The first 1,000 days of life, encompassing the period from conception to a child’s second birthday, is recognized as a window of opportunity for early interventions and, simultaneously, a phase of vulnerability for child growth and development [1,2]. This period is characterized by significant brain plasticity [3,4] and is highly susceptible to environmental influences that affect health and disease trajectories both in the short and long term [5,6].

This phase is critical for all newborns, especially for preterm infants, who are considered a high-risk population for developing neurocognitive, behavioral, and motor impairments [7]. Additionally, prematurity may lead to clinical and feeding complications, high rates of hospitalization, and significant healthcare costs [8,9]. The challenges associated with preterm birth demand early intervention approaches and multidisciplinary support [10].

It is estimated that 1 in 10 infants is born before 37 weeks of pregnancy. In 2020 alone, more than 13 million Preterm Newborns (PTNBs) were born worldwide. Complications from prematurity are the leading causes of death among children under five years old [11].

In Brazil, prematurity is a significant public health issue. Data from the Sistema de Informações sobre Nascidos Vivos (SINASC, Live Birth Information System) indicates that approximately 11% of births in the country are preterm [12]. This high rate is associated with factors such as socioeconomic conditions and unequal access to prenatal care. Furthermore, complications related to prematurity are among the primary causes of neonatal morbidity and mortality in Brazil [13].

Supporting these findings, the 2023 World Health Organization report highlights that this number of preterm births remains a major challenge and has not significantly declined for several decades. Affecting multiple countries, it deserves greater attention on the global health agenda. The authors argue that, for countries to achieve Sustainable Development Goal 3 – ending preventable neonatal deaths and enhancing human capital throughout the life course – urgent action is required to prevent preterm births and improve the quality of care for preterm infants [9].

Improving care quality requires understanding the various factors influencing this process, including nutrition – a particularly challenging aspect because of the complexity and heterogeneity of preterm births and their impact on a child’s metabolic programming [14].

To date, no studies have been identified that elucidate the nutritional characteristics of PTNBs during the first 1,000 days. This study aims to describe the maternal gestational, neonatal, and nutritional characteristics of these infants during hospitalization and after discharge, up to two years of age.

The present study conducted a descriptive analysis of maternal gestational, neonatal, and nutritional data during the first 1,000 days of life of preterm newborns (PTNBs) participating in the “Pre-Grow Cohort” at the Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira (IFF/FIOCRUZ, National Institute of Women, Children and Adolescents Health Fernandes Figueira).

This cohort included newborns with a gestational age of less than 32 weeks or a birth weight below 1,500 g, clinically stable, without congenital malformations, genetic syndromes, or infections from the TORCHS group (toxoplasmosis, rubella, cytomegalovirus, herpes, and syphilis), Zika virus, or human immunodeficiency virus.

Those who developed intracranial hemorrhage grades III and IV, severe neurological impairment, necrotizing enterocolitis, bronchopulmonary dysplasia, patent ductus arteriosus with surgical indication, exclusive parenteral nutrition for more than 7 days, those who remained on nil by mouth for more than 5 days, gastrointestinal surgery, and Rh isoimmunization were excluded.

A convenience sample was used, and PTNBs were evaluated from birth and admitted to the Pre-Grow Cohort upon meeting the inclusion and exclusion criteria. All data were collected by a team of multidisciplinary researchers trained for the project’s activities at every stage.

PTNBs admitted to the Pre-Grow Cohort between 2012 and 2016, with complete data, were included in the study. The selected variables were retrieved from medical records and clinical charts of the Pre-Grow Cohort. Data encompassed maternal characteristics during pregnancy, neonatal and nutritional characteristics during hospitalization, and after hospital discharge, up to 24 months of corrected age, as detailed in Figure 1.

Maternal variables included pre-pregnancy weight, pre-pregnancy body mass index, gestational weight gain, nutritional status according to the new Brazilian population curves [15], presence of multiple gestations, and gestational comorbidities such as hypertension and gestational diabetes mellitus.

