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.

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.

Balancing Patient Access to Fetoscopic Laser Photocoagulation for Twin-to-Twin Transfusion Syndrome With Maintaining Procedural Competence: Are Collaborative Services Part of the Solution?

The benefits of fetoscopic laser photocoagulation (FLP) for treatment of twin-to-twin transfusion syndrome (TTTS) have been recognized for over a decade, yet access to FLP remains limited in many settings. This means at a population level, the potential benefits of FLP for TTTS are far from being fully realized. In part, this is because there are many centers where the case volume is relatively low. This creates an inevitable tension; on one hand, wanting FLP to be readily accessible to all women who may need it, yet on the other, needing to ensure that a high degree of procedural competence is maintained. Some of the solutions to these apparently competing priorities may be found in novel training solutions to achieve, and maintain, procedural proficiency, and with the increased utilization of 'competence based' assessment and credentialing frameworks. We suggest an under-utilized approach is the development of collaborative surgical services, where pooling of personnel and resources can improve timely access to surgery, improve standardized assessment and management of TTTS, minimize the impact of the surgical learning curve, and facilitate audit, education, and research. When deciding which centers should offer laser for TTTS and how we decide, we propose some solutions from a collaborative model.

Dichorionic triamniotic triplet pregnancy complicated by twin anemia polycythemia sequence: the place of fetal therapy.

Monochorionic twins as part of a high order multiple pregnancy can be an unintended consequence of the increasingly common practice of blastocyst transfer for couples requiring in vitro fertilisation (IVF) for infertility. Dichorionic triamniotic (DCTA) triplets is the most common presentation, and these pregnancies are particularly high risk because of the additional risks associated with monochorionicity. Surveillance for twin-to-twin transfusion syndrome, including twin anemia polycythemia sequence, may be more difficult, and any intervention to treat the monochorionic pair needs to balance the proposed benefits against the risks posed to the unaffected singleton. Counseling of families with DCTA triplets is therefore complex. Here, we report a case of DCTA triplets, where the pregnancy was complicated by threatened preterm labour, and twin anemia polycythemia sequence (TAPS) was later diagnosed at 28 weeks. The TAPS was managed with a single intraperitoneal transfusion, enabling safe prolongation of the pregnancy for over 2 weeks until recurrence of TAPS and preterm labour supervened. Postnatal TAPS was confirmed, and all three infants were later discharged home at term corrected age, and were normal at follow-up. This case highlights that in utero therapy has an important role in multiple pregnancies of mixed chorionicity, and can achieve safe prolongation of pregnancy at critical gestations.

Can we predict sleep-disordered breathing in pregnancy? The clinical utility of symptoms.

Sleep-disordered breathing (SDB) is reported commonly during pregnancy and is associated with an increased risk of adverse maternal and fetal outcomes, but the majority of these data are based upon self-report measures not validated for pregnancy. This study examined the predictive value of screening questionnaires for SDB administered at two time-points in pregnancy, and attempted to develop an 'optimized predictive model' for detecting SDB in pregnancy. A total of 380 women were recruited from an antenatal clinic in the second trimester of pregnancy. All participants completed the Berlin Questionnaire and the Multivariable Apnea Risk Index (MAP Index) at recruitment, with a subset of 43 women repeating the questionnaires at the time of polysomnography at 37 weeks' gestation. Fifteen of 43 (35%) women were confirmed to have a respiratory disturbance index (RDI) > 5 h(-1) . Prediction of an RDI > 5 h(-1) was most accurate during the second trimester for both the Berlin Questionnaire (sensitivity 0.93, specificity 0.50, positive predictive value 0.50 and negative predictive value 0.93), and the MAP Index [area under the receiver operating characteristic (ROC) curve of 0.768]. A stepwise selection model identified snoring volume, a body mass index (BMI)≥32 kg m(-2) and tiredness upon awakening as the strongest independent predictors of SDB during pregnancy; this model had an area under the ROC curve of 0.952. We conclude that existing clinical prediction models for SDB perform inadequately as a screening tool in pregnancy. The development of a highly predictive model from our data shows promise for a quick and easy screening tool to be validated for future use in 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.

Sleep-disordered breathing does not impact maternal outcomes in women with hypertensive disorders of pregnancy.

OBJECTIVE: Sleep-disordered breathing (SDB) is characterised by intermittent hypoxemia, sympathetic activation and widespread endothelial dysfunction, sharing pathophysiologic features with the hypertensive disorders of pregnancy. We sought to determine whether coexisting SDB would adversely impact the outcomes of women with gestational hypertension (GH) and preeclampsia (PE), and healthy matched controls. STUDY DESIGN: Women diagnosed with GH or PE along with BMI- and gestation-matched normotensive controls underwent polysomnography in late pregnancy to establish the presence or absence of SDB (RDI ≥ 5). Clinical outcomes of hypertensive disease severity were compared between groups, and venous blood samples were taken in the third trimester and at delivery to examine for any impact of SDB on the anti-angiogenic markers of PE. RESULTS: Data was available for 17 women with PE, 24 women with GH and 44 controls. SDB was diagnosed in 41% of the PE group, 63% of the GH group and 39% of the control group. Women with PE and co-existing SDB did not have worse outcomes in terms of gestation at diagnosis of PE (SDB = 29.1 (25.9, 32.1) weeks vs. no SDB = 32.0 (29.0, 33.9), p = n.s.) and days between diagnosis of PE and delivery (SDB = 20.0 (4.0, 35.0) days vs. no SDB = 10.5 (9.0, 14.0), p = n.s.). There were also no differences in severity of hypertension, antihypertensive treatment and biochemical, haematological and anti-angiogenic markers of PE between SDB and no SDB groups. Similar results were observed among women with GH. Healthy control women with SDB were no more likely to develop a hypertensive disorder of pregnancy in the later stages of pregnancy (SDB = 5.9% vs. no SDB = 7.4%, p = n.s.). Increasing the threshold for diagnosis of SDB to RDI ≥ 15 did not unmask a worse prognosis. CONCLUSION: The presence of SDB during pregnancy did not worsen the disease course of GH or PE, and was not associated with high blood pressure or anti-angiogenic markers of hypertensive disease amongst healthy pregnant women. Given the numerous reports of the relationship between SDB and diagnosis of hypertensive disorders of pregnancy, it appears more work is required to distinguish causal, versus confounding, pathways.

