Open-access Prevalence and associated factors of mother-reported jaundice in newborns

SUMMARY

OBJECTIVE:  Newborns’ jaundice is the result of bilirubin accumulation as fetal hemoglobin is metabolized by the immature liver. This study aimed to estimate the prevalence of mother-reported newborn jaundice and associated factors.

METHODS:  A cross-sectional study was carried out using data from a longitudinal study involving 914 children. The data were reviewed using Poisson regression with a robust estimator in a hierarchical model in which the sociodemographic variables constituted the first level, those related to the conditions of the pregnancy constituted the second level, and those related to the report of jaundice, the third level. Prevalence ratios and their relevant confidence intervals were estimated.

RESULTS:  The prevalence of reported jaundice in newborns was 17.9%. The variables late pregnancy, urinary infection during pregnancy, and preterm and post-term birth were independently statistically associated with a higher prevalence of newborn jaundice reports.

CONCLUSION:  We can conclude that mother-reported newborn jaundice was 17.9% associated with maternal and birth aspects.

KEYWORDS:
Jaundice; Newborn; Child health; Prevalence

INTRODUCTION

Hyperbilirubinemia, or jaundice, is a common benign condition in newborns and is one of the main causes of hospitalization in the first week of life1,2. Jaundice is observed in approximately 60% of full-term newborns and in 85% of premature newborns in their first week of life1,3,4.

Jaundice resulting from an increase in the indirect bilirubin fraction gives the skin a bright yellow or orange hue5,6. Conditions associated with direct hyperbilirubinemia give the skin a greenish-yellow color. However, these differences are only noticeable at very high levels of the pigment5,6.

In countries with few resources, kernicterus, defined as bilirubin encephalopathy that occurs when bilirubin serum levels are greater than 20 mg/dL in full-term neonates or lower in premature infants, continues to be an important and underestimated factor in neonatal morbidity and mortality7. In low- and middle-income countries, approximately 500,000 newborns per year develop extreme hyperbilirubinemia conditions (≥25 mg/dL), leading to approximately 114,000 neonatal deaths and 75,000 cases of kernicterus7,8. The main reason for this high morbidity and mortality is the inability to measure bilirubin levels adequately8,9.

Several papers have been published on neonatal jaundice, and a study published in the United States in 2018 revealed that the prevalence of neonatal jaundice was 55.2% of newborns. The study showed that 10% of black-skinned babies were diagnosed with jaundice observed due to hyperbilirubinemia but did not present with clinical jaundice10.

Family and healthcare professionals play an important role in the clinical diagnosis of early jaundice. A study of 1,666 mothers of babies with jaundice was carried out to assess mothers’ knowledge and practice regarding neonatal jaundice. The study showed that 77% of mothers had moderate to high knowledge about neonatal jaundice, demonstrating the relevance of mothers’ participation in the care of newborns with jaundice11.

Therefore, knowledge about the clinical evolution of these conditions and the presence of associated factors is essential for the adequate healthcare of newborns, as epidemiological characterization is extremely important so that primary and secondary care measures can be planned and carried out. This will enhance not only the reduction of jaundice prevalence but also the therapeutic and prognostic improvement. The objective of this study was to estimate the prevalence of mother-reported neonatal jaundice and identify associated factors in newborns.

METHODS

This was an epidemiological study with a cross-sectional design using data from a longitudinal study called Coorte Brasil Sul12 being developed in Palhoça, a municipality with approximately 220,000 inhabitants located in the metropolitan region of Florianópolis, SC. The study population was composed of children born in 2009, examined in 2015, and who are still being monitored. In the baseline study12, the following parameters were used to calculate the sample: population of 1,270 6-year-old children, anticipated prevalence of the outcome unknown (p=50%), 95% confidence level, and 2% relative error, which generated a minimum sample of 831 children. An additional number of children (10%) was added to compensate for any refusals, which yielded a final sample of 914 children randomly drawn from all 37 public schools and 19 private educational institutions in the municipality.

