Low weight/length ratio at birth is associated with hospitalizations during the first year of life: a cohort studyAbstract
The aim is to study the association of a low birth weight/length ratio (W/L) with the risk of hospitalizations during the first year of life (YOL). Cohort study of live births from Ribeirão Preto, Brazil in 2010 and 2011. Low W/L was defined as below the 3rd percentile for gestational age (GA) and sex according to the Intergrowth 21st. Single and multiple Cox proportional hazards models were modelled. 4,087 children were included, of which 741 (18.1%) had been hospitalized at least once during the first YOL. In the univariate analysis, the factors associated with increased risk of the outcome were: low W/L, inadequate prenatal care, maternal hypertension, black skin color, and using the public health system. In the multivariate analysis, a low birth W/L was associated with greater risk of all hospitalizations [adjusted hazard ratio (aHR) 2.67, 95% confidence interval [95%CI] 1.98, 3.60], but this association disappeared when we excluded neonatal hospitalizations (aHR 1.58, 95%CI 0.98, 2.54). A low birth W/L for GA and sex was not associated with an increased risk of hospitalizations during the first YOL beyond the neonatal period in a Brazilian cohort of live births.
Key words:
Weight/length ratio; Anthropometry; Hospitalization; Morbidity; Birth cohort
Resumo
O objetivo é estudar a associação de uma razão peso/comprimento (P/C) baixa ao nascer com o risco de hospitalizações durante o primeiro ano de vida (PAV). Estudo de coorte de nascidos vivos em Ribeirão Preto, Brasil em 2010 e 2011. P/C baixa foi definida como abaixo do 3º percentil para idade gestacional (IG) e sexo de acordo com Intergrowth 21st. Modelos de riscos proporcionais de Cox simples e múltiplos foram usados. 4.087 crianças foram incluídas (51,5% da coorte original), das quais 741 (18,1%) foram hospitalizadas pelo menos uma vez durante o PAV. Na análise univariável, os fatores associados a maior risco do desfecho foram: P/C baixa, pré-natal inadequado, hipertensão materna, cor da pele negra e usar o sistema público de saúde. Na análise multivariável, a P/C baixa ao nascer foi associada a maior risco de hospitalizações [hazard ratio ajustada (HRa) 2,67; intervalo de confiança de 95% (IC95%) 1,98; 3,60], mas esta associação desapareceu quando excluímos as hospitalizações neonatais (HRa 1,58; IC95% 0,98; 2,54). A razão P/C ao nascer baixa para IG e sexo não foi associada a maior risco de hospitalizações durante o PAV além do período neonatal em uma coorte de nascidos vivos brasileiros.
Palavras-chave:
Razão peso/comprimento; Antropometria; Hospitalização; Morbidade; Coorte de nascimento
Resumen
El objetivo es estudiar la asociación de una relación peso/talla (P/T) baja al nacer con el riesgo de hospitalizaciones durante el primer año de vida (PAV). Estudio de cohorte de nacidos vivos en Ribeirão Preto, Brasil, en 2010 y 2011. P/T bajo se definió como debajo del percentil 3 para la edad gestacional (EG) y el sexo según Intergrowth 21st. Se utilizaron modelos de riesgos proporcionales de Cox simples y múltiples. Se incluyeron 4.087 niños (51,5% de la cohorte original), de los cuales 741 (18,1%) fueron hospitalizados al menos una vez durante la NAV. En el análisis univariable, los factores asociados con mayor riesgo del resultado fueron: relación P/T baja, atención prenatal inadecuada, hipertensión materna, color de piel negro y uso del sistema de salud público. En el análisis multivariable, la relación P/T se asoció con un mayor riesgo de hospitalizaciones [índice de riesgo ajustado (IRa) 2,67; intervalo de confianza del 95% (IC95%) 1,98; 3,60], pero esta asociación desapareció cuando excluimos las hospitalizaciones neonatales (IRa 1,58; IC95% 0,98; 2,54). La baja relación P/T al nacer para EG y sexo no se asoció con un mayor riesgo de hospitalizaciones durante el PAV más allá del período neonatal en una cohorte de nacidos vivos brasileños.
