Rare Variants in BNC2 Are Implicated in Autosomal-Dominant Congenital Lower Urinary-Tract Obstruction.

Congenital lower urinary-tract obstruction (LUTO) is caused by anatomical blockage of the bladder outflow tract or by functional impairment of urinary voiding. About three out of 10,000 pregnancies are affected. Although several monogenic causes of functional obstruction have been defined, it is unknown whether congenital LUTO caused by anatomical blockage has a monogenic cause. Exome sequencing in a family with four affected individuals with anatomical blockage of the urethra identified a rare nonsense variant (c.2557C>T [p.Arg853∗]) in BNC2, encoding basonuclin 2, tracking with LUTO over three generations. Re-sequencing BNC2 in 697 individuals with LUTO revealed three further independent missense variants in three unrelated families. In human and mouse embryogenesis, basonuclin 2 was detected in lower urinary-tract rudiments. In zebrafish embryos, bnc2 was expressed in the pronephric duct and cloaca, analogs of the mammalian lower urinary tract. Experimental knockdown of Bnc2 in zebrafish caused pronephric-outlet obstruction and cloacal dilatation, phenocopying human congenital LUTO. Collectively, these results support the conclusion that variants in BNC2 are strongly implicated in LUTO etiology as a result of anatomical blockage.

Why are women deciding against birth in alongside midwifery units? A prospective single-center study from Germany.

OBJECTIVES: For healthy women entering labor after an uneventful pregnancy, advantages of birth in midwife-led models of care have been demonstrated. We aimed to study the level of awareness regarding care in alongside midwifery units (AMU), factors involved in the decision for birth in obstetrician-led units (OLU), and wishes for care and concerns about birth in women registering for birth in OLU who would have been eligible for care in AMU. METHODS: Healthy women with a term singleton cephalic fetus after an uneventful pregnancy course booking for birth in OLU were prospectively recruited. Data were collected by questionnaire. RESULTS: In total, 324 questionnaires were analyzed. One quarter (23.1%) of participants never had heard of care in AMU. Two thirds (64.2%) of women had made their choice regarding model of care before entering late pregnancy; only 16.4% indicated that health professionals had the biggest impact on their decision. One-to-one care and the availability of a pediatrician were most commonly quoted wishes (30.8 and 34.0%, respectively), and the occurrence of an adverse maternal or perinatal event the greatest concern (69.5%). CONCLUSIONS: Although the majority of respondents had some knowledge about care in AMU, expressed wishes for birth matching core features of AMU and concerns matching those of OLU, a decision for birth in OLU was taken. This finding may be a result of lack of knowledge about details of care in AMU; additionally, wishes and concerns may be put aside in favor of other criteria.

[HIV Test in Pregnancy - 100% Not Reached in 2020]. / HIV-Test in der Schwangerschaft ­ 2020 noch nicht bei 100.

INTRODUCTION: In 2019 38 million people were living with HIV worldwide, more than half of them girls and women. Knowledge about maternal HIV status enables HIV transmission prophylaxis, reducing mother-to-child transmission<1%. We aimed to investigate the implementation of the mandatory documentation of counseling and optional HIV testing in the maternity records as recommended in the German maternity guidelines. METHODS: In the Obstetric Department of the University Hospital Bonn, maternity records were reviewed from June to October 2020, and pregnant women were interviewed regarding the patients' recall of counseling and HIV testing as well as their attitude towards a universal screening strategy using an anonymous questionnaire. RESULTS: Documentation was incomplete in 11% of maternal records: in 8% there was neither documentation of counseling nor of HIV testing, in 3% documentation of counseling only. In 291 questionnaires 47% of pregnant women could not recall counselling. 90% of pregnant women were in favor of universal HIV testing in pregnancy, 9% were undecided, and 1% opposed it. 55% would support change from an "opt-in" to an "opt-out" screening policy in pregnancy. SUMMARY: Documentation of counseling and HIV testing was incomplete in 11% of cases, and nearly half of the women could not recall counselling. New strategies from midwives and obstetricians need to be developed to achieve universal HIV testing in pregnant women leading to zero HIV mother-to-child transmissions.

