Sleep‐disordered breathing and pregnancy outcomes: The impact of maternal oxygen saturation

To investigate pathological associations between sleep‐disordered breathing (SDB) and pregnancy outcomes.

meters) and other comorbidities.The interest in pregnancy sleep disorders increased with the rising obesity rate in the obstetric population.Moreover, it is well known that pregnancy predisposes women to develop or worsen OSAHS due to pregnancy-induced physiological changes in the respiratory system, including mucosal hyperemia, narrowing of the oropharyngeal diameter, decreased functional residual capacity, and higher oxygen consumption.Up to one-third of pregnant women report snoring in the third trimester. 1Obesity and maternal age are consistent and independent risk factors of gestational OSAHS. 2 Among obese women, the rate of OSAHS is about 15%-20%, suggesting that a high proportion of women are entering pregnancy affected by this condition.Facco et al. 3 reported an OSAHS prevalence in the high-risk pregnancy population (e.g., obesity, chronic hypertension, pre-gestational diabetes, history of pre-eclampsia, and twin pregnancy) of 30% and 47% in the first and third trimesters, respectively. 3Some evidence suggests that OSAHS exposes pregnant women to a higher risk of adverse events, including increased length of hospitalization, hypertensive disorders of pregnancy, 4 gestational diabetes, 5 congestive heart failure, and pulmonary embolism, 6 as well as fetal growth restriction (FGR), stillbirth, and preterm birth. 7deed, data from the general population have linked OSAHS with cardiovascular disorders.Bourjeily et al. 8 recently demonstrated a higher risk of congenital anomalies and peripartum resuscitation in babies from mothers with OSAHS.0][11] By contrast, some pregnancy-related changes, such as preference for the lateral sleep position and the respiratory rate increase due to hormonal changes, may be protective.The impact of OSAHS on both the mother and her baby prompted us to assess targeted screening and interventions in the high-risk population.3][14] As the results on this topic are inconsistent, this area warrants further research.Therefore, we consider it essential, both diagnostically and preventively, to characterize the impact of decreased maternal oxygenation, mainly due to the obesity condition placing pregnant patients at higher risk of OSAHS development on pregnancy outcomes.tween May 2016 and September 2019, all women admitted to the Maternal-Fetal Medicine Unit of the Department of Obstetrics and Gynecology, ASST-Spedali Civili di Brescia & University of Brescia, Italy, for an outpatient assessment of their obesity were consecutively enrolled.Participants gave their written informed consent.Demographic and clinical data were collected from obstetric charts.Women were included if they had evidence of all the following conditions: pre-pregnancy BMI ≥30, singleton gestation, delivery at our obstetrics unit, and nocturnal pulse oximetry performed during pregnancy.The study cohort was strictly selected according to the following exclusion criteria: multiple pregnancies, pre-pregnancy BMI <30, and delivery in other hospitals.

| Statistical analysis
After Levene's test for homoscedasticity, independent-samples Welch t-test was performed to analyze the difference between means for continuous variables.Continuous variables were tested visually for normality using Q-Q plots and were expressed as mean ± SD, while categorical variables were expressed as frequency (n) and percentage of the sample.The χ 2 test was used to assess differences between proportions.Multivariate regression analysis using the 'enter' method was performed to assess the association between basal oxygen saturation, the total number of desaturation events, ODI, maternal age, BMI at test time, gravidity, ethnicity, and hypertensive disorders of pregnancy as dependent variables, and FGR or congenital abnormalities as independent variables.Statistical analysis was performed using IBM SPSS Statistics 20 for Windows, version 20.0 (IBM Corp., Armonk, NY, USA).All values were twotailed, and statistical significance was set at P < 0.05.

