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ORIGINAL ARTICLE
Year : 2019  |  Volume : 22  |  Issue : 5  |  Page : 591-597

Maternal and perinatal outcomes after caesarean delivery in early and late onset preeclampsia with HIV positive and HIV negative South African Women


Optics and Imaging Centre, Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa

Date of Acceptance14-Dec-2018
Date of Web Publication15-May-2019

Correspondence Address:
Dr. O A Onyangunga
Optics and Imaging Centre, Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban - 4001
South Africa
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/njcp.njcp_364_16

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   Abstract 


Objective: We analyzed the maternal and perinatal outcomes in early onset preeclampsia (EOPE) and late onset preeclampsia (LOPE) pregnant women who had scheduled caesarean deliveries. We sub-analyzed the two categories into HIV positive and HIV negative. Patients and Methods: This prospective study was conducted at a regional hospital in Durban, South Africa during 14 months. A total of 14304 deliveries were registered. Out of the 1759 preeclampsia, 351 (19.9%) were EOPE and 1408 (80.1%) were LOPE. Hundred and twenty preeclamptics (n = 120) scheduled for caesarean delivery were selected and divided into two categories namely EOPE (n = 60) and LOPE (n = 60). Each preeclampsia category was then further stratified into HIV positive (n = 30) and HIV negative (n = 30) groups. Maternal demographic, clinical details for preeclampsia, blood laboratory tests, maternal, and perinatal outcomes were recorded. Results: Women with EOPE were older compared to those with LOPE (P = 0.0001). Also the HIV positive women were older compared to the HIV negative groups in both EOPE and LOPE categories (P = 0.03). However, multiparous and primiparous were predominant in EOPE and LOPE categories, respectively (P = 0.00 and P = 0.00). The severity of hypertension and the HIV status did not differentiate the 2 groups. Overall, maternal complications (eclampsia, persistent postpartum hypertension, HELLP syndrome, maternal death) and poor fetal outcomes occurred predominately in EOPE. Conclusion: This study confirms the heterogeneity of preeclampsia and shows that the timing of onset of this pregnancy disorder is important to disease severity. Further HIV status influences maternal and neonatal outcome.

Keywords: Early and late onset pre-eclampsia, HELLP syndrome, HIV-1 infection, pre-eclampsia


How to cite this article:
Onyangunga O A, Naicker T A, Moodley J. Maternal and perinatal outcomes after caesarean delivery in early and late onset preeclampsia with HIV positive and HIV negative South African Women. Niger J Clin Pract 2019;22:591-7

How to cite this URL:
Onyangunga O A, Naicker T A, Moodley J. Maternal and perinatal outcomes after caesarean delivery in early and late onset preeclampsia with HIV positive and HIV negative South African Women. Niger J Clin Pract [serial online] 2019 [cited 2019 Jul 24];22:591-7. Available from: http://www.njcponline.com/text.asp?2019/22/5/591/258272




   Introduction Top


Hypertensive disorders of pregnancy (HDP) are a leading cause of pregnancy-related morbidity and mortality in South Africa.[1] Recently, the International Society for the Study of Hypertension in Pregnancy (ISSHP) classified HDP into chronic hypertension, gestational hypertension and preeclampsia (PE)—de novo or superimposed on chronic hypertension and white coat hypertension. Preeclampsia was also classified into mild and moderate sub-categories (non-severe hypertension), severe preeclampsia and the HELLP syndrome. The ISSHP further suggested that for clinical purposes, preeclampsia can be divided into early- and late-onset preeclampsia. Early-onset preeclampsia (EOPE) manifests before 33 weeks + 6 days gestation while late-onset preeclampsia (LOPE) presents at or after 34 weeks of gestation.[2],[3] Early- and late-onset preeclampsias share some pathogenic roots, but risk factors vary and often lead to different outcomes. Therefore, the two preeclampsia categories should be treated as distinct entities from an etiologic, clinical, and prognostic standpoint.[4],[5],[6],[7],[8] Preeclampsia is a major cause of maternal and fetal morbidity and mortality worldwide. The estimated number of maternal deaths caused by preeclampsia is 60000 annually.[9] The World Health Organization (WHO) reports that HDP which includes preeclampsia (PE) accounts for approximately 16% of maternal deaths in developed countries, 9% in Africa and Asia, and as many as 26% in Latin America and the Caribbean.[10],[11]

