Clinics in Perinatology

Published by WB Saunders
Print ISSN: 0095-5108
Publications
Present generation mechanical ventilators are available with advanced microprocessor-based technology. Greater emphasis is being placed on the patient controlling the ventilator, rather than the physician controlling it. Pressure support ventilation (PSV) is a form of patient-triggered ventilation that supports spontaneous breathing during mechanical ventilation. It is flow-cycled, allowing the patient to determine the inspiratory time and rate. Each spontaneous breath is terminated when inspiratory flow decelerates to a predefined percentage of peak flow. At present, strict comparisons of the usefulness of PSV with other modalities of synchronized ventilation in newborns remain limited. This article reviews the principles and clinical applications of PSV for newborns who have respiratory failure.
 
Information regarding lung mechanics and pulmonary function may be used to influence the selection of tiny infant ventilator settings and thus minimize the risk for lung injury during mechanical ventilation. Data regarding compliance and resistance are presented in comparison to various ventilator settings.
 
Data on body water content and distribution in normally grown neonates weighing 500 to 1000 grams are presented, compared to data from full-term neonates, and discussed in the context of the continuum in growth from fertilized ovum to neonate at term.
 
VVLBW infants pose a challenge in the management of their hemodynamic changes. Data are just accumulating regarding the hemodynamic variables in this very special group. We have described several newly developed methods of monitoring hemodynamic variables in infants less than 1000 gm. In the coming decade, some of these methods may become more refined and routine.
 
The limits set for aggressive management of the VLBW infant have gradually been lowered in vitrue of the successful survival at each birth weight. It appears that, with each reduction in the birth weight at which maximal efforts should be used, enough babies have survived to encourage us to continue. As we drive to bring the limit of viability to lower gestations and lower birth weights, we are finding some biologic limitations to extra-uterine survival that present technology and knowledge cannot overcome. Unquestionably, there is a need for more comprehensive statistics to allow us to define the lower limit of survival.
 
Today, in all ventilated neonates, an increase in survival rate and an improved long-term outcome can be seen. Technological advances of the past decade in infant ventilators have enabled ventilation of neonates weighing even <500 gm. Preliminary studies on surfactant replacement therapy for <1000 gm infants have shown that early surfactant treatment in the delivery room reduces the need for higher ventilatory support. A significant decrease in neonatal mortality was seen in our neonatal ICU over a decade. Instead of defining an 'ideal ventilator' or 'ideal patterns of ventilation in infants with birth weight <1000 gm and their outcomes. Because understanding proper assisted ventilation techniques requires knowledge of lung development, we will review this briefly.
 
This study was undertaken to identify the pathologic processes in premature infants weighing less than 1000 gm who require surgery, and the outcome of such operations. These neonates required surgery for NEC and PDA. Congenital anomalies were not encountered in our series. No increased mortality due to surgery was observed, and overall mortality was comparable for infants less than 1000 gm and for premature infants with similar diseases. We conclude that surgery in premature infants less than 1000 gm is performed for acquired diseases, and mortality is not increased by the need for surgery.
 
This article is a review of the various factors relating to fetal and neonatal mortality in infants of a particular birth weight. Factors influencing survival positively also are considered, including various presentations and some specific maternal factors.
 
This article examines clinical issues regarding gut maturation, gut colonizatiion, gut luminal starvation, a germ-free gut, and the role of enteral intake in the pathogenesis of necrotizing enterocolitis (NEC) in very low birth weight neonates and micropremies. NEC is identified as the final common pathway for a variety of etiologic mechanisms, only one of which is consistent with the enteral-based theory of NEC. The technique of minimal enteral intake ("gut priming") is discussed as a strategy to maintain the normal ontological processes of the developing gut ex utero. A combination of enteral plus parenteral intake is described to achieve nutritional goals.
 
