Mode of birth in twins: data and reflections.

Our primary objective was to compare neonatal and maternal outcomes in women with twin pregnancies, beyond 32 weeks, having a planned vaginal birth or a planned caesarean section (CS). This was a retrospective cohort study from a single tertiary centre over nine years. 534 sets of twins ≥32 + 0 weeks of gestation were included. 401 sets were planned vaginally and 133 sets were planned by CS. We compared a composite adverse perinatal outcome (perinatal mortality or serious neonatal morbidity; five minute APGAR score ≤4, neurological abnormality and need for intubation) and a composite maternal adverse outcome (major haemorrhage, trauma or infection) between the groups. There were no significant differences. Given the similarity of these results with several other larger studies of twin birth, we sought to look at reasons why there is still a rising rate of CS for twin births. We further make suggestions for keeping this rate to a sensible minimum. Impact statement What is already known on this subject? The largest randomised controlled study comparing planned vaginal birth with planned CSs for lower risk twins between 32 and 39 weeks of gestation, showed no added safety from planned CS. However, in most of the Western countries this conclusion has failed to increase the number of planned vaginal births for lower risk twins. What do the results of this study add? This observational study from a single tertiary centre provides external validation of the twin trial results in a practical day-to-day setting. It also provides insights as to how planned vaginal birth can be developed and maintained, with a key focus on safety and maternal participation in decision making. It does focus on consent and providing accurate data. What are the implications of these findings for clinical practice and/or further research? There are good grounds to encourage vaginal birth for low-risk twin pregnancies. The trend of rising caesarean rates in low-risk twin pregnancies worldwide will erode important skills for the conduct of vaginal births without any clear benefit for mothers or babies. The current situation demands careful thought about implementing innovative training opportunities for younger obstetricians. Finally, we need intelligent responses to many non-evidence-based factors which can drive clinical practice.

Incidence of CMV co-infection in HIV-positive women and their neonates in a tertiary referral centre: a cohort study.

Co-infection with CMV in HIV-positive pregnant women is associated with perinatal mother-to-child transmission (MTCT) of both viruses. This retrospective study reports on the incidence of maternal and neonatal CMV (presence of anti-CMV IgG and IgM, CMV DNA PCR and/or CMV virus isolation) in high-risk pregnancies due to maternal HIV infection, MTCT of HIV and/or CMV. One hundred and eleven maternal samples and 75 matched neonatal samples were available for HIV and subsequent CMV testing. In this cohort of HIV-positive pregnant women, 96 (86.5 %) serum samples were anti-CMV IgG positive. In nine (9.4 %) of these, anti-CMV IgM was detected, and in none of them a maternal primary CMV infection was suspected. Fifty-seven (51.8 %) maternal serum samples were tested retrospectively by CMV DNA PCR; one sample was positive (0.9 %). All matched neonates were tested for HIV by PCR in the first month of life; HIV transmission was detected in one case. In 74 (67.2 %) of neonates, CMV testing was performed. Sixty-six of these serum samples were tested retrospectively by CMV DNA PCR. Two newborns (2.7 %) showed laboratory markers for CMV infection (one by detection of CMV DNA in plasma, and one by isolation of CMV from a urine sample). In the follow-up, neither of these two showed clinical signs for active CMV disease. We discussed these findings in the light of the national official guidelines. All CMV transmissions occurred due to maternal reinfection or endogenous reactivation. This suggests the success of highly active antiretroviral therapy in preventing MTCT of HIV and CMV disease and highlights the importance of adequate care and follow-up.

Pregnancy complications in HIV-positive women: 11-year data from the Frankfurt HIV Cohort.