Model of care and chance of spontaneous vaginal birth: a prospective, multicenter matched-pair analysis from North Rhine-Westphalia.

BACKGROUND: Advantages of midwife-led models of care have been reported; these include a higher vaginal birth rate and less interventions. In Germany, 98.4% of women are giving birth in obstetrician-led units. We compared the outcome of birth planned in alongside midwifery units (AMU) with a matched group of low-risk women who gave birth in obstetrician-led units. METHODS: A prospective, controlled, multicenter study was conducted. Six of seven AMUs in North Rhine-Westphalia participated. Healthy women with a singleton term cephalic pregnancy booking for birth in AMU were eligible. For each woman in the study group a control was chosen who would have been eligible for birth in AMU but was booking for obstetrician-led care; matching for parity was performed. Mode of birth was chosen as primary outcome parameter. Secondary endpoints included a composite outcome of adverse outcome in the third stage and / or postpartum hemorrhage; higher-order obstetric lacerations; and for the neonate, a composite outcome (5-min Apgar < 7 and / or umbilical cord arterial pH < 7.10 and / or transfer to specialist neonatal care). Statistical analysis was by intention to treat. A non-inferiority analysis was performed. RESULTS: Five hundred eighty-nine case-control pairs were recruited, final analysis was performed with 391 case-control pairs. Nulliparous women constituted 56.0% of cases. For the primary endpoint vaginal birth superiority was established for the study group (5.66%, 95%-CI 0.42% - 10.88%). For the composite newborn outcome (1.28%, 95%-CI -1.86% - -4.47%) and for higher-order obstetric lacerations (2.33%, 95%-CI -0.45% - 5.37%) non-inferiority was established. Non-inferiority was not present for the composite maternal outcome (-1.56%, 95%-CI -6.69% - 3.57%). The epidural anesthesia rate was lower (22.9% vs. 41.1%), and the length of hospital stay was shorter in the study group (p < 0.001 for both). Transfer to obstetrician-led care occurred in 51.2% of cases, with a strong association to parity (p < 0.001). Request for regional anesthesia was the most common cause for transfer (47.1%). CONCLUSION: Our comparison between care in AMU and obstetrician-led care with respect to mode of birth and other outcomes confirmed the superiority of this model of care for low-risk women. This pertains to AMU where admission and transfer criteria are in place and adhered to.

Analysis of cesarean section rates in two German hospitals applying the 10-Group Classification System.

OBJECTIVES: In Germany, cesarean section (CS) rates more than doubled within the past two decades. For analysis, auditing and inter-hospital comparison, the 10-Group Classification System (TGCS) is recommended. We used the TGCS to analyze CS rates in two German hospitals of different levels of care. METHODS: From October 2017 to September 2018, data were prospectively collected. Unit A is a level three university hospital, unit B a level one district hospital. The German birth registry was used for comparison with national data. We performed two-sample Z tests and bootstrapping to compare aggregated (unit A + B) with national data and unit A with unit B. RESULTS: In both datasets (national data and aggregated data unit A + B), Robson group (RG) 5 was the largest contributor to the overall CS rate. Compared to national data, group sizes in RG 1 and 3 were significantly smaller in the units under investigation, RG 8 and 10 significantly larger. Total CS rates between the two units differed (40.7 vs. 28.4%, p<0.001). The CS rate in RG 5 and RG 10 was different (p<0.01 for both). The most relative frequent RG in both units consisted of group 5, followed by group 10 and 2a. CONCLUSIONS: The analysis allowed us to explain different CS rates with differences in the study population and with differences in the clinical practice. These results serve as a starting point for audits, inter-hospital comparisons and for interventions aiming to reduce CS rates.

Testosterone serum levels are not predictive of maternal virilization in hyperreactio luteinalis.

