increase physical activity of Malawian toddlers.

Effect of iron supplementation on cognition in Greek preschoolers.

OBJECTIVE: To examine effects of iron supplementation on vigilance, attention and conceptual learning in preschool children in Greece. DESIGN: Randomized Double-Blind Placebo Controlled trial of iron. Randomization stratified by iron status and day care center (DCC). SETTING: Nine public DCCs in Athens, Greece. SUBJECTS: In all, 49 3-4-y olds (21 anemic, 28 good iron status) with birth weight not less than 2500 g, currently healthy; benign past medical history, IQ > or =1 s.d. below the age-adjusted mean, serum Pb < or =200 ppb (none exceeded 50 ppb), and height, weight and head circumference for age > or =10th percentile. Anemia defined as: (1) pretreatment Hgb <112 g/l and TS <16% and ferritin <12 microg/L OR (2) Hgb rise of >10 g/l (T2-T0) with iron supplementation. Good iron status was defined as baseline levels of Hgb >120 g/l and either TS >20% or serum ferritin >12 microg/l. INTERVENTION: The intervention consisted of a 2-month supplementation of 15 mg iron (and MV) vs placebo (MV alone). RESULTS: After iron treatment, the anemic subjects made significantly fewer errors of commission (14% higher specificity, P<0.05), exhibited 8% higher accuracy (P<0.05) and were significantly more efficient (mean difference=1.09, P<0.05) than those given placebo. These effects of iron were not found among preschoolers with good iron status. No effects of iron treatment were found on the Oddity Learning task. CONCLUSIONS: This study demonstrated that iron supplementation of iron-deficient anemic preschoolers results in an improvement in discrimination, specifically selective attention.

Maternal and fetal stress are associated with impaired lactogenesis in humans.

Studies in animals indicate that various types of stressful stimuli can depress lactation, but there is much less information in humans. Experimental studies in breastfeeding women have shown that acute physical and mental stress can impair the milk ejection reflex by reducing the release of oxytocin during a feed. If this occurs repeatedly, it could reduce milk production by preventing full emptying of the breast at each feed. Prospective observational studies indicate that both maternal and fetal stress during labor and delivery (e.g., urgent Cesarean sections or long duration of labor in vaginal deliveries) are associated with delayed onset of lactation. The effects of chronic emotional stress on lactation are not known. Mothers who experience high levels of stress during and after childbirth should receive additional lactation guidance during the first week or two postpartum.

Iron supplementation of breast-fed Honduran and Swedish infants from 4 to 9 months of age.

OBJECTIVE: The objective was to study the effects of iron supplementation on hemoglobin and iron status in 2 different populations. STUDY DESIGN: In a randomized, placebo-controlled, masked clinical trial, we assigned term Swedish (n = 101) and Honduran (n = 131) infants to 3 groups at 4 months of age: (1) iron supplements, 1 mg/kg/d, from 4 to 9 months, (2) placebo, 4 to 6 months and iron, 6 to 9 months, and (3) placebo, 4 to 9 months. All infants were breast-fed exclusively to 6 months and partially to 9 months. RESULTS: From 4 to 6 months, the effect of iron (group 1 vs 2 + 3) was significant and similar in both populations for hemoglobin, ferritin, and zinc protoporphyrin. From 6 to 9 months, the effect (group 2 vs group 3) was significant and similar at both sites for all iron status variables except hemoglobin, for which there was a significant effect only in Honduras. In Honduras, the prevalence of iron deficiency anemia at 9 months was 29% in the placebo group and 9% in the supplemented groups. In Sweden, iron supplements caused no reduction in the already low prevalence of iron deficiency anemia at 9 months (<3%). CONCLUSION: Iron supplementation from 4 to 9 months or 6 to 9 months significantly reduced iron deficiency anemia in Honduran breast-fed infants. The unexpected hemoglobin response at 4 to 6 months in both populations suggests that regulation of hemoglobin synthesis is immature at this age.

Nutrition, growth, and complementary feeding of the breastfed infant.

Although additional research is needed on many of the issues discussed herein, the following conclusions are well substantiated by the evidence available to date: Breast milk alone can meet nutrient needs during the first 6 months, with the possible exception of vitamin D in certain populations and iron in infants of relatively low birth weight. Complementary foods offered before 6 months of age tend to displace breast milk and do not confer any growth advantage over exclusive breastfeeding. Breast milk continues to provide substantial amounts of key nutrients well beyond the first year of life, especially protein, fat, and most vitamins. Breastfed infants tend to gain less weight and usually are leaner than are formula-fed infants in the second half of infancy. This difference does not seem to be the result of nutritional deficits but rather infant self-regulation of energy intake. New growth charts based on infants breastfed throughout the first year of life are being developed by WHO. The nutrients most likely to be limiting in the diets of breastfed infants are minerals, such as iron, zinc, and calcium. Using the following guidelines can help to ensure that the nutrient needs of the breastfed child are met: Continue to breastfeed as often as the infant desires. Aim for a variety of complementary foods, with fruits, vegetables, and animal products (e.g., meat, fish, poultry, or egg) offered daily. Iron-fortified cereals and meats can provide adequate iron. Calcium can be obtained from cheese, yogurt, and other dairy products (although fresh cow's milk is not recommended before 12 mo). Avoid giving too much juice. Be alert to any signs that the child's appetite, growth, or development is impaired. When in doubt, a balanced vitamin-mineral supplement is advisable. Make mealtimes enjoyable.

