The Journal of Maternal-Fetal & Neonatal Medicine

ISSN: 1476-7058 (Print) 1476-4954 (Online) Journal homepage: http://www.tandfonline.com/loi/ijmf20

The effect of maternal anemia on maternal and

neonatal outcomes in twin pregnancies

Amit Kosto, Rania Okby, Maya Levy, Ruslan Sergienko & Eyal Sheiner

To cite this article: Amit Kosto, Rania Okby, Maya Levy, Ruslan Sergienko & Eyal Sheiner (2015):
The effect of maternal anemia on maternal and neonatal outcomes in twin pregnancies, The
Journal of Maternal-Fetal & Neonatal Medicine, DOI: 10.3109/14767058.2015.1084616

To link to this article: http://dx.doi.org/10.3109/14767058.2015.1084616

Published online: 15 Sep 2015.

Submit your article to this journal

Article views: 39

View related articles

View Crossmark data

Full Terms & Conditions of access and use can be found at

http://www.tandfonline.com/action/journalInformation?journalCode=ijmf20

Download by: [University of Otago] Date: 19 September 2015, At: 07:17

 http://informahealthcare.com/jmf
ISSN: 1476-7058 (print), 1476-4954 (electronic)

J Matern Fetal Neonatal Med, Early Online: 14

! 2015 Taylor & Francis. DOI: 10.3109/14767058.2015.1084616

ORIGINAL ARTICLE

The effect of maternal anemia on maternal and neonatal outcomes in

twin pregnancies
Amit Kosto1, Rania Okby1, Maya Levy1, Ruslan Sergienko2, and Eyal Sheiner1
1
Department of Obstetrics and Gynecology, Faculty of Health Sciences, Soroka University Medical Center, Ben-Gurion University of the Negev, Beer-
Sheva, Israel and 2Department of Public Health, Ben-Gurion University of the Negev, Beer-Sheva, Israel

Abstract Keywords
Downloaded by [University of Otago] at 07:17 19 September 2015

Objective: The objective of this study is to investigate the effect of second trimester anemia on Maternal anemia, maternal morbidity,
maternal and perinatal outcomes in twin pregnancies. pregnancy complications, twin gestation
Methods: A retrospective population-based study was conducted, comparing maternal and
neonatal outcomes in women carrying twins, with second trimester anemia (defined as History
hemoglobin510 g/dl) to those without anemia (defined as hemoglobin4or equal to 10 g/dl).
Deliveries occurred in a tertiary medical center in 2013. Received 10 July 2015
Results: During the study period, there were 307 twin deliveries. Hemoglobin levels were Revised 15 August 2015
available for 247 (80.4%) twins; 66 (26.7%) of these had anemia (510 g/dl) during the second Accepted 16 August 2015
trimester. Women with second trimester anemia had a higher parity (p 0.03), and needed Published online 14 September 2015
more blood transfusions than those with hemoglobin level4or equal to 10 g/dl (OR 1.6; 95%
CI 1.112.43, p50.001). No significant differences were noted between the groups regarding
other obstetrical outcomes or regarding perinatal outcomes.
Conclusion: Second trimester anemia in women carrying twins is associated with a high parity
and increases the risk for blood transfusions. However, in our population, maternal anemia in
twin gestations does not increase the risk for adverse perinatal outcome.