BACKGROUND: Elevated concentrations of circulating testosterone are present in hyperreactio luteinalis (HL), a pregnancy-specific, self-limited condition. HL is associated with maternal virilization in about 30% of cases. The correlation between testosterone levels and maternal virilization has not yet been quantified. Our aim was to identify a testosterone cut-off level which may allow to predict maternal virilization. METHODS: A literature research was performed. Publications were chosen if serum testosterone concentrations and presence or absence of maternal virilization was mentioned. Additionally, we report serial levels of steroids analyzed by Liquid chromatography-tandem mass spectrometry (LC-MS/MS) in one case of HL managed at our institution. RESULTS: In all, 31 cases fulfilled the search criteria. We found significant overlap between testosterone levels in asymptomatic women and women with signs of virilization (range 6.2-37.3 nmol/l and 13.7-197.5 nmol/l, respectively). The method applied for testosterone analysis was mentioned in three reports only. Peak serum testosterone concentration in our case was 120.3 nmol/l. CONCLUSION: From the available data, maternal virilization in HL cannot be predicted by the level of circulating testosterone. However, comparability of results is hampered by the analytical methods applied. LC-MS/MS should preferably be used for reporting concentrations of circulating testosterone.

Maternal and neonatal outcome of births planned in alongside midwifery units: a cohort study from a tertiary center in Germany.

BACKGROUND: For healthy women entering birth after uneventful pregnancy, midwife-led models of care have the potential to reduce interventions and increase the vaginal birth rate. In Germany, 98.4% of women are giving birth in consultant-led obstetric units. Alongside midwifery units (AMU) have been established in 2003. We compared the outcome of women registered for planned birth in the AMU at our hospital with a matched group of low-risk women who gave birth in standard obstetric care during the same period of time. METHODS: We used a retrospective cohort study design. The study group consisted of all women admitted to labor ward who had registered for birth in AMU from 2010 to 2017. For the control group, low-risk women were selected; additionally, matching was performed for parity. Mode of birth was chosen as primary outcome parameter for the mother. For the neonate, a composite primary outcome (5-min Apgar < 7 or umbilical cord arterial pH < 7.10 or transfer to specialist neonatal care) was defined. Secondary outcomes included epidural anesthesia, duration of the second stage of labor, episiotomy, obstetric injury, and postpartum hemorrhage. Non-inferiority was assessed, and multiple logistic regression analysis was performed. RESULTS: Six hundred twelve women were admitted for labor in AMU, the control group consisted of 612 women giving birth in standard obstetric care. Women in the study group were on average older and had a higher body mass index (BMI); birthweight was on average 95 g higher. Non-inferiority could be established for the primary outcome parameters. Epidural anesthesia and episiotomy rates were lower, and the mean duration of the second stage of labor was shorter in the study group; second-degree perineal tears were less common, higher-order obstetric lacerations occurred more frequently. Overall, 50.3% of women were transferred to standard obstetric care. Regression analysis revealed effects of parity, age and birthweight on the chance of transfer. CONCLUSION: Compared to births in our consultant-led obstetric unit, the outcome of births planned in the AMU was not inferior, and intervention rates were lower. Our results support the integration of AMU as a complementary model of care for low-risk women.

Survey of alongside midwifery-led care in North Rhine-Westfalia, Germany.

Background Alongside midwifery-led care (AMC) was introduced in Germany in 2003. The aim of our study was to collect data about the utilization of AMC within North Rhine-Westfalia (NRW), Germany's most populous state, and to collect information regarding the approach used for implementation of AMC and providers' experiences in day-to-day work. Methods Quantitative data were collected by questionnaire, telephone interview and comparative analysis of documents created for use in AMC. Qualitative data were compiled by questionnaire and workshop. Results Seven obstetric departments offer AMC in NRW. On average, 3.4% of women gave birth in these AMC units, corresponding to 0.3% of all births in NRW. For the establishment of AMC, institutional, organizational, professional and formal arrangements were undertaken. An eligibility and transfer checklist was agreed upon between midwives and obstetricians. Both professions were faced with skepticism. Daily work in AMC resulted in improved teamwork between the two professions and increased job satisfaction for midwives. Acquisition of manual skills and time constraints were the major challenges. Conclusion The low utilization of AMC is not due to the concept of care itself or difficulties with its implementation, nor to a lack of eligible women. Reasons may be insufficient awareness about AMC or a lack of interest in this type of care.

