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.

Nutrition survey in Tabasco, Mexico: nutritional status of preschool children.

Nutritional status of 149 preschool children was evaluated using anthropometric, biochemical, and dietary measures. Stool samples were collected from 111 children for analysis of gastrointestinal parasites. Sixty-eight percent of the children were below the 3rd percentile of height-for-age, using Mexican reference data, but only 15% were below the 10th percentile of weight-for-height. The percentage of children with low biochemical values was: Hb, 14% less than 11 g/100 ml; hematocrit, 16% less than 34%; vitamin A, 36% less than 20 micrograms/100 ml; ascorbic acid, 47% less than 0.2 mg/100 ml; and riboflavin, 47% with EGR-AC greater than or equal to 1.35. None of the subjects had levels of serum albumin less than 3.5 g/100 ml. The average dietary intake was less than two-thirds of the Mexican Recommended Dietary Allowances for vitamin A, niacin, iron, calcium, and riboflavin. Energy and protein intake averaged 81 and 99% of the Recommended Dietary Allowances, respectively. Girls had significantly poorer growth and dietary intake than boys. Gastrointestinal parasites were detected in 75% of the stool samples, but no negative relationship between nutritional status and infection with the most common species (Ascaris, Trichuris, and Strongyloides) was found. Children were significantly thinner in the summer when diarrhea was most prevalent.

Nutrition survey in Tabasco, Mexico: patterns of infant feeding.

Information on infant feeding was collected from 149 mothers of 744 children born over a period of 25 yr in an area of Tabasco, Mexico which has experienced rapid economic development. From 1953 to 1978, there was an increase in bottle-feeding, primarily as a supplement to breast-feeding, while the proportion of infants exclusively breast-fed declined from 69 to 48%. This trend was accompanied by a decrease in the average duration of lactation: the percentage of infants breast-fed 12 months or more declined from 73 to 45%. Mothers living within the area of an agricultural development project completed in 1973 were more likely to bottle-feed than mothers outside the project. The consequences of supplemental bottle-feeding for continued lactation, infant health, and child spacing require further investigation.

Cross-cultural patterns of growth and nutritional status of breast-fed infants.

Growth patterns and iron status of infants who were breast-fed throughout their first year of life were examined in four populations: 1) a group of high socioeconomic status in California (the DARLING Study), 2) infants of normal birth weight (NBW) but from low-income families in Honduras, 3) low-birth-weight (LBW), full-term infants in Honduras, and 4) infants in Ghana. z Scores were calculated by using both the current National Center for Health Statistics reference data and a pooled data set based on breast-fed infants in six industrialized countries. The NBW infants in Honduras showed rapid growth in the first few months and were similar in weight-for-age to the DARLING infants until approximately 9 mo. By contrast, the LBW infants remained far below the other cohorts throughout the first 12 mo, despite an initial period of catch-up growth. In the Ghanaian infants, weight-for-age faltered beginning at 3-4 mo, but length-for-age did not falter until after 9 mo. Weight-for-length was highest in the NBW Honduran infants and lowest in the Ghanaian infants. When z scores were adjusted for birth weight and maternal height, no significant faltering was evident in either weight or length in any of the cohorts during the first 12 mo. Thus, when breast-feeding is continued during the first year of life and efforts are made to ensure adequate complementary feeding after 6 mo, if growth faltering occurs it is probably attributable to prenatal factors and maternal stature. Population differences in iron status reflected variation in birth weight and in the use of iron-rich foods. Therefore, efforts to prevent child stunting and malnutrition must pay attention to prenatal as well as postnatal factors.

Effects of dieting and physical activity on pregnancy and lactation.

Concerns regarding weight control and fitness during the reproductive years have prompted questions about dieting and physical activity among pregnant and lactating women. Dieting to lose weight is never recommended during pregnancy, even among obese women. Once lactation is established, moderate energy restriction to achieve a weight loss of < or = 2 kg/mo is probably safe for women who are overweight initially. There are several potential risks and benefits of exercise during pregnancy and lactation. The data available indicate that moderate aerobic exercise is safe and beneficial for most women, if appropriate guidelines are followed.

