Non-severe Hypertension Research Articles

Choosing blood pressure thresholds to inform pregnancy care in the community: An analysis of cluster trials.

To inform digital health design by evaluating diagnostic test properties of antenatal blood pressure (BP) outputs and levels to identify women at risk of adverse outcomes. Planned secondary analysis of cluster randomised trials. India, Pakistan, Mozambique. Women with in-community BP measurements and known pregnancy outcomes. Blood pressure was defined by its outputs (systolic and/or diastolic, systolic only, diastolic only or mean arterial pressure [calculated]) and level: normotension-1 (<135/85 mmHg), normotension-2 (135-139/85-89 mmHg), non-severe hypertension (140-149/90-99 mmHg; 150-154/100-104 mmHg; 155-159/105-109 mmHg) and severe hypertension (≥160/110 mmHg). Dose-response (adjusted risk ratio [aRR]) and diagnostic test properties (negative [-LR] and positive [+LR] likelihood ratios) were estimated. Maternal/perinatal composites of mortality/morbidity. Among 21 069 pregnancies, different BP outputs had similar aRR, -LR, and +LR for adverse outcomes. No BP level (even normotension-1) was associated with low risk (all -LR ≥0.20). Across outcomes, risks rose progressively with higher BP levels above normotension-1. For each of maternal central nervous system events and stillbirth, BP ≥155/105 mmHg showed at least good diagnostic test performance (+LR ≥5.0) and BP ≥135/85 mmHg at least fair performance, similar to BP ≥140/90 mmHg (+LR 2.0-4.99). In the community, normal BP values do not provide reassurance about subsequent adverse outcomes. Given the similar performance of BP cut-offs of 135/85 and 140/90 mmHg for hypertension, and 155/105 and 160/110 mmHg for severe hypertension, digital decision support for women in the community should consider using these lower thresholds.

Sex and gender in hypertension guidelines.

This paper reviews 11 current and previous international and some selected national hypertension guidelines regarding sex and gender-related differences. Those differences can be attributed to biological sex and to gender differences that are determined by socially constructed norms. All reviewed guidelines agree on a higher hypertension prevalence in men than in women. They also concur that evidence does not support different blood pressure thresholds and targets for treatment between men and women. Differences refer in addition to the differences in epidemiological aspects to differences in some morphometric diagnostic indices, e.g., left ventricular mass or the limits for daily alcohol intake. Concerning practical management, there are hardly any clear statements on different procedures that go beyond the consensus that blockers of the renin-angiotensin system should not be used in women of childbearing age wishing to become pregnant. Some further sex-specific aspects are related to differences in tolerability or drug-specific side effects of BP-lowering drugs. There is also a consensus about the need for blood pressure monitoring before and during the use of contraceptive pills. For management of pregnancy, several guidelines still recommend no active treatment in pregnant women without severe forms of hypertension, despite a wide consensus about the definition of hypertension in pregnancy. A disparity in treatment targets when treating severe and non-severe hypertension in pregnancy is also observed. Overall, sex-specific aspects are only very sparsely considered or documented in the evaluated guidelines highlighting an unmet need for future clinical research on this topic.

