Dr Fergus McCarthy takes a look at the news this month…

Nordqvist  et al examined the impact of timing of probiotic milk consumption during pregnancy on the incidence of preeclampsia and preterm delivery.1

The authors conducted a population-based prospective cohort study in Norway between 1999 and 2008. Data from 70, 149 singleton pregnancies resulting in live-born babies from the Norwegian Mother and Child Cohort Study was used. These were women with no chronic disease who answered questionnaires, no placenta previa, cerclage, serious malformation of fetus and first enrolment pregnancy. Nulliparous women only (n=37,050) were included in the preeclampsia analysis. Both iatrogenic and spontaneous preterm delivery (between gestational weeks 22+0 and 36+6) with spontaneous term controls (between gestational weeks 39+0 and 40+6) were included in the preterm delivery analysis resulting in 34,458 cases.

Probiotic milk intake in late pregnancy (but not before or in early pregnancy) was significantly associated with lower preeclampsia risk (adjusted OR: 0.80 (95% CI 0.68 to 0.94) p-value: 0.007). Probiotic intake during early (but not before or during late pregnancy) was significantly associated with lower risk of preterm delivery (adjusted OR: 0.79 (0.64 to 0.97) p-value: 0.03). The authors demonstrated an association between timing of probiotic milk consumption during pregnancy and the incidence of the adverse pregnancy outcomes preeclampsia and preterm delivery. This work may inform future randomised controlled trials which investigate the use of probiotics as a promising public health measure to reduce adverse pregnancy outcomes.

Bellos et al examined the association between Helicobacter pylori infection and pre-eclampsia by conducting a meta-analysis of observational studies.2 Helicobacter pylori has been previously linked with preeclampsia through its effects on angiogenesis and activation of inflammatory cytokines.

The authors conducted a systematic review and selected all observational studies (both prospective and retrospective) that reported the incidence of preeclampsia among women with H. Pylori infection. Fourteen studies were finally included in this review, which included a total number of 9787 women. Nine percent of these had preeclampsia (879 women). H. pylori IgG seropositivity was significantly more prevalent in preeclamptic than in healthy pregnant women (9391 women, OR: 2.32, 95% CI [1.55, 3.46]). The frequency of anti-CagA antibodies was also higher in pregnancies complicated with preeclampsia (3275 women, OR: 3.97, 95% CI [1.55, 10.19]). The findings of this systematic review suggest that H. pylori infection doubles the risk of developing preeclampsia.

Orabona et al in their research evaluated maternal hemodynamics in asymptomatic women with a previous pregnancy affected by hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome and compared these findings to those of women with previous pre-eclampsia (PE) and controls with a previous uncomplicated pregnancy.3

Women with a history of PE (n = 60) or HELLP syndrome (n = 49) and matched healthy controls (n = 60) underwent echocardiography at 6 months to 4 years after delivery, recording left ventricular (LV) dimensions, ejection fraction (LVEF) and mass, right ventricular (RV) tricuspid annular plane systolic excursion and fractional area change (FAC). Diastolic filling (E/A and E/E’ ratios) and tissue Doppler imaging were evaluated for both ventricles and the myocardial performance index was calculated.

Only women with previous HELLP syndrome showed significant LV concentric hypertrophy (20.4%). However, in both HELLP and PE groups, LV concentric remodeling (46.9% and 46.7%, respectively), diastolic dysfunction and reduced LVEF (14.3% and 21.7%, respectively) were documented. RV variables did not differ significantly between cases and controls, except for FAC and E/E’ ratio, which were slightly impaired in women with previous HELLP syndrome compared to those with previous PE (16.3% vs 10.0%, P = 0.04; 14.3% vs 3.3%, P = 0.03, respectively).

The significant overlap of echocardiographic features in women with previous PE and HELLP syndrome suggests that both these conditions adversely affect long term cardiovascular function and share the same pathophysiology. HELLP syndrome may lead to more severe cardiovascular remodeling in the short to medium term after delivery.