Delayed clamping of the umbilical cord improves hematologic status of Guatemalan infants at 2 mo of age.

Iron deficiency anemia is a serious health problem that affects the physical and cognitive development of children. Therefore, it is important to develop cost-effective interventions to improve the hematologic status of the millions of children affected by this condition worldwide. We studied 69 Guatemalan infants who had been randomly assigned to one of three groups at the time of delivery: 1) cord clamping immediately after delivery (n = 21); 2) clamping when the cord stopped pulsating, with the infant placed at the level of the placenta (n = 26); or 3) clamping when the cord stopped pulsating, with the newborn placed below the level of the placenta (n = 22). Maternal and infant hematologic assessments were performed at the time of delivery and 2 mo postpartum. At baseline the groups had similar socioeconomic, demographic, and biomedical characteristics and the newborns had similar hematocrit status. Two months after delivery, infants in the two groups with delayed cord clamping had significantly higher hematocrit values and hemoglobin concentrations than did those in the early-clamping group. The percentage with hematocrit values < 0.33 was 88% in the control group compared with 42% in group 2 and 55% in group 3 (P = 0.01). These results suggest that waiting until the umbilical cord stops pulsating (approximately 1 min after delivery) is a feasible low-cost intervention that can reduce anemia in infants in developing countries.

Lactation performance of exercising women.

To determine whether vigorous exercise affects lactation performance, we compared well-nourished exercising (n = 8) and sedentary (n = 8) women whose infants were 9-24 wk old and exclusively breast-fed. Measurements included resting metabolic rate (RMR); maximum oxygen consumption (VO2max); plasma prolactin, cortisol, insulin, and T3; and body composition. Each subject completed a 3-d record of dietary intake, physical activity, and milk volume (by test weighing) and collected 24-h milk samples. Exercising women differed significantly from control subjects in VO2max (46.4 vs 30.3 mL.kg-1.min-1), percent body fat (21.7 vs 27.9%), total energy expenditure (3169 vs 2398 kcal/d), and energy intake (2739 vs 2051 kcal/d). There was no difference between the groups in plasma hormones or milk energy, lipid, protein, or lactose content. Exercising subjects tended to have higher milk volume (839 vs 776 g/d) and energy output in milk (538 vs 494 kcal/d). Thus, there was no apparent adverse effect of vigorous exercise on lactation performance.

Postprandial changes in the content and composition of nonprotein nitrogen in human milk.

The effect of a meal on human milk (HM) total nitrogen (TN) and nonprotein nitrogen (NPN) content and composition was examined. Two studies were performed in which milk and blood samples were collected 2-3 h after subjects consumed either a test breakfast or lunch. To monitor the rate of transfer of plasma urea into milk, two women were given [15N]2-urea with the meal. Milk TN concentrations were not significantly different from premeal values. However, concentrations of milk NPN, urea nitrogen, and alanine were increased by greater than or equal to 20% over premeal values. [15N]2-Urea appeared in plasma and milk within 15 min and reached maximum enrichments of 10% and 5.5% in plasma and milk, respectively. Several HM NPN components increase in concentration postprandially; however, these concentrations were not always correlated with changes in plasma concentrations, suggesting that milk NPN may also reflect metabolic activities within the mammary gland.

Maternal weight-loss patterns during prolonged lactation.

Weight and triceps-skinfold thickness were measured until 24 mo postpartum in matched cohorts of women who breast-fed for > or = 12 mo (BF; n = 46) or < or = 3 mo (FF; n = 39). In the BF group, breast-feeding frequency and breast-milk energy output were determined every 3 mo until 18 mo. Weight loss from 1 to 12 mo postpartum was significantly greater in BF than in FF women (4.4 vs 2.4 kg, P < 0.05), due primarily to differences in weight loss from 3 to 6 mo. BF mothers had a net loss in triceps-skinfold thickness whereas FF mothers gained fat at this site (-0.4 vs 2.4 mm, P < 0.05). Breast-feeding frequency and total time breast-feeding were related to weight loss in the BF group from 6 to 12 mo. Maternal weight did not differ significantly between 12 and 24 mo in either group. We conclude that lactation enhances weight loss postpartum if breast-feeding continues for at least 6 mo.