S-10-2: OPTIMAL BLOOD PRESSURE TARGET TO PREVENT SEVERE HYPERTENSION IN PREGNANCY: A SYSTEMATIC REVIEW AND META-ANALYSIS

Objective: Severe hypertension in pregnancy is a hypertensive crisis that requires urgent and intensive care due to its high maternal and fetal mortality. However, there still remain some discrepancies between guidelines in a target blood pressure to prevent severe hypertension in pregnancy. This study aimed to find the optimal blood pressure (BP) levels to prevent severe hypertension in pregnant women with nonsevere hypertension. Design and method: We searched Ovid MEDLINE and the Cochrane Library to identify all randomized controlled trials, which compared effects of antihypertensive drugs and placebo/no treatment or more intensive and less intensive BP-lowering treatments on adverse maternal and fetal pregnancy outcomes among pregnant women with nonsevere hypertension. A random effects model meta-analysis was performed to estimate the pooled risk ratio (RR) and 95% confidence interval (CI) for the outcomes. Results: Forty RCTs with 6355 patients were included in this study. BP lowering treatment significantly prevented severe hypertension (RR, 0.46; 95% CI, 0.37 to 0.56), preeclampsia (RR, 0.82; 95% CI, 0.69 to 0.98), severe preeclampsia (RR, 0.38; 95% CI, 0.17 to 0.84), placental abruption (RR, 0.52; 95% CI, 0.32 to 0.86), and preterm birth (before 37 weeks; RR, 0.81; 95% CI, 0.71 to 0.93), while the risk of small for gestational age infants was increased (RR, 1.25; 95% CI, 1.02 to 1.54). An achieved systolic blood pressure (SBP) of lower than 130 mmHg reduced the risk of severe hypertension to nearly one-third compared with an achieved SBP of 140 mmHg or higher, with a significant interaction of the BP levels achieved with BP lowering therapy. There was no significant interaction between BP lowering treatment and the subtypes of hypertensive disorders of pregnancy, including gestational hypertension, preeclampsia, and chronic hypertension. Conclusions: BP lowering treatment aimed at a SBP of lower than 130 mmHg and accompanied by careful monitoring of fetal growth might be recommended to prevent severe hypertension among pregnant women with nonsevere hypertension.

S3060 Labetalol, a Common Antihypertensive, an Uncommon Cause of Drug-Induced Liver Injury (DILI)

Introduction: Labetalol is an antihypertensive medication (AHM) commonly used as first line agent for non-severe hypertension in pregnancy. We present a case of DILI in a young woman transitioned to labetalol while attempting to conceive. Case Description/Methods: A 35-year-old woman with a h/o hypertension, hashimoto's thyroiditis, anxiety, obesity (BMI 34) was admitted to our hospital for abdominal pain, jaundice, pruritus and aminotransferase (LFT) elevations. She had been admitted previously at an outside facility with nausea, anorexia, and elevated LFTs (ALT 1264, AST 1419, ALP 294, TBili 5) 20 weeks after initiation of labetalol. There were no h/o alcohol abuse or risk factors for hepatitis B/C. Home medications including labetalol were stopped. Imaging studies including MRCP showed no evidence of biliary obstruction. Infectious workup (hepatitis A/B/C/E, CMV, HSV, EBV) and drug/tox screen were negative. A liver biopsy showed acute hepatocellular injury without eosinophils, steatosis, cholestasis or fibrosis; differentials included DILI and infectious hepatitis. LFTs improved, patient was discharged and labetalol restarted. Two weeks later, she presented to our hospital with worsening jaundice. Admission labs: ALT 905, AST 1553, ALP 257, TBili 19.8, INR 1.4 and creatinine 1. On exam, there was no stigmata of chronic liver disease or encephalopathy. Labetalol was discontinued. Infectious, hereditary, metabolic were negative. ANA was positive (1:320) homogenous pattern with mild elevation in IgG. Prednisolone 40 mg daily was started with rapid improvement in LFTs. At 8 week follow up, she was asymptomatic and LFTs were near normal (Tbili 2); prednisolone was tapered. Discussion: Mild to moderate, transient aminotransferase elevations are noted in up to 8% of patients on labetalol. But they are asymptomatic and resolve even with continuation of the medication. Severe liver injury however is rare and rapid resolution typically ensues after cessation of the drug. However acute liver failure, death and OLT have been reported. There are isolated case reports and small case series of labetalol induced DILI, mostly in pregnant women. In a case series, 3 out of 11 patients died and 1 of 5 patients who had liver biopsy had chronic active hepatitis. The mechanism of labetalol hepatic injury is believed to be idiosyncratic. Inadvertent rechallenge has been shown to cause recurrence of DILI. We present this case to increase awareness of labetalol induced DILI as it is the most commonly used AHM in pregnant women.

