Analysis of maternal mortality in Berlin, Germany - discrepancy between reported maternal mortality and comprehensive death certificate exploration.

OBJECTIVES: The Organisation for Economic Cooperation and Development (OECD) estimates an average maternal mortality rate (MMR) of around 3.4 maternal deaths per 100,000 live births for 2019-2021, based on relevant diagnoses on death certificates. However, Germany does not currently have a registry for recording the number of maternal deaths. The aim of this study is to identify the actual number of maternal deaths in Berlin between 2019 and 2022, as well as sources of underreporting and causes of death. METHODS: Potential maternal mortality cases were identified through a search at the Berlin Central Archive for Death Certificates, inquiring women aged 15-50 years with indications of present or recent pregnancy on the death certificate. To cross match the database, an additional search at the Charité University Hospital Berlin was carried out, checking each individual file for pregnancy-association. RESULTS: The data search resulted in 2,316 women, 18 of which presented an association to pregnancy. Of these, 12 could be classified as maternal mortality cases (MMR 7.8/100,000). The additional search in a university setting revealed two further maternal mortality cases without prior indication of pregnancy on the death certificate. This results in a total MMR of 9.1/100,000 live births, which is over double the official estimate by the OECD. CONCLUSIONS: Based on our findings in Berlin, it can be estimated that there is significant underreporting regarding maternal death cases in Germany. A more comprehensive recording system is needed to more accurately portray maternal mortality.

Spectrum of congenital anomalies of the kidney and urinary tract (CAKUT) including renal parenchymal malformations during fetal life and the implementation of prenatal exome sequencing (WES).

OBJECTIVES AND BACKGROUND: Congenital malformations of the kidney and urinary tract (CAKUT) have a prevalence of 4-60 in 10,000 livebirths and constitute for 40-50% of all end stage pediatric kidney disease. CAKUT can have a genetic background due to monogenetic inherited disease, such as PKD or ciliopathies. They can also be found in combination with extra-renal findings as part of a syndrome. Upon detection of genitourinary malformations during the fetal anomaly scan the question arises if further genetic testing is required. The purpose of this study was to determine the phenotypic presentation of CAKUT cases and the results of exome analysis (WES). METHODS: This is a retrospective analysis of 63 fetal cases with a diagnosis of CAKUT or DSD at a single center between August 2018 and December 2022. RESULTS: A total of 63 cases (5.6%) out of 1123 matched CAKUT phenotypes including renal parenchyma malformations. In 15 out of 63 WES analysis a pathogenic variant was detected (23.8%). In fetuses with isolated CAKUT the rate of detecting a pathogenic variant on exome sequencing was five out of 44 (11.4%). Ten out of 19 fetuses (52.6%) that displayed extra-renal findings in combination with CAKUT were diagnosed with a pathogenic variant. CONCLUSIONS: WES provides an increase in diagnosing pathogenic variants in cases of prenatally detected CAKUT. Especially in fetuses with extra-renal malformations, WES facilitates a gain in information on the fetal genotype to enhance prenatal counselling and management.

Advanced maternal age (AMA) and 75 g oGTT glucose levels are pedictors for insulin therapy in women with gestational diabetes (GDM).

OBJECTIVES: Gestational diabetes (GDM) is a common complication during pregnancy that is strongly associated with adverse fetal and maternal outcomes. Advanced maternal age (≥35 years) is a known risk factor for GDM. Studies advocate that GDM comprises distinctive metabolic entities, suggesting an individualized approach based on early pregnancy characteristics (such as 75 g oGTT values, maternal age, obstetric history). METHODS: The oGTT blood glucose levels of 1,664 women were categorized into isolated fasting hyperglycemia (GDM-IFH), isolated postprandial hyperglycemia (GDM-IPH) and combined hyperglycemia (GDM-CH), using the levels of the fasting, 1 h and 2 h values after glucose application. These three subtypes were analysed regarding baseline characteristics as well as fetal and maternal outcome in the context of maternal age. RESULTS: This analysis reveals that the 75 g oGTT levels and maternal age can distinguish metabolic phenotypes in women with GDM. The overall rate of insulin therapy required was higher in women from the GDM-CH group and increased with maternal age (31.7 %, 38.2 %, <35 years, ≥35-39 years respectively, vs. total insulin rate 22.3 %, p-value <0.001). Women ≥35 years displayed a significantly higher caesarean delivery (CD) rate (<35 years 34.6 %, 38.4 %, 41.1 % vs. ≥35 years 54.8 %, 47.6 %, 46.5 %, GDM-IFH, GDM-IPH, GDM-CH respectively, p-value <0.001). CONCLUSIONS: Women with fasting hyperglycemia, especially those with combined hyperglycemia and advanced maternal age (AMA) display a higher risk for unfavorable perinatal outcome. A categorization based on oGTT values and maternal age, as well as other characteristics can facilitate a basis for clinical risk stratification. Women at risk should receive an individualized and intensified perinatal care as well as interventional therapies.

Glucose Levels of the Oral Glucose Tolerance Test (oGTT) Can Predict Adverse Pregnancy Outcomes in Women with Gestational Diabetes (GDM).

