Altitude Modifies the Effect of Parity on Birth Weight/Length Ratio: A Study Comprising 2,057,702 Newborns between 1984 and 2020 in Austria.

(1) Background: Lower birth weight among newborns in higher altitudes has been well documented in previous literature. Several possible causes for this phenomenon have been investigated, including biophysiological adaptation, epigenetic or genetic mechanisms or lifestyle changes. This is the first study to show the effect modification of altitude and parity on the birth weight length ratio (BWLR) in women resident in moderate altitudes compared to a low sea level.; (2) Methods: This population-based study obtained data on altitude (0-300, 300-500, 500-700,700-900, >900 m), parity (1, 2, …, 7, 8/9), birth weight and length on all births in Austria between 1984 and 2020 from birth certificates provided by Statistics Austria. The BWLR was calculated, and the effect of moderate altitude and parity was estimated using multivariable linear mixed models adjusting for predefined variables. Sub-group regression analyses were conducted by altitude group. (3) Results: Data on 2,057,702 newborns from 1,280,272 mothers were analyzed. The effect of parity on BWLR, as indicated by the difference of BWLR between the first- and second-born infants, ranged between 1.87 to 2.09 g per centimeter across all altitude groups. Our analyses found that the effect of parity on BWLR diminished from parity three onwards at altitude 0-300, whilst the effect of parity on BWLR continued to increase at higher than 300 m and was most notable in the highest altitude group >900 m. (4) Conclusions: Findings from our study indicated that the negative effect of increasing altitude on BWLR was deprived for newborns of higher parity. It shows that the residential altitude can modify the effect of parity on BWLR.

Universal gestational diabetes screening and antepartum stillbirth rates in Austria-A population-based study.

INTRODUCTION: Occult or untreated gestational diabetes (GDM) is a well-known risk factor for adverse perinatal outcomes and may contribute to antepartum stillbirth. We assessed the impact of screening for GDM on the rate of antepartum stillbirths in non-anomalous pregnancies by conducting a population-based study in 974 889 women in Austria. MATERIAL AND METHODS: Our database was derived from the Austrian Birth Registry. Inclusion criteria were singleton live births and antepartum stillbirths ≥24+0 gestational weeks, excluding fetal congenital malformations, terminations of pregnancy and women with pre-existing type 1 or 2 diabetes. Main outcome measures were (a) overall stillbirth rates and (b) stillbirth rates in women at high risk of GDM (i.e., women with a body mass index ≥30 kg/m2 , history of previous intrauterine fetal death, GDM, previous macrosomic offspring) before (2008-2010, "phase I") and after (2011-2019, "phase II") the national implementation of universal GDM screening with a 75 g oral glucose tolerance test in Austrian pregnant women by 2011. RESULTS: In total, 940 373 pregnancies were included between 2008 and 2019, of which 2579 resulted in intrauterine fetal deaths at 33.51 ± 5.10 gestational weeks. After implementation of the GDM screening, a statistically significant reduction in antepartum stillbirth rates among non-anomalous singletons was observed only in women at high risk for GDM (4.10‰ [95% confidence interval (CI) 3.09-5.43] in phase I vs. 2.96‰ [95% CI 2.57-3.41] in phase II; p = 0.043) but not in the general population (2.76‰ [95% CI 2.55-2.99] in phase I vs. 2.74‰ [95% CI 2.62-2.86] in phase II; p = 0.845). The number needed to screen with the oral glucose tolerance test to subsequently prevent one case of (non-anomalous) intrauterine fetal death was 880 in the high-risk and 40 000 in the general population. CONCLUSIONS: The implementation of a universal GDM screening program in Austria in 2011 has not led to any significant reduction in antenatal stillbirths among non-anomalous singletons in the general population. More international data are needed to strengthen our findings.

Predicting singleton antepartum stillbirth by the demographic Fetal Medicine Foundation Risk Calculator-A retrospective case-control study.

