Maternal sleep behaviours preceding fetal heart rate events on cardiotocography.

In Australia, a significant proportion of stillbirths remain unexplained. Recent research has highlighted nocturnal maternal behaviours as potentially modifiable contributors. This study determined whether sleep-related behaviours including sleep position and sleep-disordered breathing adversely affect fetuses overnight, in both uncomplicated pregnancies and those at increased risk due to hypertensive disorders or fetal growth restriction (FGR). All participants underwent polysomnography with time-synchronized fetal heart rate (FHR) monitoring (cardiotocography - CTG) in late pregnancy. CTGs were analysed for abnormal FHR events, including decelerations and reduced variability, by two blinded observers and exported into the sleep study to temporally align FHR events with sleep behaviours. For each FHR event, 10 control epochs with normal FHR were randomly selected for the same participant. Conditional logistic regression assessed the relationships between FHR events and sleep behaviours. From 116 participants, 52 had a total of 129 FHR events overnight; namely prolonged decelerations and prolonged periods of reduced variability. Significantly more FHR events were observed in women with FGR and/or a hypertensive disorder compared with uncomplicated pregnancies (P = 0.006). FHR events were twice as likely to be preceded by a change in body position within the previous 5 min, compared with control epochs (P = 0.007), particularly in hypertensive pregnancies both with and without FGR. Overall, FHR events were not temporally related to supine body position, respiratory events or snoring. Our results indicate that most fetuses tolerate sleep-related stressors, but further research is needed to identify the interplay of maternal and fetal conditions putting the fetus at risk overnight. KEY POINTS: Maternal sleep behaviours including supine position and sleep-disordered breathing are potential contributors to stillbirth but much of this work is based on self-reported data. Using time-synchronized polysomnography and cardiotocography, we found that nocturnal fetal heart rate decelerations were more likely to be preceded by a change in body position compared with epochs containing normal fetal heart rate, particularly in hypertensive pregnancies with or without fetal growth restriction. There was no temporal relationship between maternal sleeping position, snoring or apnoeic events and an abnormal fetal heart rate overnight. We conclude that most fetuses can tolerate sleep-related stressors with no evidence of fetal heart rate changes indicating compromised wellbeing. Further work needs to identify how sleep behaviours contribute to stillbirth risk and how these intersect with underlying maternal and fetal conditions.

Fetal heart rate events during sleep, and the impact of sleep disordered breathing, in pregnancies complicated by preterm fetal growth restriction: An exploratory observational case-control study.

OBJECTIVES: To evaluate fetal heart rate (FHR) patterns during sleep in pregnancies complicated by preterm fetal growth restriction (FGR). To determine whether co-existing sleep-disordered breathing (SDB) impacts on acute FHR events or perinatal outcome. DESIGN: Observational case control study. SETTING AND POPULATION: Women with preterm FGR and gestation-matched well grown controls (estimated fetal weight above the 10th percentile with normal Doppler studies); tertiary maternity hospital, Australia. METHODS: A polysomnogram, a test used to measure sleep patterns and diagnose sleep disorders, and concurrent cardiotocography (CTG), were analysed for respiratory events and FHR changes. MAIN OUTCOME MEASURES: Frequency of FHR events overnight in FGR cases versus controls and in those with or without SDB. RESULTS: Twenty-nine patients with preterm FGR and 29 controls (median estimated fetal weight 1st versus 60th percentile, P < 0.001) underwent polysomnography with concurrent CTG at a mean gestation of 30.2 weeks. The median number of FHR events per night was higher among FGR cases than among controls (3.0 events, interquartile range [IQR] 1.0-4.0, versus 1.0 [IQR 0-1.0]; P < 0.001). Women with pregnancies complicated by preterm FGR were more likely than controls to be nulliparous, receive antihypertensive medications, be supine at sleep onset, and to sleep supine (32.9% of total sleep time versus 18.3%, P = 0.03). SDB was common in both FGR and control pregnancies (48% versus 38%, respectively, P = 0.55) but was generally mild and not associated with an increase in overnight FHR events or adverse perinatal outcome. CONCLUSIONS: Acute FHR events overnight are more common in pregnancies complicated by preterm FGR than in pregnancies with normal fetal growth. Mild SDB was common in late pregnancy and well tolerated, even by fetuses with preterm FGR. TWEETABLE ABSTRACT: Mild sleep-disordered breathing seems well tolerated even by highly vulnerable fetuses.

