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ORIGINAL ARTICLE
Abstract
Background . Anemia in pregnancy contributes to poor outcome for mother and child in low-income countries. This study
analyzes adverse maternal and fetal outcome after severe anemia in pregnancy in rural Ghana. Methods. A cohort study in
two (sub)district hospitals, including 157 pregnant women exposed to severe anemia (HbB/8.0 g/dl) and 152 nonexposed
pregnant women (Hb ]/10.9 g/dl), matched for age and parity strata. Adverse outcomes analyzed were postpartum
hemorrhage, need for blood transfusion, maternal mortality, low birth-weight, and perinatal mortality. Results. Compared
to nonexposed women, exposed women had an increased risk of maternal death (5/157 versus 0/152). Fetal outcome did not
significantly differ between the study groups, although perinatal mortality was increased with exposure to Hb B/7.0 g/dl (OR
3.1; 95%CI 1.0 /9.4), and low birth-weight was increased with exposure to Hb B/6.0 g/dl (OR 2.5; 95%CI 1.2 /5.4). Overall
fetal outcome was significantly better when hemoglobin prior to childbirth was at least 8.0 g/dl (OR 3.9; 95%CI 1.6 /9.6),
body mass index at least 20 kg/m2 (OR 2.8; 95%CI 1.5 /5.3), and number of antenatal visits at least 4 (OR 2.0; 95%CI
1.1 /3.7). Conclusions . Severe anemia in pregnancy results in relatively poor maternal and fetal outcome. Apparently
maternal risks increase prior to fetal risks. In order to improve maternal and fetal outcome, it is recommended that district
hospitals in low-income countries make prevention, early diagnosis, and treatment of severe anemia in pregnancy a priority.
Key words: Anemia in pregnancy, maternal outcome, fetal outcome, low-income countries
Anemia in pregnancy is a common problem in low- although anemia in early pregnancy seems to be
income countries. It substantially contributes to associated with an increased risk of low birth-weight
poor outcome in both mother and child. Its effects or preterm birth (8,9). This study analyzes the effect
on maternal health include reduction of immune of severe anemia in pregnancy (HbB/8.0 g/dl) on
response, danger of heart failure, and aggravation of maternal and fetal outcome in a cohort of women in
the risks of childbirth (1,2). Maternal anemia during rural Ghana.
pregnancy may lead to poor fetal outcome through
growth retardation or perinatal death, while the risks
Methods
of infant morbidity and mortality are also increased
(3/7). However, it is not yet clearly known to what This cohort study was carried out at the district
extent these maternal and fetal risks are affected by hospital in Berekum and the subdistrict hospital in
anemia in pregnancy in low-income countries. Simi- Yeji, both in rural Ghana. From January 1, 1999 till
larly, little knowledge is available on the relation January 31, 2000, women who were treated for
between pregnancy outcome and severity of anemia, severe anemia in pregnancy (HbB/8.0 g/dl) were
gestational age at onset or duration of anemia, entered into the study, matched for age and parity
Correspondence: Jules H. Schagen van Leeuwen, Department of Obstetrics and Gynaecology, St. Antonius Hospital, PO Box 2500, 3430 EM Nieuwegein,
The Netherlands. E-mail: jsvleeuw@knmg.nl
with nonexposed women (Hb ]/10.9 g/dl) who at- were tested in a similar manner. The significance
tended the study hospitals for childbirth. This paper level was set at 5%.
deals with the results regarding maternal and fetal
outcome; the pregnancy component of the study as
Results
well as study setting and population are described in
detail elsewhere (10). In the study period 175 women had been treated for
Information concerning pregnancy outcome was severe anemia in pregnancy, but follow-up of preg-
collected from hospital records. When an exposed nancy outcome was complete for only 157 women
woman did not report at one of the hospitals for (89.7%). The nonexposed group, with 100% com-
childbirth, despite the advice to give birth in plete follow-up, consisted of 152 women.
hospital, she was traced and visited at home. Median age among women in the exposed group
Information concerning pregnancy outcome was was 22 years (range 16 /45) and 24.8% were
gathered from the woman, her relatives or husband, younger than 20 years of age. Median parity was 0
or from closely connected people in the same village. (range 0 /9), with 57.3% nullipara. Among parous
In case of birth at a health facility other than the women, 24.2% reported a previous cesarean section,
study hospitals, that facility was visited to obtain postpartum hemorrhage, or perinatal death. Ex-
details from their records. Nonexposed women were, posed women had been severely anemic with a
median lowest Hb of 6.5 g/dl. After treatment the
due to practical reasons, entered in the study before
median Hb had increased to 9.5 g/dl when last
or after their childbirth in the two hospitals, but
measured in pregnancy. The median age among
always exclusively based upon their nonanemic
nonexposed women was 22 years (range 16 /42) and
status during pregnancy, age, and parity.
