Newborn anthropometry and early outcomes in HIV-exposed newborns receiving PMTCT care

INTRODUCTION

Maternal human immunodeficiency virus (HIV) infection has been consistently linked to adverse birth outcomes, including anaemia, post-neonatal mortality, pre-term birth, low birth weight, and small-for-gestational-age newborns.^[1-5] These outcomes are further exacerbated by factors such as rural residence and pregnancy history.^[2] Despite the widespread use of highly active antiretroviral therapy (HAART), the risk of adverse perinatal outcomes remains high,^[6] which highlights the urgent need for targeted interventions and improved prenatal care for pregnant women with HIV infection.

Newborn babies born to HIV-positive mothers on HAART have been found to have lower birth weights and other anthropometric parameters compared to those born to healthy mothers.^[3,7,8] The burden of HIV in sub-Saharan Africa presents significant challenges in perinatal care, with gaps in neonatal HIV-related care, prevention of perinatal HIV transmission, and programme implementation.^[9-11]These challenges are compounded by the lack of perinatal palliative care, particularly in low-resource settings.^[12]Addressing these challenges requires strategies such as safe sex education, increased access to antenatal care, and gender empowerment.^[10,11] However, further research is needed to develop guidelines and programmes for optimal perinatal care in this context.

Previous studies, largely from developed countries, have characterised mother-to-child HIV transmission and demonstrated its adverse effects on perinatal outcomes, including pre-term birth, low birth weight, and small-for-gestational-age newborns.^[1] This impact is further compounded by altered immune responses in both mothers and their newborns, leading to negative pregnancy outcomes and increased susceptibility to infections in HIV-exposed uninfected newborns.^[13] However, the long-term consequences of these altered immune responses on infant health are yet to be fully understood.^[13] Maternal HIV infection is also associated with increased infectious morbidity and mortality, as well as decreased growth measures in HIV-exposed uninfected newborns.^[14] However, there remains a significant gap in understanding these reproductive health issues for women living with HIV in resource-poor environments or underdeveloped countries like Nigeria.^[15] Indeed, understanding early growth patterns and immediate postnatal outcomes among HIV-exposed newborns is essential for pediatricians involved in newborn care, growth monitoring, and early intervention in resource-limited settings.

We, therefore, hypothesised that maternal HIV infection is associated with adverse newborn outcomes, including lower birth weight, reduced anthropometric measures, and lower Appearance-Pulse-Grimace-Activity-Respiration (APGAR) scores, with differing relationships among anthropometric parameters according to maternal HIV status. Accordingly, this study aimed to examine the association between maternal HIV status and newborn anthropometry, gestational age (GA), and APGAR scores. The objectives were to compare HIV-exposed and HIV-unexposed newborns in Uyo, Nigeria, and to examine relationships among anthropometric and clinical variables using multivariable analytical approaches. The high prevalence of HIV in this setting provides an appropriate context to address this knowledge gap and generate findings relevant to clinical practice and health policy.^[16] Using an observational comparative design, this study contributes locally generated data describing differences in newborn anthropometry and immediate newborn status by maternal HIV status.

MATERIAL AND METHODS

RESULTS

Correlations and multiple linear regression

Pearson correlation analysis revealed significant associations. HIV-exposed and HIV-unexposed newborns showed correlations between GA and birth weight (r = 0.566/0.372; p = <0.001), GA and chest circumference (0.617/0.378; p = <0.001/0.001), GA and newborn length (0.539/0.403; p = <0.001), birth weight and head circumference (0.764/0.391; p = <0.001), chest circumference (0.714/0.483; p = <0.001), newborn length (0.677/0.528; p = <0.001), head and chest circumference (0.675/0.478; p = <0.001), head circumference and length (0.574/0.309; p = <0.001/0.003) and chest circumference and length (0.458/0.528; p = 0.002/<0.001). Only HIV-exposed newborns showed GA– head circumference correlation (0.686; p = <0.001). In HIV- unexposed newborns, maternal age correlated with birth weight (r = 2212–0.210; p = 0.044) and head circumference (0.224; p = 0.037) [Figures 1 and 2].