Multimedia in improving informed consent for caesarean section: A randomised controlled trial.

BACKGROUND: Multimedia modules have been used as an adjunct to improve patient knowledge and recall for various elective surgical procedures, but have been incompletely evaluated in patients undergoing caesarean section. AIMS: To compare the use of a supplementary multimedia module with written information in improving the informed consent process prior to elective caesarean section. MATERIALS AND METHODS: This was a prospective randomised controlled trial (ACTRN12616000430437). Primary outcomes were knowledge and anxiety scores immediately following the intervention and on the day of surgery. Secondary outcomes were patient satisfaction, length of stay, time to cessation of analgesia, and patient assessment of the consent types. RESULTS: Seventy-five patients completed the study. Both multimedia module and written information groups demonstrated a significant increase in knowledge scores with no difference between the groups. In the multimedia-assisted consent group, scores improved from baseline by +2.31 (P < 0.001) immediately after watching the multimedia module and by +2.41 (P < 0.001) on the day of surgery. In the written information group, scores improved by +1.76 (P < <0.001), and +2.31 (P < 0.001) respectively. There was no adverse impact on anxiety in either group. Patient-reported understanding (92.4% vs 78.5%, P = 0.001), and helpfulness (90.1% vs 73.3%, P = 0.001) was significantly higher in the multimedia module group than in the written information group. The multimedia module was assessed as 'slightly too long' and provided 'slightly too much information'. CONCLUSIONS: Multimedia modules are a valuable adjunct to traditional processes of obtaining informed consent for elective caesarean section and should be offered and made available to patients prior to surgery.

Sleep-disordered breathing in hypertensive disorders of pregnancy: a BMI-matched study.

Sleep-disordered breathing is more common in hypertensive disorders during pregnancy; however, most studies have not adequately accounted for the potential confounding impact of obesity. This study evaluated the frequency of sleep-disordered breathing in women with gestational hypertension and pre-eclampsia compared with body mass index- and gestation-matched normotensive pregnant women. Women diagnosed with gestational hypertension or pre-eclampsia underwent polysomnography shortly after diagnosis. Normotensive controls body mass index-matched within ±4 kg m-2 underwent polysomnography within ±4 weeks of gestational age of their matched case. The mean body mass index and gestational age at polysomnography were successfully matched for 40 women with gestational hypertension/pre-eclampsia and 40 controls. The frequency of sleep-disordered breathing in the cases was 52.5% compared with 37.5% in the control group (P = 0.18), and the respiratory disturbance index overall did not differ (P = 0.20). However, more severe sleep-disordered breathing was more than twice as common in women with gestational hypertension or pre-eclampsia (35% versus 15%, P = 0.039). While more than half of women with a hypertensive disorder of pregnancy meet the clinical criteria for sleep-disordered breathing, it is also very common in normotensive women of similar body mass index. This underscores the importance of adjusting for obesity when exploring the relationship between sleep-disordered breathing and hypertension in pregnancy. More severe degrees of sleep-disordered breathing are significantly associated with gestational hypertension and pre-eclampsia, and sleep-disordered breathing may plausibly play a role in the pathophysiology of pregnancy hypertension in these women. This suggests that more severe sleep-disordered breathing is a potential therapeutic target for reducing the prevalence or severity of hypertensive disorders in pregnancy.

Concordance of maternal and paternal decision-making and its effect on choice for vaginal birth after caesarean section.

BACKGROUND: The proportion of women who plan for a repeat elective caesarean section (CS) is one of the major determinants of the overall rate of CS, and programs aiming to reduce the rate of CS have not been greatly successful. To date, there appear to have been no large studies directly addressing paternal influences on decision-making regarding vaginal birth after caesarean (VBAC). This study aimed to compare the reactions of fathers and mothers to the prospect of VBAC. METHODS: Couples were recruited from three Australian hospitals and were eligible with a singleton pregnancy, a normal morphology ultrasound, and where there was no condition in the new pregnancy that would preclude a vaginal birth. Questionnaires were scheduled for 20 weeks' gestation, 32-36 weeks' gestation and six weeks postnatal and were sent separately to each partner. RESULTS: Seventy-five couples completed the full sets of questionnaires during the study period. In total, 31 women (41%) ultimately attempted vaginal delivery, and 44 (59%) were delivered by planned CS. When the paternal rating of risk fell between the second and third trimesters, the couple were likely to attempt VBAC (P < 0.05). Where the maternal rating of importance was 3 or less, 92% had a planned CS compared to 63% for the same paternal scores (P = 0.02). CONCLUSION: This study suggests that interventions that improve the paternal perceptions of risk during a pregnancy might increase the chance that a couple will attempt VBAC.