Effects of exclusive breastfeeding for four versus six months on maternal nutritional status and infant motor development: results of two randomized trials in Honduras.

To examine whether the duration of exclusive breastfeeding affects maternal nutrition or infant motor development, we examined data from two studies in Honduras: the first with 141 infants of low-income primiparous women and the second with 119 term, low birth weight infants. In both studies, infants were exclusively breastfed for 4 mo and then randomly assigned to continue exclusive breastfeeding (EBF) until 6 mo or to receive high-quality, hygienic solid foods (SF) in addition to breast milk between 4 and 6 mo. Maternal weight loss between 4 and 6 mo was significantly greater in the exclusive breastfeeding group (EBF) group than in the group(s) given solid foods (SF) in study 1 (-0.7 +/- 1.5 versus -0.1 +/- 1.7 kg, P < 0.05) but not in study 2. The estimated average additional nutritional burden of continuing to exclusively breastfeed until 6 mo was small, representing only 0.1-6.0% of the recommended dietary allowance for energy, vitamin A, calcium and iron. Women in the EBF group were more likely to be amenorrheic at 6 mo than women in the SF group, which conserves nutrients such as iron. In both studies, few women (10-11%) were thin (body mass index <19 kg/m(2)), so the additional weight loss in the EBF group in study 1 was unlikely to have been detrimental. Infants in the EBF group crawled sooner (both studies) and were more likely to be walking by 12 mo (study 1) than infants in the SF group. Taken together with our previous findings, these results indicate that the advantages of exclusive breastfeeding during this interval appear to outweigh any potential disadvantages in this setting.

Exclusively breastfed, low birthweight term infants do not need supplemental water.

UNLABELLED: Breast milk intake, urine volume and urine-specific gravity (USG) of exclusively breastfed, low birthweight (LBW) term male infants in Honduras were measured during 8-h periods at 2 (n = 59) and 8 (n = 68) wk of age. Ambient temperature was 22-36 degrees C and relative humidity was 37-86%. Maximum USG ranged from 1.001 to 1.012, all within normal limits. CONCLUSIONS: We conclude that supplemental water is not required for exclusively breastfed, LBW term infants, even in hot conditions.

Predictors of growth from 1 to 18 months among breast-fed Ghanaian infants.

OBJECTIVE: To examine factors associated with the physical growth of breast-fed Ghanaian infants during the first 18 months of life. DESIGN: A community-based longitudinal study. SETTING: The study was carried out in Techiman, a district capital and major food trading center in the Brong Ahafo region of Ghana. SUBJECTS: One-month old infants (n=216) with birth weight >/= 2.5 kg were recruited from Maternal and Child Health Centers. METHOD: From 6 to 12 months, infants were provided with one of four types of nutritionally enhanced complementary foods. Anthropometric assessments were completed monthly from 1 to 12 months and every other month from 12 to 18 months. Information was collected on household characteristics, morbidity from common infections and dietary intakes. Blood samples were collected at 6 and 12 months to assess iron, zinc, riboflavin and vitamin A status. Multiple regression analysis was used to examine factors associated with growth during the age intervals of 1-6, 4-6, 6-12 and 12-18 months as well as size attained at 12 and 18 months. RESULTS: Prevalence of diarrhea and fever were negatively associated with growth during the first year of life. No significant relationship was found between respiratory illness (defined as cough or purulent nasal discharge) and growth. With the exception of dietary zinc intake, dietary variables were generally not significantly associated with growth. Maternal education was positively associated with growth during most of the age intervals. CONCLUSION: These findings suggest that interventions to reduce morbidity and improve the education of girls may benefit children's growth in this population. SPONSORSHIP: Nestle Foundation; Rockefeller Foundation African Dissertation Internship Award; Fulbright Scholarship. European Journal of Clinical Nutrition (2000) 54, 41-49

Predictors of micronutrient status among six- to twelve-month-old breast-fed Ghanaian infants.

