Measurement of maternal serum soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF), and the ratio between the two, has been shown to predict preeclampsia. In women with suspected preeclampsia, an sFlt-1: PlGF ratio below 38 rules out the need for delivery in the subsequent week with a negative predictive value of 99.3% (95% CI 97.9 to 99.9%) (Zeisler H et al. , N Engl J Med 2016;374:13-22). This test may be of particular benefit for women at low risk of developing the disease in the short term, as it may reduce unnecessary follow-up, investigations and admissions (Cerdeira ASet al. , Hypertension 2019;74:983–990).But do these biomarkers have a potential use in women after preeclampsia is diagnosed? This has not been studied extensively. In this issue of BJOG, Peguero and colleagues report the results of a study in which the changes in sFlt-1 and PlGF levels were examined in 63 women with early-onset preeclampsia from diagnosis to delivery (Peguero A et al. , BJOG 2020). Whilst no association between the change in PlGF levels and the development of adverse outcomes was evident, changes in sFlt-1 levels were significantly more pronounced in women who later developed complications and negatively associated with interval to delivery. This change (i.e., the delta sFlt-1) also outperformed a previously published risk score and the use of sFlt-1 at admission only.Because prevention is better than cure, identifying high-risk women early and modifying their risk is desirable. Prediction of preeclampsia can now be achieved at 11 to 14 weeks of gestational age by calculation of individual patient risk. The risk calculation is based on a combined screening test that incorporates maternal characteristics, medical history and biomarkers (mean arterial pressure, uterine artery Doppler and PlGF) alongside first trimester combined screening for fetal aneuploidy. This test is particularly accurate for predicting early-onset preeclampsia, identifying nine out of ten of these severe cases (O’Gorman N et al. , Am J Obstet Gynecol. 2016;214(1):103 e1- e12). More importantly, when this high-risk group is given prophylaxis using aspirin 150 mg from the first trimester to 36 weeks, the rate of preeclampsia before 37 and before 32 weeks is reduced by more than 60% and 90%, respectively (Rolnik DL et al. , N Engl J Med. 2017;377(7):613-22). A recent implementation study demonstrated that early screening is not only feasible in a public health care setting, but is also associated with a significant reduction in the rate of preterm preeclampsia and nearly total physician compliance of aspirin use (29% with usual care versus 99% when combined screening is used) (Guy GP et al. , BJOG 2020).Nevertheless, not all women will undergo such early screening, and not all cases will be avoided by aspirin: some women will still develop preeclampsia, and early-onset disease will remain a significant cause of morbidity and mortality, disproportionally driving the disease burden. Hence, the findings of Peguero and colleagues are important and suggest that serial sFlt-1 measurements following a diagnosis of early-onset preeclampsia can still allow risk stratification – identifying women at lower risk of complications who may be eligible for expectant management, and those at higher risk who require prompt administration of steroids and timely transfer to tertiary health care facilities.No disclosures: Completed disclosure of interest forms are available to view online as supporting information.
Objective: Universal screening has been proposed as a strategy to identify asymptomatic individuals infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and mitigate transmission. We aimed to investigate the rate of positive tests among pregnant women attending routine antenatal care. Design: Cross-sectional prevalence study. Setting: Antenatal clinic at three maternity hospitals (one tertiary referral hospital and two secondary maternities) in Melbourne, Australia. Population: Asymptomatic pregnant women attending routine antenatal care and pregnant women undergoing testing with symptoms of possible coronavirus disease. Methods: SARS-CoV-2 testing was offered to all pregnant women attending face-to-face antenatal visits and to those attending the hospital with symptoms of possible coronavirus disease, between 6th and 19th of May 2020. Testing was performed by multiplex-tandem polymerase chain reaction (PCR) on combined oropharyngeal and nasopharyngeal swabs. Main Outcome Measures: Proportion of positive SARS-CoV-2 tests. Results: SARS-CoV-2 testing was performed in 350 women, of whom 19 had symptoms of possible COVID-19. The median maternal age was 32 years (IQR 28 to 35 years), and the median gestational age at testing was 33 weeks and four days (IQR 28 weeks to 36 weeks and two days). All 350 tests returned negative results (p̂ = 0%, 95% CI 0 to 0.86%). Conclusion: The rate of asymptomatic coronavirus infection among pregnant women in Australia during the study period was negligible, which reflected reassuringly low levels of community transmission.