[Treatment of HIV in Pregnancy - Progress Over One Decade]. / Behandlung von HIV in der Schwangerschaft ­ Entwicklung über eine Dekade.

INTRODUCTION: Worldwide, 37 million people are infected with HIV; more than 50% are women. Currently, MTCT (mother-to-child transmission) can be reduced to<1%. The intention of the present study was to analyze the development of (1) the course of pregnancy of HIV-infected women, (2) the mode of delivery and (3) the post-exposure prophylaxis of the newborn over the last decade. METHODOLOGY: In this retrospective study, data from HIV-infected women who between 2005 and 2016 received care at the HIV outpatient department and gave birth at the Department of Obstetrics at University Hospital Bonn was analyzed. Furthermore, neonatal data was collected and HIV-MTCT was evaluated. RESULTS: In the 2005-2016 study period, 87 pregnancies in 61 women were identified. Seventy babies were born alive at the Department of Obstetrics, University Hospital Bonn. 53% of these women were of African origin. The median of CD4+ cell count was 510 cells/ml (IQR 444); however, 32 women (52%) had more than 500 cells/ml. During the antenatal period, the HI viral load had been suppressed completely in 77% of women (<50 HIV-1-RNA copies/ml) and was<400 HIV-1-RNA copies/ml in 92% of women. The elective cesarean section rate fell significantly from 77% in the years 2005-2011 to 58% in 2012-2016. The proportion of deliveries after 37 weeks of gestation increased markedly from 60% to 69% after 2012. Additionally, while between 2005-2011 the birth weight of 78% of the newborns was between the 10th and 90th percentile, this proportion increased to 92% after 2012. Fifty-four of 70 newborns (77%) were classified as having low to normal HIV transmission risk. A vertical HIV transmission from mother to child did not occur (0/70). CONCLUSIONS: Between 2005 and 2016 no vertical HIV transmission from mother to child occurred (0/70). Due to the change in treatment strategy, the elective cesarean section rate fell significantly as well the rate of premature births. An optimal interdisciplinary collaboration builds the basis for successful treatment of HIV in pregnancy.

Successful treatment of acute promyelocytic leukemia in pregnancy with single-agent all-trans retinoic acid.

PURPOSE: The diagnosis of acute promyelocytic leukemia (APL) in pregnancy is an uncommon, life-threatening emergency. Choice of treatment and management of complications are challenging. METHODS: We report the case of a patient with diagnosis of APL at gestational age (GA) 24 + 4. We describe the interdisciplinary management during pregnancy and delivery and provide a 2-year follow-up. Existing reports on APL in pregnancy are summarized. RESULTS: Single-agent induction therapy with all-trans retinoic acid (ATRA) was started and resulted in normalization of blood cell counts after 32 days. Vaginal delivery of a healthy baby occurred at GA 34 + 4. Consolidation therapy consisted of four courses of ATRA and arsenic trioxide (ATO). Less than 100 cases of APL in pregnancy are published. Misdiagnosis as HELLP syndrome with fatal outcome may occur. Combination therapies (ATRA-plus anthracyclines) were used in the majority of reports. CONCLUSIONS: Diagnosis and treatment of APL during pregnancy continues to be a challenge requiring interdisciplinary team work. Single-agent ATRA therapy may evolve as a safe and less-toxic treatment modality.

Pregnancy in Women With a Mechanical Heart Valve: Data of the European Society of Cardiology Registry of Pregnancy and Cardiac Disease (ROPAC).