The renovation of the neonatal intensive care unit at The New York Hospital has served to test several new ideas about the design of intensive care facilities for infants. Our experience has supported our original feelings that smaller rooms rather than large open spaces offer significant advantages to both staff and families of patients. The radial arrangement of beds around a central supply module has concentrated our available floor space immediately around the patient's bed while providing convenient access to virtually all supplies used in infant care with a minimum of labor devoted to stock maintenance. The anticipation of our relationships with supportive services such as radiology and biochemistry has allowed us to integrate these functions smoothly into the design of the unit in such a way that service and patient care are generally improved as a result of this advance planning. In short, the design has proved conceptually sound but shares flaws that many units before ours have recognized. You cannot have too much storage space or too much floor space. In general, this design has vindicated our original concept that facility design should offer unique solutions to individual problems. It is difficult to generalize about what will and what will not work in a particular setting. But, in general, careful consideration and good planning are excellent investments in the future success of a design for a new ICU or a facility renovation.
 
The widespread use of chloramphenicol in the newborn infant prior to an adequate appreciation of the special characteristics of the mechanism of action of the drug in the neonate led to the tragic saga of the gray syndrom. Some 20 years later, we possess considerably more insight into the effects of chloramphenicol and the handling of the drug by the newborn infant. This insight should allow for the use of this potentially valuable drug in a safe and effective manner. The availability of sensitive and specific assays for chloramphenicol makes therapeutic monitoring feasible and such monitoring should add to the safety of the use of chloramphenicol in the newborn infant.
 
A great deal of experience with intrauterine transfusions has been generated in medical centers around the world since Liley's original report. This review will consider the benefits and risks of this technique in the modern management of Rh hemolytic disease. Modifications of technique, complications, survival data, and long-term follow-up studies will be discussed.
 
Although the physician has attempted to understand the relationship of yellow jaundice to newborn infants for 2000 years and although kernicterus has been described for 100 years, 1980 finds us with new data, new interpretations of old data, and new questions about old data which force us to reconsider and reevaluate our understanding of hyperbilirubinemia, the development of kernicterus, and the therapies we utilize. Factors that must be considered are the physiologic mechanisms by which bilirubin is catabolized and excreted; the physiologic and pathologic factors that affect the catabolism and distribution of bilirubin; the mechanism by which central nervous system bilirubin toxicity occurs, that is, bilirubin encephalopathy and kernicterus; the degree of accuracy, reliability, and clinical applicability of the laboratory tests by which potential bilirubin toxicity is judged; and the value of the available methods by which bilirubin levels are modifed or lowered in the jaundiced premature and full-term infant. This article reviews these factors and summarizes the understanding of the problems and practices as viewed from the perspective of the practicing clinician.
 
Since the premature nursery has become a neonatal intensive care unit, the survival rates of low birth weight infants have radically improved. Survival among infants weighing as little as 1500 gm is nearly as good as that among full-term infants. Mortality among infants with hyaline membrane disease has been reduced to as little as 10 per cent of the cases referred to neonatal intensive care units. For these improvements, clinicians and parents can acknowledge the use of such sophisticated, expensive, and invasive techniques as intra-aortic monitoring of blood pressure and oxygenation, assisted positive pressure ventilation, total parenteral nutrition with amino acid solutions, and aggressive management of surgical problems. Improvements in maternal and neonatal transport services have made these services available to wider areas, thus serving large numbers of mothers and infants. The time has come to address the question of provision of intensive care to the very low birth weight infant: how small is too small with the technical facilities available to neonatologists at the start of a new decade?
 
Survival of extremely premature infants has been significantly higher in the last decade than previously, and may well have improved during this time. The majority of infants greater than or equal to 25 weeks' gestation survive today. Survival of infants 23 and 24 weeks' gestation is significantly lower, but is by no means negligible. Reports of survival of infants less than 23 weeks or less than 500-g birth weight are not unique. Moreover, the maximum survival of infants less than or equal to 25 weeks possible with current state-of-the-art care is not known. Currently available data do not allow survival of the individual extremely low-birth weight or extremely premature infant to be predicted with clinically acceptable accuracy. The concept of a limit of viability is vague and clinically and ethically simplistic. The provision of neonatal intensive care is not necessarily beneficial or justified merely because it affords some minimal chance of survival. This phrase should not be used to summarize the complex issues involved in balancing maternal and neonatal risks and benefits of intrapartum and neonatal care of the extremely low-birth weight or the extremely premature fetus and infant, the suffering of the infant and family, parental values and autonomy, and consumption of limited communal resources. It should be deleted from our vocabulary.
 
