Trends in rates of multiple vascular disruption defects, Atlanta, 1968-1989: is there evidence of a cocaine teratogenic epidemic?

Research suggests that, perhaps through mechanisms initiated by vasoconstriction and leading to vessel thrombosis or embolism, cocaine causes vascular disruption defects, and that frequent cocaine use during early pregnancy could disrupt multiple organ systems in the fetus. We hypothesized that if cocaine is an important cause of multiple vascular disruption defects, a rising prevalence of cocaine use by mothers during pregnancy should be accompanied by rising rates of these defects in their offspring. Using data from the Metropolitan Atlanta Congenital Defects Program, we identified all infants born in Atlanta from 1968 through 1989 who had nonsyndromic, provisional vascular disruption defects affecting more than one organ system: 61 infants (78%) had gastrointestinal and genitourinary defects, 7 (9%) had gastrointestinal and abdominal wall defects, 2 (3%) had gastrointestinal and limb reduction defects, 2 (3%) had limb reduction and abdominal wall defects, 2 (3%) had central nervous system and gastrointestinal defects, 2 (3%) had genitourinary and limb reduction defects, 1 (1%) had genitourinary and abdominal wall defects, and 1 (1%) had central nervous system and genitourinary defects. The prevalence of Atlanta infants with more than one vascular disruption defect is 0.13 per 1,000 live births. Chi-square analysis for trends showed no increase in prevalence during the study period. Our data are from one of the first population-based studies in which trends for defects potentially caused by maternal cocaine use are examined; the results of our study show no significant change in the prevalence of multiple vascular disruption defects over time.(ABSTRACT TRUNCATED AT 250 WORDS)     

A new syndrome with prenatally diagnosed thoracoschisis, hiatal hernia and extremities' agenesis: case report

Thoracoschisis is a very rare congenital anomaly and is usually associated with limb and abdominal wall defects forming part of limb-body wall complex. We here present a case of a 29-week-4-day pregnancy ended with intrauterine demise. Postmortem examination revealed hiatal hernia, thoracoschisis and protrusion of some part of liver from this defect, left forearm agenesis and right arm and right hand agenesis. The findings accompanying thoracoschisis in this presented case exclude any previously reported related syndrome and we believe that this is a new syndrome.     

A case report of ectopia cordis and omphalocele

A rare congenital defect in fusion of the anterior chest wall resulting in an extrathoracic location of the heart. Cantrell''s pentalogy is a congenital anomaly resulting from embryologic development defect and consists of the following: A deficiency of the anterior diaphragm, a midline supraumbilical abdominal wall defect, a defect in the diaphragmatic pericardium, congenital intracardiac abnormalities, and a defect of the lower sternum. Here we report a rare case of ectopic cordis with omphalocele.     

Absence of limbs and gross body wall defects: an epidemiological study of related rare malformation conditions.

The study is based on almost 10 million births and reports on 215 infants with two unusual malformations: amelia and gross body wall defect. Amelia without body wall defect was present in 116 cases, 67 had body wall defects without amelia, and 32 had both. The total rate was 2.2 per 100,000 births. The infants were divided into five mutually exclusive groups. There were 40 infants (0.4 per 100,000) with agenesis of the body stalk, 18 with amelia and other types of gross body wall defects (0.2 per 100,000), 56 with amelia and malformations other than gross body wall defects (0.6 per 100,000), 41 with amelia (with or without other limb reduction defects) but no nonlimb malformations (0.4 per 100,000), and 60 infants with gross body wall defects of a type other than agenesis of body stalk and without amelia (0.6 per 100,000). A weak trend of decreasing prevalence of these malformations was found during the observation period. Infants with agenesis of the body stalk and infants with amelia combined with other types of gross body wall defects occurred at an increased rate in infants of young women. This maternal age effect is also found with gastroschisis, but not with omphalocele, and may indicate etiological or pathogenetic similarities between gastroschisis and the two former groups of defect. In infants with amelia, additional limb reduction defects could be of any type: transverse, longitudinal, or intercalary. Therefore, amelia may be the end result of different types of disturbances of limb morphogenesis. There was an increased rate of twinning. The relationship with amniotic band syndrome is discussed.     

