Maternal risk factors for neonatal jaundice

Eur J Transl Myol 28 (3): 257-264, 2018

Maternal risk factors for neonatal jaundice: a hospital-based cross-

sectional study in Tehran
Reza Tavakolizadeh (1), Anahita Izadi (2), Golnar Seirafi (3), Leila Khedmat (4), Sayed
Yousef Mojtahedi (5)

(1) Department of Pediatrics, Tehran University of Medical Sciences, Tehran, Iran; (2)
Department of Pediatric Infection Disease, Tehran University of Medical Science, Tehran,
Iran; (3) School of Medicine, Ziaeian Hospital, Tehran University of Medical Sciences,
Tehran, Iran; (4) Department of Social Medicine, Tehran University of Medical Sciences,
Tehran, Iran; (5) Department of Pediatrics, Ziaeian Hospital, Tehran University of Medical
Sciences, Tehran, Iran
This article is distributed under the terms of the Creative Commons Attribution Noncommercial License (CC BY-NC 4.0) which permits
any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.

Abstract
Diagnosis and timely treatment of neonatal jaundice is critical to preventing its dangerous side
effects. Knowing the predisposing factors of neonatal jaundice is still a serious debate, which
can be effective in controlling jaundice and the primary problem. The aim of this study was to
evaluate maternal risk factors that contribute to the Hyperbilirubinemia among newborns
admitted to Imam Khomeini and Ziaeean hospitals during 2015. We collected random
samplings for the current study. Medical records for all newborns with jaundice were examined
for risk factors associated with Hyperbilirubinemia. All variables were analyzed by SPSS
software, version 19. Chi-square test and T-test were applied to evaluate qualitative and
quantitative data, respectively. Our findings revealed that maternal age, weight, BMI, WBC,
Hb, PLT, birth in the first pregnancy, numbers of pregnancies and prolonged delivery were
significantly associated with bilirubin levels. Preventing the risk correlated with maternal
factors or identifying neonates with these risk factors is important in effective management of
infants. Therefore, the evaluation of neonatal jaundice in health care services should always be
considered as a fundamental policy.

Key Words: Neonatal jaundice, bilirubin, pregnancy, risk factors, health care
Eur J Transl Myol 28 (3): 257-264, 2018

Neonatal jaundice is a common condition that occurs jaundice, which can be related to genetic and/or
during the transitional period after birth.1-3. This geographic variables.7 Early diagnosis of infants at high
unpreventable condition occurrs in 60% of term and risk of severe hyperbilirubinemia plays an important
80% of preterm neonates all over the word. Jaundice is role in facilitating the timely and appropriate prevention
one of the most common causes of neonatal readmission of disease within the first 14 days of birth.7,11 Clinical
to hospital.1 It usually begins on the second day after symptoms of hyperbilirubinemia are primarily seen in
birth and lasts two to three days to reach normal levels the head and face, and then affect the organs of the
of bilirubin in most cases without treatments.4,5 On the trunk and the limb due to increased serum levels of
other hand, neonate population may show severe bilirubin. It is noteworthy that increasing hemoglobin
jaundice, or even jaundice that develops into acute release from breakdown of red cells due to high
bilirubin encephalopathy or kernicterus.6,7 hemoglobin leads to jaundice at birth.12,13. This disease
Hyperbilirubinemia is primarily important because there may also be due to decreased hepatic excretion of
is a close relationship between the increase in bilirubin.14,15 Since jaundice may have serious side
unconjugated bilirubin levels and neurotoxic effects that effects on the health of infants, consideration should be
can lead to long-term complications such as cerebral given to its associated factors in newborns. Kernicterus
palsy, kernicterus and hearing impairment.8-10 Severe is one of the most important diseases that complications
jaundice is a serious life-threatening problem, and of the disease are sometimes so dangerous. Considering
several factors interfere with the development of severe the fact that jaundice is one of the common causes of

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Eur J Transl Myol 28 (3): 257-264, 2018

Table1. Association of some maternal factors with the level of bilirubin

Bilirubin Mother's age Mother's Mother's Weight Height BMI

breathing heart rate
number
p-value 0.02 0.44 0.85 0.001 0.19 0.01
10-14.9 Mean 29.37 14.93 89.04 80.43 162.65 30.42
SD 6.21 2.91 6.04 7.42 4.09 2.94
15-19.9 Mean 25.94 14.48 88.42 75.03 161.45 28.78