Society of Obstetricians and Gynaecologists Pakistan (SOGP) Hypertensive Disorders in Pregnancy Guidelines- 2022

The Society of Obstetricians &amp; Gynecologist Pakistan Hypertensive Disorders of Pregnancy (SOGP- HDP) guideline is evidence based practical clinical guide to the management of pregnant women with hypertension. It defines hypertension, preeclampsia &amp; severe hypertension, encourages measuring blood pressure (BP) accurately, preferably by automated/mercury blood pressure monitors. The guideline gives an approach to screening, risk prediction and prevention of preeclampsia and management of hypertensive disorders of pregnancy. The guideline emphasizes experienced team management approach and mandatory hospital protocols for the management of pregnant women with hypertension. The aim is to have locally tailored easy to follow protocols for preconception care, screening, prevention and management of women at risk of preeclampsia; management of chronic hypertension in pregnancy, antihypertensive therapy for severe and non-severe hypertension. In addition, it discusses post-partum management, contraception, follow-up, discusses risk of recurrence and long-term follow up for women with preeclampsia to mitigate future cardio-metabolic risks to maternal health associated with hypertensive disorders of pregnancy

Tight control of blood pressure in pregnant women with nonsevere hypertension: expectations for decreasing adverse maternal and fetal pregnancy outcomes

Tight control of blood pressure in pregnant women with nonsevere hypertension: expectations for decreasing adverse maternal and fetal pregnancy outcomes

Optimal blood pressure target to prevent severe hypertension in pregnancy: A systematic review and meta-analysis.

Severe hypertension in pregnancy is a hypertensive crisis that requires urgent and intensive care due to its high maternal and fetal mortality. However, there is still a conflict of opinion on the recommendations of antihypertensive therapy. This study aimed to identify the optimal blood pressure (BP) levels to prevent severe hypertension in pregnant women with nonsevere hypertension. Ovid MEDLINE and the Cochrane Library were searched, and only randomized controlled trials (RCTs) were included if they compared the effects of antihypertensive drugs and placebo/no treatment or more intensive and less intensive BP-lowering treatments in nonsevere hypertensive pregnant patients. A random effects model meta-analysis was performed to estimate the pooled risk ratio (RR) for the outcomes. Forty RCTs with 6355 patients were included in the study. BP-lowering treatment significantly prevented severe hypertension (RR, 0.46; 95% CI, 0.37-0.56), preeclampsia (RR, 0.82; 95% CI, 0.69-0.98), severe preeclampsia (RR, 0.38; 95% CI, 0.17-0.84), placental abruption (RR, 0.52; 95% CI, 0.32-0.86), and preterm birth (< 37 weeks; RR, 0.81; 95% CI, 0.71-0.93), while the risk of small for gestational age infants was increased (RR, 1.25; 95% CI, 1.02-1.54). An achieved systolic blood pressure (SBP) of < 130 mmHg reduced the risk of severe hypertension to nearly one-third compared with an SBP of ≥ 140 mmHg, with a significant interaction of the BP levels achieved with BP-lowering therapy. There was no significant interaction between the subtypes of hypertensive disorders of pregnancy and BP-lowering treatment, except for placental abruption. BP-lowering treatment aimed at an SBP < 130 mmHg and accompanied by the careful monitoring of fetal growth might be recommended to prevent severe hypertension.

Gestational Hypertension and Preeclampsia: An Overview of National and International Guidelines.

