Home telemonitoring versus hospital care in complicated pregnancies in the Netherlands: a randomised, controlled non-inferiority trial (HoTeL).

BACKGROUND: Women with complicated pregnancies often require hospital admission. Telemonitoring at home is a promising alternative that fulfils a worldwide need in obstetric health care. Moreover, the COVID-19 pandemic has accelerated the transformation to digital care. The aim of this study was to evaluate safety, clinical effectiveness, patient satisfaction, and costs of home telemonitoring against hospital care in complicated pregnancies. METHODS: We did a multicentre, randomised, controlled, non-inferiority trial in six hospitals (four general teaching hospitals and two university hospitals) in the Netherlands (located in Utrecht, Amsterdam, and Groningen). Women aged 18 years and older with singleton pregnancies (>26 weeks gestation) requiring monitoring for pre-eclampsia, fetal growth restriction, fetal anomaly, preterm rupture of membranes, reduced fetal movements, or history of fetal death were included in the study. Participants were randomly assigned to either hospital admission or telemonitoring in (1:1), stratified for the six diagnoses for inclusion and the six centres of inclusion, using block randomisation (block sizes of four and six). When assigned to telemonitoring, participants went home with devices for cardiotocography and blood pressure measurements and had daily contact with their care providers after digitally sending their home measurements. When assigned to hospital admission, participants received care as usual on the ward until the postpartum period. The primary outcome was a composite of adverse perinatal outcomes assessed after delivery, including mortality; an Apgar score below 7 after 5 min or an umbilical arterial pH at birth below 7·05; maternal morbidity; admission of the newborn to the neonatal intensive care unit; and rate of caesarean section. The primary outcome was assessed in the intention-to-treat population. The non-inferiority margin for the primary outcome was a 10% absolute increase in composite primary endpoint based on baseline 20% incidence. The study was registered at the Dutch Trial Registration (NL5888) and is now closed to new participants. FINDINGS: From Dec 1, 2016, to Nov 30, 2019, 201 pregnant women were randomly assigned to an intervention procedure. 101 women were allocated to the telemonitoring group and 100 to the hospital admission group. One participant in the telemonitoring group withdrew consent before the intervention was initiated, and 100 participants were analysed for the primary outcome. In the hospital admission group, four participants did not receive the allocated intervention because they did not accept hospital admission. 100 participants in each group were analysed for the primary outcome according to the intention-to-treat principal. No participants were lost to follow-up. The primary outcome occurred in 31 (31%) of 100 participants in the telemonitoring group and in 40 (40%) of 100 participants in the hospital admission group. Adjusted for centre of inclusion, diagnosis, and nulliparity, the risk difference in primary outcome between both groups was 10·3% (95% CI -22·4 to 2·2) lower in the telemonitoring group, below the pre-defined non-inferiority margin of 10% absolute increase. A similar distribution for each of the individual components within the composite primary outcome was seen between groups. Five serious adverse events were reported: one neonatal death in the hospital admission group, in addition to one intra-uterine fetal death, two neonatal deaths, and one case of eclampsia in the telemonitoring group, all unrelated to the study. INTERPRETATION: This non-inferiority trial shows the first evidence that telemonitoring might be as safe as hospital admission for monitoring complicated pregnancies. FUNDING: Stichting Achmea Gezondheidszorg and ICT Healthcare Technology Solutions.

HOspital care versus TELemonitoring in high-risk pregnancy (HOTEL): study protocol for a multicentre non-inferiority randomised controlled trial.