SD 5.91 2.39 6.13 5.48 3.54 1.89

20-24.9 Mean 28.17 13.67 88.33 78.50 160.83 30.43
SD 5.71 2.73 1.63 7.18 3.06 3.55
Total Mean 28.81 14.82 88.92 79.54 162.41 30.17
SD 6.24 2.83 5.96 7.38 4.00 2.87

SD, Standard Deviation

hospitalization of newborns, attention can be paid to maternal demographic data and other data was provided
timely diagnosis and prevention of it. On the other hand, for collecting data. Maternal information
the rapid treatment of jaundice or timely prevention will Maternal information, including maternal age during
be cost-effective in annual costs due to reduced pregnancy (over 35 and under the age of 18), first
hospitalization of newborns. To the best of our pregnancy, number of pregnancy, inter-pregnancy
knowledge, the evaluation of the causes and risk factors intervals of 3 years, type of delivery, Oxytocin
of neonatal jaundice in newborns has not been Induction of labor, premature rupture of membranes
comprehensively performed in Iran, while we are (PROM), prolonged labor, cesarean section, multiple
confronted with the spread of the disease among the birth in the current pregnancy, respiratory rate during
newborns. Therefore, it is advisable to have a systematic pregnancy, number of heart beats during pregnancy,
and effective program for evaluation of causes and risk maternal weight during pregnancy, body mass index,
factors of jaundice in newborns. Prevention of jaundice losing weight during pregnancy, history of abortion,
risks requirs extensive and accurate analyses that should were obtained from all mothers.
be continuously and repeatedly peformed. The present
study was set out to assess the effects of maternal Inclusion criteria: Getting jaundice.
factors on neonatal jaundice with the aim of determining Exclusion criteria: Exclusion criteria included
modifiable risk factors to reduce occurrence and incomplete medical records that were beyond the
consequences of severe jaundice in newborns. control of the researcher; however, the additional
Materials and Methods sample size was considered to be about 20%.

Ethical considerations Sample size calculation

All ethical principles of the Helsinki II declaration were
alfa= 0.05 Z1-a/2= 1.961150776 2
followed. Newborns’ parents were informed and written z 1
 pq
consent forms were collected. d= 0.03 n 2
2
p= 0.96 n= 165 d
Data Collection
This cross-sectional study was performed on 2207 term An additional 20 percent sample size was added to
newborns (<15 days) with hyperbilirubinemia (>15 prevent loss and withdrawal. p = first pregnancy as
mg/dl), who admitted to the neonatal intensive unit of previously described.24,25 The sample size was finally
the Ziaeean and Imam Khomeini Hospitals, Tehran, calculated as 200. The data were subsequently collected
Iran, from April 2010 to May 2016. The records of all and entered in the questionnaire, followed by statistical
infants in terms of the maternal risk factors for neonatal analysis based on SPSS software version 19. the
jaundice have been investigated. Neonates born with obtained data was entered into cod sheet and master
jaundice in the birth admission were selected based on sheet. Qualitative variables were presented as
the neonatal outcome indicator. Data were obtained frequency, while quantitative variables were calculated
from medical records and interview sessions with the as mean, range, and standard deviation. Chi-square test
mothers by study staff. A checklist consisting of was applied to examine qualitative data, while

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 Maternal risk factors for neonatal jaundice
Eur J Transl Myol 28 (3): 257-264, 2018

Table2. Relationship of first pregnancy with neonatal jaundice based on the different bilirubin levels

P=0.01 Bilirubin Total

10-14.9 15-19.9 20-24.9
First/child Yes Number 49 18 2 69
Percent 30.1% 58.1% 33.3% 34.5%
No Number 114 13 4 131
Percent 69.9% 41.9% 66.7% 65.5%
Total Number 163 31 6 200
Percent 100.0% 100.0% 100.0% 100.0%

Relationship of some maternal blood factors with jaundice

Bilirubin Maternal Hemoglobi Mean corpuscular volume Plate Hem
white blood n let atocr
cells it
p-value 0.001 0.04 0.77 0.001 0.88
10-14.9 Mean 12.26 12.09 87.33 222.72 34.09
SD 4.03 1.79 5.93 72.61 4.03
15-19.9 Mean 10.04 12.79 86.51 281.77 34.22
SD 2.48 1.40 5.08 62.72 2.28
20-24.9 Mean 9.10 13.27 87.17 243.67 33.35
SD 1.53 1.37 2.81 60.48 1.27
Total Mean 11.82 12.24 87.20 232.50 34.09
SD 3.88 1.75 5.72 73.74 3.75