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Figure 1:

(a and b) Annotated correlation heatmaps of newborn variables: (a) shows the relationships among maternal and neonatal variables in HIV-exposed newborns (n = 48). Positive correlations are shown in red and negative correlations in blue. Significance levels are denoted as follows: *(r ≥ 0.20), **(r ≥ 0.40). (b) shows the relationships among maternal and neonatal variables in HIV-unexposed newborns (n = 96). Significance levels are denoted as follows: * (r ≥ 0.20), ** (r ≥ 0.40). The heatmaps display Pearson correlation coefficients between maternal and neonatal variables among HIV-exposed [Figure 1a] and HIV-unexposed [Figure 1b] newborns. Color Scale: (1) Shades of red indicate positive correlations, (2) Shades of blue indicate negative correlations, (3) Deeper hues represent stronger correlations. Statistical Significance Annotations: (1) *denotes moderate correlation (r ≥ 0.20), (2) **denotes strong correlation (r ≥ 0.40). These annotations provide a visual summary of both the direction and strength of relationships among maternal age, gestational age and newborn anthropometric parameters (birth weight, head circumference, chest circumference and length).

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Multiple linear regression showed strong explanatory power for predicting birth weight.

For HIV-exposed newborns,

R² = 0.832 (F = 49.690; p = <0.001) with equation: y = −4.965 + 0.018*(sex) + 0.082*(head circumference) + 0.123*(chest circumference) + 0.027*(newborn length); head circumference (p = 0.038) and chest circumference (p = <0.001) were significant predictors.

For HIV-unexposed newborns,

R² = 0.701 (F = 48.002; p = <0.001) with equation: y = −5.044–0.019*(sex) + 0.064*(head circumference) + 0.094*(chest circumference) + 0.060*(newborn length); head circumference (p = 0.002), chest circumference (p = <0.001) and newborn length (p = <0.001) were significant predictors [Table 4 and Figures 2-4].

Table 4: Multivariable models of birth weight and GA-adjusted differences in newborn anthropometry and APGAR measures, including GA-adjusted odds of APGAR <7, stratified by HIV exposure status.

Model summary: HIV-exposed newborns (n=48)

Predictor

Coefficient (B)

Standard error

t-value

P-value (P>|t|)

95% CI (0.025)

95% CI (0.975)

Intercept (Constant)

−4.965

0.617

−8.050

0.000*

−6.211

−3.718

Sex of newborn

0.018

0.082

0.219

0.828

−0.147

0.183

Head circumference (cm)

0.082

0.038

2.145

0.038*

0.005

0.159

Chest circumference (cm)

0.123

0.024

5.078

0.000*

0.074

0.171

Newborn length (cm)

0.027

0.016

1.697

0.097

−0.005

0.060

Model summary: HIV-unexposed newborns (n=96)

Predictor

Coefficient (B)

Standard Error

t-value

P-value (P>|t|)

(0.025)

(0.975)

Intercept (Constant)

−5.044

0.686

−7.351

0.000*

−6.408

−3.679

Sex of newborn

−0.019

0.059

−0.324

0.747

−0.136

0.098

Head circumference (cm)

0.064

0.020

3.251

0.002*

0.025

0.104

Chest circumference (cm)

0.094

0.019

4.918

0.000*

0.056

0.132

Newborn length (cm)

0.060

0.015

4.038

0.000*

0.031

0.090

Dependent variable=Birth weight *Statistically significant regression (at p < 0.05)

GA- and sex-adjusted differences in newborn anthropometry and APGAR scores by HIV exposure group

Outcome

n

Adjusted mean difference*(Exposed vs. Unexposed)

(0.025)

(0.975)

p-value

Birth weight (kg)

124

−0.267

−0.433

−0.100

0.002*

Head circumference (cm)

118

−1.026

−1.697

−0.355

0.003*

Chest circumference (cm)

118

−0.974

−1.751

−0.197

0.014*

Newborn length (cm)

118

−1.285

−2.313

−0.258

0.015*

APGAR 1 min

124

−0.921

−1.618

−0.224

0.010*

APGAR 5 min

121

−0.593

−1.035

−0.152

0.009*

*Statistically significant at P<0.05

GA- and sex-adjusted odds of APGAR<7 by HIV exposure group.

