The future health risks of adverse pregnancy outcomes … and other research

Pregnancy: the natural stress test

Pregnancy and childbirth can be worrying times, and the news that adverse pregnancy outcomes are associated with an increased risk of dying younger will ramp up anxiety, but it also offers scope to shift the dial.

This national Swedish cohort study of more than two million women found that any of five major adverse pregnancy outcomes (preterm delivery, small for gestational age, pre-eclampsia, other hypertensive disorders, and gestational diabetes) was associated with increased mortality risks that remained elevated up to 46 years later. The major causes of death included cardiovascular and respiratory disorders and diabetes.

Pregnancy has been called a “natural stress test” that unmasks future health risks. But are these pre-existing risks that were going to play out anyway or are they new risks? This study suggests the latter. It used co-sibling data and found that familial factors (genetic and environmental) accounted for only a small part of the effect. This suggests that all five major adverse pregnancy outcomes are independent risk factors for premature mortality. That’s a stark message for a pregnant woman to hear, but it can be framed as an early warning system to trigger enhanced monitoring, prevention, and treatment of chronic disease. Further studies are needed to find which interventions really work.

JAMA Intern Med doi:10.1001/jamainternmed.2024.0276

Time-restricted eating: is it a myth?

Does it matter when we eat? I think of food intake like filling the car with petrol—so long as there's fuel, it really doesn't matter when you top it up. My preferred way of eating is Nigella-style late night snacking. But Michael Mosely and others argue that giving the body a break from eating by fasting intermittently, only eating within a 12 hour period, or at least avoiding food in the three hours before bedtime, can have myriad health benefits.

This 12 week, small, single site study included 41 women with average age of 59 years and mean body mass index of 36. The study looked at whether adults with obesity and pre-diabetes or established diet-controlled diabetes lost more weight if they stuck to time-restricted eating (TRE) of 10 hours with 8% of calories eaten before 1 pm or ate the same number of calories and proportion of nutrients but in a usual eating pattern of ≥16 hours per day with at least half their calories consumed after 5 pm. There was no difference in weight loss (−2.3 v−2.6 kg) and no change in glycaemic measures. The study is too small to attach much importance to it, but any study that confirms a personal preference is always welcome.

Ann Intern Med doi:10.7326/M23-3132

How do we solve a problem like CKD?

What are we to do with chronic kidney disease (CKD)? There’s a big gap between optimal care based on guidelines and what happens (or doesn’t happen) in practice.

This US study of 15 966 patients with moderate to high risk CKD found that a multipronged primary care intervention (using the electronic health record, an e-consultation with a nephrologist, pharmacist-led medication review, and patient education) didn’t reduce the risk of CKD progression or improve hypertension control compared with usual care delivered by a primary care physician over a 17 month follow-up. More people took ACE inhibitors or angiotensin receptor blockers in the intervention group (rate ratio 1.21), but that didn’t translate into better hypertension control or substantial differences in the rate of fall in estimated glomerular filtration rate or progression to end stage kidney disease (7.6% v 8.6%). It was a lot of effort for minimal, if any, gains.

JAMA Intern Med doi:10.1001/jamainternmed.2024.0708

Leaking valves

Severe aortic regurgitation is treated by replacing the aortic valve. But for those at high surgical risk or with age related degenerative aortic regurgitation, transcatheter aortic valve implantation (TAVI) is an option. TAVI is well established for patients with aortic stenosis, but the transcatheter heart valve devices are tricky to position and anchor properly when treating aortic regurgitation. A new device—the JenaValve Trilogy—has been developed to try to overcome some of the technical problems associated with TAVI in aortic regurgitation.

This study of 180 patients, funded by JenaValve Technology, gave Trilogy transcatheter heart valve a guarded thumbs up. It was safe (2% deaths, 2% strokes at 30 days) and effective (technical success in 95% patients) for patients at high surgical risk with symptomatic aortic regurgitation in terms of short term outcomes and improved cardiac output. But there was a relatively high need for pacemaker implantation (24%). There was also a problem in identifying who is at highest risk and standardising frailty scoring. If researchers across the field all agreed to use a simple, reliable tool such as the Clinical Frailty Scale that would be a good start.

Lancet doi:10.1016/S0140-6736(23)02806-4

Forever blowing bubbles

Clear cell renal cell carcinoma (ccRCC), so called because the cells look like soap bubbles under a microscope, is the most common type of kidney cancer. Improvements in disease-free survival have been found in patients given post-surgical adjuvant pembrolizumab (an anti-programmed death 1 (PD-1) antibody that works by unblocking T cells that are inactivated by ligand proteins PD-L1 and PD-L2 on cancer cells). The question remains whether overall survival improves too.

In this interim phase 3 randomised study involving 994 patients with ccRCC who had undergone nephrectomy within the past three months and were at increased risk of recurrence, adjuvant pembrolizumab was associated with a significant improvement in overall survival compared with placebo (91.2% v 86% at 48 months). This translates to a 38% lower risk of death. There were more serious adverse events in the pembrolizumab group (20.7% v 11.5%), which is a worry, although there were no deaths attributable to the drug.

N Engl J Med doi:10.1056/NEJMoa2312695