Steven E. Calvin

Survival and follow-up of infants born at 23 to 26 weeks of gestational age: Effects of surfactant therapy

Abstract Little information is available regarding the effect of surfactant on outcome for infants born at or before 26 weeks of gestation. We addressed this issue by reviewing records of 310 infants born at gestational ages of 23 through 26 weeks who were admitted to our nursery from 1986, when surfactant was introduced, through 1990. Surfactant was administered to 154 infants (5 during a single-dose prevention study, 25 during a multiple-dose prevention study, 124 while receiving a Food and Drug Administration treatment investigational new drug); 156 infants were not treated with surfactant. Seventy-three percent of the treated infants survived, compared with 55% of the nontreated infants. Increased survival occurred at all gestational ages between 23 and 26 weeks but were greatest in infants born at 23 and 24 weeks. At follow-up, no differences in neurologic outcome were detected between surfactant-treated and nontreated infants. We conclude that surfactant use in extremely premature infants improves survival rates without increasing the proportion of impaired survivors. (J P EDIATR 1994;124: 119-24)

Microstructure and Mechanics of the Chorioamnion Membrane with an Emphasis on Fracture Properties

Abstract:  The normal mechanical functioning of an intact chorioamnion (CA) membrane is essential to successful human reproduction. The amnion and the chorion, separately and together as the bilayer chorioamnion, serve barrier and container functions throughout gestation, and these two important roles are required from conception to birth. The event associated with the “breaking of waters” is a landmark event in labor and delivery. Mechanical rupture of the CA membrane is part of the natural sequence of term delivery, but has serious implications when rupture occurs prior to term; preterm premature rupture of the CA membrane (PPROM) is associated with one‐third of premature births. The current manuscript reviews PPROM from a clinical, anatomical, and mechanical perspective with a special focus on the clinically relevant fracture properties of these membranes. Emphasis is given to the link between membrane structure and properties at macroscopic and microscopic length scales. Because it has been demonstrated that the mechanical properties of prematurely failed membranes are not different from membranes of the same gestational age that have remained intact, membrane failure is a local process that must be explored in terms of local changes in structure and properties of isolated portions of the membrane. Future diagnostic techniques aimed at detection of changes in membrane structure (including thickness) and altered mechanical stiffness or strength may allow for prefailure diagnosis of membrane weak spots, thus opening the door for potential intervention and treatment techniques for preterm membrane rupture.

Uniaxial and biaxial mechanical behavior of human amnion

Chorioamnion, the membrane surrounding a fetus during gestation, is a structural softtissue critical for maintaining a successful pregnancy and delivery. However, themechanical behavior of this tissue membrane is poorly understood. The structuralcomponent of chorioamnion is the amnion sublayer, which provides the membrane’smechanical integrity via a dense collagen network and is the focus of thisinvestigation. Amnion uniaxial and planar equi-biaxial tension testing was performedusing cyclic loading and stress-relaxation. Cyclic testing demonstrated dramatic energydissipation in the first cycle followed by less hysteresis on subsequent cycles.Fractional energy dissipation per cycle was strain dependent, with greatest dissipationat small strain levels. Stress-relaxation testing demonstrated a level-dependent responseand continued relaxation after long relaxation times. A nonlinear viscoelastic(separable) hereditary integral approach was inadequate to model the amnion responsedue to intrinsic coupling of the strain- and time-dependent responses.

Mechanical failure of human fetal membrane tissues

Mechanical integrity of the chorioamnion membrane, and the component chorion and amnion layers, was assessed with biaxial puncture testing. Fetal membranes were obtained from term placentas following labored natural delivery or scheduled cesarean section. Preterm specimens were obtained from deliveries prior to 37 weeks gestation. Dividing and peripheral membranes were obtained from multiple gestation pregnancies. Specimens were gripped between parallel plates with circular openings and loaded with an instrumented, hand-held blunt probe until rupture occurred. Peak force was recorded and rupture sites were examined. Defects in multi-layered membranes differed in both size and shape in the individual layers. Compared with chorion and whole chorioamnion, amnion was more mechanically sensitive to different obstetrical conditions. Amnion varied in response at different physical locations within the same patient. Membrane and component puncture force data were used to calculate biaxial failure strength. Membrane stresses arising from amniotic fluid pressure were computed as a function of gestational age, and compared to membrane strength to examine the criterion for membrane failure in vivo. Possible mechanical conditions for preterm membrane rupture were examined.

Is pulsed Doppler velocimetry useful in the management of multiple-gestation pregnancies?

Few studies have addressed the significance of umbilical artery pulsed Doppler velocimetry in multiple gestation. Level II ultrasonography and pulsed Doppler studies were performed in 94 twin pairs and seven sets of triplets, which yielded data on 207 fetuses. A systolic/diastolic ratio was calculated for each fetus; abnormal pulsed Doppler velocimetry showed high correlation with adverse pregnancy events. Those with abnormal Doppler findings tended to be born 3 to 4 weeks earlier and to exhibit a greater number of stillbirths and structural malformations, as well as greater morbidity, when compared with fetuses without abnormal Doppler results. Fifteen of 17 infants with abnormal antenatal waveforms suffered serious morbidity. Seven were small for gestational age, and two were borderline for small for gestational age. An additional five infants with abnormal waveforms were appropriate for gestational age but were either recipient or donor in the twin transfusion syndrome. Eleven fetuses with this syndrome are described. Donor twins tended to be severely small for gestational age, with 7 of the 11 infants showing elevated systolic/diastolic ratios. Amniotic fluid volume tended to be diminished in the donors sac but normal or increased in the recipients sac. The observations in the study correlate with suspected physiologic changes of this syndrome. Because present findings suggest that fetuses with abnormal velocimetry suffer increased morbidity and mortality, a more rational method of management that uses Doppler data is suggested for multiple gestations.

Fracture Resistance of Human Amnion

While normal delivery requires disruption of the placental membranes (the “breaking of waters”), in one third of premature births delivery results from with mechanical rupture of the placental membranes prior to full-term gestation [1]. The biomechanical investigation of membrane rupture has thus been a subject of recent study [2–5]. In particular, mechanical investigations aimed specifically at understanding the membrane rupture process have concluded that the chorioamnion membrane bilayer breaks in two separate events, such that the chorion and amnion component layers fail independently, and that the delamination of the chorioamnion may represent a significant fraction of the total mechanical work done in membrane rupture [5]. The amnion is the stiffer and stronger of the two membrane layers, consisting primarily of a dense type I collagen network.Copyright