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/an-hydramnion 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 duringin speculainvestigation. 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 intra-amniotic 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 continuous amnioinfusion through the subcutaneously implanted perinatal port system with amniotic fluid like hypo-osmotic solution in “classic PPROM” less than 28/0 weeks’ gestation shows promise but must be proved in future prospective randomized studies. Systemic antibiotics administration in “pre-PPROM” without infection and hospitalization are also of questionable benefit and needs to be further evaluated in well-designed randomized prospective studies to evaluate if it is associated with any neonatal benefit as well as the relationship to possible adverse effect of antibiotics on to fetal development and neurological outcome.

Acute respiratory infections (ARIs) are the most common childhood illnesses worldwide whereby the reported frequency varies widely, often depending on type of assessment. Symptom diaries are a powerful tool to counteract possible under-reporting, particularly of milder infections, and thus offer the possibility to assess the full burden of ARIs. The following analyses are based on symptom diaries from participants of the German birth cohort study LoewenKIDS. Primary analyses included frequencies of ARIs and specific symptoms. Factors, which might be associated with an increased number of ARIs, were identified using the Poisson regression. A subsample of two hundred eighty-eight participants were included. On average, 13.7 ARIs (SD: 5.2 median: 14.0 IQR: 10–17) were reported in the first two years of life with an average duration of 11 days per episode (SD: 5.8, median: 9.7, IQR: 7–14). The median age for the first ARI episode was 91 days (IQR: 57–128, mean: 107, SD: 84.5). Childcare attendance and having siblings were associated with an increased frequency of ARIs, while exclusive breastfeeding for the first three months was associated with less ARIs, compared to exclusive breastfeeding for a longer period. This study provides detailed insight into the symptom burden of ARIs in German infants.

Aims: The elastic properties of circumscribed tissues (e.g., tendons, lymph nodes, prostates, brain tumors) are of considerable clinical interest. The purpose of this study was thus to compare the Intra-/Inter-observer variation and accuracy in vitro of point shear wave elastography (pSWE) with that of 2D-SWE and to assess 2D-SWE’s precision with variable ROI (vROI) incircumscribed objects.Material and methods: Round targets (Elasticity QA Phantom Model 049) were examined for varying degrees of stiffness (8, 14, 45, and 80 kPa) and diameters (20/10 mm). Three ultrasound systems and four probes were applied (pSWE: Acuson/S3000 9L4/4C1 and Epiq7 C51, 2D-SWE: Aplio/500 PVT375BT). Three different ROIs were used, namely fixed ROI (fROI) and variable ROI: rectangular-best-fitted ROI, and round-best-fitted ROI. Each measurement was performed twice by four observers.Results: A total of 3,604 measurements were conducted. The intra-observer variation of 2D-SWE measurements indicated better agreement (Intraclass Correlation Coefficient (ICC) = 0.971; 95% CI=[0.945; 0.985]), than for the pSWE measurements (ICC = 0.872; 95% CI=[0.794; 0.92]). With both methods, the shear wave elastography applied showed low inter-observer variation: ICC = 0.980; 95% CI=[0.970; 0.987]. However, a significant difference was observed between fROI (pSWE) and vROI (2D-SWE) on circumscribed objects in terms of accuracy. The lowest degree of observationerror was detected in situations where the ROI was not “best fitted”, but placed within the target of 3mm from the border (target diameter: 20mm; mean relative error = 0.15).Conclusions: When estimating the elastic properties of circumscribed tissues, the different measurement techniques performed by commercial shear wave elastography systems reveal a strong susceptibility for observational errors, depending upon the fixed vs. variable ROI of the pSWE vs. 2D-SWE technique.

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. An amniotic fluid replacement port system was implanted in seven patients with PPROM and anhydramnion starting at the 20th 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. 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. 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.

Objective: To investigate the impact of undertaking long‐distance air travel to a specialized medical center while pregnant in order to undergo fetoscopic laser coagulation (FLC) for twin‐to‐twin transfusion syndrome (TTTS).Methods: A retrospective cohort study was conducted of women with TTTS who travelled by air (n = 16) or land (n = 61) to the Centre of Perinatal Diagnosis and Microinvasive Fetal Surgery, Mainz, Germany, between January 1, 2006, and December 31, 2010. All women underwent FLC on arrival at the study center. Neonatal outcome, postoperative neonatal survival rates, and rates of adverse effects were recorded.Results: The postoperative survival rate for a single twin was 100.0% (n = 16) in the flight group and 98.3% in the land transportation group (n = 60). The postoperative survival rate for both twins was 81.3% in the flight group (n = 13) and 75.4% (n = 46) in the land transportation group. No differences in neonatal outcome or the rate of adverse effects were observed between the 2 groups. No flight‐related pregnancy complications were recorded.Conclusion: Long‐distance air travel to a specialized tertiary care medical center is sufficiently safe to warrant recommendation to pregnant women with TTTS who require FLC.

Objective: To determine if intrauterine intraumbilical supplementation with amino acids (AA) and glucose can improve neonatal outcome of severe growth restricted human fetuses (IUGR).Methods: Prospective pilot study of intrauterine treatment of severe IUGR fetuses [n=14, 27 weeks of gestation (range 23–31)] with cerebroplacental ratio <1, with long-term intraumbilical AA and glucose supplementation (10% of feto-placental blood volume/day) using a perinatal port system alone (n=5) or combined with hyperbaric oxygenation (n=1, HBO) vs. control group (n=8).Results: The duration of continuous intraumbilical AA/glucose supplementation was 11 (6–13) days. Daily intravascular fetal nutrition significantly prolonged the brain sparing to delivery interval by 24 (14–33) days vs. 5.6 (2–12) days in controls. Fetal nutrition reduced blood flow resistance in the placental circulation but did not affect the Doppler profile of cerebral arteries. Higher weight gain of 113.5 (36–539) g was observed following supplementation compared to 33.3 (8–98) g in the control group (P<0.05). In spite of this, fetuses below 28 weeks of gestation did not sufficiently benefit from infused commercial AA. We found a reduced fetal plasma concentration of the essential AA histidine, threonine, lysine and arginine, and non-essential AA taurine, in severe IUGR fetuses in both groups. Long-term supplementation with a commercial AA formula led to a slight, but not significant, reduction of histidine, threonine, lysine, arginine, asparagine and glutamine. However, the concentration of tryptophan and glutamic acid slightly increased. HBO can be combined with AA supplementation via a port system. In one case, the port system was also successfully used for fetal blood transfusion.Conclusions: Intravascular treatment of IUGR with fetal nutrition can prolong pregnancy with severe placental insufficiency and brain sparing for many weeks. However, rather than normalizing AA concentrations, an enhanced AA imbalance was observed in IUGR fetuses following supplementation. These deviations in AA concentrations prevent the recommendation for use of commercial AA solutions for prenatal treatment of extreme preterm IUGR fetuses.