Browsing INFANT Research Centre by Author "Al Khalaf, Sukainah"
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- ItemAssociation between hypertensive disorders of pregnancy and the risk of asthma, eczema and allergies in offspring: A systematic review and meta-analysis(John Wiley & Sons, Inc., 2020-10-09) Conlan, Nicola; Maher, Gillian M.; Al Khalaf, Sukainah; McCarthy, Fergus P.; Khashan, Ali S.; Health Research BoardObjective: Conduct a systematic review and meta‐analysis examining the association between hypertensive disorders of pregnancy (HDP) and risk of asthma, eczema, food allergies and allergic rhinitis in the offspring. Design: A systematic review and random‐effects meta‐analyses were used to synthesize the published literature. PRISMA guidelines were followed throughout. Two independent reviewers carried out data extraction and quality assessment of included studies. Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to assess certainty of findings. Data Sources: A systematic search of PubMed, Embase, Web of Science and CINAHL was performed from inception of databases‐21 April 2020, supplemented by hand‐searching reference lists of included articles. Eligibility Criteria: Two reviewers independently reviewed titles, abstracts and full‐text articles. English language, cohort, case‐control and cross‐sectional published studies examining the association between HDP (primary exposure: pre‐eclampsia; secondary exposures: all other HDP) and asthma, eczema, food allergies and allergic rhinitis were included. Results: Of the 2833 studies retrieved, 14 studies met inclusion criteria. Of these, 11 studies reported evidence of association between HDP and atopic disorders. Thirteen studies reported estimates for asthma. Seven of these included adjusted estimates (including 3 645 773 participants) for a pre‐eclampsia‐asthma relationship resulting in a pooled odds ratio (OR) of 1.14 (95% CI: 1.04, 1.26) (I2 = 62%). However, this OR was reduced to 1.08 (95% CI: (0.78, 1.48) when the large registry‐based cohort studies were excluded, and only studies using parent‐reported measures to determine a diagnosis of asthma were included. Four studies included adjusted estimates (including 254 998 participants) for other HDP and asthma (pooled OR: 1.02, 95% CI: 0.96, 1.09) (I2 = 0%). Two studies provided adjusted estimates (including 1 699 663 participants) for a pre‐eclampsia‐eczema relationship (pooled OR: 1.06, 95% CI: 0.98, 1.14) (I2 = 0%). One study including pre‐eclampsia‐food allergies was identified (OR: 1.28, 95% CI: 1.11, 1.46). Three studies examined a HDP (including pre‐eclampsia) and allergic rhinitis relationship, with effect estimates ranging from 1.14 to 2.10. Studies were classified as low or low‐moderate risk of bias, while GRADE certainty of findings were low to very low. Conclusions: While pre‐eclampsia was associated with a possible increased risk of asthma in offspring, there was no evidence for a relationship between other HDP and asthma. There is a lack of published literature examining the association between HDP and eczema, food allergy and allergic rhinitis. Further primary research is warranted to gain a better understanding of the association between HDP and the risk of childhood atopic disease.
