Computerized fetal heart rate analysis in early preterm fetal growth restriction

Objective: To assess the value of computerized cardiotocography (cCTG) with calculation of fetal heart rate (FHR) short-term variability (STV) in early preterm fetal growth restriction (FGR) for prevention of fetal death and neonatal asphyxia, neonatal morbidity, and 2-year neurodevelopmental impairment. Methods: This was a retrospective cohort study of all women who were admitted to the Amsterdam University Medical Center-AMC between 2003 and 2015 due to FGR and/or pre-eclampsia, and who were delivered by prelabor Cesarean section, or had a fetal death, before 32 weeks' gestation. STV of all available cCTG registrations during the 5 days preceding fetal death or delivery was calculated retrospectively, and FHR decelerations were classified visually as absent, 1–2/h or recurrent (> 2/h). Adverse outcome endpoints were defined as fetal death, neonatal asphyxia at birth (including fetal death), neonatal death, major neonatal morbidity and 2-year neurodevelopmental outcome. A simulation analysis was performed to assess the incidence of adverse outcome using two thresholds for cCTG: (1) highly abnormal (STV < 2.6 ms before 29 weeks and < 3.0 ms thereafter, and/or recurrent FHR decelerations); and (2) moderately abnormal (STV < 3.5 ms before 29 weeks and < 4.0 ms thereafter, and/or recurrent FHR decelerations). Three management strategies were assessed using a strict schedule for the frequency of cCTG recordings: (1) cCTG without use of fetal arterial Doppler; (2) cCTG with additional fetal arterial Doppler after 29 weeks; and (3) cCTG with additional fetal arterial Doppler after 27 weeks. Results: Included were 367 pregnancies (3295 cCTG recordings), of which 20 resulted in fetal death and 347 were delivered by Cesarean section before the onset of labor. Cesarean delivery was indicated by fetal condition in 94% of cases and by maternal condition in 6%. Median gestational age at delivery was 30 (interquartile range (IQR), 28–31) weeks and median birth weight was 900 (IQR, 740–1090) g. Six cases of fetal death were not anticipated by standard practice using visual assessment of CTG. A last highly abnormal cCTG was associated with fetal death and with neonatal asphyxia (including fetal death; n = 99), but not with major neonatal morbidity and 2-year neurodevelopmental outcome. Moderately abnormal cCTG had no significant association with any endpoint. Simulation analysis showed that a strategy that combined cCTG results with umbilicocerebral ratio or umbilical absent or reversed end-diastolic flow could detect all fetal deaths. Conclusions: Computerized CTG in combination with fetal arterial Doppler, with a strict protocol for the frequency of recordings, is likely to be more effective than visual CTG assessment for preventing fetal death in early preterm FGR

Epidural analgesia and emergency delivery for presumed fetal compromise:post-hoc analysis of RAVEL multicenter randomized controlled trial

Objective: To investigate the association between epidural analgesia (EDA) vs patient-controlled remifentanil analgesia (PCRA) and emergency delivery for presumed fetal compromise, in relation to birth-weight quintile.Methods: This was a post-hoc per-protocol analysis of the RAVEL multicenter equivalence randomized controlled trial. Non-anomalous singleton pregnancies between 36 + 0 and 42 + 6 weeks' gestation were randomized at the time of requesting pain relief to receive EDA or PCRA. The primary outcome was emergency delivery for presumed fetal compromise. Secondary outcomes included mode of delivery and neonatal outcomes. Analysis was performed according to birth-weight quintile and was corrected for relevant confounding variables.Results: Of 619 pregnant women, 336 received PCRA and 283 received EDA. Among women receiving EDA, 14.8% had an emergency delivery for presumed fetal compromise, compared with 8.3% of women who received PCRA. After adjusting for parity, women receiving EDA had higher odds of presumed fetal compromise compared to those receiving PCRA (odds ratio, 1.69 (95% CI, 1.01–2.83)). A statistically significant linear-by-linear association was observed between presumed fetal compromise and birth-weight quintile (P = 0.003). The incidence of emergency delivery for presumed fetal compromise was highest in women receiving EDA and delivering a neonate with a birth weight in the lowest quintile.Conclusions: Intrapartum EDA is associated with a higher rate of emergency delivery for presumed fetal compromise compared to treatment with PCRA. Birth-weight quintile is a strong predictor of this outcome, independent of pain management method.</p

