Risk Factors During Pregnancy and Birth-Related Complications in HIV-Positive Versus HIV-Negative Women in Denmark, 2002–2014

M Ørbæk; K Thorsteinsson; E Moseholm Larsen; TL Katzenstein; M Storgaard; IS Johansen; G Pedersen; D Bach; M Helleberg; N Weis; A-M Lebech

Disclosures

HIV Medicine. 2020;21(2):84-95. 

In This Article

Abstract and Introduction

Abstract

Objectives: We aimed to compare risk factors for adverse pregnancy outcomes in women living with HIV (WLWH) with those in women of the general population (WGP) in Denmark. Further, we estimated risk of pregnancy- or birth-related complications.

Methods: A retrospective cohort study including all WLWH who delivered a live-born child from 2002 to 2014 and WGP, matched by origin, age, year and parity, was carried out. We compared risk factors during pregnancy and estimated risk of pregnancy- and birth-related complications using multivariate logistic regression.

Results: A total of 2334 pregnancies in 304 WLWH and 1945 WGP were included in the study. WLWH had more risk factors present than WGP during pregnancy: previous caesarean section (CS) (24.7% versus 16.3%, respectively; P = 0.0001), smoking (14.2% versus 7.5%, respectively; P = 0.0001) and previous perinatal/neonatal death (2.3% versus 0.9%, respectively; P = 0.03). We found no difference between groups regarding gestational diabetes, hypertensive disorders, low birth weights or premature delivery. More children of WLWH had intrauterine growth retardation (IUGR) [adjusted odds ratio (aOR) 1.9; 95% confidence interval (CI) 1.1–3.2; P = 0.02]. Median gestational age and birth weight were lower in children born to WLWH. WLWH had a higher risk of emergency CS (EmCS) (aOR 1.6; 95% CI 1.2–2.1; P = 0.0005) and postpartum haemorrhage (aOR 1.4; 95% CI 1.0–1.9; P = 0.02) but not infection, amniotomy, failure to progress, low activity-pulse-grimace-appearance-respiration (APGAR) score or signs of asphyxia.

Conclusions: WLWH had more risk factors present during pregnancy, similar risks of most pregnancy- and birth-related complications but a higher risk of postpartum haemorrhage and EmCS compared with WGP. Children born to WLWH had lower median birth weights and gestational ages and were at higher risk of IUGR.

Introduction

Management of pregnant woman with HIV infection has evolved significantly over the past 25 years in light of advancements in antiretroviral therapy (ART) and a better understanding of the prevention of perinatal HIV transmission. In the USA and Europe, the risk of mother-to-child transmission (MTCT) in women living with HIV (WLWH) with viral suppression and who do not breastfeed is < 1%, independent of mode of delivery.[1–3]

Pregnancy in WLWH compared with women of the general population (WGP) has been associated with several adverse outcomes for both mothers and infants.[4,5] Possible maternal complications include pre-eclampsia, gestational diabetes and premature rupture of membranes (PROM). Moreover, the birth itself renders the mother at risk of several other harmful events, including emergency caesarean section (EmCS), postpartum haemorrhage and infections.[6–10] Previous studies have shown that children born to WLWH are at higher risk of prematurity, asphyxia, growth restriction and low birth weight.[6,11,12] However, much of the research has shown contradictory results,[5,6,11,13–15] which may be explained by differences in national recommendations and changing guidelines regarding ART and mode of delivery. And it has been questioned if pregnant WLWH constitute a subpopulation with risk factors beyond HIV infection causing bias in results.[9]

Vaginal delivery is a safe mode of delivery in WLWH with viral suppression and does not increase the risk of MTCT.[3,10,16] However, far more WLWH still deliver by caesarean section (CS), including elective caesarean section (ECS) and EmCS, compared to WGP.[16] CS and especially EmCS increase the risk of complications for both mothers and children.[10,17] The risk of complication is likely to be higher in WLWH with impaired immune function.[4] However, with ART and the restoration of immune function, it is possible that the previously shown risks of complications are no longer present.

This study aimed to compare known risk factors in pregnancy between WLWH and their matched controls. Further, we examined whether WLWH and their children are at greater risk of complications related to pregnancy and birth and whether the differences in complications could be explained by mode of delivery or risk factors during pregnancy.