OBJECTIVES: The aim of the study was to assess pregnancy complications in HIV-positive women and changes in the rates of such complications over 11 years in the Frankfurt HIV Cohort. METHODS: There were 330 pregnancies in HIV-positive women between 1 January 2002 and 31 December 2012. The rate of pregnancy-related complications, such as gestational diabetes mellitus (GDM), pre-eclampsia and preterm delivery, the mode of delivery and obstetric history were analysed. Maternal and neonatal morbidity/mortality as well as HIV mother-to-child transmission (MTCT) were evaluated. RESULTS: In our cohort, GDM was diagnosed in 38 of 330 women (11.4%). Five women (1.5%) developed pre-eclamspia or hypertension. In 16 women (4.8%), premature rupture of membranes (PROM) occurred and 46 women (13.7%) were admitted with preterm contractions. The preterm delivery rate was 36.5% (n = 122), and 26.9% of deliveries (n = 90) were between 34+0 and 36+6 weeks of gestation. Over the observation period, the percentage of women with undetectable HIV viral load (VL) increased significantly (P < 0.001), from 26.1% to 75%, leading to obstetric changes, including an increase in the rate of vaginal deliveries (P < 0.001), from no vaginal births to 50%. The preterm delivery rate decreased significantly (P < 0.001), from 79.2% to 8.3%. There were no significant changes in the rate of GDM, pre-eclampsia, PROM or preterm contractions. CONCLUSIONS: In the 11 years of our analysis, there was a significant reduction in the rate of preterm deliveries and an increase in the vaginal delivery rate, possibly reflecting changes in treatment policies in the same period and the availability of more effective antiretroviral therapy options. The rates of complications such as GDM, pre-eclampsia, preterm contractions, PROM and postnatal complications were stable over the 11 years, but were still increased compared with the general population.

Prenatal ultrasound screening for fetal anomalies and outcomes in high-risk pregnancies due to maternal HIV infection: a retrospective study.

OBJECTIVE: To assess the prevalence of prenatal screening and of adverse outcome in high-risk pregnancies due to maternal HIV infection. STUDY DESIGN: The prevalence of prenatal screening in 330 pregnancies of HIV-positive women attending the department for prenatal screening and/or during labour between January 1, 2002 and December 31, 2012, was recorded. Screening results were compared with the postnatal outcome and maternal morbidity, and mother-to-child transmission (MTCT) was evaluated. RESULTS: One hundred of 330 women (30.5%) had an early anomaly scan, 252 (74.5%) had a detailed scan at 20-22 weeks, 18 (5.5%) had a detailed scan prior to birth, and three (0.9%) had an amniocentesis. In seven cases (2.12%), a fetal anomaly was detected prenatally and confirmed postnatally, while in eight (2.42%) an anomaly was only detected postnatally, even though a prenatal scan was performed. There were no anomalies in the unscreened group. MTCT occurred in three cases (0.9%) and seven fetal and neonatal deaths (2.1%) were reported. CONCLUSION: The overall prevalence of prenatal ultrasound screening in our cohort is 74.5%, but often the opportunity for prenatal ultrasonography in the first trimester is missed. In general, the aim should be to offer prenatal ultrasonography in the first trimester in all pregnancies. This allows early reassurance or if fetal disease is suspected, further steps can be taken.

Outcome in single and twin pregnancies at 20 to 24 weeks gestation: ten years experience in one perinatal center.

OBJECTIVE: The aim of this investigation was to evaluate the outcome at 20 to 24 weeks gestation of twin and singleton extremely low birth weight infants. STUDY DESIGN: The authors conducted a retrospective cohort study of live newborns at 20 to 24 weeks gestation admitted to one neonatal intensive care unit (NICU) from 2000 to 2009. Outcome mortality and predictors of outcome were evaluated. Results were compared for twin and singleton infants. RESULTS: The cohort of infants consisted of 60 singleton infants and 17 twins. The results suggest an increased risk of death for twins when compared with singletons. A correlation between neonatal C-reactive protein (CRP) and bacterial culture positive results on admission to NICU might be a predictor of neonatal outcome. CONCLUSION: In extremely low birth weight infants, twin delivery is associated with an independent increased risk of death. Both first- and second-born twins are at increased risk.

Prenatal management of diaphragmatic rhabdomyosarcoma presenting with fetal hydrops.

