The Effect of Human Immunodeficiency Virus-1 Infection On Low Birth Weight, Mother To Child HIV Transmission and Infants' Death in African Area
The Effect of Human Immunodeficiency Virus-1 Infection On Low Birth Weight, Mother To Child HIV Transmission and Infants' Death in African Area
The Effect of Human Immunodeficiency Virus-1 Infection On Low Birth Weight, Mother To Child HIV Transmission and Infants' Death in African Area
http://www.scirp.org/journal/ojog
ISSN Online: 2160-8806
ISSN Print: 2160-8792
DOI: 10.4236/ojog.2019.92017 Feb. 2, 2019 158 Open Journal of Obstetrics and Gynecology
T. Youssouf et al.
women HIV infection (adjusted relative risk, 2.02; p = 0.000; 95% confidence
interval (2.17 - 4.10)). There is no significant difference between mother to
child HIV transmission rate in the two HIV-infected pregnant women (10
infected children in group 2: MTCT rate 4.5%) and 3 infected children in
group 1 (MTCT rate: 2.7%) (p = 0.56; RR, 0.59; CI 95% (0.18 - 4.39)). In mul-
tivariate analysis, LBW was associated with infant death (p = 0.001; RR =
2.04; CI 95% [1.04 - 5.05]). The median weight of infant at the moment of
death in group 1 was 851 g (IQR: 520 - 1833 g). Significant relationship was
found between infant death among LBW newborn with mother WHO stage 2
(p = 0.004; adjusted RR = 3.22; CI 95% [2.25 - 6.00]), CD4 T cells count < 350
cells/mm3 (p = 0.005; RR = 2.81; CI 95% [1.20 - 4.11]), PI regimens (p =
0.030; RR = 1.00; CI 95% [1.28 - 3.80]). Conclusion: We confirm increased
risk of low birth weight and mother HIV-1 infection and we identified
strongest association between mortality in infant born to HIV-1 infected
mother and LBW.
Keywords
Low Birth Weight, Human Immunodeficiency Virus, Infection,
Mother to Child Transmission, Newborn Death, Mali
1. Introduction
The main risk in human immunodeficiency virus positive pregnant women
widely studied is the transmission of the virus to newborn [1]. The potential ad-
verse effects of HIV-1 infection during pregnancy on weight at birth and infant
mortality are few studies, mostly from African English speaking countries.
Another possible risk is the influence of this infection on neonate anthropome-
tric characteristics [2] [3]. But this is a controversy subject in scientific domain.
Indeed for some authors [4] [5] [6] [7], children born to HIV infected mothers
have higher risk of LBW. A study that took place in Cote d’Ivoire confirmed that
this LBW is associated to antiretroviral treatment (ART) [8] while for Minkoff
[9], there is no relationship between HIV and LBW.
Independently of infant HIV infection, LBW constitutes one of the strongest
causes of newborn mortality [2] [10]. In populations with a high prevalence of
HIV infection, maternal HIV, status and LBW are likely to be important deter-
minants of child survival [11]. Is women HIV infection an additional risk factor
of infant death? Most of studies examined association between LBW in HIV in-
fected patients without discrimination of types of the virus. Also, few surveys
about LBW among HIV-1 infected women examined the association between
LBW and mother to child HIV transmission (MTCT) and risk factors of new-
born outcome.
A better understanding of risk factors of LBW born to HIV-1 infected mother
and the relationship between mother to child HIV transmission (MTCT) and
LBW would help in developing countries to undertake interventions to reduce
LBW and its consequences in HIV positive women and so to reduce HIV trans-
mission to child born to HIV infected mother in that situation. The particulari-
ties of this study are: firstly, that study took place in a West African French
speaking country where this area has not been thoroughly studied; secondly, it
took place in a low HIV prevalence country and thirdly this study is about LWB
and newborn death among HIV-1 infected women. We reported the results of
the relationship between HIV-1 maternal infection and anthropometric charac-
teristics of the child at birth. The objectives of our study were to determine risk
factors of LBW among HIV-1 infected mother, to evaluate newborn death risk
factors and to determine the rate of HIV transmission from mother to child in
this LBW delivery context.
decide their delivery way and the calendar of following of the future babies.
Data were collected from our obstetric files, daily updating by a midwife and
an obstetrician performed in data management. The supports used to complete
this database are: complete obstetric files, complete neonatal PMTCT unit files,
on-call registries of midwives, surgical reports, admissions records for emergen-
cy unit and hospital birth registries. The children lost to follow-up were retired
from the analysis.
All patients were screened for highly active antiretroviral treatment (HAART)
eligibility according world health organization (WHO) stages, absence of medi-
cal contraindications to HAART, adherence of treatment, mode of feeding
(formula or breast feeding) of future baby. According eligibility criteria, preg-
nant HIV-1 infected women initiated HAART.