Introduction increased RBCs is the high metabolic demand, which in

turn causes increased secretion of erythropoetin by up to 50%
In the last few decades, there has been an increase in the rate
more than the usual level, finally causing RBCs production to
of twin gestations worldwide. According to the Central
rise [6]. These two factors are part of the natural maternal
Bureau of Statistics in Israel, between 2005 and 2010, the rate
accommodation in reaction to the needs of the growing uterus
increased by 6.8% [1]. This is attributed mainly to the
and fetus [7].
increasing use of fertility treatments and an upraise in the
The significant rise in blood plasma volume as opposed to
average age of women giving birth [2]. One of the most
the moderate rise in RBCs leads to a fall in the serum
common hematologic effects on the mother during pregnancy
hemoglobin (Hb) concentration, creating a physiological
both in singleton and twin gestations is the appearance of
anemia in pregnant women which reaches its peak at the
maternal physiological anemia [3].
end of the second trimester and the beginning of the third
The incidence of physiological anemia in singleton
trimester [8]. This drop in Hb concentration decreases blood
gestations ranges between 16% and 29% of all pregnancies.
viscosity and is thought to enhance placental perfusion,
There are two factors contributing to the cause of anemia;
providing better maternalfetal gas and nutrient exchange [9].
the first factor is an increase in blood plasma volume by
In women carrying twins the blood plasma volume
50% compared with a non-pregnant woman [4], due to an
increases by 1020% more than in women carrying a
increased activity of rennin and simultaneously decreased
singleton [10], and the total amount of RBCs increases at
levels of atrial natriuretic peptide (ANP) [5]. The second
the same rate as in singletons. As a result, the prevalence of
factor is an increase in red blood cells (RBC) by 25%
maternal anemia is higher in twin gestations [11].
compared with a non-pregnant woman. The reason for
The influence of anemia on maternal and neonatal
outcomes in singleton pregnancies has previously been
studied. An association has been found between maternal
anemia and preterm delivery (PTD) as well as low birth
Address for correspondence: Amit Kosto, Department of Obstetrics and
weight (LBW) in singletons [12].
Gynecology, Faculty of Health Sciences, Soroka University Medical
Center, Ben-Gurion University of the Negev, Beer-Sheva, Israel. A recent meta-analysis found that maternal anemia was
E-mail: kostoamit@gmail.com associated with higher risk for PTD, LBW, and post-partum
 2 A. Kosto et al. J Matern Fetal Neonatal Med, Early Online: 14

death [13]. Twin pregnancies are at a higher risk for maternal Table 1. Demographic characteristics of twins with and without second
trimester anemia.
and neonatal complications [14]. A study by Rouse et al.,
pertaining to women who had anemia and underwent a Anemia No anemia
cesarean delivery (CD), found that women with twin gesta- Parameters (n 66) (n 181) p values
tions needed more blood transfusions than women with a
Maternal age 30.9 5.4 31.1 5.5 0.9
singleton [15]. The present study was aimed to examine Ethnicity
whether maternal anemia in the second trimester is associated Jewish 33 (28.7%) (71.3%) 82 0.513
with adverse maternal and neonatal outcomes in twin Bedouin (25%) 33 (75%) 99
Fertility treatment 59 (32.6%) 27 (41%) 0.2
pregnancies.
Chorionicity
Dichorionic 57 (89.1%) 154 (87%) 0.669
Materials and methods Monochorionic 7 (10.9%) 23 (13%)
Parity
A retrospective population-based study was conducted to 0 16 (24.2%) 66 (36.5%) 0.03
examine whether maternal anemia is associated with obstet- 1 14 (21.2%) 42 (23.2%)
2-4 31 (47%) 50 (27.6%)
rical complications and adverse perinatal outcomes. The 5+ 5 (7.6%) 23 (12.7%)
study was approved by the ethics committee of the institute.
The study population included all registered twin births in Values are presented as mean SD, median (interquartile range) or
n (%).
the Soroka University Medical Center, a tertiary hospital, in
2013. During the study period, there were 307 twin deliveries.
Downloaded by [University of Otago] at 07:17 19 September 2015

