Risk factors for neonatal respiratory distress : Moroccan retrospective study

Abstract

AimThe aim of the study was to determine the risk factors for neonatal respiratory distress.MethodsThis retrospective analytical study was conducted at the National Reference Center for Neonatology and Nutrition at Children’s Hospital, University Hospital Centre Ibn Sina of Rabat from January 1, 2021 to December 31, 2022. During the study period, 630 newborns who met the inclusion criteria were included in 2 groups: neonates with respiratory distress (n = 421) and neonates without respiratory distress (n = 209). The identification of risk factors was carried out using bivariate as well as multivariate analyses.Results630 births were collected during this period. Neonatal respiratory distress was multifactorial. Statistical analysis revealed mostly maternal anemia (OR=18.10; CI95 (7.5-43.55); P < .05), diabetes (OR=3.65; CI95 (1.98-6.72); P = .001), caesarean section (OR=4.23; CI95 (1.54-11.59); P = .001), prematurity (OR=2.45; CI95 (1.41-4.26); P = .01).ConclusionScreening, management, and reduction of neonatal respiratory distress remain a crucial challenge, requiring early coordination between pediatricians and obstetricians to obtain reliable data and identify newborns at risk.

Keywords

Introduction

The birth of newborns is associated with intrinsic and extrinsic alterations that ensure the transition from the intrauterine to the extrauterine environment, particularly at the pulmonary and cardiovascular levels. Generally, the newborn adapts naturally to extrauterine conditions. However, in some cases, this natural adaptation fails, leading to cardiac arrest associated with hypoxia and severe neurological damage, requiring immediate and rapid management.¹
Neonatal respiratory distress is caused by a deficit in oxygen supply leading to a change in the physiologic state of the newborn. This incident compromises the vital prognosis of the infant in particular by alternating phases of hypoxia and acidosis. Additionally, neonatal respiratory distress is often the product of a number of vectors such as hyaline membrane disease, late amniotic fluid resorption, prematurity, fetal asphyxia, and neonatal infections. In underdeveloped countries, neonatal respiratory distress is more common given lower socioeconomic conditions and more prevalent risk factors leading to perinatal complications such as poor or absent infrastructure.² These factors threaten maternal and fetal survival.
In addition to the lack of research, there is a lack of information on this syndrome in Morocco, so we aimed this study to provide valuable data in order to help identify the frequency of respiratory distress and the risk factors associated with this major public health problem in newborns in the neonatal unit of Children’s Hospital of Rabat.
In Morocco, Neonatal Respiratory Distress Syndrome (NRDS) is recognized as a major public health problem and a constant concern in neonatology units due to its frequency and severity. Our results highlight the importance of specific risk factors in the development and severity of NRDS and can be used to inform evidence-based NRDS management protocols in the Neonatal Intensive Care Unit (NICU), develop strategic planning for obstetric management, and hopefully set the basis for further epidemiological studies.

Materials and Methods

Study Population and Design This retrospective analytical study was conducted at the National Reference Center for Neonatology and Nutrition at Children’s Hospital of Rabat from 1 January 2021 to 31 December 2022. The study concerned hospitalized newborns for neonatal respiratory distress. As a tertiary hospital, the neonatal unit of Children’s Hospital of Rabat is one of the main neonatal units in Morocco. Through consecutive convenience sampling, we included all complete and eligible files of newborns admitted within the early neonatal period (first seven days of life). Data were extracted from the files into a case record form. Study Variables Data collection was carried out by a documentary technique consisting of studying the medical records of each neonate. All data were entered using an information sheet containing the following sections: • Maternal and obstetrical characteristics • Characteristics of the newborn • Evaluation of the patient • Dependent variable: neonatal respiratory distress • Independent variables: ‣ Socio-demographic characteristics: age, residence, marital status, educational and socioeconomic status of the mother, gestational age and area of origin ‣ Obstetrics-related factors: gravidity, parity, current mode of delivery ‣ Newborn characteristics (sex, birth weight, Apgar score, Silverman score, and time to respiratory distress > or <3 hours) ‣ Immediate resuscitation at birth ‣ Amniotic rupture ‣ Maternal pathologies during pregnancy (gestational diabetes, pre-eclampsia, goiter, asthma and anemia) ‣ Evaluation of the severity is based on a Silverman score, which is composed of inspiratory and expiratory categories of movements The scale of the Silverman score ranges from 0 to 2: • Neonatal moderate respiratory distress corresponding to Silverman ≤4 • Intense Neonatal Respiratory Distress corresponding to Silverman between 4–6 • Very intense Neonatal Respiratory Distress corresponding to Silverman >6 Inclusion Criteria Symptomatic or asymptomatic neonates hospitalized for clinical management of neonatal respiratory distress were included. Exclusion Criteria - All newborns with congenital malformations - Incomplete data sheets - Respiratory distress of surgical origin Definitions of Used Terms • Neonatal respiratory distress is defined by the presence of at least one of the following elements: abnormal respiratory rate (tachypnea >60 breaths/min; bradypnea <30 breaths/min; respiratory pauses, or apnea) or signs of labored breathing (expiratory grunting, nasal flaring, intercostal recessions, xyphoid recessions or thoracoabdominal asynchrony). Silverman’s score: a score greater than 7 indicates that the baby is in respiratory failure. • Delay of care at birth: refers to the time it takes to seek care after the onset of labor that is longer than 1 hour • Primiparous: a woman pregnant for the first time • Multiparous: a woman who has had multiple births • Premature rupture of membranes (PROM): rupture of the membranes (amniotic sac) before labor begins Data Analysis • The descriptive analysis of the variables was based primarily on class size and proportions. Mean and standard deviations were used as measures of central tendency and dispersion. Qualitative variables were compared using the chi-square test or Fisher’s exact test. The Kolmogorov-Smirnov test was used for the study of the distribution of the variables. Pearson’s correlation test was performed to understand the relationships between quantitative variables. Comparisons of means of quantitative variables for different classes of qualitative variables were performed using the Student’s t-test for independent samples. After verification of the different conditions of the test for all statistical tests, P < .05 was considered significant. Ethical Approval • This study was approved by the Biomedical Research Ethics Committee CERB of the Faculty of Medicine and Pharmacy (Date: 02.24.2021, Decision No: N/R: File n° C64/20) • This study is a part of the research project “Near Miss Neonatal in Morocco“