BACKGROUND: Pregnant women with a mechanical heart valve (MHV) are at a heightened risk of a thrombotic event, and their absolute need for adequate anticoagulation puts them at considerable risk of bleeding and, with some anticoagulants, fetotoxicity. METHODS AND RESULTS: Within the prospective, observational, contemporary, worldwide Registry of Pregnancy and Cardiac disease (ROPAC), we describe the pregnancy outcome of 212 patients with an MHV. We compare them with 134 patients with a tissue heart valve and 2620 other patients without a prosthetic valve. Maternal mortality occurred in 1.4% of the patients with an MHV, in 1.5% of patients with a tissue heart valve (P=1.000), and in 0.2% of patients without a prosthetic valve (P=0.025). Mechanical valve thrombosis complicated pregnancy in 10 patients with an MHV (4.7%). In 5 of these patients, the valve thrombosis occurred in the first trimester, and all 5 patients had been switched to some form of heparin. Hemorrhagic events occurred in 23.1% of patients with an MHV, in 5.1% of patients with a tissue heart valve (P<0.001), and in 4.9% of patients without a prosthetic valve (P<0.001). Only 58% of the patients with an MHV had a pregnancy free of serious adverse events compared with 79% of patients with a tissue heart valve (P<0.001) and 78% of patients without a prosthetic valve (P<0.001). Vitamin K antagonist use in the first trimester compared with heparin was associated with a higher rate of miscarriage (28.6% versus 9.2%; P<0.001) and late fetal death (7.1% versus 0.7%; P=0.016). CONCLUSIONS: Women with an MHV have only a 58% chance of experiencing an uncomplicated pregnancy with a live birth. The markedly increased mortality and morbidity warrant extensive prepregnancy counseling and centralization of care.

Array-based molecular karyotyping in fetal brain malformations: Identification of novel candidate genes and chromosomal regions.

BACKGROUND: For the majority of congenital brain malformations, the underlying cause remains unknown. Recent studies have implicated rare copy number variations (CNVs) in their etiology. METHODS: Here, we used array-based molecular karyotyping to search for causative CNVs in 33 fetuses of terminated pregnancies with prenatally detected brain malformations and additional extracerebral anomalies. RESULTS: In 11 fetuses, we identified 15 CNVs (0.08 Mb to 29.59 Mb), comprising four duplications and eleven deletions. All larger CNVs (> 5 Mb) had also been detected by prenatal conventional karyotyping. None of these CNVs was present in our 1307 healthy in-house controls (frequency < 0.0008). Among these CNVs, we prioritized six chromosomal regions (1q25.1, 5q35.1, 6q25.3-qter, 11p14.3, 15q11.2-q13.1, 18q21.1) due to their previous association with human brain malformations or owing to the presence of a single gene expressed in human brain. Prioritized genes within these regions were UBTD2, SKA1, SVIP, and, most convincingly, GPR52. However, re-sequencing of GPR52 in 100 samples from fetuses with brain malformations or patients with intellectual disability and brain malformations revealed no disease-causing mutation. CONCLUSION: Our study suggests chromosomal regions 1q25.1, 5q35.1, 6q25.3-qter, 11p14.3, 15q11.2-q13.1, and 18q21.1 to be involved in human brain development. Within three of these regions, we suggest UBTD2, GPR52, and SKA1 as possible candidate genes. Because the overall detection rate of array-based molecular karyotyping was slightly higher (23%) than that of conventional prenatal karyotyping (20%), we suggest it's use for prenatal diagnostic testing in fetuses with nonisolated brain malformations.

Rupture of renal artery aneurysm during late pregnancy: clinical features and diagnosis.

PURPOSE: Rupture of renal artery aneurysm during pregnancy is a severe complication with high mortality and morbidity for mother and fetus, and diagnosis is difficult. The clinical presentation is easily confused with more common conditions like placental abruption, and most of the cases are diagnosed with timely delay. METHODS: We present the case of a patient with spontaneous rupture of an aneurysm of the left renal artery during late pregnancy and summarize the previous reports of ruptured renal artery aneurysm during pregnancy and early postpartum period. RESULTS: Regarding all published cases up to now (n = 32), 65.6% of mothers and 40.6% of fetuses survived. The rupture occurred in 68.7% in the third trimester and in 6.3% shortly postpartum. In our case, the increase of maternal serum lactate in a hemodynamically stable patient lead to diagnosis. CONCLUSIONS: Ruptured renal artery aneurysm should be included in the differential diagnosis for pregnant or peripartum patients presenting with flank pain. Early diagnosis and immediate intervention are important for achieving better outcomes for mother and fetus. Careful surveillance and laboratory results like serum lactate may lead to diagnosis even in hemodynamically stable patients.