17.8% were younger than 20 years of age. Median
History of present and any previous pregnancies,
parity was 0 (range 0/8), with 57.2% nullipara.
mode of delivery, place of birth, and birth attendant
Among parous women, 27.7% reported a previous
were recorded, as well as postpartum hemorrhage,
cesarean section, postpartum hemorrhage, or peri-
defined as a blood loss after birth ]/500 ml. Blood natal death. Median lowest Hb among nonexposed
loss was measured in hospitals or maternity clinics, women was 11.0 g/dl. Median Hb measured prior
but estimated by comparison with examples of to childbirth was 11.5 g/dl and 4.6% had a Hb ]/
known volumes as more or less than 500 ml in 14 g/dl. The study groups did not significantly differ
home births. Maternal deaths, circumstances of in age, parity, or poor obstetric history. The 18
death, and their main cause were recorded. Fetal women lost to follow-up were not significantly
outcome was recorded as live birth, stillbirth, or different from the other exposed women considering
neonatal death. Birth weight was recorded in grams their age, parity, residence, antenatal care visits,
in hospitals and maternity clinics, and estimated by body mass index, or lowest hemoglobin. They did,
comparison with other babies as above or below however, have a significantly lower hemoglobin level
2500 g in home births. Gestational age at birth was when last measured (mean 8.2 g/dl, SD 1.7; p B/
not recorded, as reliable information on this was 0.05).
generally lacking.
Data were entered in Epi-Info, version 6.04, and
validated. Differences in proportions between the Maternal outcome
exposed and nonexposed groups were assessed by Of 157 women exposed to severe anemia, two
x2-tests and odds ratios were calculated adjusted for aborted before a gestational age of 28 weeks. Details
age. The study design made use of stratum matching of childbirth were unknown for one woman,
between exposed and nonexposed women for both although it was known that she did deliver a live
age and parity, but as these two variables were found baby. One woman died while pregnant. Of the
to be colinear, analysis was stratified for age only. remaining 153 women, 141 (92.2%) gave birth
Differences in means were assessed with Students t - vaginally (133 spontaneously, 8 assisted), while 12
test for normally distributed variables. A logistic (7.8%) were delivered by cesarean section. Of the
regression model (SPSS 10.0) was fitted to assess 152 controls, 132 (86.8%) had a vaginal birth (123
which variables significantly contributed to the spontaneously, 9 assisted) and 20 (13.2%) were
variability in outcome of singleton babies of exposed delivered by cesarean section. The mode of delivery
and nonexposed women. The model was fitted was not significantly different between the two
through stepwise elimination of variables not sig- groups. Births were supervised by a trained atten-
nificantly contributing to the fit of the model, after dant (doctor, midwife) in 80.4% of women exposed
which interactions between the remaining variables to severe anemia: 64.7% gave birth in hospital,
Severe anemia in pregnancy in rural Ghana 51
low birth-weight (B/2,500 g). In the nonexposed Table III. Low birth-weight in exposed and nonexposed groups
group 21 (13.7%) babies were born with low birth-
weight. Mean birth-weight of singletons in the Singletons only Low birth (Age-adjusted)
weight (%) OR (95%CI)
exposed group was 2,802 g (SD 565), and in the
nonexposed group 2,996 g (SD 444), a difference of Nonexposed 20/151 (13.2) 1
194 g (p B/0.05). Birth weight of twins was low at a Exposed, lowest Hb B/8.0 g/dl 26/138 (18.8) 1.4 (0.7 /2.7)
mean of 2,120 g (SD 385); 14/17 (82.4%) twins Exposed, lowest Hb B/7.0 g/dl 17/90 (18.9) 1.4 (0.7 /2.8)
with a known birth weight weighed under 2,500 g. Exposed, lowest Hb B/6.0 g/dl 16/56 (28.6) 2.5 (1.2 /5.4)
Exposed, lowest Hb B/5.0 g/dl 13/30 (43.3) 4.2 (1.8 /10.1)
Supervision of birth was not significantly related to Exposed, last Hb ]/10.9 g/dl 3/34 (8.8) 0.8 (0.2 /2.7)
birth weight. Exposed, last Hb 8.0 /10.8 g/dl 13/80 (16.3) 1.1 (0.5 /2.4)
Confounding by differences in multiple pregnancy Exposed, last Hb B/8.0 g/dl 10/24 (41.7) 3.3 (1.3 /8.5)
between exposed and nonexposed women was Body mass index ]/20 kg/m2, 14/121 (11.6) 1
nonexposed
avoided by calculating age-adjusted OR of low
Body mass index B/20 kg/m2, 6/30 (20.0) 2.3 (0.8 /7.2)
birth-weight for singletons only. Compared to sin- nonexposed