OBJECTIVE: To assess the risk of singleton intrauterine fetal death (IUFD) in women by the demographic setting of the online Fetal Medicine Foundation (FMF) Stillbirth Risk Calculator. METHODS: Retrospective single-centre case-control study involving 144 women having suffered IUFD and 247 women after delivery of a live-born singleton. Nonparametric receiver operating characteristics (ROC) analyses were performed to predict the prognostic power of the FMF Stillbirth risk score and to generate a cut-off value to discriminate best between the event of IUFD versus live birth. RESULTS: Women in the IUFD cohort born a significantly higher overall risk with a median FMF risk score of 0.45% (IQR 0.23-0.99) compared to controls [0.23% (IQR 0.21-0.29); p<0.001]. Demographic factors contributing to an increased risk of IUFD in our cohort were maternal obesity (p = 0.002), smoking (p<0.001), chronic hypertension (p = 0.015), antiphospholipid syndrome (p = 0.017), type 2 diabetes (p<0.001), and insulin requirement (p<0.001). ROC analyses showed an area under the curve (AUC) of 0.72 (95% CI 0.67-0.78; p<0.001) for predicting overall IUFD and an AUC of 0.72 (95% CI 0.64-0.80; p<0.001), respectively, for predicting IUFD excluding congenital malformations. The FMF risk score at a cut-off of 0.34% (OR 6.22; 95% CI 3.91-9.89; p<0.001) yielded an 82% specificity and 58% sensitivity in predicting IUFD with a positive and negative predictive value of 0.94% and 99.84%, respectively. CONCLUSION: The FMF Stillbirth Risk Calculator based upon maternal demographic and obstetric characteristics only may help identify women at low risk of antepartum stillbirth.

Antepartum stillbirth rates during the COVID-19 pandemic in Austria: A population-based study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 has had dramatic effects on the pregnant population worldwide, increasing the risk of adverse perinatal outcomes. OBJECTIVE: To assess the incidence of antepartum stillbirth (aSB) during the COVID-19 pandemic in Austria. METHODS: We collected epidemiological data from the Austrian Birth Registry and compared the rate of aSB (i.e., fetal death at or after 24+0 gestational weeks) during the pandemic period (March-December 2020) and in the respective pre-pandemic months (2015-2019). RESULTS: In total, 65 660 pregnancies were included, of which 171 resulted in aSB at 33.7 ± 4.8 gestational weeks. During the pandemic, the aSB rate increased from 2.49‰ to 2.60‰ (P = 0.601), in contrast to the significant decline in preterm deliveries at or before 37 gestational weeks from 0.61‰ to 0.56‰ (relative risk [RR] 0.93; 95% confidence interval [CI] 0.91-0.96; P < 0.001). During the first lockdown, the aSB rate significantly increased from 2.38‰ to 3.52‰ (P = 0.021), yielding an adjusted odds ratio of 1.57 (95% CI 1.08-2.27; P = 0.018). The event of aSB during the COVID-19 pandemic was strongly related with increased fetal weight and maternal obesity. CONCLUSION: In Austria, there has been an overall increase in the incidence of aSB during the pandemic with a significant peak during the first lockdown.

Exposure to night-time light pollution and risk of prolonged duration of labor: A nationwide cohort study.

BACKGROUND: Light pollution (LP) is a ubiquitous environmental agent that affects more than 80% of the world's population. This large nationwide cohort study evaluates whether exposure to LP can influence obstetric outcomes. METHODS: We analyzed Austrian birth registry data on 717 113 cases between 2008 and 2016 and excluded cases involving day-time delivery, <23 + 0 gestational weeks, and/or birthweight <500 g, induction of labor, elective cesarean, or cases with missing data. The independent variable, that is, degree of night-time LP, was categorized as low (0.174 to <0.688 mcd/m2 ), medium (0.688 to <3 mcd/m2 ), or high (3 to <10 mcd/m2 ). Duration of labor and adverse neonatal outcomes served as outcome measures. RESULTS: Cases in regions with high LP (odds ratio [OR], 1.43; 95% confidence interval [CI], 1.30-1.57) and medium LP (OR, 1.22; 95% CI, 1.14-1.31) showed increased odds of prolonged labor (P < .0001 each). Newborns born in regions with high LP (OR, 1.12; 95% CI, 1.07-1.16) and medium LP (OR, 1.07; 95% CI, 1.04-1.10) showed increased odds of experiencing adverse outcomes (P < .0001 each). Preterm delivery <28 + 0 weeks was also associated with the degree of LP (P = .04). CONCLUSIONS: Night-time LP negatively interferes with obstetric outcomes. The perceived influence of LP as an environmental agent needs to be re-evaluated to minimize associated health risks.

