Research Article: Hindawi Biomed Research International Volume 2018, Article Id 7162478, 6 Pages
Research Article: Hindawi Biomed Research International Volume 2018, Article Id 7162478, 6 Pages
Research Article
A Retrospective Study on the Risk of Respiratory Distress
Syndrome in Singleton Pregnancies with Preterm Premature
Rupture of Membranes between 24+0 and 36+6 Weeks, Using
Regression Analysis for Various Factors
Received 30 April 2018; Revised 30 August 2018; Accepted 18 September 2018; Published 4 October 2018
Copyright © 2018 Anna Niesłuchowska-Hoxha et al. This is an open access article distributed under the Creative Commons
Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is
properly cited.
Aim. This study aimed to investigate the cause of respiratory distress syndrome (RDS) in neonates from singleton pregnancies with
preterm premature rupture of membranes (pPROM) between 24+0 and 36+6 weeks by using regression analysis for various factors.
Methods. In 175 singleton pregnancies with pPROM, 95 cases of RDS (54,29%) were diagnosed. In all cases the following information
was collected: latency period of PROM, gestational age at birth, Umbilical Artery Pulsatility Index (UA PI), Middle Cerebral Artery
Pulsatility Index (MCA PI), fetal distress, antenatal steroids use, delivery type, pregnancy hypertension disease, gestational glucose
intolerance or diabetes, neonatal laboratory parameters, gender, weight, Apgar score, and other neonatal complications. Logistic
regression analysis was used to investigate the effect of variables on RDS. Results. The results of logistic regression analysis showed
that the following variables are closely correlated with RDS: female gender (OR=0.52; 95%CI:0.28-0,97), antenatal steroids use
(OR=0,46; 95%CI:0,34-0,64), abnormal UA PI and MCA PI (OR=2.96; 95%CI:1,43-6,12) (OR=2.05; 95%CI:1,07-3,95), fetal distress
(OR=2.33; 95%CI:1,16-4,71), maternal HGB (OR=0.69; 95%CI:0,5-0,96), and neonatal RBC, HGB (OR=0.32; 95%CI:0,19-0,55)
(OR=0.75; 95%CI:0,65-0,88). Conclusions. The main RDS risk factors in premature neonates are gender, abnormal fetoplacental
circulation, and fetal distress. The laboratory parameters such as lower RBC and HGB count are observed in infants with RDS.
fetal distress, intraventricular hemorrhage, and respiratory Other diagnostic criteria used in this study were [9–12]
distress syndrome [7, 8]. fetal distress as a significant abnormality in the fetal heart
Respiratory distress syndrome (RDS) is one of the most rate according to the result of fetal heart rate monitoring;
common causes of neonatal respiratory failure and neonatal congenital infection as fetal-neonatal infectious diseases
death. The underlying pathogenesis of RDS involves devel- such as pneumonia /septicemia caused by intra-amniotic
opmental immaturity of lungs, leading to inadequate pul- infection; neonatal anaemia as HGB lower than 18 g/dl; IVH
monary surfactant production [9]. It was previously believed was diagnosed using transfontanel ultrasonography; all IVH
that the most significant RDS factor is the prematurity. grades were included in the study.
Despite many studies, the reason for the occurrence of RDS Logistic regression analysis was used to investigate the
still remains unclear. effect of variables on neonatal RDS. Univariate and multi-
variate logistic regression models were created. A p<0.05 was
2. Objectives considered to be statistically significant.
Table 1: Univariate logistic analysis of various factors for preterm neonatal RDS.
Table 2: Multivariate logistic analysis of various factors for preterm neonatal RDS.
0 5 10 15 20 25 30
Odds Ratios
Figure 1: Odds ratios and confidence intervals for variables affecting the occurrence of preterm neonatal RDS–univariate logistic regression.