The data were obtained from the computerized medical files

of each birth. Each file included information about the course
of pregnancy and delivery. Patients that had no available Hb
test from the second trimester of pregnancy were excluded
from the study (n 60). The institutional computerized birth
database was combined with the hematological laboratory
data. When multiple measurements of Hb were available, the
first lowest value of Hb during the second trimester of
pregnancy was extracted from the laboratory data. Anemia
was defined as hemoglobin less than 10 g/dl [16]. Obstetric
complications and adverse perinatal outcomes were recorded
for women with and without anemia, during the second
trimester of pregnancy.
PTD was defined as delivery before 37 completed weeks of
gestation. Small for gestational age (SGA) was defined as
estimated fetal weight below the 10th percentile.
The following clinical characteristics were collected for
each delivery: maternal age, ethnicity (Jewish, or Arab-
Bedouin), fertility treatment, parity, chorionicity and gesta-
tional age at delivery.
The following obstetrical characteristics were examined:
gestational diabetes mellitus, preeclampsia, post-partum
hemorrhage, need for blood transfusion, cesarean delivery
(CD), PTD537 weeks gestation, and early PTD534 weeks
gestation. The following perinatal outcomes were assessed for
each twin: fetal gender, birth weight, congenital malforma-
tions, perinatal mortality, SGA, and low Apgar score (57) at
1 min and at 5 min.
Statistical significance was determined using the 2 test,
the Fisher exact test for differences between qualitative
variables, and the t-test for differences between continuous
variables.
Odds ratios (OR) and their 95% confidence intervals (CI)
were calculated. p50.05 was considered statistically
significant.
Results
During the study period, there were 307 twin deliveries. Of
those deliveries, Hb levels were available for 247 (80.4%); of
these, 66 (26.7%) had anemia and 181 (73.3%) had normal Hb
levels during the second trimester.
Demographic and clinical characteristics of the study
population are presented in Table 1. There was no difference
in maternal age or ethnicity between twins gestations with
maternal anemia compared to twins gestations without
maternal anemia. Patients with anemia during the second
trimester were more likely to have higher parity (p 0.03)
compared with non-anemic patients. Table 2 presents obstet-
ric characteristics of women with and without anemia during
the second trimester. Patients with anemia were more likely to
receive blood transfusions (p values50.001, OR 1.6, 95%
CI 1.112.43). There were no significant differences
between the groups regarding the rate of gestational dia-
betes mellitus, preeclampsia, post-partum hemorrhage, CD,
and PTD.
A comparison of perinatal outcomes between the groups is
summarized in Table 3. Twins of the anemic patient had a
higher rate of SGA than the non-anemic patient, but this
difference was not statistically significant. There was no
significant difference between the groups regarding the rate of
LBW, congenital malformations, perinatal mortality, and low
Apgar score (57) at 1 min and at 5 min.
Discussion
Since maternal anemia in twin pregnancies is considered
more significant (lower Hb values) than in singleton
pregnancies [10], understanding its significance and conse-
quences is of major importance. The main finding of our
study is that anemia during the second trimester of pregnancy
is not a risk factor for adverse perinatal outcome in twin
pregnancies. Nevertheless, it was noted to be a risk factor for
the need of blood transfusion. This can be explained by the
fact that the Hb levels in twin pregnancies are probably lower
than those in singletons.
Although anemia was associated with sub-optimal preg-
nancy outcomes mainly due to LBW and PTD [1214], our
study did not find those factors as significant in twin gestation
maternal anemia. Furthermore, even without anemia, there is
a high prevalence of SGA and PTD in twin gestations [17].
Common causes for PTD include infection or inflamma-
tion, vascular disease, and uterine over distension [18].
 DOI: 10.3109/14767058.2015.1084616 Effect of maternal anemia on twin pregnancies 3
Table 2. Pregnancy outcome for twins with and without second trimester anemia.

Parameters Anemia (n 66) No anemia (n 181) OR 95% CI p values

Preeclampsia 7 (10.6%) 12 (6.6%) 1.1 0.821.67 0.3
Post partum hemorrhage 1 (1.5%) 3 (1.7%) 0.9 0.551.72 0.9
Blood transfusion 16 (24.2%) 14 (7.7%) 1.6 1.112.43 50.001
Gestational diabetes mellitus 3 (4.5%) 7 (3.9%) 1.04 0.691.58 0.81
Cesarean delivery
First twin 35 (53%) 112 (61.9%) 0.9 0.771.06 0.21
Second twin (53%) 35 115 (63.5%) 0.8 0.751.04 0.13
Preterm birth (537 weeks) 37 (56.1%) 112 (61.9%) 0.9 0.81.09 0.4
Early preterm birth (534 weeks) 20 (30.4%) 45 (24.9%) 1.07 0.891.29 0.4

Values are presented as n (%). CI, confidence interval; OR, odds ratio.

Table 3. Neonatal outcome for twins with and without second trimester anemia.