HIV infection is a major public health concern worldwide[12],[13] and is a significant cause of maternal deaths in South Africa.[1] HIV/AIDS contributes to 40.5% of maternal deaths in South Africa.[1] The province of KwaZulu-Natal with 23.1% of maternal deaths is also the epicentre of the HIV global pandemic. It is a serious obstetric dilemma that young woman of reproductive age are at risk of HIV infection.[14] Importantly HIV infection superimposed upon pregnancy induced hypertensive pregnancies, occur frequently hence presents a unique paradigm to study these two co-morbidities. Previous studies in the same province have reported a prevalence of 12% for PE.[15] In the other hand the prevalence of HIV at the time of the study was approximately 39%. Our group[16],[17] has done a case control study on prevalence of PE in HIV affected pregnancies and maternal and fetal outcomes of HIV positive patients admitted to intensive care units respectively. Pre-eclampsia and HIV infection are immune related thus might have significant interaction with each other. Literature has reported conflicting results of the effect of HIV on the incidence of PE[16],[18],[19] hence, this study aims to analyse the maternal and perinatal outcomes of HIV negative and positive pregnant women who had scheduled caesarean deliveries for EOPE and LOPE in South African women.


   Patients and Methods Top


Ethical approval was obtained from the Biomedical Research Ethics Committee, University of KwaZulu-Natal (BE: 040/12). This prospective study was conducted at a regional hospital in Durban, South Africa within a period of 14 months from September 2012 to November 2013. A total of 14304 deliveries were registered at the obstetric unit, of which 1759 were preeclamptic. Three hundred and fifty one (19.9%) were EOPE and 1408 (80.1%) were LOPE.

The preeclamptic study group was recruited via convenient sampling from the planned and emergency caesarean deliveries.[20] The sample size was determined by a biostatistician based on the prevalence of preeclampsia in South African. Patients with PE (n = 120; BP ≥140/90 mmHg and proteinuria ≥1+ on dipstick or 24 hours proteinuria of 300 mg) were divided into 2 groups according to gestational age namely EOPE (n = 60; <33 weeks + 6 days) and LOPE (n = 60; ≥34 weeks at the time of diagnosis). Each PE category was then further stratified into HIV positive (n = 30) and HIV negative cohorts (n = 30) as shown in [Figure 1]. Written informed consent was obtained from patients scheduled for caesarean delivery.
Figure 1: Flow diagram illustrating the sub-categories of preeclampsia and their HIV status. *HIV- = HIV negative; HIV+ = HIV positive; PE = Preeclampsia

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Preeclampsia was stratified into mild/moderate and severe [Figure 1]. Severe hypertension was defined as systolic blood pressure ≥160 mmHg and or diastolic blood pressure ≥110 mmHg; mild to moderate PE was defined when systolic blood pressure <160 mmHg and diastolic blood pressure <110 mmHg. Early persistent postpartum hypertension was defined as blood pressure ≥140/90 mmHg 48 hours post-delivery. In the antepartum period, blood pressure was initially monitored half hourly until the high blood pressure was “stabilized” followed by four hourly intervals measurement. After caesarean delivery, the blood pressure was checked at an hour interval for 24 hours. Records were taken at every 4 hours up to 48 hours after delivery. Women's weight at the initiation of antenatal care and at the time of delivery was recorded. The difference between the 2 measurements was considered as the weight gain during pregnancy. We used the ratio between the weight gain and gestational age at delivery to evaluate the impact of weight gain on EOPE and LOPE.

All HIV infected women received HAART (Highly Active Antiretroviral Therapy). Women with diabetes, previous history of hypertension, auto immune disease, history of seizures, chorioamnionitis, intrauterine death, and multiple pregnancies were excluded. Demographic, clinical and obstetrical data of all patients were recorded in a structured format.