Infective Endocarditis Requiring Mitral Valve Replacement During Second Trimester of Pregnancy.

Infective endocarditis requiring mitral valve replacement during pregnancy is a rare event. We present a case of infective endocarditis of the mitral valve during second trimester and report maternal and perinatal outcomes. Prompt identification and interdisciplinary treatment is crucial; maternal and fetal follow-up including serial fetal neurosonography is recommended.

Unilateral Non-Hemorrhagic Adrenal Infarction in Pregnancy: Case Series and Literature Review.

To summarize the evidence on non-hemorrhagic adrenal infarction (NHAI) and identify questions arising in diagnosis and management, cases in the PubMed database were merged with our case series. A total of 92 publications were retrieved, 15 of which reported on NHAI during pregnancy. Including the four in our case series, 24 cases have been described so far. Severe, unremitting pain requiring opioid analgesia was the leading symptom, often combined with nausea and vomiting. Laboratory results were non-contributory in most cases. Diagnosis was established via MRI in nine cases (37.5%) and via CT in six (25%); nine patients (37.5%) underwent both investigations. Location was predominantly on the right side (n = 16, 66.7%). In addition to analgesia, anticoagulation with heparin was commenced in 18 cases (75%). When thrombophilia screening was performed, major thrombogenic polymorphisms were detected in six cases (33.3%). One woman developed signs of adrenal insufficiency. The reported perinatal outcome was unremarkable. Unilateral NHAI has emerged as a rare but important cause of severe abdominal pain in pregnancy. The threshold to perform an MRI in pregnant women with characteristic clinical findings should be low. To prevent fetal radiation exposure, diagnostic imaging via CT should be avoided. In addition to symptomatic treatment with opioid analgesia, initiation of anticoagulant treatment should be strongly considered.

Maternal and Perinatal Outcome in a Contemporary Cohort of Patients with Portal Hypertension: A Single-Center Experience.

BACKGROUND: Portal hypertension in pregnancy is characterized by an increased perinatal and maternal complication rate. The purpose of this study was to evaluate the perinatal and maternal outcomes of these high-risk pregnancies at our tertiary center. METHODS: We identified pregnancies with portal hypertension in our departmental database for the years 2013 to 2021. The medical history and perinatal and maternal data were extracted from medical records. RESULTS: Eleven cases were identified. In pregnancy, delivery and postpartum, complications occurred in 72.7% of cases and included among others ascites, subclavian thrombosis, variceal-ligation-induced ulcer bleeding and postoperative hemorrhage. The cesarean delivery rate was 72.7% (n = 8); five of these were done for obstetric or fetal indications. The rate of preterm birth and admissions to neonatal intensive care unit were high (54.5% and 45.5%, respectively). CONCLUSIONS: Our case series substantiates the high maternal and perinatal complication rates seen in portal hypertension. The prevention of thromboembolic and bleeding complications was the main challenge. Care by an interdisciplinary team of experts is crucial for a successful perinatal and maternal outcome.

Placenta Accreta Spectrum Prophylactic Therapy for Hyperfibrinolysis with Tranexamic Acid.