Institutional guidelines on maternal care and investigations following antepartum stillbirth - a national survey.

BACKGROUND: Antepartum stillbirth, i.e., intrauterine fetal death (IUFD) above 24 weeks of gestation, occurs with a prevalence of 2.4-3.1 per 1000 live births in Central Europe. In order to ensure highest standards of treatment and identify causative and associated (risk) factors for fetal death, evidence-based guidelines on clinical practice in such events are recommended. Owing to a lack of a national guideline on maternal care and investigations following stillbirth, we, hereby, sought to assess the use of institutional guidelines and clinical practice after IUFD in Austrian maternity units. METHODS: A national survey with a paper-based 12-item questionnaire covering demographic variables, local facilities and practice, obstetrical care and routine post-mortem work-up following IUFD was performed among all Austrian secondary and tertiary referral hospitals with maternity units (n = 75) between January and July 2019. Statistical tests were conducted using Chi2 and Fisher's Exact test, respectively. Univariate logistic regression analyses were performed to calculate odds ratio (OR) with a 95% confidence interval (CI). RESULTS: 46 (61.3%) obstetrical departments [37 (80.4%) secondary; 9 (19.6%) tertiary referral hospitals] participated in this survey, of which 17 (37.0%) have implemented an institutional guideline. The three most common investigations always conducted following stillbirth are placental histology (20.9%), fetal autopsy (13.1%) and maternal antibody screen (11.5%). Availability of an institutional guideline was not significantly associated with type of hospital, on-site pathology department, or institutional annual live and stillbirth rates. Post-mortem consultations only in cases of abnormal investigations following stillbirth were associated with lower odds for presence of such guideline [OR 0.133 (95% CI 0.018-0.978); p = 0.047]. 26 (56.5%) departments consider a national guideline necessary. CONCLUSIONS: Less than half of the surveyed maternity units have implemented an institutional guideline on maternal care and investigations following antepartum stillbirth, independent of annual live and stillbirth rate or type of referral centre.

Cardio-pathogenic variants in unexplained intrauterine fetal death: a retrospective pilot study.

To describe the prevalence and spectrum of cardio-pathogenic variants in singleton fetuses after unexplained intrauterine fetal death (IUFD). DNA from post-mortem fibroblastic tissue samples of 16 fetuses after unexplained IUFD was retrieved at two tertiary university hospitals for clinical exome sequencing with subsequent filtering of 122 cardio-specific genes to elucidate underlying cardio-pathogenic variants. In total, we included 12 (75%) male and four (25%) female fetuses who were stillborn at a median gestational age of 34+6 (23+2-40+5) weeks. In two (12.5%) fetuses no cardio-pathogenic variants were found. In 14 (87.5%) fetuses, overall 33 variants were detected in 22 cardio-specific genes, involving 14 (63.63%) genes associated with cardiomyopathy, six (27.27%) arrhythmogenic susceptibility genes and two (9.09%) arrhythmia and cardiomyopathy associated genes. Among the 33 variants, five (15.2%) were classified as likely benign according to the American College of Medical Genetics and Genomics; 28 (84.8%) variants were considered as variants of uncertain significance. Compared to a cohort of explained IUFDs, the cases with and without fetal variants in cardiac genes differed not significantly regarding maternal age, previous history of stillbirth, time of stillbirth or fetal sex. Unexplained stillbirth may be caused by cardio-genetic pathologies, yet a high number of variants of uncertain significance merit a more detailed post-mortem examination including family segregation analysis.