OBJECTIVES AND BACKGROUND: Gestational diabetes (GDM) is a common pregnancy complication defined as a glucose intolerance diagnosis during pregnancy. GDM is strongly associated with adverse fetal and maternal outcomes. In Germany, to screen and diagnose GDM we use a 1 h 50 g oGCT (oral glucose challenge test) followed by a 2 h 75 g oGTT if the first was pathological. This analysis examines the correlation of 75 g oGTT glucose levels and fetomaternal outcome. METHODS: Data from 1664 patients from a gestational diabetes consultation clinic at the Charité University Hospital in Berlin, Germany, were analyzed retrospectively from 2015 to 2022. The 75 g oGTT blood glucose levels were categorized into isolated fasting hyperglycemia (GDM-IFH), isolated post-load hyperglycemia (GDM-IPH) and combined hyperglycemia (GDM-CH), using the levels of the fasting, 1 h and 2 h values, after glucose application. These subtypes were compared based on their baseline characteristics as well as fetal and maternal outcome. RESULTS: GDM-IFH and GDM-CH women displayed higher pre-conceptional BMI and required insulin therapy more frequently (p < 0.001). The GDM-IFH group was at higher risk of having a primary cesarean section (p = 0.047), while GDM-IPH women were significantly more likely to have an emergent cesarean section (p = 0.013). The offspring of GDM-IFH and GDM-CH women were born with a significantly higher mean birthweight (p < 0.001) and birth weight percentiles (p < 0.001) and were at increased risk of being large for gestational age (LGA) (p = 0.004). Women from the GDM-IPH group delivered significantly more neonates who were small for gestational age (p = 0.027) or with low fetal weight <30th percentile (p = 0.003). CONCLUSION: This analysis shows a strong association between the glucose response pattern in the 75 g oGTT and adverse perinatal fetomaternal outcome. The differences among the subgroups, specifically concerning insulin therapy, mode of delivery and fetal growth, suggest an individualized approach to prenatal care after a GDM diagnosis.

Cervical ripening as an outpatient procedure in the pandemic - minimizing the inpatient days and lowering the socioeconomic costs.

OBJECTIVES: With an increasing incidence of labor induction the socioeconomic costs are increasing and the burden on hospital capacities is rising. In addition, the worldwide SARS-CoV-2 pandemic asks for improvements in patient care during pregnancy and delivery while decreasing the patient-staff contact. Here, we are retrospectively analyzing and comparing a mechanical ripening device that is utilized as an outpatient procedure to misoprostol and dinoprostone as inpatient induction methods in a low risk cohort. METHODS: This is a retrospective comparative analysis of obstetric data on patients who presented for cervical ripening and labor induction. Ninety-six patients received a mechanical ripening agent as an outpatient procedure. As a control group, we used 99 patients with oral misoprostol (PGE1) and 42 patients with vaginal dinoprostone (PGE2) for cervical ripening in an inpatient setting. Data from 2016 until 2020 were analysed. RESULTS: Baseline characteristics showed no significant differences. Delivery modes were similar in all groups. The time period from patient admission to onset of labor was significantly shorter in the outpatient group (p<0.001): 10.9 h/0.5 days (±13.6/0.6) for osmotic dilator vs. 17.9 h/0.7 days (±13.1/0.5) for oral misoprostol vs. 21.8 h/0.8 days (±15.9/0.7) for vaginal dinoprostone. With 20.4 h/0.8 days (±14.3/0.6) the osmotic dilator group displayed significantly the shortest inpatient stay from admission to delivery (p=0.027). The patient subgroup of misoprostol had 25.7 h/1.1 days (±14.9/0.6) of inpatient stay from admission to delivery and the patient group of dinoprostone 27.5 h/1.1 days (±16.0/0.7). There were fewer hospital days in the outpatient group: 84.9 h/3.5 days vs. 88.9 h/3.7 days vs. 93.6 h/3.9 days (outpatient osmotic dilator vs. inpatient misoprostol and dinoprostone, respectively). CONCLUSIONS: New approaches are required to decrease individual contacts between patients and staff while maintaining a high quality patient care in obstetrics. This analysis reveals that outpatient mechanical cervical ripening can be as safe and effective as inpatient cervical ripening with PGE1/PGE2, while lowering patient-staff contact and total hospital stays and therefore decreasing the socioeconomic costs.

Cervical ripening after cesarean section: a prospective dual center study comparing a mechanical osmotic dilator vs. prostaglandin E2.

OBJECTIVES: Worldwide, the overall cesarean section is rising. Trial of labor after cesarean (TOLAC) is an overall safe option with an immediate impact on neonatal and maternal short- and long-term health. Since the use of prostaglandins in cervical ripening is associated with an increased risk of uterine rupture, mechanical methods as balloon catheters or osmotic dilators have been suggested for cervical ripening prior to induction of labour. Here we are analyzing and comparing the VBAC rate, as well as maternal and fetal outcome in cervical ripening prior to TOLAC. METHODS: This prospective dual center study analyses maternal and neonatal outcomes of TOLAC in women with an unfavorable cervix requiring cervical ripening agent. The prospective application of an osmotic dilator (Dilapan-S, n=104) was analysed in comparison to the retrospective application of off-label dinoprostone (n=102). RESULTS: The overall fetal and neonatal outcome revealed no significant differences in both groups. Patients receiving cervical ripening with the osmotic dilator delivered vaginally/by ventouse in 52% of cases, compared to 53% when using dinoprostone (p=0.603). The interval between application to onset of labor was significantly higher in the osmotic dilator group (37.9 vs.20.7 h, p=<0.001). However, time from onset of labor to delivery was similar in both groups (7.93 vs. 7.44 h, p=0.758). There was one case of uterine rupture in the dinoprostone group. CONCLUSIONS: Our data shows that the application of the osmotic dilator leads to similar outcomes in VBAC rate and time from onset of labor to delivery as well as safety in both groups compared to off-label use dinoprostone. Cervical ripening using the mechanical dilator is a viable and effective option, without the risk of uterine hyperstimulation.