The Healthy People 2000 objectives for breastfeeding were to move the breastfeeding initiation rate to 75% from 54% and the breastfeeding continuation rate to 50% at age 6 months from the 1988 baseline of 21%. The 1996 data indicated that the goal will not be met either for initiation or duration in spite of governmental strategic planning and coalition building, the acknowledgement of the benefits of breastfeeding by professional associations, the implementation of the Baby-Friendly Hospital Initiative, or the efforts of individual health professionals. Clearly, there is still work to be done. The Baby-Friendly Hospital Initiative was organized within Baby-Friendly USA too late in the decade to have had any impact on the 1996 data. It may take an additional decade before sufficient hospitals and birthing centers are engaged in the process to make a measurable difference in duration. Work protection legislation was not introduced until 1998. A national breastfeeding committee was not formed until 1998. National breastfeeding promotion programs were still either in the planning stage or in early stages of implementation in 1996. There is no paid maternity leave guaranteed by legislation for women in the United States. The International Code on Marketing has not been addressed, except to propose ways of examining the issue. The blueprints developed by the Surgeon General's Workshop on Breastfeeding and the Call for Action workshop enumerated strategies that will be carried over to the 2010 objectives. New blueprints will be developed to meet the 2010 goals, but it is not enough to strategize and plan. The substantive advantages of breastfeeding make accomplishment of the goals imperative if we are to achieve "health for all."
 
Extracorporeal membrane oxygenation was established as a standard of care by demonstrating its ability to save lives in moribund infants. The designs of early studies provided no living cohorts of similarly ill patients by which to measure accurately other (and perhaps to many more important) outcomes of interest: long-term neurodevelopmental outcomes or cost. Prospective cohort studies of neurodevelopmental outcomes post-ECMO demonstrate: (1) because ECMO, as used, saves lives, there will be an increase in the absolute number of handicapped children surviving; (2) there is little evidence that ECMO creates a relative increase in the percent of handicapped children surviving severe respiratory failure. The high direct costs of an ECMO program are measured and well publicized. When such costs are compared with similar therapies in other fields (in such terms as cost per survivor), the cost of ECMO does not seem to be an outlier. Trials of newer therapies, such as iNO, show the capacity to decrease the use of ECMO but have failed to demonstrate either cost-effectiveness or better long-term outcomes. It has not been shown that either society or individual patients have benefited from the decreased need for ECMO.
 
The HIV problem will inexorably increase over the next decade, with an increasing proportionate impact upon women and children over the next decade. HIV will become endemic, essentially worldwide. Some regions in the developed world may be relatively spared if current trends continue. This may reduce the willingness to expend necessary resources, particularly if trends toward increasing isolationism continue. There are already signs of a world becoming "bored" with AIDS and the chronicity of a difficult problem. This engenders an atmosphere ripe for increasing discrimination, with the development of loopholes in protective legislation. Already in the United States, some lawsuits concerning health care access among employees have been decided in the employer's favor, permitting them to restrict access to health insurance, despite other regulations which might have protected such workers. Similarly, some HIV-infected health care workers have been dismissed or lost their privileges in the 1990s, despite passage of the Americans with Disabilities Act as well as preceding legislation. It remains to be seen how society will cope with these complicated issues. The view of AIDS in 2004 presented above is pessimistic. There are some important rays of hope. Recent innovative vaccine work and new theoretical models may put us on the road to success, both with preventive and therapeutic vaccines. In particular, the first success in eliciting protection against vaginal HIV exposure, albeit partial, was reported in mid 1993. In a simian immunodeficiency virus (SIV) in vivo experimental model, cellular immunity to SIV was induced in macaques without their developing any signs of SIV infection. These macaques after rechallenge with low-dose SIV remained free of detectable SIV, so there may be an element of protection associated with specific cellular immune responses to immunodeficiency viruses. However, very high-dose SIV rechallenge experiments in similar macaques still led to acquisition of active SIV infection, suggesting that any such protection was only partial. It is also possible that cellular immune protection may be of varying efficacy against different types of exposure, particularly parenteral versus mucosal (such as sexual) exposures. There is also reason for specific optimism concerning interventions that might directly reduce the risk of perinatal transmission. Data from studies of twins suggest that a substantial proportion of perinatal transmission does not occur until after labor has commenced. Thus, caesarian sections may potentially reduce the risk of transmission to the fetus in some cases.(ABSTRACT TRUNCATED AT 400 WORDS)
 