This study describes the factors associated with hemoglobin and plasma ferritin, zinc and retinol concentrations and erythrocyte riboflavin status among 208 Ghanaian infants who participated in a complementary feeding intervention trial from 6 to 12 mo of age. Anthropometric, morbidity and dietary data were collected regularly from 1 to 12 mo; blood samples were collected at 6 and 12 mo. The prevalence of low micronutrient status at 6 and 12 mo, respectively, was as follows: hemoglobin <100 g/L, 30 and 34%; plasma ferritin <12 microg/L, 17 and 43%; plasma zinc <10.7 micromol/L, 4 and 6%; plasma retinol <0.7 micromol/L, 26 and 26%; erythrocyte riboflavin <200 umol/L of packed red cells, 14 and 10%. Multiple regression was used to identify factors significantly associated with micronutrient status. From 6 to 12 mo, fever prevalence was associated with a decrease in hemoglobin, but an increase in erythrocyte riboflavin concentrations, and diarrhea prevalence was related to a decrease in plasma retinol. Seasonal differences were evident for most of the indicators of micronutrient status, and elevated C-reactive protein levels (indicative of recent infection) were related to lower hemoglobin, retinol and zinc concentrations but higher ferritin and erythrocyte riboflavin concentrations. Weight at birth or at 1 mo of age was positively related to iron, zinc and vitamin A status, but a more rapid weight gain was associated with depletion of iron stores. Socioeconomic status was related to higher hemoglobin, riboflavin and zinc concentrations. The feeding of a micronutrient-fortified food was positively associated with plasma ferritin and retinol concentrations at 12 mo. These results suggest that prenatal factors, socioeconomic status, dietary intake and morbidity all influence infant micronutrient status, and that fortification of complementary foods is one potential avenue for preventing deficiencies.

Promoting exclusive breastfeeding for 4-6 months in Honduras: attitudes of mothers and barriers to compliance.

Prospective and retrospective data on maternal attitudes and obstacles to exclusive breastfeeding (EBF) were collected from Honduran mothers of low birthweight (1500-2500 g), term infants who were enrolled in an intervention study to compare infant outcomes in those who were randomly assigned to breastfeed exclusively for either 4 or 6 months. Perceived advantages of EBF were that it was easier, more practical and economical, and resulted in better infant health and growth. Disadvantages included the perceived time demand, concerns that the infant would accept solids less readily, and fears that breast milk alone was insufficient. The majority of study participants said that they would choose to exclusively breastfeed their next infant to 6 months. Although there were many obstacles to EBF, particularly in the first few weeks, women who persevered became enthusiastic proponents of EBF. Messages to promote EBF need to target the entire community, not just mothers, and should focus on addressing common misconceptions and alerting women to potential problems before they occur.

A randomized, community-based trial of the effects of improved, centrally processed complementary foods on growth and micronutrient status of Ghanaian infants from 6 to 12 mo of age.

BACKGROUND: Koko, a fermented maize porridge used as the primary complementary food in Ghana, has been implicated in the high prevalence of child malnutrition. Weanimix, a cereal-legume blend developed by the United Nations Children's Fund and the Ghanaian government, has been promoted as an alternative. OBJECTIVE: We evaluated the effect of feeding Weanimix and 3 other locally formulated, centrally processed complementary foods on the nutritional status of 208 breast-fed infants. DESIGN: Infants were randomly assigned to receive 1 of 4 foods from 6 to 12 mo of age: Weanimix (W), Weanimix plus vitamins and minerals (WM), Weanimix plus fish powder (WF), and koko plus fish powder (KF). Dietary and anthropometric data were collected regularly. Blood was collected at 6 and 12 mo of age to assess iron, zinc, vitamin A, and riboflavin status. Before and after the intervention, cross-sectional data on the anthropometric status of infants not included in the intervention (NI; n = 464) were collected. RESULTS: There were no significant differences between intervention groups in weight or length gain or in hemoglobin, hematocrit, transferrin saturation, plasma zinc, or erythrocyte riboflavin values between 6 and 12 mo of age. From 9 to 12 mo of age, z scores were lower in NI infants than in the combined intervention groups [at 12 mo: -1.71 +/- 0.90 compared with -1.19 +/- 0.93 for weight and -1.27 +/- 1.02 compared with -0.63 +/- 0.84 for length (P < 0.001 for both), respectively]. The percentage of infants with low ferritin values increased significantly between 6 and 12 mo of age in groups W, WF, and KF but not in group WM. Change in plasma retinol between 6 and 12 mo of age was significantly greater in group WM than in the other 3 groups combined (0.14 +/- 0.3 compared with -0.04 +/- 0.3 micromol/L, P = 0. 003). CONCLUSIONS: All 4 foods improved growth relative to the NI group. Infants fed WM had better iron stores and vitamin A status than those fed nonfortified foods.