Diagnostic quality of 3Tesla postmortem magnetic resonance imaging in fetuses with and without congenital heart disease.

BACKGROUND: Postmortem confirmation of prenatally diagnosed congenital heart disease after termination of pregnancy and evaluation of potential cardiac defects after spontaneous fetal or neonatal death are essential. Conventional autopsy rates are decreasing, and 1.5Tesla magnetic resonance imaging has demonstrated limited diagnostic accuracy for postmortem cardiovascular assessment. OBJECTIVE: This study aimed to evaluate the feasibility and image quality of cardiac 3Tesla postmortem magnetic resonance imaging and to assess its diagnostic accuracy in detecting fetal heart defects compared with conventional autopsy. Secondarily, the study aimed to explore whether clinical factors affect the quality of 3Tesla postmortem magnetic resonance imaging. STUDY DESIGN: A total of 222 consecutive fetuses between 12 and 41 weeks' gestation, who underwent 3Tesla postmortem magnetic resonance imaging and conventional autopsy after spontaneous death or termination of pregnancy for fetal malformations, were included. First, 3Tesla postmortem magnetic resonance imaging of each fetus was rated as diagnostic or nondiagnostic for fetal cardiac assessment by 2 independent raters. The image quality of individual cardiac structures was then further evaluated by visual grading analysis. Finally, the presence or absence of a congenital heart defect was assessed by 2 radiologists and compared with autopsy results. RESULTS: Overall, 87.8% of 3Tesla postmortem magnetic resonance imaging examinations were rated as diagnostic for the fetal heart. Diagnostic imaging rates of individual cardiac structures at 3Tesla postmortem magnetic resonance imaging ranged from 85.1% (atrioventricular valves) to 94.6% (pericardium), with an interrater agreement of 0.82 (0.78-0.86). Diagnostic imaging of the fetal aortic arch and the systemic veins at 3Tesla postmortem magnetic resonance imaging was possible from 12+5 weeks' gestation onward in 90.1% and 92.3% of cases, respectively. A total of 55 fetuses (24.8%) had at least 1 cardiac anomaly according to autopsy, 164 (73.9%) had a normal heart, and in 3 fetuses (1.4%), autopsy was nondiagnostic for the heart. Considering all examinations rated as diagnostic, 3Tesla postmortem magnetic resonance imaging provided high diagnostic accuracy for the detection of fetal congenital heart defects with a sensitivity of 87.8%, a specificity of 97.9%, and concordance with autopsy of 95.3%. 3Tesla postmortem magnetic resonance imaging was less accurate in young fetuses (<20 weeks compared with ≥20 weeks; P<.001), in fetuses with low birthweight (≤100 g compared with >100 g; P<.001), in cases after spontaneous fetal death (compared with other modes of death; P=.012), in cases with increasing latency between death and 3Tesla postmortem magnetic resonance imaging (P<.001), and in cases in which there was a high degree of maceration (maceration score of 3 compared with a score from 0 to 2; P=.004). CONCLUSION: Diagnostic 3Tesla postmortem magnetic resonance imaging assessment of the fetal heart is feasible in most fetuses from 12 weeks' gestation onward. In diagnostic images, sensitivity and, particularly, specificity in the detection of congenital heart disease are high compared with conventional autopsy. Owing to its high diagnostic accuracy, we suggest that 3Tesla postmortem magnetic resonance imaging may serve as a suitable imaging modality with which to direct a targeted conventional autopsy when pathology resources are limited or to provide a virtual autopsy when full autopsy is declined by the parents.

Working-hour phenomenon in obstetrics is an attainable target to improve neonatal outcomes.