Results

We included 630 newborns, among whom 421 had neonatal respiratory distress symptoms (NRDS). Table 1 shows that the median maternal age was 35 years (Q1-Q3: ). The distribution according to educational level was dominated by illiteracy and secondary education with respective percentages of 48.2% and 44.2%, P < .05. On the other hand, the university level was only 7.6% of the population. The mean gestational age of the newborns was 36.8±8.86 gestational weeks; socioeconomic status was low in 54.2% of the cases and medium in only 45.8%, P < .05. Table 2 indicates that among 421 neonates with neonatal respiratory distress, 190 were female and 231 were male, with a sex ratio of 1.21; the sex of the neonate had no effect on neonatal respiratory distress in our study (P = .62). The mean birth weight was 3000 g (Q1-Q3: [2100;4050]). The cesarean section prevailed in 80.5% of cases, with a significant statistical difference P < .05; early rupture of membranes >12 hours was 84.1% and aspect of amniotic fluid (55.1%) P < .05. The main maternal and neonatal pathologies associated with respiratory distress were anemia (P < .05), pre-eclampsia (P = .02), maternal infection (P < .05), and gestational diabetes (P < .05). The main identified causes of respiratory distress were transitory tachypnea (16.5%), maternal-fetal infection (19.6%), hyaline membrane disease (30.1%), and prematurity (54%). Multiple regression statistical analysis primarily incriminated anemia (OR=18.10; 95 CI (7.5-43.55); P < .05), diabetes (OR=3.65; 95 CI (1.98-6.72); P = .001), cesarean section (OR=4.23; 95 CI (1.54-11.59); P = .001), prematurity (OR=2.45; 95 CI (1.41-4.26); P = .01), appearance of amniotic fluid (OR=27.9; 95 CI (13.46-55.34); P < .005), premature rupture of membranes (OR=5.40; 95 CI (2.58-11.29); P < .05), and early resuscitation at birth (OR=30.95; 95 CI (13.65-70.13); P < .05) (Table 3).