Palabras clave:
Relación peso/talla; Antropometría; Hospitalización; Morbilidad; Cohorte de nacimiento
Introduction
In Brazil, in 2021 and 2022, almost four million children and adolescents younger than 19 years were hospitalized1. Among these, more than one million were younger than one year. In this group, the main causes for hospitalization include perinatal morbidity (56%), infectious diseases (12%), and respiratory diseases (12%). Early childhood illnesses are, at least in part, associated with perinatal conditions. Exposure to adverse perinatal conditions increase the risk of hospitalizations within the first year of life2. Moreover, the risk of hospitalization in children younger than five years increases with male gender, low-income families, order of birth, tobacco exposure, living in rural areas, short duration of breastfeeding, malnutrition, maternal age, low maternal education level, higher household density, low birth weight (LBW), and prematurity2,3.
Oliveira and Barbieri4 studied the effects of perinatal factors on health outcomes in a Brazilian birth cohort. They found that, among others, gestational age (GA) and LBW (<2,500 g) were associated with greater risks of hospitalizations during the first year of life. In the absence of other Brazilian studies, similar findings were reported in a large German birth cohort (2007-2013), in which very low birth weight (VLBW, <1,500 g) and LBW (1,500-2,500 g) were associated with higher risks of hospitalizations during the first year of life after the perinatal period5. In a Swedish birth cohort (1973-1994), birth weight was strongly associated with overall health (all-cause and cause-specific hospitalizations and sickness absences) during infancy, after which it weakens throughout childhood and adolescence, and increases again in adulthood6.
However, LBW is often a proxy for prematurity and/or intrauterine growth restriction (IUGR), not necessarily a cause of morbidity per se. This is important because birth weight alone does not accurately reflect the newborn body composition and has been criticized because the cut-off of <2,500 g is the same across all GAs7.
In this regard, Villar et al.8 studied the accuracy of three anthropometric ratios commonly used to estimate body composition in newborns: weight/length ratio (W/L, kg/m), body-mass index (BMI, kg/m²), and ponderal index (PI, kg/m³). They showed that W/L by GA was a better predictor of fat mass (FM) and fat-free mass (FFM) than BMI or PI, independently of sex, GA, and timing of measurement8. However, to the best of our knowledge, there is no study investigating the association of low birth W/L and hospitalizations during the first year of life. Therefore, this study aimed at investigating whether a low W/L at birth (<3rd percentile for sex and GA) is independently associated with hospitalizations during the first year of life in a Brazilian birth cohort.
Patients and methods
This is a retrospective analysis of prospectively collected data from a cohort study of all births from two Brazilian cities (Brazilian Ribeirão Preto and São Luís Birth Cohort Studies - BRISA)9,10. For this study, only children born at Ribeirão Preto were eligible. The cohort study was approved by the institutional review board (IRB) (#11157/2008 and #4250/2016) and was conducted according to the Brazilian regulations on medical research. For this analysis, the need for signed informed consent was waived by the IRB. This study followed the STROBE recommendations11.
Briefly, part of the mothers started being followed-up during pregnancy (prenatal cohort, one visit with 5 months of gestation), while most entered the study upon delivery (birth cohort). Data collection took from January 2010 to June 2011. Ribeirão Preto is in the countryside of São Paulo state, Brazil, and has a human development index of 0.8, higher than most of the country. Participants were recruited in all maternities, public and private. The mothers were interviewed by trained researchers a few hours after delivery, given they consented and were able to answer the questions, which comprised: demographics, general and reproductive health, past conditions, habits, pregnancy course, prenatal care, delivery, and the newborn. Anthropometric measurements of the newborn were collected from medical charts.
After inclusion and the assessment at birth, all mothers/children were invited to a follow-up visit after their first birthday, which occurred between 2011 and 2013. Trained researchers collected information on mental health, habits, contraception, feeding, general health of the children, among others. The children underwent blood draw, oral health assessment, and anthropometric measurements.
Variables
The main outcome was the answer to the question: “Was the child admitted to a hospital anytime since birth up to their first birthday?”. They could answer yes, no, or do not know. A second question was used to determine if hospitalizations occurred in the neonatal period or after: “If yes, how old was the child on their first hospitalization?”