Immune profiling of SARS-CoV-2 infection during pregnancy reveals NK cell and γδ T cell perturbations.

Pregnancy poses a greater risk for severe COVID-19; however, underlying immunological changes associated with SARS-CoV-2 during pregnancy are poorly understood. We defined immune responses to SARS-CoV-2 in unvaccinated pregnant and nonpregnant women with acute and convalescent COVID-19, quantifying 217 immunological parameters. Humoral responses to SARS-CoV-2 were similar in pregnant and nonpregnant women, although our systems serology approach revealed distinct antibody and FcγR profiles between pregnant and nonpregnant women. Cellular analyses demonstrated marked differences in NK cell and unconventional T cell activation dynamics in pregnant women. Healthy pregnant women displayed preactivated NK cells and γδ T cells when compared with healthy nonpregnant women, which remained unchanged during acute and convalescent COVID-19. Conversely, nonpregnant women had prototypical activation of NK and γδ T cells. Activation of CD4+ and CD8+ T cells and T follicular helper cells was similar in SARS-CoV-2-infected pregnant and nonpregnant women, while antibody-secreting B cells were increased in pregnant women during acute COVID-19. Elevated levels of IL-8, IL-10, and IL-18 were found in pregnant women in their healthy state, and these cytokine levels remained elevated during acute and convalescent COVID-19. Collectively, we demonstrate perturbations in NK cell and γδ T cell activation in unvaccinated pregnant women with COVID-19, which may impact disease progression and severity during pregnancy.

Polysomnographic analysis of maternal sleep position and its relationship to pregnancy complications and sleep-disordered breathing.

Links between supine "going to sleep" position and stillbirth risk have led to campaigns regarding safe maternal sleep position. This study profiles the distribution of sleep positions overnight and relationships to sleep onset position during pregnancy, and the relationships between supine sleep, sleep-disordered breathing (SDB), and pregnancy outcomes. Data from three prospective cohort studies evaluating SDB in healthy and complicated pregnancies were pooled. All participants underwent one night of polysomnography in late pregnancy and birth outcome data were collected. 187 women underwent polysomnography at a median gestation of 34 weeks'. The left lateral position was preferred for falling asleep (52%) compared to supine (14%), but sleep onset position was the dominant sleep position overnight in only half (54%) of women. The median percentage of sleep time in the supine position was 24.2%; women who fell asleep supine spent more time supine overnight compared to those who began non-supine (48.0% (30.0,65.9) vs. 22.6% (5.7,32.2), p < .001). Women with growth-restricted fetuses were more likely to fall asleep supine than those with well-grown fetuses (36.6% vs. 7.5%, p < .001). Positional SDB was observed in 46% of those with an RDI ≥ 5. Sleep onset position was the dominant position overnight for half of the sample, suggesting that sleep onset position is not always a reliable indicator of body position overnight. Supine sleep was related to fetal growth restriction and birthweight at delivery, though causality cannot be inferred. It is critical that we pursue research into verifying the important relationship between supine sleep and increased stillbirth risk, and the mechanisms behind it.

Circulating syndecan-1 is reduced in pregnancies with poor fetal growth and its secretion regulated by matrix metalloproteinases and the mitochondria.