Not every aspect of sonographic examination reveals karyotypic abnormalities. Ultrasound examination of a fetus with trisomy 21 generally reveals normal amniotic fluid, normal placentation, and normal fetal growth. In addition, other chromosomal abnormalities have many of the same sonographic findings as Down syndrome, and many findings have a large overlap with phenotypically normal fetuses. The importance of second-trimester ultrasound screening for Down syndrome has remained great because of its ease of use and relative effectiveness. Trained sonographers can adjust the relative risk for trisomy 21 and alter the need for genetic amniocentesis. It is important that parents understand the limitations of a screening test and the risks and benefits of possible subsequent confirmatory testing. If a major structural abnormality is identified on ultrasound, karyotype determination should be considered. Nuchal thickness in the first or second trimester remains the most clinically useful marker for trisomy 21. The predictive value of all the markers depends on the population studied and can be modified by a host of biochemical markers and historical factors. If fetal karyotype analysis could be performed without sampling through the uterus, prenatal diagnosis could be offered to all pregnant women, and screening would be unnecessary. Despite its limitations, ultrasound will have an important role in prenatal diagnosis at least until isolating and testing fetal cells from maternal blood or other sources becomes practical and widely available. Whether used alone or in conjunction with additional biochemical or molecular serum markers, ultrasound is an important and powerful tool in prenatal genetic evaluation.
 
Human milk provided by healthy and well-nourished mothers is believed to cover the infant's nutrient requirements during the first half year of life. It is composed of a mixture of nutritive components as well as other bioactive factors with relevant physiologic effects in the neonate infant. Human milk composition has a dynamic nature and varies with time postpartum, during a nursing, and with the mother's diet and certain diseases. The changes of human milk composition with time of lactation seem to match the changing needs of the growing infant over time. Human milk proteins are a source of peptides, amino acids, and nitrogen for the infant, but also in the protein fraction reside other properties of human milk that may benefit the breastfeeding infant. Specific whey proteins are involved in the development of the immune response (immunoglobulins), whereas others participate in the nonimmunologic defense (lactoferrin). In addition, human milk contains a complex mixture of oligosaccharides that are present only in minute amounts in other mammal's milk. They may act as inhibitors of bacterial adhesion to epithelial surfaces, and thus play an important role in preventing infectious diseases in the newborn infant. Oligosaccharides may also promote the development of a so-called bifidus flora. In the next years, future research will lead to improved characterization of human milk components and elucidation of their individual mechanisms of action, which will increase our knowledge about the properties of human milk and the benefits of breastfeeding for the infant.
 
There has been an increase in hyperbilirubinemia in the newborn population and, perhaps, an increase in bilirubin encephalopathy. The early discharge of newborns from hospital has made it necessary for us to reorient our thinking about bilirubin levels in the first 24 to 48 hours of life and alter our approach to follow-up. The pediatrician must evaluate and follow infants who have risk factors for the development of severe hyperbilirubinemia, paying particular attention to the breast-feeding, near-term infant.
 
Vasodilators have demonstrated efficacy in neonates with depressed myocardial function. The magnitude of benefit depends on the preexisting hemodynamic state and concurrent treatment modalities. In patients with increased filling pressures, vasodilators increase cardiac output with negligible effect on MAP, with volume resuscitation to restore pretreatment filling pressures offering additional benefit. The rationale for use in neonatal respiratory disease remains less clear, with no vasoactive drug showing selective pulmonary vasodilatation. Benefit no doubt accrues from the improved coronary perfusion that occurs with reduction in filling pressures. In addition, reduced interventricular diastolic dependence and thereby improved ventricular compliance, as well as the afterload-reducing effect of decreased chamber size, may significantly reduce the effect of the lung disease on myocardial functioning.
 