Materials and Methods. Study Design and Population: The study design and population have been described in a previous study on mode of delivery.[16] We conducted a retrospective matched cohort study including all WLWH giving birth to live-born children in Denmark between 1 January 2002 and 31 December 2014. Exclusion criteria were HIV diagnosis after delivery, unknown mode of delivery and invalid Personal Identification Number (PIN), a unique 10-digit number assigned to all Danish residents at birth or immigration. Only singleton pregnancies were included and every pregnancy was treated as a separate case. WLWH were divided into three groups reflecting a change in guidelines in 2007, where vaginal delivery was accepted in WLWH with viral load (VL) < 1000 HIV-1 RNA copies/mL (2002–2006, 2007–2008 and 2009–2014). Using the Danish Medical Birth Registry, WLWH were individually matched at random 1:5 on maternal origin, age at delivery and parity to WGP. Women with unknown parity were set to be nulliparous. HIV characteristics for WLWH were extracted from medical records.[16] Using the PIN, we linked to the following registries.

The Medical Birth Registry: From this registry, we retrieved information regarding date of birth, gestational age, birth weight and pregnancy- and birth-related complications.

The National Patient Registry: From this registry, we extracted all diagnoses regarding pregnancy, comorbidities and other risk factors during pregnancy, birth, and complications of pregnancy or birth using the International Classification of Diseases, 10th revision (ICD-10) codes DO0-999 and DZ3–399.

Statistics Denmark: From the registries at Statistics Denmark, we collected data on the maternal country of birth.

Outcomes: The primary outcomes of this study were risk factors during pregnancy comparing WLWH and WGP, including high body mass index (BMI > 25), smoking, prior perinatal deaths, prior CS, viral hepatitis (chronic hepatitis B and C) and psychiatric disorders (DO993B1–5).

Secondary outcomes were pregnancy- or birth-related complications.

Pregnancy-related complications included PROM (<37weeks) and preterm premature rupture of membranes (PPROM; <37weeks) which subsequent may cause prolonged birth (>6hours) or EmCS, intrauterine growth retardation (IUGR) or placental insufficiency (DO365A-E), gestational diabetes mellitus (GDM), hypertensive disorders [pre-eclampsia, eclampsia and haemolysis elevated liver enzymes low platelets (HELLP) syndrome], preterm delivery (< 37 weeks) and birth weight < 2500 g.

Birth-related complications included amniotomy, failure to progress (DO62–639), indications of asphyxia (DO363 + DO68–688), low activity-pulse-grimace-appearance-respiration (APGAR) score, perineal laceration (2th–4th degree or episiotomy), EmCS (DO821A-C), postpartum haemorrhage (> 500 mL) and infections (DO86-DO869, i.e. all postpartum infections, including urinary tract infections, endometriosis and wound infections).

Statistical Analyses: Categorical variables were reported as counts and percentages and compared using the χ2 test or Fisher's exact test, as appropriate. Continuous variables were summarized as mean and 95% confidence interval (CI) or median and interquartile range (IQR) and compared using the Wilcoxon rank sum test.

Individual multivariate logistic regression was performed to identify differences in risk of complications. Odds ratios (ORs) and CIs were estimated and adjusted a priori. Pregnancy-related complications were adjusted for viral hepatitis, smoking, psychiatric disorders, age (< 30 or ≥ 30 years old) and parity. Low birth weight was additionally adjusted for prematurity. Birth-related complications were adjusted for smoking, age (< 30 or ≥ 30 years old), parity, previous CS, year and mode of delivery. Failure to progress, amniotomy and perineal lacerations were only assessed in women undergoing vaginal delivery. To control for repeated testing, a combined P-value was estimated for variables spending more than one degree of freedom in the logistic regression. Individuals with missing explanatory values were excluded from the multivariate regression analyses. The validity of the model was tested using the Hosmer and Lemeshow goodness-of-fit test. SAS statistical software version 9.3 (SAS Institute Inc., Cary, NC) was used for data analysis and P-values < 0.05 (two-sided) were considered statistically significant.

Ethics: The project was approved by Danish Data Protection (J. no. 2012-41-0904), the National Board of Health (J. no. 7-604-04-2/4) and the Danish Patient Safety Authority (case no. 3-3013-406/1-3). According to Danish law, approval from the National Committee on Health Research Ethics was not required as no biomedical interventions were performed.

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