gleton babies of nonexposed women, singleton Body mass index ]/20 kg/m2, 12/94 (12.8) 3.1 (0.5 /2.5)
babies of all women exposed to severe anemia were exposed
not significantly more likely to have low birth- Body mass index B/20 kg/m2, 14/44 (31.8) 3.1 (1.3 /7.6)
exposed
weight. However, when the lowest maternal hemo-
Age ]/20 years, nonexposed 11/121 (8.9) 1
globin had been below 6.0 g/dl, singleton babies of Age B/20 years, nonexposed 9/27 (33.3) 5.1 (1.7 /16.0)
exposed women had a significantly higher risk of low Age ]/20 years, exposed 17/104 (16.3) 2.0 (0.8 /4.9)
birth-weight (OR 2.5; 95%CI 1.2 /5.4; Table III). Age B/20 years, exposed 9/34 (26.5) 3.7 (1.2 /11.1)
Low birth-weight was also significantly more often
seen in singleton babies of women who remained
severely anemic at the end of their pregnancy (OR schistosomiasis, severe anemia, hemoglobin prior to
3.3; 95%CI 1.3 /8.5), or who had a body mass index childbirth, body mass index, number of antenatal
B/20 kg/m2 (OR 3.1; 95%CI 1.3 /7.6). Teenage visits, gestational age at first contact) and entered in
pregnancy was associated with low birth-weight in the model. After stepwise removal and testing of any
both exposed (OR 3.7; 95%CI 1.2 /11.1) and interactions, the number of antenatal visits, body
nonexposed groups (OR 5.1; 95%CI 1.7 /16.0). mass index, and hemoglobin prior to childbirth
To assess which combination of factors signifi- significantly contributed to the variability of the
cantly influenced fetal outcome, it was categorized as singletons outcome (at a 5% significance level).
good (live baby with a birth weight ]/2,500 g) or Together these variables explained approximately
adverse (perinatal death and/or birth weight 15% of the variability in outcome. Singleton babies
B/2,500 g). Possible explanatory variables were of women whose hemoglobin prior to childbirth was
identified. Multiple pregnancy was excluded, as at least 8.0 g/dl, were 3.9 times more likely to have a
this variable was found to be colinear with outcome, good outcome than babies of those who had a lower
and also would violate the assumption of indepen- hemoglobin at the end of pregnancy (mutually
dence of the binomial distribution. As the number of adjusted OR 3.9; 95%CI 1.6 /9.6). Singleton babies
twins was relatively small (20/316; 6.3%), the of women with a body mass index of at least 20 kg/
sensitivity of the study was not seriously affected. m2 were 2.8 times more likely to have a good
Malaria, intestinal parasitosis, supervision of birth, outcome than babies of women with a lower body
and lowest hemoglobin were all colinear with ex- mass index (mutually adjusted OR 2.8; 95%CI 1.5 /
posure to severe anemia in pregnancy (Hb B/8.0 g/ 5.3). Singleton babies of women who attended an
dl), and thus not used in the modeling. Sickle cell antenatal clinic at least four times during their
and HIV status, both untreatable in the setting of the pregnancy were 2.0 times more likely to have a
study, were combined into one variable, as these good outcome than babies of women who visited less
disorders each had a low prevalence in the study often (mutually adjusted OR 2.0; 95%CI 1.1 /3.7).
group. For the same reason urinary tract infection
and schistosomiasis, both treatable disorders, were
Discussion
combined into one variable. Number of antenatal
visits was dichotomized as B/4 visits or ]/4 visits, as The study results provide evidence that severe
a minimum of 4 antenatal visits is locally recom- anemia in pregnancy is associated with a poor
mended. Of the remaining variables, seven were maternal outcome. Although mode of delivery, risk
significantly related to the singletons outcome at a of postpartum hemorrhage, and risk of manual
10% significance level (age, urinary tract infection/ removal of placenta were similar in exposed and
Severe anemia in pregnancy in rural Ghana 53
nonexposed groups, women in the exposed group in low-income countries. In our study exposure to
tended more often to need a blood transfusion at hemoglobin levels of 8.0 g/dl or less, despite sub-
birth, compared to nonexposed women. The study sequent recovery, significantly increased maternal
group (n /309) was rather small to assess differ- risks. Fetal risks started to increase significantly with
ences in maternal mortality, and the number of exposure to hemoglobin levels below 7.0 g/dl (peri-
adverse maternal events was not adequate for further natal death) or below 6.0 g/dl (low birth weight).