Neonatal variables included birth weight, length, and head circumference at birth and 24 months of corrected age, along with their respective Z-scores, classification at birth, gestational age, and sex.

Birth weight was measured using a Filizola® scale with 5-gram precision. Length was measured using a specific ruler suited to the incubator and crib, and head circumference was measured with a non-stretchable measuring tape accurate to 1 mm, adjusted to the head anteriorly in the supraorbital region and posteriorly over the occipital prominence. Z-scores were calculated using Intergrowth curves [16]. Newborns were classified as Small for Gestational Age (SGA, birth weight less than the 10th percentile), Appropriate for Gestational Age (AGA, birth weight was greater than or equal to the 10th percentile and less than or equal to the 90th percentile), or Large for Gestational Age (LGA, birth weight was greater than the 90th percentile).

At 24 months, weight was measured using a high-precision scale (0.01 kg), length with a standardized anthropometric ruler, and head circumference with a non-stretchable millimeter tape. Corresponding Z-scores for age were calculated using WHO Anthro software [17].

Gestational age at birth was calculated based on first-trimester ultrasound or, in its absence, the date of the mother’s last menstrual period. In addition, the Corrected Age (CA) was used, which is a measure used to assess the development and growth of premature babies, adjusting the baby’s chronological age based on their prematurity, that is, it is the age the baby would have been if they had been born at 40 weeks. The CA is calculated by subtracting the number of weeks left to complete the gestation from the baby’s chronological age. In the present study, the CA was adjusted up to 2 years of age.

Nutritional variables were collected from information recorded in the medical records by the attending physicians of the study. The selected variables referred to the beginning and the number of days of life that the baby received Human Milk (HM) and/or Infant Formula (IF), during hospitalization and after discharge, as well as the form of administration (breast, cup or bottle), the ingredients added (thickeners, sugary flours and fruits) to the preparation of IF and/or cow’s milk and the maximum age at which the baby received any HM and stopped receiving IF.

Breastfeeding was defined as any human milk intake, whether from the mother or a milk bank. Exclusive breastfeeding was defined as receiving only human milk, regardless of the administration method.

Regarding the introduction of food, information was included on the first meal offered and its consistency, as well as the food groups present at lunch and dinner, the offer of juices and their presentation (natural or artificial) and the consumption of ultra-processed foods These data were collected by the multidisciplinary team of the specialized follow-up outpatient clinic for PTNB care and recorded in the medical record. The care protocol includes the assessment of feeding readiness and questions about feeding in the last 24 hours, as well as some specific foods, such as juices, sugars and ultra-processed foods. Routine post-discharge consultations were carried out at 1, 2, 4, 6, 9, 12, 18 and 24 months of corrected age.

The choice of information separated by food groups, juices and ultra-processed foods followed the Dietary Guidelines for Brazilian Children Under 2 Years of Age [18].

Data were stored using Research Electronic Data Capture (REDCap) software [19] and analyzed with IBM®SPSS® (version 22). For data analysis, a descriptive approach was used that provided a comprehensive view of the population characteristics and variables of interest. Continuous variables were analyzed using means and standard deviations, and categorical variables were expressed as frequencies and percentages.

The Pre-Grow Cohort was approved by the Human Research Ethics Committee of the Fernandes Figueira Institute, CAAE: 00754612.9.0000.5269. The Informed Consent Form was requested from the parents/guardians of the participants for their inclusion in the study. This study did not receive private or public funding.

Of the 93 infants eligible for the study, 82 had complete information in the database and medical records and were therefore included in the study.

The population consisted mostly of PTNB with appropriate weight for gestational age (AGA) (65.9%), female (63.4%), with a mean (minimum and maximum) birth weight of 1,287 g (675-2085 g), length of 38.6 cm (29-49 cm), head circumference of 27.5 cm (22-31.5 cm), and gestational age at birth of 30.5 weeks (25-35 weeks). At 24 months of age, the infants had adequate weight, length, and head circumference for their age, following a growth trajectory close to the expected one (Table 1).

