World Journal of AIDS, 2011, 1, 1-7
doi: 10.4236/wja.2011.11001 Published Online March 2011 (http://www.SciRP.org/journal/wja)
Copyright © 2011 SciRes. WJA
1
Risk Factors for Prematurity among Neonates
from HIV Positive Mothers in Cameroon
Taguebue J1,2, Monebenimp F2, Zingg W1, Mve Koh V3, Atchoumi A3, Gervaix A1, Tetanye E2
1Department of Pediatrics and Adolescent Medicine, University Hospitals of Geneva, Geneva, Switzerland; 2Department of Pediat-
rics, University of Yaoundé Hospital, Yaoundé, Cameroon; 3Department of Gynecology and Obstetrics, University of Yaoundé Hos-
pital, Yaoundé Cameroon.
Email: walter.zingg@hcuge.ch
Received March 11th, 2011; revised March 15th, 2011; accepted March 18th.
ABSTRACT
Objective: Human immunodeficiency virus (HIV) infection is the most important chronic health condition among
women in childbearing age in sub-Saharan Africa. There is sparse data about socio-economic factors in the context
with adverse outcome in pregnancy. The objective of the study was to identify such factors for prematurity, low birth
weight (LBW) and intrauterine growth retardation (IUGR) in infants born to HIV-positive women in Cameroon. Meth-
ods: The study was done in Yaoundé between December 2001 and November 2007. Neonates born to HIV-positive
mothers were monitored and clinical data as well as socio-economic factors were tested for association with prematur-
ity, LBW and IUGR. Findings: In total, 264 neonates were analyzed. More prematurity occurred when mothers at-
tended less than 4 prenatal care visits (OR [95% CI]: 2.7 [1.21 - 6.05]; p = 0.015). HIV-classification > 1 resulted in
more IUGR (OR [95% CI]): 3.15 [1.4 - 7.4]; p = 0.01) and LBW (2.20 [1.1 - 4.6]; p = 0.03). Single women were more
likely to attend 4 prenatal care visits or more (OR [CI95%]: 2.4 [1.6 - 3.4]; p < 0.001); higher education resulted in
better compliance with anaemia p rophylaxis (OR [CI95%]: 3.0 [1.5 - 5.8]; p = 0.002) and antimalaria prophylaxis (OR
[CI95%]: 2.1 [1.4 - 3.3]; p < 0.001); and was associated with early HIV diagnosis (p = 0.003). Conc lus ion : Prenatal
care improves outcome in pregnancy of HIV-positive women. Single mothers compared to women in family settings are
more likely to attend prenatal care visits, and HIV was diagnosed earlier in pregnancy in this population. More effort
should be put to address women in family settings to early diagnose HIV and to increase compliance with prenatal
care.
Keywords: Neonates, HIV, Pregnancy, Prematurity, Low Birth Weight, I ntr a ut eri ne Growth Retardation, Cameroon,
Africa, Education
1. Introduction
Low birth weight (LBW), prematurity and intrauterine
growth (IUGR) is associated with considerab le morbidity
and mortality in the neonatal period as well as in the first
year and adult life [1-5]. LBW often is due to IUGR,
prematurity or a combination of both. However, other
factors such as a lower socio economic status, a single-
parent family, extreme maternal age at delivery ( < 20 or
> 34 years), a lower education level, short intervals be-
tween pregnancies, multiple pregnancy, tobacco and/or
alcohol use during pregnancy, low weight gain during
pregnancy, and chronic illness of the mother have been
associated with LBW as well [6-10].
Human immunodeficiency virus (HIV) infection with
or without acquired immunodeficiency syndrome (AIDS)
is the most important chronic health condition among
women in childbearing age in sub-Saharan Africa with
an estimated 12.2 millions women affected. The overall
HIV prevalence in Cameroun is 5.5%. The prevalence
among women in childbearing age shows geographical
distribution between 5.7% up to more than 12% [11].
Studies from central Africa found that HIV-positive moth-
ers are especially at risk for preterm childbirth or giving
birth to a child with IUGR or LBW [12-15]. There is a
direct correlation between vertical HIV transmission,
LBW and a high mortality [16-19].
Before 2008, ART was not available free of charge for
the HIV-treatment during pregnancy in Cameroon.