Fetal malignant tumors are rare. We present a case of intrauterine diagnosis of a diaphragmatic tumor presenting with fetal hydrops at 32 weeks' gestation. The sonographic findings were bilateral pleural effusion, ascites and skin edema. A large right-sided diaphragmatic tumor was identified. Owing to the findings on ultrasound and magnetic resonance imaging a solid malignant tumor was suspected. The pleural effusions were drained and malignant cells identified. Because of rapid tumor progression Cesarean section was performed and a hydropic female newborn was delivered at 34 + 0 weeks' gestation. There was no sign of metastatic disease. Postnatally tumor biopsy revealed an alveolar rhabdomyosarcoma. Therapy included chemotherapy and secondary surgical intervention. After a good primary response with complete remission after 6 months, the rhabdomyosarcoma relapsed at 12 months with cerebral metastasis. The prognosis was poor.

[Hereditary holoprosencephaly--late diagnosis in spite of recurrence]. / Familiäre Holoprosencephalie--Späte Diagnose trotz Wiederholungsfall.

Holoprosencephaly (HPE) is a serious malformation of the central nervous system which occurs between the 18th and 28th day of gestation. HPE can appear in different manifestations within one family. The diagnosis of HPE can be performed in an early sonographic scan between the 12th and the 14th week of gestation, according to the guidelines for the examination of the foetal nervous system. The history of a pregnant woman with a previous birth of a foetus with cerebral malformation and having a partner with minor signs for HPE justifies an intensified sonographic examination and molecular analysis. An amniocentesis was done just for the basic analysis, not for further genetic testing. However, it is very important to have information about a recurrency risk for every subsequent pregnancy.

[Breech presentation - more than just caesarean vs. spontaneous birth]. / Beckenendlagengeburt - mehr als Sectio vs. Spontangeburt.

The cesarean section rate and the associated complications are still rising in Germany. An important indication is term breech in singletons. Not significant data concerning a higher morbidity or mortality in vaginal breech birth indicate the cesarean but a deficit in education and experience.

[Doppler studies of gestational diabetes in the third trimester]. / Plazentare Widerstandsmessung bei Gestationsdiabetes im III. Trimenon.

PURPOSE: Gestational diabetes (GDM) is related to increased maternal and neonatal morbidity. Maternal hyperglycemia causes fetal hyperglycemia and consequently fetal hyperinsulinism. The impaired glucose metabolism will lead to prenatal and postnatal complications. The main issue of this study is the influence of GDM in evaluating Doppler flow measurements in the umbilical artery (UA). MATERIALS AND METHODS: Pregnancies from gestational age > 34 + 0 were included in this case control study. The study period was 18 months. The last Doppler measurement in pregnancies with GDM (diet-controlled and insulin-dependent) was compared to the healthy control group. Our collected data included the last prenatal Doppler flow recordings (resistance index (RI) in the umbilical artery (UA)). RESULTS: In women with diet-controlled GDM, a significant decrease in the RI (p = 0.002) in the UA has been observed. Insulin-treated diabetic and healthy control pregnancies showed no difference in the RI. CONCLUSION: Doppler flow examinations with RI measurements in patients with GDM differ significantly with respect to healthy controls. In insulin-treated women the RI indices are not different from the control group, while in the diet-controlled group a significant decrease was noted and additionally might show a possible maternal metabolic dysfunction.

Fetal hydrops, hyperechogenic arteries and pathological doppler findings at 29 weeks: prenatal presentation of generalized arterial calcification of infancy - a novel mutation in ENPP1.

Prenatal diagnosis of generalized arterial calcification of infancy (GACI) (OMIM #208000) is difficult and rare. There are various known gene mutations in ENPP1 (ectonucleotide pyrophosphatase/phosphodiesterase 1) locus 6q22-q23. We present a case of suspected intrauterine diagnosis at 29 weeks of gestation in a consanguineous couple. The sonographic findings were fetal hydrops (hydrothorax, skin edema, ascites, pericardial effusion and polyhydramnion), echogenic great arteries and pathological Doppler findings. An intrauterine therapy with bisphosphonates was considered, but delayed due to rapid deterioration in fetal Doppler flows with suspected fetal asphyxia. The couple was informed about the most unfavorable prognosis in fetal hydrops, however, they opted for elective delivery. A cesarean section was performed. Early neonatal death occurred due to primary intracranial hemorrhage. Postmortem and genetic testing confirmed a novel mutation in the ENPP1 gene.