SD, Standard Deviation

quantitative data were statically analyzed by T-test, p < that 30.1% of infants in the first maternal delivery had a
0.05 was considered statistically significant. bilirubin level of 10 to 14.9, followed by bilirubin levels
of 15-19.9 (58.1%) and bilirubin levels of 20- 24.9
Results and Discussion (33.3%). Table 4 demonstrates that 38.7% of natural
A list of maternal data is provided in Table 1. Regarding childbirth (Vaginal delivery) was categorized to the
the mean age of the mother, the maternal age was bilirubin level, where ranged from 10-14.9; while the
significantly associated with different levels of bilirubin bilirubin level in the range of 15-19.9 mg/dL was
(p = 0.02), indicating a significant correlation of attributed to a frequency of 54.8% ; Furthermore,
maternal age with incidence of jaundice. Maternal bilirubin values ranged from 20- 24.9 mg/dL in 33.3%
weight, and BMI showed also significant differences of neonates. The delivery mode was not associated with
among different levels of bilirubin (p = 0.001; p = 0.01). the incidence of hyperbilirubinemia (p = 0.2; Table 4).
As matter of fact, our findings suggest that the Regarding to oxytocin infusion, there was no significant
aforementioned variables were associated with neonatal difference between oxytocin infusion and disease
jaundice. Respiratory rate at delivery, maternal heart incidence (p = 0.5; Table 4). According to the data of
rate and height had a significant difference at various this study, there was a significant relationship between
levels of bilirubin, and were found to be linked to prolonged delivery and the incidence of neonatal
incidence of jaundice (p = 0.44; p = 0.85 p = 0.19). jaundice (p= 0.03, Table 4). Moreover, 46.6% of
Table 2 shows the association of some maternal blood infants, who showed premature rupture of membranes
factors with jaundice. The statistical analysis revealed (PROM), had a bilirubin level in the range of 10-14.9
that maternal WBC, PLT and Hb had a significant mg/dL, followed by bilirubin levels in the range of 15-
relationship with jaundice (p = 0.001; p = 0.001; p = 19.9 (61.3%) and 20- 24.9 mg/dL (33.3%). No
0.04), but maternal MCV, and HCT did not show association was found between PROM and different
significant correlation with bilirubin levels (p = 0.77; P levels of bilirubin (p = 0.2, Table 4). ,Om the ther hand
= 0.88). There is a significant difference in terms of neonates with different levels of bilirubin had no
birth in the first pregnancy among neonates with significant difference in maternal cesarean section (p =
different levels of bilirubin (p = 0.01; Table 2). Our 0.1, Table 5). As shown in Table 5, 16% of infants
findings also indicate that the numbers of pregnancies delivered by a multiple pregnancy showed a bilirubin
were more likely to be referred for bilirubin levels level between 10-14 mg/dL. 10-14.9; while the bilirubin
(p=0.00; Table3). In addition, interpregnancy interval of level in the range of 15-19.9 mg/dL was attributed to a
less than 3 years was not found to be linked to frequency of 6.5% and bilirubin values ranged from 20-
hyperbilirubinemia (p= 0.9; Table 3). Table 4 shows 24.9 mg/dL in 0% of neonates. It is noteworthy that no

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 Maternal risk factors for neonatal jaundice
Eur J Transl Myol 28 (3): 257-264, 2018

Table 3. Correlation of numbers of pregnancies with neonatal jaundice based on the different bilirubin levels

P=0.001 Bilirubin Total

10-14.9 15-19.9 20-24.9
number/of/pregnancy 1.00 Number of (first pregnancy) 49 18 2 69

Percent 30.1% 58.1% 33.3% 34.5%

2.00 Number of (second pregnancy) 57 5 1 63
Percent 35.0% 16.1% 16.7% 31.5%
3.00 Number of (third pregnancy) 32 6 2 40
Percent 19.6% 19.4% 33.3% 20.0%
4.00 Number of (fourth pregnancy) 21 0 0 21
Percent 12.9% 0% 0% 10.5%
5.00 Number of (fifth pregnancy) 0 2 1 3
Percent 0% 6.5% 16.7% 1.5%
6.00 Number of (sixth pregnancy) 3 0 0 3
Percent 1.8% 0% 0% 1.5%
8.00 Number of (seventh pregnancy) 1 0 0 1
Percent 0.6% 0% 0% 0.5%
Total Number 163 31 6 200
Percent 100.0% 100.0% 100.0% 100.0
%