However, standardized HIV prophylaxis with nevirapine
and zidovudine was offered at delivery. All newborns
were treated with nevirapine single dose alone (before
Risk Factors for Prematurity Among Neonates from HIV Positive Mothers in Cameroon
2
2003) or in combination with zidovudine for 4 weeks
(from 2003) [20]. With the introduction of such precau-
tion measures for vertical transmission more and more
women were offered an HIV-test during pregnancy. A
steady increase of HIV-testing revealed to what extent of
offspring was at risk for HIV and related health condi-
tions in Cameroon. The aim of this study was 1) to iden-
tify LBW, IUGR and prematurity of children born to
HIV-positive mothers; and 2) to identify modifiable risk
factors associated with LBW, IUGR and prematurity of
infants born to HIV-positive women.
2. Methods
Setting: This prospective cohort study was done at the
University of Yaoundé Teaching Hospital (UYT), one of
four university hospitals in Yaoundé. The department of
gynaecology and obstetrics at the UYT has an estimated
2250 deliveries per year.
Inclusion criteria: all neonates born to HIV positive
mothers were prospectively included in the study be-
tween December 2001 and November 2007 if: 1) they
were born at UYT; 2) has an HIV-positive mother; who 3)
attended at least one prenatal care visit at UYT. Only
cases with at least 75% of data completed as required by
the case related form (CRF) were included in the final
analysis.
Variables: Clinical data of neonates and mothers in-
cluded in the study was obtained from patient charts. All
mothers were checked clinically (fatigue, pallor) for
anaemia on the occasion of prenatal care visits and at
delivery. Haem oglobin levels were checked only if clinical
signs for anaemia were present. Syphilis was routinely
screened with a VDRL test at least once at the visit dur-
ing pregnancy.
Definitions: LBW was defined as a birth weight <2500
g. Prematurity was defined as a gestational age below 37
weeks. IUGR was defined as a birth weight below the
10th percentile of gestational age based on the UK Na-
tional Healthcare Care intrauterine growth curve. The
weight-to-length ratio (WLR) was calculated using the
Rohrer’s ponderal index (100* weight/length3 where
weight is indicated in grams and length in centimetres)
[21]. A mother was considered HIV-positive when at
least two different HIV antibody tests (either for HIV-1
or for HIV-2) were positive or if one positive antibody
test was confirmed by a western-blot. Time of HIV-di-
agnosis was stratified into four groups: 1) before preg-
nancy; 2) during the first trimester; 3) during the second
trimester; and 4) during the third trimester of pregnancy.
Clinical stage of HIV disease was classified using the
WHO clinical classification [22]. Antiretroviral therapy
(ART) was defined as any combination of at least three
antiretroviral drugs regardless of specific drug combina-
tions or whether the substances were active or not. When
available, HIV viral load, total lymphocyte cell counts,
CD4 cell counts, and CD8 cell counts were recorded. The
number of prenatal care visits was stratified into trimes-
ters and a maximum of two visits per trimester was
counted. Socioeconomic parameters such as matrimonial
status, regular income and source of income of the
mother were obtained from the patient files. Compliance
with malaria prophylaxis was obtained from the patient
charts and defined as sleeping under a mosquito net
and/or taking an intermittent treatment of 1500 mg sul-
fadoxine-pyrimethamine every 8-12 weeks beginning at
16 weeks of pregnancy. Malaria was suspected if the
mother had a fever (>38˚C) during the pregnancy or at
the time of delivery and confirmed if Plasmodium falci-
parum was detected in the blood or when symptoms re-
solved after anti-malaria treatment in the absence of
other antimicrobial agents. Anaemia prophylaxis was
defined as starting intake of iron and folic- acid daily in
the third trimester or before. Anaemia was defined as
haemoglobin of below 11 g/l. Syphilis was considered
positive if a positive VDRL test was confirmed by a
TPHA test. The diagnosis of eclampsia or preeclampsia
was done on clinical grounds.