INTRODUCTION: Pregnant women faced with complications of pregnancy often require long-term hospital admission for maternal and/or fetal monitoring. Antenatal admissions cause a burden to patients as well as hospital resources and costs. A telemonitoring platform connected to wireless cardiotocography (CTG) and automated blood pressure (BP) devices can be used for telemonitoring in pregnancy. Home telemonitoring might improve autonomy and reduce admissions and thus costs. The aim of this study is to compare the effects on patient safety, satisfaction and cost-effectiveness of hospital care versus telemonitoring (HOTEL) as an obstetric care strategy in high-risk pregnancies requiring daily monitoring. METHODS AND ANALYSIS: The HOTEL trial is an ongoing multicentre randomised controlled clinical trial with a non-inferiority design. Eligible pregnant women are >26+0 weeks of singleton gestation requiring monitoring because of pre-eclampsia (hypertension with proteinuria), fetal growth restriction, preterm rupture of membranes without contractions, recurrent reduced fetal movements or an intrauterine fetal death in a previous pregnancy.Randomisation takes place between traditional hospitalisation (planned n=208) versus telemonitoring (planned n=208) until delivery. Telemonitoring at home is facilitated with Sense4Baby CTG devices, Microlife BP monitor and daily telephone calls with an obstetric healthcare professional as well as weekly hospital visits.Primary outcome is a composite of adverse perinatal outcome, defined as perinatal mortality, 5 min Apgar <7 or arterial cord blood pH <7.05, maternal morbidity (eclampsia, HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome, thromboembolic event), neonatal intensive care admission and caesarean section rate. Patient satisfaction and preference of care will be assessed using validated questionnaires. We will perform an economic analysis. Outcomes will be analysed according to the intention to treat principle. ETHICS AND DISSEMINATION: The study protocol was approved by the Ethics Committee of the Utrecht University Medical Center and the boards of all six participating centres. Trial results will be submitted to peer-reviewed journals. TRIAL REGISTRATION NUMBER: NTR6076.

The duration of the third stage in relation to postpartum hemorrhage.

INTRODUCTION: In this study, we describe the distribution of placenta delivery and the incidence of postpartum hemorrhage in both spontaneous placental delivery and manual removal of the placenta. METHODS: A retrospective study was performed of 7603 singleton vaginal deliveries of a gestational age over 32 weeks, registered between September 2011 and 2016. We calculated the incidence of postpartum hemorrhage (≥1000 mL blood loss) per 10-minute duration of the third stage. The odds ratio for developing postpartum hemorrhage was assessed, adjusted for risk factors. The incidence of postpartum hemorrhage was compared between women that did and did not receive manual removal of placenta. RESULTS: The median duration of the third stage was 10 minutes (interquartile range 7-16 minutes). The median amount of blood loss was 300 mL (200-400 mL). The overall incidence of postpartum hemorrhage was 8.5%. With every additional 10 minutes of third-stage duration, the risk of developing postpartum hemorrhage significantly increased. In a third stage longer than 60 minutes, the incidence of postpartum hemorrhage was 21.2% without manual removal of the placenta and 70.3% with manual removal. CONCLUSIONS: The incidence of postpartum hemorrhage increases significantly from 10 to 19 minutes into the third stage. Women with the removal of the placenta had a significantly higher percentage of postpartum hemorrhage. The optimal timing for manual removal of the placenta should be investigated in a carefully designed randomized controlled trial to examine whether earlier manual removal of placenta lowers the incidence and limits the severity of postpartum hemorrhage.

Routine testing of Mycoplasma genitalium and Trichomonas vaginalis.

BACKGROUND: Mycoplasma genitalium (MG) and Trichomonas vaginalis (TV) are common sexual transmitted infections (STI). However, most STI screening programmes do not include routinely detection of these pathogens. Consequently, epidemiological data about MG and TV in the general population is lacking. The current study aims to give insight into the prevalence of both infections, thereby guiding decisions whether testing for these pathogens should be included routinely. METHODS: Between February 2013 and August 2015, all samples sent to the laboratory of Diakonessenhuis Utrecht for STI testing (i.e. testing for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG)) were additionally examined for the presence of MG and TV by means of a laboratory-developed RT-PCR. Samples were collected by our hospital or by regional general practitioners. RESULTS: A total of 5628 PCR's were evaluated. In 7.5%, one or more STI were detected. CT was found in 5% and MG was positive in 1.9%. NG was detected in 0.5% and TV was detected in 0.6% of the samples. CT was found more often in primary care than in hospital setting (9.7% vs. 3.0%, p < .05). The same was shown for NG (1.1% vs. 0.2%, p < .05). More men than women were positive for CT (11.2% vs. 3.8%, p < .05) and NG (1.4% vs. 0.3%, p < .05). CONCLUSION: MG is more prevalent than NG and TV in a regional Dutch population. Furthermore, TV is equally common as NG. Based on our prevalence data, including MG and TV in STI testing protocols should be considered in the future.