statistical analysis. Even so, there was a significant Women who were not severely anemic at childbirth
difference in the number of deaths among exposed (Hb]/8.0 g/dl) had a greater chance of giving birth
and nonexposed women. At least one maternal death to a live baby of normal birth weight. Apparently
could have been avoided, had a blood transfusion maternal risks increase prior to fetal risk, which
been available. Only one death was possibly directly suggests that the definition of severe anemia as a
due to severe anemia in pregnancy, while four hemoglobin concentration below 7.0 g/dl, as given
women died of other causes. This shows the hidden by the WHO, may be more useful for assessing risks
contribution of anemia in pregnancy to maternal to the child than to the mother. A cut-off point for
mortality (11). The case fatality rate among women severe anemia of 8.0 g/dl has been suggested, based
exposed to severe anemia was high at 3.2%. Re- upon seasonal variation in the prevalence of anemia
markably, although they had been exposed to low (B/8.0 g/dl) related to malaria and iron deficiency
hemoglobin levels (5/7.0 g/dl), all five women re- (19). The findings of our study seem to support a
covered quite well (Hb ]/8.5 g/dl). It appears that higher cut-off point, in particular in view of maternal
severe anemia in pregnancy is, even after treatment, risks.
an important risk factor for maternal death. Exposure to severe anemia in pregnancy (Hb
In this study severe anemia in pregnancy ( B/8.0 g/ B/8.0 g/dl) in itself did not significantly contribute
dl) was not associated with poor fetal outcome. to the variability of fetal outcome in this analysis, but
Women exposed to Hb B/7.0 g/dl, however, had a rather recovery of hemoglobin levels to at least 8.0 g/
threefold increased risk of perinatal mortality, and dl. Therefore, in addition to exposure to severe
women exposed to Hb B/6.0 g/dl had a doubling of anemia in pregnancy, its duration and gestational
the risk of low birth-weight. Women whose hemo- age at onset could be important. This assumption is
globin level had not recovered to at least 8.0 g/dl supported by other findings, which detected an
before childbirth also had increased risks of perinatal association between low birth-weight and maternal
mortality and low birth-weight. Low birth-weight is anemia diagnosed in the first trimester (8). It is
an important determinant of infant mortality (6). In recommended that severe anemia in pregnancy is
addition, maternal anemia and low birth-weight swiftly treated, and hemoglobin levels corrected
contribute to infant anemia, due to insufficient iron before childbirth, to limit negative effects on fetal
storage in the prenatal period (5,12). outcome.
The relationship between hemoglobin concentra- When women regularly attended antenatal care
tion in pregnancy and fetal outcome follows a their chance of good fetal outcome was increased.
U-shape, with an increasingly poor outcome at Lack of a trained supervisor to attend birth was
both extremes. The association of poor fetal out- associated with a very poor fetal outcome. Inade-
come with high maternal hemoglobin levels, related quate antenatal and birth care played a role in three
to (pre)-eclampsia, has been described in high of the five maternal deaths in this study. These
income countries (4,13). This relationship of out- results clearly point towards the importance of
come and high hemoglobin was not confirmed by competent care during pregnancy and childbirth.
our findings, possibly because of the low prevalence Presently emergency obstetric care is emphasized as
of high hemoglobin levels. the key for reduction of maternal and fetal risks. It
Many studies have described the increased risk of remains important, however, to appreciate that
perinatal mortality (3,4,14 /16) and low birth- nonemergency antenatal and birth care also form
weight (3 /5,7,12,17) associated with low maternal part of essential obstetric services, as this provides
hemoglobin concentration. Comparison is difficult, opportunities for prevention and early detection of
however, due to different definitions of anemia. complications (20,21).