- ItemThe impact of maternal chronic hypertension and chronic kidney disease on the risk of adverse pregnancy outcomes and long-term cardiovascular disease: a population-based epidemiology study(University College Cork, 2022-08-31) Al Khalaf, Sukainah; Khashan, Ali; McCarthy, Fergus; O'Reilly, Eilis; Ministry of Health – Kingdom of Saudi ArabiaBackground and aims: The prevalence of chronic hypertension (CH) and chronic kidney disease (CKD) have increased among pregnant women in recent decades. Given the improvement in antenatal care over the last few decades, it is still unclear whether the risk of adverse pregnancy outcomes (APOs) among women with CH and/or CKD has decreased. There is limited evidence on the association between antihypertensive treatment and APOs in women with CH. Although there is evidence that women with a history of APOs have an increased risk of cardiovascular disease (CVD), it remains unclear whether pre-pregnancy hypertension and the occurrence of APOs would influence this association. The aim of this PhD project was to investigate the impact of maternal CH and/or CKD and antihypertensive treatment on the risk of APOs and long-term CVD. Structure and methods: This thesis includes eight chapters: Introduction, Methods, two systematic review articles on the impact of CH and CKD on APOs, three original research articles, and Discussion. Data from the Swedish National Registers were analysed to examine the associations between CH/CKD and the risk of APOs over the last three decades. Data from the UK CALIBER platform were used to investigate: i) the association between CH and APOs, with a focus on the role of antihypertensive treatment and control of hypertension, and ii) the associations between pre-pregnancy hypertension and subsequent diagnosis of 12 different CVDs, considering the role of APOs on these associations. Adverse pregnancy outcomes were pre-eclampsia, preterm birth, stillbirth, Caesarean section and small for gestational age (SGA). The statistical methods were done using logistic regression models for the Swedish data, logistic regression models with propensity score matching for the antihypertensive treatment analyses, while the associations between pre-pregnancy hypertension and CVD were analysed using stratified Cox models. All statistical models were adjusted for several potential confounders. Results: Systematic reviews and meta-analyses: CH was associated with 5-fold increased odds of pre-eclampsia and approximately 2-fold increased odds of stillbirth, preterm birth, and SGA, compared to women without CH. Women with treated CH (compared to untreated normotensive women) had higher odds of APOs. However, the results were inconsistent when outcomes were compared between treated and untreated women with CH; no increased odds of superimposed pre-eclampsia or other APOs were observed, except for 86% increased odds of SGA. Findings from the meta-analysis suggested that women with CKD had higher odds of pre-eclampsia, Caesarean section, preterm birth, very preterm birth, and SGA. All causes of CKD were associated with increased odds of pre-eclampsia, preterm birth, and SGA, with stronger associations in women with diabetic CKD, particularly for preterm birth [adjusted odds ratio (aOR): 4.76, (95% confidence interval (CI), 3.65–6.21)] and SGA [aOR: 4.50, (95% CI, 2.92–6.94)]. The findings according to the severity of kidney disease showed that later stages of CKD were associated with a greater odds of APOs than earlier stages. Swedish National Registers: The overall findings from this study suggested that the odds of APOs remain high in women with CH and/or CKD, and the odds persisted independent of parity, maternal age, and body mass index, among other potential confounders. No association was found between CKD and stillbirth. All causes of CKD were associated with higher odds of pre-eclampsia, emergency Caesarean section, and medically indicated preterm birth, and the ORs were higher in women with diabetic CKD, renovascular disease, and congenital kidney disease than other CKD subtypes. CALIBER studies: The results suggested a higher odds of APOs in women with CH (treated and untreated) compared to untreated normotensive women. In women with CH, those requiring treatment (versus untreated) had 17%, 25%, and 80% increased odds of superimposed pre-eclampsia, preterm birth, and fetal growth restriction (FGR), respectively. However, these results were mainly attributable to the level of blood pressure (BP) control among the treated group; as similar results were found between the untreated and treated women with CH who achieved tight control (BP<135/85 mmHg) for all assessed outcomes except for a 59% decreased odds of superimposed pre-eclampsia and a 55% increased odds of FGR. Pregnant women with CH who were