Gestational hypertension and preeclampsia are leading causes of maternal and perinatal morbidity and mortality worldwide. Τhe lack of effective screening and management policies appears to be one of the main reasons. The aim of this study was to review and compare recommendations from published guidelines on these common pregnancy complications. A descriptive review of guidelines from the National Institute for Health and Care Excellence, the Society of Obstetric Medicine of Australia and New Zealand, the International Society of Hypertension, the International Society for the Study of Hypertension in Pregnancy, the European Society of Cardiology, the International Federation of Gynecology and Obstetrics, the Society of Obstetricians and Gynaecologists of Canada, the American College of Obstetricians and Gynecologists, the International Society of Ultrasound in Obstetrics and Gynecology, the World Health Organization, and the US Preventive Services Task Force on gestational hypertension and preeclampsia was carried out. There is an overall agreement that, in case of suspected preeclampsia or new-onset hypertension, blood and urine tests should be carried out, including dipstick test for proteinuria, whereas placental growth factor-based testing is only recommended by the National Institute for Health and Care Excellence and the European Society of Cardiology. In addition, there is a consensus on the recommendations for the medical treatment of severe and nonsevere hypertension, the management of preeclampsia, the appropriate timing of delivery, the optimal method of anesthesia and the mode of delivery, the administration of antenatal corticosteroids and the use of magnesium sulfate for the treatment of eclamptic seizures, the prevention of eclampsia in cases of severe preeclampsia, and the neuroprotection of preterm neonates. The reviewed guidelines also state that, based on maternal risk factors, pregnant women identified to be at high risk for preeclampsia should receive low-dose aspirin starting ideally in the first trimester until labor or 36 to 37 weeks of gestation, although the recommended dose varies between 75 and 162 mg/d. Moreover, most guidelines recommend calcium supplementation for the prevention of preeclampsia and discourage the use of other agents. However, controversy exists regarding the definition and the optimal screening method for preeclampsia, the need for treating mild hypertension, the blood pressure treatment targets, and the postnatal blood pressure monitoring. The development and implementation of consistent international protocols will allow clinicians to adopt effective universal screening, as well as preventive and management strategies with the intention of improving maternal and neonatal outcomes.

Anti-hypertensive use for non-severe gestational hypertension in Botswana: A case-control study.

The fetal risks and benefits of antihypertensives to treat gestational hypertension in pregnancy are understudied, particularly in low- and middle-income countries. We performed a nested case-control study within a retrospective cohort of obstetrical patients in Botswana from 2014 to 2019. We included women carrying singletons who developed new onset non-severe hypertension (140-159mmHg systolic or 90-109mmHg diastolic blood pressure) after 20weeks of pregnancy. Cases were defined as women with either small-for-gestational-age (SGA) infants or stillbirth, analyzed separately; controls were otherwise similar women without the adverse outcome in each analysis. We identified 1932 cases of SGA (7925 controls) and 316 cases of stillbirth (9619 controls). Cases with SGA were more likely to have used an anti-hypertensive than controls (33% vs 29%, adjusted odds ratio [aOR] 1.28, 95% confidence interval [CI] 1.15-1.43). Cases with stillbirth were more likely to have used an anti-hypertensive than controls (42% versus 29%, aOR 1.45, 95% CI 1.14-1.83). Anti-hypertensive use for new-onset gestational hypertension was associated with an increased risk of having an SGA infant or a stillbirth among women who never developed severe hypertension. These data support conduct of a randomized clinical trial to determine the appropriate use of anti-hypertensives in non-severe gestational hypertension.

A literature review and best practice advice for second and third trimester risk stratification, monitoring, and management of pre‐eclampsia

A literature review and best practice advice for second and third trimester risk stratification, monitoring, and management of pre‐eclampsia

Management of Hypertension in Pregnancy

Abstract Hypertension in pregnancy is currently defined as a systolic blood pressure (BP) of 140 mmHg or more, or a diastolic BP of 90 mmHg or more. This level of BP warrants antihypertensive therapy. Treating to a target BP of 135/85 mmHg halves the risk of severe hypertension that is itself associated with adverse maternal and perinatal outcomes, similar in magnitude to preeclampsia. While based on the results of the Control of Hypertension in Pregnancy Study (CHIPS) trial, this finding is consistent with all antihypertensive trials to date. Also, in the CHIPS trial, “tight” BP control also halved the risk of progression to thrombocytopenia and elevated liver enzymes for the mother, without adverse effects for the fetus or newborn. This was true regardless of the gestational age at which BP control was instituted. While methyldopa, labetalol, and nifedipine are the most commonly-recommended oral antihypertensives, it is not clear that one antihypertensive agent has advantages over the others for treatment of non-severe hypertension in pregnancy. No antihypertensives, including renin-angiotensin-aldosterone system (RAAS) inhibitors, have been shown to be teratogenic, although there may be an increase in malformations associated with the underlying condition of chronic hypertension. Atenolol and RAAS inhibitors should not be used once pregnancy is diagnosed, based on fetotoxicity. At present, BP treatment targets used in clinic are the same as those used at home as the differences are quite variable among hypertensive women. For treatment of acute severe hypertension, the most commonly-recommended antihypertensives are oral nifedipine, IV labetalol, and IV hydralazine, although oral agents have also been shown to be effective in the majority of women; while concerns raised about IV hydralazine-induced maternal hypotension and its consequences have not been confirmed, this medication may be an inferior antihypertensive to oral nifedipine. While treatment recommendations are based on evidence, women should be engaged in decision-making, as their values may alter target BP and antihypertensive choice. Future work will clarify the optimal target BP based on home BP measurements; whether BP targets should be lowered further if the definition of hypertension is based on a lower BP; which, if any, antihypertensive medication for non-severe hypertension is better with regards to maternal and perinatal outcomes; and whether factors beyond BP level (such as variability, race, and other physiological variables) should inform antihypertensive therapy in pregnancy.

