Mid-trimester preterm premature rupture of membranes (PPROM), defined as rupture of fetal membranes prior to 28 weeks of gestation, complicates approximately 0.4%-0.7% of all pregnancies. This condition is associated with a very high neonatal mortality rate as well as an increased risk of long-and short-term severe neonatal morbidity. The causes of the mid-trimester PPROM are multifactorial. Altered membrane morphology including marked swelling and disruption of the collagen network which is seen with PPROM can be triggered by bacterial products or/and pro-inflammatory cytokines. Activation of matrix metalloproteinases (MMP) have been implicated in the mechanism of PPROM. The propagation of bacteria is an important contributing factor not only in PPROM, but also in adverse neonatal and maternal outcomes after PPROM. Inflammatory mediators likely play a causative role in both disruption of fetal membrane integrity and activation of uterine contraction. The "classic PPROM" with oligo/anhydramnion is associated with a short latency period and worse neonatal outcome compared to similar gestational aged neonates delivered without antecedent PPROM. The "high PPROM" syndrome is defined as a defect of the chorio-amniotic membranes, which is not located over the internal cervical os. It may be associated with either a normal or reduced amount of amniotic fluid. It may explain why sensitive biochemical tests such as the Amniosure (PAMG-1) or IGFBP-1/alpha fetoprotein test can have a positive result without other signs of overt ROM such as fluid leakage with Valsalva. The membrane defect following fetoscopy also fulfils the criteria for "high PPROM" syndrome. In some cases, the rupture of only one membrane -either the chorionic or amniotic membrane, resulting in "pre-PPROM" could precede "classic PPROM" or "high PPROM". The diagnosis of PPROM is classically established by identification of nitrazine positive, fern positive watery leakage from the cervical canal observed during in specula investigation. Other more recent diagnostic tests include the vaginal swab assay for placental alpha macroglobulin-1 test or AFP and IGFBP1. In some rare cases amniocentesis and infusion of indigo carmine has been used to confirm the diagnosis of PPROM. The management of the PPROM requires balancing the potential neonatal benefits from prolongation of the pregnancy with the risk of intraamniotic infection and its consequences for the mother and infant. Close monitoring for signs of chorioamnionitis (e.g. body temperature, CTG, CRP, leucocytes, IL-6, procalcitonine, amniotic fluid examinations) is necessary to minimize the risk of neonatal and maternal complications. In addition to delayed delivery, broad spectrum antibiotics of penicillin or cephalosporin group and/or macrolide and corticosteroids have been show to improve neonatal outcome [reducing risk of chorioamnionitis (average risk ratio (RR) = 0.66), neonatal infections (RR = 0.67) and abnormal ultrasound scan of neonatal brain (RR = 0.67)]. The positive effect of continuo...

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It has been demonstrated with invasive techniques in fetal lambs that the ratio of ductus venosus to umbilical vein blood flow rate (DV/UV ratio) increases during hypoxemia and infusion of catecholamines. Recently it was found in human fetuses using pulsed wave Doppler ultrasound equipment that the DV/UV ratio in fetuses with intrauterine growth restriction was significantly increased. The aim of the present study was to show in fetal lambs whether routine Doppler ultrasound devices were capable of determining the DV/UV ratio with sufficient reliability. The experiments were performed on seven near-term instrumented fetal lambs using pulsed wave Doppler ultrasound to measure flow rates (derived, in milliliters per min, from the intensity-weighted mean velocity (Vmean) and the vessel's cross-sectional area) in the ductus venosus and intra-abdominal umbilical vein. Fetal hypoxemia was induced by administering a low-oxygen gas to the ewe (5-7% oxygen, 2% carbon dioxide). Fetal arterial pO2 and heart rate decreased significantly during maternal hypoxia. The proportion of umbilical venous return passing through the ductus venous in controls was 36 +/- 5% (mean +/- SD). This increased to 53 +/- 6% (p < 0.001) because the umbilical venous blood flow fell during late hypoxemia when the heart rate had decreased by 20%. Severe hypoxemia tended to reduce the mean velocity (Vmean) and the minimum velocity (Vmin) (based on the maximum velocity envelope curve) in the ductus venosus, descending aorta and inferior vena cava. The pulsatility index of the umbilical artery significantly increased at the end of hypoxemia. We conclude that determination of the proportion of umbilical vein blood flow entering the ductus venosus by Doppler ultrasound in a clinical setting may contribute to the detection and evaluation of fetal distress.