Problems posed by prenatal diagnosis of abdominal wall malformations

The authors present 6 observations of in utero detected abdominal wall defect : 2 laparoschisis and 4 omphaloceles. In three cases the diagnosis have been done prior week 20, by systematic AFP assay for amniocentesis performed for cytogenetic or metabolic reasons; the pregnancy was terminated. In three other cases, the pregnancy was complicated by hydramnios after week 30; amniocentesis for AFP and echography were performed to detect fetal malformations after associated with hydramnios. The detected abdominal wall anomaly was not alone: two fetus had an abnormal caryotype (trisomy 18), three other presented a polymalformative syndrome, a Beckwith-Wiedemann syndrome was discussed for the last child. The in utero diagnosis of omphalocele or laparoschisis implicates difficulties for genetic counselling, particularly if the diagnosis is done prior week 20. These anomalies can be treated with surgical management, but frequency of associated malformations must be underlined. it is important for genetic counselling to know the family history, the amniotic fluid cells caryotype, and an ultrasound scanning performed to reveal any other malformations.     

The extended latissimus dorsi flap in repair of anterior abdominal wall defects

Large abdominal wall defects (ventral hernias) can be difficult to repair. Some defects are not amenable to primary repair or the use of synthetic mesh because of repeated recurrence or wound infection. In complicated situations such as that mentioned above, the extended latissimus dorsi muscle flap has been used to repair upper and middle abdominal wall defects. This method has been utilized in six patients, and there has been no recurrence of the defect or evidence of a lumbar hernia. The follow-up has been from 7 to 66 months. The extended latissimus dorsi muscle flap has proven to be an excellent alternative in the repair of complicated abdominal wall defects.     

Omphalocele and gastroschisis: Black-White disparity in infant survival

BACKGROUND: Racial/ethnic variations in the occurrence of abdominal wall defects have been previously noted but it remains poorly understood whether race/ethnicity is a determinant of survival among affected infants. METHODS: Study was conducted on cases of gastroschisis and omphalocele recorded for the years 1983-1999 at the New York Congenital Malformation Registry. Adjusted and unadjusted hazard ratios were generated from a Proportional Hazards Regression model to compare survival among affected Blacks, Hispanics and Whites. The major end point of analysis was differences in all cause mortality among infants with abdominal wall birth defects across different racial/ethnic groups. RESULTS: Among the three racial/ethnic groups, 1481 infants were diagnosed with either omphalocele (978 or 66%) or gastroschisis (503 or 34%). Overall infant mortality rate (IMR) was 182 per 1000, with 74% of the deaths occurring within the first 28 days of life. Omphalocele infants had significantly higher infant mortality (IMR = 215 per 1000) than infants with gastroschisis (IMR = 118 per 1000)[p < 0.0001]. Overall, Black infants with abdominal wall defects had lower mortality indices than Whites and Hispanics. However, when considered as separate disease entities, Black infants were twice as likely to survive as compared to Whites if they had omphalocele [Adjusted Hazard Ratio (AHR) = 0.52; 95% Confidence Interval (CI) = 0.37-0.74], and twice as likely to die as Whites if they had gastroschisis instead (AHR = 2.23; 95% CI = 1.16-4.28). For both defect subtypes, Hispanics have risks for infant mortality comparable to Whites. CONCLUSIONS: The natural history of omphalocele and gastroschisis co-varies with race. Black infants with gastroschisis have worse survival outcomes while those with omphalocele have better chances of survival than their White or Hispanic counterparts.     