Perforated NEC in the fragile, premature infant remains a complex neonatal and surgical problem. Future investigation into the basic mechanisms of the intestinal inflammatory response in the premature neonate may allow for preventive strategies in the management of NEC. Until then, surgical management for perforated NEC will remain a necessary intervention to treat the complications of this disease. The two most commonly used surgical strategies for perforated NEC are laparotomy, bowel resection, and enterostomy versus primary peritoneal drainage. There are no compelling, prospective, controlled data supporting one procedure over the other. Although there are several surgical options for treating perforated NEC, definitive evidence-based guidelines for the best surgical treatment in terms of survival outcome remain to be determined.
 
Sonographic technology has given the prenatal diagnostician the ability to accurately visualize fetal malformations. This article demonstrates the currently available capability of applying sonographically derived information concerning fetal dysmorphology to our knowledge of genetic disorders and syndromes. As a result, there can be a significant improvement in the management and counseling of these patients. After an initial discussion of normal embryology, principles of abdominal ultrasonography are discussed and applied to the following anomalies: omphalocele, gastroschisis, diaphragmatic hernia, duodenal atresia, other intestinal atresias and stenoses, renal anomalies, and obstructive uropathies.
 
The prenatal diagnosis and antepartum management of congenital diaphragmatic hernia and anterior abdominal wall defects are reviewed. In addition, the intrapartum and neonatal considerations and management strategies are discussed.
 
Omphalocele and gastroschisis are among the more common neonatal surgical conditions. Although they share many clinical features and management is similar, there are important embryological and epidemiological differences. Gastroschisis is characterized by a high incidence of prematurity and the invariable occurrence of malrotation. The most striking finding in omphalocele is the 76 per cent incidence of associated anomalies. Lethal trisomy was present in 20 percent, congenital heart disease in 20 percent, and Beckwith's syndrome in 14 percent of patients. In this series, survival rate was 72 percent for gastroschisis and 56 percent for omphalocele (74 percent for excluding trisomies and one untreated patient with vesicointestinal fissure). Continued improvement in the survival rate of infants with abdominal wall defects can be expected if the following principles are observed: adequate fluid replacement, maintenance of body temperature, nasogastric decompression, and antibiotic therapy before and during operation; recognition of associated life-threatening anomalies, particularly Beckwith's syndrome, which require concomitant treatment; staged repair of the defect using silicone elastomer prosthesis if primary closure without tension is not possible; performance of enterostomy rather than primary anastomosis if bowel resection is necessary; and early and adequate metabolic support by parenteral nutrition.
 
Most neonatal abdominal masses will be due to benign retroperitoneal lesions such as hydronephrosis and multicystic dysplastic kidney. Although history and physical examination, plain radiographs and ultrasonography will confirm most diagnoses, severe unilateral hydronephrosis, hemorrhagic neuroblastoma, and intraperitoneal cysts may provide diagnostic difficulties. Masses identified by prenatal ultrasound need careful evaluation as they may represent normal structures, nonsignificant variants, or physiologically significant anomalies. Many lesions will require operative intervention, which can be safely performed in small infants by trained personnel at facilities with appropriate support services. Genuine controversy exists in the management of some of these lesions including MDK, renal vein thrombosis, and acalculous cholecystitis.
 
