Leonhard Schäffer

Physiologically low oxygen concentrations in fetal skin regulate hypoxia-inducible factor 1 and transforming growth factor-beta3.

In the first‐trimester mammalian fetus, skin wounds heal with perfect reconstitution of the dermal architecture without scar formation. Understanding environmental molecular regulation in fetal wound healing may reveal scar‐limiting therapeutical strategies for the prevention of postnatal scarring wound repair. Therefore, we performed studies on fetal skin oxygenation and skin and wound expression of hypoxia‐inducible factor 1α (HIF‐1α) in the sheep model in vivo and performed studies on the potential relevance of HIF‐1α during wound healing in vitro. Skin oxygen partial pressure levels were hypoxic throughout normal development. In nonscarring fetal skin at gestation day (GD)60, HIF‐1 α could be detected neither in healthy nor in wounded tissue. At GD100, in wounds with minimal scar formation, HIF‐1 α was expressed in fibroblasts and was markedly up‐regulated at the wound edge. In scarring fetal wounds at GD120, HIF‐1 α was predominantly expressed in inflammatory cells. Expression of transforming growth factor β3 (TGF‐β3), a potent antiscarring cytokine, overlapped with HIF‐1 α expression at GD100. HIF‐1 α‐deficient mouse embryonic fibroblasts showed impaired migratory capabilities and demonstrated that TGF‐β3, but not proscarring TGF‐β1, manifests hypoxia‐ and HIF‐1α‐dependent regulation. In conclusion, HIF‐1‐dependent regulation of a potent antiscarring cytokine may provide new strategies for antiscarring manipulation of wound healing.

Antenatal betamethasone administration alters stress physiology in healthy neonates.

OBJECTIVE: To analyze hypothalamic-pituitary-adrenal axis balance in healthy newborns after antenatal betamethasone treatment for lung maturation where delivery could be prolonged until or near term. METHODS: In a prospective observational study, salivary cortisol and cortisone levels were measured at the fourth day of life during resting conditions and in response to a pain-induced stress event in 23 neonates with antenatal exposure to a single course of betamethasone (2×12 mg) and compared with 40 controls. The mean interval between betamethasone treatment and delivery was 60±23 days. RESULTS: On day 4 of life, neonates in the control group exhibited a significant increase in cortisol and cortisone from baseline levels after the stress induction (1.175–2.4 ng/mL for cortisol and 11.35–18.15 ng/mL for cortisone [both P<.05]), whereas, in betamethasone-exposed neonates, cortisol and cortisone stress response was not significantly different from baseline levels (1.39–1.6 ng/mL for cortisone [P=.76] and 14.8–17.1 ng/mL for cortisol [P=.69]). No influence of gestational age at betamethasone administration (P=.76) or gestational age at delivery (P=.71) on stress response patterns was observed in a multiple stepwise regression. CONCLUSION: A single course of antenatal betamethasone treatment induces a suppression of stress reactivity in healthy newborns. LEVEL OF EVIDENCE: II

Nuchal cords in term and postterm deliveries--do we need to know?

Objective: To analyze the effect of nuchal cords on perinatal features at delivery of term and postterm pregnancies. Methods: A total of 11,748 women with planned vaginal deliveries, including 9,574 term and 2,174 postterm deliveries, were analyzed for intrapartum events, clinical peripartum management, mode of delivery, and neonatal outcome. The presence of nuchal cords was diagnosed clinically at the time of delivery. Data were obtained from our perinatal database between 1995 and 2004 for retrospective analysis. Results: The incidence of nuchal cords in term and postterm deliveries was 33.7% and 35.1%, respectively. Multiple nuchal cords were present in 5.8% of term and 5.5% of postterm deliveries. Intrapartum signs of fetal compromise were increased in all groups, albeit not all reaching statistical significance in postterm deliveries. Meconium staining was significantly increased only in multiple nuchal cords of postterm deliveries (42.1% compared with 30.1%, P < .05). Mode of delivery was unchanged in all nuchal cord groups. Unfavorable neonatal blood gas values were significantly more frequent in all nuchal cord groups. Nevertheless, 5-minute Apgar scores less than 7 were not more common, and admission to neonatal unit was not required more frequently. Neonatal mean birth weight was significantly lower in all nuchal cord groups. Conclusion: Nuchal cords do not influence clinical management at delivery, and neonatal primary adaption is not impaired. Our data show that ultrasonographic nuchal cord assessment is not necessary at the time of admission for delivery. Level of Evidence: II-3

Blunted stress response in small for gestational age neonates.

There is evidence that adverse conditions during intrauterine development affect future health of the offspring. Hypothalamus-pituitary-adrenal (HPA) axis dysregulation is assumed to play an important role in the association of small for gestational age (SGA) and the pathogenesis of hypertension and the metabolic syndrome. Stress response patterns in SGA neonates may identify a link with intrauterine-induced permanent maladaptation of the HPA axis. Salivary cortisol and cortisone levels were therefore analyzed during resting conditions and in response to a pain-induced stress event in SGA (<5th percentile) and appropriate for gestational age (AGA) neonates born ≥34 wk of gestation. In AGA neonates, salivary cortisol and cortisone levels significantly increased after the stress event (p < 0.05). In contrast, SGA infants exhibited a blunted steroid release after stress induction (p = 0.76, p = 0.65, respectively). No influence of mode of delivery (p = 0.93), gender (p = 0.21), and gestational age (p = 0.57) on stress response patterns was observed in a multiple stepwise regression. SGA neonates show a blunted physiologic activation of the HPA axis in response to a stress stimulus. Thus, intrauterine-induced alteration of HPA axis regulation seems to persist into the postnatal period and represents a prerequisite for the hypothesis of HPA axis involvement in the fetal origin of adult diseases.