The independent variables were maternal factors (age, skin color, years of education, marital status), gestational factors (prenatal care, GA, delivery type, type of health system, and smoking, diabetes, and hypertension during pregnancy), and newborn factors (sex, W/L, 5th-minute Apgar score <7).
GA was determined from the date of the last menstrual period before pregnancy and the first ultrasound exam. GA was estimated primarily from the date of the last menstrual period, unless it differed by more than 7% from the GA estimated by the ultrasound, in which case the latter was considered12. Prenatal care was analyzed as adequate (at least six appointments) or inadequate. W/L was categorized as low when below the 3rd percentile for GA and sex according to the Intergrowth 21st reference13.
Statistical analysis
Bivariate comparisons were made using Student’s t test, Mann-Whitney’s U test, or Fisher’s exact test, as appropriate. Cox proportional hazards models were used to investigate the association of low W/L and hospital admissions in the first year of life. Crude and adjusted hazard ratios (HR) were calculated along with their corresponding 95% confidence intervals (95%CI). The variables used in model adjustment were selected with the help of the DAGitty tool (http://www.dagitty.net). Significance was set at 5%. Stata SE 14.0 (StataCorp, USA) was used.
Results
Among the 8,342 births in the database, stillbirths (n=42), children who died within the first year of life (n=68), and twins (n=188) were not included. The final database contained 8,044 eligible infants. Among these, 4,126 (51.5%) attended to the follow-up visit, but 39 had missing data. There were 741 children (18.1%) who had been hospitalized at least once during the first year of life (Figure 1).
Flowchart of participant selection from the BRISA cohort database (Ribeirão Preto-SP, Brazil, 2010).
The mothers were usually young adults (20-34 years-old), mostly white, married or in stable relationships, and with 9-11 years of education. The mothers of children who were hospitalized were significantly younger, more frequently non-white, had a higher prevalence of hypertension during pregnancy (Table 1). Almost all mothers received adequate prenatal care, mostly in the Brazilian public health system (SUS), but more than a half underwent a cesarean delivery (Table 2). The mothers of children who were hospitalized were less likely to have received adequate prenatal care, and used the public health system more frequently.
Hospitalized children were mostly boys, with lower GA and 1st and 5th-minute Apgar scores, more frequently born preterm and with a low 5th-minute Apgar scores (<7), had lower birth weight, length, head circumference, and W/L ratio (Table 3). The proportion of children with a low birth W/L was higher in children who were hospitalized (7.7% vs. 2.2%).
For our main objective, Table 4 presents the variables associated with hospitalization during the first year of life, including or not hospitalizations at birth in a neonatal intensive care unit (NICU). In the univariate analysis, several factors were associated with increased risk of the outcome: low W/L, inadequate prenatal care, hypertension during pregnancy, black skin colors, and using the public health system. When we excluded neonatal hospitalizations in a NICU, the results were similar, adding low socioeconomic level (classes D/E) and less than 12 years of education. However, in the multivariate analysis, after adjusting for the other independent variables, a low birth W/L was associated with greater risk of all hospitalizations (aHR 2.67, 95%CI 1.98; 3.60), but this association disappeared when we excluded neonatal hospitalizations (aHR 1.58, 95%CI 0.98; 2.54). The only variable independently associated with greater hazard of hospitalization beyond the neonatal period was hypertension during pregnancy (aHR 1.32, 95%CI 1.05; 1.66).
Discussion
In this study, in a large Brazilian cohort of live births, we showed that a low birth W/L was associated with an increased risk of hospitalizations during the first year of life, but not beyond the neonatal period, even after adjustment for prenatal care, maternal hypertension, skin color, socioeconomic level, educational status, and using the public health system.
Rüdiger et al, in a very large German birth cohort, showed that children born with VLBW (<1,500 g) had a 3.9-fold higher risk of hospitalization - with a distinct morbidity pattern - during their first years of life, compared to normal birth weight infants, even after adjusting for sex, area of living, and the presence of previous perinatal hospitalization5. In that study, the cumulative hospitalization was 72% for VLBW, 39% for LBW, and 22% for normal birth weight infants, which is similar to our data (71.4% for VLBW, 29.9% for LBW, and 16.9% for normal birth weight infants).