In summary, trauma occurs relatively frequently among pregnant patients. Various anatomic and physiologic changes of pregnancy may alter the type of injury experienced by pregnant women. These changes may also alter the manifestations of given injuries and the treatment required to reestablish maternal-fetal hemostasis. Fortunately, most trauma experienced by pregnant individuals is minor and is associated with good prognosis for both the mother and her fetus. Blunt trauma as a result of automobile collision is the most frequent form of serious injury involving pregnant women. However, several cases of penetrating abdominal wounds have also been reported. Both blunt and penetrating trauma may frequently injure the uterus. Fetal intracranial injury and fracture, as well as abruption, often occur as a result of blunt trauma. Multiple direct fetal, placental, and cord injuries have been reported as a result of penetrating trauma. Both blunt and penetrating trauma frequently cause injury to other intraabdominal organs, and blunt trauma is associated with an especially high incidence of pelvic fracture and retroperitoneal hemorrhage. Laparotomy is often required to treat such injuries. At the time of the laparotomy, difficult decisions are required in determining whether the fetus is best delivered or left in utero. Recent technologic advances for assessing fetal status may be helpful in these decisions. Rarely, a mother may expire with her living fetus undelivered, and a rapid postmortem cesarean section may save the fetal life. During the last several years, the prognosis for both trauma victims and gravid women with complicated pregnancies and their fetuses has improved markedly. Hopefully, during the next several years, the knowledge and therapeutic modalities developed to treat each group will be combined to provide optimal care for the pregnant trauma victim and her fetus.
 
The embryology of the anterior abdominal wall and umbilical cord is presented at the start of this article. A chronologic explanation of the abnormal embryology and resulting anomalies is presented in tabular form. This method of presentation demonstrates the effect of the timing of abnormal development on the pathophysiology and severity of the lesion. Techniques involved in the prenatal diagnosis of these abnormalities are described st the beginning of the article. Each of the developmental anomalies of the abdominal wall is then reviewed, again in chronologic order of embryologic development. Anomalies of the umbilical cord are reviewed at the end of the article.
 
The pregnant patient with abdominal pain can be one of the most difficult diagnostic challenges to both the obstetrically and nonobstetrically oriented physician. Pregnancy is accompanied by maternal physiologic and anatomic changes that may alter the symptoms and normal response to intraabdominal disease. The following discussion reviews the more common causes of abdominal pain in the gravid patient which are unrelated to pregnancy. If not diagnosed and managed early, these conditions may be associated with increased maternal and fetal mortality.
 
Abdominal wall defects (AWDs) are a common congenital surgical problem in fetuses and neonates. The incidence of these defects has steadily increased over the past few decades due to rising numbers of gastroschisis. Most of these anomalies are diagnosed prenatally and then managed at a center with available pediatric surgical, neonatology, and high-risk obstetric support. Omphaloceles and gastroschisis are distinct anomalies that have different management and outcomes. There have been a number of recent advances in the care of patients with AWDs, both in the fetus and the newborn, which will be discussed in this article.
 
Dysmorphogenesis of the central nervous system (CNS) can be broadly classified within a pathogenetic framework. Natural deformations result from aberrant mechanical forces, such as intrauterine constraint, and may result in craniosynostosis and abnormally shaped calvaria and brains. Dysplasia is reflected in altered gyral patterns and heterotopias, while disruptions in morphogenesis produce more serious consequences. Examples are early amnion rupture sequence, porencephaly, and atelencephaly/aproscencephaly. Malformations are diagnosed prenatally with increasing frequency and include such recognized entities as neural tube defects (anencephaly, encephalocele, myelomeningocele), holoprosencephaly, agenesis of the corpus callosum, and Dandy-Walker and Arnold-Chiari malformations. By maintaining a pathogenetic view of congenital anomalies of the CNS, the variability of anatomic features and role of etiologic factors may be better comprehended.
 
THOP is a relatively common condition whose long-term effects remain uncertain. The preponderance of evidence indicates that at the very least THOP is a marker of elevated risk of neurodevelopmental adversity, but whether this association is truly causal and whether thyroxine treatment in the neonatal period can prevent adverse outcome is as yet unknown. Since the number of infants born and surviving at very early gestations continues to increase, the importance of this condition will be magnified in the future. The major difficulty in establishing the causal role of THOP is the tangled time order of events in the early neonatal period. It is therefore unlikely that further observational studies will advance understanding. Energies should be focused on Assessing neurodevelopment objectively in survivors in each of the TRH trials. Developing a new multicenter trial of newborn supplementation with thyroid hormone that is carefully planned to have sufficient power to assess neurodevelopment in treated and untreated infants under a variety of baseline conditions.
 