Statistical Analysis: Sample size calculation was done
using US-data and data from Rwanda as specific data on
LBW in Cameroun are not available[19,23]. Categorical
variables were compared using the x2 test; continuous
variables were summarized as means or medians and
compared using the Wilcoxon rank sum test. We used
logistic regression to investigate the association between
potential risk factors and IUGR as defined as birth
weight < 10th percentile. We first investigated all poten-
tial risk factors in univariate analysis. Variables associ-
ated with an increased risk for IURG with a p-value < 0.2
were analyzed in multivariate analysis. A p-value < 0.05
was considered statistically significant and only variables
meeting this criteria were kept in the final model. All
statistical analyses were conducted using Stata 10.0
(Stata Corporation, College Station, Texas; USA).
3. Results
Enrolment: Among a total of 15379 children born at
UYT during the study period, 496 children were born to
HIV-1-positive mothers (Figure 1): 119 neonates were
excluded because their mothers did not have prenatal
care at UYT and therefore information about pregnancy
was not obtainable; 113 neonates were excluded from
final analysis because documents were less than 75%
complete. A total of 264 neonates were included in the
final analysis (Figure 1).
Patient Characteristics: A total of 264 neonates with a
mean gestational age of 38.7 (SD: ± 2. 5 w eeks) were
Copyright © 2011 SciRes. WJA
Risk Factors for Prematurity Among Neonates from HIV Positive Mothers in Cameroon3
Figure 1: Enrolment of neonates from HIV infected moth-
ers for the study on risk factors of low birth weight (LBW)
and intrauterine growth retardation (IUGR), University of
Yaoundé Teaching Hospital, Cameroon (December2001-
November 2007). (1UYT: University of Yaoundé Teaching
Hospital)
Table 1. Characteristics of neonates born from HIV positive
mothers, University of Yaoundé Teaching Hospital, Cam-
eroon (December2001- November 2007).
Mean (SD1) Median (IQR2)
Weight, g 3025.5 (599) 3,093 (2,752-3,388)
Length, cm 48.9 (3.2) 50 (48-51)
Head circumfere nc e , cm 33.6 (2.4) 34 (33-35)
Weight to length ratio 2.56 (0.36) 2.53 (2.34-2.74)
Gestational ages, weeks 38.7 (2.5) 39 (38-40)
Age (mothers) , years 27.9 (4.8) 27 (25-31)
1SD: standa r d d eviation. 2IQR: interquartile range.
included and analysed in the study (Table 1). Ten neo-
nates were twins (3.8%) and 128 (48.5%) were female. A
total of 39 (14.8%) had a LBW, 24 (9.1%) had an IUGR
and 36 (13.6%) were premature. The mean birth weight,
the mean birth length and the mean head circumference
were 3026 g (SD: ± 599 g), 48.9 cm (SD: ± 3.2 cm) and
33.6 cm (SD: ± 2.4 cm), respectively; the median
weight-to-length ratio was 2.53 (interquartile range
[IQR]: 2.34 – 2.74); 26 (9.8%) neonates had a weight-to-
length ratio below the 10th percentile (Table 1). A total
of 259 HIV-positive mothers were included an d analysed
in the study (Table 2). The median age was 27 years
(IQR: 25-31 years) at the time of delivery. A total of 149
(58%) were married, and 148 (57%) were jobless. Only
10 (4%) HIV-positive mothers were illiterates. Most
Table 2. Characteristic of HIV-positive mothers, University
of Yaoundé Teaching Hospital, Cameroon (December2001-
November 2007).
HIV classification st age 2 or 3, n (%) 28/259 (10.8)
Syphilis, n (%) 8/259 (3.1)
Anaemia, n (%) 34/259 (13.1)
Single, n (%) 149/259 (57.5)
Jobless, n (%) 148/259 (57.1)
Education
Illiterate, n (%) 10/259 (3.9)
Primary s ch o ol le v el , n (%) 67/259 (25.9)
Secondary school level, n (%) 128/259 (49.4)
University level, n (%) 54/259 (20.8)
mothers ended school at secondary school level [n = 128
(49%)], followed by 67 (26%) who ended school at a
primary school level, and 54 (21%) who had a university
degree.