Management of Preeclampsia in Low- and Middle-Income Countries: Lessons to Date, and Questions Arising, from the PRE-EMPT and Related Initiatives

Abstract Preeclampsia remains associated with an increased risk of maternal and perinatal morbidity and mortality, and the burden of that excess risk is largely borne by pregnant women and their families in low- and middle-income countries (LMICs). Therefore, the Bill &amp; Melinda Gates Foundation funded the PREeclampsia – Eclampsia Monitoring, Prevention, and Treatment (PRE-EMPT) initiative to accelerate progress. From PRE-EMPT, and related activity, have come a number of impactful findings. First, there is increasing global support for broadening the definition of preeclampsia to include women with hypertension and either significant proteinuria or evidence of target organ damage or fetoplacental compromise (including evidence angiogenic imbalance). Second, using blood pressure (BP) data from the Community-Level Interventions for Preeclampsia trials in India, Mozambique, and Pakistan, acquired on validated-for-pregnancy, semi-automated, low-cost BP devices, there are now population-level, rather than facility-based, estimates for the burden of pregnancy hypertension (sub-categorized into preeclampsia (4%–6%), gestational hypertension (7%–12%), and chronic hypertension (0.3%–0.6%)). Third, there is an identified need to understand biological pathways that underlie the causation of preeclampsia in LMICs. Fourth, the Community-Level Interventions for Preeclampsia trials have shown that providing at least eight antenatal contacts, in this case using digital health-supported community health workers, cost-effectively reduces the burden of maternal (by 60%), fetal (60%), and neonatal (40%) mortality. Fifth, what is the utility and cost-effectiveness of routine proteinuria screening of normotensive pregnant women? Sixth, clinical risk factor-based prediction of preeclampsia remains most relevant for most women in LMICs; calcium replacement (≥1 g/day) and low-dose aspirin (100–175 mg/day) are the most useful directly preventative interventions. However, achieving sustainable development goals (SDGs) not directly related to health are more likely to reduce the global burden of preeclampsia and its consequences. Seventh, should a woman develop preeclampsia, personalized maternal time-of-disease risk estimates are available through the PIERS (Preeclampsia Integrated Estimate of RiSk) models, either with (fullPIERS) or without (miniPIERS) access to laboratory testing. Assessment of perinatal risks in LMICs is largely driven by gestational age; however, evidence of significant angiogenic imbalance may identify risk of intrauterine fetal death. Eighth, Control of Hypertension in Pregnancy Study trial data show that women with non-severe pregnancy hypertension (systolic BP 140–159 mmHg or diastolic BP (dBP) 90–109 mmHg) should receive an antihypertensive medication for a target dBP of 85 mmHg. Ninth, for women with severe pregnancy hypertension (systolic BP ≥160 mmHg or dBP ≥110 mmHg), oral antihypertensive management with either nifedipine, labetalol, or, less so, methyldopa will lower BP into the non-severe hypertension range. Tenth, magnesium sulfate remains the sole agent of choice for preventing and treating eclamptic seizures. Eleventh, corticosteroids should be administered to women at risk of delivery &lt;35+0 weeks’ gestation. Twelfth, although delivery of the placenta initiates resolution of the maternal syndrome of preeclampsia, decisions to initiate delivery should be guided by gestational age and maternal and fetal status. Many women will experience significant postpartum deterioration; delivery should not be equated with “cure”. Thirteenth, whether the development of preeclampsia identifies women at increased risk for early-onset cardiovascular disease in LMICs must be determined.

