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Abstract
Introduction HIV can greatly impact the quality of life of pregnant women and may cause adverse pregnancy outcomes, such as preterm birth (PB) and mother-to-child transmission (MTCT). The purpose of this study was to analyse the influencing factors of PB and MTCT in HIV-positive pregnant women.
Methods HIV-positive pregnant women in Henan Province between January 2016 and December 2022 were selected for the study. Data were collected through the Management Information System for the Prevention of MTCT of HIV, syphilis and hepatitis B. Information on their demographic and clinical characteristics, treatment status and pregnancy outcomes was collected. A logistic regression model and χ2 automatic interaction detector (CHAID) decision tree model were used to analyse the correlation factors of PB and MTCT.
Results The average age of the 1073 study participants was 28.44 years, with an incidence of 11.93% for PB and 6.71% for MTCT. Hepatitis B virus or hepatitis C virus coinfection (OR=3.686, 95% CI 1.630 to 8.333) and Han nationality (OR=0.426, 95% CI 0.194 to 0.936) were risk factors for PB. Unknown HIV infection prior to pregnancy (OR=2.006, 95% CI 1.233 to 3.264) and primipara (OR=5.125, 95% CI 1.202 to 21.849) were risk factors for MTCT. The CHAID decision tree model was used to screen for the six and two influencing factors of PB and MTCT in HIV-positive women, respectively.
Conclusion Early HIV testing, scientific counselling, precise maternal HIV infection assessment and targeted prevention measures can help prevent PB and MTCT in HIV-positive pregnant women.
- Infectious disease/HIV
- Risk Factors
- Epidemiology
Data availability statement
Data are available upon reasonable request. Data are available upon request from the corresponding author.
This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
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STRENGTHS AND LIMITATIONS OF THIS STUDY
This retrospective cohort study aimed to analyse the factors influencing preterm birth (PB) and mother-to-child transmission (MTCT) in HIV-positive pregnant women.
The combination of χ2 automatic interaction detector and the logistic regression model better identified high-risk groups.
For the first time, large-scale cumulative data from 1073 HIV-positive pregnant women in Henan, China, were used to analyse the influencing factors of PB and MTCT.
Monitoring data from the information systems used in this study may lead to inadequate collection of other risk factors, such as viral load data, the level of immunosuppression, classification of caesarean section deliveries and the timing of HIV diagnosis during pregnancy.
The primary purpose of this study was to explore the influence of PB and MTCT in HIV-positive pregnant women, so the rates of MTCT were not adjusted and could not be compared with the MTCT rates reported in other studies.
Introduction
HIV infection is a global public health issue that poses a serious threat to people’s health and life. The WHO estimated that 39.9 million people were living with HIV at the end of 2023.1 In 2022, 52 058 new AIDS cases were reported in China, and the number of deaths due to AIDS was 18 885, which is 6.4 times the total number of deaths from other class A and B infectious diseases.2 The main impact of HIV-positive pregnant women on fetal health is the risk of vertical transmission of HIV, which is the leading cause of HIV infection in children. Additionally, HIV may increase the risk of adverse pregnancy outcomes, such as preterm birth (PB), the leading cause of death in children under 5 years of age, which seriously reduces the quality of birth of newborns.3 4
In 2007, the WHO launched the Global Initiative to Eliminate Mother-to-Child Transmission (EMTCT) of Syphilis and HIV.5 In July 2011, the United Nations issued a political declaration calling for increased efforts to eliminate HIV infection and AIDS.6 In the third edition of the Global Guidelines for the EMTCT of HIV, syphilis and hepatitis B virus issued by the WHO in 2021, the initiative and goal of eliminating HIV should be achieved by 2030.7 Since 2001, China has implemented comprehensive prevention and control measures to prevent mother-to-child transmission (MTCT) of HIV/AIDS on a pilot basis. These measures have now been rolled out across the country, and the MTCT rate of HIV/AIDS has been reduced from 12.8% in 2005 to 3.3% in 2021. Henan is located in the middle and lower reaches of the Yellow River in the central and eastern parts of China. Since 2001, Henan Province has carried out mother-to-child prevention in two pilot areas (counties), including maternal HIV testing and counselling; drug blocking; and other intervention measures, with severe epidemics (Shangcai County and Shihe District). By 2007, this has gradually expanded to 31 key counties. In 2009, a province-wide programme was launched. Centers for Disease Control and Prevention, midwifery and maternal and child healthcare institutions are required to conduct HIV testing and interventions for pregnant women.