prescribed methyldopa (versus β-blockers) had 43%, 59%, and 44% increased odds of superimposed pre-eclampsia, preterm birth, and very preterm birth, but 66% lower odds of FGR. No differences in outcomes were found in women who were prescribed calcium-channel-blockers (versus β-blockers) except for 94% increased odds of preterm birth. The magnitude of the associations increased with increasing BP, and the strongest associations were observed in women with severe hypertension (BP≥ 160/90 mmHg). In treated women with CH, less-tight (BP≥135/85 mmHg) versus tight (BP<135/85 mmHg) control was associated with almost 2-fold higher odds of superimposed pre-eclampsia, very preterm birth, and a 3-fold higher odds of severe hypertension. During the 20-year study period, 16,499 CVD incident were observed, of which two-thirds (66%) had occurred in young women (under 40 years). Pre-pregnancy hypertension (versus no pre-pregnancy hypertension) was associated with a 2-fold higher risk of any subsequent CVD. When the results were subclassified according to the presence of APOs, the strongest associations were found in women with pre-pregnancy hypertension and APOs across the 12 CVD; with almost a 3-fold increased risk to develop any subsequent CVD, an 8-fold increased risk of coronary heart disease, and a 10-fold increased risk of heart failure, compared to those who remained normotensive without APOs. Conclusions: This thesis indicated that CKD and CH were associated with a wide range of APOs than the general obstetric population. Therefore, multidisciplinary prenatal consultation and antenatal management should be provided for these women with close monitoring during pregnancy. If antihypertensive treatment is required, clinicians might consider tighter control during pregnancy as better outcomes were observed in women with tightly controlled hypertension. β-blockers might be superior in reducing APOs than methyldopa, with an exception for FGR, which was higher in the β-blockers group. Finally, the findings suggested strong associations between pre‐pregnancy hypertension with subsequent CVD, with a greater risk among women who had pre-pregnancy hypertension and APOs. Pre-pregnancy hypertension should be managed adequately during pregnancy to reduce the risk of APOs and subsequently reduce the risk of CVD, which emphasizes that a history of reproductive risk factors (including APOs) should be considered in screening tools for CVD beyond the postpartum period to optimize long-term cardiometabolic health in women.
- ItemRole of antihypertensive treatment and blood pressure control in the occurrence of adverse pregnancy outcomes: a population-based study of linked electronic health records(American Heart Association, 2022-05-03) Al Khalaf, Sukainah; Khashan, Ali S.; Chappell, Lucy C.; O'Reilly, Éilis J.; McCarthy, Fergus P.Background: Chronic hypertension (CH) adversely impacts pregnancy. It remains unclear whether antihypertensive treatment alters these risks. We examined the role of antihypertensive treatment in the association between CH and adverse pregnancy outcomes. Methods: Electronic health records from the UK Caliber and Clinical Practice Research Datalink were used to define a cohort of women delivering between 1997 and 2016. Primary outcomes were preeclampsia, preterm birth (PTB), and fetal growth restriction (FGR). We used multivariable logistic regression to compare outcomes in women with CH to women without CH and propensity score matching to compare antihypertensive agents. Results: The study cohort consisted of 1 304 679 women and 1 894 184 births. 14 595 (0.77%) had CH, and 6786 (0.36%) were prescribed antihypertensive medications in pregnancy. Overall, women with CH (versus no CH), had higher odds of preeclampsia (adjusted odds ratio [aOR], 5.74 [95% CI, 5.44–6.07]); PTB (aOR, 2.53 [2.39–2.67]); and FGR (aOR, 2.51 [2.31–2.72]). Women with CH prescribed treatment (versus untreated women) had higher odds of preeclampsia (aOR, 1.17 [1.05–1.30]), PTB (1.25 [1.12–1.39]), and FGR (1.80 [1.51–2.14]). Women prescribed methyldopa (versus β-blockers) had higher odds of preeclampsia (aOR, 1.43 [1.19–1.73]); PTB (1.59 [1.30–1.93]), but lower odds of FGR (aOR, 0.66 [0.48–0.90]). Odds of adverse outcomes were similar in relation to calcium channel blockers (versus β-blockers) except for PTB (aOR, 1.94 [1.15–3.27]). Among women prescribed treatment, lower average blood pressure (<135/85 mm Hg) was associated with better pregnancy outcomes. Conclusions: Treatment with antihypertensive agents and control of hypertension ameliorates some effects but higher risks of adverse outcomes persist. β-Blockers versus methyldopa may be associated with better pregnancy outcomes except for FGR. Powered trials are needed to inform optimal treatment of CH during pregnancy.