Impact of BMI on clinical outcomes of NOAC therapy in daily care - Results of the prospective Dresden NOAC Registry (NCT01588119).

Direct acting non-Vitamin K antagonist oral anticoagulants (NOAC) are characterized by a fixed dosing regimen. Despite the potential for relative underdosing due to large distribution volumes, dose adjustments for patients with high body mass index (BMI) are not recommended. Since efficacy and safety data in obese patients are scarce, we evaluated the impact of BMI on clinical outcomes in daily care patients treated with NOAC for stroke prevention in atrial fibrillation or venous thromboembolism. Using prospectively collected data from a non-interventional registry, cardiovascular (CV), major bleeding events (MB) and all-cause mortality were evaluated according to BMI classes. All outcome events were centrally adjudicated using standard scientific definitions. Between November 1st 2011 and December 31st 2016, 3432 patients were enrolled into the registry (61.3% rivaroxaban; 20% apixaban; 10.1% dabigatran, 8.6% edoxaban; mean follow-up 998.1 ±â€¯542.9 days; median 1004 days). With increasing BMI (range 13.7-57.2 kg/m2), the proportion of patients receiving standard (vs. reduced) NOAC dose increased from 64.7% (underweight) to 78.9% (obesity). Although obese patients had more cardiovascular risk factors compared to normal weight patients, on-treatment rates of clinical outcomes (CV, MB, all-cause-mortality) were lowest in overweight and obese patients. In a large set of real-life NOAC recipients we found no indication that high BMI is associated with inferior NOAC effectiveness or safety, which is in line with recent epidemiological data of a "BMI paradox" that indicates a somewhat protective effect of higher BMI regarding unfavourable outcomes also in patients receiving fixed dose NOAC anticoagulation without dose adjustment for higher BMI.

Maternal CD4+ microchimerism in HIV-exposed newborns after spontaneous vaginal delivery or caesarean section.

BACKGROUND: Maternal CD4+ cell microchimerism may be greater after caesarean section compared to spontaneous vaginal delivery and could cause mother-to-child transmission (MTCT) in HIV-exposed newborns. AIMS: To evaluate maternal CD4+ cell microchimerism in HIV-exposed newborns after spontaneous vaginal delivery or caesarean section. STUDY DESIGN AND SUBJECTS: In this prospective single-centre study, neonates whose mothers were infected with HIV and had normal MTCT risk according to the German Austrian Guidelines were considered for study enrolment. Maternal CD4+ cell microchimerism in the newborns' umbilical cord blood was measured and compared by mode of delivery. RESULTS: Thirty-seven HIV-infected mothers and their 39 newborns were included in the study. None of the 17 (0.0%) newborns delivered vaginally had quantifiable maternal CD4+ cells (95% confidence interval (CI): 0.00-0.00) in their circulation at birth compared with four of 16 (25.0%) newborns delivered via planned caesarean section, who showed 0.01-0.66% maternal cells (95% CI: -0.06-0.16; P=0.02) in their circulation. The intention to treat analysis, which included six additional newborns delivered by unplanned caesarean section, showed quantifiable maternal CD4+ cells in one (0.05%; 95% CI: -0.02-0.04) of 23 (4.3%) newborn at birth compared to four of 16 (25.0%) born via planned caesarean section (95% CI: -0.06-0.16; P=0.04). There was no MTCT in any of the newborns. CONCLUSION: In this small cohort, spontaneous vaginal delivery in HIV-infected women with normal MTCT risk was associated with lower maternal CD4+ cell transfer to newborns compared to planned caesarean section.

Conservative Management of Placenta Accreta/Increta after Vaginal Birth.

