Although WHO has defined the upper limit of prematurity as a gestational age of 36 weeks and 6 days, the lower limit is determined by fetal organ development and advances in high-risk obstetric and neonatal intensive care. Dramatic decreases in neonatal mortality rates and gestational age-specific neonatal mortality rates have been associated with a concomitant lowering of the limit of viability (Alexander et al., 1999; Allen et al., 2000, Appendix B). A current concern is that a biological limit has been reached and that major new technological advances will be required for any further lowering of the limit of viability (Hack and Fanaroff, 1999).
A limiting factor in interpreting all studies of survival and complications at the lower limit of viability is the accuracy of gestational age determination. In these studies, various proportions of each population sample studied did not have ultrasound confirmation of the dates of conception. At the limit of viability, each week of gestation makes a difference in the rate of survival of an infant born preterm and the complications that the infant may encounter (Allen et al.,
1993; Wood et al., 2000). However, how much information is lost in these studies because of incorrect gestational age data? Could some of the infants who were born at 22 or 23 weeks of gestation and who survived have been misclassified and have actually been born at 24 or 25 weeks of gestation? Improvements in the accuracy of gestational age data will provide more reliable data on survival and outcomes at the limit of viability and enhance clinicians' ability to counsel the parents.
For infants born at the lower limit of viability, the aggressiveness of resuscitation at delivery varies considerably from region to region, as does the degree to which parents participate in the medical decision making (Hakansson et al., 2004; Haumont, 2005; Ho and Saigal, 2005; Lorenz and Paneth, 2000; Partridge et al., 2005; Appendix C). Infants born at 22 to 25 weeks gestation die if they are not resuscitated at birth and provided with neonatal intensive care. Many studies do not report the proportion of live births who were resuscitated. Concerns about the ultimate survival of infants born at the limit of viability to adulthood and the likelihood of significant disability or chronic illness, pain and suffering cause parents and health providers to question how these infants should be managed. Although most very immature infants die during the first day after birth, another concern is that further advances in neonatal intensive care may merely prolong their dying for days to weeks. Although there are sporadic reports of survival at the lowest gestational ages (21 or 22 weeks gestation) or birthweights (400 grams), some have defined the lower limit of viability as that gestational age or birthweight at which 50% survive (Alexander et al., 1999; Allen et al., 2000).
Discussion of the management and survival of infants born at the lower limit of viability requires extreme precision and attention to how mortality and outcome rates are calculated. For example, data should be provided as to what proportion of infants were resuscitated at delivery and provided with neonatal intensive care. The proportion of infants with congenital anomalies, especially anomalies that contribute to the infant's death, should be reported. Care should also be taken to describe the chronological age at which survival is ascertained. The conventional definition of the neonatal mortality rate excludes infants who survive past 28 days but who die before they leave the NICU. Likewise, studies that report survival to the time of NICU discharge may miss deaths later in the first year of life that would be captured by infant mortality rates.
Table 2-2 Definitions of Spontaneous Abortion, Fetal Death, Stillbirth and Live Birth
Fetal death or stillbirth
Abortion occurring without medical or mechanical means to empty the uterus.
Death before the complete expulsion or extraction from its mother of a product of conception, irrespective of the duration of pregnancy. The death is indicated by the fact that after such separation, the fetus does not breathe or show any other evidence of life, such as beating of the heart, pulsation of the umbilical cord, or definite movement of voluntary muscles. A death that occurs at 20 or more weeks of gestation constitutes a fetal death and after 28 weeks it is considered a late fetal death.
The term used to record a birth whenever the newborn at or sometime after birth breathes spontaneously, or shows any other sign of life such as a heartbeat or definite spontaneous movement of voluntary muscles. Heartbeats are to be distinguished from transient cardiac contractions, and respirations are to be distinguished from fleeting respiratory efforts or gasps.
Sources: CDC, 2004e, Cunningham et al. 2005
When reviewing mortality rates for infants born at the limit of viability, attention to the denominator used to calculate mortality rates at the limit of viability is important (Allen et al., 1993; Evans and Levene, 2001). Many tertiary-care NICUs report birth weight- and gestational age-specific mortality rates that use the number of infants admitted to the NICU as the denominator. However, many infants born at 22 to 25 weeks gestation die shortly after delivery, and are never admitted to a NICU. In addition, a large proportion of infants born at a gestational age of less than 23 weeks or with a birth weight of less than 500 grams are stillborn (60 to 89 percent and 68 to 77 percent, respectively) (Sauve et al., 1998; Wood et al., 2000).
Although there are guidelines for distinguishing between a fetal death and live birth exist (Table 2-2), the clinical distinction is not as clear as one might think. A fetal death occurs before the fetus is completely delivered and excludes induced terminations. The clinician must distinguish between evidence of life (e.g., beating heart, pulsation of the umbilical cord, or the movement of voluntary muscles) from transient or fleeting cardiac contractions, gasps, or jerks of the limbs. This is most difficult in born at 21 to 24 weeks of gestation. How many of these infants have been categorized in the past as live births instead of fetal deaths is unknown, as is how this categorization varies from region to region and even among health care providers at the same institution. A willingness to resuscitate a very immature infant who has a transient heart beat or gasp at delivery changes the classification of that infant from a fetal death to an infant death. This type of change in how an infant is classified has only a small impact on the preterm birth rate (because so many more infants are born after 26 weeks gestation), but could contribute substantially to rising U.S. Infant Mortality Rates. The use of perinatal mortality rates (the number of deaths of infants with gestational ages greater than 20 weeks/1,000 total births) may be a more useful measure of the outcomes of very preterm infants, since it includes infants who are stillborn and infants who die immediately after birth.
Marked regional variations in the management and the rates of survival of infants born at the lower limit of viability and variations in the methods used to estimate gestational age make it difficult to evaluate trends over time with respect to live birth rates by gestational age and fetal death rates (Costeloe et al., 2000; Lorenz et al., 2001; Sanders et al., 1998; Tyson et al., 1996). For infants born at the lower limit of viability, an accurate estimate of gestational age is essential for guiding discussions about the many decisions to be made during and after delivery, including the timing and mode of delivery and whether antenatal steroids and aggressive resuscitation should be used at the time of delivery. Discussions of management and outcomes should focus not on when survival is possible, but on a working definition of the limit of viability, when chances of survival, or of survival without major disability, are substantial (for example, 50%). Furthermore, better measures of fetal and infant maturity have the potential to improve the clinical care that is provided, improve the ability to predict short- and long-term outcomes, and assist families and health care providers in making difficult care management decisions.
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The first trimester is very important for the mother and the baby. For most women it is common to find out about their pregnancy after they have missed their menstrual cycle. Since, not all women note their menstrual cycle and dates of intercourse, it may cause slight confusion about the exact date of conception. That is why most women find out that they are pregnant only after one month of pregnancy.