Relationship between the number of pregnancies and neonatal jaundice

P=0.9 Bilirubin Total

10-14.9 15-19.9 20-24.9

interpregnancy interval No Number 106 20 4 130
of less than 3 years
Percent 65.0% 64.5% 66.7% 65.0%
Yes Number 57 11 2 70
Percent 35.0% 35.5% 33.3% 35.0%
Total Number 163 31 6 200

Percent 100.0% 100.0% 100.0% 100.0%

significant difference was found between twins and higher serum bilirubin levels in neonates of younger
disease incidence among neonates with different levels mothers.16 A previous study has also suggested that
of bilirubin (p= 0.2). The history of abortion did not maternal age ≥30 years can be linked to increased risk
show a significant relationship with the incidence of for neonates.17 Another study by Özdek et al.
disease (p = 0.2; Table 5). demonstrated that mothers who have more weight than
Jaundice is a complication that may lead to death in the the advised amount may be at risk of neonatal
first month of birth and infants who are still alive suffer jaundice.18 Conversely, many studies have reported that
from many disorders including mental retardation this variable was not correlated with
(Intellectual disability), mobility and balance disorders, hyperbilirubinemia.19,20 In the present study, the mean
seizures, hearing loss at high frequencies, and speech age of mothers in patients was determined as 28.8 years
impairment. Protecting and promoting the health of (Maximum: 43 years; Minimum: 17 years). Based on
infants as a vulnerable group in the health services has a the findings, the mean age of mothers in newborns with
special place. Therefore, evaluation of neonatal jaundice moderate jaundice was lower than other forms of
in health care services should always be considered as a disease and the most cases of jaundice were observed in
fundamental policy. Nearby, early detection of its risk the first pregnancy (34.5%, 69 cases). In other studies,
factors can be effective in preventing disease in high- CBC level and its related parameters have not been
risk mothers-infants. Our study showed that maternal studied in the mother. One of the strengths of this study
age, weight, BMI, WBC, Hb, PLT, birth in the first is to examine the level of maternal blood parameters. It
pregnancy, numbers of pregnancies and prolonged seems that the levels of WBC, Hb, and PLT have a
delivery were significantly correlated with bilirubin significant correlation with the incidence of neonatal
levels. Maternal age was found to be statistically jaundice. However, it was found that that there was not
significant in statistical analysis. Srivastav et al., found an increasing risk for neonatal jaundice with maternal

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 Maternal risk factors for neonatal jaundice
Eur J Transl Myol 28 (3): 257-264, 2018

Table 4. Relationship between delivery method and jaundice in different levels of bilirubin

P=0.2 Bilirubin Total

10-14.9 15-19.9 20-24.9
Type of delivery Normal vaginal Number 63 17 2 82
delivery (NVD) Percent 38.7% 54.8% 33.3% 41.0%
Caesarean section Number 100 14 4 118
(CS) Percent 61.3% 45.2% 66.7% 59.0%
Total Number 163 31 6 200
Percent 100.0% 100.0% 100.0% 100.0%

Relationship between oxytocin infusion and jaundice in different levels of bilirubin

P=0.5 Bilirubin Total

10-14.9 15-19.9 20-24.9

Oxytosin injection Yes Number 147 26 5 178
Percent 90.2% 83.9% 83.3% 89.0%
No Number 16 5 1 22
Percent 9.8% 16.1% 16.7% 11.0%
Total Number 163 31 6 200
Percent 100.0% 100.0% 100.0% 100.0%

Association between prolonged delivery and incidence of jaundice in different levels of bilirubin
P=0.03 Bilirubin Total
10-14.9 15-19.9 20-24.9
Prolonged Yes Number 72 20 1 93
Percent 44.2% 64.5% 16.7% 46.5%
No Number 91 11 5 107
Percent 55.8% 35.5% 83.3% 53.5%
Total Number 163 31 6 200
Percent 100.0% 100.0% 100.0% 100.0%

Association between PROM and neonatal jaundice in different levels of bilirubin

P=0.2 Bilirubin Total
10-14.9 15-19.9 20-24.9
PROM Yes Number 76 19 2 97
Percent 46.6% 61.3% 33.3% 48.5%
No Number 87 12 4 103
Percent 53.4% 38.7% 66.7% 51.5%
Total Number 163 31 6 200
Percent 100.0% 100.0% 100.0% 100.0%