The phenomenal developments in molecular genetics and technological refinements which have occurred over the past decade are revolutionizing the area of prenatal genetics. State-of-the-art care commences with comprehensive preconceptional counseling. Prenatal diagnosis is now feasible from the moment of conception onward. Imaging techniques have allowed non-invasive diagnosis while minimally invasive techniques concentrate on sampling maternal blood for fetal cells or markers of feto-placental metabolism. Invasive techniques are rapidly expanding and becoming safer, comprising of chorionic villus sampling, early amniocentesis, midtrimester amniocentesis as well as very early fetoscopy and umbilical vein sampling.
 
Cesarean delivery is indicated at any stage in the labor process in the presence of nonreassuring fetal status or when conservative measures fail in the setting of abnormal labor. In the absence of maternal or fetal indications for expedited delivery, cesarean delivery is not indicated for latent phase disorders. When to intervene for protracted labor is arguable, but slow rates of labor progress are consistent with safe vaginal delivery. Cesarean delivery in the second stage should be avoided for at least 4 hours if there is progressive fetal descent.
 
The external examination of the perineum in the neonate so often provides normal results that it may be neglected, especially if the infant has acute problems in the chest, cranium, or abdomen. A thorough search for abnormalities in the delivery room and nursery may provide a clue to more serious problems elsewhere and prevent embarrassment later when the abnormality is discovered by the parents. This discussion is divided according to anatomic areas: the scrotum either abnormally large or empty, the penis, and miscellaneous conditions in the perineum.
 
Persistent pulmonary hypertension poses a significant problem to the surgeon managing an infant with congenital diaphragmatic hernia. It is likely that a number of abnormalities contribute to this pathophysiologic entity. These include: (1) in the hypoplastic lung the overall cross-sectional area of the pulmonary vascular bed is reduced, (2) the muscular arteries are hypertrophied and extend more peripherally than normal, (3) the pulmonary vessels are more labile than normal and are overly sensitive to the normal stimuli of vasoconstriction, and (4) the immature surfactant-deficient lung is predisposed to barotrauma and atelectasis, resulting in alveolar hypoxemia which contributes to pulmonary hypertension. All of these interfere with the ability of the lung to accept the increase in pulmonary blood flow required by the transitional circulation. If this impairment reaches a level such that the lung cannot accept the right ventricular output then pulmonary hypertension will ensue and a poor outcome can be anticipated.
 
There are many causes of congenital anomalies in man. Unknown causes account for 65 to 70 per cent, genetically transmitted diseases 20 per cent, environmental factors 10 per cent, and chromosomal aberrations 3 to 5 per cent. Fetal anomalies traverse a spectrum from minimal involvement such as polydactyly to those incompatible with life such as renal agenesis. The role of the health care team is to provide appropriate genetic counseling and intrapartum evaluation to those parents who have conceived previous fetuses with congenital malformations or who have a family history of such a predisposition. Superimposed upon this responsibility is that of maintaining an index of suspicion in apparently 'normal' pregnancies for indications of fetal malformations. Until recently the prenatal diagnosis of congenital anomalies was limited to those which manifested their presence by either biochemical or chromosomal aberrations noted in analysis of amniotic fluid obtained during the second trimester. With the advent of fetoscopy, as well as real time and high contrast gray scale ultrasound, structural anomalies can now be evaluated by direct visualization of fetal anatomy. This review focuses on the use and interpretation of modalities which enable the clinician to diagnose structural anomalies during the second and third trimesters of pregnancy.
 
Congenital diaphragmatic hernia results in abnormal lung development. There is a global hypoplasia with both lungs affected, the ipsilateral lung more severely. This results in a reduction in the number of bronchial divisions and a decrease in the quantity and maturity of the alveoli. The pneumocytes are dysfunctional, resulting in a total quantitative and qualitative reduction in surfactant and a decrease in antioxidant enzyme activity.
 