Prediction of fetal and neonatal outcomes after preterm manifestations of placental insufficiency:systematic review of prediction models

Objectives: To identify all prediction models for fetal and neonatal outcomes in pregnancies with preterm manifestations of placental insufficiency (gestational hypertension, pre-eclampsia, HELLP syndrome or fetal growth restriction with its onset before 37 weeks' gestation) and to assess the quality of the models and their performance on external validation. Methods: A systematic literature search was performed in PubMed, Web of Science and EMBASE. Studies describing prediction models for fetal/neonatal mortality or significant neonatal morbidity in patients with preterm placental insufficiency disorders were included. Data extraction was performed using the CHARMS checklist. Risk of bias was assessed using PROBAST. Literature selection and data extraction were performed by two researchers independently. Results: Our literature search yielded 22 491 unique publications. Fourteen were included after full-text screening of 218 articles that remained after initial exclusions. The studies derived a total of 41 prediction models, including four models in the setting of pre-eclampsia or HELLP, two models in the setting of fetal growth restriction and/or pre-eclampsia and 35 models in the setting of fetal growth restriction. None of the models was validated externally, and internal validation was performed in only two studies. The final models contained mainly ultrasound (Doppler) markers as predictors of fetal/neonatal mortality and neonatal morbidity. Discriminative properties were reported for 27/41 models (c-statistic between 0.6 and 0.9). Only two studies presented a calibration plot. The risk of bias was assessed as unclear in one model and high for all other models, mainly owing to the use of inappropriate statistical methods. Conclusions: We identified 41 prediction models for fetal and neonatal outcomes in pregnancies with preterm manifestations of placental insufficiency. All models were considered to be of low methodological quality, apart from one that had unclear methodological quality. Higher-quality models and external validation studies are needed to inform clinical decision-making based on prediction models.</p

Gestational age and socio demographic factors associated with school performance at the age of 12 years, a population based study

BackgroundGestational age is positively associated with cognitive development, but socio-demographic factors also influence school performance. Previous studies suggested possible interaction, putting children with low socio-economic status (SES) at increased risk of the negative effects of prematurity.ObjectivesTo investigate the association between gestational age in weeks, socio-demographic characteristics, and school performance at the age of 12 years among children in regular primary education.MethodsPopulation-based cohort study among liveborn singletons (N = 860,332) born in the Netherlands in 1999–2006 at 25–42 weeks' gestation, with school performance from 2011 to 2019. Regression analyses were conducted investigating the association of gestational age and sociodemographic factors with school performance and possible interaction.ResultsSchool performance increased with gestational age up to 40 weeks. This pattern was evident across socio-demographic strata. Children born at 25 weeks had −0.57 SD (95% confidence interval −0.79, −0.35) lower school performance z-scores and lower secondary school level compared to 40 weeks. Low maternal education, low maternal age, and non-European origin were strongly associated with lower school performance. Being born third or later and low socioeconomic status (SES) were also associated with lower school performance, but differences were smaller than among other factors. When born preterm, children from mothers with low education level, low or high age, low SES or children born third or later were at higher risk for lower school performance compared to children of mothers with intermediate education level, aged 25–29 years, with intermediate SES or first borns (evidence of interaction).ConclusionsHigher gestational age is associated with better school performance at the age of 12 years along the entire spectrum of gestational age, beyond the cut-off of preterm birth and across socio-demographic differences. Children in socially or economically disadvantaged situations might be more vulnerable to the negative impact of preterm birth. Other important factors in school performance are maternal education, maternal age, ethnicity, birth order and SES. Results should be interpreted with caution due to differential loss to follow-up

Gestational age and socio demographic factors associated with school performance at the age of 12 years, a population based study