MCV, and HCT. Nevertheless, conversely, a study as delivery mods, twins, interpregnancy interval of less
indicated that maternal haemoglobin was not than 3 years were found to be associated with neonatal
demonstrated to affect the bilirubin levels in jaundice. In agreements with previous studies, there was
physiological jaundice.19 Further studies are needed to no an increasing risk for neonatal jaundice with the
clarify the role of blood factors mentioned in the current delivery mode, where was not correlated with the
study. Our finding suggested that birth in the first incidence of hyperbilirubinemia.
pregnancy, numbers of pregnancies and prolonged labor It has been previously reported that mode of delivery
could be important risk factors in current study could be liked to jaundice and its severity 19,20-24
population. In our study population, some factors such Contrary, it has been previously revealed that naturally

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 Maternal risk factors for neonatal jaundice
Eur J Transl Myol 28 (3): 257-264, 2018

Table 5. Association between neonatal hyperbilirubinemia and cesarean section

P=0.1 Bilirubin Total

10-14.9 15-19.9 20-24.9
History of cesarean Yes Number 58 6 3 67
section (CS) Percent 35.6% 19.4% 50.0% 33.5%
No Number 105 25 3 133
Percent 64.4% 80.6% 50.0% 66.5%
Total Number 163 31 6 200
Percent 100.0% 100.0% 100.0% 100.0%
Correlation between neonatal hyperbilirubinemia and multiple births in the current pregnancy (twin)
P=0.2 Bilirubin Total
10-14.9 15-19.9 20-24.9
Multiple birth YES Number 26 2 0 28
in the current Percent 16.0% 6.5% 0%. 14.0%
pregnancy NO Number 137 29 6 172
(twin) Percent 84.0% 93.5% 100.0% 86.0%
Total Number 163 31 6 200
Percent 100.0% 100.0% 100.0% 100.0%
History of abortion and risk of hyperbilirubinemia
P=0.2 Bilirubin Total
10-14.9 15-19.9 20-24.9
History of Yes Number 81 11 4 96
abortion Percent 49.7% 35.5% 66.7% 48.0%
No Number 82 20 2 104
Percent 50.3% 64.5% 33.3% 52.0%
Total Number 163 31 6 200
Percent 100.0% 100.0% 100.0% 100.0%

delivered subjects are likely to be at higher risk for neonatal jaundice in our study population. In consist
neonatal jaundice, when comparing with those born by with the current study, Scrafford, et al, reported a
cesarean section, indicating the importance of delivery significant association of prolonged labor with jaundice,
mode as a risk factors for jaundice.25,26 The conflicting possibly the clinical relationship between longer labor
findings could be linked to types of variables, types of and cephalohematoma may play a role in this event.10,30
study, sample size and study condition, where can affect Furthermore, no significant association was found
to data analysis. On the other hand, no significant between PROM and neonatal jaundice, however PROM
difference was found between oxytocin infusion and has been described to affect some of the parameters
disease incidence, while oxytocin is involved in involved in the health of fetuses and infants, such as
bilirubin metabolism and has been described to be a neonatal jaundice, platelet parameters and erythrocyte
risk factor for the development of neonatal jaundice, parameters 31, Further evaluation are required to clarify
induction of labor with oxytocin may associated with the role some of mentioned variable that were not
hypoosmotic and lytic effects (increased red blood cell showed correlation with neonatal jaundice. Twins was
lysis), resulting in hyperbilirubinemia 26-28. However, it not important risk factors in the current study, several
is recommended that this factor be assessed with a reported risk factors were not found in the current study
higher sample size. Excessive application of oxytocin to be correlated with jaundice in neonates such as twins
during labor and cesarean section have been defined 32-35
. As matter of fact twins was found to be correlated
as risk factors.25, 26 In the present study, cesarean with hyperbilirubinemia in some investigations, but we
section was not found to be associated with did not find such association in our studies. In consist
hyperbilirubinemia. Hyperbilirubinemia might be with our study, Scrafford et al. did not demonstrate
exacerbated by cesarean section, in comparison to correlation between twins and hyperbilirubinemia.10 The
natural births 11. On the other hand, mode of delivery number of multiple births was very low in the current
has been not found to be significantly associated with study (N=28), whereas caution should be observed in its
incidence of hyperbilirubinemia.29 As mentioned in interpretation; thereby, may reduce the statistical power
results, prolonged labor remained obviously linked to for determining the statistically strong association

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 Maternal risk factors for neonatal jaundice
Eur J Transl Myol 28 (3): 257-264, 2018

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delivery type and jaundice severity among
newborns referred to Ghaem Hospital within a 6-

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