Prenatal Care: A total of 96 (37%) mothers were first
para, 82 (32%) second, 35 (13%) third, and 46 (18%)
fourth para or more. Most (202; 78%) attended 4 prenatal
care visits or more, 30 (12%) attended 3 visits, 22 (8%)
attended 2 visits, and 4 (2%) attended only one visit. HIV
was diagnosed among 89 (34%) mothers before preg-
nancy, among 74 (29%) mothers in the first trimester,
among 63 (24%) in the second trimester and among 33
(13%) in the third trimester of pregnancy. Most HIV-
positive mothers were at WHO-stage 1 at delivery [231
(89%)], 23 (9%) were at stage 2 and 5 (2%) at stage 3.
Only 13 (5%) mothers were offered antiretro v iral therapy
(ART) during pregnancy. HIV laboratory parameters
such as viral load, CD4 cell counts, and CD8 cell counts
were obtained only for 6 (2%) HIV-positive women.
Anaemia prophylaxis was observed by the majority of
the mothers 243 (94%). There was significantly more
anaemia (p = 0.003) among mothers without taking a
combination of folic acid and iron. Malaria prophylaxis
was observed by 211 (81%) mothers. Sixteen (6%) were
diagnosed with malaria in the third trimester or at deliv-
ery. There was no significant association between com-
pliance with malaria prophylaxis and clinical disease (p =
0.20). Eight mothers (3%) were diagnosed with syphilis
and received benzathine penicillin treatment during
pregnancy. No ne onate was found with congenital syph i-
lis.
Risk factor Analysis: Multivariate analysis showed that
twins were significantly more at risk for LBW (OR [95%
CI]: 11.5 [3.1 - 43.5]; p < 0.001), or being preterm (13.5
Copyright © 2011 SciRes. WJA
Risk Factors for Prematurity Among Neonates from HIV Positive Mothers in Cameroon
Copyright © 2011 SciRes. WJA
4
[3.5-52.5]; p < 0.001) than singletons. HIV-classification
> 1 was significantly associated with IUGR (OR [95%
CI): 3.15 [1.4-7.4 ]; p = 0.01) and LBW (2.20 [1 .1 - 4.6];
p=0.03) but not with prematurity ( p = 0.82). Risk factors
for prematurity are summarized in Table 3. Less than 4
prenatal care visits were associated with prematurity (OR
[95% CI]: 2.7 [1.21 - 6.05]; p = 0.015). Risk factors for
IUGR are summarized in Table 4. Significant associa-
tions with IUGR were detected for lower gestational age
(p < 0.001) and when the clinical stage of the HIV-posi-
tive mother was higher than WHO-classification 1 at
delivery. Although not significant, a trend for malaria
disease in pregnan cy (OR [95% CI]: 3.82 [0.93 - 15 .7]; p
= 0.06) was detected for IUGR.
WHO-classification 3 (OR [95% CI]: 11.0 [1.68 -
72.0]; p = 0.01), malaria disease in pregnancy (OR [95%
CI]: 3.90 [1.05 - 14.5]; p = 0.04) and syphilis in preg-
nancy (OR [95% CI]: 6.87 [1.38 - 34.1]; p = 0.02) were
significantly associated with a weight-to-length ratio
below the 10th percentile.
Higher education was significantly associated with at-
tending 4 or more prenatal care visits (OR [CI95%]: 2.4
[1.6 - 3.4]; p < 0.001); similarly, women with higher
education were more likely to respect anaemia prophy-
laxis (OR [CI95%]: 3.0 [1.5 - 5.8]; p = 0.002) and anti-
malaria prophylaxis (OR [CI95%]: 2.1 [1.4 - 3.3]; p <
0.001). Furthermore, higher education was associated
with early HIV- diagnosis (p = 0.003).
Table 3. Risk factor analysis for prematurity (gestational age <37 weeks) among neonates born from HIV positive mothers,
University of Yaoundé Teaching Hospital, Cameroon (December2001 - November 2007).