4 BioMed Research International
Neonatal HGB
Neonatal PLT
Figure 2: Odds ratios and confidence intervals for variables affecting the occurrence of preterm neonatal RDS-multivariate logistic regression.
of all PROM cases [1, 2, 8, 13, 16]. In this study pPROM of preterm deliveries [28] while Laban M et al. find that
frequency was 3,07% which is similar to the one given in the measurement of fetal lung volume (FLV) or pulmonary artery
literature. resistance index (PA-RI) can help to predict RDS in preterm
According to Zanardo et al., RDS developed in 55.4% of fetuses [29].
the examined newborns from pregnancies complicated by The results of this study show that congenital infec-
pPROM [17], whereas JoonHo LEE et al. report that, in South tion and fetal distress are strong RDS factors. A similar
Korea, the RDS was diagnosed in 47% of the cases [18]. In correlation was observed in many studies [9, 18, 19, 26,
this study, RDS amounted 54.29% which is comparable to the 30]. Fetal distress may lead to birth asphyxia. Asphyxia
percentages mentioned above. together with congenital infection causes the direct injury
The results of this study show that gender; antenatal to the fetal lungs and alveolar type II cells, decreasing
steroid use; abnormal UA PI and MCA PI; fetal distress; the synthesis and releasing surfactant [9, 31, 32]. Fetal-
and congenital infection are the main risk factors of RDS in neonatal lung inflammation increases the permeability of the
preterm neonates from pPROM pregnancies. alveolar-capillary membrane to both fluid and solutes. This
This study shows that among female gender there is lower results in plasma proteins entering the alveolar hypophase,
incidence of RDS in preterm neonates. The relative risk of which further inhibits the function of surfactant [9, 31,
RDS is 0,52 times lower for females than males. These data 32].
are confirmed in the literature [9, 19–21]. It was found that In this study relationship between the lower count of
in gestation the female fetal lung produces surfactant earlier RBC, HGB, PLT, and RDS was found. Correct levels of
than the male one. The reasons for this may be as follows: RBC, HGB, and PLT vary depending on the gestational age
(1) androgens delay lung fibroblast secretion of fibroblast- and prematurity; i.e., the less mature the newborn is, the
pneumocyte factor, which can delay the development of lower the values are [33, 34]. Another factor affecting the
alveolar type II cells and reduce the release of surfactant; RBC, HGB, and PLT values was the increased percentage of
(2) androgens slow fetal lung development by adjusting newborns with IUI and prolongation of PROM latency, who
the signalling pathways of epidermal growth factor and are characterized by significantly lower count of RBC, HGB,
transforming growth factor-beta; (3) estrogen promotes the and PLT compared to noninfected newborns [34, 35].
synthesis of phospholipids, lecithin, and surfactant proteins A
There is also higher incidence of RDS in newborns
and B; and (4) estrogen also improves fetal lung development
affected by other complications such as anaemia, congenital
by increasing the number of alveolar type II cells and by
infection, and intraventricular hemorrhage. This was also
increasing the formation of lamellated bodies [9, 22–25].
reflected in the literature [2, 13, 16, 31, 36]. Furthermore,
Our study confirms that antenatal steroids' use reduces
in this study the occurrence of RDS was associated with
the risk for RDS. This fact results in the current international
lower PLT count; its deficiency leads to bleeding. Additional
recommendations of the Royal College of Obstetricians and
PLT reduction risk factors are prematurity and intrauterine
Gynaecologists (RCOG) in dealing with various accepted
infection [33]. This leads to the occurrence of both RDS and
dosage schemes of corticosteroids.
intraventricular hemorrhage [34].
Neonatal breathing disorders can be caused by circulatory
system diseases. The main factors in this group are congenital
heart disease, pulmonary hypertension, and congestive heart 6. Conclusions
failure [26, 27]. No reports were found regarding fetopla-
cental circulation in relation to the development of neonatal The main risk factors of RDS in premature neonates are
RDS. However, the abnormal UA PI, MCA PI correlates with gender, abnormal fetoplacental circulation, and fetal distress.
centralization of the cardiovascular system, which after the Other neonatal complications such as anaemia, congenital
birth is an additional risk factor for RDS on the background of infection, and intraventricular haemorrhage increase the risk
cardiovascular failure. Büke et al. concluded that pulmonary of RDS coexistence. The laboratory parameters abnormalities
artery acceleration time to ejection time ratio (PATET) such as lower RBC, HGB, and PLT count are observed in
is a promising noninvasive tool to predict RDS in cases infants with RDS.