Duffy et al performed a systematic review of primary outcomes and outcome measure reporting in randomised trials evaluating treatments for preeclampsia.4 Randomized controlled trials evaluating treatments for preeclampsia published in any language were included. Overall, 79 randomized trials including data from 31,615 women were included. Of those, 38 (48%) reported 35 different primary outcomes; 28 were maternal outcomes and seven were fetal/neonatal outcomes. Three randomized trials reported composite outcomes, incorporating between six and nine outcome components. The method of definition or measurement was infrequently or poorly reported. Even when outcomes were consistent across trials, different methods of definition or measurement were frequently described.

This systematic review highlights the deficits in outcome reporting in studies involving women with preeclampsia. In randomized trials evaluating interventions for preeclampsia, critical information related to the primary outcome, including definition and measurement, is regularly omitted. This group is now focusing on developing a core outcome set for preeclampsia trials, which would help to inform primary outcome selection and outcome measure reporting.

Using data from the ASPRE (Combined Multimarker Screening and Randomized Patient Treatment with Aspirin for Evidence-Based Preeclampsia Prevention) trial, Rolnik et al examined the performance of screening for preterm pre-eclampsia.5

ASPRE was a prospective first-trimester multicenter study on screening for preterm preeclampsia in 26,941 singleton pregnancies by means of an algorithm that combines maternal factors, mean arterial pressure, uterine artery pulsatility index and maternal serum pregnancy-associated plasma protein-A and placental growth factor at 11-13 weeks’ gestation. Eligible women with an estimated risk for preterm preeclampsia of > 1 in 100 were invited to participate in a double-blind trial of aspirin (150 mg per day) vs placebo from 11-14 until 36 weeks’ gestation, which showed that, in the aspirin group, the incidence of preterm preeclampsia was reduced by 62%. In the screened population, the detection rates and false-positive rates for delivery with preeclampsia < 37 and ≥ 37 weeks were estimated after adjustment for the effect of aspirin in those receiving this treatment.

The study population of 25,797 pregnancies included 180 (0.7%) cases of preterm preeclampsia, 450 (1.7%) of term preeclampsia and 25,167 (97.6%) without preeclampsia. In combined first-trimester screening for preterm preeclampsia with a risk cut-off of 1 in 100, the detection rate was 76.7% (138/180) for preterm preeclampsia and 43.1% (194/450) for term preeclampsia, at screen-positive rate of 10.5% (2707/25 797) and False positive rate of 9.2% (2375/25 797).

The performance of screening in the ASPRE study was comparable with that of a study of approximately 60,000 singleton pregnancies used for development of the algorithm; in that study, combined screening detected 76.6% of cases of preterm PE and 38.3% of term preeclampsia at a false positive rate of 10%.


  1. Nordqvist M, Jacobsson B, Brantsaeter AL, Myhre R, Nilsson S, Sengpiel V. Timing of probiotic milk consumption during pregnancy and effects on the incidence of preeclampsia and preterm delivery: a prospective observational cohort study in Norway. BMJ Open. 2018;8(1):e018021.
  2. Bellos I, Daskalakis G, Pergialiotis V. Helicobacter pylori infection increases the risk of developing preeclampsia: A meta-analysis of observational studies. Int J Clin Pract. 2018;72(2).
  3. Orabona R, Vizzardi E, Sciatti E, et al. Maternal cardiac function after HELLP syndrome: an echocardiography study. Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology. 2017;50(4):507-513.
  4. Duffy JMN, Hirsch M, Gale C, et al. A systematic review of primary outcomes and outcome measure reporting in randomized trials evaluating treatments for pre-eclampsia. Int J Gynaecol Obstet. 2017;139(3):262-267.
  5. Rolnik DL, Wright D, Poon LCY, et al. ASPRE trial: performance of screening for preterm pre-eclampsia. Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology. 2017;50(4):492-495.