Objective To assess outcome after fetoscopic laser coagulation (FLC) 21.0 (range, 17.4-24.6) weeks vs. 20.6 (range, 15.9-24.6) 34.1 (range, 25.0-38.4) weeks and controls at 34.0 (range, 25.0-40.3)

Background Women have a markedly increased lifetime risk for cardiovascular morbidity and mortality following hypertensive disorders of pregnancy. Arterial stiffness is regarded as a target parameter for reducing cardiovascular risk and can be modified by lifestyle changes. Methods In a prospective, randomised, controlled interventional study, starting 6 weeks postpartum, the effect of nutritional intervention combined with an intensive 6-month cardiovascular exercise programme on arterial stiffness was investigated by means of pulse wave velocity (PWV) in 38 women with severe hypertensive disorder of pregnancy (preeclampsia with or without pre-existing hypertension and/or HELLP syndrome). A reference group was formed with postpartum women without pregnancy complications or known cardiovascular risk and the arterial stiffness was studied by means of PWV at the time of delivery. The PWV was measured in the intervention and control groups within a week after delivery and after 32 weeks (6 weeks + 6 months). A feasibility analysis was performed in addition. Results 29 of 38 women with severe hypertensive disorder of pregnancy and 38 postpartum women in the reference group were included in the analysis (intervention group n = 14; control group n = 15; reference group n = 38). Adherence to a) the nutritional counselling and b) the intensive cardiovascular exercise programme was 73% and 79% respectively. A clinically significant difference (d = 0.65) in pulse wave velocity between the intervention and control groups was found after 6 months (6.36 ± 0.76 vs. 7.33 ± 2.25 m/s; group × time: p = 0.632). The PWV of the intervention group corresponded to that of the reference group at the end of the study (6.36 ± 0.76 m/s vs. 6.5 ± 0.70; d = 0.19), while the results in the control group differed markedly from this (7.33 ± 2.25 m/s; d = 0.56). Conclusion The study documents the feasibility of lifestyle intervention with physical exercise after delivery (starting 6 weeks postpartum). The intervention showed a significant clinical effect by reducing arterial stiffness to the level of the reference group. Before this intervention can be included in the standard of care and prevention, follow-up studies must confirm these results and the medium-term effects on cardiovascular risk.

Objective: This study aims to treat patients with preterm premature rupture of the membranes (PPROM) and anhydramnion using continuous amnioinfusion through a subcutaneously implanted port system. Methods: An amniotic fluid replacement port system was implanted in seven patients with PPROM and anhydramnion starting at the 20 th week of gestation (range, 14-26 weeks) for long-term amnioinfusion. Saline solutions (2 L/day; Jonosteril ® , Sterofundin ® , isotonic NaCl 0.9% solution, lactated Ringer's solution) and a hypotonic aqueous composition with reduced chloride content similar to the electrolyte concentration of human amniotic fluid were used for the continuous amnioinfusion. Results:The mean duration of the PPROM delivery interval continued for 49 days (range, 9-69 days), with 3 weeks of amnioinfusion via the port system (range, 4-49). The newborns showed no signs of lung hypoplasia. Conclusion: Long-term lavage of the amniotic cavity via a subcutaneously implanted port system in patients with PPROM and anhydramnion may help prolong the pregnancy and avoid fetal lung hypoplasia. A hypotonic aqueous composition with reduced chloride content similar to human amniotic fluid can be safely used for amnioinfusion. Prospective randomized studies are ongoing.

Bacterial infection is one of the main causes of preterm premature rupture of membranes (PPROM) leading to preterm delivery, pulmonary hypoplasia, sepsis and joint deformities. Expectant management, broad-spectrum antibiotics and antenatal corticosteroids are routinely used in this condition with very limited success to prevent bacteremia, chorioamnionitis, funisitis and intra-amniotic infection syndrome. Here, we report a case in which we attempted to treat PPROM at 26⁺³ weeks of gestation with anhydramnion colonized by multiresistant Klebsiella. A perinatal port system was implanted subcutaneously at 28⁺⁰ weeks of gestation, enabling long-term continuous lavage of the amniotic cavity with a hypotonic aqueous composition similar to human amniotic fluid combined with intra-amniotic antibiotic application. The patient gave birth to a preterm female infant at 31⁺¹ weeks without any signs of infection. The girl was discharged with a weight of 2,730 g in very good condition. In the follow-up examinations at 5 months and 1 year of age, there was no apparent neurological disturbance, developmental delay or Klebsiella colonization.