Tratamiento farmacológico de la hipertensión arterial no severa durante el embarazo, el posparto y la lactancia

Hypertension (HTN) in pregnancy is defined as systolic blood pressure ≥ 140 and/or diastolic blood pressure ≥ 90 mmHg. Based on the values, it is classified as non-severe (< 160/110 mmHg) and severe (≥ 160/110 mmHg). Before starting treatment in non-severe HTN, white- coat HTN should be ruled out. If outpatient management is possible, pharmacological initiation is suggested with sustained high values, avoiding < 120/80 mmHg. Safe drugs during pregnancy are methyldopa, labetalol, and nifedipine-retard. The use of nifedipine-XL or amlodipine can be considered with a lower level of evidence of safety. Diuretics, atenolol, and other beta-blockers for antihypertensive purposes is not recommended in this period. Renin-angiotensin-aldosterone system inhibitors are strictly contraindicated. In postpartum and breastfeeding, the same therapeutic regimen used during pregnancy can be maintained, trying early withdrawal of methyldopa. During puerperium, amlodipine and enalapril are safe, with minimal excretion in breast milk.

Severe antepartum hypertension and associated peripartum morbidity among pregnant women in an urban tertiary care medical center.

Hypertensive disorders of pregnancy are a leading cause of maternal morbidity and mortality. Although acute severe hypertension carries with it a poor prognosis, treatment is often delayed and not universal. A total of 654 patients were assessed for the impact of hypertensive disorders of pregnancies on maternal and fetal morbidity and divided into three groups: normotensive (Group I, N=306), non-severe hypertension (Group II, N=248) and severe-range hypertension with blood pressure (BP) episodes ≥160 systolic or ≥105 diastolic (Group III, N=100). Retrospective demographic and medical information was abstracted from patients' medical records to collect study data. The main outcomes assessed were composite maternal adverse events,fetal adverse events, and time to treatment. Patients in Group III had higher systolic (182 vs 155 vs 133) and diastolic (106 vs 95 vs 81) BPs compared to patients in Groups II and I. Patients in Group III had a significantly higher incidence of maternal adverse events (26.0% vs 6.5% vs 2.0%, respectively; p<0.001) and higher neonatal composite adverse events (52.0% vs 17.7% vs 26.1%, respectively; p<0.001) as compared to patients in Groups II and I. Only 52.2% of patients in Group III were treated within recommended 60minutes or less. Patients with severe hypertension antepartum have higher associated maternal and fetal adverse events while treatment is often delayed. Further studies should evaluate the effects of adequate time to treatment for severe hypertension. Steps should also be taken to standardize identification and reporting of severe maternal morbidity.

Antihypertensive drug therapy for women with non-severe hypertensive disorders of pregnancy: a systematic review and meta-analysis.

Hypertensive disorders of pregnancy (HDP) represent a frequent disorder among pregnancies. Women with severe hypertension in pregnancy are at increased risk of maternal complications and require antihypertensive drug therapy. This study aimed to systematically review randomized control trials of antihypertensive drug(s) treating non-severe hypertension during pregnancy to estimate the effectiveness and safety of this intervention. On May 8, 2018, we searched PubMed, Cochrane Library, and Ichu-Shi with no restriction on publication year. We selected randomized control trials that involved women with HDP being treated with antihypertensive drug(s) as intervention. Fourteen trials (1804 women) were identified for meta-analysis. There were no significant differences in the risk of maternal death (373 women; risk ratio (RR) 0.70; 95% confidence interval (CI) 0.04 to 11.45), proteinuria (1214 women; RR 1.00; 95% CI 0.67 to 1.49), side effects (360 women; RR 2.69; 95% CI 0.32 to 22.64), cesarean section (1239 women; RR 0.97; 95% CI 0.82 to 1.15), neonatal and birth death (1548 women; RR 0.80; 95% CI 0.43 to 1.49), preterm birth (904 women; RR 0.86; 95% CI 0.53 to 1.39), or small for gestational age infants (1082 women; RR 1.04; 95% CI 0.66 to 1.63) with antihypertensive drug therapy versus placebo or no treatment. The current review suggests that antihypertensive drug therapy does not reduce or increase the risk of maternal or perinatal outcomes. Further studies are needed to build reliable estimates of the effectiveness and safety of antihypertensive drug therapy for women with HDP.