| RE SULTS
We consecutively enrolled 112 obese women with a singleton pregnancy between May 2016 and September 2019.All women were screened for OSAHS through three screening questionnaires (Berlin, Epworth, and Swift) to assess sleepiness snoring, and apnea.Among these, 44/112 (39.3%) showed a pulse oximetry trace suggestive of nocturnal oxygen desaturations (positive pulse oximetry, group 1), while 68/112 (60.7%) had a normal trace (negative pulse oximetry, group 2).Among patients included in group 2, 34/68 women (50.0%) underwent nocturnal polysomnography, of whom 16/68 (23.5%) showed pathological results.No differences were observed in terms of OSAHS symptom presence or absence between the two groups.
Demographics and baseline characteristics of the study cohort are reported in Table 1.Pre-pregnancy BMI and at test were significantly higher in women with positive versus negative pulse oximetry.The pulse oximetry parameters of the two groups are shown in Table 2.In group 1, lower baseline values of SaO 2 %, average desaturation percentage, and nadir have been documented.Also, these patients presented higher ODI, SaO 2 % < 90% time, and total number of desaturation events which were characterized by a shorter duration (Table 2; Figure 1).No differences in pregnancy complications, gestational age at delivery, cesarean section, and postpartum hemorrhage rates have been documented.Similar incidences of neonatal acidosis, NICU admission, and neonatal complications were observed in the two groups.The incidence of respiratory distress syndrome was higher in group 1 (P = 0.082).Newborns of women with positive pulse oximetry showed a significantly higher rate of congenital anomalies than the others (P = 0.017) (Table 3).
Similar results regarding BMI both pre-pregnancy and at the time of testing, length of second labor stage, and presence of congenital abnormalities can be documented when comparing pregnant women who tested positive on pulse oximetry and polysomnography with those who tested negative on pulse oximetry (Table 4).Also, lower Epworth sleepiness scale values and respiratory distress syndrome (RDS) incidence have been documented.

TA B L E 1
Demographic and clinical characteristics of women with positive (group 1) or negative (group 2) pulse oximetry.Stepwise multivariate regression analysis showed that basal oxygen saturation was independently associated with FGR after correction for maternal BMI, age, gravidity, ethnicity, and hypertensive pregnancy disorders, while it was not independently associated with congenital abnormalities (Table 5).No correlations were observed for the total number of desaturation events or ODI with FGR or congenital abnormalities.In all multivariate analyses, BMI at the test significantly correlates with congenital abnormalities onset (Tables 6   and 7).