Coffee consumption as a factor in iron deficiency anemia among pregnant women and their infants in Costa Rica.

The influence of coffee consumption on hematological and trace element status was studied in two groups of pregnant, low-income Costa Rican women: coffee drinkers (greater than or equal to 450 mL/d, n = 22) and coffee nondrinkers (0 mL/d, n = 26). Groups had similar income, education, prenatal care, age, parity, weight, height, pregnancy weight gain, prenatal iron supplementation, energy, protein, Fe, and vitamin C intake and infant sex and gestational age. Maternal hemoglobin (Hb) and hematocrit (Hct) at 8 mo gestation, cord blood Hb and Hct, infant birth weight and Hb and Hct at 1 mo of age, and breast-milk Fe concentration were significantly lower in the coffee group than in the noncoffee group. The association of coffee with infant Hb and Hct was independent of maternal Fe status and birth weight. These results are consistent with our previously reported data in rats and indicate that maternal coffee intake may contribute to maternal and infant anemia.

Stress during labor and delivery and early lactation performance.

The amount of stress experienced by both the mother and fetus during labor and delivery varies considerably and is likely to be different in primiparous and multiparous women. In this study we explored relations between the birth experience and lactation performance of 40 women. Stress hormones were measured in serum or plasma during pregnancy, parturition (cord and maternal blood), and lactation. Milk samples were obtained and breast-feeding frequency was recorded each day during the first 2 wk postpartum. Four outcomes were used as markers of lactogenesis: the time when the subject first felt fullness in the breasts, 24-h milk volume on day 5 postpartum, milk lactose concentration on day 5, and the day of appearance of casein in the milk as determined by gel electrophoresis. There were significant intercorrelations among the outcome variables, except for milk lactose. Compared with multiparous women, primiparous mothers experienced a delay in breast fullness and lower milk volume on day 5. In multiple regression analyses excluding subjects who had cesarean deliveries (n = 5), markers of both fetal and maternal stress during labor and delivery (cord glucose concentration and maternal exhaustion score) were associated with delayed breast fullness and casein appearance; delayed casein appearance was also associated independently with a longer duration of labor. Milk volume on day 5 was lower in women with higher exhaustion scores, and, in multiparous women, those who breast-fed less frequently on day 2. The milk lactose concentration was inversely related to pregnancy weight gain. These results indicate that primiparity, long labor, stress to the mother and fetus during labor and delivery, and elevated cord glucose concentrations are risk factors for delayed lactogenesis.

Breast milk composition: fat content and fatty acid composition in vegetarians and non-vegetarians.

Milk from vegetarians contained a lower proportion of fatty acids derived from animal fat and a higher proportion of polyunsaturated fatty acids derived from dietary vegetable fat. No significant differences were observed between dietary groups in percent fat in the milk or in proportions of fatty acids synthesized de novo in the mammary gland. Among women consuming less than 35 g animal fat per day, percent milk fat was significantly correlated with animal fat intake. Among women consuming greater than 35 g animal fat, percent fat in milk was positively correlated with percent of C10:0, C12:0, and C18:3 and negatively correlated with percent of C16:0 and C18:0 in the milk fat. These findings suggest that there is a maximum amount of C16:0 and C18:0 that can be taken up from the blood and subsequently secreted into the milk.

Determinants of energy, protein, lipid, and lactose concentrations in human milk during the first 12 mo of lactation: the DARLING Study.