The impact of HIV infection and corresponding prevention and treatment measures on maternal pregnancy outcomes has gradually gained attention as the efficacy of mother-to-child transmission prevention (PMTCT) has improved. Understanding the factors that influence adverse pregnancy outcomes in HIV-positive pregnant women is crucial to further reduce the incidence of these adverse outcomes. In recent years, foreign studies have confirmed that HIV infection and antiviral therapy (ART), including stillbirth and PB, increase the risk of adverse pregnancy outcomes.8 However, most of these studies are concentrated in developed countries and Africa, whose economic level, medical conditions and disease burden are different from those in China.9–13 At present, no studies have evaluated the factors influencing adverse pregnancy outcomes in HIV-positive pregnant women in Henan Province, and only one study has focused on evaluating the effects of a mother-to-child block in Henan Province.14
The aim of this study was to understand the occurrence of PB and MTCT in HIV-positive pregnant women and to explore influencing factors. The results of this study could provide valuable insights into interventions to prevent MTCT of HIV and improve the overall health of HIV-positive women and their newborns, thereby contributing to the ultimate goal of eliminating MTCT of HIV.
Methods
Data source
The PMTCT programme is a crucial initiative aimed at mitigating the risk of MTCT and enhancing the overall well-being of women and children. Their goal will be accomplished through the provision of comprehensive testing, counselling services, targeted interventions and treatment measures. The PMTCT management information system is a dedicated platform for effectively managing and tracking the implementation of the PMTCT.
This was a retrospective cohort study, and pregnant women with HIV reported by the PMTCT information system in Henan Province between January 2016 and December 2022 were selected as participants. Medical institutions are responsible for the registration, follow-up and investigation of case information of HIV-positive pregnant women who visit medical services and data network reporting through the PMTCT Management Information System. The system collects basic patient information, pregnancy-related information, HIV-related behaviours and medical conditions, newborn health information and other relevant information.
Inclusion and exclusion criteria
The inclusion criteria for this study were as follows: (1) resident of Henan Province; (2) delivery from 1 January 2016 to 31 December 2022; (3) gestational age of 28–42 weeks; and (4) singleton live birth. The exclusion criteria were as follows: missing neonatal HIV status information and multiple pregnancies.
Indicators and definitions
This study included sociodemographic characteristics such as age, race, education level, occupation, marital status and pregnancy-related information such as gravidity and parity, pregnancy-induced hypertension, gestational diabetes, moderate–severe anaemia, pregnancy with HBV/HCV/syphilis and mode of delivery. HIV infection information such as whether HIV infection was known prior to this pregnancy, the maternal period of HIV detection, route of HIV infection, ART and HIV status of the husband/sex partner were also included.
Moderate-to-severe anaemia during pregnancy was defined as a haemoglobin level <110 g/L,15 and the haemoglobin concentration in this study was tested during the third trimester. Pregnancy-induced hypertension includes pre-existing hypertension, gestational hypertension with preeclampsia, pre-existing hypertension with superimposed gestational hypertension and proteinuria, as well as unclassifiable hypertension.16 Gestational diabetes was diagnosed via a 75 g oral glucose tolerance test (OGTT) at 24–28 weeks gestation if one or more of the following plasma glucose values were met or exceeded: fasting (5.1 mmol/L), 1 hour (10.0 mmol/L) or 2 hours (8.5 mmol/L) at 75 g OGTT at 24–28 weeks gestation.17 18
The outcome indicators of this study were PB and MTCT. PB is defined as delivery before 37 completed weeks of gestation.19 According to the Technical Points of Intervention Services for PMTCT, infants born to HIV-positive pregnant women should be tested three times at the following intervals: within 48 hours, 6 weeks and 3 months after birth.20 The diagnostic criteria were as follows: (1) if two out of the three nucleic acid tests yield positive results, it can be confirmed as HIV positive; (2) if no early diagnosis is made or if the test result is negative, the HIV antibody test can be conducted again at 12 months after birth. If the test result was negative, an AIDS diagnosis was excluded. If the HIV antibody test result is positive at 12 months of age, HIV antibody testing should be conducted again at 18 months of age. If the test result is still positive, efforts should be made to supplement the tests (including antibody confirmation tests and nucleic acid tests) in a timely manner to confirm the infection status.