Hypertension in pregnancy: Pathophysiology and treatment.

Hypertensive disorders of pregnancy, an umbrella term that includes preexisting and gestational hypertension, preeclampsia, and eclampsia, complicate up to 10% of pregnancies and represent a significant cause of maternal and perinatal morbidity and mortality. Despite the differences in guidelines, there appears to be consensus that severe hypertension and non-severe hypertension with evidence of end-organ damage need to be controlled; yet the ideal target ranges below 160/110 mmHg remain a source of debate. This review outlines the definition, pathophysiology, goals of therapy, and treatment agents used in hypertensive disorders of pregnancy.

444. Influence of gestational age at initiation of antihypertensive therapy – secondary analysis of chips trial data

Introduction For hypertensive women in the Control of Hypertension In Pregnancy Study (ISRCTN 71416914), we assessed whether the maternal benefits of ‘tight’ control could be achieved, whilst minimising any potentially negative effect on fetal growth, by delaying initiation of antihypertensive therapy until later in pregnancy. Objective In this secondary, exploratory analysis, we examined the relationship between gestational age at randomisation and major CHIPS outcomes (including birthweight 10th centile and preterm birth). Methods For the 981 women with non-severe, chronic or gestational hypertension randomised to ‘less tight’ (target diastolic blood pressure, 100 mmHg) or ‘tight’ (target 85 mmHg) control, we used mixed effects logistic regression to examine whether effect of ‘less tight’ (vs. ‘tight’) control on major outcomes was dependent on gestational age at randomisation, adjusting for baseline factors as in the primary analysis and including an interaction term between gestational age at randomisation and treatment allocation. Gestational age was considered categorically (quartiles) and continuously (linear or quadratic form), and optimal functional form selected to provide best fit to the data based on the Akaike information criterion. Results Randomisation before (but not after) 24 weeks’ to ‘less tight’ (vs. ‘tight’) control was associated with fewer babies with birthweight 10th centile ( p interaction = 0.005), but more preterm birth ( p interaction = 0.043), and no effect on perinatal death or high-level neonatal care > 48hr ( p interaction =0.354). For the mother, ‘less tight’ (vs. ‘tight’) control was associated with more severe hypertension at all gestational ages, but particularly so before 28 weeks ( p interaction = 0.076). Discussion In women with non-severe, chronic or gestational hypertension, there seems to be no gestational age at which ‘less tight’ (vs. ‘tight’) control is the preferred management strategy to optimise maternal or perinatal outcomes.

218. Implementation of the PIERS on the Move mobile health app in the Community Level Interventions for Pre-eclampsia trials

Background The PIERS on the Move (POM) app was implemented as part of a complex health system intervention in the CLIP (Community Level Interventions for Pre-eclampsia; NCT01911494) Trials in India, Pakistan and Mozambique. POM guides community health workers through an antenatal/postnatal assessment and provides recommendations for referral to a nearby facility with immediate treatment with MgSO4 and methyldopa when hypertension is detected, based on disease severity. Objective To evaluate the implementation of the POM app based on population coverage, compliance and recommendation acceptance. Methods As per the protocol, coverage was measured as the proportion of women receiving one or more POM home visit out of all pregnancies registered in the intervention area and compliance was measured as the proportion of women receiving the minimum standard of monthly POM home visits. Acceptance of recommendation and was summarized and rates of outcome for women in intervention areas with and without a recommendation presented. Results In total 21,416/36,077 eligible women received 151,893 POM visits (76.2% antepartum, 23.8% postpartum) during the CLIP Trials. Coverage was 90.0% in India, 56.6% in Pakistan and 61.2% in Mozambique. Compliance rates were 55.4% in India; 63.4% in Pakistan; and 77.0% in Mozambique. Rate of triage recommendation was 5.6% (1194/21,416) of the covered population in total. The primary reason for referral was non-severe hypertension. Women’s acceptance of recommendations was 77.0% overall. In intervention clusters, the rate of adverse maternal outcomes in women who received recommendations compared to those who did not was higher in India (11.7% vs 4.3%) and Mozambique (11.3% vs. 7.7%) but similar in Pakistan (5.0% vs. 5.0%). Conclusion During the CLIP Trials there was good coverage and compliance and a high rate of community acceptance of triage recommendations after implementation of the POM app but limited apparent impact on maternal health outcomes.