The separation of anatomic components technique for the reconstruction of massive midline abdominal wall defects: anatomy, surgical technique, applications, and limitations revisited

Reconstruction of massive abdominal wall defects has long been a vexing clinical problem. A landmark development for the autogenous tissue reconstruction of these difficult wounds was the introduction of "components of anatomic separation" technique by Ramirez et al. This method uses bilateral, innervated, bipedicle, rectus abdominis-transversus abdominis-internal oblique muscle flap complexes transposed medially to reconstruct the central abdominal wall. Enamored with this concept, this institution sought to define the limitations and complications and to quantify functional outcome with the use of this technique. During a 4-year period (July of 1991 to 1995), 22 patients underwent reconstruction of massive midline abdominal wounds. The defects varied in size from 6 to 14 cm in width and from 10 to 24 cm in height. Causes included removal of infected synthetic mesh material (n = 7), recurrent hernia (n = 4), removal of split-thickness skin graft and dense abdominal wall cicatrix (n = 4), parastomal hernia (n = 2), primary incisional hernia (n = 2), trauma/enteric sepsis (n = 2), and tumor resection (abdominal wall desmoid tumor involving the right rectus abdominis muscle) (n = 1). Twenty patients were treated with mobilization of both rectus abdominis muscles, and in two patients one muscle complex was used. The plane of "separation" was the interface between the external and internal oblique muscles. A quantitative dynamic assessment of the abdominal wall was performed in two patients by using a Cybex TEF machine, with analysis of truncal flexion strength being undertaken preoperatively and at 6 months after surgery. Patients achieved wound healing in all cases with one operation. Minor complications included superficial infection in two patients and a wound seroma in one. One patient developed a recurrent incisional hernia 8 months postoperatively. There was one postoperative death caused by multisystem organ failure. One patient required the addition of synthetic mesh to achieve abdominal closure. This case involved a thin patient whose defect exceeded 16 cm in width. There has been no clinically apparent muscle weakness in the abdomen over that present preoperatively. Analysis of preoperative and postoperative truncal force generation revealed a 40 percent increase in strength in the two patients tested on a Cybex machine. Reoperation was possible through the reconstructed abdominal wall in two patients without untoward sequela. This operation is an effective method for autogenous reconstruction of massive midline abdominal wall defects. It can be used either as a primary mode of defect closure or to treat the complications of trauma, surgery, or various diseases.     

Abdominal wall partitioning (the accordion effect) for reconstruction of major defects: a retrospective review of 10 patients

Ten patients underwent abdominal wall reconstruction using the technique of abdominal wall partitioning. All defects were closed in the midline by approximating fascia to fascia with the assistance of a general surgeon. One patient had skin grafted small bowel. Five patients had chronically infected mesh and previous failed attempts at repair. Four patients had large ventral hernias following gastric reduction operations and massive weight loss. No defect in any dimension was less than 20 cm. All patients had secure abdominal wall repair by reconstruction of a midline anchor for the abdominal wall musculature. One patient was lost to follow-up after 3 weeks. The average follow-up time for the remaining nine patients was 18.6 months (range, 6 months to 4.7 years). One patient required readmission to the hospital for management of a limited area of skin necrosis. Two patients had minor wound infections, and three patients had subcutaneous seromas, all of which were managed on an outpatient basis. One patient developed a 2 x 2-cm subxiphoid hernia recurrence. Technical details include subcutaneous undermining of the abdominal skin to the anterior axillary lines bilaterally, mobilization of the viscera to expose the white lines of Toldt bilaterally, and parallel, parasagittal, staggered releases of the transversalis fascia, transversalis muscle, external oblique fascia, external oblique muscle, and rectus fascia. These multiple releases allow expansion and translation of the abdominal wall by an accordion-like effect. This accordion-like effect allows closure of abdominal wall defects that are substantially larger than what can be closed with current techniques.     

Pentalogy of Cantrell: report of a case with consanguineous parents

Pentalogy of Cantrell is a syndrome evidencing five anomalies: a midline, upper abdominal wall abnormality; lower sternal defect; anterior diaphragmatic defect; diaphragmatic pericardial defect, and congenital abnormalities of the heart. Its prevalence is one in every 65,000 live births and a survival rate that is low if the fall the five defects are present or the gravity of the cardiac anomalies. It may be diagnosed during the first trimester obstetric ultrasound. For postnatal care, emission-computed tomography and magnetic resonance imaging is recommended for a clear definition of the extent of the defect and to design a course of corrective surgery. Herein, a case of pentology of Cantrell is reported for a child offspring of consanguineous parents.     