The presence of coexisting sleep-disordered breathing among women with hypertensive disorders of pregnancy does not worsen perinatal outcome.

OBJECTIVE: To determine whether the presence of co-existing sleep-disordered breathing (SDB) is associated with worse perinatal outcomes among women diagnosed with a hypertensive disorder of pregnancy (HDP), compared with normotensive controls. STUDY DESIGN: Women diagnosed with HDP (gestational hypertension or preeclampsia) and BMI- and gestation-matched controls underwent polysomnography in late pregnancy to determine if they had coexisting SDB. Fetal heart rate (FHR) monitoring accompanied the sleep study, and third trimester fetal growth velocity was assessed using ultrasound. Cord blood was taken at delivery to measure key regulators of fetal growth. RESULTS: SDB was diagnosed in 52.5% of the HDP group (n = 40) and 38.1% of the control group (n = 42); p = .19. FHR decelerations were commonly observed during sleep, but the presence of SDB did not increase this risk in either the HDP or control group (HDP group-SDB = 35.3% vs. No SDB = 40.0%, p = 1.0; control group-SDB = 41.7% vs. No SDB = 25.0%, p = .44), nor did SDB affect the total number of decelerations overnight (HDP group-SDB = 2.7 ± 1.0 vs. No SDB = 2.8 ± 2.1, p = .94; control group-SDB = 2.0 ± 0.8 vs. No SDB = 2.0 ± 0.7, p = 1.0). Fetal growth restriction was the strongest predictor of fetal heart rate events during sleep (aOR 5.31 (95% CI 1.26-22.26), p = .02). The presence of SDB also did not adversely affect fetal growth; in fact among women with HDP, SDB was associated with significantly larger customised birthweight centiles (43.2% ± 38.3 vs. 16.2% ± 27.0, p = .015) and fewer growth restricted babies at birth (30% vs. 68.4%, p = .026) compared to HDP women without SDB. There was no impact of SDB on measures of fetal growth for the control group. Cord blood measures of fetal growth did not show any adverse effect among women with SDB, either in the HDP or control group. CONCLUSION: We did not find that the presence of mild SDB worsened fetal acute or longitudinal outcomes, either among women with HDP or BMI-matched normotensive controls. Unexpectedly, we found the presence of SDB conferred a better prognosis in HDP in terms of fetal growth. The fetus has considerable adaptive capacity to withstand in utero hypoxia, which may explain our mostly negative findings. In addition, SDB in this cohort was mostly mild. It may be that fetal sequelae will only be unmasked in the setting of more severe degrees of SDB and/or underlying placental disease.

Effects of maternal obstructive sleep apnoea on fetal growth: a prospective cohort study.

OBJECTIVE: The objective of this study is to determine whether obstructive sleep apnea (OSA) is associated with reduced fetal growth, and whether nocturnal oxygen desaturation precipitates acute fetal heart rate changes. STUDY DESIGN: We performed a prospective observational study, screening 371 women in the second trimester for OSA symptoms. 41 subsequently underwent overnight sleep studies to diagnose OSA. Third trimester fetal growth was assessed using ultrasound. Fetal heart rate monitoring accompanied the sleep study. Cord blood was taken at delivery, to measure key regulators of fetal growth. RESULTS: Of 371 women screened, 108 (29%) were high risk for OSA. 26 high risk and 15 low risk women completed the longitudinal study; 14 had confirmed OSA (cases), and 27 were controls. The median (interquartile range) respiratory disturbance index (number of apnoeas, hypopnoeas or respiratory related arousals/hour of sleep) was 7.9 (6.1-13.8) for cases and 2.2 (1.3-3.5) for controls (p<0.001). Impaired fetal growth was observed in 43% (6/14) of cases, vs 11% (3/27) of controls (RR 2.67; 1.25-5.7; p = 0.04). Using logistic regression, only OSA (OR 6; 1.2-29.7, p = 0.03) and body mass index (OR 2.52; 1.09-5.80, p = 0.03) were significantly associated with impaired fetal growth. After adjusting for body mass index on multivariate analysis, the association between OSA and impaired fetal growth was not appreciably altered (OR 5.3; 0.93-30.34, p = 0.06), although just failed to achieve statistical significance. Prolonged fetal heart rate decelerations accompanied nocturnal oxygen desaturation in one fetus, subsequently found to be severely growth restricted. Fetal growth regulators showed changes in the expected direction- with IGF-1 lower, and IGFBP-1 and IGFBP-2 higher- in the cord blood of infants of cases vs controls, although were not significantly different. CONCLUSION: OSA may be associated with reduced fetal growth in late pregnancy. Further evaluation is warranted to establish whether OSA may be an important contributor to adverse perinatal outcome, including stillbirth.