CD4 T cell count and viral load (VL) were measured upon enrolment and
around 32 - 34 wks of gestation from the first day of last menstruation date.
We didn’t include in this study pregnant women with diseases classically re-
sponsible to LBW (high blood pressure, anemia, sickle cell disease, twin preg-
nancy) or macrosomia (diabetes). We didn’t include also HIV-2 and HIV1 + 2
infected pregnant women.
Study variables analyzed were: newborns anthropometric characteristics (birth
weight, body length and head circumference), maternal viral load, maternal
WHO stage, antiretroviral treatment (ART) regimens of the mothers, newborn
type of feeding, sex of newborn, MTCT HIV rate, HIV status of newborn, age of
newborn at death. The quantification limit of VL was <50 copies/ml.
3. Results
Of 12.077 births recorded in this study within 531 cases of pregnant women
HIV-1 infected (4.4%). Of the 531 HIV-1 positive pregnant women, we rando-
mized 111 women who delivered newborn with LBW (group e1) and 222
HIV-1 positive pregnant who delivered newborn whose weight ≥ 2500 g
(group 2). Of the remaining 11.546 patients we randomized 222 HIV negative
pregnant women who delivered newborn weight < 2500 g (group 3). The rate
of newborns with LBW in the study has been 20.9% (111/531); during the
same period the rate of newborn whose birth weight among HIV negative pa-
Table 1. Relation between the CD4 T Cell, Viral load (VL), status of newborn, weight at birth, sex of the newborn, newborn death,
HAART regimen and moment of ART initiation at Gabriel Touré Teaching Hospital from January 2011 to 2016 (Univariate and
adjusted risk relative analysis).
Newborn Death
Yes 17 (15.3) 13 (5.9) 2 (0.9) 0.002 4.14 (2.19 - 4.21) 0.001 2.04 (1.04 - 5.05)
CD4 T Cells/mm 3
<350 76 (68.5) 49 (22.1) - 0.000 3.03 (1.89 - 3.16) 0.001 2.04 (1.04 - 5.05)
[350 - 500] 16 (4.4) 43 (19.4) - 0.020 5.34 (2.89 - 9.02) 0.042 0.21 (0.94 - 6.00)
≥500 19 (17.1) 130 (58.5) - 0.002 4.07 (1.57 - 4.00) 0.059 1.00 (0.33 - 1.88)
<50 28 (58.3) 66 (61.7) - 0.416 0.51 (0.60 - 1.93) 0.78 0.49 (0.81 - 1.01)
Status of newborn
Hypotrophy 70 (63.1) - 97 (47.6) 0.004 2.05 (1.12 - 1.36) 0.000 3.00 (1.032 - 6.10)
Premature 41 (36.9) - 124 (55.9) 0.031 1.34 (1.26 - 2.45) 0.052 0.34 (0.17 - 1.53)
Sex of newborn
Male 62 (55.9) 121 (54.5) 113 (50.9) 0.070 0.24 (0.70 - 2.20) - - -
Female 49 (44.1) 101 (45.5) 109 (49.1) 0.821 0.20 (0.40 - 1.90) - - -
[520 - 1500] 47 (42.3) - 83 (37.4) 0.010 1.13 (1.05 - 5.07) 0.000 2.02 (2.17 - 4.10)
Before Pregnancy 49 (44.1) 32 (14.4) - 0.036 3.20 (2.13 - 5.22) 0.006 2.11 (1.09 - 3.99)
During Pregnancy 51 (45.9) 166 (74.8) - 0.041 0.01 (1.01 - 2.02) 0.061 0.02 (1.02 - 1.99)
2INTI + 1IP 21 (18.9) 28 (12.6) - 0.030 1.01 (1.28 - 3.80) 0.030 1.001 (1.28 - 3.80)
3INTI 6 (5.4) 3 (1.4) - 0.041 1.21 (1.99 - 2.11) 0.058 1.51 (0.99 - 3.66)
Table 2. Relation between LBW and newborn death in multivariate analysis according CD4 T Cell, Viral load (VL), mother WHO
stage, status of newborn, weight at birth, sex of the newborn, newborn death, HAART regimen and moment of ART initiation at
Gabriel Touré Teaching Hospital from January 2011 to 2016.
Infant Death
Variables Group 1 Group 2
p-value Adjusted RR CI
N = 17 (%) N = 13 (%)
1 2 (11.8) 1 (7.7)
3 5 (29.4) 3 (23.1)
4 3 (17.6) 4 (30.8) -
CD4 T Cells/mm 3
VL a Birth (copies/ml)
Sex of Newborn
Infant Feeding
4. Discussion
Our study demonstrated clearly that LBW is higher among HIV-1 infected
pregnant women (20.9%) than HIV-negative one (16.5%). It showed also that
the main risk factors of LBW among HIV-1 infected mother were low CD4 T
cells count, ART regimen before beginning of pregnancy and ART regimen
containing PI (Table 1). Hypotrophy and birth weight less than 1500 g were as-
sociated to mother HIV-1 infection.