Continuous independent quality control for fetal ultrasound biometry provided by the cumulative summation technique

To apply the cumulative summation (CUSUM) technique for an evaluation of the learning process of sonographic fetal weight estimation at term in combination with the z‐scores of biometry determinants and to assess the time of appearance and sources of errors.

Sonographic prediction of macrosomia cannot be improved by combination with pregnancy-specific characteristics

To evaluate the predictive value of a combination of sonographic, clinical and demographic data for detecting fetal macrosomia compared to ultrasound fetal weight estimation alone.

Minimally invasive, imaging guided virtual autopsy compared to conventional autopsy in foetal, newborn and infant cases: study protocol for the paediatric virtual autopsy trial.

BackgroundIn light of declining autopsy rates around the world, post-mortem MR imaging is a promising alternative to conventional autopsy in the investigation of infant death. A major drawback of this non-invasive autopsy approach is the fact that histopathological and microbiological examination of the tissue is not possible. The objective of this prospective study is to compare the performance of minimally invasive, virtual autopsy, including CT-guided biopsy, with conventional autopsy procedures in a paediatric population.Methods/DesignFoetuses, newborns and infants that are referred for autopsy at three different institutions associated with the University of Zurich will be eligible for recruitment. All bodies will be examined with a commercial CT and a 3 Tesla MRI scanner, masked to the results of conventional autopsy. After cross-sectional imaging, CT-guided tissue sampling will be performed by a multifunctional robotic system (Virtobot) allowing for automated post-mortem biopsies. Virtual autopsy results will be classified with regards to the likely final diagnosis and major pathological findings and compared to the results of conventional autopsy, which remains the diagnostic gold standard.DiscussionThere is an urgent need for the development of alternative post-mortem examination methods, not only as a counselling tool for families and as a quality control measure for clinical diagnosis and treatment but also as an instrument to advance medical knowledge and clinical practice. This interdisciplinary study will determine whether virtual autopsy will narrow the gap in information between non-invasive and traditional autopsy procedures.Trial RegistrationClinicalTrials.gov: NCT01888380

Newborn weight charts underestimate the incidence of low birthweight in preterm infants

OBJECTIVE The objective of the study was to compare sonographic fetal weight estimates with newborn weight charts and analyze the predictive accuracy of the ponderal index (PI) in preterm infants. STUDY DESIGN We generated sonographic reference curves for fetal weight and PI estimates from a database of fetal biometric records from 12,589 term deliveries. We then plotted sonographic and newborn weight and PI of 2406 preterm newborns on these curves and compared them with published newborn weight charts. RESULTS The third centiles of sonographic and newborn weights diverged markedly between 25 and 36 weeks of gestation and by more than 400 g at 32-33 weeks. In contrast, sonographic and newborn PI values were similar despite uncertainties as to fetal length. CONCLUSION We suggest using sonographic reference fetal weights to screen preterm newborns for low birthweight. Uncertainties in fetal length threaten the reliability of the PI.

Evaluation of fetal anthropometric measures to predict the risk for shoulder dystocia

To evaluate the quality of anthropometric measures to improve the prediction of shoulder dystocia by combining different sonographic biometric parameters.

Risk factors of uterine rupture with a special interest to uterine fundal pressure

Abstract Purpose: Uterine rupture is a rare but serious event with a median incidence of 0.09%. Previous uterine surgery is the most common risk factor. The aim of our study was to analyze retrospectively women with uterine rupture during labor and to evaluate postulated risk factors such as uterine fundal pressure (UFP). Methods: Twenty thousand one hundred and fifty-two deliveries were analyzed retrospectively. Inclusion criteria were 22 weeks and 0 days–42 weeks and 0 days of gestation, singleton pregnancy and cephalic presentation. Women with primary cesarean section were excluded. A logistic regression analysis adjusting for possible risk factors was conducted and a subgroup analysis of women with unscarred uterus was performed. Results: Twenty-eight cases of uterine rupture were identified (incidence: 0.14%). Uterine rupture was noticed in multipara patients only. In the multivariate analysis among all study patients, only previous cesarean section remained a statistically significant risk factor [adjusted odds ration (adj. OR) 12.52 confidence interval (CI) 95% 5.21–30.09]. In the subgroup analysis among women with unscarred uterus (n=19,415) three risk factors were associated with uterine rupture: UFP (adj. OR 5.22 CI 95% 1.07–25.55), abnormal placentation (adj. OR 20.82 CI 95% 2.48–175.16) and age at delivery >40 years (adj. OR 4.77 CI 95% 1.44–15.85). Conclusions: The main risk factor for uterine rupture in the whole study population is previous uterine surgery. Risk factors in women with unscarred uterus were UFP, abnormal placentation, and age at delivery >40 years. The only factor which can be modified is UFP. We suggest that UFP should be used with caution at least in presence of other supposed risk factors.