Cardiopathic effects of dichloroacetate in the fetal Long-Evans rat.

Dichloroacetic acid (DCA) is a by-product of the chlorine disinfection of water and may occur in treated water at levels exceeding 100 micrograms/L. Previous studies revealed teratogenic effects, particularly heart malformations, at high doses (900-2,400 mg/kg given on days 6-15 of pregnancy). In a series of three studies, groups of 7-10 Long-Evans rats were dosed with 1,900 mg/kg of DCA on days 6-8, 9-11, or 12-15; with 2,400 mg/kg on days 10, 11, 12, or 13; and with 3,500 mg/kg on days 9, 10, 11, 12, or 13, in an attempt to determine the most sensitive period and further characterize the heart defect. In a fourth study, six dams were treated with 1,900 mg/kg of DCA days 6-15 of pregnancy, and 56 fetuses were harvested for light microscopy of the heart. Eight control fetuses from four litters were also examined. No heart malformations were seen in the groups treated with 1,900 mg/kg DCA days 6-8 but were present in the group treated on days 9-11 and 12-15, with the higher incidence occurring on days 12-15. Single doses of 2,400 mg/kg DCA given on days 10, 11, 12, or 13 resulted in a much lower incidence of cardiac malformations, which occurred only on days 10 and 12. The high dose of DCA (3,500 mg/kg) did not increase the incidence of heart defects but showed that dosing on day 9 as well as on days 10 and 12 would produce the defect. The defects seen were characterized as high interventricular septal defects (H-IVSD). Light microscopy showed that the defect was caudal to the semilunar valves, with the anterior right wall of the aorta communicating with the right ventricle. Another aspect of the defect is at the level of the semilunar valves, with the right cusp or sinus of Valsalva in communication with the right ventricle. The defects are discussed more fully and methods for further study suggested.     

Risks associated with "components separation" for closure of complex abdominal wall defects

The reconstruction of complex abdominal wall defects can often pose a significant challenge to surgeons and their patients. Complex ventral hernias may result from large tumor resections, trauma from gunshot wounds, or infections following routine abdominal surgery. "Components separation" of the abdominal musculature uses advancement of local autologous tissue, when available, to close large ventral wall defects. The authors report on a retrospective chart review of 30 patients who underwent components separation for the closure of complex abdominal defects. The study group was 50 percent female, with a mean age of 45 years, body mass index of 33.2 kg/m2, and abdominal defect size of 240 cm2. On average, 20 percent of patients had preoperative wound infections, 30 percent had intraoperative bowel enterotomies, and 33 percent required prosthetic mesh for closure. Total surgery time averaged 4.8 hours, with a mean postoperative stay of 12.5 days and follow-up of 9.5 months. The recurrence rate was 10 percent; postoperative complications included midline ischemia, infection, and dehiscence occurring at rates of 20, 40, and 43 percent, respectively. This study provides a comprehensive review of the risks and complications associated with the treatment of complex ventral hernias and those associated with abdominal "components separation."     

Linking teratogen information service and birth defects registry databases to improve knowledge of birth defect status

BACKGROUND: Although teratogen information services (TISs) obtain maternal exposure information from their callers, such services often do not know if the pregnancies were affected by a birth defect. This study attempted to improve the completeness of this information for Texas Teratogen Information Service (TTIS) callers by linking their records with the Texas Birth Defects Registry (TBDR) and Texas birth certificates (TBCs). METHODS: A total of 344 expectant mothers called TTIS with expected dates of delivery between 1 January 2000 and 31 December 2001. These pregnancies were linked with TBDR and TBC data. The percentages of pregnancies with known birth defect information both before and after the linkage were compared. RESULTS: The TTIS originally collected birth defect status information for 101 of the 344 callers (29.4%) and 0.6% of all 344 callers or 2.0% of callers with birth defect status information had a pregnancy affected by a birth defect. Linking TTIS records with TBDR and TBC data helped to raise the percentage of callers with birth defect status information from 29.4% to 71.5%. Among those callers, the percentage known to have birth defects increased from 2.0% to 4.1%. The sensitivity of TTIS follow-up calls in identifying birth defects was 50%, and the specificity was 100%. CONCLUSIONS: Linking TTIS caller records with TBDR and TBC data significantly increased both the percentage of pregnancies with birth defect status information and the percentage of pregnancies identified as affected by birth defects. Such linkage may be a good approach by which TISs can increase the completeness of their birth defect status information.     