Factors associated with concentrations of energy-yielding nutrients in human milk were examined at 3, 6, 9, and 12 mo postpartum in the DARLING (Davis Area Research on Lactation, Infant Nutrition and Growth) Study. Samples were obtained by complete expression of alternate breasts over 24 h. Milk energy density was highly correlated with lipid concentration; both were positively related to maternal percent of ideal body weight (%IBW) at 6, 9, and 12 mo and negatively related to milk volume at 3 mo and to parity at 12 mo. Milk protein concentration was negatively related to milk volume at 6 and 9 mo and positively related to nursing frequency at 6 mo and %IBW at 9 mo. Milk lactose concentration was positively related to milk volume at 6 and 9 mo and to continued amenorrhea at 9 mo. In a subsample who completed dietary records, protein intake was positively associated with lipid concentration after 16 wk postpartum but not before. These findings suggest that milk composition is more sensitive to maternal factors such as body composition, diet, and parity during later lactation than during the first few months.

Energy and protein intakes of breast-fed and formula-fed infants during the first year of life and their association with growth velocity: the DARLING Study.

Intake and growth were compared between matched cohorts of infants either breast-fed (BF) or formula-fed (FF) until > or = 12 mo of age. Total energy intake at 3, 6, 9, and 12 mo averaged 0.36, 0.34, 0.35, and 0.38 MJ.kg-1.d-1 (85.9, 80.1, 83.6, and 89.8 kcal.kg-1.d-1) among BF infants vs 0.41, 0.40, 0.39, and 0.41 MJ.kg-1.d-1 (98.7, 94.7, 93.6, and 98.0 kcal.kg-1.d-1) among FF infants, respectively. Protein intake was 66-70% higher in the FF than in the BF group during the first 6 mo. Differences in energy and protein intakes were significant at 3, 6, and 9 mo. Gains in weight and lean body mass were lower in BF than in FF infants from 3 to 9 mo. BF infants gained more weight and lean body mass per gram protein intake but not per megajoule intake. Although growth differences between groups were related to differences in intake, there is no evidence of any functional advantage to the more rapid growth of FF infants.

Breast-fed infants are leaner than formula-fed infants at 1 y of age: the DARLING study.

Anthropometric indexes from 1 to 24 mo were compared between matched cohorts of infants either breast-fed (BF, n = 46) or formula-fed (FF, n = 41) until > or = 12 mo. Neither group received solid foods before 4 mo. Weight-for-length was significantly greater among FF infants from 7 to 24 mo. In both groups, skinfold thickness (triceps, biceps, subscapular, flank, and quadriceps) and estimated percent body fat (%FAT) increased rapidly during the first 6-8 mo and declined thereafter. At all sites except biceps, FF infants had larger skinfold thicknesses in later infancy (particularly 9-15 mo) than did BF infants; %FAT was significantly higher from 5 to 24 mo. Lower energy intake among BF infants explained the difference between groups. Maternal and infant fatness were positively correlated at 12-24 mo. Breast-milk lipid and energy concentration were unrelated to infant fatness. These results indicate that infants BF for > or = 12 mo are leaner than their FF counterparts.

Between-day and within-day variability in the relation between heart rate and oxygen consumption: effect on the estimation of energy expenditure by heart-rate monitoring.

Estimation of energy expenditure (EE) by heart-rate (HR) monitoring (HRM) assumes that the relation between HR and oxygen consumption (VO2) is stable between days and within a day. To evaluate this assumption, 12 healthy subjects underwent an HR-VO2 calibration session on two mornings and two afternoons, with one morning and one afternoon session on the same day. Measurements were made while subjects were supine, sitting, standing while shifting body weight side-to-side, and walking at four intensities. Subjects wore an HR monitor during waking hours on another day (15.1 +/- 1.5 h). Regression analysis was used to determine the relation between HR and VO2 in the sedentary and active HR ranges, and four EE values (HRM-EE) based on the four calibration sessions were calculated for each subject. The four group mean HRM-EE values were nearly identical (CV: 1.1%). The regression equations generated from the four calibration sessions did not differ significantly for the group as a whole, but for some subjects there were significant differences among sessions in the slope of the active regression equation (P = 0.005). Intraindividual CVs for HRM-EE were generally < 10%, but ranged from 0.1% to 24.7%. In general, within an individual, HR was more variable than was VO2, and intraindividual variability in EE was associated with intraindividual variability in the flex HR and sedentary HR range. HRM is appropriate for assessment of EE for a group; however, caution is recommended when HRM is used for individual determinations of EE.