Statistical analysis

Data were analyzed using SPSS version 23 (IBM, USA). Results are expressed as mean ± standard deviation (SD). Parametric data was analysed using the Independent t-test, Pearson Chi-Square test, whilst non-parametric data was analysed using the Mann-Whitney U test. A P value of <0.05 was considered as statistically significant.


   Results Top


Maternal demographic characteristics in early and late onset preeclampsia

The demographic features of the EOPE and LOPE categories are presented in [Table 1]. Irrespective of the HIV status, the mean maternal age was higher in the EOPE (27.9 ± 7.0 years) vs the LOPE (25.1 ± 6.03 years) category. The age mean in the HIV positive group was higher compared to the HIV negative group (P = 0.0001). The parity in EOPE and LOPE (2.1 ± 1.2 and 1.8 ± 0.9, respectively) were similar (P = 0.1). However, primiparous were more frequent in LOPE compared to EOPE (P = 0.001). The parity in the HIV negative and positive LOPE sub-groups were statistically different (2.2 ± 0.5 and 1.6 ± 1.0; P = 0.03).
Table 1: Maternal age and parity in early and late onset preeclampsia

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Clinical and obstetrical parameters studied in early and late preeclampsia

The systolic and diastolic blood pressure were similar in both EOPE and LOPE categories (P = 0.9) [Table 2]. Among the 53 cases of severe PE, 32 (60.37%) were from the EOPE category and 21 was from the LOPE category. Out of the 32 women, 20 (62.2%) were HIV negative and 12 (37.8%) were HIV positive (P = 0.0001). Furthermore, severe PE were predominately found in the HIV negative LOPE 17 (80.9%) compared to HIV positive LOPE 4 (19.1%) group (P = 0.000). The mean proteinuria by dipstick analysis was significantly different in EOPE (++) vs LOPE (+) (P = 0.02). The gestational age at delivery differed in EOPE (33.1 ± 9 weeks) compared to LOPE (36.8 ± 1.7 weeks) categories (P = 0.001). We observed a lower gestational age in HIV negative EOPE (32.9 ± 2.60 weeks) compared to HIV positive EOPE (33 ± 1.7 weeks) (P = 0.05). The LOPE sub-groups did not show any difference (P = 0.4).
Table 2: Clinical data of early and late onset preeclampsia

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Irrespective of HIV status, maternal weight in EOPE (75.6 ± 18.3 kg) was higher than the LOPE category (72.1 ± 18.1 kg) (P = 0.0001). The weight gain was 7.2 ± 5.5 kg and 7.6 ± 5.2 kg for EOPE and LOPE, respectively. Weight gain was lower in both HIV positive EOPE (6.4 ± 5.4 kg) and LOPE (6.3 ± 4.4 kg) compared to the HIV negative EOPE (7.9 ± 5.6 kg and LOPE (8.6 ± 5.5 kg) (P = 0.001) groups. The weight gain/gestational age ratios in EOPE (3:20) was lower compared to that of LOPE (5:20) categories (P = 0.05).

Laboratory findings early and late onset preeclampsia

Maternal hemoglobin level (<11 g/dl) were similar in both EOPE and LOPE. The level of urea, creatinine, uric acid, alkaline phosphatase, alanine transaminase, and aspartate transaminase were higher in EOPE compared to the LOPE categories except for lactate dehydrogenase. There was a lower CD4 count in the EOPE (367.71 ± 149.04) compared to the LOPE (462.44 ± 311.1) categories (P = 0.032).

Indications for caesarean delivery in early and late pre-eclampsia

Regardless of HIV status, caesarean delivery for severe PE as indication occurred more frequently in LOPE (n = 21) compared to EOPE (n = 3) categories (P = 0.001). Based on HIV status, the number of caesarean deliveries was equal between EOPE and LOPE and their subgroups [Table 3]. All 22 cases of caesarean deliveries for severe and preterm PE occurred in the EOPE category. Furthermore, elective caesarean delivery for oligohydramnios (n = 4; 80%) in HIV positive EOPE (P = 0.001) and for previous caesarean delivery (n = 13; 65%) in HIV positive LOPE (P = 0.02) were more frequent than the HIV negative EOPE group.
Table 3: Indications for caesarean delivery in early and late onset preeclampsia (HIV positive and negative)