Statistical methods
SPSS V.22.0 software was used for statistical analysis, and the χ2 test was used for single factor analysis of PB rates and MTCT rates. PB and MTCT were used as dependent variables, and the statistically dependent indicators from the univariate analysis were used as independent variables in combination with medical significance. Logistic stepwise regression was used for multivariate analysis, and forward progression was used for independent variable screening. The inclusion criterion for independent variables was α=0.05, and the exclusion criterion was α=0.10. The inspection level was α=0.05 for each bilateral test.
The χ2 automatic interaction detector (CHAID) decision tree model was constructed via SPSS Modeller V.18.0 software to screen for MTCT of HIV and analyse the relationships among factors. Classification rules: (1) tree growth: severity level of growth ‘branches’ segmentation α Merge=0.05, α Split=0.05. (2) Tree pruning: using the prepruning method, the maximum number of growth layers of the decision tree was 5. (3) This study conducted a 10-fold cross validation.
The CHAID model and logistic regression model were combined to analyse the influencing factors and the interaction between factors of MTCT of HIV, which could maximise the advantages of the two models and better identify high-risk groups.
Results
Participants
From 2016 to 2022, a total of 1089 pregnant women in Henan Province were diagnosed with HIV infection (excluding 13 cases of multiple pregnancies and 3 cases with missing information). A cohort of 1073 HIV-positive pregnant women were included in the analysis (figure 1), with an average age of 28.44±6.13 years. The PB rate was 11.93%, and the incidence of MTCT was 6.71% (online supplemental table 1).
Supplemental material
Sample size flow chart of study participants in Henan, China from 2016 to 2022.
Univariate analysis of factors affecting PB and MTCT in HIV-positive pregnant women
The PB rates of HIV-positive women of different nationalities, hepatitis types and delivery modes were significantly different (p<0.05), and the results are shown in table 1. The incidence of PB in the Han population (12.70%) was higher than that in other nationalities (5.83%). The incidence of PB in pregnant women coinfected with HBV/HCV (32.14%) was greater than that in pregnant women without HBV/HCV. The incidence of PB was the highest in women who delivered by caesarean section (17.14%).
The participant characteristics and comparison between HIV-positive pregnant women with and without premature birth and mother-to-child HIV transmission events
There were statistically significant differences in MTCT rates according to education level, history of HIV infection and parity (p<0.05), and the results are shown in table 1. The incidence of MTCT (11.48%) in the group with a college education or higher was greater than that in the group with primary school education or lower (8.76%) and the group with middle and high school education (4.94%). The incidence of MTCT was greater in women with unknown HIV infection prior to this pregnancy (10.16%) than in women with known HIV infection prior to pregnancy (5.34%). The incidence of MTCT was the highest among primiparas (11.11%) and the lowest among those with a parity greater than 2 (2.38%). The incidence of MTCT in pregnant women who started ART before pregnancy (6.63%) was lower than that in pregnant women who started ART at gestation (12.66%) and intrapartum (10.34%).
Logistic regression analysis of factors affecting PB and MTCT in HIV-positive pregnant women
Logistic regression analysis revealed that nationality, HBV/HCB coinfection and mode of delivery were associated with PB (table 2). Compared with that in the Han population, the incidence of PB was lower in the other nationality groups (OR=0.426, 95% CI 0.194, 0.936). HBV/HCV coinfection was a risk factor for PB (OR=3.686, 95% CI 1.630, 8.333). Women who delivered by caesarean section (OR=1.868, 95% CI 1.276, 2.734) had a greater incidence of PB than those who delivered vaginally.
Association between HIV-positive pregnant women’s characteristics and preterm birth
Logistic regression analysis revealed that education and parity were associated with MTCT (table 3). The risk of MTCT was lower in the middle and high school education group than in the primary school education group (OR=0.502, 95% CI 0.303, 0.968). The risk of MTCT was greater in pregnancies with unknown HIV infection prior to this pregnancy (OR=2.006, 95% CI 1.233, 3.264). The probability of MTCT was greater in primiparas (OR=5.125, 95% CI 1.202, 21.849) than in women with a parity >2.