Parameters Anemia (n 66) No anemia (n 181) OR 95% CI p values

Fetal gender-first twin
Female 36 (54.5%) 84 (46.4%) 0.9 0.781.06 0.25
male (45.5%)30 (53.6%)97
Downloaded by [University of Otago] at 07:17 19 September 2015

Fetal gender-second twin

Female 40 (60.6%) 81 (44.8%) 0.8 0.720.98 0.02
male 26 (39.4%) 100 (55.2%)
Birth weight (g)52500 g
First twin 43 (65.2%) 123 (68%) 1.03 0.871.21 0.67
Second twin 45 (68.2%) 132 (72.9%) 1.06 0.891.27 0.46
SGA (510 percentile) 13 (19.6%) 20 (11.0%) 1.24 0.931.65 0.07
Apgar score575 min
First twin 4 (6.1%) 10 (5.6%) 1.02 0.731.44 0.8
Second twin 4 (6.1%) 7 (3.9%) 1.1 0.741.83 0.4
Fetal malformation 6 (9.1%) 32 (17.7%) 0.84 0.720.99 0.09
Perinatal mortality 4 (6.1%) 7 (3.9%) 1.1 0.731.82 0.46

Values are presented as n (%). CI, confidence interval; OR, odds ratio.

Physiological stimuli to the onset of parturition, including
over distension, placental corticotrophin-releasing hormone,
and lung maturity factors, may be stronger in multiple
pregnancies due to the increased fetal and placental mass. The
treatments that prevent PTD in singleton pregnancies, such as
progesterone and cervical cerclage, appear to be ineffective in
multiple pregnancies [19]. This might suggest that PTD in
singleton gestation has a different mechanism as opposed to
that of twin gestation, and anemia might not be related.
In our study, there was a difference in the rate of SGA
newborns between the anemic and non-anemic mothers, but
this difference did not reach statistical significance. One
explanation might be the relatively small sample size.
Another explanation could be that SGA is a lot more
common in twins than singletons. In singletons, at 40 weeks
the median birth weight is 3289 g. This birth weight is
achieved by a pair of twins at 31 weeks, when the median of
the total fetal birth weight for both twins is 3358 g [20]. After
this gestational age, the growth rate becomes slower [21].
However, the growth of twin fetuses is commonly assessed
and interpreted using singleton-based growth charts [22]. This
practice may lead to an overestimation of IUGR in twins [23].
Anemia was associated with high parity in our study. The
effect of high parity on the development of maternal anemia
in singleton pregnancies is associated with iron depletion,
which is considered more common in multiparous than in
nulliparous women. Iron deficiency is the most common
cause of anemia in pregnancy worldwide [12,24].
Although lower values of Hb were previously found in
twin gestations as opposed to singleton gestations, informa-
tion regarding the maternal and perinatal effects of anemia in
twins is lacking in the medical literature. This comprehensive
database allowed us to access pregnancy information that was
obtained in a retrospective manner. It is important to
emphasize that we based our diagnosis of anemia on maternal
Hb levels, while the gold standard test for iron deficiency
anemia in pregnancy is ferritin levels [25]. Furthermore, there
is no correlation between Hb and ferritin levels in anemic and
non-anemic pregnant women [22].
Our study has several inherent weaknesses due to its
retrospective nature, such as the potential for missing data.
However, the data reported by an obstetrician directly after
delivery and skilled medical secretaries routinely reviewed
the information prior to entering it into the database, thereby
minimizing recall bias. Coding was done after assessing the
medical prenatal care records together with the routine
hospital documents. Additionally, our study population is
relatively small, which affects the significance of some of our
results.
In conclusion, our study found that women carrying twins
who had maternal anemia were at higher risk for the need of
blood transfusion. Careful surveillance should be maintained
in pregnancies of anemic parturient.
Future prospective studies should focus on the significance
of maternal anemia during the second trimester in twin