It has not yet been clarified at what hemoglobin The maternity units of both study hospitals
level anemia in pregnancy starts to affect maternal generally attend to women with complications of
and fetal outcome, and how seriously outcome is pregnancy or birth. Even the nonexposure group
affected (18). Very few prospective studies concern- consisted of hospital attenders at rather high risk,
ing maternal and fetal outcome after severe anemia indicated by the high percentage of women with a
in pregnancy have been performed, and even fewer poor obstetric history (27.7% of parous women) and
54 D. Geelhoed et al.
with cesarean sections (13.2%). Still, this group pregnancy and maternal and fetal outcome in low-
performed significantly better than women exposed income countries.
to severe anemia in pregnancy, as far as maternal and
fetal outcomes were considered. To ensure an
Conclusions
economic recruitment of women who had not been
exposed to any degree of anemia during pregnancy, In view of poor maternal and fetal outcome after
they were selected near childbirth, and thus gener- severe anemia in pregnancy, it is recommended that
ally entered later in the study than exposed women. district hospitals in low-income countries make
Therefore no conclusions can be drawn about prevention, early diagnosis and treatment of severe
differences in abortion rate. The late selection of anemia in pregnancy a priority. The current WHO
nonexposed women might have led to an uncon- definition point for severe anemia in pregnancy
scious preference to include women with a good (HbB/7.0 g/dl) might be inadequate for this pur-
pregnancy outcome. Among attenders of both study pose; a cut-off point of 8.0 g/dl could be more
hospitals, however, anemia in pregnancy is very appropriate. Adequate referral services for the man-
common, especially among young nulliparous wo- agement of emergency complications must be com-
men. It was quite difficult to find a sufficiently large plemented by nonemergency maternity care to
prevent and detect complications during pregnancy
number of nonanemic women of suitable age and
and childbirth, in order to improve maternal and
parity to comprise an adequate nonexposure group.
fetal outcome.
This difficulty would have prevented any possible
preference for women with a good pregnancy out-
come.
Follow-up of exposed women was high in this
study at 89.7%, certainly in view of the relatively References
poor infrastructure in the study districts. Among 1. Guidotti RJ. Anaemia in pregnancy in developing countries.
exposed women with home births, however, the Br J Obstet Gynaecol. 2000;107:437 /8.
/ /
reliable than in the case of health facility births. 3. Lone FW, Qureshi RN, Emanuel F. Maternal anaemia and its
Particularly when information had to be gathered impact on perinatal outcome. Trop Med Int Health. 2004;9: / /
from people other than the woman herself, and 486 /90.
4. Scholl TO, Hediger ML. Anemia and iron-deficiency anemia:
when it concerned nonfatal events such as birth
compilation of data on pregnancy outcome. Am J Clin Nutr.
weight or blood loss, trustworthiness may have been 1994;59:492S /500S.
/ /
compromised. To remedy this problem extensive 5. Verhoeff FH, Brabin BJ, Chimsuku L, Kazembe P, Broadhead
double-checking was done with as many people as RL. Malaria in pregnancy and its consequences for the infant
in rural Malawi. Ann Trop Med Parasitol. 1999;93:S25 /33.
closely concerned as possible, and in cases of / /
results can unfortunately not account for any poten- 8. Hamalainen H, Hakkarainen K, Heinonen S. Anaemia in the
tial confounding by these variables. In view of the first but not in the second or third trimester is a risk factor for
size of the odds ratios it is, however, unlikely that low birth weight. Clin Nutr. 2003;22:271 /5. / /
recovery from severe anemia in pregnancy or to have 10. Geelhoed D, Agadzi F, Visser L, Ablordeppey E, Asare K,
skilled care at childbirth, as well as poor nutri- ORourke P et al. Severe anemia in pregnancy in rural Ghana:
A case /control study of causes and management. Acta Obstet
tional status, are probably associated with poverty,
Gynecol Scand 2005 (in press).
and it seems likely that most women with poor 11. van den Broek N. Anaemia in pregnancy in developing
maternal or fetal outcome suffer from socioeconomic countries. Br J Obstet Gynaecol. 1998;105:385 /90. / /
WJ. Evaluer lanemia maternelle severe et ses consequences: 20. Measham DM, Kallianes VD (eds) Issues in Essential
la valeur dun simple examen de la coloration de conjunctives Obstetric Care. Report of a Technical Meeting of the Inter-
palpebrales. Cah Sante. 1999;9:12 /7.
/ / Agency Group for Safe Motherhood (1995). New York:
17. Brabin BJ, Ginny M, Sapau J, Galme K, Paino J. Con- Population Council, 1996.
sequences of maternal anaemia on outcome of pregnancy in a 21. World Health Organization. Antenatal Care. Report of a
malaria endemic area in Papua New Guinea. Ann Trop Med Technical Working Group (1994). Geneva: World Health
Parasitol. 1990;84:11 /24.
/ / Organization, WHO/FRH/MSM/96.8, 1996.