Binary endpoint

n

Adjusted OR* (Exposed vs. Unexposed)

(0.025)

(0.975)

p-value

APGAR at 1 min<7

124

2.84

0.90

8.92

0.074

APGAR at 5 min<7

121

2.84

0.68

11.82

0.151

*Statistically significant at p < 0.05

Sensitivity models adjusted for GA, sex, maternal age and booking status

Outcome

n

Adjusted mean difference†

(0.025)

(0.975)

p-value

Birth weight (kg)

123

−0.258

−0.431

−0.085

0.004†

Head circumference (cm)

117

−1.113

−1.806

−0.420

0.002†

Chest circumference (cm)

117

−0.988

−1.804

−0.172

0.018†

Newborn length (cm)

117

−1.439

−2.507

−0.370

0.009†

APGAR 1 min

123

−0.739

−1.455

−0.024

0.043†

APGAR 5 min

120

−0.537

−0.992

−0.083

0.021†

†Statistically significant at p < 0.05. APGAR: Appearance-Pulse-Grimace-Activity-Respiration, GA: Gestational age, CI: Confidence interval, OR: Odds ratio

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Figure 2:

Four (a-d) scatter plots with fitted linear regression lines showing the relationship between newborn anthropometric measurements and birth weight. (a) Scatter plot of HIV-unexposed newborns showing the relationship between chest circumference (cm) and birth weight (kg), with an R² = 0.589 and regression equation y = 2.2 + 0.17*x. (b) Scatter plot of HIV-exposed newborns showing the relationship between chest circumference (cm) and birth weight (kg), with an R² = 0.751 and regression equation y = 3.29 + 0.2*x. (c) Scatter plot of HIV-unexposed newborns showing the relationship between head circumference (cm) and birth weight (kg), with an R² = 0.381 and regression equation y = 2.42 + 0.17*x. (d) Scatter plot of HIV-exposed newborns showing the relationship between head circumference (cm) and birth weight (kg), with an R² = 0.713 and regression equation y = 5.06 + 0.24*x.

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Figure 3:

Multilinear Regression: Residuals, R², Coefficients and Significance: These are two (a and b) multilinear regression analysis histograms showing normal distribution of the predicted values of birth weight (y) based on the regression model. (a) HIV-positive mothers: model includes sex of newborn, head circumference, chest circumference and newborn length; mean standardised residual: −1.48 ± 0.953, R² = 0.832. (b) HIV-negative mothers: same predictors; mean standardised residual: 3.45 ± 0.976, R² = 0.701.

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Figure 4:

These are two (a and b) multilinear regression analysis scatter plots showing the predicted values of birth weight (y) based on the regression model, with separate plots for each significant predictor. (a) shows a scatter plot of multilinear regression analysis exploring the prediction of birth weight of HIV-exposed newborns using their sex, head circumference, chest circumference and newborn length. (b) shows a scatter plot of multilinear regression analysis exploring the prediction of birth weight of HIV-unexposed newborns using their sex, head circumference, chest circumference and newborn length.

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DISCUSSION

This study examined the association between maternal HIV status and newborn anthropometry, GA, and early birth outcomes among deliveries in Uyo, Nigeria, comparing HIV-exposed and HIV-unexposed newborns. Maternal age and GA at delivery were broadly similar between groups; however, HIV-exposed newborns demonstrated significantly lower APGAR scores at 1 and 5 min, as well as reduced birth weight, head circumference, chest circumference, and body length. These differences highlight less favorable early adaptation and growth among HIV-exposed newborns despite comparable gestational maturity. In addition, relationships between birth weight and key anthropometric measures differed by HIV exposure status, underscoring the complex influence of maternal HIV infection on early newborn growth patterns in this setting. For pediatric practice, these findings highlight the need for closer growth surveillance and early supportive care among HIV-exposed newborns, even in the era of maternal antiretroviral therapy.