Fetal growth restriction is a leading cause of stillbirth that often remains undetected during pregnancy. Identifying novel biomarkers may improve detection of pregnancies at risk. This study aimed to assess syndecan-1 as a biomarker for small for gestational age (SGA) or fetal growth restricted (FGR) pregnancies and determine its molecular regulation. Circulating maternal syndecan-1 was measured in several cohorts; a large prospective cohort collected around 36 weeks' gestation (n = 1206), a case control study from the Manchester Antenatal Vascular service (285 women sampled at 24-34 weeks' gestation); two prospective cohorts collected on the day of delivery (36 + 3-41 + 3 weeks' gestation, n = 562 and n = 405 respectively) and a cohort who delivered for preterm FGR (< 34 weeks). Circulating syndecan-1 was consistently reduced in women destined to deliver growth restricted infants and those delivering for preterm disease. Syndecan-1 secretion was reduced by hypoxia, and its loss impaired proliferation. Matrix metalloproteinases and mitochondrial electron transport chain inhibitors significantly reduced syndecan-1 secretion, an effect that was rescued by coadministration of succinate, a mitochondrial electron transport chain activator. In conclusion, circulating syndecan-1 is reduced among cases of term and preterm growth restriction and has potential for inclusion in multi-marker algorithms to improve detection of poorly grown fetuses.

Pre-eclampsia is associated with altered expression of the renal sodium transporters NKCC2, NCC and ENaC in urinary extracellular vesicles.

Pre-eclampsia is a hypertensive disorder of pregnancy characterised by hypertension and sodium retention by the kidneys. To identify changes in sodium uptake proteins in the tubules of the distal nephron, we studied their expression in urinary extracellular vesicles or exosomes (uEVs). Urine was collected from women with pre-eclampsia or during normal pregnancy, and from healthy non-pregnant controls. uEVs were isolated by centrifugation and analyzed by Western blot. Expression, proteolytic cleavage and phosphorylation was determined by densitometric analysis normalized to the exosome marker CD9. Results showed a significant increase in phosphorylation of the activating S130 site in NKCC2, the drug target for frusemide, in women with pre-eclampsia compared with normal pregnant women. Phosphorylation of the activating sites T101/105 in NKCC2 was similar but the activating T60 site in NCC, the drug target for thiazide diuretics, showed significantly less phosphorylation in pre-eclampsia compared with normal pregnancy. Expression of the larger forms of the α subunit of ENaC, the drug target for amiloride, was significantly greater in pre-eclampsia, with more fragmentation of theγ subunit. The differences observed are predicted to increase the activity of NKCC2 and ENaC while reducing that of NCC. This will increase sodium reabsorption, and so contribute to hypertension in pre-eclampsia.

Chorioamnionitis Occurring in Women With Preterm Rupture of the Fetal Membranes Is Associated With a Dynamic Increase in mRNAs Coding Cytokines in the Maternal Circulation.

BACKGROUND: Preterm prelabor rupture of the fetal membranes (PPROM) is a significant contributor to the morbidity and mortality of preterm birth, particularly in the setting of chorioamnionitis. No sensitive or specific diagnostic or predictive test currently exists for the accurate diagnosis of chorioamnionitis. Our aim was to measure messenger RNA (mRNA) coding cytokines in the maternal blood and examine whether they were increased in association with chorioamnionitis at delivery. METHODS/RESULTS: We performed a prospective cohort study of women recruited with PPROM at a mean gestational age of 28.9 weeks at risk of developing chorioamnionitis. Blood was sampled from participants, and the expression of mRNA coding for proinflammatory genes was measured in women with and without chorioamnionitis at the time of delivery as well as gestation-matched healthy controls. Expression was measured using quantitative polymerase chain reaction (PCR) and also digital PCR. Interleukin 1ß (IL1B) mRNA expression in maternal blood was elevated in women with chorioamnionitis compared to gestation-matched controls. Importantly, among women admitted with PPROM, digital PCR confirmed a significant increase in IL1B expression in maternal blood in women with chorioamnionitis compared to women without chorioamnionitis. Polymerase chain reaction array revealed that CD14, nuclear factor of κ light polypeptide gene enhancer in B-cells 1 (NFKB1), and tumor necrosis factor receptor super family-interacting serine-threonine kinase 1 mRNA were significantly increased in women with chorioamnionitis compared to controls. Digital PCR confirmed that NFKB1 mRNA was significantly increased in patients with chorioamnionitis compared to controls and that CD14 levels increased over time in patients with PPROM having chorioamnionitis. CONCLUSION: Measuring circulating proinflammatory mRNA in women with PPROM may distinguish those with chorioamnionitis from those without, in turn providing better targeted therapies and appropriate timing of delivery.