BACKGROUND: To report on prophylactic therapy for hyperfibrinolysis with tranexamic acid (TXA) during expectant management (EM) in the placenta accreta spectrum (PAS). METHODS: This is a monocentric retrospective study of women with PAS presenting at our hospital between 2005 and 2021. All data were retrospectively collected through the departmental database. RESULTS: 35 patients with PAS were included. EM was planned in 25 patients prior to delivery. Complete absorption of the retained placenta was seen in two patients (8%). Curettage was performed in 14 patients (56%). A hysterectomy (HE) was needed in seven (28%) patients; 18 patients (72%) underwent uterus-preserving treatment without severe complications. The mean duration of EM was 107 days. The mean day of onset of hyperfibrinolysis and beginning of TXA treatment was day 45. The mean nadir of fibrinogen level before TXA was 242.4 mg/dL, with a mean drop of 29.7% in fibrinogen level. CONCLUSIONS: Our data support EM as a safe treatment option in PAS. Hyperfibrinolysis can be a cause of hemorrhage during EM and can be treated with TXA. To our knowledge, this is the first cohort of patients with EM of PAS in whom coagulation monitoring and use of TXA have been shown to successfully treat hyperfibrinolysis.

Effect of Lifestyle Interventions during Pregnancy on Maternal Leptin, Resistin and Offspring Weight at Birth and One Year of Life.

Lifestyle during pregnancy impacts the health of the mother and child. However, the extent to which physical activity affects maternal biomarkers and factors that might influence birth weight remains unclear. We analysed data from two lifestyle interventions in which the effects of an exercise programme (2x/week, 60-90 min) on the course of pregnancy with regard to adipokines and offspring were evaluated. A total of 70 women participated in this study (45, intervention group; 25, control group). Anthropometric data and maternal fasting serum leptin and resistin levels were measured at three time points (approximately 14th (T1), 24th (T2), and 36th (T3) weeks of gestation). Neonatal/child data were retrieved from screening examinations. Independent of the intervention, we found a positive correlation between the fat mass at T1 and both leptin and resistin levels at all time points. Leptin level was significantly higher in the control group at T3; however, no differences between the groups were found for resistin. The birth weight was influenced by the birth length, fat mass at T1/T3, and resistin level at T2. The BMI-SDS at one year of age was influenced by maternal fat-free mass at T3 and resistin at T1/T2. Even if these results can only be interpreted cautiously, lifestyle interventions during pregnancy are important in promoting maternal and child health. Further randomised controlled trials and translational studies are warranted to clarify the underlying mechanisms.

Obstetric Medicine: the protocol for a prospective three-dimensional cohort study to assess maternity care for women with pre-existing conditions (ForMaT).

Background: Pregnancies in women with pre-existing medical conditions are on the rise. These pregnancies are characterized by an increased rate of maternal and perinatal complications, which can result in higher health care expenditures and altered pregnancy experiences. The purpose of this study is to integrally analyze maternity care for women with pre-existing conditions in the framework of a risk-adapted, interdisciplinary care by recording three substantial parts of maternity care: (1) maternal and perinatal outcome; (2) hospital costs and reimbursements covering the period from preconception counseling or initial antenatal visit to discharge after birth; and (3) women's experience of reproductive choice and becoming a mother in the presence of a pre-existing condition. Methods: In this observational, prospective, longitudinal, and monocentric cohort study, we aim to include a total of 1,500 women over a recruitment period of 15 months. Women registering for care at the Department of Obstetrics and Prenatal Medicine, University Hospital Bonn, Germany, are allocated to three groups based on their health and risk status: women with pre-existing conditions, as well as healthy women with obstetric risk factor and healthy women with a low-risk pregnancy. Participants are observed from time of initial consultation until discharge after birth. Analysis focuses on (1) maternal and perinatal outcome, especially rate of severe maternal and neonatal morbidity; (2) costs and reimbursements; and (3) surveys to capture of women's experience and health-related quality of life during the time of reproductive choice, pregnancy, and childbirth in the presence of pre-existing medical conditions. Discussion: With its complex three-dimensional design, the ForMaT-Trial is aiming to provide a comprehensive analysis of pregnancy and childbirth in women with pre-existing conditions. The results may serve as a basis for counseling and care of these women. By analyzing costs of specialized care, data for discussing reimbursement are generated. Lastly, our results may increase awareness for the perception of reproductive choice, pregnancy and motherhood in this continuously rising population.Clinical trial registration: German Clinical Trials Register, DRKS00030061, October 28, 2022.