gestations using a larger study population.
 4 A. Kosto et al.
Declaration of interest
The authors report no conflicts of interest.
References
1. The Central Bureau of Statistics in Israel. Available from: http://
www.cbs.gov.il/publications/lidot/lidot_all_1.pdf [last accessed
Sept 3 2015].
2. Russell RB, Petrini JR, Damus K, et al. The changing epidemiology
of multiple births in the United States. Obstet Gynecol 2003;101:
12935.
3. Tzur T, Weintraub AY, Sergienko R, Sheiner E. Can anemia in the
first trimester predict obstetrical complications later in pregnancy?
J Matern Fetal Neonatal Med 2012;25:24547.
4. American College of Obstetricians and Gynecologists. ACOG
Practice Bulletin No.95: anemia in pregnancy. Obstet Gynecol
2008;112:2017.
5. Lund CJ, Donovan JC. Blood volume during pregnancy.
Significance of plasma and red cell volumes. Am J Obstet
Gynecol 1967;98:394403.
6. Ueland K. Maternal cardiovascular dynamics. VII. Intrapartum
blood volume changes. Am J Obstet Gynecol 1976;126:6717.
7. Letsky E. The haematological system. In: Hytten F, Chamberlain
Downloaded by [University of Otago] at 07:17 19 September 2015
G, eds. Clinical physiology in obstetrics. 2nd ed. Oxford: Blackwell
Scientific Publications; 1991:3982.
8. Whittaker PG, Macphail S, Lind T. Serial hematologic changes and
pregnancy outcome. Obstet Gynecol 1996;88:339.
9. Mani S, Duffy TP. Anemia of pregnancy. Clin Perinatol 1995;22:
593607.
10. Kametas NA, McAuliffe F, Krampl E, et al. Maternal cardiac
function in twin pregnancy. Obstet Gynecol 2003;102:80615.
11. Goodnight W, Newman R, Society of MaternalFetal Medicine.
Optimal nutrition for improved twin pregnancy outcome. Obstet
Gynecol 2009;114:112134.
12. Levy A, Fraser D, Katz M, et al. Maternal anemia during pregnancy
is an independent risk factor for low birthweight and preterm
delivery. Eur J Obstet Gynecol Reprod Biol 2005;122:1826.
J Matern Fetal Neonatal Med, Early Online: 14
13. Haider BA, Olofin I, Wang M, et al. Nutrition Impact Model Study
Group (anaemia). Anemia, prenatal iron use, and risk of adverse
pregnancy outcomes: systematic review and meta-analysis. BMJ
2013;346:f3443.
14. Young BC, Wylie BJ. Effects of twin gestation on maternal
morbidity. Semin Perinatol 2012;36:1628.
15. Rouse DJ, MacPherson C, Landon M, et al. National Institute of
Child Health and Human Development Maternal-Fetal Medicine
Units Network. Blood transfusion and cesarean delivery. Obstet
Gynecol 2006;108;8917.
16. Cunningham FG, Gant NF, Leveno KJ, et al. Williams obstetrics,
21st ed. New York: McGraw-Hill; 2001.
17. Joseph K, Liu S, Demissie K, et al. The Fetal and Infant Health
Study Group of the Canadian Perinatal Surveillance System.
A parsimonious explanation for intersecting perinatal mortality
curves: understanding the effect of plurality and of parity. BMC
Pregnancy Childbirth 2003;3:3.
18. Goldenberg RL1, Culhane JF, Iams JD, Romero R. Epidemiology
and causes of preterm birth. Lancet 2008;371:7584.
19. Stock S, Norman J. Preterm and term labour in multiple
pregnancies. Semin Fetal Neonatal Med 2010;15:33641.
20. Blickstein I. Is it normal for multiples to be smaller than
singletons? Best Pract Res Clin Obstet Gynaecol 2004;18:
61323.
21. Grumbach K, Coleman BG, Arger PH, et al. Twin and singleton
growth patterns compared using US. Radiology 1986;158:23.
22. Doom EC, Delbaere I, Martens G, Temmerman M. Birth weight for
gestational age among Flemish twin population. Facts Views Vis
Obgyn 2012;4:429.
23. Breathnach FM, Malone FD. Fetal growth disorders in twin
gestations. Semin Perinatol 2012;36:17581.
24. Chang SC, OBrien KO, Nathanson MS, et al. Hemoglobin
concentrations influence birth outcomes in pregnant African-
American adolescents. J Nutr 2003;133:234855.
25. Tiwari M, Kotwal J, Kotwal A, et al. Correlation of haemoglobin
and red cell indices with serum ferritin in Indian women in second
and third trimester of pregnancy. Med J Armed Forces India 2013;
69:316.