VACTERL-H associated with central hypothyroidism: a case report

The VACTERL-H syndrome is a rare combination of vertebral anomalies, anal atresia, congenital heart defects, tracheo-esophageal fistula, abnormalities of kidneys and limb anomalies together with hydrocephalus. This condition is recognized as a hereditary entity with poor prognosis. We present a newborn weighing 3400 g, born by cesarean section to a 27 years old mother who had had an irregular antenatal follow-up. The patient had severe hydrocephalus, proximal esophageal atresia and distal tracheoesophageal fistula, gastric outlet obstruction, imperforated anus and recto-urethral fistula, patent ductus arterious, a bifid scrotum, a vertebral defect, sacral dimple and central hypothyroidism. The patient had no limb defects. The association of central hypothyroidism and VACTERL-H has previously not been reported.     

Maternal asthma,asthma medication use,and the risk of congenital heart defects

BACKGROUND: Asthma is a common problem that complicates pregnancy. Several drugs are considered acceptable for use during pregnancy, although none have been classified as safe. Few studies have assessed the health impact of maternal asthma/medication use on the fetus. METHODS: A population‐based case‐control study was conducted in New York State to determine if cardiac congenital malformations in offspring were associated with maternal use of asthma medication and/or maternal asthma. Cases were cardiac anomalies in the New York State Congenital Malformations Registry. Controls were live births without any major birth defects randomly selected from birth certificates and frequency matched by year of birth. Data were collected through a 30 min telephone interview. Exposure was maternal asthma/medication use, maternal asthma/no medication use, no asthma/medication use, and no asthma/no medication use (reference). RESULTS: A total of 502 (59.4%) cases and 1,066 (53.8%) controls participated. A positive association was seen between any heart defect and women with asthma who used medication (OR 2.38; 95% CI: 1.18, 4.82). No significant associations were observed between heart defects and either women with asthma who did not use medication or women without asthma who used asthma medications. When considering types of medication used, offspring of women with asthma who used bronchodilators had an increased risk of any heart defect (OR 2.20; 95%CI: 1.05, 4.61). CONCLUSIONS: These results suggest that both maternal asthma status (controlled vs. uncontrolled; severe vs. mild) and asthma medication use, particularly bronchodilators, may play a role in cardiac malformations in offspring. Birth Defects Research (Part A), 2009. © 2008 Wiley‐Liss, Inc.     

The concept of fillet flaps: classification, indications, and analysis of their clinical value