In this issue of BJOG, Mendoza and colleagues report in an observational study the occurrence of a preeclampsia-like syndrome in six out of eight pregnant patients with novel coronavirus disease (COVID-19) who were admitted to the Intensive Care Unit (ICU) with severe pneumonia (Mendoza M, et al. BJOG 2020). There were no symptoms of preeclampsia amongst the 34 pregnant women who had mild forms of COVID-19. Importantly, the authors recorded not only routine laboratory test results, but also measured biophysical and biochemical markers that are typically altered in women with preeclampsia (uterine artery pulsatility index on Doppler ultrasound, serum soluble fms-like tyrosine kinase-1 [sFLT-1] and placental growth factor [PlGF]). Such markers were normal in five of the six cases, in whom the symptoms of preeclampsia resolved after improvement of the maternal clinical situation.The intriguingly high cumulative incidence of preeclampsia symptoms in women with severe coronavirus disease needs to be interpreted with caution due to the observational nature of the study, the small number of pregnant women with severe infection and the possible role of confounding factors. The normal biomarker results in most cases, nevertheless, suggest that severe coronavirus disease can lead to symptoms that mimic those of preeclampsia in the absence of defective placentation, which is further corroborated by the resolution of the symptoms without the delivery of the placenta when overall clinical improvement occurs. It is plausible that such manifestations are the result of widespread inflammation and endothelial damage, in a process that has been denominated “cytokine storm”, responsible for many of the symptoms of the coronavirus-related organ injury (Mehta P, et al. Lancet 2020;395:1033-34) This mechanism includes activation of inflammation pathways that convert arachidonic acid to prostaglandins, thromboxane and eicosanoids, ultimately provoking significant cytokine release. The cascade of events, however, does not appear to influence the levels of specific preeclampsia angiogenic and anti-angiogenic markers such as sFLT-1 and PlGF.A normal sFLT-1: PlGF ratio in women with clinically suspected preeclampsia can be reliably used predict the short-term absence of disease (Zeisler H, et al. N Engl J Med 2016;374:13-22). Although the definition of preeclampsia has changed over the last 20 years to incorporate less specific clinical features of end-organ damage, biomarkers will likely become part of the disease definition in the years to come or, at least, a valuable tool to select subgroups of women at higher risk of preeclampsia-related morbidity and mortality who require closer monitoring or immediate delivery.While larger cohorts derived from national datasets or international registries of coronavirus disease in pregnancy will be essential to confirm or refute this association, the preliminary data published in this study indicate that delivery during severe coronavirus disease should not be based on preeclampsia symptoms alone, particularly at early gestational ages, and that the use of ultrasound and serum biomarkers such as the sFLT-1: PlGF ratio might help to guide clinical management by distinguishing hypertension and endothelial dysfunction caused by COVID-19-related inflammation from true preeclampsia.No disclosures: A completed disclosure of interest form is available to view online as supporting information.
Objective: To investigate the incidence of structural and chromosomal abnormalities in cases of fetal oedema on early ultrasound prior to non-invasive prenatal testing (NIPT). Design: Retrospective cohort study. Setting: Tertiary obstetric ultrasound clinic in Melbourne, Australia. Population: Women undergoing pre-NIPT ultrasound examination from January 2013-November 2018 with fetal crown-rump length (CRL) of 28-43 mm. Methods: Cases of reported fetal oedema or increased nuchal thickness were included. Clinical information was collected from the clinic’s patient management database. Oedema was subclassified as isolated nuchal oedema (>2.2 mm) or generalised oedema/hydrops by two operators blinded to pregnancy outcomes. Main Outcome Measures: Incidence of chromosomal or structural defects following the detection of fetal oedema. Results: We identified 104 cases of reported fetal oedema with a CRL between 28-44 mm. Nuchal oedema and generalised oedema were present in 40 (38.5%) and 64 (61.5%) cases respectively. Outcomes were available in 93 cases (89.4%). Relevant chromosomal anomalies were identified in 21.5% (20/93), occurring in 12.1% (4/33) of the nuchal oedema and 26.7% (16/60) of the generalised oedema/hydrops cases. Structural anomalies with normal karyotype were found in an additional four (4.3%) cases. Miscarriage occurred in four (4.3%) cases and termination of pregnancy in 18 cases (19.4%). Oedema resolved by 11-13+6 weeks in 81.9% and these cases had less adverse outcomes than those with NT≥3.5 mm (10.9% vs 76.5%, p<0.001). Conclusions: Fetal oedema in early pregnancy is associated with a high incidence of structural or chromosomal abnormalities, and these rates increase with progressive severity.