Univariate model Multivariate model
OR P 95%CI OR P 95%CI
Prenatal care visits < 4 0.48 0.06 0.22-1.04 2.71 0.015 1.21-6.05
Anaemia 1.43 0.47 0.55-3.74 - - -
Malaria 0.90 0.89 0.20-4.13 - - -
HIV stage >1 1.11 0.82 0.46-2.66 - - -
Syphilis 0.90 0.92 0.11-7.56 - - -
Twins 11.2 <0.001 2.97-42.8 13.8 <0.001 3.53-54.41
Sex 0.82 0.58 0.41-1.66 - - -
Mother age at delivery 1. 19 0.15 0.94-1.52 1.15 0.29 0.89-1.48
Previous pregnancy 1.13 0.44 0.83-1.55 - - -
Marital status 0.70 0.33 0.34-1.45 - - -
Higher education 1.03 0.91 0.65-1.62 - - -
Income 1.17 0.67 0.58-2.36 - - -
Table 4. Risk factor analysis for IUGR (Weight <10th percentile) among neonates born from HIV positive mothers, University
of Yaoundé Teaching Hospital, Cameroon (December2001 - November 2007).
Univariate model Multivariate model
OR P 95%CI OR P 95%CI
Gestational age 0.76 <0.001 0.66 – 0.872 0.75 <0. 001 0.64 – 0.87
Prenatal care visits < 4 0.71 0.20 0.42 – 1.19 0.78 0.45 0.41- 1.48
Anaemia 0.96 0.95 0.27 – 3.41 - - -
Malaria 2.49 0.17 0.65 – 9.45 3.8 0.063 0.93 – 15.7
HIV stage >1 3.16 0.003 1.49 – 6.71 3.15 0.008 1.35 – 7.36
Syphilis 1.44 0.73 0.17 – 12.28 - - -
Twins 2.62 0.24 0.52 – 13.13 - - -
Sex 1.12 0.78 0.48 – 2.60 - - -
Previous pregnancy 0.85 0.45 0.57 – 1.28 - - -
Marital status 1.59 0.27 0.68 – 3.71 - - -
Higher education 0.73 0.26 0.43 – 1.26 - - -
Income 1.30 0.53 0.56 – 3.02 - - -
Risk Factors for Prematurity Among Neonates from HIV Positive Mothers in Cameroon5
4. Discussion
This is the first and largest cohort study on neonates born
to HIV-positive mothers in Central Africa. Three modi-
fiable risk factors for LBW, IUGR or prematurity were
detected: 1) poor prenatal care; 2) maternal HIV clinical
stage of WHO-classification >1 at deliver y; 3) an d syph i-
lis and malaria disease in pregnancy, resp ectively. While
an advanced clinical stage of HIV infection was associ-
ated with prematurity as well as IUGR, poor prenatal
care was associated with prematurity and syphilis or ma-
laria was associated with IUGR.
Poor prenatal care in the absence of maternal illness
has been shown to be associated with adverse outcome
such as LBW in Pakistan and Madagascar [24-26]. A
study which was done in the US did not show a differ-
ence between two groups of different numbers of prena-
tal care visits [27]. However, the mean number of visits
was high (9 visits vs. 14 visits) compared to our popula-
tion as well as to other populations in developing coun-
tries. Prenatal care visits among HIV-positive women
must be considered much more important. The finding
that prematurity is associated with less prenatal care vis-
its among a population without antiretroviral treatment as
ours suggests that non-HIV-specific care is fundamental
in the prevention of prematurity. Prenatal care includes
physical examination, control of fetal growth and devel-
opment, giving advice for a healthy diet, and motivating
mothers to respect prophylaxis for malaria, anaemia and
neural tube defects. Women attending prenatal care visits
are more likely to respect such recommendations as we
have seen in our population where the association be-
tween the number of consultations and compliance with
anaemia prophylaxis was significant (p < 0.001).
Women with higher education were significantly more
likely to attend prenatal care visits and to observe pro-
phylaxis recommendations for anaemia, neural tube de-
fects and malaria in our study. However, education level
as well as other maternal socio-economic factors such as
being married, having a job, or having regular income
was not found to be significantly associated with LBW,
IUGR or prematurity. This is most likely due to th e study
size. Maternal illiteracy has been shown to be a risk for
adverse outcome in pregnancy [6,7,12,16]. Similarly,
even if a direct association between maternal education
and LBW, IUGR or prematurity could not have been
shown in our study, women with higher education at-
tended prenatal care more often and were more likely to
respect advice for prophylaxis. Higher education was
found more often among unmarried women. Thus, un-
married parenting women in our study were more likely
to seek prenatal care. The finding that most HIV-positive
women in our study were single represents an overall
trend in Cameroon. The fact that single mothers in our
study were more likely to seek help from hospital institu-
tions can be interpreted as a positive finding. Once ART
is made widely available for the treatment of pregnant
women, regular prenatal care visits are essential. Thus it
is good to know that single mothers who represent the
majority of pregnant HIV-positive women can be moti-
vated for regular prenatal controls. On the other hand, in
industrialized countries it has been shown that prenatal
stress is associated with prematurity and LBW [28]. Sin-
gle parenting women usually face considerable pressure
while working and car ing for a child already wh en being
pregnant and being HIV-positive makes this even worse.