BACKGROUND: Giving birth in a health care facility does not guarantee high-quality care or favorable outcomes. The working-hour phenomenon describes adverse outcomes of institutional births outside regular working hours. OBJECTIVES: The objectives of the study were to evaluate whether the time of birth is associated with adverse neonatal outcomes and to identify the riskiest time periods for obstetrical care. STUDY DESIGN: This nationwide retrospective cohort study analyzed data from 2008 to 2016 from all 82 obstetric departments in Austria. Births at ≥ 23+0 gestational weeks with ≥500 g birthweight were included. Independent variables were categorized by the time of day vs night as core time (morning, day) and off hours (evening, nighttime periods 1-4). The composite primary outcome was adverse neonatal outcome, defined as arterial umbilical cord blood pH <7.2, 5 minute Apgar score <7, and/or admission to the neonatal intensive care unit. Multivariate logistic regression was used to develop a model to predict these adverse neonatal outcomes. RESULTS: Of 462,947 births, 227,672 (49.2%) occurred during off hours and had a comparable distribution in all maternity units, regardless of volume (<500 births per year: 50.3% during core time vs 49.7% during off hours; ≥500 births per year: 50.7% core time vs 49.3% off hours; perinatal tertiary center: 51.2% core time vs 48.8% off hours). Furthermore, most women (35.8-35.9%) gave birth between 2:00 and 5:59 am (night periods 3 and 4). After adjustment for covariates, we found that adverse neonatal outcomes also occurred more frequently during these night periods 3 and 4, in addition to the early morning period (night 3: odds ratio, 1.05; 95% confidence interval, 1.03-1.08; P < .001; night 4: odds ratio, 1.08; 95% confidence interval, 1.05-1.10; P < .001; early morning period: odds ratio, 1.05; 95% confidence interval, 1.02-1.08; P < .001). The adjusted odds for adverse outcomes were lowest for births between 6:00 and 7:59 pm (odds ratio, 0.96; 95% confidence interval, 0.93-0.99; P = .006). CONCLUSION: There is an increased risk of adverse neonatal outcomes when giving birth between 2:00 and 7:59 am. The so-called working-hour phenomenon is an attainable target to improve neonatal outcomes. Health care providers should ensure an optimal organizational framework during this time period.

Impact of fetal maceration grade on risk of maternal disseminated intravascular coagulation after intrauterine fetal death - A retrospective cohort study.

Disseminated intravascular coagulation (DIC) is a life-threatening event that is the endpoint of a pathologically activated cascade leading to excessive consumption of platelets culminating in bleeding. Several diseases are known to be associated with DIC, some of which may also occur during pregnancy or the puerperium. One of the potential risk factors that have been considered as a potential trigger for DIC is the retention of a highly macerated fetus after intrauterine fetal death (IUFD). However, sparse evidence exists on its clinical implication on hemostasis parameters. In this retrospective single-center study, we investigated the role of fetal maceration grades 0-III on the risk of DIC in 91 women following IUFD between gestational weeks (+days) 22 + 0 and 41 + 6 between 2003 and 2017. We calculated the Erez DIC-score after consideration of maternal platelet count (PC), prothrombin time (PT) and fibrinogen (Fib) and correlated the findings with fetal maceration grade. Mean (±SD) age of women was 32.1 ± 6.7 years. Neither maternal hemostasis parameters (PC, PT, Fib), nor the Erez score showed a statistically significant difference between maceration grades 0-III with median values of 1 for all four grades (maceration grade I: range 0 to 27; I: 0 to 51; II: 0 to 52; III: 0 to 39). We therefore conclude, that the pathophysiology of DIC in women after singleton IUFD is unrelated to the degree of fetal maceration.

Men's sexual response to female partner's intranasal oxytocin administration for hypoactive sexual desire disorder: an open prospective cohort study.