Association between HIV-positive pregnant women’s characteristics and mother-to-child HIV transmission events
CHAID decision tree model analysis of factors affecting PB and MTCT in HIV-positive pregnant women
The analysis results of the CHAID decision tree for preterm delivery of HIV-positive pregnant women revealed 12 nodes and seven terminal nodes (nodes 2, 5, 7, 9, 10, 11 and 12), as shown in figure 2A. The results of the CHAID model revealed that HBV/HCV coinfection, mode of delivery, whether HIV infection was known prior to this pregnancy, age, maternal period of HIV detection and route of HIV infection were risk factors for PB. When the first layer of the tree was divided according to HBV/HCV coinfection, the incidence of PB with HBV/HCV coinfection (32.14%) was significantly greater than that without HBV/HCV coinfection (11.39%). The CHAID model revealed an interaction between non-HBV/HCV coinfection and mode of delivery, and the incidence of PB in HIV-positive women without HBV/HCV coinfection and caesarean section delivery increased from 11.39% to 17.16%. Among women who delivered by caesarean section, there was an interaction between HIV infection history and the maternal period of HIV detection. Additionally, the incidence of PB increased from 20.10% to 47.37% among women with known HIV infection prior to this pregnancy and during the period of testing at intrapartum or postpartum. Among women who gave birth vaginally or by unknown means, there was an interaction between age and route of HIV infection, with the incidence of PB increasing from 22.22% to 40.91% among women younger than 20 years of age who contracted HIV through sexual transmission.
Classification tree chart of decision tree analysis on factors influencing preterm birth and mother-to-child HIV transmission events in HIV-positive women.
The analysis results of the CHAID decision tree for MTCT of HIV-positive pregnant women revealed four nodes and three terminal nodes (nodes 2, 3 and 4), as shown in figure 2B. The results of the CHAID model revealed that parity and the maternal period of HIV detection were influential factors for MTCT. At the first level of the tree, the incidence of MTCT in primipara (11.11%) was significantly greater than that in primipara (5.10%). The CHAID model revealed that there was an interaction effect between parity and the maternal period of HIV detection; the incidence of MTCT increased from 11.11% to 25.93% in women who were primiparas, and the time of detection was intrapartum or post partum.
Discussion
The average incidence of PB in HIV-positive pregnant women in Henan Province from 2016 to 2022 was 11.93%, showing a trend of relative fluctuation and decline. The PB rate of HIV-positive women in Henan Province was greater than that in Hunan Province (7.9%).21 In addition, the PB rate of HIV-positive women in Henan Province was similar to that of HIV-positive women in Nigeria (11.1%) reported by Ezechi et al 22 and lower than that of HIV-positive women in Botswana (18.4%) reported by Zash et al.23 Differences in preterm delivery among HIV-positive women in different regions, in addition to differences in sample size and inclusion criteria across studies, might also be related to differences in socioeconomic conditions, medical levels and prevention measures for MTCT across different regions. From 2016 to 2022, the average incidence of MTCT among HIV-positive pregnant women in Henan Province was 6.71%, showing a downwards trend; however, there were large fluctuations which may be associated with the small sample size. This finding also revealed that the measures taken in Henan Province in recent years to prevent MTCT of HIV have been more effective.
Among the 1073 pregnant women included in this study, 55.17% were in the fertile active period (25–35 years old), 88.82% were Han, 86.21% had a junior high school education or lower, and 56.48% were farmers, which is consistent with the characteristic distribution of the overall HIV population in China.24 Moreover, pregnant women aged 20–25 years accounted for a relatively high proportion (23.49%), and the incidence of PB and MTCT in this age group was relatively high (11.51% and 9.52%, respectively). Therefore, when carrying out HIV prevention and control education activities, the target audience for public health should be expanded beyond women of childbearing age. This is important because the average marriage and childbearing ages in rural China are earlier than those in urban areas.25
This study revealed that coinfection with HBV/HCB increases the risk of PB in HIV-positive women. HIV coinfection with HBV has been shown to increase the risk of low birth weight and PB.26 27 Previous studies have shown that HIV and HBV infection interact and that HIV-HBV coinfection increases the risk of PB.28 Owing to the immune system damage caused by HIV infection, the adverse effects of HBV infection on HIV-positive pregnant women may be greater than those in the general population, which in turn increases the liver toxicity of ART.29 HBV infection can increase the side effects of highly active antiretroviral therapy.30 This finding is inconsistent with the results of a study conducted in France, which revealed that HIV-HBV coinfection had no significant effect on pregnancy outcomes.31 Studies have shown that HIV coinfection with HCV can increase the risk of adverse pregnancy outcomes, which is consistent with the results of this study.32 However, there is limited research on the mechanisms by which HIV coinfection with HCV increases the risk of PB. In vitro studies have shown that HCV infection of human trophoblast cells can cause ultrastructural changes.33 The mechanism by which PB is caused by HCV remains unclear and requires further study. On the basis of the current findings, the incidence of PB in HIV-positive women can be reduced by screening and treating HIV-positive women for HCV before pregnancy.