Discussion

In this study, we registered 420 newborns with respiratory distress (66.6%); several risk factors for respiratory distress were identified. Age was a determinant of neonatal respiratory distress in our study. The median age of our patients was 35 years (Q1-Q3: [22;36]). Maternal age between 30 and 40 is known to be associated with morbidity and neonatal respiratory distress, explained by the increased risk of chronic diseases such as diabetes and hypertension at this age.^3-4
In our sample, there was a relationship between low maternal education and neonatal respiratory distress. Low education level seems to limit perinatal health care and the use of medical services due to lack of awareness and information. Many studies have shown that the rate of fetal respiratory distress is inversely proportional to the mother’s level of education.⁵ This could be due to better diet, hygiene, and greater use of health services by educated women. In Morocco, lack of access to emergency neonatal care is widespread among women living in rural and isolated communities, far from medical facilities.
54.9% were male with a sex ratio of 1.21. Our results were not significant regarding the association between neonatal respiratory distress and gender. This is contradictory, because male gender is a risk factor for respiratory distress due to the frenative effect of androgens on surfactant synthesis, which delays lung maturation compared to females.⁶ Conversely, female fetuses produce surfactant earlier and have more developed lung parenchyma and airways.^7-8
The average weight was 3000 g (Q1-Q3: [2100;4050]); neonatal respiratory distress was higher in newborns weighing less than 2500 g. Thus, 54.4% of newborns were hypotrophic, 13.5% eutrophic, and 32.1% macrosomic. Our study agrees with study,⁹ which explains that hypotrophy is secondary to chronic hypoxia induced by hypertension and reduced nutrient delivery due to decreased uteroplacental perfusion. Doppler velocimetry analysis of umbilical artery blood flow correlates with increased respiratory complications in neonates of hypertensive mothers.¹⁰
Oxygen therapy was systematically used in all cases of respiratory distress. Our study reports that a majority (94.4%) of newborns were not resuscitated at birth (oxygen therapy, artificial ventilation). This confirms that management at birth presents major difficulties. Newborns often come from peripheral health centers and district hospitals, with referrals made by poor quality, non-medical transport. Alamneh et al. identified main risk factors for birth asphyxia as fetal distress, instrumental delivery, low birth weight, non-cephalic presentation, preterm, prolonged labor, co-morbidity during pregnancy, and meconium-stained amniotic fluid (MSAF). Most of these factors are preventable through holistic care for pregnancy, labor, and delivery. Intervention strategies should target these factors to reduce neonatal mortality associated with birth asphyxia.¹¹
Neonatal respiratory distress is closely related to cesarean section, consistent with studies showing a ten times higher incidence of neonatal airway complications. The delay in resorption of alveolar fluid during programmed cesarean section induces hormonal imbalance of catecholamines and defective lung maturation, leading to neonatal respiratory distress.^12-13 Theoretically, this delay induces hormonal imbalance and defective maturation of fetal lungs.¹⁴
The relationship between maternal diabetes mellitus (DM) and neonatal respiratory distress syndrome (RDS) has long been recognized. Our results align with meta-analyses suggesting maternal DM increases risk of neonatal RDS, especially when diabetes is not well controlled. Maternal hyperglycemia causes carbohydrate metabolism disorders in the developing embryo, creating oxidative stress.¹⁵
Our results also align with studies¹⁶ showing that serious complications lead to intensive care unit admission, burdening healthcare units. Attention to healthcare needs of pregnant women can help identify preeclampsia earlier and minimize complications. High blood pressure and proteinuria are main characteristics of preeclamptic patients, affecting maternal and fetal organs.¹⁷
Our results confirm that anemia is a global problem with serious consequences for mothers and babies. Even though anemia in pregnancy is treatable, data show associations between maternal anemia and severe adverse maternal and perinatal outcomes.^18-19 Our findings robustly demonstrate an independent link between severe anemia and SDR. Although our results do not explain a direct maternal cause of anemia, iron and folic acid deficiencies can be incriminated, probably due to inadequate nutrition and low socioeconomic status. Prevention and treatment of anemia during pregnancy and postpartum should remain a global public health and research priority.

Limitations

Our study was retrospective and our database was limited, with many parameters missing. We conducted this study during COVID-19; thus, access to different units was not free.

Conclusion

Neonatal respiratory distress is multifactorial and requires special attention. This study highlighted the seriousness of this syndrome. It also showed that the main risk factors are prematurity, cesarean section, gestational diabetes, anemia, and pre-eclampsia. Consequently, a thorough understanding of these factors enables us to implement preventive strategies.
We can propose the following recommendations:
- Strengthening the technical and human resources of the neonatology department, referral hospitals, and provincial hospitals
- Training in neonatal resuscitation techniques during classes
- Early medical referral of severe cases is essential
- Improving the health status of mothers and newborns