Aim: Aim of the study was to show that conservative management with preservation of the uterus and of fertility is possible in patients with placenta accreta/increta after vaginal delivery. Method: A retrospective analysis of patients with placental attachment disorders after vaginal delivery was done in a perinatal centre between November 2009 and April 2011. The patient collective was identified using the ICD-10 codes for placenta accreta/increta/percreta, and patient records were analysed for risk factors, maternal morbidity, preservation of the uterus and of fertility, and neonatal outcome. Results: Three cases of placenta increta were identified in the last 1.5 years out of a total of 1457 vaginal deliveries, and all 3 cases were treated conservatively. Mean maternal age was 35.3 years; gestational age ranged from 39 to 41 weeks, and mean duration between delivery of the child and delivery of the placenta was 44.67 days (range: 14-100 days). Two patients developed symptoms of endomyometritis, including fever, leukocytosis and increased CRP levels. All 3 women were successfully managed with preservation of the uterus. Conclusion: In selected cases with placenta accreta/increta after vaginal delivery, it is possible to avoid surgical procedures, particularly hysterectomy procedures, and successfully manage these patients conservatively with preservation of the uterus.

[Side effects of antiretroviral treatment for transmission prophylaxis in preterm and near-term infants]. / Unerwünschte Wirkungen der antiretroviralen Prophylaxe der HIV-Transmission bei Frühgeborenen unter 35 Schwangerschaftswochen.

BACKGROUND: The aim of this study was to assess the frequency of side effects of antiretroviral treatment in transmission prophylaxis in preterm and near-term infants with a history of HIV-positive mothers. METHODS: A retrospective single-centre study of all neonates born to HIV-positive mothers between 2001 and 2005 and receiving antiretroviral prophylaxis was performed. Respiratory distress was documented as well as possible side effects from antiretroviral drug treatment, e. g., anaemia, need for transfusion, liver and kidney dysfunction, depression of white blood cell count, feeding problems and nosocomial infections. A comparison was made between a group of preterm infants of less than 35 weeks of gestation with one of near-term neonates of more than 34 weeks. To evaluate the influence of prematurity on the frequency of symptoms, a matched pairs group of 50 preterm infants was established as the control group. RESULTS: Anaemia at birth (24 vs. 27 %), transient signs of liver impairment (24 vs. 16.5 %) or kidney dysfunction (4 vs. 0.8 %) as well as nosocomial infections were not significantly more frequent in the preterm group than in near-term group of HIV-exposed infants. Respiratory distress (56 vs. 13 %), postnatal anaemia (84 vs. 27 %). leucocytopenia (36 vs. 4 %), feeding problems (88 vs. 42 %), and blood transfusion (32 vs. 7 %) were more common in the preterm infants. The frequency of feeding problems remained markedly elevated when preterm HIV-exposed neonates were compared to preterm controls. Respiratory distress in near-term infants was seen in 13 % of the cases and 2.6 % of them had to be ventilated artificially. This was a higher frequency than in babies delivered by elective Caesarean section without maternal HIV history. CONCLUSIONS: Transmission prophylaxis in offspring of HIV-positive mothers may give rise to adverse effects. Their frequency is higher in preterm infants than in near-term infants. However; this may be related to prematurity, and not to the antiretroviral treatment itself.

[Identification of preeclampsia by cDNA-gene expression profiling in human placentas and serum -- a pilot study]. / Identifikation von Präeklampsiepatientinnen mittels cDNA-Genexpressionsprofilen an humanen Plazentaproben und Serum -- eine Pilotstudie.

OBJECTIVE: Preeclampsia is associated with significant maternal and fetal morbidity and mortality. The etiology remains unclear. For the accurate diagnosis and the prevention of preeclampsia it seems to be important to find a diagnostic tool that identifies risk patients before symptoms occur. With a new approach, the cDNA-Array analysis, human placentas and blood from preeclamptic and healthy pregnant women were examined for differentially expressed genes to find typical genes expression profiles. MATERIAL AND METHODS: In this pilot study, cDNA array analysis with a 19 200 gene array of placenta and blood samples from three preeclamptic patients have been performed to classify this samples based on expression patterns. RESULTS: Comparing normal placenta and blood from healthy delivered women (n = 4), a subset of 200 genes repeatedly found to be differentially expressed in preeclampsia. The placenta and blood samples from preeclampsia were accurately grouped by their individual gene expression patterns. CONCLUSIONS: These results suggest that the use of cDNA array is a tool to identify gene expression patterns in preeclampsia. With this set of differentially expressed genes in conjunction with sample clustering algorithms the identification of preeclampsia in placenta or blood samples is possible.