Further studies would have to reveal what “stress” means
in the setting of a developing country such as Cameroon
and whether the association would be similar.
The finding that illiterate women are less likely to at-
tend prenatal care visits is troubling. Such women are
more often married and although they have a regular in-
come and their nutritional status may be better they de-
pend largely on their husbands while their illiteracy is a
handicap to find a job. This prevents them from obtain-
ing appropriate information about precaution measures in
pregnancy. As a consequence, they have a low compli-
ance with prophylaxis measures and worse, HIV-infection
often is diagnosed not before the third trimester or at
delivery (p < 0.001). In the light of efficient
HIV-prophylaxis by ART during pregnancy which are
now - available this finding is worrying. Much effort will
have to be invested in reaching and motivating married
women to get tested for HIV before or early in pregnancy
and to attend regular prenatal care visits.
Our risks for adverse outcomes such as LBW, IUGR
and prematurity were similar to a study among 1500
women for maternal risk factors [29]. A total of 11.7%
were HIV-positive and 9.9% had malaria (61% in our
study). Rates for prematurity were similar but our study
showed a higher proportion of LBW (15% vs. 8%).
Similar to our study there was a significant association
between IUGR and maternal malaria in pregnancy. Our
numbers are in line also with others studies in developing
countries [9-11,16,30]. It is somewhat surprising that our
rates of adverse outcome were not much higher consid-
ering the fact that all women we included in our study
were HIV-positive. The most likely explanation for this
is the fact that most HIV-positive women 236 (91%) in
our study had HIV-disease of WHO-classification 1.
Consequently, HIV-disease as measured by the WHO-
classification in our study was independently associated
with IUGR. HIV-status alone does not predict adverse
outcome but severity of HIV-disease and AIDS does.
Thus, a populatio n of HIV-positive women shou ld not be
considered to be homogeneous.
Copyright © 2011 SciRes. WJA
Risk Factors for Prematurity Among Neonates from HIV Positive Mothers in Cameroon
6
The main limitation of our study is the study size al-
though we describe the largest cohort of neonates born to
HIV-positive women. Given the high proportion of
women representing HIV-classification 1 our cohort al-
most matches a normal population and associations be-
tween socio-economic factors and stress most likely are
too small to detect in a cohort of 259 mothers and their
264 children. Larger studies must address this issue. A
further shortcoming is that only half the children born to
HIV-positive mothers were included in the study becaus e
the lack of information would have been unmanageable
otherwise. Especially information of women excluded
because they had no prenatal care visit at UYT would be
of interest as many of them may not have attended any
prenatal care visit at all.
In summary, this is the first and largest cohort study
about neonates born to HIV-po sitive mothers in the Cen-
tral Africa sub-region. The study showed that, in a rela-
tively healthy HIV-population with most women of
WHO-classification 1, prenatal care other than HIV-
control significantly improves outcome in pregnancy.
Single women with h igher education were more likely to
attend prenatal care visits and comply with prevention
measures for anaemia and malaria. Furthermore, HIV
was diagnosed earlier in this population . Women in fam-
ily settings on the other side were less likely to seek as-
sistance in the hospital for pregnancy and HIV was di-
agnosed rather late. In the future, more effort must be
invested to address women in family settings in Camer-
oon in order to 1) early diagnose HIV; and 2) offer
HIV-treatment in time and increase compliance with
preventive strategies for adverse outcomes such as anae-
mia, malaria and neural tube defects of the child.
5. Acknowledgements
We thank Christine Ngo-Gweth, Brice Tagne-Kengny
and Mr. Anaba as well as the team from the labour room
of UYT for their valuable contribution to the study.
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