This article reviews renal, neurologic, cardiac, and pulmonary abnormalities in the term infant following perinatal asphyxia. The relationship of oliguria to central nervous system abnormalities is discussed, as well as the relationship of current measures of fetal hypoxia and long-term neurologic outcome.
 
We have reviewed the current status of prenatal diagnosis for chromosomal indications and for neural tube defects. The number of pregnancies monitored will increase as greater resources become available and as public education about genetics increases. The methodology has proved to be a powerful means of preventing the birth of individuals with significant genetic defects, thereby sparing both parents and society from the burdens produced by such disorders. In the future, it is likely to be even more effective.
 
We have reviewed the prenatal diagnosis and management of abnormalities in the urologic system. Urologic anomalies may be caused by embryologic aberrations, genetic disease, or a nonrandom association with other structural abnormalities. There is a wide range of prognoses, depending on the cause and the impact of the anomaly on the production of amniotic fluid. Management focuses on obtaining an accurate prenatal diagnosis, providing appropriate counseling, and ensuring the proper surveillance or treatment before and after birth.
 
Among the many causes of PPHN may be numbered several cardiovascular malformations. This article introduces the concept of PPHN due to congenital heart disease, illustrates each of the five categories of congenital heart disease that present as PPHN, and outlines noninvasive approaches for diagnosis of congenital heart disease in infants with PPHN.
 
Midtrimester abortion may be accomplished by a variety of techniques, alone or in combination. Comprehensive care of patients who require or request pregnancy termination in the second trimester must include careful assessment of medical and psychological conditions. Special attention needs to be paid to gestational age, and for many cases ultrasonography should be part of the evaluation. With the variety of techniques and combinations available, physicians can now individualize patient care to minimize morbidity and mortality while improving patient comfort and well being.
 
Chronic, subacute decidual hemorrhage (ie, abruptio placenta and retrochorionic hematoma formation) is an important contributor to preterm parturition. Such hemorrhage induces thrombin from decidual tissue factor, which plays a pivotal role in the development of preterm premature rupture of membranes and preterm delivery by acting through protease-activated receptors to promote the production of pro-inflammatory cytokines, and matrix-degrading metalloproteinases. Severe, acute abruption can lead to maternal and fetal mortality. Current management of abruption is individualized based on severity of disease, underlying etiology, and gestational age.
 
The majority of what we know about the development of the absorptive process is derived from animal studies, studies in human fetal or stillborn tissues, and epidemiologic investigations derived from clinical experience. One can readily ascertain from this review that the absorption of nutrients in the intestine of the premature infant relates to a dynamic developmental process in which the consecutive stages are pre-programmed but can also be regulated by environmental factors. An understanding of these factors may lead to therapeutic intervention in premature infants, as has been the case for the developing lung and respiratory distress syndrome. Application of this knowledge to the critically ill premature infant in the intensive care unit will need to proceed cautiously, but it is likely to yield major benefits in terms of decreased short- and long-term morbidity in these highly vulnerable patients.
 
The newborn infant's skin is not a complete barrier to the absorption of externally applied agents, particularly if it is damaged, diseased, or immature. Immaturity is the most important factor that determines percutaneous absorption. Very immature infants in the early neonatal period have a poorly developed epidermis, which is readily permeable to drugs. The main consequences of percutaneous absorption are hazardous. Topically applied agents are absorbed, causing toxic systemic effects that may result in illness and even death without the cause being recognized. No drug or antiseptic agent should be applied to the premature infant's skin without consideration of the effects that might result from percutaneous absorption. On a more optimistic note, the relatively permeable skin could be an advantage to the preterm infant by providing an alternative method of drug administration. The drug theophylline for example can be absorbed and produce therapeutic blood levels for up to 3 days after a single topical application. There is a need for the development of transdermal drug delivery systems for the newborn infant similar to those currently used for therapy in adults.
 
Top-cited authors
Barbara J Stoll
  • Emory University
Joseph Volpe
  • Harvard Medical School
Daniel J Ledbetter
  • Seattle Children's Hospital
David W Kays
  • Johns Hopkins Medicine
Max R Langham
  • The University of Tennessee Health Science Center