Few studies in West Africa examined the association between LBW and
mother HIV-1 infection. In a cross-sectional study conducted by Sombié [3] in
Bobo-Dioulasso from January 1995 to May 1996, LBW was more frequent
among children born to HIV-infected mothers than among those born to unin-
fected mothers (23.37% versus 15.6%; p = 0.006). In the multivariate analysis, he
demonstrated that mother HIV infection was a risk factor of LBW (p < 0.001).
Data from Cote d’Ivoire [8] about ART and prevention of peripartum and post-
natal HIV transmission in West Africa and from Senegal [12] about PMTCT,
found association between LBW and mother HIV infection without discrimina-
tion between the types of virus. For Tonwe [8], multivariate analysis showed low
birth weight (<2500 g) was the only factor associated with acquisition of HIV
infection, with an adjusted hazard ratio of 5.63 (p = 0.006; 95% CI [1.62 -
19.49]). Other studies confirm this relationship between LBW and HIV infec-
tion. Indeed for Ratchanee [13] in Thailand, kamenga [14] in Kinshasa and Mar-
tin [15] in USA, LBW was strongly associated to maternal HIV infected status.
In a study that evaluated maternal HIV infection and other sexually transmitted
diseases and LBW, Kamenga [14] reported a newly double prevalence of LBW
(21% versus 11%, odds ratio 2.1; 95% CI [1.3 - 3.5]). However some authors be-
lieved there is no relationship between LBW and mother HIV infection. It is the
case in Minkof [9] study that did not found any influence between child birth
weight and HIV infection although the growth retardation is common among
newborns from HIV positive women.
In Africa, particularly in Mali, pregnant HIV infected women usually consult
later when they had advanced HIV disease, exposing them to opportunistic or
repeat infections. These infections led to premature births that were more fre-
quent in our patients in group 1 whose CD4 T cells count rate was three times
lower. In Tanzania, Dreyfus [16] found in a multivariate-adjusted linear regres-
sion that CD4 cell count < 200 cells/mm3 was significantly associated with LBW.
However, for Kamenga [14] maternal T4 lymphocyte level is not associated with
LBW.
Analysis of Table 1 shows that the proportion of LBW was not different if
ART is initiated during pregnancy or during delivery. When treatment is started
early, children were smallest at birth [17]. Our results are confirmed by a me-
ta-analysis that found after adjusting for several factors, HAART used pre-conception
was associated with an increased risk for preterm delivery (p = 0.009; adjusted
OR, 5.0; 95% CI [1.5 - 17.0]) and LBW (p = 0.001; OR, 3.6; 95% CI [1.7 - 7.7])
[18]. Indeed, we believe that if HIV testing is done before the beginning of
pregnancy and when treatment is instituted early, this would improve the im-
mune status of the patient and then reduce the risk and recurrence of opportu-
nistic infections and then avoid LBW. Some authors [17] [19] incriminated PI in
the occurrence of low birth weight while for Tonwe [8] antiretroviral treatment,
irrespective of class, is more associated with weight at birth. This risk is lower
among mothers treated with drugs containing no PI (OR = 0.58; 95% CI. [0.41 -
0.84]) compared to the group of women treated with mono therapy [19]. But it
was higher in women treated with PI and women treated without PI [19]. So, he
concluded that delivery of very LBW was associated with the use of PI although
this association was not significant [19]. Women receiving PI-containing drugs
had a deeper immunological status more than those who had not been treated by
PI regimen [17]. Therefore, they CD4 T cells count rate was so lower their health
requires a prescription of powerful antiretroviral regimen to make viral load
undetectable and to reduce the frequency of opportunistic infections.
Regarding the term of pregnancy and HAART regimen, our results were not
consistent with data of the literature which reported preterm and very preterm
newborns rates significantly associated with antiretroviral treatment [17]. Our
study preterm delivery rate is higher than that reported in France [17] (10.5%
including 2 cases of mother treated by PI), USA [15] (19%) and Burkina Faso (2
cases) [3]. Data from Côte d’Ivoire [8] found no significant difference in the
rates of premature births (gestational age < 37 wk) between the two groups
comparing short and long treatments regimens (7.8% and 7.9%, p = 1.00).