Maternal characteristics during pregnancy are presented in Table 1. Anthropometric data were available for 70 pregnant women, most of whom had adequate pre-pregnancy nutritional status (57.1%) and excessive weight gain during pregnancy (49.3%). Regarding comorbidities, most pregnant women did not develop gestational diabetes (92.1%) or hypertension (69.5%). A large number of twin pregnancies were observed (65.9%).

Table 2 presents the results regarding the intake of human milk and/or infant formula during hospitalization. Of the 82 PTNBs, all received human milk during hospitalization, however, 22 infants (26.8%) received exclusively human milk, and infant formula was offered to 60 PTNBs (73.2%) during their stay, starting at 33 weeks of corrected age.

Table 3 presents the results regarding the intake of human milk and/or infant formula after hospital discharge. After hospital discharge, only 2 PTNBs (2.4%) continued to receive exclusively human milk until the introduction of complementary feeding, 25 babies (30.5%) received only IF, and 55 (67.1%) received mixed feeding (human milk and infant formula). The method of administration of IF chosen for most babies (96.3%) was the bottle, and IF was offered until 60 weeks of corrected age. Of these infants, 45.1% had some ingredient added to the preparation of the IF and/or cow’s milk, and most of them were sugary flours (39.0%).

Cow’s milk and/or dairy products were used by most infants (91.3%) and started at a mean corrected age of 48 weeks (5 to 103 weeks).

Table 4 presents the results of the introduction of complementary feeding which occurred at 6.1 (±1.9) months of corrected age. All infants were attended and guided by the study’s pediatric team at the IFF/FIOCRUZ follow-up outpatient clinic.

The first food offered was fruit (89.0%) and in the form of puree (69.1%). The age for starting lunch and dinner was after 7 and 8 months of corrected age, respectively, and most (57.3%) started offering with all food groups present in the meal. The offer of ultra-processed foods to infants occurred before 11 months of corrected age. Most infants (77.8%) received juice before 8 months of corrected age, with 58.0% being natural juice.

This study highlighted significant findings in the first 1000 days of life of PTNBs that are amenable to intervention to prevent current and future diseases, such as excessive maternal weight gain during pregnancy, reduced duration of HM provision, and inadequate introduction of certain foods.

Regarding maternal variables during pregnancy, our study revealed results that differed from recent data presented by the Sistema de Vigilância Alimentar e Nutricional (SISVAN, Food and Nutrition Surveillance System), which showed that more than half of pregnant women receiving primary care presented overweight or obesity [20]. In the present study, most pregnant women were classified as eutrophic, but they presented weight gain above recommendations, as observed in another study with more than 700 pregnant women in the city of São Paulo [21]. Studies have shown that excess weight during pregnancy is a risk factor for excess weight and adiposity in infants during childhood and for increased chances of developing other chronic non-communicable diseases, such as obesity, in later years of life [22,23]. There is a great interest in research in this area to understand epigenetic modifications, metabolic programming mechanisms, and the determinants of the adult phenotype [6]. Metabolic programming is an adaptation process that occurs early in life, where the maternal environment during pregnancy is influenced by environmental factors [24,25] and excessive weight gain in women during pregnancy makes the maternal environment suboptimal and is a strongly associated environmental factor with the increased risk of age-related diseases [26].

For Lackovic et al., excessive gestational weight gain is related to adverse pregnancy outcomes, such as hypertensive disorders, gestational diabetes, and affects early motor development in infants [27].

Hypertensive disorders occur in 5 to 15% of pregnancies and represent one of the major causes of maternal morbimortality [28]. In the present study, hypertension was diagnosed in 30.5% of pregnant women, a result similar to that found by Guida et al. [29], in a multicenter study conducted in Brazil, where the prevalence of this disorder among women with premature births was 28.2%. These higher values may be due to the fact that the study populations were exclusively with PTNBs. It is known that changes in blood pressure values during pregnancy are a risk factor for premature births, besides adverse neonatal outcomes, such as babies with low birth weight and small for gestational age [28,30,31]. These data reinforce the importance of strategies for early detection and management of arterial hypertension during pregnancy.