BioMed Research International 5
Data Availability [15] Al-Qa‘Qa‘K and F. Al-Awaysheh, “Neonatal outcome and pre-
natal antibiotic, treatment in premature rupture of membranes,”
The data used to support the findings of this study are Pakistan Journal of Medical Sciences, vol. 21, pp. 441–444, 2005.
available from the corresponding author upon request. [16] G. Paula, L. da Silva, and M. Moreira, “Repercussions of
premature rupture of fetal membranes on neonatal morbidity
Conflicts of Interest and mortality,” Cadernos de Saúde Pública, vol. 24, pp. 2521–
2531, 2008 (Portuguese).
The authors declare that they have no conflicts of interest. [17] V. Zanardo, S. Vedovato, E. Cosmi et al., “Preterm premature
rupture of membranes, chorioamnion inflammatory scores and
neonatal respiratory outcome,” BJOG: An International Journal
References of Obstetrics & Gynaecology, vol. 117, no. 1, pp. 94–98, 2010.
[1] T. P. Canavan, H. N. Simhan, and S. Caritis, “An evidence-based [18] J. Lee, H. S. Seong, B. J. Kim, J. K. Jun, R. Romero, and
approach to the evaluation and treatment of premature rupture B. H. Yoon, “Evidence to support that spontaneous preterm
of membranes: Part I,” Obstetrical & Gynecological Survey , vol. labor is adaptive in nature: Neonatal RDS is more common
59, no. 9, pp. 669–677, 2004. in “indicated” than in “spontaneous” preterm birth,” Journal of
Perinatal Medicine, vol. 37, no. 1, pp. 53–58, 2009.
[2] A. Caughey, J. Robinson, and E. Norwitz, “Contemporary
Diagnosis and Management of Preterm Premature Rupture of [19] M. H. Jones, “Charioamnionitis and Subsequent Lung Function
Membranes,” Reviews in Obstetrics and Gynecology, vol. 1, pp. in Preterm Infants,” PLoS ONE, vol. 8, p. e81193, 2013.
11–22, 2008. [20] A. Greenough, “Risk factors for respiratory morbidity in
[3] B. Furman, I. Shoham-Vardi, A. Bashiri, O. Erez, and M. Mazor, infancy after very premature birth,” Archives of Disease in
“Clinical significance and outcome of preterm prelabor rupture Childhood - Fetal and Neonatal Edition, vol. 90, no. 4, pp. F320–
of membranes: Population-based study,” European Journal of f323, 2005.
Obstetrics & Gynecology and Reproductive Biology, vol. 92, no. [21] D. K. Stevenson, “Sex differences in outcomes of very low
2, pp. 209–216, 2000. birthweight infants: the newborn male disadvantage,” Archives
[4] B. M. Mercer, “Preterm premature rupture of the membranes,” of Disease in Childhood - Fetal and Neonatal Edition, vol. 83, no.
Obstetrics & Gynecology, vol. 101, no. 1, pp. 178–193, 2003. 3, pp. 182F–185.
[5] B. M. Mercer, R. L. Goldenberg, P. J. Meis et al., “The Preterm [22] H. C. Nielsen and J. S. Torday, “Sex differences in avian
Prediction Study: Prediction of preterm premature rupture of embryo pulmonary surfactant production: Evidence for sex
membranes through clinical findings and ancillary testing,” chromosome involvement,” Endocrinology, vol. 117, no. 1, pp. 31–
American Journal of Obstetrics & Gynecology, vol. 183, no. 3, pp. 37, 1985.
738–745, 2000. [23] T. Seaborn, M. Simard, P. R. Provost, B. Piedboeuf, and Y.