The results of this study revealed that primipara was a major risk factor for MTCT in HIV-positive pregnant women. This may be because the rupture of the membrane before delivery is longer in primiparas than in parturients. Duliège et al reported that when twins were born to HIV-positive pregnant women, the first child was often infected, whereas the second child was not. This may be because the first child is exposed to uterine vaginal secretions for a longer time than the second child is.34 A French study revealed that MTCT was three times greater in the first newborn than in the second newborn.35 However, an African study did not find birth order to be an important risk factor for infection in twins.36 A prospective study revealed that the risk of MTCT doubled after 4 hours of membrane rupture prior to delivery.37 In addition, a meta-analysis revealed that the risk of vertical transmission increased by 2% per hour extension of membrane rupture time.38 This finding also suggests that HIV screening should be strengthened during prepregnancy and early pregnancy in primiparous women, antiviral treatment should be administered and MTCT should be actively prevented.
The results of the CHAID decision tree model in this study suggested that the time of HIV detection during intrapartum or post partum was one of the risk factors for MTCT in HIV-positive pregnant women. Studies have shown that pregnant women diagnosed with HIV during childbirth are less likely to use antiviral therapies.39 The results from a Brazilian study revealed that delayed detection increased the probability of MTCT in HIV-positive women (RR=16.3; 95% CI 3.6 to 73.0).40 This finding also suggests that improving the HIV detection rate in early pregnancy is one of the key factors for effectively reducing MTCT of HIV. In addition, the results of this study also revealed that, compared with the history of HIV infection, the probability of MTCT of newly discovered HIV infection was greater, possibly because the probability of receiving antiviral treatment earlier in pregnant women with previously discovered HIV infection was greater.
This study was the first to analyse the influencing factors of PB and MTCT in HIV-positive pregnant women in Henan Province, using cumulative data from the entire province, to provide a basis for the implementation of HIV prevention programmes. This study has several limitations. First, due to the use of monitoring data from an information system, there is insufficient collection of other risk factors for MTCT and PB. For example, owing to the limited capacity for viral load detection in most grassroot areas, we did not mandate the inclusion of viral load data in the information system. This also led to a significant amount of missing data, which hindered our ability to obtain accurate viral load information. The information regarding the level of immunosuppression could not be obtained from the information system. We were unable to distinguish between selective and emergency caesarean section deliveries through the system data, which made it difficult to accurately determine the relationship between the mode of delivery and PB. Second, data from the information system were obtained during a 7-year period from 2016 to 2022, and since then, there have been changes in the information system regarding the period of HIV detection. We were unable to obtain accurate information on the timing of HIV diagnosis during pregnancy for 37.47% of the pregnant women between 2016 and 2020, which may have resulted in some degree of information bias. Finally, the primary purpose of this study was to explore the influence of PB and MTCT in HIV-positive pregnant women, so the rates of MTCT were not adjusted and could not be compared with the MTCT rates reported in other studies.
Conclusion
There are several factors affecting PB and MTCT in HIV-positive pregnant women, and comprehensive multisectoral prevention and control are needed. Earlier implementation of HIV testing and counselling, more scientific clinical assessment of maternal infection status, and implementation of targeted comprehensive prevention and control measures can help prevent PB and MTCT in HIV-positive pregnant women.
Data availability statement
Data are available upon reasonable request. Data are available upon request from the corresponding author.
Ethics statements
Patient consent for publication
Ethics approval
This study involves human participants and was approved by the ethics committee of The Third Affiliated Hospital of Zhengzhou University (2023-(PRE)058). Due to the retrospective nature of the study, informed consent was not required.
References
Footnotes
Contributors MZ designed the study, conducted the data analysis and drafted the main manuscript. JH, HZ and JX contributed to the data collection. YC, CS and FX contributed to prepared figures and tables. HQ and MH provided technical support and guidance. All authors have reviewed the manuscript and agreed to the published version of the manuscript. MH is responsible for the overall content as guarantor.
Funding This work was supported by Joint Construction Project of Medical Science and Technology Breakthrough Plan of Henan Province (LHGJ20220554), Maternal and Child Taige Care and Prevention of Mother to Child Transmission Fund of China Association for STD and AIDS Prevention and Control (PMTCT202206) and PhD research startup foundation of the Third Affiliated Hospital of Zhengzhou University (BS20230103).
Competing interests None declared.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Provenance and peer review Not commissioned; externally peer reviewed.
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