| DISCUSS ION
Our study assessed the correlation between oxygen pulse oximetry in the first trimester of pregnancy and adverse perinatal outcomes in a cohort of obese women.Interestingly, we found a higher rate of congenital abnormalities in obese patients with altered nocturnal pulse oximetry.Moreover, our findings documented the role of maternal basal oxygen saturation in predicting the occurrence of FGR.It is well known that the incidence of OSAHS in pregnancy varies according to maternal BMI, being 8.5% in normal-weight pregnant women and 62% in obese subjects, 20 thus suggesting a close link between the two conditions, probably due to an inflammatory pathway.Furthermore, it has been postulated that fat accumulation in the body's upper portion, especially around the neck, may play a crucial role in promoting OSAHS. 21Evidence from the literature documented associations between OSAHS and a wide range of pregnancy disorders, including hypertensive disorders, cesarean delivery, NICU admissions, pre-eclampsia, gestational diabetes, glomerular filtration rate, congenital anomalies, and resuscitation at birth.Therefore, OSAHS during pregnancy, regardless of whether it is a pre-existing condition or of new onset, can impair the pregnancy outcome.However, the underlying mechanisms are still not described in detail, and further molecular and pathophysiological studies are required.In addition, it would be valuable to consider this study, along with others documenting comparable results, as a way to develop innovative OSAHS screening approaches targeting obese women to reduce the risk of adverse pregnancy outcomes TA B L E 2 Pulse oximetry parameters of the two groups.F I G U R E 1 Descriptive comparison of the pulse oximetry parameters from the two groups.ODI, oxygen desaturation index.* P < 0.05; ** P < 0.001.
through dedicated treatment and follow-up protocols.The association between OSAHS in pregnancy and placental-related complications have already been documented. 22,23It has been demonstrated that OSAHS is linked to oxidative stress, systemic inflammation, and endothelial dysfunction due to chronic hypoxemia occurring during apnea episodes.Placental syndromes share similar findings, making OSAHS play a key role, along with the vascular and metabolic impairment observed in obesity, in determining the adverse outcomes described in the present study, which are consistent with those reported in the literature.
The association between high BMI levels and congenital abnormalities, likely due to fat-related metabolic abnormalities interfering with embryonic development, is another finding reported in the literature.In this picture, sleep disorders could be an additional driver besides being worsened by excessive weight.
This study provides useful hints regarding the impact of desaturation on pregnancy outcomes and OSAHS diagnosis applicable within a multidisciplinary context to develop management strategies tailored to individual obese pregnant women.These insights could be crucial for implementing preventive and therapeutic strategies, including sleep disorder screening tests, dietary and lifestyle adjustments, and the adoption of nocturnal ventilation systems such as continuous positive airways pressure.Also, it is worth clarifying that pulse oximetry should not be seen as a diagnostic substitute for polysomnography but as a first-line screening tool to identify pregnant women at higher risk of OSAHS development.Although we consider that this study has been conducted by employing reproducible criteria in terms of both patient enrollment and procedure execution, applicable at other centers, we acknowledge some limitations.7][18][19] Also, a sample size estimation for assessing congenital abnormalities has not been performed due to the consecutive patients' enrollment within a pre-determined temporal range.
In conclusion, screening questionnaires for sleep disorders are an easy-to-use and low-cost tool to identify women requiring pulse oximetry evaluation.Focusing on the obese pregnant population, those with altered nocturnal pulse oximetry in the first trimester of gestation are at higher risk of developing congenital abnormalities.Basal oxygen saturation seems to predict the occurrence of FGR independently of several confounders.Large prospective and multi-center studies are needed to confirm our findings, which may impact the obstetric management of pregnant women.
TA B L E 3 Pregnancy outcome of women with positive or negative pulse oximetry.
oximetry were analyzed through the nVISION Data Management Software from Nonin Medical Inc. to formulate oximetry reports which were analyzed at the Sleep Respiratory Disease Outpatient Clinic of the Respiratory Medicine Unit, ASST-Spedali Civili di Brescia & University of Brescia.Each report showed the following data: basal oxygen saturation, total desaturation events, number of events per hour (oxygen desaturation index [ODI]), duration of events, average desaturation, and Nadir.Patients with positive nocturnal pulse oximetry were asked to perform polysomnography.Patients with an ODI equal to or greater than 10 were considered to be at OSAHS-related risk.In addition, patients at 21 weeks (or less) of pregnancy with an ODI greater than 5 were considered worthy of further investigation.A full-night unattended respiratory polysomnography was performed for each patient with positive nocturnal pulse oximetry.A specialized polysomnography technician connected the device to the patients.The polysomnography recording montage consisted of a nasal cannula, thoracic and abdominal respiratory effort bands, body position sensor, pulse oximetry, and snore sensor.Patients were taught how to disconnect the device, which was retrieved by the same technician the following day, and keep a sleep diary.Two portable diagnostic sleep recorders were used to screen the sleep apnea: Embletta MPR from Embla Systems Inc (now Natus) and Somtè 234gm from Somtè Compumedics.Records were first analyzed through the manufacturer-dedicated software-RemLogic-E v-3.4.1 and Somtè v-2.10 for Embletta MPR and Somtè 234gm, respectively-and then manually checked by the investigator for artifact removal and final validation.The polysomnography report showed the following data: total recording time, total sleep time, Apnea-Hypopnea Index (AHI), ODI, average desaturation drop, average SpO 2 , minimum SpO 2 , and number of snoring events.Maternal comorbidities (e.g., chronic hypertension, diabetes mellitus, autoimmune disorders, thyroid and renal diseases) and pregnancy complications (e.g., hypertensive disorders of pregnancy, gestational diabetes, FGR, intrahepatic cholestasis, and preterm birth) were investigated as well as the delivery mode, postpartum complications, and perinatal outcomes (e.g., gestational age at birth, birth weight, Apgar score, umbilical artery pH, admission to the neonatal intensive care unit [NICU], respiratory distress, malformations, and infections).

TA B L E 4
(a) Demographic and clinical characteristics of women with positive polysomnography and negative pulse oximetry.(b) Pregnancy outcome of women with positive polysomnography and negative pulse oximetry.