Declarations

References

1. Zec SL, Selmanovic K, Andrijic NL, Kadic A, Zecevic L, Zunic L. Evaluation of drug treatment of bronchopneumonia at the pediatric clinic in Sarajevo. Med Arch. 2016;70(3):177-181. doi:10.5455/medarh.2016.70.177-181
   Article · PubMed · Google Scholar
2. Nascimento-Carvalho AC, Ruuskanen O, Nascimento-Carvalho CM. Wheezing independently predicts viral infection in children with community-acquired pneumonia. Pediatr Pulmonol. 2019;54(7):1022-1028.
   PubMed · Google Scholar
3. Abdelgabar SA, Babikr WG, Elhussein AB, Hummeida ME. Risk of respiratory morbidity in term infants delivered by elective cesarean delivery. Int J Med Sci Public Health. 2016;5:973-977. doi:10.5455/ijmsph.2016.10022016351
   Article · PubMed · Google Scholar
4. Wyckoff MH, Aziz K, Escobedo MB, et al. Neonatal resuscitation: 2015 American Heart Association guidelines update for cardiopulmonary resuscitation and emergency cardiovascular care. Pediatrics. 2015;136(suppl 2). doi:10.1161/cir.0000000000000267
   Article · PubMed · Google Scholar
5. Beaujouan É, Reimondos A, Gray E, Evans A, Sobotka T. Declining realisation of reproductive intentions with age. Hum Reprod. 2019;34(10):1906-1914. doi:10.1093/humrep/dez150
   Article · PubMed · Google Scholar
6. Bongen E, et al. Sex differences in the blood transcriptome identify robust changes in immune cell proportions with aging and influenza infection. Cell Rep. 2019;29(7):1961-1973.e4. doi:10.1016/j.celrep.2019.10.019
   Article · PubMed · Google Scholar
7. Silveyra P, Fuentes N, Rodriguez Bauza DE. Sex and gender differences in lung disease. Adv Exp Med Biol. 2021;1304:227-258. doi:10.1007/978-3-030-68748-9_14
   Article · PubMed · Google Scholar
8. Shibata M, Ogawa K, Kanazawa S, et al. Association of maternal birth weight with the risk of low birth weight and small-for-gestational-age in offspring: a prospective single-center cohort study. PLoS One. 2021;16(5). doi:10.1371/journal.pone.0251734
   Article · PubMed · Google Scholar
9. Barreto CTG, Tavares FG, Theme-Filha M, Farias YN, Pantoja LN, Cardoso AM. Low birthweight, prematurity, and intrauterine growth restriction: results from the baseline data of the first indigenous birth cohort in Brazil. BMC Pregnancy Childbirth. 2020;20(1):781. doi:10.1186/s12884-020-03491-w
   Article · PubMed · Google Scholar
10. Mehari M, Maeruf H, Robles CC, et al. Advanced maternal age pregnancy and its adverse obstetrical and perinatal outcomes in Ayder Comprehensive Specialized Hospital, northern Ethiopia, 2017: a comparative cross-sectional study. BMC Pregnancy Childbirth. 2020;20(1):60. doi:10.1186/s12884-020-2740-6
    Article · PubMed · Google Scholar
11. Alamneh YM, Negesse A, Aynalem YA, et al. Risk factors of birth asphyxia among newborns at Debre Markos Comprehensive Specialized Referral Hospital, northwest Ethiopia: unmatched case-control study. Ethiop J Health Sci. 2022;32(3):513-522.
    PubMed · Google Scholar
12. Tefera M, Assefa N, Mengistie B, Abrham A, Teji K, Worku T. Elective cesarean section on term pregnancies has a high risk for neonatal respiratory morbidity in developed countries: a systematic review and meta-analysis. Front Pediatr. 2020;8:286. doi:10.3389/fped.2020.00286
    Article · PubMed · Google Scholar
13. Saddi YIA, Baythoon MB, Tahir AG. The timing of elective caesarean deliveries and early neonatal respiratory morbidity in term neonates. J Fac Med. 2018;60:38-42.
    PubMed · Google Scholar
14. Raveloharimino H, Fiangoa F, Ratianarison F, Rabesandratana HN. Epidemioclinical profile of respiratory distress seen at the CME CHU PZAGA Mahajanga. Rev Malg Ped. 2018;1:34-41.
    PubMed · Google Scholar
15. Li Y, Wang W, Zhang D. Maternal diabetes mellitus and risk of neonatal respiratory distress syndrome: a meta-analysis. Acta Diabetol. 2019;56:729-740. doi:10.1007/s00592-019-01327-4
    Article · PubMed · Google Scholar
16. Khan B, Allah Yar R, Khakwani AK, Karim S, Arslan Ali H. Preeclampsia incidence and its maternal and neonatal outcomes with associated risk factors. Cureus. 2022;14(11). doi:10.7759/cureus.31143
    Article · PubMed · Google Scholar
17. Mou AD, Barman Z, Hasan M, et al. Prevalence of preeclampsia and the associated risk factors among pregnant women in Bangladesh. Sci Rep. 2021;11(1):21339. doi:10.1038/s41598-021-00839-w
    Article · PubMed · Google Scholar
18. Kadhim Jasim S, Al-Momen H, Al-Asadi F. Maternal anemia prevalence and subsequent neonatal complications in Iraq. Open Access Maced J Med Sci. 2020;8:71-75. doi:10.3889/oamjms.2020.3593
    Article · PubMed · Google Scholar
19. Menon KC, Ferguson EL, Thomson CD, et al. Effects of anemia at different stages of gestation on infant outcomes. Nutrition. 2016;32(1):61-65. doi:10.1016/j.nut.2015.07.009
    Article · PubMed · Google Scholar

Tables

Additional Information

Publisher’s Note
Bayrakol MP remains neutral with regard to jurisdictional and institutional claims.

Rights and Permissions