Data were collected through interviews in which mothers in their dwelling addresses were asked about their children’s prenatal, perinatal, and neonatal period descriptions. The team of investigators from Coorte Brasil Sul12 was responsible for the data collection, together with the community health agents, all duly trained for the purpose.

In the present study, the dependent variable was the mother’s report on the occurrence of jaundice in the newborn, answering the question “Did the newborn have jaundice/yellowing during the first 29 days of life?” (yes/no). The independent variables were child’s gender; child’s skin color (categorized as white and non-white); mother’s education at the time of giving birth (categorized as up to 8 years of complete schooling and more than 8 years); mother’s age at child’s birth (categorized as less than 19, between 20 and 34, and greater than 35 years of age); number of prenatal visits (categorized as up to 6 and 7 or more); mode of delivery (vaginal or cesarean section); smoking, alcoholic beverages use, and use of illicit drugs during pregnancy (all, yes and no); occurrence of diabetes, hypertension, and infectious diseases during pregnancy (all, yes and no); preterm birth (categorized as up to 37 and 38 weeks or more); birth weight (categorized as up to 2,500 g and more than 2,500 g); birth weight by gestational age-GA (categorized as low for GA, adequate for GA, and high for GA); APGAR index in the first and fifth minutes (categorized as up to 7 and above 7); and head circumference (categorized as less than 32 cm, greater than 35 cm, and between 33 and 34 cm).

The data were displayed in an Excel software spreadsheet and later exported to the SPSS Statistics for Windows software, version 18.0 (SPSS Inc., Chicago, IL, United States), where they were analyzed using Poisson regression with a robust estimator, hierarchical with the stepwise forward strategy. Prevalence ratios and their 95% confidence intervals were estimated. The hierarchical analysis model proposed for this study included three levels. The sociodemographic variables constituted the first level, the variables associated with pregnancy conditions constituted the second level, and the variables associated with the report of jaundice constituted the third level (Figure 1).

Figure 1
Hierarchical conceptual structure in blocks for reporting newborn jaundice.

Initially, a bivariate analysis was carried out, with all the variables from each hierarchical level. A model was developed with the first-level variables that presented p<0.20. In this block, variables that presented p<0.05 were maintained. Subsequently, the second-level variables were added, which in the bivariate analysis presented p<0.20. At this point, the second-level variables that presented p>0.05 were removed from the model. The sociodemographic variables that presented statistical significance in the first stage of the multivariate model were maintained, regardless of the level of significance presented after the introduction of variables related to the conditions of the pregnancy. Thus, a two-level model was created. Subsequently, third-level variables were introduced, which in the bivariate analysis presented p<0.20. Variables from this third level that presented p<0.05 were maintained in the model without removing the variables from the previous levels. Thus, a three-level final model ensued.

This study complied with the ethical principles established in the Resolution of the National Health Council no. 466/2012 and was approved by the Research Ethics Committee of the Universidade do Sul de Santa Catarina under CAAE No.: 38240114.0.00005369.

RESULTS

A total of 914 children were included in the study. The prevalence of mothers reporting newborn jaundice was 17.9% (95%CI 15.4; 20.3).

The results of the bivariate analysis showed that no variable from the first level (socioeconomic) was associated. The associated second-level variables (pregnancy conditions) were children born to mothers who had had a late pregnancy and had a 7.0% higher prevalence of jaundice reports (PR=1.07; 95%CI 1.01; 1.12) (p=0.013) compared to non-late pregnancy women. Urinary tract infection during pregnancy was associated with a 7.0% higher prevalence (PR=1.07; 95%CI 1.04; 1.11) (p<0.001). The occurrence of infectious diseases during pregnancy was also associated with a higher 6.0% prevalence (PR=1.06; 95%CI 1.02; 1.09) (p=0.001) compared to the non-occurrence of infectious diseases. As to the third level (birth conditions), preterm births had a 10.0% higher prevalence (PR=1.10; 95%CI 1.03; 1.17) (p=0.005), and post-term births had a 12.0% higher prevalence (PR=1.12; 95%CI 1.03; 1.22) (p=0.009) compared to those born at term. Children born weighing up to 2,500 g at birth had a 9.0% higher jaundice prevalence (PR=1.09; 95%CI 1.02; 1.16) (p=0.008) compared to those weighing more than 2,500 g (Table 1).