Another environmental factor that has an effect on the infant’s metabolic programming is breastfeeding. HM provides unique nutrients and bioactive compounds that are crucial for the growth of preterm newborns, in addition to reducing sepsis, necrotizing enterocolitis, and improving neurodevelopment. Initiating breastfeeding early in the Neonatal Intensive Care Unit (NICU) with strategies such as skin-to-skin contact enhances these benefits [32,33].

In the present study, during hospitalization, 26.8% of infants received exclusive human milk, a value higher than that found by Oliveira and Volkmer [34] in a cohort conducted in a NICU in the southern region of the country, which was 16.1%, and by Dias et al. [35] in a cross-sectional study, which found that only 2.4% of infants received exclusive human milk until discharge. A retrospective study in a hospital in the Brazilian Federal District with infants admitted to the NICU found that 3.0% of PTNBs received exclusive human milk during hospitalization [36]. The care profile of IFF, which belongs to the Baby-Friendly Hospital Initiative, with actions aimed at promoting breastfeeding and the presence of a human milk bank, may reflect the higher values found in the present study.

After hospital discharge, IF was offered to 80 (97.6%) infants, of which 55 received mixed feeding (human milk and infant formula) and 25 received infant formula only. Only 2 received exclusive breastfeeding until the introduction of complementary foods. These findings are consistent with other studies in the literature that show a marked decrease in exclusive breastfeeding rates after hospital discharge [37,38] and the difficulty of maintaining breastfeeding in PTNBs, whether because of low maternal milk production resulting from preterm birth (stress, hospitalization, complications) or difficulties of the PTNB itself (morbidities, immaturity for sucking, poor weight gain, increased nutritional needs) [38,39].

Public policies [40] aimed at promoting breastfeeding have become increasingly prevalent, as breast milk is considered the most suitable food for any newborn. The American Academy of Pediatrics [41] acknowledges the benefits of breast milk for PTNBs, because of its balanced chemical composition and easy absorption, reduced risk of complications, and improved cognitive development, among other factors. Therefore, human milk is recommended in neonatal intensive care units, both milks extracted from the mother and immediately offered to the newborn, and that obtained from human milk banks.

Current data on breastfeeding practices in Brazil show that the prevalence of exclusive breastfeeding up to six months of age in full-term infants and continued breastfeeding in the first year of life are still below the values recommended by the World Health Organization [42]. According to the Estudo Nacional de Alimentação e Nutrição Infantil (ENANI, Brazilian National Survey on Child Nutrition) [43], the prevalence of exclusive breastfeeding in infants under six months in Brazil was 45.8% and continued breastfeeding in the first year of life was 43.6%. The median duration of exclusive breastfeeding was 3 months and of any breastfeeding was 15.9 months.

Since 2010, Brazil has implemented the National Policy for the Promotion, Protection, and Support of Breastfeeding, a fundamental pillar of child health. This policy aims to foster strategic actions to encourage and monitor breastfeeding. Among the existing actions, we can highlight the implementation of rooming-in in public hospitals with the Kangaroo Method, the creation of Human Milk Banks, the Baby-Friendly Hospital Initiative, and the Norma Brasileira para Comercialização de Alimentos para Lactentes (Norm for Marketing of Breast-milk Substitutes). These initiatives are justified by the complexity of interventions aimed at breastfeeding and the need to guarantee the right to breastfeed [44].

However, the maintenance of breastfeeding remains a challenge for both term and preterm infants. There is a need to strengthen the debate on this topic and to reinforce effective actions to encourage breastfeeding [43].