Tissue of amputated or nonsalvageable limbs may be used for reconstruction of complex defects resulting from tumor and trauma. This is the "spare parts" concept.By definition, fillet flaps are axial-pattern flaps that can function as composite-tissue transfers. They can be used as pedicled or free flaps and are a beneficial reconstruction strategy for major defects, provided there is tissue available adjacent to these defects.From 1988 to 1999, 104 fillet flap procedures were performed on 94 patients (50 pedicled finger and toe fillets, 36 pedicled limb fillets, and 18 free microsurgical fillet flaps).Nineteen pedicled finger fillets were used for defects of the dorsum or volar aspect of the hand, and 14 digital defects and 11 defects of the forefoot were covered with pedicled fillets from adjacent toes and fingers. The average size of the defects was 23 cm2. Fourteen fingers were salvaged. Eleven ray amputations, two extended procedures for coverage of the hand, and nine forefoot amputations were prevented. In four cases, a partial or total necrosis of a fillet flap occurred (one patient with diabetic vascular disease, one with Dupuytren's contracture, and two with high-voltage electrical injuries).Thirty-six pedicled limb fillet flaps were used in 35 cases. In 12 cases, salvage of above-knee or below-knee amputated stumps was achieved with a plantar neurovascular island pedicled flap. In seven other cases, sacral, pelvic, groin, hip, abdominal wall, or lumbar defects were reconstructed with fillet-of-thigh or entire-limb fillet flaps. In five cases, defects of shoulder, head, neck, and thoracic wall were covered with upper-arm fillet flaps. In nine cases, defects of the forefoot were covered by adjacent dorsal or plantar fillet flaps. In two other cases, defects of the upper arm or the proximal forearm were reconstructed with a forearm fillet. The average size of these defects was 512 cm2. Thirteen major joints were salvaged, three stumps were lengthened, and nine foot or forefoot amputations were prevented. One partial flap necrosis occurred in a patient with a fillet-of-sole flap. In another case, wound infection required revision and above-knee amputation with removal of the flap.Nine free plantar fillet flaps were performed-five for coverage of amputation stumps and four for sacral pressure sores. Seven free forearm fillet flaps, one free flap of forearm and hand, and one forearm and distal upper-arm fillet flap were performed for defect coverage of the shoulder and neck area. The average size of these defects was 432 cm2. Four knee joints were salvaged and one above-knee stump was lengthened. No flap necrosis was observed. One patient died of acute respiratory distress syndrome 6 days after surgery.Major complications were predominantly encountered in small finger and toe fillet flaps. Overall complication rate, including wound dehiscence and secondary grafting, was 18 percent. This complication rate seems acceptable. Major complications such as flap loss, flap revision, or severe infection occurred in only 7.5 percent of cases. The majority of our cases resulted from severe trauma with infected and necrotic soft tissues, disseminated tumor disease, or ulcers in elderly, multimorbid patients.On the basis of these data, a classification was developed that facilitates multicenter comparison of procedures and their clinical success. Fillet flaps facilitate reconstruction in difficult and complex cases. The spare part concept should be integrated into each trauma algorithm to avoid additional donor-site morbidity and facilitate stump-length preservation or limb salvage.     

An algorithm for abdominal wall reconstruction

Acquired abdominal wall defects result from trauma, previous surgery, infection, and tumor resection. The correction of complex defects is a challenge to both plastic and reconstructive and general surgeons. The anatomy of the abdominal wall, as well as considerations in patient assessment and surgical planning, are discussed. A simple classification of abdominal wall defects based on size, depth, and location is provided. Publications regarding the various abdominal reconstruction techniques are reviewed and summarized to familiarize the reader with the treatment options for each particular defect. Finally, an algorithm is presented to guide the surgeon in selecting the optimal reconstructive technique.     

Defekt von Femur und Fibula mit Amelie,Peromelie oder ulnaren Strahldefekten der Arme Ein Syndrom

Six cases are described in which defects of the femora are associated with deformities of the upper limbs. From the available literature all cases (55) were selected in which femoral defects were associated with upper limb deformities. It became apparent that most if not all of these cases belong to a well defined syndrome. Arm deformities associated with femoral defect do not usually include the most common types, but specific rare types, namely amelia, peromelia ending at the level of the elbow, brachioradial synostosis and ulnar defects. In the syndrome in question sometimes either arm shows a different type of these deformities, which is further evidence that all cases may be considered to represent one category. In the majority of cases there is also a defect of the fibula and the fibular rays. The etiology is unknown. Familial occurrence has not been observed. Parental age does not appear to be a factor. In no case was there a thalidomide history. A history of radiation exposure during pregnancy was present in two previously published cases. Other limb deformities associated with radiation exposure in utero are quoted from the literature. Some of them are similar, but not exactly identical to the syndrome in question.Thalidomide deformities, in which the radial and tibial rays are preferentially affected, are clearly distinct. Similar defects of the femorae and fibulae but not of the arms are occasionally seen in children born to diabetic mothers.