However a higher proportion of LBW (<2500 g) was observed in neonates whose
mothers had received HAART (26.3%) compared to patients having received a
short course of ART (12.4%) for PMTCT regimen (p < 0.0001). These differenc-
es persisted after adjusting for maternal body mass index, CD4 T cells count and
the WHO clinical stage [8]. In Malawi, prematurity rate was higher in women on
highly active antiretroviral therapy (HAART) (14.1%, 476/3384) than in women
on mono/dual therapy (10.1%, 107/1061), even after adjusting for ethnicity, ma-
ternal age, clinical status and injecting drug use as use as the source of HIV ac-
quisition (p = 0.001; adjusted OR, 1.51, 95% CI [1.19 - 1.93]). Delivery at <35
weeks was even more strongly associated with HAART (p < 0.001; OR, 2.34; 95%
CI [1.64 - 3.37]). For Townsend [20], the effect was the same whether or not
HAART included a protease inhibitor. In a study that analyzed adverse birth
outcome in HIV infected women in Botswana, Chen [21] reported that patients
continuing HAART from before pregnancy had higher odds of preterm delivery
(adjusted OR, 1.2; 95% CI [1.1, 1.4]), small newborn for gestational age (adjusted
OR, 1.8; 95% CI [1.6, 2.1]). In the same survey, among women initiating antire-
troviral therapy in pregnancy, HAART use was associated with higher odds of
preterm delivery (adjusted OR, 1.4; 95% CI [1.2, 1.8]), small newborn for gesta-
tional age (adjusted OR, 1.5; 95% CI [1.2, 1.9]) [21]. So, he concluded HAART
receipt during pregnancy was associated with increased preterm delivery and
small gestational age [21].
In Bobo-Dioulasso, mean birth weight, birth size and head circumference did
not significantly differ between the children of HIV-infected and uninfected
mothers [3]. Maternal HIV infection appears to be associated with LBW and
small birth size [3].
The rate of HIV transmission from mother to child was twice lower than
women who delivered normal weight newborns. However there was no signifi-
cant difference between mother to child HIV transmission rate in the two HIV-1
infected pregnant women (MTCT rate 4.5%) and LBW group 1 (MTCT rate:
2.7%) (p = 0.56; RR, 0.59; 95% CI [0.18 - 4.39]). All infected newborns were
breastfed and had not received optimal management [17], pattern observed
among Milogo-Traore [22] and Khuong-Josses studies [17]. Breastfeeding that is
not formally indicated in developed countries is often the only logical choice in
our limited resources countries to feed these children living generally in a preca-
rious situation.
Premature birth is a cause of MTCT if maternal treatment is initiated late (af-
ter 28 weeks of gestation). When it occurs, HAART drugs had not enough time
to decrease the mother’s plasma HIV viral load, enhance immune function and
reduce dramatically the HIV transmission to the newborn [8]. The viral load, sex
of newborn, CD4 cells count ≥ 350 cells/mm3, 3INTI and 2 INRTI plus 1
INNRTI regimens were not associated with the occurrence of LBW. VL was un-
detectable in similar rate in both groups of HIV infected women in our study.
Another risk related to low birth weight in HIV infected mother is newborn
and infant death [2]. During the 18 months follow-up, we reported 17 newborn
and infant deaths in the group 1 and 13 newborn and infant deaths in group 2.
Infant death was two time more associated to newborn LBW (adjusted RR =
2.04). In multivariate analysis, LBW was associated with newborn and infant
death (p = 0.01; RR, 3.55; 95% CI [1.22 - 4.19]). The main risk factors of child
death were mother WHO stage 2 (p = 0.004; adjusted RR, 3.22; 95% CI [2.25 -
6.00]), PI regimens (p = 0.030; RR, 1.001; 95% CI [1.28 - 3.80]). Among HIV in-
fected children in the both groups, we recorded two deaths of children in the
group 1 (2/17 being 11.8%) and 3 in the group 2 (3/13 being 23.1%). No statisti-
cally significant difference was found according to infant death and infant feed-
ing practice (p = 0.171). These results are confirmed by Tanzania study con-
ducted by Ruilan [2] that found that after adjustment, LBW was associated with
a 2-fold increased risk of infant mortality (RR = 2.40; 95% CI 1.45 - 3.95). Infant
death in our study was negatively influenced by LBW and mother’s CD4 T cells
count < 350 cells/mm3 (p = 0.005; RR, 2.81; CI [1.20 - 4.11]), contrarily to MTCT
of the virus that was not related to LBW (Table 2); but this conclusion could be
discussed because of the very low rate of HIV infant infection in our study.
5. Conclusion
The occurrence of LBW in HIV-1 infected women is relatively more frequent
than HIV negative mothers. These newborn low birth weights are mainly related
to low CD4 T cells count (<350 cells/mm3), ART regimens containing PI, and
ART initiated before beginning of pregnancy. Newborn death was strongly re-
lated to LBW in our patients. No relationship has been found between newborn
low birth weight and MTCT of HIV. These results confirm that efforts to reduce
the incidence of LBW are necessary to enhance the benefices of PMTCT pro-
gram.
Conflicts of Interest
There is no conflict of interest for authors in that submitted manuscripts.
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