Table 1
Sociodemographic variables, pregnancy, and birth conditions.

Significantly higher and independent prevalence of mothers reporting newborns jaundice indicated by the final hierarchical and adjusted model was due to late pregnancy with a 6% higher prevalence (PR=1.06; 95%CI 1.01; 1.12) (p=0.025); urinary infection during pregnancy with 13% higher prevalence (PR=1.13; 95%CI 1.06; 1.21) (p<0.001); preterm newborns with 10% higher prevalence (PR=1.10; 95%CI 1.03; 1.17) (p=0.005); and post-term newborns with 12% higher prevalence (PR=1.12; 95%CI 1.03; 1.17) (p=0.005) compared to full-term newborns (Table 2).

Table 2
Final hierarchical model for mother-reported jaundice in newborns.

DISCUSSION

Jaundice in newborns is a complex disease and has several determining factors that interact with its development, which is why the hierarchical analysis model of variables was used in the present study. After careful selection and analysis of the variables, it was found that late pregnancy, urinary tract infections during pregnancy, preterm newborns, and post-term newborns were independently associated with a greater prevalence of mother-reported jaundice in newborns. Among these variables, urinary infection during pregnancy had the highest magnitude of prevalence of mother-reported neonatal jaundice.

Urinary tract infection during pregnancy is a condition that showed a 13% greater prevalence of jaundice reports compared to mothers who did not experience this pathology. No direct relationship between gestational urinary tract infection and neonatal jaundice was found in the literature. However, there are studies that state that some drugs used to treat bacterial infections in the urinary tract, such as sulfonamides, can potentially cause harm in the case of lower bilirubin levels because they displace bilirubin from albumin, thereby increasing the free bilirubin fraction13,14.

Preterm newborns (<37 weeks of gestational age) have a 10% higher prevalence of jaundice occurrence compared to full-term newborns, which corroborates a study that places preterm birth as a risk factor for the development of neonatal jaundice15. This is mainly due to increased bilirubin production, immaturity in the uptake and conjugation of bilirubin, and increased enterohepatic circulation of bilirubin due to intestinal immaturity15,16. Out of the 125 newborns entered in the US voluntary registry of kernicterus, 24% were born preterm17. Preterm newborns have red blood cells with a shorter life cycle and, therefore, have relatively increased bilirubin production rates compared to healthy full-term newborns18.

It was observed that post-term newborns (>42 and a half weeks) had a 12% higher prevalence of jaundice than newborns at term. Post-term birth, as well as pre-term birth, are a risk factor for the development of neonatal jaundice15,19. On the contrary, the Guidelines of the American Academy of Pediatrics report that children born after 40 weeks or more of pregnancy and who were formula-fed have a very low risk of developing severe hyperbilirubinemia20.

In relation to maternal age, late pregnancy (over 35 years of age) was associated with a 6% higher prevalence of children with neonatal jaundice. In a study, maternal age was statistically significant with regard to the child’s serum bilirubin levels21. Mothers aged above or equal to 30 years constituted a greater risk for the development of jaundice in newborns22.

This study has limitations due to its retrospective nature, based on reports provided by mothers, which may be affected by memory bias. Thus, the lack of objective data, such as laboratory tests that could provide an objective diagnosis, demands caution in the interpretation of our results. Furthermore, the cross-sectional design, although it involves a large sample, can only point to associations and not to a causal relationship, which demands other studies with longitudinal methodology. However, the maternal role in the search for early diagnosis as an initial step for appropriate investigation and consequent success in jaundice management or treatment cannot be neglected. Therefore, the factors found in this study can contribute to the understanding of jaundice in newborns and help develop management methods to prevent the condition.