[6] D. P. van der Ham, V. S. Kuijk, and B. C. Opmeer, “Can Tremblay, “Sex hormone metabolism in lung development and
neonatal sepsis be predicted in late preterm premature rupture maturation,” Trends in Endocrinology & Metabolism, vol. 21, no.
of membranes?” Development of a prediction model European 12, pp. 729–738, 2010.
Journal of Obstetrics & Gynecology and Reproductive Biology, [24] H. C. Nielsen, “Androgen receptors influence the production
vol. 176, pp. 90–95, 2014. of pulmonary surfactant in the testicular feminization mouse
[7] T. Y. Khashoggi, “Outcome of pregnancies with preterm prema- fetus,” The Journal of Clinical Investigation, vol. 76, no. 1, pp. 177–
ture rupture of membranes,” Saudi Medical Journal, vol. 25, no. 181, 1985.
12, pp. 1957–1961, 2004. [25] E. Bresson, T. Seaborn, M. Côté et al., “Gene expression profile
[8] E. Parry, “Managing PROM and PPROM,” O&G Magazine, vol. of androgen modulated genes in the murine fetal developing
8, pp. 35–38, 2006. lung,” Reproductive Biology and Endocrinology, vol. 8, article no.
[9] J. Liu, N. Yang, and Y. Liu, “High-risk Factors of Respiratory 2, 2010.
Distress Syndrome in Term Neonates: A Retrospective Case- [26] E. Bancalari, “Changes in the pathogenesis and prevention
control Study,” Balkan Medical Journal, vol. 33, no. 1, pp. 64–68, of chronic lung disease of prematurity,” American Journal of
2014. Perinatology, vol. 18, no. 1, pp. 1–9, 2001.
[10] R. J. Martin, A. A. Fanaroff, and M. C. Walsh, Martin’s Neonatal- [27] K. Krystyna and W. Kawalec, Pediatria, 2006, Wydawnictwo
Perinatal Medicine: Diseases of the Fetus and Infant, Elsevier Lekarskie PZWL.
Mosby Inc., st. Louis, Miss, USA, 9th edition, 2011. [28] B. Büke, E. Destegül, H. Akkaya, D. Şimşek, and M. Kazandi,
[11] E. Helwich, M. Bekiesińska-Figatowska, and R. Bokiniec, “Prediction of neonatal respiratory distress syndrome via pul-
“Rekomendacje dotyczące badań obrazowych ośrodkowego monary artery Doppler examination,” The Journal of Maternal-
układu nerwowego u płodów i noworodków,” Journal of Ultra- Fetal and Neonatal Medicine, pp. 1–6, 2017.
sonography, vol. 14, no. 57, pp. 203–216, 2014. [29] M. Laban, G. Mansour, A. El-Kotb, A. Hassanin, Z. Laban,
[12] L. A. Papile, J. Burstein, R. Burstein, and H. Koffler, “Incidence and A. Saleh, “Combined measurement of fetal lung volume
and evolution of subependymal and intraventricular hemor- and pulmonary artery resistance index is more accurate for
rhage: a study of infants with birth weights less than 1,500 gm,” prediction of neonatal respiratory distress syndrome in preterm
Journal of Pediatrics, vol. 92, no. 4, pp. 529–534, 1978. fetuses: a pilot study,” The Journal of Maternal-Fetal and Neona-
[13] J. M. Alexander and S. M. Cox, “Clinical course of premature tal Medicine, pp. 1–7, 2017.
rupture of the membranes,” Seminars in Perinatology, vol. 20, [30] M. Kacerovsky, “Prelabor rupture of membranes between 34
no. 5, pp. 369–374, 1996. and 37 weeks: the intraamniotic inflammatory response and
[14] G. Merenstein and L. Weisman, “Premature Rupture of the neonatal outcome,” American Journal of Obstetrics Ginecology,
Membrenes,” Semin Perinatol, vol. 20, pp. 375–380, 1996. pp. e1–10, April 2014.
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