OBJECTIVE: To study sexual function, quality of life, and depression in men, whose female partners are undergoing double-blind placebo-controlled randomized treatment for hypoactive sexual desire disorder (HSDD). DESIGN: Open prospective cohort study of 22 weeks. SETTING: Academic medical center. PATIENT(S): Male partners of 30 premenopausal and postmenopausal women with HSDD. INTERVENTION(S): Baseline, 3-month, and 5-month assessment (for 8 weeks each) of male response to female partner's use of oxytocin nasal spray (32 IE) and placebo within 50 minutes before sexual intercourse. MAIN OUTCOME MEASURE(S): Primary outcome parameters were Sexual Life Quality Questionnaire-Male, Sexual Activity Record, Partner Performance Questionnaire, and Hamilton Depression Scale. RESULT(S): Male Sexual Life Quality questionnaire improved significantly from -7.4 ± 9.9 at baseline to 8.2 ± 12 with female partners' treatment with oxytocin nasal spray and to 10.8 ± 13.8 with placebo. Frequency of intercourse improved slightly but not significantly from 6.3 ± 3.9 at baseline to 7.3 ± 4 with female oxytocin therapy, but not with placebo. Male desire and arousal remained stable throughout the study period. Evaluation of female partners' performance by men improved significantly from 8.9 ± 2.8 at baseline to 10.6 ± 2.2 with oxytocin and to 11.2 ± 2.6 with placebo. CONCLUSION(S): Female treatment with either oxytocin or placebo for HSDD significantly improves male sexual quality of life and evaluation of female partner's sexual performance with no difference between oxytocin and placebo on any outcome parameters. A nonsignificant improvement was seen in the frequency of intercourse, male arousal, desire, satisfaction, and Hamilton depression scale. CLINICAL TRIAL REGISTRATION NUMBER: NCT02229721.

Brainstem Tuberculoma in Pregnancy.

We report a case of a Somali refugee who presented in the second trimester of her first pregnancy with a four-week history of gradual right-sided sensomotoric hemisyndrome including facial palsy and left-sided paresis of the oculomotorius nerve causing drooping of the left eyelid and double vision. Cranial magnetic resonance imaging revealed a solitary brainstem lesion. Upon detection of hilar lymphadenopathy on chest X-ray (CXR), the diagnosis of disseminated tuberculosis with involvement of the central nervous system was confirmed by PCR and treatment induced with rifampicin, isoniazid, pyrazinamide, and ethambutol. The patient had a steady neurological improvement and a favorable pregnancy outcome.

Effect of long-term intranasal oxytocin on sexual dysfunction in premenopausal and postmenopausal women: a randomized trial.

OBJECTIVE: To assess the effect of on-demand intranasal oxytocin administration on female sexual function and activity. DESIGN: Randomized, prospective, double-blind, placebo-controlled, crossover trial with duration of 22 weeks. SETTING: Academic medical center. PATIENT(S): Thirty pre-and postmenopausal women with sexual dysfunction. INTERVENTION(S): Over 8 weeks, intranasal oxytocin (32 IU) or placebo self-administered by women within 50 minutes before sexual intercourse; after a washout period of 2 weeks, crossover with patients switched to the alternate group for another 8 weeks. MAIN OUTCOME MEASURE(S): Primary outcome parameter: Female Sexual Function Index (FSFI); secondary outcome parameters: Female Sexual Distress Scale (FSDS), Sexual Quality of Life-Female (SQOL-F), Sexual Interest and Desire Inventory-Female (SIDI-F), and Hamilton depression scale (HDS). RESULT(S): After oxytocin and placebo, the FSFI score increased by 26% and 31%, SQOL-F score by 144% and 125%, and SIDI-F score by 29% and 23%, respectively (repeated measures analysis of variance between groups). After oxytocin and placebo, the FSDS score decreased by 36% and 45%, respectively (repeated measures analysis of variance between groups). There was no statistically significant treatment, sequence (placebo first/second), or interaction effect. CONCLUSION(S): Long-term intranasal oxytocin and placebo administration both improved sexual function and symptoms of depression in women over time with no treatment, sequence (placebo first/second), or interaction effect. CLINICAL TRIAL REGISTRATION NUMBER: NCT02229721.

Severe pelvic abscess formation following caesarean section.

We report a case of a 24-year-old woman with severe pelvic abscess formation 2 weeks after secondary caesarean section. The isolated pathogens were a mixture of Gardnerella vaginalis, Mycoplasma hominis and Ureaplasma urealyticum. After initial resistance to systemic antibiotic treatment, she underwent radiologically-guided drainage of the abscesses, whereon she had a continuous recovery.