We can conclude that the jaundice rate of mother-reported newborns was 17.9%, which is associated with variables related to maternal and birth aspects. This finding can contribute to the development of primary care conduct and public policies since hyperbilirubinemia is involved in different important biological processes.

REFERENCES

  • 1. National Institutes for Health and Clinical Excellence. Neonatal jaundice (Clinical Guidelines 98). 2010.
  • 2. Anderson NB, Calkins KL. Neonatal indirect hyperbilirubinemia. Neoreviews. 2020;21(11):e749-60. https://doi.org/10.1542/neo.21-11-e749
    » https://doi.org/10.1542/neo.21-11-e749
  • 3. Hegyi T, Kleinfeld A. Neonatal hyperbilirubinemia and the role of unbound bilirubin. J Matern Fetal Neonatal Med. 2022;35(25):9201-7. https://doi.org/10.1080/14767058.2021.2021177
    » https://doi.org/10.1080/14767058.2021.2021177
  • 4. IBGE. Cidades e estados. Palhoça. 2024. [cited on 2024 Feb 06]. Available from: https://www.ibge.gov.br/cidades-e-estados/sc/palhoca.html
    » https://www.ibge.gov.br/cidades-e-estados/sc/palhoca.html
  • 5. Pichon JB, Riordan SM, Watchko J, Shapiro SM. The neurological sequelae of neonatal hyperbilirubinemia: definitions, diagnosis and treatment of the kernicterus spectrum disorders (KSDs). Curr Pediatr Rev. 2017;13(3):199-209. https://doi.org/10.2174/1573396313666170815100214
    » https://doi.org/10.2174/1573396313666170815100214
  • 6. Par EJ, Hughes CA, DeRico P. Neonatal hyperbilirubinemia: evaluation and treatment. Am Fam Physician. 2023;107(5):525-34. PMID: 37192079
  • 7. Geest BAM, Mol MJS, Barendse ISA, Graaf JP, Bertens LCM, Poley MJ, et al. Assessment, management, and incidence of neonatal jaundice in healthy neonates cared for in primary care: a prospective cohort study. Sci Rep. 2022;12(1):14385. https://doi.org/10.1038/s41598-022-17933-2
    » https://doi.org/10.1038/s41598-022-17933-2
  • 8. Okwundu CI, Olowoyeye A, Uthman OA, Smith J, Wiysonge CS, Bhutani VK, et al. Transcutaneous bilirubinometry versus total serum bilirubin measurement for newborns. Cochrane Database Syst Rev. 2023;5(5):CD012660. https://doi.org/10.1002/14651858.CD012660.pub2
    » https://doi.org/10.1002/14651858.CD012660.pub2
  • 9. Campo González A, Alonso URM, Amador RF, Ballesté LI. Comparación de dos métodos diagnósticos de ictericia neonatal. Rev Cubana Pediatr. 2012;84(1):67-72.
  • 10. Brits H, Adendorff J, Huisamen D, Beukes D, Botha K, Herbst H, et al. The prevalence of neonatal jaundice and risk factors in healthy term neonates at National District Hospital in Bloemfontein. Afr J Prim Health Care Fam Med. 2018;10(1):e1-6. https://doi.org/10.4102/phcfm.v10i1.1582
    » https://doi.org/10.4102/phcfm.v10i1.1582
  • 11. Amirshaghaghi A, Ghabili K, Shoja MM, Kooshavar H. Neonatal jaundice: knowledge and practice of Iranian mothers with icteric newborns. Pak J Biol Sci. 2008;11(6):942-5. https://doi.org/10.3923/pjbs.2008.942.945
    » https://doi.org/10.3923/pjbs.2008.942.945
  • 12. Traebert J, Lunardelli SE, Martins LGT, Santos KD, Nunes RD, Lunardelli AN, et al. Methodological description and preliminary results of a cohort study on the influence of the first 1,000 days of life on the children’s future health. An Acad Bras Cienc. 2018;90(3):3105-14. https://doi.org/10.1590/0001-3765201820170937