In exploring the impact of maternal HIV on newborn outcomes, our study revealed intriguing insights into the demographic and obstetric characteristics of mothers and the subsequent effects on their newborns. We found a predominance of younger mothers, a high proportion of whom attended antenatal care and delivered at term, irrespective of their HIV status. This demographic profile aligns with previous studies by Shivamurthy et al., Fouché et al., Braddick et al., and Gonzalez et al., who found similar obstetrics parameters, indicating that maternal age and antenatal care play crucial roles in maternal and neonatal health outcomes.^[20-23] Despite comparable obstetric parameters between HIV-positive and HIV-negative mothers, our study identified significant differences in birth outcomes, including APGAR scores and anthropometric measurements, highlighting the nuanced influence of HIV infection on newborn health. The significant difference observed in APGAR scores at 1, 5, and 10 min between HIV-exposed and HIV-unexposed newborns underscored distinct early newborn adaptation challenges. In this cohort, APGAR scores at 1 and 5 min were lower among HIV-exposed newborns, suggesting differences in immediate newborn status and adaptation at birth. APGAR scoring is, however, influenced by GA, transitional physiology, maternal medications, resuscitation practices, and observer variability; therefore, APGAR differences should be interpreted cautiously and not as definitive evidence of specific pathology or long-term outcome.^[18,24-28] Our findings support the pragmatic need for careful delivery-room assessment and early newborn monitoring of HIV-exposed newborns in resource-limited prevention of mother-to-child transmission (PMTCT) settings, while recognising that additional clinical and laboratory data would be required to explain mechanisms.^[2,4,24-28] Notably, Rencken et al. found that newborns with lower APGAR scores go on to develop inferior neurobehavioral functioning, showing the possible adverse outcomes in these HIV exposed newborns with lower APGAR scores.^[24] Indeed, these findings underscore the need for vigilant monitoring and early intervention strategies for newborns born to HIV-positive mothers. Furthermore, future research should delve deeper into the underlying mechanisms and long-term implications of these early newborn adaptations among newborns born to HIV-positive mothers.

Furthermore, our study identified significant associations between maternal HIV status and newborn anthropometric parameters, including birth weight, head circumference, chest circumference, and newborn length. HIV-exposed newborns exhibited lower mean birth weights and smaller head and chest circumferences compared to their HIV-unexposed counterparts. These findings echo those of previous studies by Fouché et al., Chalaschika et al., Trivedi et al., Mabaya et al., and Saavedra et al. Wilkinson et al., thus suggesting that maternal HIV infection may impair foetal growth and development, possibly through direct viral effects or other associated maternal factors (peculiar to HIV-positive mothers) which make their in-utero environment hostile for optimal foetal development of their newborns.^{[21,27,29-32]} In exploratory analyses, we did not detect statistically significant differences in anthropometry or APGAR scores by maternal HAART exposure; however, these comparisons were underpowered and potentially confounded and should be interpreted as hypothesis-generating rather than definitive, just like in the study by Fouché et al.^[21] These observed features highlight the need for tailored interventions aimed at optimising foetal growth and minimising adverse outcomes in HIV-exposed newborns, potentially through enhanced prenatal monitoring and nutritional support strategies.