ADAM12s and PP13 as first trimester screening markers for adverse pregnancy outcome.

BACKGROUND: The aim of the study was to assess the screening performance of first trimester maternal serum measurements of A-disintegrin-and-metalloprotease 12-s (ADAM12s) and placental protein 13 (PP13) for preeclampsia (PE), gestational hypertension (GH) and small-for-gestational-age (SGA) fetuses. METHODS: In this retrospective case-control study 220 pregnant women were matched for gestational and maternal age at sampling. Results were expressed as multiples of the median (MoM) and compared using Kruskal-Wallis and Mann-Whitney U-test. Screening performance was assessed by receiver operator characteristics (ROC) curves and area under the curve (AUC). RESULTS: Seventeen cases of PE, 30 cases of GH and eight cases of SGA fetuses were matched with 165 controls. ROC-analysis yielded AUCs for ADAM12s and PP13 of 0.63 and 0.59 for PE, 0.68 and 0.57 for GH and 0.59 and 0.62 for SGA, respectively. Combined ADAM12 and PP13 did not improve the AUC value. When the specificity was set at 80%, corresponding detection rate of ADAM12s was 52% for GH. CONCLUSIONS: Combined ADAM12s and PP13 measurements do not predict adverse pregnancy outcome, but decreased first trimester ADAM12s levels are associated with GH.

Longitudinal Doppler measurements of spiral artery blood flow in relation to uterine artery blood flow.

OBJECTIVE: The purpose of this study was to examine the longitudinal relationship between Doppler flow velocity waveforms of the spiral artery (SA) and uterine artery (UA) in pregnant women. METHODS: Ninety-seven primigravidas with uncomplicated singleton pregnancies were analyzed. Spiral artery and combined UA velocity waveforms were assessed by transabdominal color Doppler sonography at gestational ages of 11 through 13, 14 through 17, and 18 through 24 weeks; each measurement was performed twice. The pulsatility index (PI) was calculated for the left and right UA, and the results were averaged as a combined UA. In addition, the presence of UA bilateral notching was reported. Bland-Altman plots and generalized estimating equations were used to assess intraobserver variability and the longitudinal relationship between SA and UA blood velocities. RESULTS: A total of 284 UA and 263 SA Doppler flow measurements were analyzed. Intraobserver variability rates for the SA and UA were 0.54 and 0.90, respectively. Results showed a continuous decrease of the mean PI in the SA and UA with increasing gestational age. Uterine artery bilateral notching was reported in 35%, 9%, and 3% of the cases at gestational ages of 11 through 13, 14 through 17, and 18 through 24 weeks. Generalized estimating equation analysis showed a significant correlation (r = 0.41) between the SA and UA (P < .0001). CONCLUSIONS: Uterine artery Doppler measurements in early pregnancy seem to accurately reflect peripheral resistance of SAs. Furthermore, trophoblastic invasion seems a continuous process in the first half of pregnancy, in which early UA bilateral notching is a physiologic event.

Decreased plasma levels of metastin in early pregnancy are associated with small for gestational age neonates.

OBJECTIVE: To investigate whether pregnancies with small for gestational age (SGA) neonates, defined as customized birth weight below the 10th centile, are associated with altered levels of metastin in maternal plasma in the first trimester. STUDY DESIGN: Maternal blood was obtained between 8 and 14 weeks of pregnancy. Levels of metastin were measured in pregnancies with (n = 31) or without SGA-neonates (n = 31), matched for gestational age at venipuncture. Measurement of beta-hCG was included to study the influence of gestational age and placental volume on plasma levels of the measured markers. RESULTS: Metastin was significantly lower in SGA-pregnancies compared to an equal number of matched uneventful pregnancies (metastin: 1376 +/- 1317 pmol/L vs 2035 +/- 1260 pmol/L, p = 0.035; mean +/- standard deviation). beta-hCG levels were not different. CONCLUSION: Metastin is significantly lower in maternal plasma in the first trimester, in pregnancies with SGA-neonates. It might therefore be used in combination with other markers for risk estimation of growth impairment in the first trimester.