    » https://doi.org/10.1590/0001-3765201820170937
  • 13. Thyagarajan B, Deshpande SS. Cotrimoxazole and neonatal kernicterus: a review. Drug Chem Toxicol. 2014;37(2):121-9. https://doi.org/10.3109/01480545.2013.834349
    » https://doi.org/10.3109/01480545.2013.834349
  • 14. Forna F, McConnell M, Kitabire FN, Homsy J, Brooks JT, Mermin J, et al. Systematic review of the safety of trimethoprim-sulfamethoxazole for prophylaxis in HIV-infected pregnant women: implications for resource-limited settings. AIDS Rev. 2006;8(1):24-36. PMID: 16736949
  • 15. Olusanya BO, Kaplan M, Hansen TWR. Neonatal hyperbilirubinaemia: a global perspective. Lancet Child Adolesc Health. 2018;2(8):610-20. https://doi.org/10.1016/S2352-4642(18)30139-1
    » https://doi.org/10.1016/S2352-4642(18)30139-1
  • 16. Raju TN. Developmental physiology of late and moderate prematurity. Semin Fetal Neonatal Med. 2012;17(3):126-31. https://doi.org/10.1016/j.siny.2012.01.010
    » https://doi.org/10.1016/j.siny.2012.01.010
  • 17. Watchko JF. Bilirubin-induced neurotoxicity in the preterm neonate. Clin Perinatol. 2016;43(2):297-311. https://doi.org/10.1016/j.clp.2016.01.007
    » https://doi.org/10.1016/j.clp.2016.01.007
  • 18. Pettersson M, Eriksson M, Albinsson E, Ohlin A. Home phototherapy for hyperbilirubinemia in term neonates-an unblinded multicentre randomized controlled trial. Eur J Pediatr. 2021;180(5):1603-10. https://doi.org/10.1007/s00431-021-03932-4
    » https://doi.org/10.1007/s00431-021-03932-4
  • 19. Du L, Ma X, Shen X, Bao Y, Chen L, Bhutani VK. Neonatal hyperbilirubinemia management: clinical assessment of bilirubin production. Semin Perinatol. 2021;45(1):151351. https://doi.org/10.1016/j.semperi.2020.151351
    » https://doi.org/10.1016/j.semperi.2020.151351
  • 20. Murzakanova G, Räisänen S, Jacobsen AF, Sole KB, Bjarkø L, Laine K. Adverse perinatal outcomes in 665,244 term and post-term deliveries-a Norwegian population-based study. Eur J Obstet Gynecol Reprod Biol. 2020;247:212-8. https://doi.org/10.1016/j.ejogrb.2020.02.028
    » https://doi.org/10.1016/j.ejogrb.2020.02.028
  • 21. Dong XY, Wei QF, Li ZK, Gu J, Meng DH, Guo JZ, et al. Causes of severe neonatal hyperbilirubinemia: a multicenter study of three regions in China. World J Pediatr. 2021;17(3):290-7. https://doi.org/10.1007/s12519-021-00422-3
    » https://doi.org/10.1007/s12519-021-00422-3
  • 22. Lu L, Li JH, Dai XF, Wei JB, Chen LH, Hu JF. Impact of advanced maternal age on maternal and neonatal outcomes in preterm birth. Ginekol Pol. 2022;93(2):134-41. https://doi.org/10.5603/GP.a2021.0224
    » https://doi.org/10.5603/GP.a2021.0224
  • Funding:
    Fundação de Amparo à Pesquisa e Inovação do Estado de Santa Catarina (FAPESC): auxílio nº 09/2015.

Publication Dates

  • Publication in this collection
    25 Oct 2024
  • Date of issue
    2024

History

  • Received
    15 May 2024
  • Accepted
    19 July 2024
location_on
Associação Médica Brasileira R. São Carlos do Pinhal, 324, 01333-903 São Paulo SP - Brazil, Tel: +55 11 3178-6800, Fax: +55 11 3178-6816 - São Paulo - SP - Brazil
E-mail: ramb@amb.org.br
rss_feed Acompanhe os números deste periódico no seu leitor de RSS
Reportar erro