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Maternal morbidity and mortality in early and late onset preeclampsia

Only one case of eclampsia was recorded in LOPE group within 24 hours after delivery. Imminent eclampsia, HELLP syndrome, and early post-partum persistent hypertension were the major adverse events that occurred predominantly in the EOPE group. These complications were associated with severe renal and liver impairment (P = 0.001). The EOPE group had a longer in-hospital stay compared to the LOPE group (4.7 ± 3.5 versus 3.6 ± 1.1 days; P = 0.05), respectively [Table 4].
Table 4: Maternal complications in early and late preeclampsia (HIV positive and negative)

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Perinatal outcomes in early and late preeclampsia

Perinatal outcome is outlined in [Table 5]. Birth weight was significantly different between the EOPE (2148 ± 739 g) and LOPE (2900 ± 536 g) categories. The placental weight in the EOPE group was less than that of the LOPE group (P = 0.05). Intra-uterine growth restriction (IUGR) or small for gestational age and fetal distress were more frequent in EOPE than the LOPE categories. The Apgar score at first minute (7.2 ± 1.3 vs 7.9 ± 0.5) and fifth minute (8.5 ± 1.0 vs 8.9 ± 0.3) minute were significantly lower in the EOPE compared to the LOPE group (P = 0.002 and P = 0.001, respectively). These neonates stayed longer in hospital compared to those of the LOPE group (5.17 ± 2.47 vs 1.06 ± 0.86 days; P = 0.0001).
Table 5: Relevant perinatal data in early and late preeclampsia (HIV positive and negative mothers)

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   Discussion Top


In our study, maternal age was significantly higher in EOPE compared to the LOPE category. These results are similar to previous studies.[21],[22] Advanced maternal age has been reported to be associated with EOPE.[22],[23] Fang et al.[22] and Leung et al.[23] showed statistically significant differences in maternal age and incidence of PE development. Leung et al.[23] studied two populations (Australian and British) and showed an odds ratio (OR) (95% CI) of 2.06 and 1.40 for the age group <25 years, 0.80 and 1.05 for 26–30 years age group, 0.73 and 0.54 for 31–35 years age group, 1.12 and 1.13 for a 36–40 years age group, and 2.02 and 1.83 for >40 years group in Australia and UK, respectively. Despite the ORs in Australia and the UK being different, they were higher in both extreme reproductive ages. Other reports[24],[25],[26] found no difference in maternal age between EOPE and LOPE suggesting that this may be due to the age of first pregnancy. Indeed in high-income countries, LOPE occurs more frequently in the older age group. An interesting finding in our study was the higher age in the HIV positive EOPE compared to the HIV negative subgroup. Gene interactions in different age groups, regulating the development of PE in the HIV infected mother is plausible.[27],[28] A literature review implicates a possible maladaptation to pregnancy changes in advanced aged women; loss of vascular compliance, decline vascular responsiveness to endothelium-dependent vasodilators, down-regulation of gene expression of angiogenesis as co-responsible factors for the early and late occurrence of PE.[29],[30] Maternal age also influences myometrium and vasculature gene expression which impair placental implantation and development,[29] this finding however needs further investigation.

Primiparity has been cited as a higher risk factor for PE development,[21],[22],[23],[24],[25],[26] the pathogenic mechanism of which is unclear. Primipaternity and long interval between coitus among the primiparous women has been postulated as possible causal factors.[31] A number of studies[16],[17],[18],[19] have found primiparity more frequent in LOPE rather than EOPE; a similar observation was noted in our study. In contrast Madzali et al.[32] in a retrospective study reported 56.0% nulliparous in EOPE and 53.9% in LOPE group. Whilst Gulec et al.[33] found no difference in the frequency of primiparity in both EOPE and LOPE, suggesting further investigations to clarify these controversies are warranted.