In the study by Helgertz and Nilsson6, in Sweden, the association between LBW and all-cause and cause-specific hospitalizations and sickness absence was strong during infancy, weakened during childhood and adolescence, and increased again in adulthood. The authors also demonstrated that the effect of birth weight on hospitalizations is stronger among children of less educated mothers, which is consistent with our findings.
In the study by Oliveira and Barbieri4, which analyzed the same database as we did, the independent risk factors for hospitalization in the first year of life were maternal hypertension during pregnancy, use of the public health system, preterm birth (<37 weeks), male sex, LBW (<2,500 g), and 5th-minute Apgar score <74. However, similarly to our findings, the association of LBW and hospitalizations was only significant up to 30 days of life.
In all these previous studies, the proxy for suboptimal fetal growth was LBW, which can be misleading. The cut-off of 2,500 g was established in the beginning of the 20th century, when GA calculation was not routine, and the definition of preterm birth was based on weight, length, and morphological features of the newborn7. Because the same cut-off is inappropriately applied over all GAs, we hypothesized that a variable that could be adjusted for GA and sex and that better reflected the newborn body composition, that is, the W/L ratio, could be more strongly associated with the outcome of hospitalizations during the first year of life, which, in fact, occurred. The relative risks reported by Oliveira & Barbieri for LBW were 1.58 (95%CI 1.27; 1.96) and 1.46 (95%CI 1.17; 1.82), lower than the HR what we found, 2.67 (95%CI 1.98; 3.60).4 Another reason to abandon LBW as a predictor for infant morbidity is the so-called epidemiologic paradox of LBW: countries and regions with higher levels of socioeconomic development and lower infant mortality rates have been consistently reporting higher LBW rates14. The explanations for the paradox include underreporting of live births in less developed regions and the availability of perinatal care services over underlying social conditions.
For older children, WHO adopts BMI over body weight because the former is a better surrogate for adiposity15. However, Villar et al.8 demonstrated that, for newborns, W/L for age reflects neonatal body composition, in terms of lean mass, fat mass, and fat percentage, better than BMI for age. The association between a low birth W/L and perinatal morbidity is not new. In 1997, Williams et al published a study involving newborns ≤34 weeks of GA, in which a low birth W/L was associated with poorer perinatal outcomes, including death. This association was stronger than that of SGA16. In the following year, the same authors reported that a low birth W/L, as a surrogate for asymmetrical intrauterine growth, was best associated with poorer neonatal outcomes (cerebral palsy and death), even after adjusting for preterm and twin birth17.
The explanation for a greater association of W/L with perinatal morbidity is that LBW alone is not the causative factor5. In fact, it has been replaced by measures of birth weight adequacy: small (SGA), adequate (AGA), and large (LGA) for GA. SGA newborns have higher morbidity when compared to AGA newborns, even if they weight >2,500 g at birth7. Therefore, using the adequacy of birth weight for GA seems more reliable than birth weight alone in predicting risk of morbidity and mortality18. Currently, the gold standard for classification of anthropometric indices at birth are the Intergrowth 21st standards because Villar et al.8 showed that W/L better estimates neonatal body composition than BMI. However, our results showed that being born with a low W/L, that is, being wasted, does not seem to increase morbidity in the first year of life beyond the neonatal period. This is different from what was shown in the studies by Rüdiger and Helgertz5,6. Possible explanations for this discrepancy are that the W/L ratio is a more specific measure of wasting, while the LBW criterion (<2,500 g at any GA) probably incorporate other prenatal exposures and intrinsic patient factors, such as preterm birth, IURG, congenital malformations, among others, which can be more strongly associated with infancy and childhood morbidity than wasting alone.
This study has many limitations. First, not all infants in the birth cohort were included in the analysis, only those attending to the follow-up visit. However, there were no differences between those included or not regarding birth characteristics, but small differences in maternal factors. Briefly, non-participant mothers were more frequently younger than 20 years, had ≤8 or ≥12 years of education, were from social classes A/B or D/E, were smokers, received less prenatal care, and underwent cesarean deliveries in the private health system. All these differences, although statistically significant, given the large sample size, are of little magnitude. Second, the information on hospital admissions was retrospective and, therefore, can be memory biased.
Conclusion
A low birth W/L for GA and sex was associated with an increased risk of hospitalizations during the first year of life, but not beyond the neonatal period in a Brazilian cohort of live births.
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