BackgroundGestational age is positively associated with cognitive development, but socio-demographic factors also influence school performance. Previous studies suggested possible interaction, putting children with low socio-economic status (SES) at increased risk of the negative effects of prematurity.ObjectivesTo investigate the association between gestational age in weeks, socio-demographic characteristics, and school performance at the age of 12 years among children in regular primary education.MethodsPopulation-based cohort study among liveborn singletons (N = 860,332) born in the Netherlands in 1999–2006 at 25–42 weeks' gestation, with school performance from 2011 to 2019. Regression analyses were conducted investigating the association of gestational age and sociodemographic factors with school performance and possible interaction.ResultsSchool performance increased with gestational age up to 40 weeks. This pattern was evident across socio-demographic strata. Children born at 25 weeks had −0.57 SD (95% confidence interval −0.79, −0.35) lower school performance z-scores and lower secondary school level compared to 40 weeks. Low maternal education, low maternal age, and non-European origin were strongly associated with lower school performance. Being born third or later and low socioeconomic status (SES) were also associated with lower school performance, but differences were smaller than among other factors. When born preterm, children from mothers with low education level, low or high age, low SES or children born third or later were at higher risk for lower school performance compared to children of mothers with intermediate education level, aged 25–29 years, with intermediate SES or first borns (evidence of interaction).ConclusionsHigher gestational age is associated with better school performance at the age of 12 years along the entire spectrum of gestational age, beyond the cut-off of preterm birth and across socio-demographic differences. Children in socially or economically disadvantaged situations might be more vulnerable to the negative impact of preterm birth. Other important factors in school performance are maternal education, maternal age, ethnicity, birth order and SES. Results should be interpreted with caution due to differential loss to follow-up

Prediction of complications in early-onset pre-eclampsia (PREP): development and external multinational validation of prognostic models.

BACKGROUND: Unexpected clinical deterioration before 34 weeks gestation is an undesired course in early-onset pre-eclampsia. To safely prolong preterm gestation, accurate and timely prediction of complications is required. METHOD: Women with confirmed early onset pre-eclampsia were recruited from 53 maternity units in the UK to a large prospective cohort study (PREP-946) for development of prognostic models for the overall risk of experiencing a complication using logistic regression (PREP-L), and for predicting the time to adverse maternal outcome using a survival model (PREP-S). External validation of the models were carried out in a multinational cohort (PIERS-634) and another cohort from the Netherlands (PETRA-216). Main outcome measures were C-statistics to summarise discrimination of the models and calibration plots and calibration slopes. RESULTS: A total of 169 mothers (18%) in the PREP dataset had adverse outcomes by 48 hours, and 633 (67%) by discharge. The C-statistics of the models for predicting complications by 48 hours and by discharge were 0.84 (95% CI, 0.81-0.87; PREP-S) and 0.82 (0.80-0.84; PREP-L), respectively. The PREP-S model included maternal age, gestation, medical history, systolic blood pressure, deep tendon reflexes, urine protein creatinine ratio, platelets, serum alanine amino transaminase, urea, creatinine, oxygen saturation and treatment with antihypertensives or magnesium sulfate. The PREP-L model included the above except deep tendon reflexes, serum alanine amino transaminase and creatinine. On validation in the external PIERS dataset, the reduced PREP-S model showed reasonable calibration (slope 0.80) and discrimination (C-statistic 0.75) for predicting adverse outcome by 48 hours. Reduced PREP-L model showed excellent calibration (slope: 0.93 PIERS, 0.90 PETRA) and discrimination (0.81 PIERS, 0.75 PETRA) for predicting risk by discharge in the two external datasets. CONCLUSIONS: PREP models can be used to obtain predictions of adverse maternal outcome risk, including early preterm delivery, by 48 hours (PREP-S) and by discharge (PREP-L), in women with early onset pre-eclampsia in the context of current care. They have a potential role in triaging high-risk mothers who may need transfer to tertiary units for intensive maternal and neonatal care. TRIAL REGISTRATION: ISRCTN40384046 , retrospectively registered