Early onset preeclampsia is associated with preterm delivery.[18],[26],[32],[33] In our study, the gestational age at delivery for EOPE was 33 ± 1 weeks vs 36.4 ± 1.7 weeks for LOPE. In a cohort study, Li et al.[26] reported the gestational age of 32 + 1 weeks for EOPE and 37 + 2 weeks for LOPE, respectively. Similarly, Aksornphusitaphong et al.,[34] reported lower mean gestational age, for EOPE (30.5 + 3.3 weeks) and LOPE (36.8 + 2.2 weeks) at delivery; however, their results are confounded by the inclusion of diabetic patients into the cohort. Clinicians are cautious and have different views on the expectant or interventionist management of severe EOPE. Churchill et al.[35] reports that caesarean section mode of delivery did not improve maternal and fetal outcome. The differences in gestational age at time of delivery in EOPE could be related to the severity of the disease, maternal or fetal affectation, protocols and institutional facilities.

Few studies[21],[31] with vaginal and caesarean delivery report a higher mean systolic and/or diastolic blood pressure in the EOPE compared to the LOPE group. Our study was limited to caesarean deliveries and no difference in blood pressure was observed. Indeed, labor is a stressful condition for the mother and the fetus and may influence the pregnancy outcome. In our study, severe hypertension was more frequent in the EOPE compared to the LOPE category. Moreover, we noted a predominance of severe hypertension in the HIV negative subgroups suggesting the “protective role” of HIV infection for the development of PE.[18],[19]

Pre-gestational weight, body mass weight, and gestational weight gain are used to evaluate the risk of PE development.[23],[24],[36] An excessive maternal weight or weight gain is associated with the development of PE. In our study, irrespective of HIV status, the maternal weight at booking was higher in the EOPE compared to the LOPE category. Based on HIV status, we also report a lower gestational weight gain in HIV-infected women and these findings are supported by Floridia et al.[37]

The high prevalence of complications particularly the HELLP syndrome in EOPE expounds the severity and the heterogeneity of the 2 forms of PE.[30],[38] Haram et al.[39] linked polymorphism of chromosomes 2q, 5q, and 13q to PE development. Also polymorphisms of genes STOX, ERAP1, syncytin envelop gene, -670 Fas receptor as well as ACVR2A gene on chromosome 2q22, the toll like receptor -4 (TLR-4) and factor V Leiden mutation have all been implicated in the development of PE and the HELLP syndrome.[39]

Poor fetal outcome in EOPE has being attributed to severe hypoxia of the placental bed and placental microenvironment.[4],[40] Placental lesions emanating from under perfusion have also reported similar perinatal outcomes in LOPE.[4] In our study, we report a correlation between the severity of hypertension and adverse fetal outcome. Prematurity, neonatal deaths, and cost-effective issues are a concern in the management and outcome of women with EOPE. In our study, 33.3% of EOPE women delivered after 36 weeks. It is hence important, that the management of each patient be individualized in view of life threatening conditions.

A limitation of our study is the sample size; a larger cohort of preeclamptic women undergoing caesarean delivery is warranted. Nevertheless, it has the merit of giving the impact of preeclampsia and HIV infection co-morbidity on mothers who had caesarean delivery. Our study has confirmed findings such as those of Leung et al.[17] that demographic information and clinical findings are important tools in the management of PE particularly in resource limited settings. As PE is no longer considered solely an obstetrical disease, a multidisciplinary follow-up in the early and the late postpartum period is recommended.


   Conclusion Top


Our study confirms the heterogeneity of PE and shows that the timing of disease onset is an important indicator of disease severity and possibly of disease etiology. Furthermore, HIV status influences perinatal and maternal outcome. Maternal age and parity are risk factors for both EOPE and LOPE development. Although HIV infection is related to poor outcome, it has a possible protective role in the occurrence of severe PE.

Acknowledgements

The authors acknowledgement the College of Health Sciences, the Medical Education Partnership Initiative (MEPI), University of KwaZulu-Natal and the National Research Foundation (South Africa) for their financial support. We thank Dr K Maduray and Dr F Odun-Ayo for their contributions.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Figures

  [Figure 1]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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  In this article
    Abstract
   Introduction
   Patients and Methods
   Results
   Discussion
   Conclusion
    References
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