Importantly, our study carried out multivariate regression analysis for birth weight based on maternal HIV status, revealing distinct predictors for HIV-exposed and HIV-unexposed newborns. Head circumference and chest circumference emerged as significant predictors in HIV-exposed newborns, underscoring the importance of cranial and thoracic development in this vulnerable population. In contrast, head circumference, chest circumference, and newborn length were pivotal predictors in HIV-unexposed newborns, emphasising comprehensive anthropometric assessments in evaluating foetal growth and developmental outcomes, echoing the findings from previous studies by Fouché et al., Trivedi et al., and Wilkinson et al.^[21,29,32] Notably, Fouché et al. found that head and chest circumference were significant predictors in HIV-exposed newborns. In contrast, head circumference, chest circumference, and newborn length were pivotal predictors in HIV-unexposed newborns.^[21] In addition, Wilkinson et al. identified gestational mid-upper arm circumference as a predictor of lower infant anthropometric measurements, particularly in HIV-exposed newborns.^[32]Likewise, Trivedi et al. highlighted through multiple linear regression that maternal HIV clinical stage and weight were predictors of their newborns’ birthweight and length.^[29] Therefore, these predictive models underscore the importance of comprehensive anthropometric assessments as well as provide valuable insights for tailored interventions in obstetric/perinatal clinical practice, aimed at mitigating adverse birth outcomes and optimising newborns’ health in diverse maternal HIV contexts.

In summary, our study contributes novel findings to fill the knowledge gap in our environment regarding the impact of maternal HIV on newborn anthropometry, GA, and birth outcomes in a Nigerian cohort. By elucidating distinct patterns in demographic characteristics, obstetric parameters, APGAR scores, anthropometric measurements, and predictive models for birth weight, our findings underscore the complex interplay between maternal HIV status and newborn/neonatal health in our environment with high HIV prevalence.

Despite the insights gained, our study is not without limitations. First, the retrospective nature of aspects of our data from medical records introduced biases or missing data, affecting the comprehensiveness of our analyses. In addition, we could not reliably assess or adjust for several important potential confounders, including maternal anaemia, parity, pregnancy complications (e.g., hypertensive disorders/diabetes), viral load, CD4 count, maternal nutritional status, socioeconomic factors, duration/adherence to HAART, and concomitant (non-HAART) medications that may influence immediate newborn status (including APGAR scoring). Residual confounding is therefore possible. Furthermore, the study was conducted at a single centre, which may limit the generalisability of our findings to broader populations. Future research endeavours should consider multi-centre studies with larger sample sizes to enhance statistical power and improve external validity.

Moving forward, there is a pressing need for longitudinal studies to investigate the long-term effects of maternal HIV on child development beyond the neonatal period. Longitudinal assessments would provide valuable insights into developmental trajectories, cognitive outcomes, and chronic health conditions among HIV-exposed children as they age. In addition, prospective cohort studies could explore the impact of evolving HIV treatment strategies, including early initiation of antiretroviral therapy and novel therapeutic approaches, on maternal and neonatal health outcomes.

Based on our findings, we recommend that healthcare providers implement targeted interventions aimed at improving prenatal care and neonatal monitoring for HIV-positive mothers and their newborns according to the recommendations by Lindegren et al., Chi et al., McNairy et al., and Lisy in their studies.^[33-36] These studies showed that early initiation of antiretroviral therapy, nutritional supplementation, and close surveillance during pregnancy can potentially mitigate adverse birth outcomes and enhance neonatal health.^[33-36] Furthermore, these studies advocated that policymakers should also prioritise resource allocation towards maternal and child health programmes tailored to the needs of HIV-affected populations, ensuring equitable access to comprehensive care and support services.^[33-36]

Finally, while our study contributes valuable insights into the complex interplay between maternal HIV infection and newborn outcomes, continued research efforts are essential to advance our understanding and improve clinical outcomes for HIV-exposed newborns. By addressing the limitations, pursuing future research directions and implementing evidence-based recommendations, we can strive towards optimising maternal and neonatal health outcomes in settings affected by HIV/AIDS.

CONCLUSION

HIV-exposed newborns in this cohort demonstrated lower birth weights, smaller head circumferences, and lower early APGAR scores compared with HIV-unexposed newborns. GA and key anthropometric measures were closely associated with birth weight, with differing patterns observed according to HIV exposure status. These findings highlight the adverse influence of maternal HIV on early newborn growth and adaptation and underscore the importance of strengthened antenatal care, early supportive interventions, and closer postnatal monitoring to improve outcomes for HIV-exposed newborns in resource-limited PMTCT settings.