Furthermore, it is noteworthy that in the present study, nearly half of the children received IF and/or cow’s milk supplemented with some ingredient, most commonly sugary flours. The early introduction of sugar into the infant diet, as well as ultra-processed foods, promotes excessive intake of calories, salt, fat, and food additives, which may be an important factor for excessive weight gain, and also increase the risk of future diseases, tooth decay, and decreased interest in whole or minimally processed foods during a critical period for the development of taste preferences [18,45,46].

The age at which complementary feeding was introduced to the PTNBs in this study aligns with current recommendations [18,46], which consider both the infant’s readiness and a corrected gestational age of 6 months. It is important to note that these recommendations are still under debate, as PTNBs constitute a heterogeneous population and there is limited evidence available on the optimal age for introducing solid foods and its implications for health [47,48].

A multicenter clinical trial conducted by Gupta et al. [49] compared PTNBs with early introduction of complementary feeding at 4 versus 6 months corrected gestational age. According to the authors, the rate of hospital admission was higher in the 4-month group (2.5 episodes per 100 infant-months in the 4-month group versus 1.4 episodes per 100 infant-months in the 6-month group, p=0.03). The introduction of solids for these infants should consider their distinct nutritional needs, organ immaturity, increased risk of rehospitalization, and motor development delays [50].

Current recommendations suggest that the first main meal should be introduced in the sixth month of a baby’s life, and the second main meal should be introduced in the seventh month [18,45,46]. In the present study, we found that these were introduced after the seventh and eighth months of corrected age, respectively. The foods that make up the main meals should be offered in accordance with the recommendations for increasing the variety and presentation of new foods, adequate evolution of consistency, and the provision of nutrients that complement milk, which are necessary for the baby’s satisfactory development [18]. Delaying this offer is associated with food selectivity [51] and the potential development of food allergies [52].

Regarding feeding practices, it is worth noting that most babies consumed natural and/or artificial juice and ultra-processed foods before their first year of life. These data are in line with those presented by SISVAN for children aged 6 to 23 months, where 44% had already consumed ultra-processed products, 29% sugary drinks, 25% sandwich cookies, sweets and treats, and 21% instant noodles, crackers and packaged snacks, which can increase the risk of excess weight and nutritional deficiencies in all children, both those born at term and prematurely [20].

According to the Dietary Guidelines for Brazilian Children Under 2 Years of Age, juice should only be introduced after the first year of life and in limited quantities. This is because juice does not promote chewing, is low in fiber when strained, is often sweetened, and may replace water as the child’s primary beverage. Ultra-processed foods are not recommended for children in this age group [18].

The study results should be interpreted considering some limitations, as they originated from an original cohort (Pré-crescer Project) and information such as dietary intake during pregnancy and family income were not prioritized, but followed the institution’s protocol, which is based on the recommendations of the Dietary Guidelines for Brazilian Children Under 2 Years of Age [18].

Although participants were attended to in the public health system, presumably from a different social and financial condition than private network patients, the results found are similar to those of national studies.

As a strength of the work, there is a reinforcement of knowledge in the description of such a heterogeneous and vulnerable population, such as PTNBs, who, until now, have few national studies exploring nutritional aspects in the first 1000 days of life [35,53-55]. The possibility of intervention comes with visibility. The findings evidence the need for investments in continuous nutritional education in prenatal care, breastfeeding, and complementary feeding for PTNBs, in order to contribute to the promotion of maternal health and child development.

The identification of maternal, neonatal, and nutritional factors in early life is increasingly relevant, as it allows for early monitoring and the development of prevention strategies. Factors identified in the present study, such as excessive gestational weight gain, the addition of sugary flours to infant formula, and the inappropriate introduction of juices and ultra-processed foods, can be modified through effective and early interventions. This study contributes to clinical practice by providing evidence to assist healthcare professionals in counseling and nutritional guidance for pregnant women and PTNBs, a population particularly vulnerable to growth and neurodevelopmental deviations. In the field of study, the work offers a basis for future research on interventions and care practices in the first 1000 days of life, a critical phase for healthy development, enabling the refinement of health policies and the strengthening of preventive actions to minimize long-term risks.