221. Superimposed pre-eclampsia is best defined broadly – Analyses from the CHIPS Trial (Control of Hypertension In Pregnancy Study)

Background Any definition of superimposed pre-eclampsia should identify women at increased risk of adverse outcomes. Methods In the CHIPS trial, women at 14 + 0 − 33 + 6 weeks with non-severe chronic or gestational hypertension and a live fetus were randomised to ‘less tight’ (target diastolic blood pressure [dBP] 100 mmHg) or ‘tight’ control (target dBP 85 mmHg). There was no between-group difference in the primary outcome (pregnancy loss or high level neonatal care for >48 h in the first 28 d), secondary outcome (serious maternal complications before 6 weeks postpartum), or pre-eclampsia defined restrictively (by new proteinuria) or broadly (by maternal symptoms, signs, or abnormal laboratory tests). ‘Less tight’ (vs. ‘tight’) control was associated with significantly more severe hypertension, platelets Results For 981/987 women in CHIPS with outcomes, 280 (28.6%) developed pre-eclampsia defined restrictively, and 464 (47.4%) pre-eclampsia defined broadly. The broad (vs. restrictive) definition had higher sensitivity but lower specificity and classification accuracy for all outcomes but severe hypertension (Table 1). Conclusion Superimposed pre-eclampsia broadly defined can better identify true cases of risk in hypertensive pregnancy, but the potential harm of increasing false positives requires contextualisation. Table 1 https://www.dropbox.com/s/eqnuo9d0vs0sl1j/CHIPS%20%20superimposed%20PET%20Table%201.docx?dl=0 Correct class (correct classification), sens (sensitivity), spec (specificity)

Prediction of progression to severe disease in women with late preterm hypertensive disorders of pregnancy.

If hypertensive disorders of pregnancy are diagnosed before term, the benefits of immediate delivery need to be weighed against the neonatal consequences of preterm delivery. If we are able to predict which women are at high risk of progression to severe disease, they could be targeted for delivery and maternal complications might be reduced. In addition, this may prevent unnecessary preterm births in women at low risk. We developed a prediction model using data from the HYPITAT-II trail, which evaluated immediate delivery vs. expectant monitoring in women with non-severe hypertensive disorders of pregnancy between 34 and 37weeks of gestation. Univariate and multivariate logistic regression analysis were used to identify relevant variables from clinical and laboratory parameters. The performance of the resulting prediction model was assessed by receiver operating characteristic analysis, calibration and bootstrapping, using the average predicted probabilities. We included 519 women, 115 (22.2%) of whom developed severe hypertensive disorders of pregnancy. The prediction model included: maternal age (odds ratio 0.92 per year), gestational age (odds ratio 0.87 per week), systolic blood pressure (odds ratio 1.05 per mmHg), the presence of chronic hypertension (odds ratio 2.4), platelet count (odds ratio 0.996), creatinine (odds ratio 1.02) and lactate dehydrogenase (odds ratio 1.003). The model showed good fit (p=0.64), fair discrimination (area under the curve 0.76, 95% confidence interval 0.73-0.81, p<0.001) and could stratify women in three risk groups of average, intermediate and high risk (predicted probabilities <0.22, <0.44 and >0.45, respectively). In women with non-severe hypertension in pregnancy near term, progression to severe disease can be predicted. This model requires external validation before it can be applied in practice.